bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinically Functioning FSH-Secreting Pituitary Adenoma
Authors: AlNasrallah Noor , Almurshed Maryam , Aljenaee Khaled , Hajji Sulaiman 
Published: May 2021

Abstract
Background: Gonadotroph adenomas are the most common type of non-functioning pituitary adenomas. However functioning gonadotroph adenomas are rare with only a few cases reported in literature.
Clinical Case: A 42-year old man was admitted as a case of COVID-19 when an incidental finding of a pituitary gland mass was detected. Upon evaluation, the patient was found to have blurred vision and dizziness since few years, however no history of headache, seizures, visual field deficit were reported, nor clear symptoms related to anterior pituitary hypo- or hyperfunction. Pituitary MRI revealed a pituitary gland mass measuring 30x23x22 mm expanding the pituitary fossa and extending to suprasellar cistern. Initial laboratory investigations revealed low free T3 (1.8 pmol/L, normal: 3.1-6.8 pmol/L) and low free T4 (6.6 pmol/L, normal: 12-22 pmol/L) with normal TSH (3.54 mIU/L, normal: 0.27-4.2 mIU/L), high FSH (31.4 IU/L, normal: 1-18 IU/L), and high total testosterone (50.31 nmol/L, normal 8.3-32.9 nmol/L). Testicular ultrasound showed bilateral enlarged testicles (right testis 38.14 cm3 and left testis 33.38 cm3). Visual Field testing revealed monocular superior temporal defect affecting only the left eye. Patient was treated medically with levothyroxine and hydrocortisone and surgically by minimally invasive transsphenoidal resection of pituitary adenoma. Histopathology assessment confirmed the diagnosis of gonadotroph secreting adenoma, with positive immunostain for FSH. At 6 weeks postoperatively, insulin tolerance test was performed after which hydrocortisone was only prescribed during periods of stress. Anterior pituitary profile was repeated which revealed normalization of free T4 (14.3 pmol/L) and FSH (1.2 IU/L) and decrease in testosterone (0.66 nmol/L). Assessment of visual field revealed marked improvement of previous findings. Pituitary MRI was also repeated with findings of enhancing soft tissue remnants. At 12 weeks postoperatively, anterior pituitary profile revealed normalization of testosterone (11.3 nmol/L). Testicular ultrasound was repeated and showed a marked decrease in testicular volume (right testis 17.93 cm3 and left testis 21.13 cm3).
Conclusion: Functional gonadotroph adenomas are a rare subtype of pituitary adenomas which pose a diagnostic challenge and require meticulous clinical evaluation and multidisciplinary therapeutic approach.
Headache, Pituitary Apoplexy and Diabetes insipidus: Suspect Necrotizing Hypophysitis
Authors: Panthi Sujata , Miles John M , Graves Leland 
Published: May 2021

Abstract
Background: Necrotizing hypophysitis (NH) is an exceedingly rare clinical entity; we found only 5 reported cases in a literature review. CASE: A 34-year-old female with a history of primary hypothyroidism developed a headache, double vision, nausea, vomiting, decrease in appetite, galactorrhea, and weight loss. An MRI of the brain showed a 0.9 cm T2 hyperintense pituitary lesion with features suggestive of cystic degeneration or apoplexy of an adenoma There was effacement of the optic nerve anterior to the optic chiasm. Eye examination revealed optic nerve edema and a cranial nerve VI palsy. Laboratory studies revealed a normal prolactin 20.0 (3.3-26.7 ng/ml), and IGF-1 189 (RR: 66 - 303 ng/ml). The pituitary-adrenal axis and pituitary-gonadal axis appeared intact. After short treatment with dexamethasone, her primary symptom of severe headache improved but she later developed polyuria. The evaluation confirmed diabetes insipidus. Her headache worsened after the completion of the brief course of steroids. After a repeat MRI showed mild interval enlargement of the hypo-enhancing posterior pituitary, she underwent transsphenoidal pituitary tumor surgery. A biopsy showed necrotizing inflammation with foci of acute necrosis accompanied by polymorphonuclear cells. There was no granuloma seen. Special stains were negative for fungal, acid-fast, and bacterial organisms. Laboratory studies revealed negative ANA, negative ANCA, PR-3 Ab, MPO Ab, and anti-TPO Abs. The ACE enzyme was elevated at 85 (RR: 8-53 U/l), but the repeat test was within the normal range. A chest CT was not suggestive of pulmonary sarcoidosis. A post-surgery MRI demonstrated a decrease in pituitary size. Her headache worsened with a reduction in prednisone below 20 mg daily. In order to attempt further reduction in prednisone, azathioprine was started as a steroid-sparing agent. Titration of azathioprine up to 175 mg allowed prednisone to be reduced to the replacement dose of prednisone 5 mg daily. An MRI showed the pituitary mass to be unchanged. DISCUSSION: Hypophysitis is associated with diffuse enlargement and dysfunction of the pituitary gland. This case of NH is of unclear cause. There was no evidence of other inflammatory causes such as sarcoidosis, IgG4-related disease, ANCA-associated vasculitis, or infectious cause. As with typical lymphocytic hypophysitis, NH can present with sudden-onset hypopituitarism, neural compression, diabetes insipidus, and radiologic features of ischemic pituitary apoplexy. Signs and symptoms at diagnosis, as well as pituitary hormone abnormalities, vary on the degree of pituitary involvement. Pituitary adenoma commonly does not cause diabetes Insipidus. Radiologic findings consistent with ischemic pituitary apoplexy coupled with the presence of diabetes insipidus is suggestive of NH. A definitive diagnosis of NH, however, requires histopathology.
Hyponatremia as the Initial Presentation of Evolving Pituitary Apoplexy
Authors: Milosavljevic Jovan , Thomas Asha Mary 
Published: May 2021

Abstract
Pituitary apoplexy (PA) is a known, often under-recognized medical emergency and is characterized by ischemic or hemorrhagic necrosis of the pituitary gland. It is a rare clinical syndrome that occurs in 2-12% of pituitary tumors. Hyponatremia can occur secondary to hypocortisolism (12-40%) or, rarely, to the syndrome inappropriate antidiuretic hormone (ADH) secretion.
We present the case of a 69-year-old man who presented with altered mental status on post-operative day 3 from total knee replacement surgery. Initial testing revealed hyponatremia of 124 mmol/L, low serum osmolality of 266 mOsm/kg, and high urine osmolality of 664 mOsm/kg with urine sodium of 179 mmol/L. Head computerized tomography revealed a sellar mass of 1.8 x 2.4 cm. Initial testing revealed low prolactin (0.7 ng/mL), normal TSH (0.458 mcIU/mL) with borderline low free T4 of 0.72 ng/dL. Morning cortisol was 12.7 mcg/dL with ACTH of 8.5 pg/mL. Cosyntropin stimulation test was done revealing baseline cortisol of 5.8 mcg/dL (at midnight), increasing to 25.8 mcg/dL after 30 minutes and to 30.9 mcg/dL 60 minutes after cosyntropin administration. His sodium and mental status initially improved with fluid restriction and salt tablets, for the assumed syndrome of inappropriate ADH secretion. The patient remained hemodynamically stable. On the fourth day, however, his mental status deteriorated. Magnetic resonance imaging revealed expansion of sella with hyperintense mass 2.2 x 2.0 x 2.8 cm with compression of the optic chiasm. He was given stress dose hydrocortisone and levothyroxine and underwent emergency transsphenoidal resection. Biopsy revealed acute hemorrhage within infarcted adenoma. Postoperatively, both the patient’s sodium and mental status improved significantly and he was discharged to home on hydrocortisone and levothyroxine.
The main clinical concern in the management of PA remains under-diagnosis at presentation. Prognosis is dependent on management during the acute phase. PA can present as hyponatremia even in the absence of overt hypocortisolism, presumably due to inappropriate ADH secretion. Therefore, PA should be considered as one of the differential diagnoses in hemodynamically stable patients with altered mental status and hyponatremia.
Hypopituitarism as an Initial Presentation of Silent Squamous Cell Carcinoma of Lung
Authors: Zin Khin M , Meleis Mostafa , Purewal Tiffany , Holland Soemiwati W , Cheng Jennifer 
Published: May 2021

Abstract
Background: Symptomatic metastasis to the pituitary gland is a rare, life-threatening condition. A better understanding of its clinical presentation could lead to early diagnosis and also improve quality of life. In this unusual case, we present a patient with hypopituitarism as the first manifestation of undiagnosed squamous cell carcinoma of the lung. Clinical Case: A 56-year-old Caucasian female with past medical history of pre-diabetes, hypertension, hyperlipidemia, and a chronic smoker for 40 years presented with recent onset of headache for two weeks and diplopia for three days. Initial CT head was negative but MRI of brain pituitary scan revealed a large heterogeneously enhancing sellar/suprasellar mass (1.5 x 2.8 x 2.4 cm) extending into the prepontine cistern with probable bilateral cavernous sinus invasion and contacting the optic chiasm without significant compression. Physical examination showed left abducens nerve (CN VI) palsy. Lab results showed elevated prolactin at 67.4 ng/ml (normal postmenopausal: 1.8 – 20.3 ng/ml), normal IGF-1 at 136 ng/ml (normal 48- 235 ng/ml), low TSH at 0.129 µIU/ml (normal 0.3 – 4.5 µIU/ml), low normal Free T4 at 0.50 ng/dl (normal 0.5 – 1.26 ng/dl), low ACTH at 5.1 pg/ml (normal 7.2 – 63.3 pg/ml), low am cortisol at 2.6 mcg/dl (normal 8.7 – 22.4 mcg/dl), low FSH at 2.6 mIU/ml (normal postmenopausal 23.0-116.3 mIU/ml) and low LH at 0.2 mIU/ml (normal postmenopausal 15.9 - 54.0 mIU/ml). She subsequently began treatment for hypopituitarism. Given her smoking history and unusual presentation of cranial nerve palsy, a chest x-ray was ordered and revealed a left upper lobe mass. CT chest confirmed the left upper lobe mass (4.0 x 3.3 x 2.9 cm), and biopsy reported poorly differentiated squamous cell carcinoma. Decompression of the pituitary macroadenoma was performed for symptomatic improvement but was complicated with the development of central diabetes insipidus. Pathology report disclosed metastatic pituitary carcinoma, compatible with primary lung carcinoma. Following surgical resection and radiation therapy to the pituitary gland, the patient remains stable and is currently tolerating all treatment. Conclusion: In a patient with occult malignancy, pituitary metastasis is an exceedingly rare and challenging diagnosis that carries a poor prognosis. The purpose of this abstract is to raise clinical suspicion for sellar metastasis in a patient presenting with hypopituitarism and cranial nerve palsy.
Management of Persistent Cushing’s Disease Despite Prior Pituitary Adenoma Resection in a Pregnant Patient
Authors: Leiter Amanda , Shrivastava Raj , Pozharny Yevgeniya , Shah Nirali 
Published: May 2021

Abstract
Introduction: Cushing’s Disease (CD) in pregnancy is a rare, but serious disease that adversely impacts maternal and fetal outcomes. As the sole use of metyrapone in the management of CD has been rarely reported, we describe our experience using it to treat a pregnant patient with pre-existing CD. Clinical Case: The patient is a 29-year-old woman with a history of hypertension (HTN), who was diagnosed with CD a year prior to becoming pregnant based on elevated urinary free cortisol (UFC) 209 ug/24h (Reference Range (RR) 6 - 42), positive 1 mg dexamethasone suppression test, elevated ACTH 61 pg/mL (RR 0-46). and an 8 x 8 x 8 mm pituitary adenoma on magnetic resonance imaging (MRI). She underwent trans-sphenoidal adenoma resection 3 months prior to becoming pregnant; however, was found to have persistent disease based on a repeat MRI showing a residual 8 x 8 x 9 mm adenoma extending into the cavernous sinus and UFC 290 ug/24h. The patient discovered 6 weeks later that she was pregnant. She was referred to endocrinology at 12 weeks’ gestation, where she was experiencing easy bruising and taking labetalol 400 mg twice daily for HTN. UFC was 768 ug/24h and midnight salivary cortisols were 0.175 and 0.625 ug/dL (RR &lt;0.010 - 0.090). Surgery was deemed to be high risk given the proximity of the tumor to the cavernous sinus and likelihood of residual disease. She was started on metyrapone 250 mg twice a day, and was uptitrated to 1000mg three times daily by the time of delivery with a UFC of 120 ug/24h (goal &lt; 150 ug/24h). Her pregnancy was also complicated by diet-controlled gestational diabetes and cervical insufficiency requiring cerclage. Otherwise, her HTN was well controlled on labetolol and she remained normokalemic. The patient was induced at 37 weeks gestation and was given stress dose steroids along with metyrapone. She delivered a healthy baby boy without any complications. Discussion: CD during pregnancy is a rare disease, with the best outcomes in published cases seen with surgical intervention. This case highlights the use of metyrapone, a steroidogenesis inhibitor, as a sole therapy in cases where surgery is deemed to be high risk and unlikely curative due to location of the tumor. While it is effective in reducing cortisol levels, close surveillance of patients is required for worsening HTN, hypokalemia, and potential adrenal insufficiency. Though no fetal adverse events have been reported, the medication does cross the placenta and longterm effects are unknown.
Neuroinfundibulitis: Pituitary Stalk Thickening Presenting as Diabetes Insipidus
Authors: Patel Payal P , Samson Susan Leanne , Rao Sarika 
Published: May 2021

Abstract
Background: Isolated pituitary stalk thickening (PST) from neuroinfundibulitis is a rare entity that requires thorough evaluation of secondary causes and understanding of treatment options.
Clinical Case: A 55-year-old male presented with progressive polyuria and polydipsia over several months. He had no significant head injuries, headache, weight loss, fatigue or inability to exercise. His serum sodium level was 148 (135 - 145 mmol/L) with a serum osmolality 310 (275-305 mOsm/kg), and urine osmolality was 246 (40-1200 mOsm/kg) suggestive of partial diabetes insipidus (DI). A 24-hour urine collection had a volume of 9.2 liters. He had a normal hemoglobin A1c. Hormonal work-up was unremarkable with normal range his prolactin, IGF-1, and a.m. cortisol (19 mcg/dl). He was already on levothyroxine with normal thyroid function tests and negative thyroid antibodies. Water deprivation testing confirmed a diagnosis of central DI and he was started on desmopressin. Magnetic resonance imaging (MRI) of the pituitary demonstrated diffuse PST with T2 hyperintensity and loss of normal T1 hyperintensity (“bright spot”) of the posterior pituitary. Repeat imaging 3 months later showed progressive thickening. He underwent full body positron emission tomography-computerized tomography (PET-CT) which demonstrated increased metabolism of the pituitary stalk, but no other suspicious uptake in other areas. Chest X-ray, tuberculin screen, angiotensin converting enzyme, and calcium were all normal. Patient underwent transsphenoidal stalk biopsy. Pathology demonstrated fibrosis and chronic inflammation without malignancy but otherwise was nondiagnostic. Based on these findings, he was presumed to have neuroinfundibulitis and is being actively followed with MRIs and labs.
Conclusion: Isolated PST is exceedingly rare, especially in adults. The differential diagnosis includes neoplastic (germinomas, lymphoma, metastatic disease), autoimmune, and infiltrative disease (sarcoidosis, histiocytosis). One review of 38 adult patients with central DI and PST showed that almost half had neuroinfundibulitis. Of those, 4 were treated with corticosteroids and 7 were not. All patients showed reduction or resolution of PST on subsequent MRIs indicating that resolution of thickening can be spontaneous without steroid use, and can be followed by MRI and with hormone replacement for deficiencies (1). Because of the rarity of isolated neuroinfundibulitis, it is important that neoplastic and systemic diseases be ruled out in all patients with PST, as in the case of our patient.
1.Devuyst F, Kazakou P, Baleriaux D, Alexopoulou O, Burniat A, Salenave S, et al. Central diabetes insipidus and pituitary stalk thickening in adults: distinction of neoplastic from non-neoplastic lesions. European Journal of Endocrinology. 2020;183(1):95-105.
Olfactory Neuroblastoma: The Adjunctive Role of Somatostatin Agonists After Surgery
Authors: Toral Fernando Pazos , Martino Maria , Duro David Lobo , Rodriguez Isabel Martinez 
Published: May 2021

Abstract
Clinical Case: A 54 years old woman who had a right-sided nasal obstruction, rhinorrhea, and sometimes purulent discharge in 2016. In 2002 she had hyperthyroidism by Graves disease and treated for two years with remission after that. The examination of the nose revealed a dark red bleeding mass filling the area from the right nasal cavity to the nasopharynx. The biochemical and serum hormonal values were in a normal range. Urine 5 -HIIAA was 2,5 mg/24h. MRI T1 and T2-weighted images revealed a mass of 4,1 x 4,2 cm, slightly higher signal in T2 and isointense in T1, that extended into the right nasal cavity and ethmoidal sinus. A biopsy was performed, which revealed neuroendocrine characteristics. Octreotide scan with SPECT showed an intense nasal uptake. Right internal maxillary artery embolization was performed. In the next two days, the tumor was resected through a right lateral rhinotomy. Histopathological examination revealed olfactory neuroblastoma, score low grade, ki67&lt;2%. Positive immunohistochemical staining to CD56, synaptophysin, NSE, GFAP, calretinin, S-100 and chromogranin A, and negative staining to cytokeratins (CKs) (CKAPM, CKBPM, CK8/18), CD99 and Bcl-2. The resection was almost total, with no octreotide scan uptake. The post-MRI revealed a minimal residual lesion. Lanreotide treatment was introduced after surgery; the dose was 120 mg every four weeks the first year and every 8 weeks after that. No secondary effects or biochemical alterations were observed. In 2020 the octreotide scan again revealed nasal uptake showing local recurrence. This local recurrence was treated with surgery, followed by lanreotide 120 mg every 4 weeks. No residual disease has been found afterward. Discussion: A limited number of cases have been reported, but none of them were treated with somatostatin agonists. As in our case, the majority of the ON is slow-progressive and non-secreting. The patients mainly complain of local symptoms such as nasal congestion. Surgery is considered to be the first-line treatment for localized disease. In the case of a close margin of the lesion or a residual tumor, the recommendation was radiotherapy or chemotherapy for more advanced disease. We confirmed that the tumor expressed somatostatin receptors. The octreotide scan has been found helpful in the diagnosis and follow-up. We treated the patient with lanreotide with no progression of the disease for three years. Local recurrence could be treated with surgery, following by lanreotide treatment, no residual disease has been found to date. The somatostatin analogs may be a useful adjuvant therapy for stable disease without evident residual disease after surgery.
Pituitary Apoplexy and Fulminant Liver Failure
Authors: Khan Mehvish , Elias Heather Lisa , Javeed Iqra 
Published: May 2021

Abstract
Pituitary apoplexy is a rare endocrine emergency due to acute infarction or hemorrhage of the pituitary gland. It most often involves an underlying adenoma. Precipitating factors include hypertension, major surgery, coagulopathy, or medications. Fulminant liver disease giving rise to a coagulopathy can lead to an increased risk of hemorrhage into the pituitary. A 20-year-old female was transferred from British Overseas Territory for evaluation of fulminant liver failure after presenting with worsening of longstanding abdominal pain and vomiting. She was taking ciprofloxacin and metronidazole for colitis and Tylenol for pain. She denied alcohol abuse, illicit drugs or herbal supplements. Her blood pressure was 107/72 mmHg and physical exam was notable for jaundice. Labs were significant for Alanine Aminotransferase (ALT) 10277 IU/L (n&lt;35 IU/L), Aspartate aminotransferase (AST) 10886 IU/L (n&lt;40 IU/L), total bilirubin 15 mg/dl (n&lt;1.2 mg/dl), alkaline phosphatase 160 IU/L (n&lt;115 IU/L) and INR 4.9 (n&lt;1.3). She was given 100 mg of methylprednisolone. CT head without contrast (WO) completed prior to transfer showed no abnormal findings. The next day, she reported new onset severe headache and diplopia. Bilateral wrist asterixis and worsening lethargy was noted on exam. Ammonia was 278 umol/L (&lt;n 42 umol/L). CT head WO showed a 0.6 x 0.9 x 1.0 cm hyperdense area in the posterior aspect of pituitary gland concerning for apoplexy. Additional labs showed cortisol 11 ug/dL (n&lt;22 ug/dL), ACTH 2.9 pg/mL (n 7.2-63.3 pg/mL), TSH 0.04 uIU/mL (n 0.3-4.5 uIU/mL), free (F) T4 1.4 ng/dl (n 0.6-1.5 ng/dl), FT3 1.2 ng/dl (n 2.4-4.2 ng/dl), FSH 1.8 mIU/ml (n 3.5-12.5 mIU/ml), LH &lt;0.1 mIU/mL (n 2.4-12.6 mIU/ml), prolactin 49 ng/mL (n 5-23 ng/mL), and IGF-1 141 ng/mL (n 109-372 ng/mL). She was managed conservatively with hydrocortisone for secondary adrenal insufficiency and hypopituitarism. With extensive work up, no underlying cause was found for her fulminant hepatic disease. She underwent a deceased donor liver transplant. Perioperatively, she was given 200 mg methylprednisolone which was subsequently tapered to 5 mg prednisone. Postoperative course was complicated by a new right parietal lobe hemorrhage. There was no change in pituitary hemorrhage size. As her FT4 trended down to 0.6 ng/dl, along with suppressed TSH, she was started on 50 mcg of levothyroxine. Upon discharge, she was advised to follow with an endocrinologist and have her hormones revaluated once the acute phase has resolved. Pituitary apoplexy as a consequence of coagulopathy caused by liver failure has not been described before. Although she was given methylprednisolone which can suppress ACTH for up to 48 hours, ACTH deficiency is the most critical endocrine dysfunction and is present in nearly 70% of cases of pituitary apoplexy. Therefore, urgent treatment of secondary adrenal insufficiency is warranted along with thyroid hormone replacement.