bluuebunny/crossref_metadata_2025 huggingface dataset:
Giant Prolactinoma Causing Proptosis and Stroke
Authors: Wortham Joy , Sandoval Brenda , Koops Maureen , Granda-Rodriguez Ramona , Bruder Jan M
Published: May 2021

Background: Although suprasellar and cavernous sinus invasion are common in giant prolactinomas, intra-orbital extension is extremely uncommon [1]. Even less reported are cases of giant prolactinomas causing cerebral ischemia or death.

Clinical Case: A 51-year old woman presented to the ED with confusion, right-sided weakness and severe left eye proptosis with loss of vision. Five years prior, she underwent a partial transphenoidal resection for a macroprolactinoma due to acute vision changes with compression of the optic chiasm. Prior to surgery, prolactin level was elevated to 2,106 ng/mL (n 2.4-24.0 ng/mL). Post-operative MRI showed residual 2.7 x 3.1 x 2.6 cm mass. Thereafter she was prescribed cabergoline which she self-discontinued three years later. MRI of the brain at time of presentation demonstrated a 10.1 x 6.4 x 4.3 cm sellar/suprasellar mass extending into the left orbit causing severe proptosis and mass effect on the left frontal lobe, temporal lobe, midbrain, and basilar artery with encasement of the left cavernous internal carotid artery. A recent left striatocapsular infarct due to compression of the left middle cerebral artery was present. Prolactin level was elevated to 16,487 ng/mL. Neurosurgery was consulted and recommended medical management. Free thyroxine level was low and thyroid hormone replacement was started. Although the cosyntropin stimulation test showed an appropriate cortisol level peak of 21.5 mcg/dL, she was given stress dose glucocorticoids. Bromocriptine was initially started and titrated and later changed to cabergoline. Six weeks after discharge, she was readmitted with worsening confusion and seizure activity. On day 2 of admission, she decompensated. New hemorrhage inside the mass with increased vasogenic edema and a midline shift was discovered on a head CT. She underwent emergent craniotomy with surgical debulking of the tumor. Unfortunately, her mental status did not improve post-operatively. She was transitioned to hospice care and died 7 days after surgery. Surgical pathology showed a lactotroph adenoma with markedly elevated Ki67 proliferation index of 20-30%.

Conclusion: This case demonstrates an unusually aggressive macroprolactinoma causing severe proptosis, ischemic stroke and death and adds to the very few cases previously reported [2].

References: 1. Karcioglu ZA, Aden LB, Cruz AA, Zaslow L, Saloom RJ. Orbital invasion with prolactinoma: a clinical review of four patients. Ophthalmic Plast Reconstr Surg. 2002 Jan;18(1):64-71. 2. Navarro-Bonnet J, Martínez-Anda JJ, Balderrama-Soto A, Pérez-Reyes SP, Pérez-Neri I, Portocarrero-Ortiz L. Stroke associated with pituitary apoplexy in a giant prolactinoma: a case report. Clin Neurol Neurosurg. 2014 Jan;116:101-3.
TNF Alpha-Induced SOX2 Expression Promotes Hepatic Steatois in Diet-Induced Obesity Model
Authors: Shen Chen , Chen Jin Hong , Oh Haram , Park Ji Hyun
Published: May 2021

Diet-induced obesity can cause metabolic or inflammatory damage on liver. Nonalcoholic fatty liver disease (NAFLD) begins with the fat accumulation in hepatocyte, but can lead to hepatocellular carcinoma (HCC). Sex-determining region Y-box 2 (SOX2) is a critical transcription factor involving regeneration and pluripotency. The expression level of Sox2 is correlated with progression of HCC, and anti-inflammatory effects of Sox2 in mesenchymal stem cells have been found. However, the expression of Sox2 by inflammatory cytokines in hepatocyte in NAFLD or the role of SOX2 in fat accumulation has been rarely reported. Here, we found that high-fat diet feeding, with or without high fructose in drinking water, significantly upregulated SOX2 in the livers of mice. In vitro, treatment with free fatty acids (FFAs) and fructose increased SOX2 expression in FL83B cells compared with the vehicle-treated group. Furthermore, overexpression or knockdown of SOX2 in FL83B cells promoted or suppressed, respectively, triglyceride synthesis and lipid accumulation after FFAs stimulation. The expression levels of several lipogenesis-related molecules were found to be altered by SOX2 expression. In addition, among several cytokines, only the treatment of tumor necrosis factor-alpha (TNFα) increased the SOX2 expression compared with the vehicle-treated control. Further, upregulation of (TNFα) by FFA/fructose was observed, and TNFα and FFA/fructose induced SOX2 expression was abolished by pretreatment of a TNFα inhibitor. Collectively, our findings suggest that TNFα-SOX2 signaling pathway in hepatocyte may be one of targets for early prevention of the development of NAFLD.
Pachydermoperiostosis: A Rare Masquerader of Acromegaly and Thyroid Acropachy
Authors: Alkaissi Hussam R , Kubbar Alaa , Banerji MaryAnn
Published: May 2021

Background: Pachydermoperiostoasis is a rare disease of prostaglandin metabolism that presents with extensive clubbing, skin thickening, and enlargement of hands and feet, often misdiagnosed as acromegaly or thyroid acropachy.

Clinical Case: A 29-year-old male presented with progressive enlargement of hands and feet for the past three years, with increased sweating, seborrhea, acne, arthralgia, and photophobia. On examination, facial furrowing and severe clubbing in all fingers and toes was noticed, with palmoplantar hyperhidrosis, tenderness and widening around distal forearms, and increased heel pad thickness. He had nodulocystic acne, injected right eye with ptosis, normal pupil, and visual field. Slit-lamp examination showed extensive pannus formation, with yellow nodules, suggestive of phlyctenular conjunctivitis, secondary to a systemic inflammatory process. No prominent supraorbital ridge, prognathism, proptosis, goiter, or pretibial myxedema. No family history of a similar condition. Labs showed normal cell counts and metabolic panel. Normal IGF-1 (112 ng/mL, n 84-250 ng/ml), TSH (3.82 mIU/L, n 0.27-4.2 mIU/L), fT4 (1.19 ng/dL, n 0.93-1.7 ng/dL), Testosterone (354 ng/dL, n 249-836 ng/dL) and Prolactin (15.2 ng/mL, n 2.1-17.7 ng/mL). Inflammatory markers were elevated with ESR of 54 mm/hr (n 0-15 mm/hr) and CRP of 12.45 mg/L (n 1-4 mg/L). ANA, RF, anti-CCP, and HLA-B27 were negative. C3 and C4 levels were normal as well. Interferon-gamma release assay was negative. Imaging showed a normal chest X-ray. Brain MRI showed normal pituitary gland and increased scalp skin thickness with cutis verticis gyrata “undulating skin sign.” X-ray of hands and feet showed diffuse periosteal reaction. A diagnosis of pachydermoperiostosis (PDP) was made based on clinical criteria (thickened skin, periosteal reaction, and finger clubbing). PDP is a genetic disorder of prostaglandin metabolism with variable expression and incomplete penetrance. It manifests after puberty and affects males more than females with a 7:1 ratio. PDP has been recently shown to go through an inflammatory phase, in which patients may benefit from immunosuppressants or NSAIDs. PDP should be distinguished from hypertrophic pulmonary osteoarthropathy, thyroid acropachy, and acromegaly. Our patient had a normal chest radiograph and normal hormone levels (TSH, T4, and IGF-1). The patient received topical steroids and antibiotics with artificial tears for his eyes, which resulted in a good response, and was referred to a rheumatology clinic for further management.

Clinical Lesson: PDP can be mistaken for acromegaly or thyroid acropachy and should be considered in any patient with acromegaloid features with normal IGF-1 and no evident pituitary pathology. Awareness of this condition can help in reaching the diagnosis promptly.
Perplexing Infectious Etiology of a Case of Hypopituitarism and Central Diabetes Insipidus
Authors: Hans Amrita
Published: May 2021

Injury to the hypothalamus and both the anterior and posterior components of the pituitary gland is rare, but can result from infiltrative processes such as sarcoidosis, Langerhans cell histiocytosis, granulomatous with polyangiitis, and lymphocytic hypophysitis. Meningitis, pituitary infection, traumatic brain injury, and surgical instrumentation are other etiologies.

A 40 year old man with mild cognitive impairment due to remote meningitis was evaluated for progressive somnolence. He was obtunded and cerebrospinal fluid (CSF) analysis revealed 11 WBC with lymphocytic pleocytosis (90% lymphocytes), highly elevated protein of 588 mg/dL (ref range 12-60 mg/dL), and low glucose of 17 mg/dL (ref range 40-70 mg/dL). MRI Brain revealed basilar meningitis/rhombencephalitis and suspected infectious vasculitis induced right middle cerebral artery territory stroke. Of note, there was substantial T2 hyperintense signaling in the hypothalamus and pituitary areas, which has been reported with tuberculosis (TB), Coccidioidomycosis (Cocci), and the aforementioned etiologies. He received broad antimicrobials, including TB treatment and fluconazole. He developed sinus bradycardia, hypotension, hypoglycemia, and hypothermia. Labs demonstrated inappropriately normal TSH of 1.4 mclU/mL (ref range 0.35-4.94 mclU/mL), low free T4 (fT4) of 0.50 ng/dL (ref range 0.7-1.48 ng/dL) with repeat fT4 undetectably low the following day, and AM cortisol less than 0.5mcg/dL (ref range 4-22 mcg/dL). Levothyroxine and steroids were initiated. He then developed central diabetes insipidus (DI) for which DDAVP was initiated. Comprehensive infectious and autoimmune meningoencephalitis workup was unrevealing. Serum and CSF tests for Listeria PCR, Cocci antibody and antigen, and TB were negative upon multiple, serial checks spanning weeks. CSF analysis one month later showed improvement in protein level (106 mg/dL), but still with elevated WBC (10 WBCs, 98% lymphocytes). MRI one month later demonstrated improvement in edema and the areas of ischemia and vasculitis were less. His adrenal insufficiency and central DI were transient and improved, no longer requiring steroids or DDAVP. He remains on levothyroxine for central hypothyroidism.

The MRI and CSF findings point to an infectious etiology for hypopituitarism and central DI. We suspect an indolent bacteria such as Listeria or a fungus, likely Cocci, or TB meningitis. Cocci seemed to provide a unifying explanation as it classically creates infarcts and causes vasculitis. However, serial CSF tests were negative for Cocci, as well as for TB and Listeria. Marked improvement on follow up MRI also makes TB meningitis less likely as imaging would not resolve so quickly. This is a mysterious case; he improved on broad antimicrobial therapy and is being monitored closely in the outpatient setting.
Perplexing Polyuria Caused by a Rare Disorder
Authors: Wittwer Jennifer Ann
Published: May 2021

Background: Central diabetes insipidus is an uncommon condition characterized by polyuria and polydipsia. In adults, central diabetes insipidus is most commonly caused by a primary brain tumor, followed by idiopathic causes, head trauma, and neurosurgery. The presence of diabetes insipidus is often discovered prior to the underlying culprit and detection may reveal further pituitary dysfunction. Herein an unusual cause of central diabetes insipidus is presented. Case: A 35-year-old male was seen in consultation for polyuria. He initially presented with fevers, cloudy urine, and excess urine output. He indicated frequent water consumption, craving cold water and feeling persistently dehydrated with poor energy levels. During hospitalization, the patient had up to 9 liters of urine output daily, with low urine osmolality and intermittent hypernatremia. As patients’ labs were consistent with central diabetes insipidus a brain MRI was completed and showed a thickened enhancing infundibulum and some fullness of the right pituitary without a focal lesion noted, concerning for autoimmune or inflammatory hypophysitis. Other pituitary axes were evaluated, and patient was noted to have a low morning total testosterone and low IGF-1. Concurrently, the patient was discovered to have multiple bone lesions on an MRI abdomen and pelvis, which prompted a bone scan showing diffuse uptake in osseous structures. A PET scan was then obtained demonstrating mandibular uptake as well as hypermetabolic activity in both adrenal glands, the right iliac bone, bilateral femurs and humeri. Biopsy of the mandibular lesion was performed, and the specimen revealed chronic xanthogranulomatous and lymphocytic inflammation consistent with a diagnosis of Erdheim-Chester disease. The patient was discharged on desmopressin and a biologic agent for treatment of Erdheim-Chester disease. Clinical Lesson: Erdheim-Chester disease is a rare non-Langerhans histiocytic multisystem disorder that often presents with skeletal, neurologic, endocrine, cutaneous, cardiac and renal abnormalities. There is a slight male predominance of the disorder and diagnosis occurs between the 5th and 7th decade of life. Erdheim-Chester disease is a form of histiocytosis with a histologic hallmark of xanthomatous infiltration of tissues by CD68-positive foamy histiocytes. This case reflects the diagnostic delay often associated with the condition. Early identification is essential to organize a multidisciplinary team to ensure accurate diagnosis and to initiate appropriate therapy. Presently interferon-alpha is the first line treatment, but other biologics are often used and provide promising outcomes. The presented case highlights many of the idiosyncrasies associated with this rare disorder and calls attention to the possibility of Erdheim-Chester disease when an initial cause of central diabetes insipidus is not obvious.
Pituitary Metastasis Presenting With Central Diabetes Insipidus and Panhypopituitarism
Authors: Lee Donna , Kishore Preeti
Published: May 2021

Background: Metastatic involvement of the pituitary gland and infundibular stalk is rare, accounting for about 2% of all diagnosed pituitary masses. Although primary tumors from almost every organ have been reported, breast and lung cancers are the most common primary tumors to metastasize to the pituitary gland. The clinical presentation varies and can include headache, visual impairment, diabetes insipidus, and panhypopituitarism. The posterior lobe of the pituitary is more susceptible to metastatic involvement than the anterior lobe due to its direct blood supply from the systemic circulation, whereas the anterior lobe is supplied by the hypophyseal portal system. Additionally, the smaller posterior lobe can be destroyed with less metastatic volume, allowing for earlier manifestation of symptoms.

Clinical Case: An 81-year-old woman with a history of Stage IIA ER+ IDC of the left breast status post lumpectomy and axillary lymph node dissection in 1999 followed by mastectomy in 2009 due to local recurrence presented with confusion for two weeks. At the time, she had known lung metastases and was on palliative chemotherapy. CT head showed a 1.8 cm and 2.3 cm calvarial lytic lesion in the right occipital bone and at the vertex, respectively. MRI brain/pituitary revealed a well-circumscribed, enhancing suprasellar mass measuring 9 x 10 mm likely involving the pituitary infundibulum and hypothalamus with mass effect on the optic chiasm. Laboratory results were consistent with secondary adrenal insufficiency, central hypothyroidism, and hypogonadotropic hypogonadism. Prolactin was mildly elevated due to stalk effect. The patient also had hypernatremia and inappropriately low urine osmolality, which nearly tripled after administration of desmopressin, confirming central diabetes insipidus. She was subsequently started on hydrocortisone, levothyroxine, and desmopressin.

Laboratory Results: Prolactin 30.47 (reference range 4.79-23.3 mIU/mL), IGF-1 88 (17-193 ng/mL), 7am ACTH 3.4 (7.2-63.3 pg/mL), 7am cortisol 0.6 (6.2-29 µg/dL), TSH 3.03 (0.47-6.9 U/L), FT4 0.351 (0.75-2 ng/dL), FSH 0.2 (25.8-134.8 mIU/mL), LH <0.1 (7.7-58.5 mIU/mL), estradiol <5 (5-138 pg/mL); before desmopressin: Na 154 (reference range 135-145 mEq/L), urine osm 162 (50-1,200 mOsm/kg); after desmopressin: Na 143 (reference range 135-145 mEq/L), urine osm 469 (50-1,200 mOsm/kg)

Conclusion: While pituitary metastases remain rare, their prevalence is expected to increase due to more sensitive biochemical tests and imaging techniques coupled with advances in cancer therapy that help patients with metastatic disease live longer. Interesting in our case is the patient’s age, which is significantly older than the median age reported in the literature, and her presentation with total anterior and posterior pituitary insufficiency after a prolonged oncologic course marked by progression of disease.
Pituitary Stalk Interruption Syndrome in a 40-Year-Old Female With Absent Uterus and Ovaries
Authors: Aribon Pamela Ann T , Kawaji Leslie Daphne R , Ramos Freyja Diana A , Cating-Cabral Monica Therese B
Published: May 2021

Background: A patient with multiple pituitary hormone deficiencies due to a rare congenital pituitary defect also presented with an absent uterus and ovaries. Coexisting Müllerian agenesis was suspected, however hormone replacement unraveled a different story.

Case Presentation: A 40-year-old female presented with generalized body weakness and euvolemic hyponatremia. She also had cold intolerance, constipation, primary amenorrhea and dyspareunia. As a child, she was worked up for short stature but was lost to follow up. Physical examination showed Tanner stage 1 breast and pubic hair, and absence of axillary hair. She had no facial anomalies, visual abnormalities or anosmia. Hormone panel was consistent with panhypopituitarism: ACTH 5.69 pg/mL (<46 pg/mL), cortisol 1.9 ug/dL (4.30-22.40 μg/dL), TSH 3.375 uIU/mL (0.55-4.78 uIU/mL), FT4 0.51 ng/dL (0.55-4.78 uIU/mL), FT3 1.79 pg/mL (2.30-4.20 pg/mL), LH <0.07 mIU/mL (1.9-12.5 mIU/mL), FSH 0.95 mIU/mL (2.5-10.2 mIU/mL) and IGF-1 40.8 ng/dL (109-284 ng/mL). Bone age was delayed (16-year-old) but with most ossification centers fused. Pituitary MRI showed hypoplastic anterior pituitary, ectopic posterior pituitary and absent pituitary stalk suggestive of Pituitary Stalk Interruption Syndrome (PSIS). Low estradiol 19.35 pg/mL (19.5-144.2 pg/mL) in the setting of low LH and FSH was compatible with hypogonadotrophic hypogonadism. She had female-range serum testosterone level <0.007 ng/mL (0.1209-0.5946 ng/mL) and karyotype of 46XX. Transvaginal ultrasound revealed a blind vaginal pouch with absent uterus, fallopian tubes and ovaries; hence Müllerian agenesis was also considered. Hormonal replacement with prednisone, levothyroxine and conjugated equine estrogen was started. Secondary osteoporosis was treated with alendronate, calcium and vitamin D on top of estrogen therapy. Six months after initiation of estrogen, there was appearance of a small anteverted uterus and atrophic right ovary. Müllerian agenesis was ruled out and hypogonadotropic hypogonadism was proved to be the cause of the initial absence of the uterus and ovaries on imaging.

Conclusion: Increased awareness of PSIS is important since early and accurate diagnosis is crucial for timely initiation of hormone replacement. This case also demonstrates the need for reassessment after hormonal replacement in patients with severe estrogen deficiency and apparent Müllerian agenesis.
Polyuria in a Patient With a Pituitary Mass
Authors: Naha Sowjanya , Parimi Joseph Theressa Nehu , Gundluru Rajani , Liu John Chen , Syed Hasan , Gusov Timur
Published: May 2021

Background: Hypocortisolism can develop in patients with a pituitary mass because of hypopituitarism and is appropriately managed with steroid replacement. However, these patients often have co-existing endocrine derangements that can become clinically evident after administration of steroids. Clinical Case: A sixty-year-old Caucasian female with known non-small cell lung cancer on chemoimmunotherapy was admitted for management of an enlarging suprasellar mass. Her symptoms included nausea, vomiting and multiple syncopal episodes over the preceding three weeks. At the time of admission, physical examination was unremarkable. She was noted to be hypotensive with systolic blood pressure in the high 70s and was treated with intravenous fluids. Laboratory evaluation showed low random cortisol (0.99 ug/dL, n: 0.4-22.6 ug/dL), undetectable ACTH (<5 pg/mL, n: 7.2-63 pg/mL), low free thyroxine (1.01 ug/dL, n: 0.93-1.7 ug/dL), low free T3 (1.6 pg/mL, n: 2-4.4 pg/mL) and low TSH (0.023 ug/dL, n: 0.27-4.2 ug/dL), consistent with central hypothyroidism and secondary adrenal insufficiency. Importantly, she was normonatremic and normokalemic at admission. She was started on stress dose hydrocortisone (100 mg IV q8h) for presumed adrenal crisis. Following institution of steroid replacement therapy, the patient rapidly became polyuric while simultaneously developing hypernatremia. Her daily urine output peaked at 4400 mL corresponding temporally to a maximum serum sodium of 160 mmol/L. A single dose of 0.5 mg of desmopressin resulted in immediate lowering of daily urine output to 750 mL and appropriate improvement in urine osmolality from 147 mOsm/kg to 565 mOsm/kg, confirming a diagnosis of central diabetes insipidus (cDI). Conclusion: Hypocortisolism is known to impair free water excretion by stimulating arginine vasopressin (AVP) secretion through renal sodium loss and consequent volume depletion as well as direct feedback stimulation of corticotrophin releasing hormone (CRH) and AVP within the hypothalamus. Conversely steroid replacement leads to loss of feedback stimulation, unmasking cDI. This unique convergence of cDI with hypocortisolism is most often encountered in patients with hypopituitarism. Hence patients with secondary adrenal insufficiency should be carefully monitored for cDI after initiation of steroid replacement therapy.
Prolactinoma in Two Brothers - Unidentified Genetic Cause Versus Co-Incidence?
Authors: Gundluru Rajani , Liu John Chen , Parimi Joseph Theressa Nehu , Naha Sowjanya , Gusov Timur , Syed Hasan
Published: May 2021

Background: Most prolactinomas occur sporadically. Familial prolactinomas are uncommon. Clinical Case(s): A 35 YO male with no significant past medical history presented to endocrine clinic with c/o fatigue, decreased libido, and erectile dysfunction. Labs showed low total testosterone of 177 ng/dl (normal range 250-1100 ng/dl), low free testosterone of 19.9 pg/ml (normal range 46-224), low LH 1.1 (normal range 1.5-9.3 mIU/ml) with elevated prolactin of 47 ng/ml (normal range 2-18). MRI pituitary showed a 4.2x4x6 mm pituitary microadenoma. Physical exam was unremarkable except for obese body habitus. No known family history of MEN syndromes or parathyroid /calcium disorders. Dopamine agonist therapy resulted in significant improvement in testosterone levels, fatigue, and libido. One year after patient’s diagnosis his 32 YO younger brother was evaluated for c/o fatigue, inability to lose weight, left breast enlargement, galactorrhea, and decreased libido. Work up showed markedly elevated prolactin levels of 2405 ng/ml (normal range 4-15), decreased total testosterone of 70 ng/dl (normal range 249-836), low free testosterone of 4.8 pg/ml (normal range 8.7 to 25.1), FSH <0.1 mIU/ml (normal range 1.4-15.4), LH < 0.1 mIU/ml (normal range 1.7-8.6). MRI Pituitary showed a 25x28x20 mm pituitary macroadenoma invading the right cavernous sinus, encasing the right internal carotid artery, and abutting the optic chiasma. Our patient had genetic testing done for sequencing and deletion/duplication analysis of MEN1 and AIP (Aryl hydrocarbon receptor interacting protein) genes—two well identified causes of familial pituitary adenomas—and tested negative for both. His brother was treated with dopamine agonists with marked improvement in Prolactin to undetectable levels within a few weeks. His energy levels, headaches, and sexual function improved and galactorrhea resolved. However, testosterone levels remained below normal range even after 11 months, despite normal prolactin levels. Discussion: Prolactinomas are the most common functional pituitary adenomas, majority of them sporadic. Familial pituitary adenomas in non-syndromic form are rare. Familial isolated pituitary adenoma (FIPA) and Multiple endocrine neoplasia type 1(MEN 1) are two main causes of familial pituitary adenomas. In FIPA, pituitary adenomas occur as a result of mutations or deletions in aryl hydrocarbon receptor interacting protein gene (AIP). Identifying these mutations is important as pituitary adenomas in FIPA tend to be more aggressive, present at a younger age and are resistant to treatment. Our patient tested negative for both MEN 1 and AIP gene mutations. Whether our patient has an unidentified genetic cause or whether it was a coincidence that two brothers have prolactinomas is unclear.
Pulmonary Embolism in Adipsic DI: Can Desmopressin Be a Contributing Factor?
Authors: Campos-Lopes Sara , Monteiro Ana Margarida , Marques Olinda
Published: May 2021

Background: Adipsic DI (ADI) is a rare disease associated with various morbidities. One of them is venous thromboembolism (VTE). In literature there are less than 10 reported cases and scarce management orientations. Classically, in ADI, VTE risk is due to dehydration and acute hypernatremia. Desmopressin should also be considered as it has a known role in blood coagulation such as increasing platelet cohesion and promoting von Willebrand factor release. Clinical Case: A 51-year woman with past medical history of obesity class 3 and a craniopharyngioma surgically intervened 8 months before, underwent a second craniotomy due to recurrent lesion. Postoperatively the patient developed an ADI, hypopituitarism and impairement of higher brain functions namely short-term memory and sleep-wake cycles impairment. She was discharged on desmopressin 0.35mg/day, levetiracetam 1500mg/day, hidrocortisone 15mg/day, levothyroxine 75mcg/day and quetiapine 25mg/day. Two weeks after discharge, the patient was admitted to the emergency room with anorexia and malaise. Tests were consistent with PE: elevated D-dimmer levels and CT angiography revealing bilateral PE. Treatment with enoxaparin was initiated. There was no hemoconcentration or polycythemia; kidney and liver function were normal, and sodium of 148 mEq/L (135-145 mEq/L). Three days before she had normal sodium levels. Respiratory insufficiency, deep vein thrombosis and infection were excluded. The patient did not present signs of dehydration. Brain CT did not show acute alterations. There was no personal history of smoking or family history of thrombosis and the patient was not on bed rest in the previous couple of weeks. During hospital stay abdominal and pelvic CT did not reveal malignancies. The patient was discharged on enoxaparin and posteriorly underwent a mammogram and colonoscopy; both exams without relevant alterations. At the last follow-up visit, she remained hypocoagulated and with desmopressin, with no further episodes of thrombosis. Conclusion: We report for the first time a case of PE in an obese patient with ADI treated with desmopressin and without overt hypernatremia or dehydration. All previously published cases of VTE in ADI have occurred in patients presenting with moderate to severe hypernatremia (sodium 157-181 mEq/L) and some degree of dehydration at the time of the event. Obesity and a recent hospitalization may have contributed to the development of VTE but desmopressin should also be taken into consideration due to its known effects on coagulation. Thromboprophylactic treatment after pituitary surgery and during acute episodes of hypernatremia and dehydration is already warranted in ADI but we additionally suggest considering at least short-term thromboprophylaxis in obese patients with recent ADI diagnosis treated with desmopressin as they might have this additional increased thrombotic risk.
Rathke’s Cyst and Adrenal Insufficiency: A Rare Case of Hyponatremia
Authors: Sen Ranjoy , Geerthan Kalaichelvi , Kapoor Ashutosh
Published: May 2021

Background: Hyponatremia is the most common electrolyte abnormality encountered in clinical practice, the diagnosis of which can be challenging. A holistic approach with appropriate investigations is imperative to its diagnosis and management. We report this peculiar case of a patient with hypopituitarism secondary to Rathke’s cyst resulting in secondary Adrenal Insufficiency, thus causing Hyponatremia.

Case Details: A 32 year male was admitted to hospital with an intractable headache and deterioration in his general wellbeing. His admission parameters revealed a GCS of 15 with normal observations. He had no evidence of meningism and examination of all other systems was unremarkable. He was not on any regular medications and there was no history of trauma. Bloods revealed a Sodium of 122mmol/l, the rest being normal. Investigations including a CT brain, CXR, paired serum & urine osmolality, urinary sodium, Thyroid functions and a 9am cortisol were conducted. Radiological imaging was unremarkable. Subsequently, he was fluid restricted due to a euvolemic fluid status.

Serum osmolality was 246 mmol/kg (275-295 mmol/kg), Urine osmolality 847 mmol/kg, urine sodium 85 mmol/l and a 9 am serum cortisol of 29 nmol/L, in keeping with Adrenal Insufficiency.

A further decline in his Sodium to 116 mmol/L resulted in Hyponatremic Encephalopathy. In view of impending Adrenal crisis, IV hydrocortisone was commenced in conjunction with hypertonic Saline. This was followed by strict monitoring with cautious correction. An anterior Pituitary profile, serum testosterone and Prolactin were requested.

Serum Testosterone levels were 0.4nmol/L (10.0-36nmol/L), FSH- 2.5 IU/L (1.0-11.0 IU/L) and LH- 1.9 IU/L (1.5-9.3 IU/L). Serum prolactin was 85mU/L (45-375 mU/L), TSH- 0.59 mU/L (0.30-6.00 mU/L), Free T4- 13.0 pmol/L (10.4-24.5 pmol/L), IGF1-135 ug/L (60-197 ug/L).

This was suggestive of partial hypopituitarism. An MRI Pituitary revealed appearances in keeping with a Rathke’s cyst occupying the pituitary fossa without compromise of the Optic Chiasma.

Once stable, he was safely discharged with follow-up appointments planned with the Endocrine and Neurosurgical teams.

Discussion: Rathke cleft cysts are non-neoplastic cysts arising from the embryological remnants of Rathke’s pouch in the pituitary gland. Hormonal and visual manifestations can occur if these cysts enlarge and interfere with the Pituitary production and optic chiasma. A proposed mechanism causing Hyponatremia in the context of Cortisol deficiency is increased hypothalamic secretion of Corticotropin releasing hormone (CRH), a Vasopressin secretagogue. Cortisol feeds back negatively on CRH, which is removed with adrenal insufficiency. Hyponatremia is thus often seen in patients with adrenal insufficiency, caused by an inappropriate increase in vasopressin due to cortisol deficiency and inability to excrete free water.
Reduced Visual Field Activity Due to Covid-19 in a Patient With a Pituitary Macroadenoma
Authors: Rosner Matthew Norman , Aridi Ribal Al
Published: May 2021

Background: Vision changes can be the presenting symptom of pituitary macroadenomas. The first-line therapy is transsphenoidal resection except for macroprolactinomas where medical therapy with dopamine agonist (DA) is the initial treatment of choice. Surgical resection is reserved if treatment with DA did not result in decreased serum prolactin (PRL), size of adenoma and/or alleviation of symptoms. With the Covid-19 pandemic, there have been a variety of symptoms reported including ophthalmic manifestations (1). We will present how an acute decrease in vision from Covid-19 nearly led to surgical intervention of macroprolactinoma.

Clinical Case: A 61-year-old woman presented to the emergency room (ER) with complaints of headache in 6/2020. MRI Brain showed a 4.0 x 4.0 x 4.5 cm pituitary macroadenoma with suprasellar extension and invasion of the cavernous sinuses. The mass engulfed the adjacent circle of Willis, the MCAs bilaterally, the PCAs and the superior aspect of the vertebrobasilar system. Initial PRL was 7441 ng/mL (5.2-26.25 ng/mL). She was discharged on Cabergoline 0.25 mg twice weekly. Visual field exam showed mild nonspecific field defects in the right eye and larger diffuse field defects in the left eye slightly more temporal. One month later, Cabergoline dose was increased to 0.5 mg twice weekly with PRL drop to 1161.7 ng/mL. In 8/2020, she started to complain of worsening vision. Ophthalmological exam showed worsening visual fields in both eyes and the optic discs showed temporal pallor. She was referred to ER where she tested positive for Covid-19 and was admitted. CT Head showed stable partially calcified enhancing sellar and suprasellar mass. Repeat PRL was 635.6 ng/mL. Despite reduction in PRL, transsphenoidal resection was considered but was deferred to 9/2020 due to Covid-19. Follow up appointment with Neuro-ophthalmology in 9/2020 prior to scheduled surgery, showed visual field improvement with just mild nonspecific defects and surgery was canceled. PRL in 10/2020 decreased to 239.1 ng/mL. Patient’s visual fields continued to improve after recovery from Covid-19 and with reduction in PRL. It was determined that the patient’s reduction in visual fields was due to Covid-19 and not her macroadenoma.

Conclusion: There have not been many reported cases of decreased visual fields due to Covid-19 (1). Proposed mechanisms include expression of ACE-2 receptors in the aqueous humor, which is the main receptor for Covid-19, and thromboembolic disease (1). More studies and data are needed to conclude the mechanism of decreased visual fields. This will avoid unnecessary surgical interventions for patients with macroprolactinomas.

References: 1. Ho, D., Low, R., Tong, L., et al. COVID-19 and the Ocular Surface: A Review of Transmission and Manifestations. Ocul Immunol Inflamm. 2020 Jul 3;28(5):726-734.
Remitting Seronegative Symmetrical Synovitis With Subsequent IgA Hypergammaglobulinemia. A Case of Chronic Inflammation Causing Macroprolactinemia and a Misdiagnosis
Authors: Zarghamravanbakhsh Paria , Sanchez Jose Gonzalo
Published: May 2021

Prolactin is a pituitary hormone that functions in breast development and milk production in women and also plays an important role in immunoregulation and human immune responses, including autoimmune diseases. Macroprolactin, known as “big-big prolactin”, is due to the presence of marked hyperprolactinemia associated with evidence of prolactin-Ig (typically IgG4 or less frequently IgA) circulating complexes. We describes a case of 51 year-old female, with more than a 4 year history of reported hyperprolcatinemia who was treated with Cabergoline 0.5 mg weekly. Prior to treatment, she reported menses every 30-40 days, but denied galactorrhea or symptoms of sellar mass effect. Our patient had mildly elevated prolactin levels of 40-50 ng/dl. Her Thyroid function test were within normal limits. Patient had two pituitary MRIs in 2017 and 2019 which did not show sellar abnormalities. Prior to cabergolibe initiation, she was diagnosed with RS3PE syndrome (Remitting seronegative symmetrical synovitis with pitting edema) due to bilateral swelling in the dorsum of her hands. She was found to have hypergammaglobulinemia which was related to IgA elevation from chronic inflammation. Further investigation showed actual bio-active monomeric prolactin level was normal (4.8 ng/dl) and macroprolactin elevation from hypergammagolbulinemia. Before diagnosing her paraproteinemia and her macroprolactin predominance, she had received years of dopamine agonist therapy which was discontinued after diagnosis.

We report a novel association of IgA predominant hypergammaglobulinemia from a chronic rheumatologic condition, leading to a misdiagnosed hyperprolcatinemia. Care should be taken to determine monomeric Prolactin levels prior to treatment, specially when symptoms are equivocal and/or imaging studies are negative.
Tolvaptan Use in SIAD (Syndrome of Inappropriate Antidiuresis)
Authors: Burri Sushma , Parthasarathy Sathish Babu
Published: May 2021

Background: SIAD (Syndrome of Inappropriate Antidiuresis) is the commonest cause of hyponatraemia in hospital inpatients. Hyponatraemia is associated with increased length of stay and worse primary clinical outcomes. Our study aimed to evaluate the effectiveness of Tolvaptan, a selective, non-peptide, Vasopressin receptor antagonist, treatment in hospitalised patients with SIAD. Method and Baseline Characteristics: A Retrospective analysis of 9 patients treated with Tolvaptan for a confirmed diagnosis of SIAD was carried out. Information was collected from the inpatient records and biochemical test results. Serum Sodium levels on admission ranged between 104- 124mmol/ L (Normal range 136 -145 mmol/L). Average inpatient days solely due to hyponatraemia was 24 days. The number of in-patient days on fluid restriction ranged from 8-22 days depending on timing of referral to endocrine department. Tolvaptan was only started at a stable serum sodium at 118 mmol/L or greater. Four patients also had a prior trial of demeclocycline. Tolvaptan was started at its smallest dose of 7.5mg OD under strict monitoring of serum sodium with locally agreed protocol. Aetiology of SIAD included lung malignancy, acute demyelinating polyneuropathy, listeria meningitis, autoimmune encephalitis, SSRI (Selective Serotonin Reuptake inhibitor) use, Aspergillosis and Idiopathic (n=3). Results: Serum sodium level improved to >128 mmol/L in 2 days of starting Tolvaptan in all cases. After discharge, there was remote virtual clinic monitoring from the endocrinology team at 2 weeks, 4- 6 weeks and 3 months with a view to stop the medication. No adverse events were observed during use of Tolvaptan in the patient population. Tolvaptan 7.5mg OD was either stopped completely after 4-6 weeks or switched to 7.5mg alternate days depending on the clinical course of underlying pathology. Average duration of Tolvaptan treatment was 4.5 months excluding one patient with chronic lung pathology. 3 patients had further hospital admission on stopping Tolvaptan treatment and treatment with Tolvaptan had to be re-initiated. Conclusion: This study confirms the efficacy of Tolvaptan use in SIAD related hyponatremia. Tolvaptan serves as a cost effective treatment option for hospitalised patients who have either failed to respond to demeclocycline or fluid restriction. In our case cohorts, cost comparison of Low dose Tolvaptan with retrospective calculation of total inpatient days of fluid restriction and use of demeclocycline showed a better outcome and clinical effectiveness with low dose Tolvaptan. We recommend earlier use of Tolvaptan in SIAD under guidance from specialist team as a safe, cost effective and in some cases, as a hospital admission-avoidance strategy.
Underappreciation of the “Hook Effect” leading to Mismanagement of a Patient, a Tale of Preventable Disaster
Authors: Amini Mehdia , Kaur Harsimranjit , Kang Mandip , Naing Soe
Published: May 2021

Introduction: When evaluating pituitary adenomas, one needs to be cognizant of the “hook effect” - an assay artifact leading to under-reporting of extremely high prolactin levels. We report a case of a patient with a macroprolactinoma with an initial reported prolactin level of less than 1.0 ng/dl. Such an extreme case of the “hook effect” in a prolactinoma has not been reported yet.

Case Presentation: A 53-year-old male with a medical history of type II DM initially presented in 2017 with blurred vision. Vital signs and labs, including pituitary hormone levels, were all within normal range. Prolactin level was reported as less than 1.0 ng/dl (normal 2-18 ng/dl). MRI brain showed a large pituitary mass and he was diagnosed with a non-secreting pituitary macroadenoma with mass effect. The patient subsequently underwent transsphenoidal resection of the pituitary adenoma. Prolactin level was noted to be elevated at 1608 ng/dl after the procedure. Unfortunately, the patient was lost to follow up. Two years later, the patient presented again with persistent headaches and worsening vision. MRI brain revealed a large suprasellar mass, measuring at 4.9 x 4 x 3 cm, with extension into the third ventricle and left cavernous sinus, indicating a recurrence of the pituitary adenoma. Prolactin levels measured were elevated 12,030 ng/dl. At this time, the patient was started on cabergoline with significant improvement in symptoms and reduction in prolactin levels to 1792 ng/dl within 4 weeks after initiation of therapy. He is currently still in remission with weekly cabergoline therapy. Conclusion: The most used prolactin assay typically reports the presence of detectable heterotrimeric immune complex formations made up of prolactin antigens sandwiched between ‘capture antibodies‘ at one end and ‘reported antibodies’ at the other end of the prolactin antigen. In prolactinomas, prolactin levels are usually present in relative excess to the two assay antibodies. This leads to the oversaturation of antibody sites with most of prolactin being complexed to only a single antibody instead of two antibodies, thus impairing adequate immune complex formation. Only a few remaining prolactin antigen are “sandwiched” to form the heterotrimeric complex and are therefore reported as “detectable.” As a result, true prolactin levels are substantially underreported, potentially leading to incorrect diagnosis, treatment delay, exposure to surgical risk and complications and increased economic burden to the patient and the healthcare system. The best method to avoid the “hook effect” and to correctly interpret prolactin values would be to obtain prolactin levels in appropriately diluted serum specimens (10-100-fold dilution of the sample). This will lead to appropriate immune complex formations and increase the sensitivity and specificity of the prolactin assay.
A Clinical Audit on Diagnosis and Management of Hypopituitarism in Scarborough General Hospital
Authors: Abraham Santhosh , Ssemmondo Emmanuel , Abobaker Anis , Humphriss David , Pawlak Tadeusz
Published: May 2021

Objectives: The main objective was to evaluate the use and compliance to the guidelines issued by the Endocrine Society in diagnosis and management of hypopituitarism and their impact on the clinical practice in Scarborough General Hospital (SGH). Design: A retrospective review of secondary data of patients with a diagnosis of hypopituitarism in SGH. Methodology: The data was collected from both patients’ case notes and electronic medical records. Data analysis was performed using Microsoft excel. Results: 18 patients with the diagnosis of Hypopituitarism were identified. 5 patients were females and 13 were males. 11 patients aged between 60-80 years, 4 patients were between 51-60 years and 3 patients were between 31-50 years. All the patients had low cortisol levels; however, cortisol was checked at 9AM in only 4 patients. All the patients had their thyroid stimulating hormone levels checked, which were low in all of them. Free T4 levels were normal in 2 patients, and low in 16 patients. 17 patients had low follicular stimulating hormone levels, whereas 15 had low luteinising hormone levels. Testosterone levels were checked in 9 male patients out of which 7 had low levels. Insulin-like growth factor-1(IGF1) was done in all patients and levels were low in 10 patients. All those with low IGF1 had glucagon stimulation test. Serum sodium levels were low in 3 patients and high in 5 patients. Plasma osmolality was only checked in 8 patients (was high in 5 patients). Urine osmolality was checked in 10 patients, and it was low in 5 patients. Brain MRI was performed in 16 patients, and 2 patients had brain CT. The most common cause of hypopituitarism was non-functioning pituitary adenoma (44.4%), and the least common causes were empty Sella syndrome (5.6%) and craniopharyngioma (5.6%). All patients received glucocorticoid replacement therapy, 17 received thyroid hormone replacement therapy, 8 received testosterone replacement therapy, 3 received desmopressin (DDAVP) treatment, and one patient received growth hormone replacement therapy. Conclusion: This Audit shows that our practice in diagnosis and management of hypopituitarism is mostly in line with the recommendation of the Endocrine Society. However, cortisol levels were not always measured at 9:00 am and we are not compliant with performing Growth Hormone stimulation test in every patient.
Copeptin Levels Before and After Transsphenoidal Surgery for Cushing Disease: A Potential Marker of Remission
Authors: Flippo Chelsi L , Tatsi Christina , Sinaii Ninet , Sierra Maria de la Luz , Belyavskaya Elena , Lysikatos-Lyssikatos Charalampos , Keil Margaret , Scientist Nurse , Spanakis Elias , Stratakis Constantine A
Published: May 2021

Objectives: Chronic hypercortisolemia suppresses AVP secretion. Copeptin makes up the C-terminal portion of the AVP precursor pre-pro-AVP, is released in stoichiometric amounts with AVP, and is a stable surrogate marker of AVP.A post-operative increase in plasma copeptin was hypothesized to be a marker of remission of Cushing Disease (CD).

Methods: Plasma copeptin was obtained in patients with CD before and daily in the first week after transsphenoidal surgery (TSS), measured using the Brahm Kryptor Compact PLUS sandwich immunofluorescent assay. Urine output, serum sodium, urine specific gravity, and urine/serum osmolality were used to determine development of central diabetes insipidus (DI) and/or syndrome of inappropriate anti-diuretic hormone secretion (SIADH). Change in copeptin reflects pre-TSS to peak post-TSS copeptin levels. Statistical analyses were completed using non-parametric tests. Results are presented as median (inter-quartile range).

Results: Forty-four patients (64% female, 7-55 years old) were included. After TSS, 8 (18%) developed DI, 13 (30%) developed SIADH, 4 (9%) developed both DI and SIADH, and 19 (43%) developed neither. Thirty-three patients had a follow-up at 3-6 months. Overall, there was no difference in peak post-TSS copeptin for patients in remission versus those not in remission [6.1 pmol/L (4.3-12.1) vs. 7.3 pmol/L (5.4-8.4), p=0.88]. There was, also, no difference in the copeptin change for those in remission versus not in remission [2.3 pmol/L (-0.5-8.2) vs. 0.1 pmol/L (-0.1-2.2), p=0.46]. When we excluded patients who developed a water balance disorder postoperatively, there was a difference in peak post-TSS copeptin for those in remission [10.2 pmol/L (6.9-21.0)] vs. those not in remission [5.4 pmol/L (4.6-7.3), p=0.032], but not in the change in copeptin for those in remission vs. not in remission [5.1 pmol/L (0.3-19.5) vs. 1.1 pmol/L (-0.1-2.2), p=0.39].

Conclusions: Post-TSS plasma copeptin may be a useful early marker to predict remission of CD after TSS. However, the utility of this test may be limited to those who do not develop water balance disorders post-operatively. Additional studies with larger sample sizes are needed to confirm these findings and to determine a post-operative plasma copeptin cutoff level that may predict remission of CD.