Of the five options, four could be compatible with the referred symptoms. We could initially rule out central serous chorioretinopathy because by definition it occurs in young people (up to 55 years of age, more or less). The key to differentiate between the other four is that he had soft drusen in the fundus. That while not a "diagnosis" (the question could have been better worded) is a finding related to age-related macular degeneration, or age-related macular degeneration. The dry or atrophic form presents with slowly progressive visual loss. But the wet or exudative form produces acute or rapidly progressive severe visual loss (usually due to subretinal hemorrhage accompanied by metamorphopsia (image distortion due to retinal lifting). An epiretinal membrane usually has a slower course. In a macular hole, visual loss is more relevant (metamorphopsia may also be reported, but it is less likely in the acute stage). In thrombosis of the central retinal vein, visual loss is more important and does not usually explain metamorphopsia (but may have it, due to macular edema).

Of the five options, four could be compatible with the referred symptoms. [HIDDEN] because by definition it occurs in young people (up to 55 years of age, more or less). The key to differentiate between the other four is that he had soft drusen in the fundus. That while not a "diagnosis" (the question could have been better worded) is a finding related to age-related macular degeneration, or age-related macular degeneration. The dry or atrophic form presents with slowly progressive visual loss. [HIDDEN] (usually due to subretinal hemorrhage accompanied by metamorphopsia (image distortion due to retinal lifting). An epiretinal membrane usually has a slower course. In a macular hole, visual loss is more relevant (metamorphopsia may also be reported, but it is less likely in the acute stage). In thrombosis of the central retinal vein, visual loss is more important and does not usually explain metamorphopsia (but may have it, due to macular edema).

75-year-old woman diagnosed 3 years ago with soft drusen in the fundus. She reports presenting, since 2 weeks ago, metamorphopsia and significant visual loss in her right eye that prevents her from reading. Indicate the most probable diagnosis:

[Macular diseases in the elderly person].

Macular diseases in the elderly, such as age-related macular degeneration, idiopathic senile macular hole and epiretinal membrane of the macular area were studied. In 75 normal subjects aged from 20 to 78 years, retinal sensitivity in the central 10 degree visual field were examined using automated static quantitative perimetry. For background luminance of 31.5 asb, a significant reciprocal correlation was demonstrated between individual mean sensitivity and age. The influence of age on the decrease in sensitivity was proved to differ according to different test locations. To enhance contrast, an image processing procedure was applied for fluorescein angiographs of age-related pathologies which resulted in better recognition of age-related RPE pathologies were recognized. The senile disciform macular degeneration (SDMD) study group sponsored by the Ministry of Health and Welfare performed an epidemiological survey to estimate the number of patients with SDMD. The epidemiological estimation was 6,000 to 13,000 patients in the entire Japanese population. 133 eyes of uni- or bi-lateral senile macular degeneration without choroidal neovascularization and 156 opposite eyes of patients with unilateral SDMD were followed-up for choroidal neovascularization development. Choroidal neovascularization development was confirmed in 15 eyes, 5.2%. In 13 of the 15 eyes, choroidal neovascularization was proved to develop through serous RPE detachment. Also, serous drusen were shown to be to predisposed to choroidal neovascularization through serous RPE detachment. Therefore, it was concluded that senile macular degeneration should be classified into the atrophic form, predisciform or intermediate form and disciform form. In the author's previous paper, it was reported that the navel-like lesion would be a macular lesion predisposing to a senile macular hole. 49 opposite eye of patients with one eye affected by a macular hole were follow-up for macular hole development. At the initial examination, the navel-like lesion was observed in 5 of the 49 eyes. During the course of observation, navel-like lesions developed in one of the other 27 eyes with other abnormalities and in 4 of the 17 eyes without any abnormality. Finally, macular holes developed in 11 of the 49 eyes; in 10 eyes with a navel-like lesion and one eye with another abnormality. We found a 17 year old female Japanese monkey with pre-macular holes in both eyes and clinicopathological correlative study was carried out. In her right eye, photoreceptor cell loss at the foveola, circumferential retinal detachment around the area of cell loss, cystoid spaces in the detached retina, and very thin residual tissue covering the foveolar lesion were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Disappearance of soft drusen and subsequent development of choroidal neovascularization following macular hole surgery: a case report.

Drusen are important risk factor for neovascular age-related macular degeneration (AMD) and have a dynamic nature as they can enlarge, newly form, or disappear over time. There have been few reports on drusen regression or choroidal neovascularization (CNV) development after macular hole surgery. We report, to our knowledge, the first case of both drusen regression and subsequent CNV development within 7 months of successful macular hole surgery. A 73-year-old woman presented with a stage 3 full-thickness macular hole and large, confluent soft macular drusen in the right eye and a neovascular age-related macular degeneration (AMD) in the fellow eye. Four months after the successful macular hole surgery, significant regression of drusen was seen, especially in the temporal area to the fovea. Three months later, the patient developed CNV and her best-corrected visual acuity decreased to 20/100, despite further regression of macular drusen. Macular hole patients with macular soft drusen need to be carefully followed up after surgery for possible drusen regression and CNV development.

Treatment of macular serous neuroretinal detachment in tilted disk syndrome: report of 3 cases.

To describe functional and anatomic results obtained by treatment with photodynamic therapy (PDT) or intravitreal bevacizumab (Avastin, Roche) in macular serous retinal detachment associated with tilted disk syndrome. Three eyes of 3 patients with symptomatic macular serous detachment associated with tilted disc syndrome (optic disc with an oblique axis, inferonasal crescent, and inferior staphyloma) were treated. In all patients, best-corrected visual acuity (BCVA) was tested and fluorescein angiography (FA) and optical coherence tomography (OCT) were performed before and about 45 days after treatment. All patients underwent a complete ophthalmologic examination including OCT at least 6 months after treatment. The first patient was treated with one low fluence (300 mW/cm2 for 83 seconds) PDT (6 months follow-up). The second patient was treated with 3 intravitreal injections of bevacizumab 1.25 mg (33 months follow-up) and the third patient was treated with 2 low fluence PDTs at 4 months and, after 1 year, 3 intravitreal injections of bevacizumab 1.25 mg (37 months follow-up). Before treatment, all patients complained of visual loss and metamorphopsia. The OCT showed in the macular area a focal neurosensory detachment with foveal involvement. The FA showed in the macular area multiple focal areas of hyperfluorescence due to pigment epithelium atrophy and in the second and third patient also a hyperfluorescent pinpoint with minimal leakage. After treatment in all eyes, symptoms did not change, BCVA remained stable, and in OCT the foveal neuroretinal detachment was changeless. In FA, no noticeable variation of the hyperfluorescence areas was appreciated. In the second patient, the hyperfluorescent point remained unvaried, and the same occurred in the third patient after the first PDT, while after the second PDT a new leaking dot disappeared. Macular serous retinal detachment was first described in 1998 as an uncommon complication of tilted disc syndrome showing angiographic and OCT features similar to a chronic central serous chorioretinopathy. In contrast to this pathology, in our patients treatment with PDT or intravitreal bevacizumab did not succeed, probably because of a different pathogenesis of macular serous detachment. Further investigations are needed to clarify the proper therapy of this disease.

Macular hole and serous pigment epithelial detachment in bilateral acquired vitelliform lesions.

Acquired vitelliform lesions (AVLs) are associated with age-related macular degeneration and other variable macular disorders. AVLs often lead to outer retinal atrophy, sometimes accompanying a macular hole and choroidal neovascularization. The purpose of this study was to report a rare case with bilateral AVLs, in which one eye had accompanied a macular hole and the second eye a serous pigment epithelial detachment (sPED). A 66-year-old woman complained of bilateral metamorphopsia. AVLs were observed in the right eye and a flat sPED in the left eye. The best-corrected visual acuity (BCVA) was 20/17 in both eyes. Fluorescein angiography revealed local leakage in the right eye and pattern dystrophy-like hypofluorescence in both eyes. The sPED progressed with AVLs in the left eye and was treated with a combination therapy of intravitreal aflibercept, a sub-Tenon's injection of triamcinolone acetonide, and photodynamic therapy (IVA/STTA/PDT), which successfully flattened the sPED and sustained good vision for 4 years. The right eye was treated with intravitreal ranibizumab and tissue plasminogen activator, which enhanced absorption of the vitelliform material. However, 14 months later, a macular hole with typical metamorphopsia formed above a subretinal fibrotic scar at the vitelliruptive stage. Although pars plana vitrectomy closed the macular hole, enlargement of the outer retinal atrophy worsened the BCVA to 20/100. We successfully treated one eye with a sPED with AVLs using the combination therapy of IVA/STTA/PDT, while the second eye with a macular hole secondary to AVLs ultimately developed outer retinal atrophy with visual loss.

Amsler grid

Clinical significance Amsler grid can be used in detecting central visual field defects in following conditions: Age-related macular degeneration: The grid will help detecting the progression of AMD from dry form to wet form. Chance of metamorphopsia is more in wet AMD compared to dry form. Choroidal neovascular membranes: Choroidal neovascular membranes cause scotoma and metamorphopsia. It may be associated with many diseases like macular degeneration, POHS, myopic macular degeneration, trauma etc. Central serous chorioretinopathy: CSCR Causes round or oval scotoma. Macular pucker: Macular pucker also known as an epiretinal membrane cause metamorphopsia and distortions in central field of vision. Cystoid macular edema: Due to macular edema, micropsia may occur. Glaucoma: Amsler grid is useful in detecting central field defects in moderate to severe glaucoma. Macular sparing: Amsler Grid can be used to detect and accurately measure macular sparing. Types

Macular Hole -- Differential Diagnosis

Recent advancement in OCT has made it simpler to differentiate a macular hole from other similar types of smaller diameter macular pathologies of old age. From history and physical examination, round central small reddish lesions with dimness of central vision, probable differential diagnosis include: Epiretinal membrane (ERM) with a macular pseudo hole Central foveal dot hemorrhage Lamellar (aborted) macular hole Vitreomacular traction syndrome (VMTS) Foveal drusen Central areolar pigment epitheliopathy Solar retinopathy Small choroidal neovascular membrane involving center Small central serous chorioretinopathy involving center Cystoid macular edema (CME)

Macular degeneration

Other types There are a few other (rare) kinds of macular degeneration with similar symptoms but unrelated in etiology to Wet or Dry age-related macular degeneration. They are all genetic disorders that may occur in childhood or middle age. Vitelliform macular dystrophy Sorsby's fundus dystrophy is an autosomal dominant, retinal disease characterized by sudden acuity loss resulting from untreatable submacular neovascularisation Stargardt's disease (juvenile macular degeneration, STGD) is an autosomal recessive retinal disorder characterized by juvenile-onset macular dystrophy, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material. Similar symptoms with a very different etiology and different treatment can be caused by epiretinal membrane or macular pucker or any other condition affecting the macula, such as central serous retinopathy. Notable cases Judi Dench Joan Plowright Peter Sallis June Brown S. Robert Morgan See also

Metamorphopsia

Treatment and Prognosis Metamorphopsia is a symptom of several common retinal and macular diseases, therefore treating the underlying disorder can improve symptoms. For people who have conditions such as Epiretinal membrane (ERM), Macular Holes and Retinal Detachment, decreased metamorphopsia is associated with an increase in visual acuity. Quantitative evaluation of metamorphopsia is an important step in understanding visual functions of individuals with macular disorders and is an essential tool for physicians in evaluating treatment results. Types Dry (non-exudative, > 80%)—deposition of yellowish extracellular material in and between Bruch's membrane and retinal pigment epithelium (“drusen”) with gradual loss in vision. Wet (exudative, 10–15%)—rapid loss of vision due to bleeding secondary to choroidal neovascularization. Etymology Gk, meta + morphe, form, opsis, sight See also Dysmorphopsia Hallucination References Visual disturbances and blindness

Spontaneous closure of a fully developed macular hole in a severely myopic eye.

Purpose. Myopic macular holes can be difficult to close with surgery and are frequently associated with retinal detachment. We report on a case of a macular hole in a severely myopic eye that underwent spontaneous closure. Methods. An observational case study. Results. A 55-year-old female was referred to Ophthalmology for a central scotoma and metamorphopsia in the right eye. Visual acuity was 1/20 in both eyes. Fundus examination showed loss of the foveal depression, with a small yellow ring in the center of the fovea in the right eye, and a tilted optic disc and peripapillary staphyloma bilaterally. Spectral domain optical coherence tomography (SD-OCT) revealed a fully developed macular hole with a rim of thickened and slightly elevated retina in the right eye. The patient refused surgery. After 4 years of follow-up, her visual acuity improved to 20/40 in the right eye, and SD-OCT revealed spontaneous sealing of the macular hole without bare retinal pigment epithelium. Conclusions. Myopic macular holes represent a challenge regarding their management, and the prognosis is often poor.

Symptomatic age-related macular degeneration in Asian patients.

To characterize retinal and fluorescein angiographic findings of Asian patients with symptoms secondary to age-related macular degeneration (ARMD). We retrospectively reviewed 453 consecutive medical records corresponding to fluorescein angiograms performed between November 1992 and November 1995 to identify Asian patients with symptomatic ARMD. Presenting visual symptoms, best-corrected Snellen visual acuities, and retinal examination findings were determined from the medical records. Fundus photos and fluorescein angiograms were reviewed. There were 26 symptomatic eyes in 19 Asian patients with a median age of 73 years. Presenting visual symptoms included decreased visual acuity (19 eyes), metamorphopsia (5 eyes), or scotoma (2 eyes). Retinal findings included occult choroidal neovascularization (CNV) in 5 (19%) eyes, serous pigment epithelial detachment (PED) in 8 (31%) eyes, PED with CNV in 5 (19%) eyes, drusen in 5 (19%) eyes, retinal pigment epithelial atrophy in 1 (4%) eye, vitreous hemorrhage in 1 (4%) eye, and a disciform scar in 1 (4%) eye. In this cohort of Asian patients with ARMD, the majority of symptomatic eyes had either CNV (46%) or serous PED (31%).

[Clinical observations of macular hole with and without retinal detachment in high myopic eyes].

To study the clinical features and the pathogenesis of macular hole with and without retina detachment (RD) in high myopic eyes. It was a retrospective series case study. The charts of high myopic patients with macular hole at our hospital from June 2006 to February 2007 were retrospectively reviewed and analyzed. Patients were divided into two groups (the RD group and non-RD group) depending on the presence of RD or not. Their clinical data and optic coherence tomography (OCT) results were further analyzed. SPSS 13.0 was used for the statistic analysis. When comparing the quantitative aspects like age, axial length and refraction, t-test was used. Categorical data, such as sex ratio, occurrence of vitreous traction, posterior staphyloma and retinoschisis were compared by using χ(2) test. Fisher's test was used in comparing eye laterality, incidence of white hole, visual acuity and posterior vitreous detachment (PVD). During this period, there were 43 patients fitting the including criteria. Among them, 36 patents (37 eyes) were in the RD group and 7 patients (7 eyes) in the no-RD group. In the RD group, the average age was 56.1, 24.3% of them (9/37) were male; percentage of left and right eyes was (11/37) and 70.3% (26/37), respectively; average refraction was (-8.9 ± 2.2) D; average axial length was (28.7 ± 2.0) mm. Visual acuity was ≤ 0.05 (72.2%) in 26 eyes and 0.05 - 0.2 (27.8%) in 10 patients. The incidence of complete and non-complete PVD was 89.2% (33/37) and 10.8% (4/37), respectively. White hole presented in 35.1% (3/37) patients. Vitreous traction and retinoschisis presented in 27.0% (10/37) and 35.1% (13/37) patients, respectively. In the non-RD group, the average age was 47.6; 16.7% of them (1/7) were male; left and right eyes were involved in 42.9% (3/7) and 57.1% (4/7), respectively. Average refraction was (-9.0 ± 1.9) D; average axial length was (28.9 ± 1.5) mm. Vision acuity was ≤ 0.05 in 3 patients (42.9%); between 0.05 - 0.2 in 3 eyes (42.9%) and ≥ 0.2 in 1 eye (14.3%). Incidence of complete and non-complete PVD was 85.7% (6/7) and 14.3% (1/7), respectively. White hole was observed in 14.3% (1/7) patients; 42.9% (3/7) patients were accompanied with vitreous traction and 71.4% (5/7) with retinoschisis. B-scan ultrasonography showed posterior staphyloma in all 44 eyes. The results of statistical analysis showed that the gender (χ(2) = 0.008) and eye laterality (χ(2) = 0.449) as well as refraction (t = 0.193), axial length (t = -0.25) and visual acuity (χ(2) = 4.509) of these two groups were similar (P > 0.05). The incidences of vitreous traction (χ(2) = 0.709), white hole (χ(2) = 1.179), PVD (χ(2) = 0.071) and retinoschisis (χ(2) = 3.207) were also similar (P > 0.05). But the age of the non-RD group is significantly younger than the RD group (t = 1.66, P < 0.05). Various pathogenesis may involved in the occurrence of retinal detachment in highly myopic eyes with macular hole. Further study is required to improve our understanding of this entity.

Atypical Chronic Central Serous Chorioretinopathy Mimicking Vogt-Koyanagi-Harada Disease: Full Therapeutic Response to Half-Fluence Photodynamic Therapy

The aim of this case report is to describe a case of atypical central serous chorioretinopathy (CSCR) definitively diagnosed after 8 years. A 44-year-old woman presented with reduced visual acuity in her left eye. Her visual acuity was light perception with projection in the right eye and 0.15 in the left. She described a similar decline in vision in her right eye 8 years ago. At that time, she had exudative retinal detachment and was treated with systemic immunosuppressive therapy for a presumed diagnosis of Vogt-Koyanagi-Harada disease. Despite resolution of the exudative retinal detachment, macular scarring developed. Eight years later, she developed inferior exudative retinal detachment in the left eye. A diagnosis of atypical CSCR was made with the help of multimodal imaging and her left eye was successfully treated with eplerenone and half-fluence photodynamic therapy (hf-PDT). In conclusion, early diagnosis and treatment of atypical CSCR may prevent subretinal fibrosis formation and permanent vision loss. Hf-PDT and eplerenone are successful treatment options for atypical CSCR.

An Unusual Case: Self-separation of an Idiopathic Epiretinal Membrane

Self-separation or peeling of an idiopathic epiretinal membrane (ERM) in an eye with partial posterior vitreous detachment (PVD) is a rare event. A 56-year-old woman presented to our clinic with complaints of floaters in her right eye. Best-corrected visual acuity (BCVA) was 9/10 in this eye. Fundus examination and Spectral domain optical coherence tomography (SD-OCT) revealed an idiopathic ERM and Grade 3 PVD in this eye. Four months later, she had complaints of metamorphopsia in her right eye. BCVA was 7/10, while SD-OCT images of the right macula were similar to previous images. One week after the last visit, she presented again due to the sudden disappearance of her metamorphopsia complaints. BCVA had improved to 10/10. Fundus examination demonstrated that the ERM had spontaneously separated from the retinal surface as a flap floating in the vitreous and the foveal contour had returned to normal. The etiologic mechanism may be explained as the contracting forces within an immature ERM being stronger than its adhesion to the retina.

[Long-term results of the treatment of optic disc pit associated with serous macular detachment: a review of 20 cases].

The pathogenesis of the macular serous retinal detachment (SRD) associated with congenital optic disc pit remains controversial. The treatment is also discussed. Through this study, which includes the majority of the techniques available, we report our experiment in the treatment of this pathology. This was a retrospective single-centre study of 20 patients who presented with macular SRD associated with optic disc pit between 1983 and 2009. Various treatments were provided. At the beginning of the study, patients were treated only by juxtapapillary laser photocoagulation. After laser failure then as first-line treatment, laser photocoagulation was associated with intravitreal gas (C3F8) injection with postoperative facedown positioning for 2 weeks. During the past few years, all patients have been systematically treated with vitrectomy with or without internal limiting membrane (ILM) peeling, laser, and gas (C2F6) tamponade. This series consisted of 20 patients: nine men and 11 women. The patients' mean age at presentation was 29 years (range, 9-60 years). The mean time between the onset of the decrease in visual acuity (VA) and treatment was 6.1 months. None of these patients had a posterior vitreous detachment at the time of diagnosis. Six patients were treated by laser photocoagulation alone, which was successful only in two cases. Eleven patients (with laser treatment failure in three) were treated by laser and intravitreal gas injection, with a 72% success rate. We performed vitrectomy with posterior hyaloid dissection, laser, and gas tamponade in eight cases (with laser-gas treatment failure in two) with 87% success rate and no recurrence. Five of these patients had ILM peeling during the vitrectomy. The mean follow-up period was 60 months (range, 2 months to 17 years). This study shows that early treatment of macular SRD associated with optic disc pit by vitrectomy, ILM peeling, juxtapapillary photocoagulation, and gas tamponade is followed by good anatomical and functional results. This treatment is superior to the other less invasive procedures. Optical coherence tomography is an important exam for diagnosis and postoperative follow-up of patients.

[Atypical presentation of central serous choroidopathy. Case report].

Central serous choroidopathy is a macular disease, usually with a self-limited and benign course, and predominantly affects male patients between 20 and 45 years old. A 68 year-old female patient complained of decreased visual acuity of her right eye of approximately 3 weeks of onset. Best corrected visual acuity in her right eye was 20/100. Fundus examination revealed a macular serous detachment involving its centre, as well as the presence of multiple calcified drusen. Fluorescein angiography showed late parafoveal leakage in a "smokestack" pattern in the right macular area. Optical coherence tomography showed a dome-shape macular detachment, also in the right eye. The patient was observed every 2 weeks and spontaneous resolution of the macular detachment was seen a month later. Based on these clinical features, a diagnosis was made of central serous choroidopathy of atypical presentation. Atypical presentation cases of serous central choroidopathy might be seen occasionally. Hence, it is an important differential diagnosis of age related macular degeneration in patients older than 60 years.

Use of a macular buckle in the treatment of exudative age-related macular degeneration.

To evaluate a macular buckle for exudative choroidal neovascularization secondary to age-related macular degeneration (ARMD). Forty-two eyes with choroidal neovascular membranes (CNVM) secondary to ARMD underwent surgical placement of a macular buckle. A Gore-Tex strip (2.0-2.5 mm wide) was button-holed through a 5 mm diameter silicone sponge (9 mm long) and placed behind the macula underneath the CNVM by the same surgeon (Dr Peyman) in all cases. Follow-up ranged from 7-76 months (mean, 20.9 months). Of 12 eyes with classic subfoveal CNVM: 4 (33%) gained 2 or more lines of Snellen visual acuity; 3 (25%) gained 1 line, remained the same, or lost 1 line; and 5 (42%) lost 2 or more lines (range + 6 to - 6 lines). Of 22 eyes with ill-defined subfoveal CNVM: 12 (54%) gained 1 line, remained the same, or lost 1 line; and 10 (46%) lost 2 or more lines (range + 1 to - 8 lines). Eight eyes with ill-defined juxtafoveal CNVM had the following visual acuity outcomes: 5 eyes (62%) maintained the same level of Snellen visual acuity (gained 1, 0, or lost 1 line); and 3 (38%) got worse (lost 2 or more lines of Snellen visual acuity, range + 1 to - 6 lines). Ten eyes (24%) bled subretinally during the follow-up period (average 11.5 months, range 14 days to 27 months), all outside the area of indentation of the macular buckle. The macular buckle treatment for exudative subretinal choroidal neovascular membranes in ARMD stabilized visual decline and displaced significant subfoveal hemorrhage.

CYSTOID MACULAR EDEMA AND CYSTOID MACULAR DEGENERATION AS A RESULT OF MULTIPLE PATHOGENIC FACTORS IN THE SETTING OF CENTRAL SEROUS CHORIORETINOPATHY.

To report the pathogenic factors that account for cystoid macular edema and cystoid macular degeneration in chronic central serous chorioretinopathy (CSC). The clinical course and multimodal imaging findings, including fundus color photography, fundus autofluorescence, spectral-domain optical coherence tomography, and fluorescein angiography, of one eye with cystoid macular edema due to chronic CSC was documented. A 44-year old woman with a history of chronic CSC presented with progressive visual decline in the right eye. Best-corrected visual acuity was 20/40. Funduscopic examination revealed diffuse retinal pigment epithelial changes and macular edema. Fluorescein angiography demonstrated perifoveal microaneurysms and leakage in a petaloid configuration. Spectral-domain optical coherence tomography demonstrated cysts at the level of the inner nuclear layer, an epiretinal membrane, vitreomacular traction, and an attenuated retinal pigment epithelial band. Central subfield thickness was 486 μm. Three intravitreal injections of aflibercept were administered over 16 weeks following which there was resolution of leakage, release of vitreomacular traction, and resolution of microaneurysms. Central subfield thickness reduced to 379 μm, but persistent intraretinal cysts were observed. There was subjective improvement in visual symptoms, but Snellen acuity remained at 20/40. Intraretinal cystic changes in chronic CSC may be the result of multifactorial pathogenic factors and may represent the coexistence of cystoid macular edema and cystoid macular degeneration. Anti-vascular endothelial growth factor may play an important role in the treatment of cystoid macular edema caused by CSC.

[Patient with recurrent central serous chorioretinopathy who developed multiple evanescent white dots and serous retinal detachment immediately following bevacizumab administration].

A patient developed choroidal neovascularization (CNV) in one eye during treatment for bilateral recurrent central serous chorioretinopathy (CSC) and was intravitreously injected with bevacizumab; she developed multiple evanescent white dots and serous retinal detachment(SRD). A 50-year-old women had a history of CSC OD at the age of 29 years. On initial examination, CSC OD was noted, and multiple detachments of the retinal pigment epithelium OU were observed. While the CSC in the right eye was successfully treated by laser photocoagulation, it spread to both eyes following this episode. Examination of the right eye by optical coherence tomography (OCT) following the recurrence of the CSC showed slight elevation of the retinal pigment epithelial layer in the central fovea, but this finding disappeared with the resolution of the CSC. However, as the CSC combined with CNV (Gass type 2) recurred within 1 year, the patient was intravitreously injected with bevacizumab. On the day following the injection, SRD OD occurred, and on the 7th day following the injection many white lesions varying in size appeared in the deep layer of the retina, but they healed 3 weeks later, leaving only the CNV. The CNV was cured later by additional photodynamic therapy. Since the lesions of the fundus observed immediately after the bevacizumab administration resolved spontaneously without sequelae, they were retrospectively diagnosed as a white dot syndrome-like disease. The white dot syndrome-like disease is suggested as a rare complication of bevacizumab.

Unilateral central serous chorioretinopathy in a pregnant Nigerian woman.

Central serous chorioretinopathy (CSCR) is an idiopathic condition characterized by serous detachment of the neurosensory retina in the macular region. It is relatively uncommon in Africans and though pregnancy is a known risk factor, there are no previous reports of CSCR in pregnant African women. We report the case of a 35-year-old pregnant woman who presented to our clinic at gestational age of 29 weeks with a 4 months history of blurring of vision in her left eye. Examination revealed visual acuity of 6/4 on the right eye and 6/9 on the left eye. She had normal anterior segments bilaterally and a normal posterior segment on the right. However, she had left macular edema with exudates. There was no significant refractive error. Her blood pressure was normal. Investigations including electrolytes and urea, urinalysis, and blood sugar profile were all normal. She was managed conservatively, and symptoms resolved 2 weeks prior to delivery. This is a case report of CSCR in a pregnant Nigerian woman with spontaneous resolution of symptoms prior to delivery. Pregnant women should be educated about the possibility of visual problems accompanying pregnancy.

Three cases of macular hole that occurred in inferior scleral staphyloma associated with tilted disc syndrome: a case series.

The objective is to examine the clinical characteristics of three patients with macular hole that occurred in inferior posterior staphyloma associated with tilted disc syndrome. This study involved three eyes of three Japanese female patients (mean age 76.0 years, range 73-84 years) with macular hole occurring in inferior posterior staphyloma associated with tilted disc syndrome. One of the three eyes was slightly myopic, while the other two eyes were highly myopic. In all three eyes, the macular hole was found to be located in or near the margin of the inferior posterior staphyloma. In one eye, the extent of retinoschisis was rather broad in the margin of the macular hole, and another eye had a history of treatment for choroidal neovascularization. As surgical treatment, the internal limiting membrane in areas surrounding the macular hole was detached after producing artificial posterior vitreous detachment, and a gas tamponade was performed. It was found during surgery that the extensibility of the retina in the margin of the MH was decreased in the three eyes as compared with a usual macular hole. Although the macular hole was successfully closed in all three cases post surgery, the layer structure of the central retina was poorly repaired in all three cases and choroidal neovascularization remained in one case. In all three cases, corrected visual acuity remained at 0.3-0.5 post surgery. Our findings showed poor improvement of visual acuity in all three cases post surgery, even if closure of the macular hole is achieved, thus suggesting that in cases of macular hole associated with tilted disc syndrome and inferior posterior staphyloma, the presence of macular dysfunction existing prior to the onset of macular hole affects visual prognosis.

Cystoid macular edema associated with preservative-free latanoprost after uncomplicated cataract surgery: case report and review of the literature.

Cystoid macular edema associated with latanoprost administration has been reported in patients after complicated cataract surgery with coexisting risk factors. We present the first case of preservative free latanoprost associated cystoid macular edema that occurred many months after uncomplicated cataract surgery. A 65-year old Caucasian female presented in the Outpatients Clinic complaining of reduced vision and metamorphopsia in the right eye. She had undergone uneventful phacoemulsification 19 months ago in the right eye and was under treatment with preservative free latanoprost eye drops for the last 7 months for ocular hypertension. Her remaining medical and ocular history were otherwise unremarkable. Cystoid macular edema with serous retinal detachment was diagnosed in the right eye using optical coherence tomography and fluorescein angiography. Latanoprost was discontinued and brinzolamide and nepafenac eye drops were administered in the right eye. Two months later, cystoid macular edema completely resolved with restoration of visual acuity. Nepafenac eye drops were administered for another 2 months. Eight months after latanoprost cessation optical coherence demonstrated no sign of cystoid macular edema whereas a subtle epiretinal membrane was noted. Cystoid macular edema may potentially occur in patients receiving preservative free latanoprost. More interestingly, in our case it was diagnosed in a patient with a long standing pseudophakia after uncomplicated phacoemulsification. No obvious risk factor for macular edema development was recognized. Prompt diagnosis and latanoprost discontinuation resulted in complete resolution of the cystoid macular edema and functional restoration of the eye.

Vitrectomy for optic disk pit with macular schisis and outer retinal dehiscence.

To describe the outcomes of vitrectomy for optic disc pit-related maculopathy with central outer retinal dehiscence. This prospective interventional case series included seven patients with optic disc pit with macular schisis and central outer retinal dehiscence who underwent vitrectomy with internal limiting membrane peeling, barrage laser photocoagulation, and gas tamponade and were followed for at least 6 months. The surgical outcomes in terms of restoration of macular anatomy and visual improvement were recorded at each visit by fundus photography and optical coherence tomography. The mean age of the patients was 21.3 ± 8.6 years (range, 10-35 years), and the mean duration of defective vision was 6.7 ± 8.5 months (range, 1-24 months). Preoperatively, the median best-corrected visual acuity (BCVA) was 20/60 (range, 20/40 to 20/120). Full-thickness macular holes were noticed in 4 patients 1 month postoperatively. Gas tamponade was repeated in two patients with large macular holes. By the final follow-up, macular holes had closed and BCVA improved in all patients except one. Final mean central macular thickness was 176.83 ± 55.74 μ, the range being 109 μ to 256 μ. The median postoperative BCVA was 20/30 (range, 20/20 to 20/80). Six of 7 patients (85.7%) had improvement in BCVA postoperatively (mean, +2 lines; range, 1-4 lines). Five patients (71%) achieved a postoperative BCVA of ≥20/30. Best-corrected visual acuity dropped by one line in the patient with persistent macular hole. Vitrectomy with internal limiting membrane peeling can achieve excellent final surgical outcomes in optic pit maculopathy with outer retinal dehiscence despite the potential for macular hole formation.

Epiretinal membrane

Epidemiology This ocular pathology was first described by Iwanoff in 1865, and it has been shown to occur in about 7% of the population. It can occur more frequently in the older population with postmortem studies showing it in 2% of those aged 50 years and 20% in those aged 75 years. Culture In 1996, Spalding Gray (June 5, 1941 – ca. January 10, 2004), an American actor, screenwriter and playwright, released Gray's Anatomy, a film monologue describing his experiences dealing with a macular pucker and his decision to undergo surgery. In the 2011 film Paul, Ruth had Epiretinal membrane complicated by macular edema in her left vitreous cavity. See also Eye surgery References Additional references External links Macular Pucker Resource Guide from the National Eye Institute (NEI). Disorders of choroid and retina

Optic pit

Treatment for optic pit-associated macular detachment involves photocoagulation of the retina by use of an ion laser (either krypton or argon). This procedure works by burning one or more rows in between the optic disc and areas of serous retinal detachment. In most cases, macular reattachment results and visual acuity can be restored to about 20/80. This procedure may also be utilized prior to macular detachment in order to help prevent the future development of macular detachment. Other treatments for optic pit-associated macular detachment include macular buckling, gas tamponade, or vitrectomy. Some experts feel that the best results can be attained when the use of any of the above-mentioned modalities (laser photocoagulation, macular buckling, gas tamponade, and vitrectomy) are used in combination. Diagnosis Optic pits should be diagnosed by an eye care professional who can perform a thorough exam of the back of the eye using an ophthalmoscope.

Microperimetry - A New Tool for Assessing Retinal Sensitivity in Macular Diseases.

Macular disease is the leading cause of low vision in the Western world. Drusen and pigmentary irregularities are common among the rural Northern Indian population. The disease process leads to loss of central vision, metamorphopsia, macropsia or micropsia and colour vision defect. To study the retinal sensitivity changes in macular diseases using microperimetry. It was an observational study, conducted in the Department of Ophthalmology at a rural tertiary care hospital. This study was started from December 2014 until June 2016, in all patients with macular disease above the age of 20 years attending the outpatient department. Microperimetry was done for 84 eyes of 52 patients with macular disease. Mean retinal Sensitivity (MS) and fixation stability was evaluated. The statistical analysis of mean retinal sensitivity, central 2° and 4° fixation was done by calculating the mean and standard deviation using 95% confidence interval. The range of age was between 20-81 years. Majority were 32 males (62%) and 20 females (38%). Out of the 84 eyes studied, majority of the macular disease were Age-Related Macular Degeneration (AMD) (50%). Rest 50% were other macular diseases. The mean retinal sensitivity (dB) shown by microperimetry was 10.83 in AMD, 9.12 in Cystoid Macular Oedema (CME), 10.34 in Epiretinal Membrane (ERM), 10.74 in Pigment Epithelial Detachment (PED), 8.96 in Central Serous Chorioretinopathy (CSCR), 6.43 in macular dystrophy, 7.15 in Lamellar Hole (LMH), 9.8 in Pseudomacular Hole (PMH), 3 in geographic atrophy, 11.1 in macular telangiectasia, 5.6 in Berlin oedema, 12.3 in macular scar and 15.2 in haemorrhage in macula. The study showed 64% of the eyes had stable 2° central fixation, 35% had relatively unstable fixation and 1% had unstable fixation. No significant correlation between retinal sensitivity and retinal thickness in AMD was found. This study shows that microperimetry can be a useful tool for objective evaluation of macular function and progression of the disease.

[Role of vitreoretinal interface in the pathogenesis and therapy of macular disease associated with optic pits].

Although the relationship between optic pits and macular lesions was described nearly a century ago, the pathology and pathogenesis of macular detachment remain unclear. Recent OCT studies have shown schisislike spaces in connection with the disc. None of the hypotheses of pathogenesis proposed so far could have been proven. Besides the hypothesis of exudation, the role of the vitreoretinal interface is kept in the background of discussion. We describe a case of macular detachment associated with optic pit that regained full vision after pars plana vitrectomy with laser coagulation and gas tamponade over a follow-up of 26 months. The purpose of our case report is to emphasize the role of the vitreoretinal interface in the pathogenesis of macular detachment associated with optic pits. A 32-year-Caucasian woman developed macular detachment associated with an optic pit on her right eye. The vision deteriorated to 24/60. A standard three-port pars plana vitrectomy was performed. After creating a posterior vitreous detachment, all vitreoretinal adhesions were removed carefully. Peripapillary laser coagulation and gas tamponade with 15% C2F6-air mixture followed. For 26 months after surgery the macula has been flat. The vision is 60/60. Besides the exudative component of macular detachment, the vitreoretinal interface seems to play an underestimated role in the pathogenesis of maculopathy associated with optic pits. Tractional forces could explain the delay of macular detachment in young adulthood and the frequency of treatment failure after laser coagulation and gas tamponade. Pars plana vitrectomy with complete removal of all vitreoretinal adhesions should be a suitable technique in the treatment of macular detachment associated with optic pits.

Metamorphopsia

Age-related macular degeneration Epiretinal membrane and vitreomacular traction Posterior vitreous detachment Macular hole Diagnosis Tests used for diagnosis of Metamorphopsia mostly make use of subjective assessments of how a person views regular patterns. Many of these tests have a poor ability to accurately diagnose or identify a person with the disease (i.e.,poor sensitivity). The use of assessments such as a psychophysical test called preferential hyperacuity perimetry, which assesses a person’s ability to any misalignments of visual objects, may permit a more sensitive diagnosis of Metamorphopsia. Treatment and Prognosis

Bilateral macular edema in a patient treated with tamoxifen: a case report and review of the literature.

We present a case of a 41-year-old female patient with progressive bilateral visual loss. On examination, her best corrected visual acuity (BCVA) in her right eye was 3/10 and her BCVA in her left eye was 2/10. Fundus and optical coherence tomography examination revealed severe bilateral macular edema. She had been diagnosed with breast cancer 6 years ago and was receiving tamoxifen at a dosage of 20 mg/day ever since. Tamoxifen therapy was discontinued, and the patient received 250 mg of acetazolamide three times a day for a period of 1 month. Both foveae regained their normal contour within 2 months, and her vision was restored to 10/10 BCVA 3 months later. To our knowledge, this is the first case reported where bilateral intraretinal macular edema is the only retinal manifestation in a patient on oral tamoxifen.

[Surgical removal of submacular neovascularization membranes].

New techniques for vitreoretinal surgery enable the removal of submacular neovascular membranes inaccessible to laser coagulation. The present study describes the anatomical and functional results following membrane removal. Between January 1994 and June 1995, submacular neovascular membranes were removed from 56 eyes with age-related exudative macular degeneration. Thirty-one eyes had classic subfoveal membranes; 19, occult membranes; and 6 eyes, disciform fibrotic changes that had already persisted for more than 6 months. Surgery led to improved vision in 20 of the 56 eyes (36%). In 26 of the 56 eyes (44%) vision at the last follow-up was no different from preoperative vision: in 10 eyes (17%) visual acuity declined. In the group of 6 eyes with a 6-month history of exudative maculopathy, surgery produced a slight improvement in vision in most patient. Complications arose in 8 of the 56 eyes (14%), namely choroidal hemorrhage (2 eyes), a macular hole (1 eye), and peripheral retinal detachment (5 eyes). Recurrence of the membrane was seen in 5 eyes (9%). Surgical removal of submacular membranes can often lead to stabilization or even improvement of vision. Owing to the relatively high rate of complications, however, the indications must be rigorously appraised on a case-by-case basis.

[Preventive treatment using laser of age-related macular degeneration of the contralateral eye after age-related macular degeneration of the first eye].

Since 1982, and with informed patient consent, we have photocoagulated confluent drusen and limited serous pigment epithelium detachment (SPED) in the fellow eye of ten patients suffering from advanced, disciform type, age-related macula degeneration (ARMD). This treatment was only carried out on appearance of metamorphopsia. Photocoagulation was performed with either the green ray of the argon laser, or the yellow ray of a dye laser. Spots of about 200 microns were placed in a grid-like fashion among the drusen. No complications were observed due to the treatment. The follow-up period on these ten patients, eight women and two men, mean age 77 years, was two to eight years, and the three patients have died. The drusen disappeared completely in three patients and partially in one. The functional results seemed favorable in three cases. In one case of confluent drusen associated with SPED and serous retinal detachment, vision improved remarkably from 0.3 to 0.5 with a Parinaud 2, with a follow-up of five years. In another case, the improvement was from 0.4 to 0.7 but the patient died after only a few months. In another case, vision has been stable for five years. The vision of the seven remaining patients deteriorated; three cases showed central areolar sclerosis, and one case a localised new vessel with vision less than 0.1. In three cases vision dropped to 0.2 and Parinaud 6, but they have been stable for at least four years (eight years for one patient).(ABSTRACT TRUNCATED AT 250 WORDS)

A case of Nd:YAG laser-induced traumatic macular hole with good visual prognosis after vitrectomy with inverted internal limiting membrane technique.

To report an accidental case of traumatic macular hole caused by Nd:YAG laser in a dermatology clinic. A 24-year-old woman sustained a laser injury to her right eye while practicing a dermatologic treatment using a Nd:YAG laser without wearing protective goggles. She noticed sudden-onset and progressing visual loss in her right eye and consulted an ophthalmologist 2 days after injury. The best-corrected visual acuity (BCVA) of her right eye decreased to 20/133. Fundus examination showed white parafoveal flecks with a central retinal hemorrhage and underlying serous retinal detachment. The retinal sensitivity in this lesion deteriorated. Two weeks later, a full-thickness macular hole (FTMH) developed in the affected eye. She was referred to Nagoya City University Hospital where the laser damage described was observed. The BCVA was 20/67. She underwent pars plana vitrectomy performed using the inverted internal limiting membrane (ILM) flap technique and gas tamponade. One week postoperatively, the FTMH closed, the BCVA in her right eye improved to 20/50, and the retinal sensitivity in the macular area mostly improved. The BCVA gradually improved and reached 20/25 9 months after the injury. Protective goggles must be worn when using an Nd:YAG laser in the laboratory or clinical setting. In the unfortunate event of a FTMH, early vitrectomy with an inverted ILM flap technique can be helpful to achieve a good visual prognosis.

Fellow eye findings of highly myopic subjects operated for retinal detachment associated with a macular hole.

To identity anatomic risk factors involved in the onset of retinal complications causing decrease of visual acuity (VA) in the fellow eyes of highly myopic patients operated for retinal detachment with macular hole (RDMH). Cohort study. Ninety-eight patients (mean age, 51.5+/-8.0 years) with bilateral high myopia (mean myopia of the fellow eye, 20.4+/-5.5 diopters) affected by RDMH in the other eye at baseline. Evaluation of the anatomic features at baseline and during 84+/-2.7 months of follow-up by biomicroscopic examination, indirect binocular ophthalmoscopy, B-scan ultrasonography, and optical coherence tomography. Detection of anatomic features associated with onset of retinal complications causing decrease of VA during the follow-up period. The fellow eyes were divided into 2 groups according to the clinical features of the RDMH eyes: Group 1, presence of posterior vitreous detachment (PVD); and Group 2, presence of posterior vitreous schisis (PVS). At baseline, the incidence of PVD in group 1 was 31 of 47 eyes (65.9%) and the incidence of PVS in Group 2 was 42 of 51 eyes (82.3%). At the end of follow-up, group 1 eyes had a lower incidence of retinal complications causing visual decrease than group 2 eyes (group 1, 2/47 eyes; group 2, 9/51 eyes). Fellow eyes of RDMH cases with higher degree of myopia and peculiar vitreoretinal features including PVS, posterior epiretinal membrane, severe posterior staphyloma, and chorioretinal atrophy are more likely to develop retinal complications causing decrease of VA.


This question is a bit convoluted for the diagnosis of Cushing's syndrome but easy if the steps are clear. We all agree that the patient seems to have Cushing's syndrome (we rule out 1). For the diagnosis we have to measure urinary free cortisol, do a dexamethasone suppression test or measure nocturnal salivary cortisol. If hypercortisolism is confirmed, the origin should be sought; the ACTH measurement indicates the origin: suppressed in hypercortisolism of adrenal origin or prolonged use of corticoids and elevated or normal if the origin is pituitary or by ectopic ACTH secretion. (Therefore, 4 and 5 are false). If ACTH is low, a CT scan of the abdomen should be performed to locate the origin. If ACTH is normal or high, a pituitary MRI should be performed (pituitary adenomas responsible for Cushing's syndrome are very small and CT of the pituitary is less sensitive than MRI). It is very important to perform the order well to arrive at a proper diagnosis: 1st: confirm hypercortisolism or s. Cushing's syndrome, 2nd: measure ACTH to orient etiology. 3rd: imaging test according to ACTH levels. Therefore, answer 2 is false (abdominal CT is not a test to rule out s. Cushing's); an imaging test should only be done once a clear diagnosis of hypercortisolism has been made. Therefore, the true one is 3.

This question is a bit convoluted for the diagnosis of Cushing's syndrome but easy if the steps are clear. We all agree that the patient seems to have Cushing's syndrome (we [HIDDEN]). For the diagnosis we have to measure urinary free cortisol, do a dexamethasone suppression test, or measure nocturnal salivary cortisol. If hypercortisolism is confirmed, the origin should be sought; the ACTH measurement indicates the origin: suppressed in hypercortisolism of adrenal origin or prolonged use of corticoids, and elevated or normal if the origin is pituitary or by ectopic ACTH secretion ([HIDDEN]). If ACTH is low, a CT scan of the abdomen should be performed to locate the origin. If ACTH is normal or high, a pituitary MRI should be performed (pituitary adenomas responsible for Cushing's syndrome are very small and CT of the pituitary is less sensitive than MRI). It is very important to perform the order well to arrive at a proper diagnosis: 1st: confirm hypercortisolism or s. Cushing's syndrome, 2nd: measure ACTH to orient etiology. 3rd: imaging test according to ACTH levels. Therefore, answer 2 is [HIDDEN] (abdominal CT is not a test to [HIDDEN]); an imaging test should only be done once a clear diagnosis of hypercortisolism has been made. Therefore, the true one is [HIDDEN].

A 56-year-old female patient consulted for dorso-lumbar spine pain and progressive difficulty in performing usual tasks. In the last 5 years she gained weight, she has ecchymosis easily and arterial hypertension was detected. Physical examination: Obesity of central predominance, rounded facies, increased supraclavicular fat, decreased proximal muscle strength and some reddish striae in the abdomen. She has a blood glucose of 136 mg/dL and the radiological study showed osteoporosis and vertebral crushing. What do you think is the most coherent interpretation and attitude?

Postmenopausal osteoporosis, type 2 diabetes mellitus and essential hypertension, with decreased strength due to diabetic polyneuropathy.

It is necessary to rule out Cushing's disease by dexamethasone suppression test and perform a cranial CT scan.

Suggest Cushing's. Determine urinary free cortisol and basal ACTH, which serves to orient its etiology and select the most appropriate imaging technique.

It looks like Cushing's. If basal ACTH is high, it may be due to corticosteroid use or an adrenal tumor, and an MRI should be performed.

Probably has Cushing's. If the basal ACTH is low, he probably has a pituitary micro-adenoma, and a cranial CT scan should be performed.

Subclinical Cushing's syndrome.

Classic Cushing's syndrome is a rare disease with an estimated incidence of 1 case per 100,000 persons. With routine use of imaging techniques such as ultrasound and CT, adrenal masses are being detected with increased frequency. A substantial percentage of these incidentalomas are hormonally active, with 5% to 20% of the tumors producing glucocorticoids. Autonomous glucocorticoid production without specific signs and symptoms of Cushing's syndrome is termed subclinical Cushing's syndrome. With an estimated prevalence of 79 cases per 100,000 persons, subclinical Cushing's syndrome is much more common than classic Cushing's syndrome. Depending on the amounts of glucocorticoids secreted by the tumor, the clinical spectrum ranges from slightly attenuated diurnal cortisol rhythm to complete atrophy of the contralateral adrenal gland with lasting adrenal insufficiency after unilateral adrenalectomy. Patients with subclinical Cushing's syndrome lack the classical stigmata of hypercortisolism but have a high prevalence of obesity, hypertension, and type 2 diabetes. All patients with incidentally detected adrenal masses scheduled for surgery must undergo testing for subclinical Cushing's syndrome to avoid postoperative adrenal crisis. The best screening test to uncover autonomous cortisol secretion is the short dexamethasone suppression test. Because the adrenal origin of a pathologic cortisol secretion is anticipated, the author prefers a higher dexamethasone dose (3 mg instead of 1 mg) to reduce false-positive results. A suppressed serum cortisol level of less than 3 micrograms/dL (80 nmol/L) after dexamethasone excludes significant cortisol secretion by the tumor. A serum cortisol level greater than 3 micrograms/dL requires further investigation, including confirmation by high-dose dexamethasone (8 mg) suppression testing, a CRH test, and analysis of diurnal rhythm. Determination of urinary free cortisol is less useful because increased values are a late finding usually associated with emerging clinical signs of Cushing's syndrome. Patients with suppressed plasma ACTH in response to CRH generally have adrenal insufficiency after surgery and require adequate perioperative and postoperative substitution therapy. Whether patients with subclinical Cushing's syndrome should undergo adrenalectomy is a matter of debate. The author performs surgery in young patients (< 50 years), in patients with suppressed plasma ACTH, and in patients with a recent history of weight gain, substantial obesity, arterial hypertension, diabetes mellitus, and osteopenia. In completely asymptomatic patients with normal plasma ACTH concentrations and in patients older than 75 years, the author recommends a nonsurgical approach. A large prospective randomized study is necessary to evaluate the benefits of surgery versus conservative treatment in patients with subclinical Cushing's syndrome.

Screening for Cushing's syndrome: is it worthwhile?

Cushing's syndrome (CS) is a rare disease characterized by a collection of signs and symptoms, also common in the general population without elevated cortisol secretion. During the last years more patients with CS are identified earlier and with milder disease. Many of these patients are diagnosed during screening efforts performed for certain or isolated complaints like weight gain, diabetes mellitus (DM), hypertension, osteoporosis, elevated white blood cell counts and more. In this review article the most popular screening test performed in the studies cited was the 1-mg dexamethasone suppression test. Cushing is not frequent enough to support the use of routine screening in patients with morbid obesity and type 2 DM. Also only 1% of hypertensive patients have secondary hypertension due to CS. However, screening should be considered in young patients with resistant DM and/or hypertension. Among patients with osteoporosis and vertebral fractures up to 5% were diagnosed with subclinical hypercortisolism; most of these had adrenal adenoma. Screening for CS is important in subjects with adrenal incidentaloma, and many studies show a high prevalence (~10%) of Cushing or subclinical CS in these patients.

Cushing's disease: establishing the diagnosis and management approach.

A 64 year old lady, with a background history of type 2 diabetes mellitus and hypertension, presented with general deterioration of general health, poor glycemic control, difficulty in controlling blood pressure and difficulty in walking. She had past medical history of adenocarcinoma of the oesophagus, treated with surgery and subsequent chemotherapy. General examination revealed high blood glucose and blood pressure and a Cushingoid facies. Overnight dexamethasone suppression test and urinary free cortisol levels confirmed Cushing's syndrome and High dose dexamethasone suppression test showed partial suppression. CT scan of the abdomen showed bilateral hyperplasia of the adrenals with nodularity on the left side, raising the possibility of an adrenal adenoma. ACTH levels were elevated thereby ruling out autonomously functioning adrenal nodule, however increasing the possibility of ectopic ACTH secretion due to the previous medical history. MRI of the pituitary confirmed the presence of an adenoma, thereby pointing to the diagnosis of pituitary dependant Cushing's disease. The patient could not undergo further invasive investigation or surgery due to septicaemia. Medical management of Cushing's syndrome was resorted to in the interim with Ketoconazole, showing excellent response. This case depicts the need for a high index of suspicion for the diagnosis, the importance of organizing specific investigations in the appropriate order to arrive at a diagnosis and an effective management plan.

[Morbidity and mortality in Cushing's syndrome].

Endogenous Cushing's syndrome is a rare endocrine disorder that is fatal if left untreated. It can be distinguished into adrenocorticotropic hormone (ACTH)-dependent (central and ectopic Cushing's syndrome) and ACTH-independent subtypes (unilateral or bilateral adrenal adenomas). The clinical presentation of patients includes typical stigmata of cortisol excess with physical symptoms of catabolic metabolism (myopathy, striae, parchment skin, osteoporosis) and components of metabolic syndrome (diabetes mellitus, obesity, arterial hypertension, hypercholesterolemia). Biochemical diagnosis is performed in three steps: 1. Confirmation of the diagnosis by 1‑mg dexamethasone suppression test, 24‑h urine free cortisol, and measurement of late-night salivary cortisol. 2. Differentiation of ACTH-dependent Cushing's syndrome from ACTH-independent adrenal Cushing's syndrome by measurement of plasma ACTH. 3. Further subtyping by corticotropin-releasing hormone (CRH) test, inferior petrosal sinus sampling, and imaging modalities. Therapeutic decisions are made on an interdisciplinary basis. First-line therapy for all subtypes is surgery when possible; additional options for all forms include drug therapy and bilateral adrenalectomy. Despite adequate treatment, Cushing's syndrome is associated with increased long-term morbidity and mortality. Interdisciplinary and multimodal therapy management is necessary in the long term to positively influence mortality and reduced quality of life.

Coexistence of Cushing Disease With a Solitary Adrenocorticotrophic Hormone-Dependent Adrenal Adenoma.

We report a 49-year-old woman who had minimal features of Cushing syndrome and an incidentally discovered adrenal adenoma. She was subsequently diagnosed with pituitary-dependent Cushing syndrome. Laboratory and imaging studies including serum cortisol, plasma adrenocorticotrophic hormone (ACTH), high dose dexamethasone test, corticotropin-releasing hormone test, computed tomography (CT) scan, and magnetic resonance imaging were performed. A 49-year-old woman was admitted for urosepsis. An abdominal CT scan performed during the urosepsis workup showed a 2.7-cm right adrenal adenoma. She denied any abdominal striae or other symptoms. Physical examination showed normal vital signs, minimal facial fullness without central obesity, and striae. Laboratory results were as follows: 24-hour-urine cortisol 294 μg (reference 4.0-50.0), midnight serum cortisol 23.0 μg/dL (reference < 7.5), and plasma ACTH level 39 pg/mL (reference 5-27). A corticotropin-releasing hormone stimulation test showed >20% rise in serum cortisol and >35% rise in ACTH levels. A pituitary magnetic resonance image showed a 5 mm pituitary lesion. The patient underwent transsphenoidal pituitary surgery, which confirmed an ACTH-secreting lesion. Postoperatively, she required hydrocortisone replacement for the next 10 months. A follow-up adrenal CT performed 6 months later showed a decrease in the size of the adrenal adenoma (1.8 cm). This case highlights the importance of recognizing the coexistence of ACTH-dependent Cushing disease with an adrenal adenoma and partial ACTH dependency of the adrenal adenoma.

[Prevalence, etiology and clinical findings of Cushing's syndrome].

Endogenous Cushing's syndrome is a very rare entity, with an incidence of 2-4 cases per million inhabitants per year. Cases caused by ectopic ACTH secretion are under-diagnosed. Cushing's disease is the most frequent cause of endogenous Cushing's syndrome, which is 5 or 6 times more frequent than adrenal Cushing's syndrome, with an incidence of between 1.2 and 2.4 cases per million inhabitants per year. Cushing's disease is 3-8 times higher in women than in men. The frequency of adrenal tumors is 3 times higher in women, while that of Cushing's syndrome due to adrenal tumors is 3-5 times higher. Age at diagnosis of Cushing's syndrome varies according to the etiology. Most cases of Cushing's disease are due to a pituitary adenoma, although the tumor may not be visible on the available imaging techniques. ACTH-independent Cushing's syndrome is found in 20% of cases and is most frequently due to adenomas (10%) or adrenal carcinomas (8). Bilateral micronodular hyperplasia and macronodular hyperplasia are infrequent entities, representing less than 10% of all cases of ACTH-independent Cushing's syndrome. Both familial and sporadic forms exist: the familial form, or Carney complex, and ACTH-independent bilateral macronodular hyperplasia, in which the size of the adrenal glands is considerably enlarged. The signs and symptoms of Cushing's syndrome are a direct result of long-term exposure to excessive glucocorticoids. Most signs and symptoms are highly prevalent in the general population (hypertension, central obesity, diabetes mellitus or carbohydrate intolerance, osteoporosis, and characteristic phenotypical alterations).

[Cushing's syndrome: diagnostic exploration].

The diagnosis of Cushing's syndrome is one of the most perplexing and controversial problems in endocrinology. However, significant advances in the diagnosis procedures have been made in the past decade. The diagnostic studies involved in the evaluation of patients with suspected Cushing's syndrome fall into two categories: confirming the presence of true hypercortisolism and establishing the precise aetiology. Diagnosis of Cushing's syndrome: ambulatory screening relies on the overnight 1 mg dexamethasone test. Negative tests are confirmed by measuring cortisol in two 24-hour urine samples. If cortisol excretion is slightly above normal, a 48-hour low-dose dexamethasone suppression test or an intravenous infusion dexamethasone suppression test are required. Diagnosis of the aetiology of Cushing's syndrome: the first step is to establish if the hypercortisolism is ACTH-dependent or not. This step is solved by measuring plasma ACTH and cortisol in the late afternoon. Computed tomography scanning of the adrenal glands is required in ACTH-independent Cushing's syndrome. A unilateral tumour will be demonstrated in most of cases. If bilateral lesions are found, dynamic testing using cortisol releasing factor and/or metyrapone must be performed to confirm the ACTH-independency of the syndrome. In ACTH-dependent Cushing's syndrome, the major difficulty is to distinguish between a pituitary source and an ectopic source of ACTH secretion. Magnetic resonance imaging of the pituitary with gadolinium enhancement must be preferred to computed tomography scanning but its sensitivity is not better than 70-80% and false positives can occur. When no macroscopic pituitary lesion can be detected, bilateral inferior petrosal sinus sampling coupled to CRH injection for ACTH measurement will indicate the source of ACTH secretion. If this test indicates the patient has Cushing's disease, pituitary trans-sphenoidal surgery can be performed. If the test indicates the patient has ectopic ACTH-secretion, a cervico-thoraco-abdominal scanning is necessary to identify the tumour. In the case of occult tumour the hypercortisolism must be controlled by pharmacological agents and the imaging investigations must be repeated at appropriate intervals.

[Management of hypercortisolism].

Cushing's syndrome is a rare but frequently considered disease. Its diagnosis can lead to some difficulties, including confirming the effective endogenous hypercortisolism and determining its cause. The severity of this disease, the diversity of its complications and the multiple therapeutic options make its management challenging. The aim of this review is to present the most recent data about management of Cushing's syndrome, especially diagnostic approaches and therapeutic options. Our references were obtained by screening MEDLINE database from 1996 to 2006. We also included some anterior reviews and consensus statements. We retained the following points: midnight salivary cortisol is a useful tool in the diagnosis of Cushing's syndrome; the desmopressin test can help to distinguish between Cushing's syndrome and "pseudoCushing's" due to alcohol consumption or psychiatric disorders; cavernous sinus and inferior petrosal sinus sampling is indicated in the evaluation of ACTH-dependent Cushing's syndromes when pituitary imaging is normal or equivocal or when dynamic tests are contradictory; multislice computed-tomography of the chest and the abdomen and somatostatin analogue scintigraphy, eventually combined, are the best imaging procedures in occult ectopic ACTH syndromes; patients with Cushing's disease should be referred to a neurosurgeon experienced in corticotroph adenomas surgery; metabolic consequences of Cushing's syndrome, such as cardiovascular risk factors and osteoporosis need an aggressive treatment. The incidence of Cushing's syndrome is only 1/100000 per year. However, hypercortisolism is diagnosed by systematic evaluation in 2 to 5% of patients with poorly controlled type 2 diabetes and adrenal incidentalomas. Endocrinological management of the disease improves metabolic disorders in these patients. If these results are confirmed, screening for Cushing's syndrome should be systematically performed in these populations.

Cushing's syndrome

When Cushing's syndrome is suspected, either a dexamethasone suppression test (administration of dexamethasone and frequent determination of cortisol and ACTH level), or a 24-hour urinary measurement for cortisol offers equal detection rates. Dexamethasone is a glucocorticoid and simulates the effects of cortisol, including negative feedback on the pituitary gland. When dexamethasone is administered and a blood sample is tested, cortisol levels >50 nmol/l (1.81 μg/dl) would be indicative of Cushing's syndrome because an ectopic source of cortisol or ACTH (such as adrenal adenoma) exists which is not inhibited by the dexamethasone. A novel approach, recently cleared by the US FDA, is sampling cortisol in saliva over 24 hours, which may be equally sensitive, as late-night levels of salivary cortisol are high in cushingoid patients. Other pituitary hormone levels may need to be ascertained. Performing a physical examination to determine any visual field defect may be necessary if a

Cushing's disease

ACTH blood test Once Cushing's syndrome has been diagnosed, the first step towards finding the cause is measuring plasma adrenocorticotropic hormone (ACTH) concentration. A concentration consistently below 1.1 pmol/L is classified as corticotropin-independent and does not lead to a diagnosis of Cushing's disease. In such cases, the next step is adrenal imaging with CT. If plasma corticotropin concentrations are consistently above 3.3 pmol/L, then corticotropin-dependent Cushing's syndrome is most likely. Any intermediate values need to be cautiously interpreted and a corticotropin-releasing hormone (CRH) test is advised in order to confirm corticotropin dependency. If corticotropin-dependent Cushing's syndrome is determined then the next step is to distinguish between Cushing's disease and ectopic corticotropin syndrome. This is done via a combination of techniques including CRH, high-dose DST, BIPSS, and pituitary MRI.

A natural history of adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) from preclinical to clinically overt Cushing's syndrome.

A 49-year-old man was referred to our hospital for the treatment of gallstones in 1993. Bilateral adrenal nodular masses were detected incidentally by abdominal computed tomography. He had no clinical signs of Cushing's syndrome such as central obesity, striae of skin and diabetes mellitus. We performed cholecystectomy and partial adrenalectomy of right adrenal gland as a biopsy, and diagnosed him as preclinical Cushing's syndrome due to adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) based on endocrinological and histological examinations. We followed him up for 7 years. During the observation period, the sizes of both adrenal glands increased gradually, and finally serum cortisol level increased beyond normal range, and he showed a Cushingoid appearance such as moon face and central obesity. His skin became atrophic and very fragile, and the bone mineral density of his lumbar spine was extremely low. Serum cortisol level was elevated, and plasma ACTH level was always suppressed. Urinary excretion of 17-hydroxycorticosteroid and free cortisol were increased. Diurnal rhythm of cortisol and ACTH was completely lost and high dose (8 mg/day) dexamethasone did not suppress urinary 17-hydroxycorticosteroid excretion. He became clinically overt Cushing's syndrome. We recommended total adrenalectomy, but he refused it. It is important to know the natural history of preclinical Cushing's syndrome due to AIMAH when choosing an adequate treatment.

Adrenal gland

Corticosteroid overproduction Cushing's syndrome Cushing's syndrome is the manifestation of glucocorticoid excess. It can be the result of a prolonged treatment with glucocorticoids or be caused by an underlying disease which produces alterations in the HPA axis or the production of cortisol. Causes can be further classified into ACTH-dependent or ACTH-independent. The most common cause of endogenous Cushing's syndrome is a pituitary adenoma which causes an excessive production of ACTH. The disease produces a wide variety of signs and symptoms which include obesity, diabetes, increased blood pressure, excessive body hair (hirsutism), osteoporosis, depression, and most distinctively, stretch marks in the skin, caused by its progressive thinning.

Challenges in the diagnostic work-up and management of patients with subclinical Cushing's syndrome and bilateral adrenal masses.

To review the challenges encountered in the diagnostic work-up and management of patients with subclinical Cushing's syndrome (SCS) and bilateral adrenal masses to aid in the case description of a patient with SCS and adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH). We describe our experience managing a patient with AIMAH and SCS. This case report is followed by an extensive review of the literature regarding differential diagnoses, work-up including adrenal venous sampling (AVS), and treatment of SCS with bilateral adrenal masses. A 51-year-old female who was diagnosed with recent onset hypertension and diabetes mellitus type 2 was evaluated for adrenal masses discovered incidentally on computed tomography (CT). She did not have any Cushingoid features. Magnetic resonance imaging (MRI) of abdomen was performed for further evaluation. Hormonal evaluation came back consistent with SCS. The AVS results were consistent with bilateral autonomous cortisol hypersecretion without lateralization. Collectively, the findings favored the diagnosis of bilateral AIMAH. A left adrenalectomy was performed, and the patient's clinical response was favorable with improvement in blood pressure (BP) accompanied by significant weight loss. Follow-up hormonal testing for autonomous cortisol hypersecretion was within the target range. AIMAH is a rare cause of SCS. AVS is a useful diagnostic tool that helps localize the source of autonomous cortisol hypersecretion in ACTH-independent SCS with bilateral adrenal masses, especially if radiological features are inconclusive. Patients undergoing unilateral adrenalectomy should be followed for monitoring of clinical response, as well as progression of AIMAH in the contralateral adrenal gland.

Corticotropic cell

Associated diseases Cushing's Disease Corticotropic cells can have detrimental effects on the body if they express too much or too little ACTH. One such example is Cushing's disease, which can result from overproduction of ACTH in the corticotropes due to pituitary tumors known as corticotroph adenomas; this is the cause for roughly two-thirds of those diagnosed with Cushing's disease. It is also possible that this disease can result from production of ACTH in a non-pituitary tumor, known as ectopic production, or the adrenal glands can overproduce cortisol due to an adrenal tumor. This overproduction of ACTH causes an increase in cortisol levels due to increased glucocorticoid synthesis in the adrenal cortex resulting in several associated symptoms. Symptoms of Cushing's disease include: Fatty deposits in the neck or back Stretch marks (striae) Fatigue Osteoporosis Weakened immune system Hypertension

Cushing's syndrome

When any of these tests is positive, CT scanning of the adrenal gland and MRI of the pituitary gland are performed to detect the presence of any adrenal or pituitary adenomas or incidentalomas (the incidental discovery of harmless lesions). Scintigraphy of the adrenal gland with iodocholesterol scan is occasionally necessary. Occasionally, determining the ACTH levels in various veins in the body by venous catheterization, working towards the pituitary (petrosal sinus sampling) is necessary. In many cases, the tumors causing Cushing's disease are less than 2 mm in size and difficult to detect using MRI or CT imaging. In one study of 261 patients with confirmed pituitary Cushing's disease, only 48% of pituitary lesions were identified using MRI prior to surgery. Plasma CRH levels are inadequate at diagnosis (with the possible exception of tumors secreting CRH) because of peripheral dilution and binding to CRHBP.

Cushing's disease.

Cushing's disease, i.e., pituitary ACTH-secreting adenoma causing excess glucocorticoid secretion, is a rare disease with significant mortality and morbidity. Timely diagnosis and appropriate treatment can alter the course of the disease and are therefore mandatory. First step of the diagnostic work-up is the endogenous glucocorticoid excess by measurement of urinary free cortisol, cortisol circadian rhythmicity or suppression by low doses of dexamethasone. In patients with equivocal results, second line tests, such as the dexamethasone-suppressed CRH test and desmopressin stimulation, usually enable the diagnosis to be confirmed. Measurement of plasma ACTH then allows the distinction between ACTH-dependent (e.g., pituitary or extrapituitary neuroendocrine tumors) and ACTH-independent causes (e.g., adrenal tumors). The last step in the diagnostic algorithm is often the most fraught with problems as the distinction between Cushing's disease and ectopic ACTH secretion relies on judicious interpretation of several diagnostic procedures. Positive responses to stimulation with CRH and inhibition by high doses of dexamethasone, if concurrent, enable a pituitary origin to be established whereas conflicting results call for inferior petrosal sinus sampling, the latter to be performed in experienced centres only. Visualisation of the tumor at pituitary imaging is helpful but not required for the diagnosis, as microadenomas often remain undectected by MRI and/or CT scan and, on the other hand, visualisation of a non-secreting incidentaloma may be misleading. Surgical removal of the pituitary tumor is the optimal treatment choice and should be attempted in every patient. Surgical failures as well as relapses can be treated by radiotherapy, medical therapy or, if necessary, bilateral adrenalectomy. Finally, patients cured of Cushing's disease require long-term monitoring given the risk of relapse and clinical burden of associated ailments.

The frequency of type 2 diabetic patients who meet the endocrinological screening criteria of subclinical Cushing's disease.

Cushing's syndrome, including its mild form/state of adrenal-dependent subset (subclinical Cushing's syndrome; subCS), is known to enhance glucose intolerance, hypertension and obesity. Recently, subclinical Cushing's disease (subCD) has been identified, but its prevalence and the extent of consequent metabolic derangement are unclear. We screened 90 type 2 diabetic patients hospitalized in our department for subCD, according to the diagnostic guideline proposed by the working group of Japanese Ministry of Health, Welfare and Labor in 2006. Plasma ACTH and cortisol levels in the morning and at midnight were determined, and overnight 0.5 mg dexamethasone suppression test (DST) was performed. Those who showed poor cortisol suppression in DST underwent the desmopressin (DDAVP) test. Fifty-seven patients (63.3%) demonstrated abnormally high midnight cortisol levels (>or=2.5 microg/dL), while only nine of them failed to suppress plasma cortisol levels to <3 microg/dL after DST. Although none of the eight patients who underwent the DDAVP test demonstrated the anticipated paradoxical rise in plasma ACTH, these eight patients (8.9%) endocrinologically met the screening criteria of subCD. Since a considerable percentage of pituitary adenomas causing overt Cushing's disease are not identifiable in magnetic resonance imaging, many of those causing subCD may also be unidentifiable. Further follow-up studies including confirmatory testing and pituitary imaging are necessary.

Cushing Disease -- Evaluation

The most accurate test used to differentiate a pituitary adenoma from ectopic or adrenal Cushing syndrome is inferior petrosal sinus sampling. [12] [18] This invasive method measures the difference in ACTH level found in the inferior petrosal sinus (where the pituitary gland drains) compared to the periphery. [12] [18] A basal central to the peripheral ratio of over 3:1 when CRH is administered confirms the diagnosis of Cushing disease. [18] This test is considered the gold standard in diagnosing Cushing disease because it has a sensitivity and specificity of nearly 94%. Still, it is rarely used in clinical practice due to its high cost, invasiveness, rare but serious complications, and the required special expertise to perform.

Surgery_Schwartz

is diagnostic 1) Overnight DST2) 24-hour urinary free cortisol3) 11:00 pm salivary cortisol1) Plasma ACTH2) High-dose DST and urinary cortisolConfirm the diagnosisACTH gradient?Determine source of hypercortisolismDecreased ACTHLack of suppressionCT scan adrenalsIncreased ACTHPositive Increased ACTHLack of suppressionEquivocalresultsFurther testingBilateral petrosalvein samplingAdrenalsourcePituitarysourceEctopic ACTHsourceSTEPS IN DIAGNOSISDIAGNOSTIC STUDIESYesNoFigure 38-44. Diagnosis of Cushing’s syndrome. ACTH = adrenocorticotropic hormone; CT = computed tomography; DST = dexamethasone suppression test.Brunicardi_Ch38_p1625-p1704.indd 169001/03/19 11:22 AM 1691THYROID, PARATHYROID, AND ADRENALCHAPTER 38of a pituitary tumor. In patients suspected of having ectopic ACTH production, CT or MRI scans of the chest and anterior mediastinum are performed first, followed by imaging of the neck, abdomen, and pelvis if the initial studies are negative.Treatment Laparoscopic

Cushing Syndrome -- Evaluation

Serum ACTH levels can differentiate ACTH-dependent Cushing syndrome (elevated ACTH or inappropriately normal ACTH) from ACTH-independent (low ACTH level) Cushing syndrome. In patients with ACTH-dependent Cushing syndrome, the high-dose dexamethasone suppression test done by giving 8 mg dexamethasone by mouth at 2300 h and checking cortisol the next day at 0800 h, can differentiate pituitary ACTH from an ectopic ACTH source. A high-dose dexamethasone suppression test will decrease cortisol level by 50 % if the ACTH source is a pituitary adenoma, but not if ACTH is secreted by an ectopic tumor (e.g., oat cell lung carcinoma). Pituitary MRI, unenhanced CT scan of the adrenals, and chest X-ray and CT are also useful to localize the pathology.

Cushing's syndrome

Cushing's syndrome is caused by either excessive cortisol-like medication, such as prednisone, or a tumor that either produces or results in the production of excessive cortisol by the adrenal glands. Cases due to a pituitary adenoma are known as Cushing's disease, which is the second most common cause of Cushing's syndrome after medication. A number of other tumors, often referred to as ectopic due to their placement outside the pituitary, may also cause Cushing's. Some of these are associated with inherited disorders such as multiple endocrine neoplasia type 1 and Carney complex. Diagnosis requires a number of steps. The first step is to check the medications a person takes. The second step is to measure levels of cortisol in the urine, saliva or in the blood after taking dexamethasone. If this test is abnormal, the cortisol may be measured late at night. If the cortisol remains high, a blood test for ACTH may be done.

Differential diagnosis of adrenocorticotropic hormone-independent Cushing syndrome: role of adrenal venous sampling.

To outline the potential role for adrenal venous sampling in the diagnosis and management of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS). We present a case description and discuss the management of a 59-year-old woman with an 8-year history of weight gain, centripetal obesity, a round plethoric face, skin thinning, easy bruising, hirsutism, and progressive muscle weakness. The patient reported a prior personal history of asthma, type 2 diabetes mellitus, hypertension, dyslipidemia, and bilateral leg ulcers, but she denied having any personal or family history of endocrinopathy and was not taking any corticosteroid medication. Elevated midnight serum cortisol, failure to suppress cortisol levels with a low-dose dexamethasone suppression test, and undetectable plasma ACTH all indicated ACTH-independent CS. Additional investigations including dynamic tests and adrenal imaging were supported by adrenal venous sampling in order to make a diagnosis and formulate a management plan. She was ultimately noted to have bilateral functioning adrenal nodules (adenoma and adenolipoma) and underwent successful bilateral laparoscopic adrenalectomy, with postoperative glucocorticoid and mineralocorticoid replacement. Adrenal venous sampling may be an important step in the differential diagnosis of CS and localization of the source of cortisol excess. It may distinguish pheochromocytoma or benign nonfunctioning adrenal nodules from cortisol-secreting adenomas and may avoid unnecessary bilateral adrenalectomy. It can also ensure that the correct operation is completed, if required, and thus avoid the increased morbidity and mortality associated with repeated surgical interventions.

Cushing's syndrome

Strictly, Cushing's syndrome refers to excess cortisol of any etiology (as syndrome means a group of symptoms). One of the causes of Cushing's syndrome is a cortisol-secreting adenoma in the cortex of the adrenal gland (primary hypercortisolism/hypercorticism). The adenoma causes cortisol levels in the blood to be very high, and negative feedback on the pituitary from the high cortisol levels causes ACTH levels to be very low. Cushing's disease refers only to hypercortisolism secondary to excess production of ACTH from a corticotroph pituitary adenoma (secondary hypercortisolism/hypercorticism) or due to excess production of hypothalamus CRH (Corticotropin releasing hormone) (tertiary hypercortisolism/hypercorticism). This causes the blood ACTH levels to be elevated along with cortisol from the adrenal gland. The ACTH levels remain high because the tumor is unresponsive to negative feedback from high cortisol levels.

InternalMed_Harrison

Differential Diagnosis The evaluation of patients with confirmed Cushing’s should be carried out by an endocrinologist and begins with the differential diagnosis of ACTH-dependent and ACTH-independent cortisol excess (Fig. 406-10). Generally, plasma ACTH levels are suppressed in cases of autonomous adrenal cortisol excess, as a consequence of enhanced negative feedback to the hypothalamus and pituitary. By contrast, patients with ACTH-dependent Cushing’s have normal or increased plasma ACTH, with very high levels being found in some patients with ectopic ACTH syndrome. Importantly, imaging should only be used after it is established whether the cortisol excess is ACTH-dependent or ACTH-independent, because nodules in the pituitary or the adrenal are a common finding in the general population. In patients with confirmed ACTH-independent excess, adrenal imaging is indicated (Fig. 406-11), preferably using an unenhanced computed tomography (CT) scan. This allows assessment of adrenal

Neurology_Adams

Cushing disease Described in 1932 by Cushing, this condition is only about one-fourth as frequent as acromegaly. A distinction is made between Cushing disease and Cushing syndrome, as indicated in Chap. 26. The former term is reserved for cases that are caused by the excessive secretion of pituitary ACTH, which, in turn, causes adrenal hyperplasia; the usual basis is a pituitary adenoma. Cushing syndrome refers to the effects of cortisol excess from any one of several sources—excessive administration of steroids (the most common cause), adenoma of the adrenal cortex, ACTH-producing bronchial carcinoma, and, very rarely, other carcinomas that produce ACTH. The clinical effects are the same in all of these disorders and include truncal obesity, hypertension, proximal muscle weakness, amenorrhea, hirsutism, abdominal striae, hyperglycemia, osteoporosis, and in some cases a characteristic mental disorder (see “Cushing Disease and Corticosteroid Psychoses” in Chap. 49).

Cushing's syndrome

Endogenous Endogenous Cushing's syndrome results from some derangement of the body's own system of cortisol secretion. Normally, ACTH is released from the pituitary gland when necessary to stimulate the release of cortisol from the adrenal glands. In pituitary Cushing's, a benign pituitary adenoma secretes ACTH. This is also known as Cushing's disease and is responsible for 70% of endogenous Cushing's syndrome. In adrenal Cushing's, excess cortisol is produced by adrenal gland tumors, hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia. Tumors outside the normal pituitary-adrenal system can produce ACTH (occasionally with CRH) that affects the adrenal glands. This etiology is called ectopic or paraneoplastic Cushing's disease and is seen in diseases such as small cell lung cancer. Finally, rare cases of CRH-secreting tumors (without ACTH secretion) have been reported, which stimulates pituitary ACTH production.

[Cushing syndrome in children].

In pediatric patients, endogenous Cushing syndrome is an infrequent condition almost always due to one of two conditions. 1) Adrenal gland tumors account for 70% of Cushing syndromes in young pediatric patients. They cause rapidly progressive hypercorticism not due to increased ACTH production (elevated plasma and urine cortisol levels, very low ACTH and LPH levels unchanged by dexamethasone, metyrapone or CRH). Imaging techniques determine the side and spread of the tumor and look for metastases. Following surgical removal, patients with indicators of malignant disease (tumor weight above 30 g, extracapsular spread or metastases, independently from pathological data) are given op'DDD. 2) Cushing disease occurs in peripubertal patients and causes overweight with delayed statural gain. ACTH production is increased (positive dexamethasone suppression test and provocative metopirone and CRH tests) as a result of a pituitary adenoma which should be looked for by magnetic resonance imaging and whose removal ensures recovery in 50% of cases. Other therapeutic tools include op'DDD, radiation to the pituitary, and bilateral adrenalectomy as the last resort given the high risk of post-adrenalectomy pituitary tumor (50% of pediatric patients). Other causes are exceedingly rare: primary nodular hyperplasia of the adrenal glands and production of ACTH by a nonpituitary tumor. Corticosteroid treatment is the most common cause of Cushing syndrome in children.

InternalMed_Harrison

For ACTH-dependent cortisol excess (Chap. 403), a magnetic resonance image (MRI) of the pituitary is the investigation of choice, but it may not show an abnormality in up to 40% of cases because of small tumors below the sensitivity of detection. Characteristically, pituitary corticotrope adenomas fail to enhance following gadolinium administration on T1-weighted MRI images. In all cases of confirmed ACTH-dependent Cushing’s, further tests are required for the differential diagnosis of pituitary Cushing’s disease and ectopic ACTH syndrome.

Cushing's disease

ACTH stimulation test An ACTH stimulation test involving administration of corticotropin-releasing hormone (CRH) or another agent can differentiate this condition from ectopic ACTH secretion. In a patient with Cushing's disease, the tumor cells will be stimulated to release corticotropin and elevated plasma corticotropin levels will be detected. This rarely occurs with ectopic corticotropin syndrome and thus is quite useful for distinguishing between the two conditions. If ectopic, the plasma ACTH and cortisol levels should remain unchanged; if this is pituitary related, levels of both would rise. The CRH test uses recombinant human or bovine-sequence CRH, which is administered via a 100μg intravenous bolus dose. The sensitivity of the CRH test for detecting Cushing's disease is 93% when plasma levels are measured after fifteen and thirty minutes. However, this test is used only as a last resort due to its high cost and complexity.

Cushing's disease

Inferior petrosal sinus sampling IPSS (inferior petrosal sinus sampling) or BIPSS (bilateral IPSS) is a more accurate but invasive test used to differentiate pituitary from ectopic or adrenal Cushing's syndrome. A corticotropin gradient sample via BIPSS is required to confirm diagnosis when pituitary MRI imaging and biochemical diagnostic tests have been inconclusive. A basal central:peripheral ratio of over 2:1, or a ratio over 3:1 when CRH is administered, is indicative of Cushing's disease. This test has been the gold standard for distinguishing between Cushing's disease and ectopic corticotropin syndrome. The BIPSS has a sensitivity and specificity of 94% for Cushing's disease but it is usually used as a last resort due to its invasiveness, rare but serious complications, and the expertise required to perform it.

Dexamethasone suppression test

Test Procedures There are several types of DST procedures: Overnight DST - An oral dose of dexamethasone is given between 11pm and midnight, and the cortisol level is measured at 8 - 9am the next morning Two-day DST - This involves giving an oral dose of dexamethasone at six-hourly intervals for 2 days, with the cortisol level measured 6 hours after the final dose was given Intravenous DST Dexamethasone-CRT test Interpretation Low-dose and high-dose variations of the test exist. The test is given at low (usually 1–2 mg) and high (8 mg) doses of dexamethasone, and the levels of cortisol are measured to obtain the results. A low dose of dexamethasone suppresses cortisol in individuals with no pathology in endogenous cortisol production. A high dose of dexamethasone exerts negative feedback on pituitary neoplastic ACTH-producing cells (Cushing's disease), but not on ectopic ACTH-producing cells or adrenal adenoma (Cushing's syndrome).

Cushing Disease -- Evaluation

Two or more positive initial screening tests in a patient with a high pretest probability of Cushing disease confirm the biochemical diagnosis of Cushing syndrome. [12] [17] Once Cushing syndrome has been diagnosed, the first step toward finding the cause is by measuring a baseline plasma ACTH level. [15] A level consistently greater than 3.3 pmol/L is classified as corticotropin-dependent. [15] To differentiate Cushing disease from ectopic corticotropin syndrome, a corticotropin-releasing hormone (CRH) test is needed. [15] In a patient with Cushing disease, the administered CRH stimulates additional corticotropin release, resulting in an elevated plasma corticotropin level. [15] The sensitivity of the CRH test for detecting Cushing disease is 93% when plasma levels are measured at fifteen and thirty minutes. [15] Alternatively, a high-dose 48-hour dexamethasone suppression test or pituitary magnetic resonance imaging (MRI) can be used. [15]