ResearchPad - case-reports-in-unusual-pathologies-in-the-pituitary Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[MON-256 A Late-Onset Case of Sheehan’s Syndrome Presenting as Life Threatening Adrenal Insufficiency]]> OBJECTIVE

Sheehan’s syndrome or postpartum pituitary necrosis, is an important but rare cause of hypopituitarism, caused due to severe postpartum hemorrhage. Seen more commonly in the developing world, it is less common in developed countries due to advanced obstetric practices. It can present acutely but more frequently has an insidious course (onset 10-20 years later) with variable hormonal deficiencies. Here, we report a late-onset case of Sheehan’s syndrome, 24 years after the incident event, presenting as life threatening adrenal failure.


A 48-year-old female with no significant past medical history was admitted to the hospital after being found unresponsive at home. She had not seen a physician for many years. She complained of weakness and lethargy for a week and recently established care with a primary care physician. The patient was severely hypotensive in the emergency department and had an elevated temperature of 101°F. Physical examination showed no significant abnormalities. CBC and metabolic panel were not significantly altered. CSF analysis and CSF/blood cultures were negative for any infection. TSH was 4.29 mIU/mL (0.27-4.20) but the total and free T4 (fT4) were severely low at 1.1 mcg/mL (4.6-12) and 0.24 ng/dL (0.93-1.70) respectively. On further questioning, patient reported severe postpartum hemorrhage 24 years ago, needing multiple units of blood transfusion. This was followed by inability to lactate and menstruate but was never worked up as she had not seen any physician all these years. Pituitary hormonal panel was obtained, demonstrating multiple hormonal deficiencies with fT4 severely low at 0.24 ng/dL, ACTH of 2.6 pg/mL (7.2-63.3), prolactin (PRL) 1 ng/mL (4.8-23.3) and insulin like growth factor-1 (IGF-1) low at 10 ng/mL (56-194). Cortisol level was elevated in the hospital due to administration of high dose IV steroids but a morning cortisol level obtained 1 week prior by her primary was 1.5 mcg/dL (10-20). Estradiol levels were low with FSH and LH levels inappropriately normal. MRI of the pituitary was obtained which showed an empty sella turcica. Patient was diagnosed as late-onset Sheehan’s syndrome. She was started on hormone replacement with hydrocortisone followed by levothyroxine and had marked improvement in her symptoms. She continues to do well.


Our patient presented late due to lack of medical care and awareness. A great number of patients with Sheehan’s diseasae go undiagnosed due to subtle clinical presentations, thus delaying treatment. It is imperative to diagnose this condition timely with appropriate obstetric/gynecological history and clinical suspicion to avoid late manifestations of the disease, especially adrenal crisis. Patients at risk need long term follow-up. Early treatment is necessary to improve quality of life and reduce morbidity and mortality associated with this condition.

<![CDATA[SUN-288 Atypical Teratoid Rhabdoid Tumor of the Sellar Region: An Unusual Cause of Hypopituitarism]]> Background: Atypical teratoid/rhabdoid (AT/RT) tumor of the sellar region is an extremely rare malignant tumor in adults. To date, there are no definitive guidelines for optimal treatment and the prognosis of this tumor is poor. The pituitary insufficiency was rarely mentioned in previous literature and might be overlooked.

Clinical case: A 43 years old female presented to our clinic with severe periorbital pain. The magnetic resonance imaging of the brain revealed a 1.5x1.5x 3 cm sellar mass which showed inhomogeneous enhancement after gadolinium administration. Hormonal work up showed 8AM cortisol of 1.86 mcg/dL, free T4 1.0 (0.8–1.8 ng/dL), TSH 0.05 (0.3 - 4.1 uIU/ml), FSH 6.0 (1.6–9.3 IU/L), LH 1.8 (2.4–9.3 IU/L), estradiol <18.35 (80–790 pmole/L), IGF-1 96.6 (50.6–263.7 ng/ml), prolactin 56.6 ng/ml.

She underwent transsphenoidal surgery with tumor removal. The pathological result showed a mixture of pleomorphic spindle cell, oval shape tumor and poorly differentiated cell. The tumor was negative for INI1 (SMARCB1) compatible with AT/RT WHO grade IV. She developed pan hypopituitarism after surgery. She received 6 courses of 5950 cGy/25 fractions cranial irradiation and 6 courses of ifosfamide, cisplatin and etoposide. She completed the treatment regimen without significant toxicity. She continued hormonal replacement for panhypopituitarism and is still being followed at our clinic for 4 years without tumor progression or other complications.

In previously reported cases, all of the sellar AT/RT were female with a median age of 45 years old (range 20–61). The clinical presentations are rapidly enlarged sellar mass with compressive symptoms to the adjacent structures. The radiological findings of sellar AT/RT are non-specific. The diagnosis is based on histopathological findings. Presence of rhabdoid cells on histopathology and polyphenotypic immunopositivity for epithelial, mesenchymal, and neuroectodermal markers along with loss of expression of SMARCB1/INI1 help in establishing a diagnosis of AT/RT.

Currently, there are no definitive guidelines for optimal treatment. Multimodality treatment consisted of surgery, radiation and chemotherapy are the mainstays of treatment of the AT/RT. Of the 16 adults reported in the literature, 9 patients survived more than 12 months resulted in 47% of one-year survival rate. To our knowledge, this case is the sellar AT/RT with the longest survival to date.

Conclusion: AT/RT is one of the most aggressive tumors in the sellar area. Due to its aggressiveness, hypopituitarism is anticipated. Our patient had postoperative secondary adrenal insufficiency, secondary hypothyroid and hypogonadotropic hypogonadism. Apart from multimodality treatment required for tumor control, pituitary hormones should be evaluated preoperatively to prevent perioperative mortality and long-term improvement in the quality of life.

<![CDATA[SUN-290 Pituitary Hyperplasia Due to Uncontrolled Primary Hypothyroidism: Case Series and Literature Review]]> Background: Pituitary hyperplasia secondary to primary hypothyroidism results from the loss of thyroxine feedback inhibition and the subsequent overproduction of TSH.

Case 1: A 18-year-old female presented with a chronic history of spontaneous galactorrhea, headache and malaise. Autoimmune primary hypothyroidism was diagnosed, with elevated TSH of 490 mIU/L (0.3-5) and low fT4 of 0.33 ng/dL (0.63-1.34). Pituitary MRI showed an enlarged pituitary with compression of the optic chiasm. Hormonal replacement with levothyroxine 75 mcg qd was started. Five months later she was asymptomatic, and normal TSH (1.64 mIU/L) and fT4 (0.9 ng/dL) levels. A new MRI revealed normal size of pituitary gland, with no compression of the optic chiasm and an intact infundibulum.

Case 2: A 24-year-old female with type 1 diabetes and autoimmune primary hypothyroidism, presented with a five-year history of galactorrhea and oligomenorrhea. She was treated with insulin glargine 20U qd, and levothyroxine 200 mcg/day. However, patient’s adherence was bad. She consulted a primary health physician who suspected a prolactinoma after high prolactin levels (77.65, normal 2.64-13.13 ng/mL). Cabergoline was started without any clinical improvement. She then was referred to our service for follow-up. TSH results showed 500 mIU/L, with low fT4 (0.08 ng/dL). Prolactin levels was normal. Pituitary MRI revealed diffuse enlargement of the gland, with compression of infundibulum and optic chiasm. Treatment was modified to levothyroxine/liothyronine 100/20mcg 1 ½ tablet qd. After 7 months, we confirmed normal TSH (0.76 mIU/L) and fT4 (1.23 ng/dL), and the patient was asymptomatic. After 17 months, new MRI showed normal pituitary gland without any compression.

Case 3: A 23-year-old female with a history of Addison′s disease and hypothyroidism diagnosed at age 17 presented with a 6-month history of somnolence, fatigue, headache and amenorrhea. She was previously treated with hydrocortisone 25mg/day, fludrocortisone 0.1mg/day, and levothyroxine 200mcg/day. Patient’s adherence was bad, and multiple hospitalizations because of adrenal crises were reported. Her initial hormonal evaluation revealed high TSH of 460 mIU/L and low fT4 of 0.25 ng/dL, mild hyperprolactinemia (32.16 ng/mL), and very high ACTH levels (2,700 pg/mL, normal 10-100). Pituitary MRI revealed an enlarged pituitary with mild compression of the optic chiasm. Hormonal replacement was modified to fasting levothyroxine alternating 200mcg and 300mcg qd. Her last follow-up showed normal TSH (0.53 mIU/L) and fT4 (1.18 ng/dL) levels. New MRI showed normal pituitary size

Conclusion: We presented three young women, with autoimmune hypothyroidism, who developed pituitary hyperplasia and responded to proper hormonal replacement normalizing pituitary size.

Reference: Endocrinol Diabetes Metab Case Rep. 2015; 2015: 150056.

<![CDATA[MON-257 Axenfeld Rieger Syndrome: An Uncommon Cause of Growth Hormone Deficiency]]> Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder presenting with abnormal eye development, which leads to glaucoma related blindness in 50% of individuals. Associated mutations affect the transcription factors pituitary homeobox 2 gene (PITX2) and forkhead box C1 gene (FOXC1). Three types of ARS have been described. PITX2 mutation causes ARS type I, which is associated to systemic malformations, including dental hypoplasia, redundant periumbilical skin, and growth hormone deficiency (GHD).

This is the case of a 28-year-old male diagnosed with GHD during childhood. He was referred to a pediatric-endocrinologist at age 10 due to short stature. Evaluation showed a height-for-age curve below the 10th percentile. Physical examination with prominent forehead, decrease visual acuity, maxillary hypodontia, umbilical hernia, and delayed sexual maturity. Testing with reduced IGF-1 and delayed bone age. Clonidine GH stimulation confirmed the diagnosis of GDH. He was treated with somatropin, until linear growth decreased to ½ inch per year at age 16. GHD etiology was never established. At age 26, he developed progressive decrease in visual acuity. Ophthalmology evaluation disclosed polycoria, megalocornea and increase intraocular pressure, suggestive of ARS. Patient was referred to our endocrinology clinics for follow up of previous diagnosis of GHD. Based on clinical findings and history, sequence analysis and deletion/duplication testing of FOXC1, PAX6 and PITx2 were performed, with results positive for pathogenic variant PITX2, Exon 5, c.363_364delinsAA. Assessment of pituitary hormone axis was normal, and no persistent GHD found. No family members exhibited clinical signs of ARS.

Axenfeld-Rieger syndrome is a rare genetic disease. PITX homeodomain transcription factors are critical for the development of the anterior segment of the eye and pituitary. Most mutations in PITX2 affect DNA binding and transactivation that leads to defects in cell proliferation and differentiation of the Rathke’s pouch. As a result, GHD may ensue. ARS patients are usually diagnosed during childhood after the development of vision abnormalities. The diagnosis remains primarily clinical upon identification of ocular abnormalities in the iris and cornea, and increased intraocular pressure. Systemic changes are rare findings in ARS, but may include face and tooth abnormalities and isolated growth hormone deficiency. Genetic diagnosis is based on identification of mutations. An adequate management of ARS requires a multidisciplinary approach. Although ophthalmologists usually diagnose this condition, some patients initially present with isolated growth impairment. This may lead to a delay in ophthalmologic evaluation and management. Thus, in patients with GHD of unknown etiology, it is important to have a high index of suspicion of ARS in order to decrease morbidity from vision loss.

<![CDATA[SUN-286 Lymphocytic Hypophysitis Mimicking Tolosa Hunt Syndrome]]> Introduction:

Lymphocytic hypophysitis often presents with headache, hypopituitarism and visual disturbance, the latter from optic nerve compression. Rarely, it can present with diplopia from cranial nerves III, IV and VI (3.7%) and cavernous sinus involvement (1).

Clinical Case:

A 40 year old woman presented with left eye pain, blurry vision, ptosis and diplopia for 2 days, preceded by headache for 2 weeks. Exam was remarkable for left eye ptosis, mild proptosis, downward and outward gaze and inability to adduct her left eye. Endocrinological exam revealed free T4 0.67 ng/dL (Nl 0.70 - 1.48), TSH 0.67 ng/dL (Nl 0.70–1.48), estradiol <10 pg/mL, LH 1.0 mIU/mL, FSH 6.9 mIU/mL, prolactin 23.3 ng/ml (Nl 5.2–26.5) and IGF-1 95 ng/mL (Nl 52–328). Cortisol was not assessed as patient was already on steroids. Work-up revealed atypical ANCA (1:320) but normal C-ANA (<1:20), P-ANCA (<1:20), and the rest of immune work-up was negative including ACE, ESR, CRP, ANA, serine protease and myeloperoxidase. No systemic manifestations were present concerning for systemic autoimmune disease. CSF exam was unrevealing including a normal ACE level. MRI revealed an enlarged pituitary gland with suprasellar extension containing a focal area of T2 hyperintensity and slight T2 hypointensity at the posterior aspect of the gland. There was a midline, thickened infundibulum, enhancement of both cavernous sinuses and narrowing of right internal carotid artery without occlusion. Endoscopic endonasal transsphenoidal biopsy of pituitary lesion confirmed diagnosis of lymphocytic hypophysitis and did not meet criteria for IgG4 hypophysitis. After 4 weeks of prednisone, she had significant symptomatic improvement and repeat MRI showed decreased pituitary size but persistent abnormal enhancement of the pituitary gland and cavernous sinuses.


The atypical and variable clinical and radiological findings of lymphocytic hypophysitis can mimic other inflammatory, infiltrative lesions, pituitary tumor with apoplexy and Tolosa Hunt Syndrome. Tolosa Hunt syndrome is an idiopathic granulomatous inflammation of the cavernous sinus involving cranial nerves II to VI and often presenting with painful ophthalmoplegia. Pituitary involvement and carotid artery narrowing have been observed (2). Our case highlights a patient with cranial nerve III palsy and significant cavernous sinus involvement, clinically concerning for Tolosa Hunt syndrome, but confirmed by biopsy to be lymphocytic hypophysitis. There are no specific serum markers to distinguish lymphocytic hypophysitis from other entities and when uncertain, diagnosis is best established by biopsy.


1 Caturegli P, et al. Autoimmune hypophysitis. Endocr Rev 2005, 26: 599–614.

2 A. Kambe et al. A case of Tolosa-Hunt syndrome affecting both cavernous sinuses and hypophysis and associated C3 and C4 aneurysms. Surgical Neurology 65 (2006) 304–307.

<![CDATA[MON-261 Pituitary Abscess Presenting as Pituitary Macroadenoma Causing Hypopituitarism and Acute Meningitis; A Wolf in Sheep’s Clothing]]> Background: Pituitary abscess (PA) is a rare but life-threatening cause of suprasellar (SS) lesion and pituitary hormonal deficiencies with an incidence of 0.2% - 1.1%. Clinical Case: A 65‐year woman with history of transient ischemic attacks, presented with double vision for 3 months (mon) and sudden onset, severe headache. She was diagnosed with cranial nerve (CN) VI palsy. MRI brain showed 1.7 cm SS mass suggestive of pituitary macroadenoma abutting optic chiasm. Visual field testing was unreliable due to underlying visual defects. She had progressive improvement in her diplopia. She was referred to Endocrinology for worsening fatigue. Physical exam was unremarkable. Pituitary hormonal work up showed secondary hypothyroidism with TSH 1.17 mIU/L (0.4-4.5), free T4 0.6 ng/dL (0.8-1.8); hypogonadotropic hypogonadism with FSH 12 mIU/ml (23-116.3), LH 1.7 mIU/ml (10-54.7), estradiol <15 (<31); elevated prolactin due to stalk affect with prolactin level of 83.3 ng/mL (3-30). She had normal IGF-1 of 154 ng/mL (41-279), ACTH 12 pg/mL (6-50), cortisol 14.1 mcg/dL (4-22) and mildly low sodium 134 mmol/L (135-146). Levothyroxine 50 mcg daily was started. The MRI brain at 2 mon and 6 mon follow up showed stable 1.8 cm peripherally enhancing SS mass. She was planned for elective pituitary adenoma resection but prior to that that was emergently admitted to ICU with high grade fever, confusion, seizures, severe hyponatremia with sodium of 122 mmol/L (135-146) and a concern for meningitis. She had a dental crown placed 3 weeks ago. MRI brain showed increase in size of the cystic component of SS mass. She was started on empiric IV antibiotics and high dose steroids. She underwent trans-sphenoidal surgery (TSS), and actually found to have a pituitary abscess. Gram stain of purulent material was positive for neutrophils. Pathology showed pituitary gland with focal infarct and surrounding acute on chronic inflammation and fibrosis. The intra-operative abscess cultures grew Cutibacterium (Proprionibacterium) acnes. She is planned to receive 6 weeks of IV antibiotics. Conclusion: We present a case of pituitary abscess presenting as a SS mass causing hypopituitarism. It was presumed pituitary macroadenoma due to the sub-acute onset and lack of progression. She developed acute deterioration in sensorium leading to concern for meningitis and PA requiring timely diagnosis and management with trans-sphenoidal resection and IV antibiotics. Definitive diagnosis of PA is usually made post-operatively. 60% of patients with PA and new onset hypopituitarism may require long term hormone replacement. References: 1. Agyei JO, Lipinski LJ, Leonardo J. Case Report of a Primary Pituitary Abscess and Systematic Literature Review of Pituitary Abscess with a Focus on Patient Outcomes. World Neurosurg. 2017 May;101:76-92

<![CDATA[MON-253 A Rare Case of Pituitary Aspergillosis Diagnosed by CSF PCR in an Immunocompetent Patient with Headaches and Photophobia]]> Background: Pituitary aspergillosis is a rare infection usually found in the immunocompromised population. It is oftentimes mistaken for a pituitary adenoma based on similar clinical presentation and characteristic findings on MRI. Most cases require removal of the pituitary mass in order to make a diagnosis. Here we present the case of an immunocompetent patient with headaches and photophobia diagnosed with pituitary aspergillosis by CSF PCR and treated medically with voriconazole.

Clinical Case: A 40-year-old woman with a questionable history of Brucellosis presented with a 3 month history of headaches along with 2 days of nausea and vomiting. Vital signs were notable for intermittent hypotension but were otherwise within normal limits. Physical exam was notable for tenderness at the left temporal region, diaphoresis and photophobia. Patient was otherwise alert and oriented and had no visual field deficits or extraocular muscle dysfunction.

Patient was found to have central adrenal insufficiency with undetectable AM cortisol (<0.5 mcg/dL, n 3.7-19.4 mcg/dL), inappropriately normal ACTH (7 pg/mL, n 6-58 pg/mL) and central hypothyroidism with low TSH (0.057 mcIU/mL, n 0.358-3.8 mcIU/mL) and low free T4 (0.48 ng/dL, n 0.76-1.46 ng/dL). Patient initially presented with hyponatremia (Na 119 mmol/L, n 137-145 mmol/L) likely secondary to central adrenal insufficiency and central hypothyroidism. Gadolinium-enhanced pituitary MRI showed a heterogeneous 1.8 cm pituitary mass with rim enhancement concerning for hypophysitis.

Patient was started on stress-dose steroids with IV hydrocortisone 100 mg IV q8h, levothyroxine 50 mcg PO daily and empiric antibiotic therapy with ceftriaxone, doxycycline and rifampin due to suspicion for neurobrucellosis. Lumbar puncture was obtained showing low glucose (39 mg/dL, n 40-70 mg/dL), normal protein (47 mg/dL, n 12-60 mg/dL) and an elevated white count (WBC 9/mcL, n 0-5/mcL) with lymphocyte predominance (97% lymphocytes, n 40-80%). Blood and CSF cultures showed no growth at 2 weeks. CSF was sent for multiplex PCR which came back positive for Aspergillus.

Patient was discharged with voriconazole 300 mg PO BID for 1 year, levothyroxine 75 mcg PO daily and hydrocortisone 10 mg PO Qam and 5 mg PO Qpm. Three months later, repeat MRI showed resolution of the pituitary mass and patient felt well without headaches, nausea or vomiting.

Conclusion: This case demonstrates an atypical example of pituitary aspergillosis diagnosed without pituitary mass biopsy and treated medically with voriconazole. It demonstrates the possible role of CSF PCR to diagnose the condition and guide antifungal treatment.

<![CDATA[SUN-274 Pituitary Macroadenoma Treated with Peptide Receptor Radionuclide Therapy in a Patient with Common Variable Immunodeficiency - Case Report]]> Background: Nonfunctional adenomas comprise 25-35% of all pituitary tumors, 70-90% of these are gonadatroph cell adenomas. While ‘silent’ adenoma is the most common type of pituitary macroadenoma. The incidence of silent adenomas is estimated at 22/100000. Common Variable Immune Deficiency (CVID) is the most common primary immune disorder which is associated with neoplasia, mostly of the lymphatic or digestive system. We present probably the first case report of gonadotropinoma in a patient with CVID, treated with PRRT.

Clinical Case:

A 45-year-old man has been a patient at the Endocrinology Clinic for 12 years. Aged 33 years, he was diagnosed with a common variable immunodeficiency. The human immunoglobulin treatment was included. He also suffered from severe, spreading headaches. MRI of the head was performed. A 45mm tumor was found in the sella turcica, spreading to the sphenoid sinus. The tumor was slipped into the epidural reservois and both cavernous sinuses, causing compression of the internal carotid arteries and compressed the optic chiasm. Laboratory tests were as follows: TSH 2.18uIU/ml, LH 4.26mIU/ml, FSH 9.76 mIU/ml, ACTH 25.88pg/ml, PRL 18.34 ng/ml, HGH 3.9uU/ml, normal plasma and urine osmolality. So, the silent pituitary macroadenoma was diagnosed. Endoscopic transsphenoidal incomplete tumor resection was performed. The operation was complicated by massive parenchymal bleeding. Histopatological examination confirmed presence of pituitary adenoma, and immunohistochemical positive staining also of FSH (+), subunit alpha (+), TSH (+/-). A Ki67 proliferation index was 1%. After 12 months endoscopic reoperation was performed. The extent of operation was larger but not total. After 12 month the tumor mass increased (50x50x45mm). Imaging of somatostatin receptors by SPECT-CT was performed. It showed a heterogeneous radiolabel accumulation in the pituitary tumor. In 2010, 2 doses of 200mCi 90-Y-DOTATATE were administered with good effect. Tumor size was reduced to 20x23x25mm. The patient has had no headache for that time. Since 2011 he has also been treated with octreotide30 mg/month, with good therapy tolerance.


This is probably the first description of a 12-year history of complicated but successful treatment of pituitary silent macroadenoma. It was also probably the first use of PRRT in the pituitary tumor with excellent effect. The patient remains in a very good condition, without neurological symptoms and no disorders of pituitary function.

<![CDATA[MON-260 Sinonasal Papilloma Masquerading as a Pituitary Macroadenoma]]> Background: Sinonasal tumors are rare, with annual worldwide incidence of approximately 1 in 100,000, and are not commonly considered in the differential diagnosis of pituitary tumors (1). Sinonasal tumors are well known for their invasiveness, tendency to recur and association with malignancy. We present a case of sinonasal papilloma presenting as a large suprasellar mass.

Clinical Case: A 61 year-old male with a past medical history including type 2 diabetes mellitus presented with chief complaints of headaches and visual disturbances over the past 6 months. Prior to admission he experienced episodes of left eye midline deviation associated with diplopia. New onset dysphagia associated with leftward tongue deviation prompted him to seek medical attention. The social history was notable for chemical exposures in his work at a hair salon; he is sexually active with his husband. He has had no sexually transmitted infections and has been vaccinated against human papilloma virus (HPV). CT of the brain showed a large sellar mass.

A subsequent MRI of the pituitary demonstrated a large destructive mass centered on the clivus elevating the pituitary gland into the suprasellar cistern. The mass measured 6 cm x 4.5 cm in the axial plane with displacement without invasion of the cavernous sinuses. The mass extended anteriorly into the ethmoid sinuses and extended posteriorly into the prepontine cistern displacing the basilar artery.

Pituitary hormonal analysis included a 250 mcg Cosyntropin stimulation test resulting with a random cortisol of <1.0 ug/dl rising to 17.7 ug/dl following Cosyntropin administration. Additional anterior pituitary results included FSH of 3.8 mIU/ml (1.5-14 mIU/ml), LH of 1.3 mIU/ml (1.4-7.7 mIU/ml), total testosterone of 230 ng/dl (300-700 ng/dl), and prolactin 11.1 ng/ml (2.6-13 ng/ml).

Ophthalmology was consulted for visual field testing which proved normal, however a partial left cranial nerve VI palsy was noted likely secondary to cavernous sinus involvement. A biopsy of the sellar mass was obtained by bedside nasal endoscopy. The initial biopsy was consistent with a non-dysplastic, inverted sinonasal papilloma with negative HPV and P16 serologies. The patient underwent resection of the pituitary mass, with surgical pathology showing superficially invasive squamous cell carcinoma arising from sinonasal papilloma.

Conclusion: This is one of the very few cases reported in the literature of a sinonasal papilloma masquerading as a pituitary mass. Sinonasal papilloma should be considered when evaluating large destructive suprasellar tumors. Although a benign tumor, the local aggressiveness of sinonasal papilloma and the potential to give rise to squamous cell carcinoma highlights the significance of identifying this lesion.

<![CDATA[SUN-278 Isolated Hypothalamic Langerhans Cell Histiocytosis in an Adult Manifesting as Panhypopituitarism]]> Background: Langerhans Cell Histiocytosis (LCH) is a rare disease characterized by abnormal proliferation of bone marrow derived histiocytes. Although predominantly a childhood disease, LCH can occur at any age and has an incidence of one to two cases per million in adults. LCH can involve a single organ or present as disseminated disease. Sites most commonly affected are bone, skin, bone marrow and pituitary. Isolated hypothalamic LCH is a rare entity. A few reports of LCH presenting as a hypothalamic mass exist but mainly in children. Treatment of adult LCH is derived from pediatric studies, and no standard of care exists. We report a unique case of an adult with panhypopituitarism secondary to a hypothalamic mass found to be biopsy proven isolated LCH treated with Vemurafenib, a BRAF V600E inhibitor.

Clinical Case: A 66-year-old previously healthy man presented with progressively increasing confusion, cognitive decline and generalized weakness requiring hospital admission. Laboratory evaluation revealed an 8AM cortisol of 2.5 ug/dL (reference [ref] 7.0–25.0 ug/dL), ACTH of 9.3 pg/mL (ref 8–42 pg/mL), TSH of 0.106 uIU/mL (ref 0.35–5.5 uIU/mL), free T4 of 0.67 ug/dL (ref 0.7–1.25 ng/dL), LH <0.2 IU/L (ref 0.5–11 IU/L), FSH 0.6 IU/mL (ref 1–12 IU/L), total testosterone <12 ng/dL (ref 193 - 824 ng/dL), free testosterone <3.3 pg mL (ref 41.7 - 180.2 pg/mL), IGF1 41 ng/mL (ref 33–220 ng/mL) and prolactin of 31.5 ng/mL (ref 3.5–15 ng/mL). Findings were consistent with panhypopituitarism, and he was started on glucocorticoid and levothyroxine replacement therapy. MRI pituitary revealed an 18.1 x 13.8 x 15.8 mm hypothalamic mass with signal intensity alteration in the optic pathway. Patient developed polyuria with a serum sodium of 148 mmol/L (ref 136–145 mmol/L), elevated serum osmolality and low urine osmolality consistent with central DI and was started on oral DDAVP.

The patient underwent right sided neuroendoscopic intraventricular biopsy of hypothalamic mass. Pathology was consistent with LCH with immunohistochemistry staining for CD1a, Langerin and BRAFV600E, with occasional cells staining for CD68, CD163 and S100. Bone marrow biopsy was normal. A NM PET scan revealed a hypermetabolic hypothalamic mass compatible with LCH without evidence of involvement of other sites including the skeletal system. Given histopathologically confirmed BRAF-mutated LCH, treatment with Vemurafenib was initiated. Behavioral changes gradually improved, and repeat MRI brain three months after treatment revealed decrease in size of hypothalamic mass.

Conclusion: Isolated hypothalamic LCH is exceedingly rare. No clear guidelines exist for treatment of LCH in adults. BRAFV600E mutations are found in more than fifty percent of LCH cases and are associated with worse outcomes. This case demonstrates the successful use of targeted BRAF inhibitor therapy in an adult patient with BRAF mutated hypothalamic LCH.

<![CDATA[SUN-291 Presence of Aberrant Adrenocorticotropic Hormone Precursors in Two Cases of McCune- Albright Syndrome]]> Background: McCune-Albright syndrome (MAS) is a rare disorder. MAS is caused by an activating postzygotic somatic mutation in the GNAS, and, is classically defined by the occurrence of fibrous dysplasia (FD), café-au-lait skin macules, and precocious puberty. Autonomous GH and/or PRL production in MAS has been reported. However, there have been no reports of ACTH excess in MAS. Method: Plasma ACTH and serum cortisol (F) levels were assessed using electrochemiluminescence immunoassays (Eclusys ACTHTM and Eclusys Cortisol IITM, respectively; Roche Diagnostics K.K., Tokyo, Japan).Clinical Cases: Case1; 42-year-old man showed craniofacial deformities and suffered from multiple bone fractures. He was diagnosed with FD at the age of 23 years. Café-au-lait macules were found on his back. He had slightly acromegaloid features. He showed no cushingoid features. Pituitary adenoma or hyperplasia was not detected by MRI. The diagnosis of GH excess was confirmed by no suppression of serum GH levels by a 75-g oral glucose tolerance test (nadir GH: 2.34 ng/mL) and an elevated serum IGF-I level (307 ng/mL; normal range: 92-257 ng/mL). The patient was treated with monthly subcutaneous lanreotide injection and then GH excess was well controlled. Basal ACTH and F levels in blood were 40.6-63.4 pg/mL and 8.0-10.5 μg/dL, respectively. The urinary free cortisol (UFC) level was 53 μg/day. Autonomous F excess was excluded by the level of midnight F (1.2 μg/dL) and the level of F (0.2 μg/dL) after a low-dose (1 mg) dexamethasone suppression test (DST). Case2; A 32-year-old man was diagnosed with MAS and gigantism at the Pediatrics Department at the age of 5 years. Treatment of GH excess was well controlled by monthly octreotide depot. He had no acromegaloid features and no cushingoid features. Café-au-lait macules were observed from the left flank to the back. Pituitary adenoma or hyperplasia was not detected by MRI. Basal ACTH and F levels in blood were 35.5-73.1 pg/mL and 7.0-11.7 μg/dL, respectively. The UFC level was 61 μg/day. Autonomous F excess was excluded by the level of F (<0.2 μg/dL) after a low-dose (0.5 mg) DST.Possibility of primary adrenal insufficiency was excluded by ACTH stimulation test and/or insulin tolerance test in both cases. The involvement of 11β-HSD1 by GH excess and PC1/3 deficiency were also excluded. Gel exclusion chromatography was then performed. POMC and pro-ACTH were detected and the aberrant ACTH/normal ACTH ratio was 42% in both cases. Conclusion: This is the first report of the presence of aberrant ACTH precursors, particularly POMC, in MAS. A high ratio of circulating ACTH to F may suggest secretion of inactive ACTH precursors in MAS. Further investigations are required to determine whether GNAS mutations or other mechanisms are involved in the presence of aberrant ACTH precursors in MAS.

<![CDATA[MON-262 A Case of the Suprasellar Atypical Teratoid Rhabdoid Tumor (ATRT) Presenting in an Adult Treated with Intrathecal Chemotherapy]]> Background: Atypical teratoid rhabdoid tumors (ATRTs) are highly malignant tumors that usually present as a posterior fossa mass in children less than 3 years old. Only 38 cases have been reported in adults. They are also typically located in the supratentorial region. In none of the reported cases of suprasellar ATRT in the adult, intrathecal chemotherapy (via ommaya) has been used. Clinical case: A 70-year-old woman presented with a severe headache and magnetic resonance imaging (MRI) revealed a suprasellar mass measuring 2.9 x 2.1 x 3.0 cm. Shortly after her presentation, she developed an acute 3rd nerve palsy, and repeat MRI found dramatic interval growth. A transsphenoidal approach for biopsy/resection was attempted, but the lesion was not accessible via this corridor. She then underwent a right frontotemporal craniotomy and subsequently developed panhypopituitarism, including diabetes insipidus. Pathology revealed poorly differentiated malignant cells. Immunohistochemistry was positive for synaptophysin, Epithelial Membrane Antigen (EMA), Tumor protein p53, and negative for integrase interactor 1 (INI-1 antibody) with loss of expression in tumor nuclei with positive internal control in endothelial cells. These findings confirmed the diagnosis of ATRT. The Ki-67 index was 60% consistent with a highly proliferative tumor. One month later, she developed acute mental status change. Repeat computed tomography, and MRI showed recurrence of the tumor at the same location with new leptomeningeal enhancement involving the left facial nerve. Multimodal treatment was instituted, consisting of intraventricular/intrathecal chemotherapy with etoposide and topotecan plus fractionated external beam cranial irradiation (30 Gy in 10 fractions). She continued to deteriorate, and following consultation with her family, she was transferred to hospice care and died six months following her initial surgery. Conclusion: This is the first case of adult suprasellar ATRT that has been treated with intrathecal chemotherapy. There is no consensus on the best combination of chemotherapy, and often the St. Jude’s protocol used in the treatment of pediatric ATRT is used. In line with the biological behavior reported for this tumor in children and adults in different locations, the tumor was very aggressive, resulting in the patient’s death only after 6 months from the diagnosis despite aggressive surgical and medical treatment. Reference: 1. Athale, U. H., J. Duckworth, I. Odame, and R. Barr. 2009. Childhood atypical teratoid rhabdoid tumor of the central nervous system: a meta‐analysis of observational studies. J. Pediatr. Hematol. Oncol. 31:651-663. 2. Shonka N, Armstrong T (2011) Atypical teratoid/rhabdoid tumors in adults: A case report and treatment-focused review. J Clin Med Res 3: 85-92.

<![CDATA[SUN-272 Significant Response to Temozolomide in Two Aggressively Growing Pituitary Adenomas]]> Introduction: Aggressive atypical pituitary tumors are characterized by invasive growth, recurrence and resistance to standard therapies. We present two female patients with pituitary adenomas in whom multiple other therapies had failed, who presented with significant response to temozolomide. Case presentations: In patient #1 (w, 78y), the diagnosis of macroprolactinoma had been made in a community hospital and dopaminagonistic treatment with bromocriptin had been initiated. After failure to achieve significant tumor reduction under this treatment and persisting visual field disturbances, first transnasal-transphenoidal surgery (TSS) was performed in 07/2011, followed by cabergoline exposure in increasing dose due to failure to control prolactin levels. Repeat TSS and stereotactic radiosurgery were performed in both 2014 and 2018 because of invasive tumor growth and double vision. She was then put on temozolomide. Patient #2 (w, 58y) presented with apoplectic gonadotropinoma in 2013. She also underwent 3 courses of TSS as well as stereotactic radiosurgery because of repeated tumor growth leading to visual field disturbances and double vision. Despite these measures, the tumor could not be controlled and she, as well, was put on temozolomide in 2018. In both cases costs were reimbursed by the patient’s health care insurance and in both the first cycle was conducted with 150 mg/ body surface area (BSA) with escalation to 200 mg/BSA in the second. After only 2 cycles, double vision resolved in both patients and the tumor had shrunk by approximately 20% on MRI in patient #1 and even more in patient #2. In both patients, temozolomide dose was reduced again to 150 mg/BSA due to side effects. Nevertheless, in both patients tumor volume further continued to decrease under therapy. Conclusion: This promising clinical course after exposure to temozolomide with early, significant tumor shrinkage in two heavily pretreated patients with aggressive pituitary adenomas indicates that this therapy can be considered also in older patients and may yield astonishing results. Although temozolomide is increasingly becoming a therapeutic option for those patients whose pituitary tumors are refractory to standard therapies, further research and observance over time of temozolomide therapy in aggressive pituitary adenomas and carcinomas is indicated.

<![CDATA[SUN-283 Lithium Induced Partial Nephrogenic Insipidus: An Unusual Presentation]]> <![CDATA[SUN-276 Pembrolizumab-Induced Secondary Adrenal Insufficiency Presenting as Severe Hyponatremia in an 80-Year-Old Male]]> <![CDATA[SUN-270 The Exploding Pituitary - A Case of Atypical Meningitis]]> <![CDATA[MON-258 Hyperprolactinemia: An Unusual Initial Presenting Manifestation of Multiple Sclerosis]]> <![CDATA[SUN-289 Childhood-Onset, Adamantinomatous Craniopharyngioma and Successful Pregnancy: Results of Kraniopharyngeom 2000/2007]]>


: Hypopituitarism is associated with an increased risk of pregnancy complications, such as abortion, anemia, pregnancy-induced hypertension, placental abruption, premature birth, and postpartum hemorrhage. The advance of assisted reproductive techniques makes it possible to improve the pregnancy rate in hypopituitary patients. Data on female fertility, pregnancy, and outcome of offspring after childhood-onset, adamantinomatous craniopharyngioma (CP) are rare.

: Observational study on pregnancy rate and outcome of offspring after childhood-onset CP in adult, female patients recruited in KRANIOPHARYNGEOM 2000/2007.

: Since 2000, 451 CP patients (223 f / 228 m) have been recruited with high grade of completeness. 263 CP patients (128 f / 135 m) have reached adult age. 6 of 128 adult, female CP patients (5%) reported on 9 pregnancies giving birth to 10 healthy newborns.

: The median age at time of CP diagnosis was 14.9 years. Complete surgical CP resections were achieved in 3 patients. No patient underwent postoperative irradiation. 5 natural pregnancies occurred in 3 CP patients presenting with postoperative normal pituitary function. 4 pregnancies were achieved in 3 CP with hypopituitarism under assisted reproductive techniques (after in median 4.5 cycles, range: 3-6 cycles). Median maternal age at pregnancy was 30 years, ranging from 22 to 41 years. 6 of 10 babies were delivered by caesarean section. Gestational age at delivery was in median 38 weeks, ranging from 34 to 43 weeks; median birth weight was 2,920 gram (range: 2,270-3,520 gram), the rate of preterm delivery (<38 weeks of gestation) was 33%. The rate of breastfeeding was 56%. Enlargements of CP cysts occurred in 2 women during pregnancy. Other severe complications during pregnancy, delivery and postnatal period were not observed.

: Pregnancies after CP are rare (5%) and almost half of the patients (45%) achieved pregnancies after assisted reproductive techniques, which are effective and safe in CP patients. With regard to existing deficiencies of hypothalamic-pituitary axes, close monitoring and care by an experienced reproductive physician is necessary. Furthermore, MRI monitoring especially of CP cysts is recommended during pregnancy. Severe perinatal complications, birth defects, and postnatal morbidity of the mothers and their offspring were not observed. Most CP patients complained about their initial lack of information on potential fertility under assisted reproductive techniques.

<![CDATA[SUN-292 Life-Threatening Hypernatremia in Partial Diabetes Insipidus with Adipsia Due to Cranial Radiation: Diagnostic and Therapeutic Challenges]]>


: Anterior pituitary dysfunction is a known, time and dose dependent effect of cranial radiotherapy but central diabetes insipidus (CDI) has been rarely reported. We present a patient with partial CDI (PCDI) and adipsia, months after subtotal resection and radiation therapy for a large anterior cranial fossa meningioma.

: A 53-year-old woman with history of subtotal resection of a 7 cm meningioma ~2 years ago and radiation therapy (54 Gy, completed 15 months ago), was admitted to the ICU with obtundation, tachycardia (120/min), hypotension (87/52 mmHg, on vasopressors in the first 24 hours), severe hypernatremia (serum Na 170 mmol/L), and acute kidney injury (creatinine 2.11 mg/dL; baseline 1.0 mg/dL). Plasma osmolality (pOSM) was 385 mOsm/kg and urine osmolality (uOSM) was 982 mOsm/kg. MRI brain 3 months ago showed frontal lobe encephalomalacia, residual meningioma at the planum sphenoidale (1.8x3.5x2.8 cm) with cavitary lesion compatible with post-radiation necrosis. After receiving 4 litres (L) isotonic fluids and 5 L hypotonic fluids in the first 38 hours, serum Na was 168 mmol/L, creatinine 1.35 mg/dl and uOSM 386 mOsm/kg. Urine output was 2.6 L on day-1 and 1.9 L during first 7 hours on day-2. After an IV dose of 2 mcg DDAVP, uOSM increased to 784 mOsm/kg, and Na decreased to 164 mmol/L, supporting CDI diagnosis. ACTH stimulation test was normal. Levothyroxine 50 mcg daily was started for central hypothyroidism. By day-6, her mental status returned to baseline (alert only to person). DDAVP dose adjustment was challenging due to frequent fluctuation in her serum Na (130s to 150s), adipsia and urinary incontinence. On day-44, she was discharged on subcutaneous (subQ) DDAVP 0.25 mcg every 36 hours, with a serum Na of 145 mmol/L. She was readmitted 3 days later with serum Na of 164 mmol/L, followed by another prolonged hospitalization complicated by acute kidney injury and popliteal DVT. On day-64, she was discharged to a nursing facility on DDAVP 0.25 mcg subQ twice daily.

: Delayed PCDI with adipsia is an exceedingly rare but challenging complication of cranial radiation therapy. The initial uOSM (twice as high as pOSM) in our case caused a delay in diagnosis. This could reflect enhanced antidiuretic response to low circulating ADH levels, possibly due to lower rate of solute extraction in dehydration, upregulation of ADH receptors due to chronic hormone deficiency, and to a fall in glomerular filtration rate. Decrease in uOSM after hydration could be due to ADH exhaustion.

<![CDATA[SUN-275 A Rare Mutation in the TBX19 Gene Leading to Isolated ACTH Deficiency in Two Siblings]]> 500µg/dl) in a newborn led to the suspicion of THAN (transient hyperammonemia of the newborn). Subsequently, hypoglycemic and salt losing episodes with low cortisol (<0,1 ug/dl) and ACTH (<0,16 pg/ml) levels pointed to ACTH deficiency. Genetic analysis showed a homozygous mutation c.302G>A for p.(Trp101*) in the TBX19 gene (a positive regulator of the transcription of POMC and the terminal differentiation of the corticotrophs), generating a premature stop codon. This mutation has been described only once and very recently by Abali et al (Hormones 18:229; 2019) in a 4 year old girl, but unlike our patients, this girl was obviously unaffected during her neonatal period. All other pituitary axes in our patient were normal, thus congenital isolated ACTH deficiency was the final diagnosis. Hyperammonemia resolved spontaneously and the suspected diagnosis of THAN could be dismissed. Hyperammonemia had probably been due to metabolic stress.After 16 months, a younger brother was born and showed hypoglycemia, hypotension and respiratory infection during his neonatal period. Cortisol and ACTH levels were also very low, thereafter, the same TBX19 mutation was detected.Both brothers were successfully treated with oral hydrocortisone substitution (6–10 mg/sqm/day q8 with increases during stress) and thrive well, except for several infections of the upper respiratory tract in the younger brother. In summary, we report the very rare condition of familial isolated congenital ACTH deficiency with a mutation of TBX19 that has never been described in newborns. Initial presentation may be accompanied by confounding pathological lab findings, while genetic analysis together with extremely low ACTH and cortisol levels confirm the correct diagnosis. ]]>