ResearchPad - case-reports-in-classical-and-unusual-causes-of-hypopituitarism https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[MON-238 A Diagnostic “Headache” in a Pregnant Woman with Diabetes Insipidus: Blame the Placenta or the Pituitary?]]> https://www.researchpad.co/article/elastic_article_8754 Background

Diabetes insipidus (DI) occurs in 1/30,000 pregnancies and can be difficult to recognize due to normal peripartum physiology. The most common etiology is excess production of placental vasopressinase, which degrades maternal anti-diuretic hormone. Although rare, hypothalamic and pituitary disorders must also be considered in pregnant patients presenting with DI. We present the case of a pregnant woman presenting with diabetes insipidus and pituitary apoplexy.

Clinical case

We were called to see a 33 year old female with polyuria and polydipsia on post-partum day #2. She had presented to the ED at 29.4 weeks of her 5th pregnancy (G5P4) with an unrelenting headache, nausea, and vomiting for 12 hours. She was tachycardic, hypertensive, and had no focal neurologic deficits. Fetal evaluation was reassuring. Admission labs included serum sodium of 147 mEq/L (n 136-145), serum potassium 2.8 mEq/L (n 3.4-4.4), and urine specific gravity of 1.003 (n 1.005-1.030). Glycemic parameters, renal function, and hepatic function were normal. She remained tachycardic despite vigorous IV fluid administration. Overnight into hospital day #3 she began to have uterine contractions with fetal decelerations, and betamethasone was given. It was noted that she had produced 8L of urine over the preceding 24 hours. Serum sodium was 159 mEq/L with urine osmolality of 78 mOsmol/kg (n 300-900). A presumptive diagnosis of gestational DI was made and 2 mcg of subcutaneous DDAVP was given. Shortly thereafter she delivered a healthy infant. Maternal blood loss was minimal. Over the next 12 hours her urine became concentrated and her serum sodium decreased, but by the next morning she re-developed dilute polyuria.

At the time of our evaluation, her headache had resolved and she had no focal neurologic deficits. She had no apparent signs of glucocorticoid or thyroxine deficiency but had not begun to lactate. Biochemical evaluation included early morning cortisol of 4.6 ug/dL (n 3.5-18.3), TSH 0.46 uIU/mL (n 0.35-4.94), free T4 0.76 ng/dL (n 0.70-1.48), and prolactin 26.6 ng/mL (n 5.2-26.5). Pituitary MRI showed a mildly enlarged gland with central T1 hyperintensity, consistent with apoplexy. A regimen of hydrocortisone and DDAVP was initiated.

Conclusion

Pituitary apoplexy is uncommon during pregnancy but is potentially life-threatening for the mother and fetus if it goes unrecognized. The significant physiologic growth of the pituitary during pregnancy may increase the risk of apoplexy. A severe headache is the most common symptom and may be accompanied by signs of pituitary dysfunction. Although diabetes insipidus is more often caused by placental physiology, pituitary apoplexy must also be considered in a pregnant woman who has concurrent neurologic symptoms.

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<![CDATA[SAT-242 Isolated Adrenocorticotropic Hormone Deficiency Secondary to the PD-1 Inhibitor Pembrolizumab]]> https://www.researchpad.co/article/elastic_article_8678 Background: Immune checkpoint inhibitors (ICI’s) are now indicated in the treatment of several solid tumors and have improved the prognosis of patients with advanced malignancy. The expanded use of ICI’s has led to the rise of otherwise rare autoimmune sequelae. The overall incidence of ICI-induced autoimmune hypophysitis has increased to approximately 10%, but is only estimated to be 0.4% with PD-1 inhibitors specifically (1). Isolated ACTH deficiency from immune checkpoint inhibitors is rare, and very few cases secondary to the PD-1 inhibitor pembrolizumab have thus far been reported.

Clinical Case: A 75-year old woman with history of Stage IV lung adenocarcinoma presented to oncology clinic in July 2019 with progressive weakness, weight loss, and confusion for several weeks. She was found to be hypotensive and dehydrated in the clinic and subsequently was admitted to the hospital. A comprehensive infectious work-up was non-contributory. History revealed that after treatment failure with carboplatin, she was treated with pembrolizumab from January 2017 to June 2019 with excellent response. Laboratory evaluation on admission demonstrated an undetectable AM cortisol level of < 1 ug/dL (n 5-25 ug/dL) with concomitant ACTH < 5pg/mL (Roche cobas, n 7.2-63 pg/mL), consistent with central adrenal insufficiency. Testing of the remainder of the pituitary axis, including TSH (0.83uU/mL, n 0.4-4.6 uU/mL), FSH (34.7 mIU/mL, n <150mIU/mL), LH (12.6mIU/mL, n <60 mIU/mL), and IGF-1 (33ng/mL, n 34-245ng/mL), all returned within normal limits. Further chart review verified that she had not been exposed to any form of glucocorticoids within the past 6 months. MRI brain with contrast demonstrated no obvious pituitary disease. The patient was started on 5mg of prednisone daily, with significant improvement in mental status, appetite, and blood pressure. She was discharged home on maintenance prednisone for adrenal insufficiency due to presumed isolated corticotroph destruction.

Conclusions: Isolated ACTH deficiency is a very rare but potential consequence of pembrolizumab use. It can be especially difficult to diagnose in patients on chemotherapy who are at higher risk for dehydration and failure to thrive. Duration of pembrolizumab therapy should not preclude the diagnosis of isolated ACTH deficiency, as it can occur even as late as 2.5 years into therapy.

Reference: (1) Chang, L., Barroso-Sousa, R., Tolaney S., Hodi F.S., Kaiser, U.B., Min, L. Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints, Endocr Rev. 2019;40;17–65.

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<![CDATA[SAT-240 Hypothalamic Lipoma and Growth Hormone Deficiency]]> https://www.researchpad.co/article/elastic_article_8532 Introduction: Intracranial lipomas are rare, congenital lesions, most often located at the midline. Most hypothalamic lipomas are asymptomatic, but some cases have been associated with precocious puberty, hypothermia, headache and/or obesity.

Case: A 7-year-old boy was referred for short stature, and proved to be partially growth-hormone deficient. Magnetic resonance imaging (MRI) revealed a lipoma in the paramedian hypothalamus. Growth hormone treatment resulted in swift and uncomplicated catch-up growth.

Discussion: The present case appears to be the first to link hypothalamic lipoma to GH deficiency. The neuro-endocrine pathophysiology underpinning this link remains to be explored.

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<![CDATA[SAT-238 Congenital Nephrogenic Diabetes Insipidus with First Presentation as an Adult: A Case Report]]> https://www.researchpad.co/article/elastic_article_6967 Congenital Nephrogenic Diabetes Insipidus with First Presentation as an Adult: A Case Report

Background:

Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited condition, usually presenting during the first year of life. It is characterized by a renal insensitivity to arginine vasopressin. About 90% of patients are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. Females are typically asymptomatic. Here, we report female case of NDI initially presenting and diagnosed in an adult woman.

Clinical Case:

A previously well 47-year-old woman of Italian descent underwent an elective laparoscopic repair of an abdominal hernia. Her medical history included obesity and migraine headaches. She was not taking any medications prior to admission. She had a bowel perforation 6 days after surgery, necessitating an emergency right hemicolectomy and small bowel resection. Upon instituting bowel rest with nil per os (NPO), she developed severe hypernatremia (Na+ 163 mmol/L) with polyuria (>6 L/day) and dilute urine (osmolality 174 mmol/kg). Further inquiry revealed that the patient routinely drank at least 10 L/day of fluids throughout her entire adult life. Her family history was remarkable for polydipsia affecting at least additional six people across three generations (including her son, her mother, 3 maternal uncles and 1 nephew). Following administration of desmopressin 1 ug subcutaneously, her urine remained inappropriately dilute (osmolality 160 mmol/kg) with no significant change in urine output (rate 350 mL/h for 3 hours). Her arginine vasopressin level was detectable (3.2 pmol/L, reference range 0.8–3.5 pmol/L), consistent with nephrogenic diabetes insipidus. Subsequent molecular analysis of the AVPR2 gene, located on chromosome Xq28, confirmed a pathogenic mutation (c.253G>A), consistent with a p.Asp85Asn substitution resulting in decreased binding affinity between the V2 receptor and arginine vasopressin. Thus, X-linked NDI was diagnosed according to the patient’s presentation, compatible family history, and genetic analysis. When she was able to eat and drink ad lib again, a low-salt, low-protein diet along with a trial of a thiazide diuretic were recommended. The patient remained well with 3 years of follow-up.

Conclusion:

The diagnosis of congenital NDI may be delayed until adulthood because of a relatively mild phenotype and compensatory drinking behavior, so that the disorder will not be clinically apparent until a person is deprived of free water. Men and women alike can be affected by this X-linked dominant condition which should be considered in any polyuric, hypernatremic hospitalized patient.

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<![CDATA[MON-237 Primary Pituitary Lymphoma - an Unusual Guest in the Sella!]]> https://www.researchpad.co/article/elastic_article_6742 Background

Primary Pituitary Lymphoma (PPL) is a rare differential diagnosis for a sellar / suprasellar lesion. Less than 40 cases have been reported.

Case presentation

A 75-year old Chinese lady with known subclinical hypothyroidism presented with 3-day history of dull frontal headache, giddiness and diplopia. Incomplete left cranial nerve (CN) III palsy was noted with no other neurological deficit or hemodynamic instability. MRI brain and pituitary showed a T1- and T2 isointense, 2.0 x 1.1 x 1.3 cm enhancing mass arising from the left sellar region, extending to the left sphenoid and cavernous sinuses, displacing the pituitary stalk towards the right, with no optic chiasm compression. There was no imaging evidence of apoplexy.

Evaluation of anterior pituitary hormones revealed hypocortisolism (peak cortisol post 1mcg Synacthen 344 nmol/L, ACTH 3.5 ng/L [10 - 60]), subclinical hypothyroidism (free T4 9.6 pmol/L [8.8 - 14.4], TSH 7.19 mU/L [0.65 - 3.70]), normal prolactin 7.4 ug/L [5.0-27.7], mildly elevated IGF-1 193.7 mcg/L [67.0 - 189.0] with normal GH 1.0 ng/ml, and elevated FSH appropriate for menopause. Glucocorticoid replacement was started.

Though the clinical presentation was not typical of a pituitary macroadenoma, in view of symptomatic improvement and neurological stability, she was conservatively managed with plans for early repeat imaging outpatient.

Patient was readmitted 1 month later for headache and decreased left-sided visual acuity. A complete CN III palsy, and new CN II, IV and VI deficits were noted (orbital apex syndrome). Repeat MRI showed increase in the size of the sellar lesion to 2.6 x 2.1 x 1.3 cm, surrounding the optic nerve and with left cavernous and sphenoid sinus invasion. Again, there was no suggestion of apoplexy. Biopsy of the lesion was performed, and histology was consistent with Diffuse Large B-cell Lymphoma and Grade 3A Follicular Lymphoma with high proliferative index (Ki67 70%). Immunohistochemistry excluded carcinoma, meningioma and pituitary tumor. PET-CT and bone marrow aspirate confirmed the diagnosis of PPL without metastasis.

After 3 cycles of chemotherapy (Methotrexate, Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone), significant decrease in the size of the lesion was noted on repeat MRI. Only mild asymmetric soft tissue thickening remained noticeable over the left sella and cavernous sinus. Cranial nerve deficits had since completely resolved. Glucocorticoid replacement was continued in the meantime while awaiting the completion of chemotherapy.

Conclusion

PPL may present in a similar manner as pituitary apoplexy. Absence of typical imaging characteristics of apoplexy in patients with rapid symptom progression and CN involvement should alert clinicians to consider alternative diagnosis including aggressive neoplastic, inflammatory and infective lesions.

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<![CDATA[MON-235 Mycobacterium Fortuitum Infection Mimicking Sellar Chondrosarcoma in a Non-Immunosuppressed Patient: An Unusual Cause of Hypopituitarism and Oculomotor Nerve Palsy]]> https://www.researchpad.co/article/elastic_article_6667 A 32-year old male patient of central African origin presented with diplopia and left eyelid ptosis. He described a 2-month history of fatigue, weight loss (8 Kg), headaches, diffuse myalgia and night sweats. Clinical examination revealed cavernous sinus syndrome with left eyelid ptosis and weakness of eye adduction. Magnetic resonance imaging of the brain demonstrated a 36 mm mass centered on the left petroclival suture, infiltrating the sella and the pituitary gland, the ipsilateral orbital apex as well as the cavernous sinus bilaterally. The mass showed heterogenous enhancement after gadolinium injection, with elements of central necrosis and was associated with an extensive bone destruction. These radiologic features raised the hypothesis of chondrosarcoma. Chest computed tomography demonstrated multiple lung micro-nodules suspect of metastasis. Laboratory testing of the anterior pituitary function revealed low free-T4 (11 pmol/l, n = 12-22) with normal TSH (0.4 mUI/l, n=0.3-4.2), low total testosterone (1.5 ugr/l, n = 3.3-8.1) with normal LH and FSH and slight hyperprolactinemia (27 ugr/l, n = 4-15). IGF-1, 24-h urinary free cortisol, as well as morning serum cortisol and cortisol after 250 mcg ACTH stimulation test were normal. There was no evidence of diabetes insipidus. Levothyroxine was prescribed. Craniotomy was performed, for left optic nerve decompression and biopsy of the mass. Pathologic examination revealed granulomatous, giganto-cellular and necrotizing inflammation, but no evidence of malignancy. PCR for Mycobacterium tuberculosis complex was negative but Mycobacterium fortuitum was detected in sputum and also confirmed in cerebral biopsy latter. Other causes of granuloma were excluded (brucellosis, cat scratch disease, histoplasmosis, syphilis, coccidioidomycosis, tropical germs etc.). Different causes of immunosuppression (including HIV) were excluded. The patient was treated with amikacin, isoniazid and ciprofloxacin for several months and improved gradually. MRI performed one year later demonstrated significant decrease on the size of the sellar mass (more than 50% of its initial size). Central hypogonadism regressed spontaneously with decrease in tumor size, and normal testosterone levels were achieved at one-year follow-up (7 ugr/l, n = 3.3-8.1). Mycobacterium fortuitum infections of the sella turcica are poorly described in literature in non-immunosuppressed individuals. Although usually not pathogenic, histopathological examination, identification in the CNS lesion and the lungs and response to treatment are convincing evidence of a causal relationship. Differential diagnosis from malignant lesions is challenging and biopsy is necessary in order to establish the cause and offer adequate treatment.

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<![CDATA[MON-242 A Hidden Thirst: Unmasking of Central Diabetes Insipidus]]> https://www.researchpad.co/article/elastic_article_6345 Introduction:

Central diabetes insipidus (CDI) is a common pathology following traumatic brain injury, intracranial operations, medication use, and some infections. This case highlights how CDI can be unmasked when access to free water is restricted.

Case Description:

A 50 yo AAM with history of Down syndrome, hydrocephalus with ventriculo-atrial shunt, and seizure disorder treated with phenytoin, was brought in from home after three back-to-back seizures. EMS was called and intubated the patient in the field. Medical history was significant for ventriculo-peritonal shunt placed shortly after birth with revisions in 2011 and 2016. Revision in 2016 was complicated by infection with klebsiella pneumoniae. He was admitted to NSICU. Shunt evaluation showed no abnormality or obstruction. Lab work on admission at 5 am was significant for low potassium and sodium was normal. Patient was stabilized and extubated later that day. Repeat labs, at 4 pm, showed a sodium of 155 mEq/L with a normal potassium. Urine output was reviewed and significant for greater than 400 cc’s per hour for at least 2 hours. Urine osmoles (264 mOsm/kg, n 50-1200) and serum osmoles (314 mOsm/kg, n 280-295) were consistent with diabetes insipidus (DI). His IV fluid intake during this time was 3 liters bolused on admission followed by continuous fluids at 125 cc’s per hour. On review of systems, patient admitted to polydipsia and polyuria throughout the day for last several years. He reported urinating 2-3 times at night. During an admission 3 years prior for ventriculo-peritoneal shunt revision, serum sodium had risen to 159 mEq/L following his surgery and returned to normal prior to discharge. MRI pituitary during admission was negative for pituitary abnormality. To treat as well as differentiate central versus nephrogenic DI, desmopressin 1mcg IV was given. The patient was allowed to drink to thirst. Urine osmolarity increased from 159 mOsm/kg to 494 mOsm/kg after 2 hours and serum sodium slowly trended down. His urine output and thirst decreased with continued administration of desmopressin. He was discharged on a maintenance dose of 0.1 mg desmopressin twice a day. On follow up in clinic, his sodium has been maintained between 140-145.

Discussion:

This patient with CDI was compensating with large fluid intake daily as an outpatient for at least three years. His risk factors included phenytoin use as well as previous VP shunt occlusion complicated by infection which has been reported to contribute to CDI in other case reports. This case highlighted how CDI can be unmasked when a patient loses access to free water such as with altered mental status or intubation for surgery.

References

1.Central diabetes insipidus: A complication of ventriculoperitoneal shunt malfunction during pregnancy. Goolsby, Lynn et al. American Journal of Obstetrics & Gynecology, Volume 174, Issue 5, 1655-7

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<![CDATA[MON-236 Central Diabetes Insipidus in a Patient with Crohn’s Disease]]> https://www.researchpad.co/article/elastic_article_6323 Unusual Presentation of Central Diabetes Insipidus in a Patient with Crohn’s disease

Introduction

Autoimmune hypophysitis is defined as an inflammatory condition of the pituitary gland of autoimmune etiology that leads to pituitary dysfunction. There are three different histopathological categories of inflammatory hypophysitis including lymphocytic, granulomatous, and xanthomatous hypophysitis. Although, an autoimmune link has been suggested for lymphocytic hypophysitis (LH), the pathogenesis of autoimmune hypophysitis is still incompletely defined. The co-existence of LH and Crohn’s is a rare combination with only a few case reports in the literature.

Case presentation

We present a 39-year-old female with history of Crohn’s disease who presented to the ED with abdominal pain, poor oral intake and headaches. Lab work showed hypernatremia. A neck CT incidentally noted a nodular density along the superior aspect of the pituitary gland. A focused MRI of the pituitary showed abnormal thickening of the pituitary stalk with a prominent and heterogeneous gland. Endocrinology was consulted and on interview patient reported chronic headaches, polyuria and polydipsia for the past year, worsening over the past month. She denied any visual disturbances. Labs showed Na 159, K+ 4.0, serum osmolality 307, urine osmolality 178, specific gravity urine 1.006, cortisol 18, FSH 1.26, LH 0.12, prolactin 55, TSH 1.45 and free T4 0.84. Patient diagnosed with Diabetes Insipidus (DI) from LH and was started on PO desmopressin. Unfortunately, patient continued to have hypernatremia and increased urine output despite increases in the dose and frequency of the oral desmopressin. Given no clinical improvement, decision was made to switch from PO to IV desmopressin considering malabsorption of PO medication in the setting of Crohn’s disease. DI labs including plasma sodium, plasma osmolality, urine osmolality, specific gravity of urine and urine output were closely monitored. Patient’s hypernatremia and increased urine output started to improve with the switch to IV and was ultimately discharged home with intranasal desmopressin.

Discussion

Lymphocytic hypophysitis is a rare disorder predominantly affecting females during the antepartum or postpartum period. This case illustrates the importance of considering its presence in the setting of other autoimmune conditions. It also serves to illustrate the complex management and decision making followed in adjusting the desmopressin formulation in the setting of a malabsorptive disease such as Crohn’s.

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<![CDATA[SAT-241 Pituitary Stalk Interruption Syndrome Presenting as Neonatal Hypotonia]]> https://www.researchpad.co/article/elastic_article_6317 Pituitary stalk interruption syndrome (PSIS) is a rare condition that include congenital anatomic abnormalities of the pituitary gland and hypopituitarism. There is a wide variety of clinical presentation, with the age at presentation encompassing from neonatal period to adulthood and including one or more pituitary hormone deficiencies. In recent literature there is increasing recognition of PSIS presenting in the neonatal period, mostly involving hypoglycemia. Our patient is a full-term male infant who presented in the newborn period with hypotonia and hypothermia. He also had hypoglycemia, which was initially thought to be associated to hyperinsulinism in the context of gestational diabetes. Micropenis was noted on physical exam. As part of the study for hypotonia, serial thyroid function tests were obtained revealing central hypothyroidism. A low dose ACTH stimulation test was performed which revealed adrenal insufficiency. The patient was started on cortisol and thyroid hormone replacement. Brain MRI showed an ectopic neurohypophysis located along the floor of the hypothalamus, a small anterior pituitary gland, and a partially absent infundibulum, findings consistent with pituitary stalk interruption syndrome. The patient received testosterone injections for micropenis and is being followed for development of other pituitary hormone deficiencies. PSIS is a rare congenital condition that is increasingly recognized in neonates manifesting with signs of hypopituitarism.

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<![CDATA[MON-246 A Diagnostic Dilemma of Primary Versus Secondary Thyroid and Adrenal Hormone Insufficiencies: A Unique Case of Widely Metastatic Renal Cell Carcinoma After Brain Radiation]]> https://www.researchpad.co/article/elastic_article_6265 Background Identifying the etiology of hormonal insufficiency is important for correct diagnosis and for appropriate hormone supplementation. Usually multiple hormone deficiencies are driven by pituitary pathology, but here we present a case that poses a unique diagnostic and therapeutic dilemma. Clinical Case A 55 y/o lady with HTN and recently diagnosed metastatic Renal Cell Carcinoma (RCC) presented with weakness, dizziness, altered mental status, polydipsia and polyuria. Her metastases included the bilateral adrenal glands, thyroid, brain, and she had a sellar lesion displacing the pituitary as well as infundibular thickening. She had been treated with dexamethasone due to vasogenic edema, whole brain radiation, and was going to start immunotherapy (Ipilumimab&Nivolumimab). On exam she had relative hypotension and tachycardia (BP 115/58, HR 108). She was diagnosed with non-PTH mediated hypercalcemia (Ca 13.9/ 15.3 corrected for albumin 2.3, PTH 6.5, PTH-RP 69, Vitamin D-25 19.4). Her calcium normalized after fluid resuscitation and bisphosphonate treatment, but weakness and hypotension persisted. We tested thyroid and adrenal function given the location of her lesions, recent whole brain radiation, and recent steroid use. Her TSH was 0.017 (0.270 - 4.200 µIU/mL), fT4 0.84 (0.80 - 1.50 ng/dL), T3 0.59 (72.0 - 153.0 ng/dL), ACTH was 1.7 (7.2-63.3 pg/ml), cortisol 1.3 (6.0 - 18.4 ug/dL), aldosterone 3 (< or = 28 ng/dL), renin 7.87 (0.25 - 5.82 ng/mL/h), renin/aldosterone 0.4 (0.9 - 28.9). At 30 minutes after cosyntropin administration cortisol was 7.7 ug/dL, aldosterone 26 ng/dL, and at 60 minutes cortisol was 10.3 ug/dL. Hydrocortisone was initiated while tapering off dexamethasone, and levothyroxine was offered but declined. She opted to postpone further workup. Conclusion This patient presents a dilemma in identifying the primary causes of hormonal abnormalities given potential pituitary and primary thyroid and adrenal disease. The thyroid abnormalities could represent sick euthyroid physiology with lower T4 to T3 conversion or the effects of steroids which can also suppress TSH vs. hypothalamic or pituitary disease. Primary hypothyroidism from gland destruction was unlikely. The low ACTH and cortisol levels were expected since she was on dexamethasone, but low aldosterone with raised renin activity was concerning for primary adrenal insufficiency. However, after cosyntropin the suboptimal cortisol yet preserved aldosterone response supported secondary or tertiary adrenal insufficiency, and only cortisol was supplemented. Understanding her endocrine disease had implications for longer term management given that replacement may only need to be temporary and adrenal recovery might be possible. Further, the use of a 30 minute aldosterone level can be helpful in cases where multiple factors and discrepant laboratory findings may exist.

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<![CDATA[SAT-239 Combination of Immune Check Point Inhibitors Causing Hypopituitarism]]> https://www.researchpad.co/article/elastic_article_6236 Introduction: Immune Check Point inhibitors (ICI) have been associated with immune related adverse events including a wide array of Endocrinopathies particularly when a combination of ICIs is used. We present a case of Hypopituitarism secondary to CTLA-4 inhibitor Iplimumab and PD-1 inhibitor Pembrulizumab in a patient with Vulvar Melanoma.

Case Description: 49-year-old female with past medical history of Type 2 Diabetes and Vulvar Melanoma presented with nausea, vomiting and fatigue. The patient had surgical excision of Vulvular Melanoma and had been on chemotherapy with Pembrolizumab and Ipilimumab for 1 month. She was found to be hypotensive in the ER, but blood pressure improved after fluid resuscitation. Her blood sugar levels were 76 MG/DL. She denied using any insulin in the last 24 hours. AM Cortisol was <1 UG/ML. TSH was 0.205 UIU/ML with free T4 at 0.74 NG/DL. FSH was 2.5 MIU/ML. LH was 0.5 MIU/ML. Prolactin was 90.2 NG/ML. ACTH was less than 9 PG/ML. MRI of the brain showed mildly enlarged pituitary gland with suprasellar extension, measuring 10.5 mm in craniocaudal height and normal homogeneous enhancement. A diagnosis of Hypopituitarism secondary Ipilimumab and Pembrolizumab was made. She was started on steroids and thyroid replacement. The patient’s symptoms resolved, and she was discharged home in a stable condition with outpatient Endocrinology follow up.

Discussion: Immune checkpoint inhibitors (ICI) includes PD1(Programmed cell death receptor 1) inhibitors like Pembrolizumab and CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) inhibitors like Ipilimumab. CTLA-4 inhibitors have more frequently been associated with Hypophysitis leading to particularly ACTH and TSH deficiencies and causing secondary adrenal insufficiency and secondary hypothyroidism. Posterior Pituitary involvement is less common. MRI usually shows mild to moderate enlargement of the pituitary gland. ICI therapy usually does not need to be stopped. Patients commonly require long term glucocorticoid and thyroid replacement.

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<![CDATA[MON-240 Histologically Proven Lymphocytic Hypophysitis with Marked Improvement on Glucocorticoid Therapy]]> https://www.researchpad.co/article/elastic_article_6145 Background: Lymphocytic hypophysitis (LH) is a rare autoimmune disorder characterized by lymphocytic infiltration of the pituitary gland. The disease predominantly affects women, with >50% of cases presenting during pregnancy or postpartum.1 LH is often associated with other autoimmune conditions, primarily thyroiditis, and adrenalitis.2

Clinical case: A 27-year-old female presented with secondary amenorrhea for eight months. Workup revealed hyperprolactinemia (PRL 65 ng/mL) and a heterogenous pituitary mass measuring 3.3 cm in the largest dimension. Cabergoline was initiated for a presumed prolactinoma. Laboratory evaluation was significant for hypogonadotropic hypogonadism (estradiol <50 pg/mL, progesterone <1 ng/mL, FSH 2.9 mIU/mL, LH 0.45 mIU/mL) despite normalization in prolactin. She was also found to have Hashimoto’s thyroiditis (FT4 0.7 ng/dL, TSH 8.2 uU/mL with positive TPO antibodies) and was started on levothyroxine.

Repeat imaging demonstrated a 2.4 cm heterogenous expanding sellar mass with soft tissue extension to the dorsum sella concerning for a meningioma. Visual field testing was intact without evidence of chiasmal compression. She underwent trans-sphenoidal pituitary decompression surgery which was terminated prematurely due to the presence of extensive fibrous tissue in the sella. Pathology was consistent with LH. Immunohistochemical staining was positive for lymphocytic markers CD3 and CD20, confirming marked infiltration of inflammatory B-cells and T-cells. Her postoperative course was notable for panhypopituitarism. In view of the pathological findings of LH, she was started on a high dose of 40mg of prednisone daily. Within two months, sellar magnetic resonance imaging revealed a homogenous normal-appearing pituitary with a reduction in soft tissue mass in the sellar and suprasellar region. Oral contraceptive therapy was initiated for sex hormone replacement with the resumption of menses. Prednisone was gradually tapered to 5mg/day, and she was subsequently transitioned to maintenance hydrocortisone for central adrenal insufficiency.

Discussion: LH is a rare chronic inflammatory disease that should be considered in the differential diagnosis of a non-secreting pituitary mass, especially if occurring in young women presenting during pregnancy or postpartum. The condition is associated with preferential destruction of corticotroph and thyrotroph cells.3 Appropriate management remains controversial. High dose glucocorticoid therapy, to which our patient responded to dramatically, has been shown to be beneficial in reducing mass effect. Optimal treatment involves surgical resection of the pituitary mass to decompress surrounding structures.3

References:

1. JCEM, Volume 100, Issue 10, October 2015, Pages 3841-3849

2. JCEM, Volume 80, Issue 8, August 1995, Pages 2302-2311

3. Horm Res, 2007;68 Supplement 5:145-50

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<![CDATA[SAT-234 Association Between Hypogonadotrophic Hypogonadism and NARP Due to Mitochondrial Disease]]> https://www.researchpad.co/article/elastic_article_6110 Introduction: Hypogonadotropic hypogonadism is a common disorder encountered in endocrine practice with a prevalence of 1 in 10,000 men (1). We describe a patient with possible mitochondrial mutation causing him to have concurrent central hypogonadism and NARP syndrome (neuropathy, ataxia, retinitis pigmentosa). Case: 65 year old male with central hypogonadism diagnosed at age 17 was on testosterone replacement therapy off and on since then. He was diagnosed with NARP at age 49. On exam, he was OX3, BP 147/83mmHg, HR 63 bpm, wt 185lbs. Pupils were sluggish to light. Unable to assess visual fields as patient is legally blind. No gynecomastia. Cardiac and pulmonary exam were normal. Testicles were soft and the volume was 12mL. Prostate was enlarged, non tender and without nodules. He had ataxic gait, abnormal finger to nose test and strength was normal. LH <0.2 mIU/ml (N 1.2 - 10.6 mIU/ml), FSH < 0.2 mIU/ml (N 0.7 - 10.8mIU), total testosterone as low as 12ng/dL when off and 260ng/dL (N 250-1110ng/dL) while on testosterone IM. CBC, CMP, prolactin, ACTH, cortisol, Igf-I, TSH and PSA wnl. MRI brain showed cerebellar atrophy and normal pituitary. Discussion: NARP is a mitochondrial disorder characterized by neuropathy, ataxia and retinitis pigmentosa primarily affecting the nervous system. NARP results from point mutation at base pair 8993 of the mitochondrial genome in the ATPase 6 gene. Symptoms typically consist of proximal neurogenic muscle weakness, sensory neuropathy, ataxia, and retinitis pigmentosa. According to Al-Gadi et al, hypogonadism has been reported in mitochondrial disease (2). RRM2B is a nuclear-encoded mitochondrial maintenance gene. Mitochondrial DNA depletion due to ar-RRM2B mutations have been reported in association with hypogonadism. A mutation of m.8561C>G in MT-ATP6/8 causing a mitochondrial syndrome with ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotrophic hypogonadism has also been reported in a case report of two patients (3). Upon literature review, no prior cases of hypogonadotropic hypogonadism in patients with NARP have been reported. The impairment of the hypothalamic-pituitary axis appears to manifest in severe mitochondrial phenotypes. For example, the association of central hypogonadism with Kearns Sayre Syndrome (KSS). Given that both disorders are related to mitochondrial dysfunction, we propose that the hypogonadism may be linked to NARP syndrome. References Rohayem, J.et al. (2016), Causes of hypogonadotropic hypogonadism predict response to gonadotropin substitution in adults. Andrology Al-Gadi.et al. (2018). Endocrine Disorders in Primary Mitochondrial Disease. JES Kytövuori, L. et al. (2016, August 8). A novel mutation m.8561C>G in MT- ATP6/8 causing a mitochondrial syndrome with ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotropic hypogonadism.

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<![CDATA[MON-234 síNdrome de InterrupcióN del Tallo Pituitario Que Se Presenta Como Amenorrea Primaria]]> https://www.researchpad.co/article/elastic_article_6021 Pituitary stalk interruption syndrome presenting as primary amenorrhea.

The pituitary stalk interruption syndrome is a rare congenital defect that is characterized by the absence or thinning of the pituitary stalk, an absent or ectopic posterior pituitary lobe, and hypoplasia or aplasia of the anterior lobe. The clinical presentation is variable.

It is usually diagnosed in the neonatal period due to the clinical manifestations that arise as a consequence of hormonal deficiencies. However some patients are diagnosed at a latter stage in life. Growth hormone deficiency it is observed in virtually all patients and can be associated to other anterior pituitary hormonal deficiencies. There is a high frequency of associated extra-pituitary malformations including those involving the central nervous system and the craniofacial structures.

We report the case of a 19-year-old woman with primary amenorrhea, lack of secondary sexual characteristics, short stature, low body mass index due to hypergonadotropic hypogonadism and growth hormone deficiency. The remaining pituitary hormones were normal. A pelvic ultrasound revealed orthotopic ovaries and uterus that were decreased in size. Her karyotype was normal. An MRI of the sellar region revealed an ectopic posterior pituitary lobe, and anterior pituitary hypoplasia with a thin pituitary stalk. The patient was treated with estradiol valerate and norgestrel as well as with growth hormone.

In conclusion, the pituitary stalk interruption syndrome is a rare form of congenital hypopituitarism that should be considered in cases of growth hormone deficiency and primary amenorrhea particularly in the presence of extra pituitary malformations involving the central nervous system.

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<![CDATA[MON-239 Pituitary Apoplexy Induced by Gonadotropin-Releasing Hormone Agonist Administration: A Rare Complication of Prostate Cancer Treatment]]> https://www.researchpad.co/article/elastic_article_5935 Background: Pituitary apoplexy is a potentially life-threatening clinical condition associated with bleeding and/or infarction into the pituitary gland, usually within a tumor. Gonadotropin-releasing hormone (GnRH) agonists, currently used in the treatment of advanced prostate cancer, have been described in the literature as a rare cause of pituitary apoplexy.

Case: We report the case of a 69 year-old man with a known pituitary macroadenoma incidentally detected in 2016, without further investigation. He was diagnosed with prostate cancer in 2017 and underwent retropubic prostatectomy. Two years later there was evidence of histologic prostate tumor progression, so he started treatment with leuprorelin 45mg (GnRH agonist). Immediately after the first subcutaneous injection he presented with acute-onset severe headache, followed by left eye ptosis, diplopia and vomiting. Left cranial nerve III palsy was confirmed by examination in the emergency department. Head computed tomography showed a lesion in the sellar region; laboratory endocrine workup was significant for total testosterone 72.07 ng/dL (86.49 – 788.22), with no other abnormalities. Magnetic resonance imaging of the pituitary revealed tumor enlargement and a T1-hyperintense signal, compatible with recent haemorrhagic sellar content. The patient was managed conservatively with high dose steroids, and symptoms were significantly improved on discharge.

Discussion: Pituitary apoplexy induced by GnRH agonist administration is a rare complication, described in only 20 documented cases to date. The pathophysiologic mechanism involved is not clearly established and several hypotheses have been proposed: a combination of metabolic hyperactivity, cell division/tumor growth and increased intrasellar pressure, inducing ischemia in a poorly perfused adenomatous tissue given the demand. Although uncommon, healthcare professionals should be aware of this serious consequence of GnRH agonist administration and recognize the signs, preventing a delay in diagnosis and treatment.

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<![CDATA[MON-243 Atypical Presentation of Isolated Adrenocorticotropic Hormone Deficiency and Sheehan’s Syndrome]]> https://www.researchpad.co/article/Nfcc346a5-36bd-487c-9e23-66bd9aad7df6 Introduction: Isolated adrenocorticotropic hormone (ACTH) deficiency is a rare pituitary hormone deficiency defined by secondary adrenal insufficiency and normal secretion of all other pituitary hormones. Patients present with fatigue, weakness, weight loss, anorexia, nausea, low cortisol levels and low ACTH levels. Isolated ACTH deficiency is more common in males and usually presents in the fifth decade of life. Main mechanisms involved in the pathogenesis are genetics and autoimmune causes, traumatic brain injury and infarction of the pituitary postpartum, known as Sheehan’s syndrome. Sheehan’s syndrome is characterized by postpartum hemorrhage, failure to lactate and menstrual irregularities and it can occur from immediate postpartum period to years after delivery. The most common hormone deficiencies are prolactin and growth hormone. Empty sella is the most common finding on brain MRI. We are reporting a case of a woman in her third decade with isolated ACTH deficiency due to Sheehan’s syndrome two years postpartum, able to lactate, with normal menses and normal brain MRI. Clinical Case: A 33-year-old woman G3P3A0 with hypothyroidism who was referred to Endocrinology clinics due to tiredness, fatigue and weakness. She reported postpartum hemorrhage requiring 4 PRBC transfusions and IV steroids after last pregnancy 5 years ago. Patient was able to lactate after pregnancy and continued in her usual state of health until 3 years ago when she referred loss of consciousness with traumatic head injury due to hypoglycemia. At Endocrinology office physical examination and vital signs were unremarkable, including no blood pressure or heart rate variations with positional changes. Despite hypothyroidism being adequately controlled, she continued with extreme fatigue and weakness affecting her quality of life, for which cortisol and ACTH levels were ordered. Laboratories showed normal electrolytes, negative autoantibodies, cortisol 0.20 μg/dL (5-25 μg/dL) and ACTH 22 pg/mL (10-60 pg/mL) suggesting partial isolated ACTH deficiency. ACTH stimulation test was done and noted with suboptimal response. Evaluation of other anterior pituitary hormones was normal. Brain MRI showed normal pituitary gland. She was started on hydrocortisone in AM and PM and symptoms resolved. Conclusion: Immediate recognition of isolated ACTH deficiency due to Sheehan’s syndrome is necessary due to the availability of effective treatment and morbidity and mortality associated with this serious condition. To our knowledge isolated ACTH deficiency due to Sheehan’s syndrome in which the patient was able to lactate and normal findings on brain MRI has not previously been reported.References: Shivaprasad C. Sheehan’s Syndrome: Newer advances. Indian J Endocrinol Metab. 2011 Sep; 15(3): S203-207. DOI:10.4103/2230-8210.84869.

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<![CDATA[MON-245 Brain Fog: An Important Cue to Neurosarcoidosis and Its Flare-Up?]]> https://www.researchpad.co/article/N6220738e-d9b2-4111-8d57-90a0b43e7174 Introduction:

Sarcoidosis is a multisystem inflammatory disorder characterized by noncaseating granulomas in various organ systems, mainly the lung and lymphatic system. Neurosarcoidosis (NS) involving central or peripheral nervous system is uncommon and Hypothalamic-pituitary (HP) NS is rarer.

Case:

A 45-years-old African American man presented with a few days’ history of cognitive slowness (brain fog) and a sense of loss of direction. He was discharged a few months ago from another hospital after being admitted for shortness of breath and hypercalcemia of 13 mg/dl, which improved after hydration. CXR showed mediastinal and bilateral hilar enlargement. He was discharged home with outpatient pulmonary appointment but was readmitted to our hospital with altered mental status. Calcium level on this admission was 11.5 mg/dl. CT brain showed a sellar/suprasellar lesion, which was better visualized on MRI as enlargement and enhancement of pituitary gland, pituitary stalk, optic chiasm, left and right optic tract and nerves, and hypothalamus. He had left hemi-temporal field defect. Work up revealed inappropriately high normal 1,25 vitamin D, low PTH, PTrp and vitamin D. He has anterior hypopituitarism and mildly elevated prolactin. EBUS with mediastinal lymph node biopsy was non-diagnostic, however, excisional biopsy of mediastinal node showed non-caseating granuloma. ACE level, flow cytometry, infectious work up and serum IgG4 were normal.

Discussion:

NS may present as cranial nerve palsy, chronic headache with incidental HP mass and endocrine dysfunction such as diabetes insipidus, hyperprolactinemia, and anterior hypopituitarism. Visual deficits from optic atrophy or neuropathy; or change in vision from anterior uveitis are present in 41% of patients. Other non-specific presentations of NS include fatigue, cognitive difficulties (brain fog), such as impaired memory, slowed thinking, diminished attention and concentration. Hypercalcemia in sarcoidosis is due to increased intestinal absorption of calcium from increased 1,25 OH vitamin D. Though definitive diagnosis of NS is based on evidence of non-caseating granulomas from neural tissue, probable diagnosis can be made from clinical and radiologic characteristics, non-caseating granulomas at an extraneural site with no evidence of alternative disease. Steroid is the mainstay of treatment in NS and requires slow tapering. Other immunomodulators can be considered in worsening disease or patients with steroid adverse effect.

Conclusion:

Diagnosis of NS is challenging due to its rarity and difficult access to neural tissue for diagnosis. Though brain fog may not be specific for NS or its flare-up, additional neurological test or imaging should be considered especially in African American patients with hilar lymphadenopathy as 20% of NS patients may simply present with non-specific cognitive or behavioral complaints. ​

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<![CDATA[MON-241 Dome Shaped Pituitary Enlargement Warrants Detailed Endocrine Evaluation Prior to Neuro-Surgical Intervention: Case Series & Analysis]]> https://www.researchpad.co/article/N1ccde8b6-1c63-4e42-ab7f-2b2331b3890a <![CDATA[SAT-244 Inflammatory Rathke Cleft Cyst Caused Hypothalamic Panhypopituitarism]]> https://www.researchpad.co/article/N07bad465-f659-487d-b4a5-fb7a5f5dfe5d <![CDATA[MON-245 Brain Fog: An Important Cue to Neurosarcoidosis and Its Flare-Up?]]> https://www.researchpad.co/article/N44e0c45e-f1c9-44d1-b536-e775c23c6a78

Abstract

Introduction:

Sarcoidosis is a multisystem inflammatory disorder characterized by noncaseating granulomas in various organ systems, mainly the lung and lymphatic system. Neurosarcoidosis (NS) involving central or peripheral nervous system is uncommon and Hypothalamic-pituitary (HP) NS is rarer.

Case:

A 45-years-old African American man presented with a few days’ history of cognitive slowness (brain fog) and a sense of loss of direction. He was discharged a few months ago from another hospital after being admitted for shortness of breath and hypercalcemia of 13 mg/dl, which improved after hydration. CXR showed mediastinal and bilateral hilar enlargement. He was discharged home with outpatient pulmonary appointment but was readmitted to our hospital with altered mental status. Calcium level on this admission was 11.5 mg/dl. CT brain showed a sellar/suprasellar lesion, which was better visualized on MRI as enlargement and enhancement of pituitary gland, pituitary stalk, optic chiasm, left and right optic tract and nerves, and hypothalamus. He had left hemi-temporal field defect. Work up revealed inappropriately high normal 1,25 vitamin D, low PTH, PTrp and vitamin D. He has anterior hypopituitarism and mildly elevated prolactin. EBUS with mediastinal lymph node biopsy was non-diagnostic, however, excisional biopsy of mediastinal node showed non-caseating granuloma. ACE level, flow cytometry, infectious work up and serum IgG4 were normal.

Discussion:

NS may present as cranial nerve palsy, chronic headache with incidental HP mass and endocrine dysfunction such as diabetes insipidus, hyperprolactinemia, and anterior hypopituitarism. Visual deficits from optic atrophy or neuropathy; or change in vision from anterior uveitis are present in 41% of patients. Other non-specific presentations of NS include fatigue, cognitive difficulties (brain fog), such as impaired memory, slowed thinking, diminished attention and concentration. Hypercalcemia in sarcoidosis is due to increased intestinal absorption of calcium from increased 1,25 OH vitamin D. Though definitive diagnosis of NS is based on evidence of non-caseating granulomas from neural tissue, probable diagnosis can be made from clinical and radiologic characteristics, non-caseating granulomas at an extraneural site with no evidence of alternative disease. Steroid is the mainstay of treatment in NS and requires slow tapering. Other immunomodulators can be considered in worsening disease or patients with steroid adverse effect.

Conclusion:

Diagnosis of NS is challenging due to its rarity and difficult access to neural tissue for diagnosis. Though brain fog may not be specific for NS or its flare-up, additional neurological test or imaging should be considered especially in African American patients with hilar lymphadenopathy as 20% of NS patients may simply present with non-specific cognitive or behavioral complaints. ​

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