Enlargement Of Pituitary Gland Research Articles

8319 Pituitary Apoplexy Leads to the Spontaneous Resolution of Hypercortisolism Secondary to Cushing Disease: A Clinical Case

Abstract Disclosure: N. Sweis: None. J. Sanchez Perez: None. M. Fariduddin: None. R.M. Sargis: None. D.J. Toft: None. S. Reutrakul: None. Background: Pituitary apoplexy is a potentially fatal condition involving the infarction or hemorrhage of the pituitary gland. Rarely, it can occur in the setting of an ACTH-secreting pituitary adenoma. Clinical Case: A 27-year-old female with a past medical history of obesity, spontaneous miscarriages, and amenorrhea presented to the ER with an acute onset frontal headache of throbbing quality, associated with nausea and vomiting. The headache began two days prior, rapidly intensified, and did not improve with oral acetaminophen. CT of the head revealed an enlarged pituitary gland, while neurovascular imaging showed no abnormalities. Her neurologic examination was normal. She denied visual changes, photophobia, neck rigidity, fevers, chills, or recent infections. Furthermore, she endorsed a weight gain of about 40 pounds over the past year despite no change in dietary habits. This was accompanied by amenorrhea, hair thinning, itchy comedonal acne, hirsutism, and a loss of libido. Her physical examination was remarkable for the presence of cushingoid features including violaceous abdominal striae, facial acne, moon facies, a dorsal fat pad, and acanthosis nigricans around the neck and axillae. Pituitary MRI with and without contrast showed an enlarged sellar and suprasellar macroadenoma measuring approximately 2.1x1.4x1.2 cm abutting the optic chiasm. The visualized lesion contained hemorrhagic products, suggesting pituitary apoplexy. Biochemical testing on admission included a low morning plasma cortisol of 6.5 ug/dL (ref. range: 6.7-22.6 ug/dL), a 24-hour urine free cortisol of 12.0 (<=45.0 ug/24 hour), and an elevated ACTH of 145.0 pg/mL (7.2 - 63.3 pg/mL). A1c was 5.8% (<5.7%). Serum levels of prolactin, IGF1, GH, LH, FSH, TSH, Free T4, estradiol, total and bioavailable testosterone were within normal limits. She was evaluated with an ACTH stimulation test, which showed a morning cortisol level of 1.2 ug/dL at baseline, lower from prior. Cortisol levels were adequately increased at 19.6 ug/dL and 22.6 ug/dL, 30 and 60 minutes after the administration of Cosyntropin 250 mcg, respectively (>=18 ug/dL after 30-60 mins). The level of ACTH at the time was also decreased to 76.6 pg/mL. The patient was therefore started on steroid replacement therapy with hydrocortisone and later underwent transsphenoidal resection of the pituitary mass without complications. Histopathological examination of the resected mass showed pituitary adenoma cells with diffuse weak to moderate ACTH staining, most consistent with a sparsely granulated corticotroph pituitary adenoma. Conclusion: We report an interesting case of Cushing disease that spontaneously resolved after pituitary apoplexy. Our case underlines the importance of close monitoring of such patients who may rapidly undergo a period of adrenal insufficiency after hypercortisolism. Presentation: 6/3/2024

6693 Hypopituitarism in Pregnancy

Abstract Disclosure: N.A. Mcheik: None. H. Howarth: None. Background: Hypopituitarism in pregnancy requires careful management to ensure both maternal and fetal well-being. Disruptions of the pituitary gland in pregnancy can be due to adenomas, pituitary infarction, autoimmune disease, trauma, etc. Complications of hypopituitarism in pregnancy stem from inadequate production of thyroid stimulating hormone, growth hormone, gonadotropins and cortisol. Hormone replacement therapy will be necessary in such cases. For instance, patients in late pregnancy may require an increased dose of hydrocortisone due to the rise of corticosteroid-binding globulin. Patients may need increased doses of glucocorticoid therapy during labor given the major surgical stress. Antenatal care should include close follow up with endocrinologists and obstetricians and regular assessment of maternal hormone levels and fetal growth. Case: We present a case of a 37-year-old female G3P0020 at 24 weeks who presented with complaint of constant headache for 6 days. Associated with photophobia, intermittent blurry vision, nausea, and vomiting. She was admitted and given 1 g Magnesium bolus as well as Robaxin and Tylenol for headache without relief. Given persistence of symptoms and non-focal neurologic exam, MRI brain was completed that showed an enlarged pituitary gland with blood products. MRI pituitary showed an approximately 1.3 x 1.2 x 1.8 cm hemorrhagic lesion on the right side of pituitary gland with fluid level, most in keeping with hemorrhagic pituitary apoplexy. Thyroid function studies were consistent with central hypothyroidism with a low TSH 0.05, low Ft4 0.5, and normal Ft3 2.4. Luteinizing hormone was 0.1 mIU/mL (<1.5 normal in pregnancy), follicle stimulating hormone was <0.5 mIU/mL (<0.1 normal in pregnancy), estradiol >5000 pg/mL (1278-7192 normal in pregnancy), and prolactin 254 ng/mL (80-400 normal in pregnancy). IGF-1 was normal at 148 ng/ml. Morning cortisol was low at 1.8 ug/dL and ACTH was 9 pg/mL (low normal). Cortrosyn stimulation test at 60 minutes was normal at 17.7 ug/dL, however, given clinical improvement on steroids, the clinical picture is consistent with central hypoadrenalism. For treatment, she was started on IV hydrocortisone 50 mg every 8 hours and oral levothyroxine 100 mcg daily. The patient was discharged home on oral hydrocortisone 20 mg daily in the morning and 10 mg daily in the afternoon with close follow up. Conclusion: Ultimately, the management of hypopituitarism in pregnancy requires a personalized approach to hormone replacement and obstetric care and this is done through multidisciplinary care involving endocrinologists and obstetricians to optimize outcomes for both the mother and the baby. Presentation: 6/1/2024

6693 Hypopituitarism in Pregnancy

Abstract Disclosure: N.A. Mcheik: None. H. Howarth: None. Background: Hypopituitarism in pregnancy requires careful management to ensure both maternal and fetal well-being. Disruptions of the pituitary gland in pregnancy can be due to adenomas, pituitary infarction, autoimmune disease, trauma, etc. Complications of hypopituitarism in pregnancy stem from inadequate production of thyroid stimulating hormone, growth hormone, gonadotropins and cortisol. Hormone replacement therapy will be necessary in such cases. For instance, patients in late pregnancy may require an increased dose of hydrocortisone due to the rise of corticosteroid-binding globulin. Patients may need increased doses of glucocorticoid therapy during labor given the major surgical stress. Antenatal care should include close follow up with endocrinologists and obstetricians and regular assessment of maternal hormone levels and fetal growth. Case: We present a case of a 37-year-old female G3P0020 at 24 weeks who presented with complaint of constant headache for 6 days. Associated with photophobia, intermittent blurry vision, nausea, and vomiting. She was admitted and given 1 g Magnesium bolus as well as Robaxin and Tylenol for headache without relief. Given persistence of symptoms and non-focal neurologic exam, MRI brain was completed that showed an enlarged pituitary gland with blood products. MRI pituitary showed an approximately 1.3 x 1.2 x 1.8 cm hemorrhagic lesion on the right side of pituitary gland with fluid level, most in keeping with hemorrhagic pituitary apoplexy. Thyroid function studies were consistent with central hypothyroidism with a low TSH 0.05, low Ft4 0.5, and normal Ft3 2.4. Luteinizing hormone was 0.1 mIU/mL (<1.5 normal in pregnancy), follicle stimulating hormone was <0.5 mIU/mL (<0.1 normal in pregnancy), estradiol >5000 pg/mL (1278-7192 normal in pregnancy), and prolactin 254 ng/mL (80-400 normal in pregnancy). IGF-1 was normal at 148 ng/ml. Morning cortisol was low at 1.8 ug/dL and ACTH was 9 pg/mL (low normal). Cortrosyn stimulation test at 60 minutes was normal at 17.7 ug/dL, however, given clinical improvement on steroids, the clinical picture is consistent with central hypoadrenalism. For treatment, she was started on IV hydrocortisone 50 mg every 8 hours and oral levothyroxine 100 mcg daily. The patient was discharged home on oral hydrocortisone 20 mg daily in the morning and 10 mg daily in the afternoon with close follow up. Conclusion: Ultimately, the management of hypopituitarism in pregnancy requires a personalized approach to hormone replacement and obstetric care and this is done through multidisciplinary care involving endocrinologists and obstetricians to optimize outcomes for both the mother and the baby. Presentation: 6/1/2024

Hashimoto’s thyroiditis presenting solely with psychotic symptoms: A case report

This case report highlights the infrequent occurrences of myxedema psychosis and pituitary hyperplasia as secondary complications of Hashimoto’s thyroiditis. The subject of interest is a 16-year-old female patient who displayed persistent symptoms of delusions, auditory hallucinations, and depression without any discernible cause. The physical examination did not reveal any notable abnormalities. Despite a continuous 4-week treatment regimen involving antipsychotic and antidepressant medications, the patient experienced a deterioration of psychotic symptoms, which resulted in substantial impairment in social functioning. Cranial magnetic resonance imaging scan detected an enlarged pituitary gland and laboratory tests indicated abnormal thyroid function and the presence of specific thyroiditis autoantibodies. Combined with these results, thyroid ultrasound findings revealed features that were consistent with Hashimoto’s thyroiditis. Consequently, the patient was prescribed levothyroxine sodium replacement therapy, as well as low-dose antipsychotic and antidepressant medications, which led to a gradual amelioration of their psychotic symptoms. Following 6 months of treatment, the patient was ordered to stop taking the antipsychotic and antidepressant drugs but continue with levothyroxine sodium replacement therapy exclusively. The results of the 1-year follow-up demonstrated the restoration of thyroid function to normal levels, the normalization of pituitary size and structure, and the absence of any psychotic symptoms. These findings provide evidence for a diagnosis of myxedema psychosis and secondary pituitary hyperplasia caused by hypothyroidism associated with Hashimoto’s thyroiditis. This emphasizes the significance of supplementary tests in the diagnostic procedures carried out by psychiatrists.

A Rare Case of Hypophysitis Due to Tuberculosis with an Atypical Presentation of Normal Pituitary Markers

Abstract Hypophysitis developing secondary to tuberculosis is a very rare clinical entity. Hypophysitis occurs because of inflammation and it may affect the anterior, infundibulum, posterior, or entire pituitary gland. Here, we are presenting a case of a young male having tubercular meningitis who was taking antitubercular treatment for the last 2 months and was having disseminated tuberculosis. The patient presented with severe headache with fever and 4–5 episodes of vomiting. The patient presented with the affection of consciousness in the form of confusion, irritability, and disorientation. High-resolution CT thorax was suggestive of pulmonary tuberculosis (Koch’s) with centrilobular nodules and a tree-in-bud appearance. Magnetic resonance imaging brain showed prominent leptomeningeal enhancement with an enlarged pituitary gland with enlarged enhancing stalk suggestive of hypophysitis. The hypophysitis case developing secondary to tuberculosis as a very rare entity is discussed in this case report. This case is also an atypical presentation wherein the pituitary markers are normal in hypophysitis.

Imaging for assessment of cancer treatment response to immune checkpoint inhibitors can be complementary in identifying hypophysitis.

Hypophysitis is reported in 8.5%-14% of patients receiving combination immune checkpoint inhibition (cICI) but can be a diagnostic challenge. This study aimed to assess the role of routine diagnostic imaging performed during therapeutic monitoring of combination anti-CTLA-4/anti-PD-1 treatment in the identification of hypophysitis and the relationship of imaging findings to clinical diagnostic criteria. This retrospective cohort study identified patients treated with cICI between January 2016 and January 2019 at a quaternary melanoma service. Medical records were reviewed to identify patients with a documented diagnosis of hypophysitis based on clinical criteria. Available structural brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT) of the brain and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography (FDG-PET/CT) were assessed retrospectively. The main radiological outcome measures were a relative change in pituitary size or FDG uptake temporally attributed to cICI. There were 162 patients (median age 60 years, 30% female) included. A total of 100 and 134 had serial CT/MRI of the brain and FDG-PET/CT, respectively. There were 31 patients who had a documented diagnosis of hypophysitis and an additional 20 who had isolated pituitary imaging findings. The pituitary gland enlargement was mild, and the largest absolute gland size was 13 mm, with a relative increase of 7 mm from baseline. There were no cases of optic chiasm compression. Pituitary enlargement and increased FDG uptake were universally transient. High-dose glucocorticoid treatment for concurrent irAEs prevented assessment of the pituitary-adrenal axis in 90% of patients with isolated imaging findings. Careful review of changes in pituitary characteristics on imaging performed for assessment of therapeutic response to iICI may lead to increased identification and more prompt management of cICI-induced hypophysitis.

THU385 Refractory Hyperglycemia As Main Presenting Symptom In A Patient With Acromegaly

Abstract Disclosure: T. Rave: None. J. Vidovic: None. Y. Gu: None. Acromegaly is a rare disorder caused by the overproduction of growth hormone (GH) from an anterior pituitary adenoma. GH regulates glucose control and about 10% of patients with acromegaly can have complications of hyperglycemia. GH stimulates hepatic release of insulin-like growth hormone-1 (IGF-1), which increases gluconeogenesis and lipolysis and decreases glucose uptake throughout the body. The increase in gluconeogenesis and decrease in glucose uptake results in hyperglycemia. The excess release of fatty acids increases insulin resistance. In this case report we present a case of hyperglycemia resistant to multiple modes of medical management with limited acromegaly features found to have acromegaly induced hyperglycemia. A 58-year-old male with a past medical history of type II diabetes mellitus, hypertension, and obesity presented to the endocrinology clinic with treatment resistant hyperglycemia. The patient also endorsed having progressive carpal tunnel symptoms. He had been using an insulin pump and requiring 3 or more boluses per day for the last 6 months. Trulicity was added in addition to current insulin pump therapy, however, sugars remained elevated with an unimproved A1c level of 9% and a fructosamine level of 538 µmol/L correlating to an A1c of 10.8%. An IGF-1 level was sent to rule out acromegaly in the setting of carpal tunnel symptoms. The IGF-1 resulted in 580 ng/mL with a z-score of +5.1. The patient underwent a GH suppression test with a glucose load which showed a significantly elevated nadir GH level of 26.3 ng/mL. Of note, the patient did not have other acromegaly symptoms such as frontal bossing, ring or shoe enlargement, coarse facial features, headaches or vision changes. An MRI pituitary was obtained which was notable for an enlarged pituitary gland with heterogeneous signal, measuring approximately 2.0cm CC x 1.5cm AP x 1.7cm TV, with the pituitary stalk deviated to the left. At this time the intervention for hyperglycemic therapy shifted. The patient was started on octreotide and referred to neurosurgery for transsphenoidal surgery. The pathophysiology of type II diabetes is complex and multifaceted. Additionally, secondary causes of hyperglycemia must be considered in refractory cases, such as in this patient. This case highlights the importance of considering acromegaly and other hormonal conditions in the treatment of patients with uncontrolled hyperglycemia, even in otherwise asymptomatic patients. Presentation: Thursday, June 15, 2023

THU577 Acth Dependent Cushing Syndrome Identification And Management Challenges

Abstract Disclosure: B.C. Barreto: None. S. Patrick: None. H. Oktaei: None. H.O. Steinberg: None. Endogenous Cushing Syndrome(CS) is rare with an incidence of 0.2-5.0 per million people per year. 70 to 80% of CS is ACTH dependent and subclassified into Cushing Disease, Ectopic ACTH Syndrome and Ectopic CRH Syndrome. Ectopic ACTH secretion(EAS) has a variable clinical presentation. Atypical features like refractory hypokalemia in a patient with a tumoral lesion should raise suspicion. When imaging is inconclusive, differentiating between pituitary or ectopic disease includes invasive and noninvasive methods. We report a case of EAS. Case: A 57-year-old male with history of metastatic small-cell lung-cancer on palliative chemotherapy was admitted for acute coronary syndrome. Endocrinology evaluated the patient’s uncontrolled hypertension, hyperglycemia, and hypokalemia (1.5 mmol/L). He had no suppression with low dose dexamethasone (cortisol>75mcg/dL, ACTH 926pg/mL). Examination was pertinent for an elevated BMI 36.1kg/m2, hyperpigmented anterior thorax but no other stigmata of hypercortisolism. Laboratory analysis showed baseline cortisol 146.1mcg/dL(8.7-22), ACTH 590pg/ml(6-50), 24hr Urine Free Cortisol 736mcg/24h(5-50), which were not suppressed by high dose dexamethasone suppression test(HDDST). Aldosterone and PRA were undetectable. Brain MRI showed an enlarged pituitary gland, but no focal mass. CT abdomen pelvis showed bilateral adrenal hyperplasia, multiple hepatic masses, and bone lesions. Since the patient was a poor surgical candidate, medical therapy was initiated with ketoconazole 200mg TID, aldactone 50mg BID and potassium chloride 40mEq TID. After twelve days cortisol levels decrease to 65.2 mcg/dL, potassium 3.8 mmol/L and glucose 146 mg/dL. Hospitalization was complicated by a small bowel ileus. Medications were held due to poor gastrointestinal absorption and parenteral octreotide 200mcg TID was initiated. Once the ileus resolved, ketoconazole 200mg TID, eplerenone 50mg daily, and dexamethasone 0.5mg daily was started. Despite medical care, the patient eventually expired. Discussion: The HDDST can help distinguish pituitary from an ectopic ACTH overproduction. HDDST with >50% suppression, has been described with sensitivity-specificity of 60 to 100% for pituitary ACTH source. Symptomatic treatment of CS requires rapid normalization of hypercortisolism action. Surgery is the first line approach. When surgery is not an option, medical therapy should be considered. Adrenal steroidogenesis inhibitors, such as ketoconazole, are the first line due to rapid onset of action. Agents such as glucocorticoid receptor antagonists have limited availability in the inpatient setting. Somatostatin analogs and etomidate that inhibit 11-ßhydroxylase are potential options but require close monitoring. Severe hypercortisolism in the critically ill prompts the use of noninvasive evaluation tools and alternative medical approaches. Presentation Date: Thursday, June 15, 2023

FRI214 Adrenal Adenoma With Biochemical Findings Suggestive Of Cushing's Disease

Abstract Disclosure: A. Calimag: None. U. Tarabichi: None. M. Ahmad: None. M. Kazi: None. Introduction: We are presenting a case of a young female with prior history of multiple endocrinopathies presenting with a left adrenal adenoma with biochemical findings suggestive of Cushing's disease. Case Presentation: A 22-year-old female with a history of Type 1 Diabetes Mellitus was found to have a left adrenal adenoma 2.8 cm on CT. Absolute washout of 85 % and a relative washout of 63%, having 12 Hounsfield units (HU) on the non-contrast phase, findings suggestive of a benign adenoma. Further work up including 1 mg Dexamethasone suppression test (DST) showed unsuppressed plasma ACTH 17 pg/ml and total cortisol 9.4 mcg/dL. 8 mg DST showed ACTH 12 pg/ml, AM cortisol 8.8 mcg/dL, and Dexamethasone 991 ng/dl. Late night salivary cortisol 0.07 ug/dl, and 0.09 ug/dl, 24 hr urine cortisol 40.7. Other labs showed Aldosterone level was normal at 6.7, Renin level was also normal at 1.1. 24 hr urine catecholamines were Norepinephrine 35 mcg/24 hr, Epinephrine 3.9 mcg/24 hr, while urine Metanephrine level was <0.24, and normetanephrine level at 0.34. TSH 1.2mcU/ml. One day prior to surgery ACTH level was suppressed at 2.1 pg/ml drawn from a different lab. MRI of the Pituitary showed a slightly enlarged pituitary gland with uniform contrast enhancement and no definite lesion. The patient underwent a laparoscopic left adrenalectomy. Pathology showed an adrenal cortical neoplasm consistent with adrenal cortical adenoma, with no significant cytologic atypia, mitotic activity, or necrosis. Immunoperoxidase stain, the tumor is positive for inhibin and negative for PAX8. Post-op she developed adrenal insufficiency which was treated with hydrocortisone. The follow-up cortisol level was 11.3 mcg/dL when the patient was off hydrocortisone. Discussion: In this case, the biochemical exam showed elevated cortisol with ACTH not fully suppressed at both 1 mg and 8 mg DST which was done twice, and normal 24-hour urine cortisol. Determining whether this is adrenal vs pituitary mediated was one of the clinical dilemmas of this case. Initially, the patient’s ACTH was unsuppressed however the day before surgery ACTH was suppressed and the patient’s cortisol level normalized after the left adrenalectomy. Immunoassays for ACTH levels may occasionally be susceptible to analytical errors. (1-2) There are several case series and studies mentioning assay interference when using Immulite Assay versus Cobas ACTH assay. (1-2) Therefore, it is important to analyze clinical findings and biochemical testing and if lab tests are discordant, recheck using a different analytical platform in a different lab or an alternate ACTH assay to confirm ACTH levels. (1-2)

FRI339 Hypophysitis Secondary To Small Vessel Anca Vasculitistreated With Rituximab

Abstract Disclosure: A. Rivadeneira: None. N. Kumar: None. S. Banerjee: None. M. Gubbiotti: None. D. Yoshor: None. J. Kharlip: None. C.A. White: None. Introduction: Granulomatosis with polyangiitis (GPA) is an autoimmune small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCAs) that rarely involves the pituitary. Conventional treatment of GPA includes high dose glucocorticoids with cyclophosphamide. Rituximab has been used in refractory cases with high rates of remission. We present a case of pituitary GPA treated with and excellent response to rituximab. Case: 51-year-old woman with hypothyroidism, post I-131 treatment for Graves’ disease. Patient presented with 1 year of worsening fatigue, myalgias, frontal headaches, sinus congestion and epistaxis. CT sinus showed pituitary enlargement and chronic mucosal disease. MRI pituitary showed diffusely enlarged pituitary with non-visualized posterior pituitary bright spot and thickened stalk. CT chest showed 18x11 mm nodular opacity and peribronchial fibrosis. Laboratory evaluation showed ACTH 26.7 pg/mL, cortisol 13.4 mcg/dL, TSH 1.1, T4 9.7, prolactin 53 ng/dL, estradiol <20, LH 4, FSH 23. Sodium 140 and urine osm 488. There was positive p-ANCA staining and elevated serum anti-proteinase 3 antibody (PR3), 74 units (0-20). Myeloperoxidase antibody was not elevated. ESR 73 mm/h (0 - 30) and CRP 7.9 (<7.4). Due to atypical ANCA pattern (p ANCA typically is associated with MPO not PR3), pituitary biopsy was performed and showed adenohypophysis with dense lymphoplasmacytic infiltration with nodularity of the inflammatory infiltrates, some arranged peri vascularly, compatible with involvement of the pituitary gland by GPA. She began rituximab 375 mg/m2 weekly for four weeks with plan to continue every 6 months. After treatment, the patient experienced resolution of daily frontal headaches, congestion, cough and epistaxis. CT chest showed improvement of prior lung findings, and ESR/CRP normalized. Repeat pituitary MRI is pending. Discussion: Pituitary involvement is uncommon in GPA, occurring in only 3.9% of cases. It may lead to partial or complete pituitary dysfunction, particularly central diabetes insipidus (87.5%) and hypogonadism (75%). Typical MRI abnormalities include diffusely enlarged pituitary gland, thickened pituitary stalk and absence of posterior bright spot. Treatment of GPA includes a combination of corticosteroids, Cyclophosphamide, Azathioprine and Rituximab. Remission is achieved in up to two thirds of patients. Treatment of lymphocytic hypophysitis, another common cause of diffuse pituitary enlargement, relies on high dose glucocorticoids, leading to many side effects and taper is limited by worsening symptoms. This case highlights the critical role in serologic evaluation and targeted pituitary biopsy to identify the specific etiology of pituitary infiltration to help guide alternate treatment options, and the emerging role of Rituximab as a steroid sparing agent for treatment of pituitary inflammation. Presentation: Friday, June 16, 2023

Challenges of transsphenoidal pituitary surgery in severe brachycephalic dogs.

Transsphenoidal hypophysectomy is the standard surgical technique for the excision of pituitary neoplasms. Anatomy may be more obscured in brachycephalic skull types due to the crowding of soft tissue and osseous structures. We describe the unique challenges to approach the sphenoid bone and localize the correct burr hole site in severe brachycephalic dogs. A single institution retrospective case series of brachycephalic dogs with pituitary-dependent hypercortisolism (PDH). Preoperative computed tomography enabled 3D-, and cross-sectional reconstruction to plan and dry-practice the position of the ideal burr hole in relation to the sella turcica, pterygoid hamular processes, and hard palate. Rostral burring of the caudal hard palate obscuring the direct sphenoid approach necessitated adaptations to the original transsphenoidal hypophysectomy procedure. Postoperative outcomes and complications with respect to those seen in mesocephalic dogs are described. Ten brachycephalic dogs including French Bulldogs (n = 9) and a single Dogue de Bordeaux were included. All dogs were diagnosed with PDH and had preoperative advanced imaging performed on the skull. All but one dog had an enlarged pituitary gland, with a median pituitary/brain value of 0.5 (range 0.21-0.9). A total of 11 transsphenoidal hypophysectomy procedures were performed in these 10 dogs. Rostral extension of the soft palate incision into the hard palate was performed to access the burr hole site on the sphenoid bone. Major complications included aspiration pneumonia (n = 1), severe gastroesophageal reflux (n = 1), and central nervous signs (=1). All dogs survived until discharge, with a median time to follow-up of 618 days (range 79-1,669 days). Seven dogs experienced long-term remission of PDH. Brachycephalic dogs undergoing transsphenoid al hypophysectomy benefit from meticulous presurgical planning and extension of the approach into the caudal hard palate. Advanced surgical skills can render a good outcome in a technically challenging environment.

Central diabetes insipidus following COVID-19 mRNA vaccination: a case report

The coronavirus disease 2019 (COVID-19) has been a major public health emergency worldwide. Vaccines were rapidly developed and approved to prevent the spread of viral infection. However, various side effects of the COVID-19 messenger RNA (mRNA) vaccines have been reported after their commercialization. A 24-year-old man visited our emergency department with polyuria and polydipsia that occurred after he received a COVID-19 mRNA vaccine 10 days beforehand. The initial laboratory findings showed very low urine osmolality with hyperosmolar hypernatremia. Based on these findings, diabetes insipidus was suspected, and sella magnetic resonance imaging showed an enlarged pituitary gland and the absence of posterior pituitary higher intensity. After 12 hours of using oral desmopressin acetate, urine volume decreased, and after 5 days of administration, serum electrolyte and serum osmolality improved. This case report of diabetes insipidus occurring after vaccination with the BNT162b2 mRNA COVID-19 vaccine is presented as a reminder that close monitoring is necessary for patients with polyuria and polydipsia after vaccination.

Immune-related hypophysitis: An analysis of a heterogeneous entity.

e14704 Background: Immune-checkpoint inhibitors (ICIs) have led to revolutionary breakthroughs in the management of many malignancies. With the increasing use of ICIs, immune-related adverse events (irAE) have emerged and led to significant challenges and limitations. Immune-related hypophysitis, a potentially life-threatening irAE, has limited data on its diagnosis, clinical findings, and management. This was our incentive to characterize our single-institution experience with immune-related hypophysitis over the past 5 years. Methods: We retrospectively studied a cohort of adult patients who received ICIs at the Cleveland Clinic Foundation between 2017-2022. Our search was done by utilizing an outpatient oncology pharmacy database. Analyzed ICIs included atezolizumab, nivolumab, pembrolizumab, ipilimumab, avelumab, and durvalumab. The occurrence of immune-related hypophysitis was as determined by an endocrinologist or oncologist. Results: 6,615 patients received ICIs from 2017-2022, of which 27 patients were diagnosed with hypophysitis. Immune-related hypophysitis occurred with ICI monotherapy in 44.4% and combined therapy (ipilimumab and nivolumab) in 55.5%. The most commonly implicated agents were ipilimumab (74%), followed by nivolumab (59.3%), pembrolizumab (18.5%), and durvalumab (3.7%). In patients receiving ipilimumab-nivolumab, hypophysitis was detected after a median duration of 65 days (range: 29-163 days) from ICI initiation, compared to 58 days (38-112) with ipilimumab alone and 155 days (8-294) with pembrolizumab. Hypophysitis was grade 1 in 18.5%, grade 2 in 29.6%, grade 3 in 37%, and grade 4 in 14.8% of all patients. No hypophysitis-related deaths occurred. Signs and symptoms included constitutional symptoms (fever, anorexia, myalgia) in 88.89%, severe/intractable headaches in 40.7%, gastrointestinal complaints in 29.6%, dermatologic findings in 7.4%, visual symptoms in 7.4%, and syncope in 3.7% of all patients. Lab findings included abnormalities of TSH in 77.78%, ACTH in 70.60%, FSH and/or LH in 52.63%, and a positive ACTH stimulation test in 69.3%. Imaging findings were present in 62.5% of patients, and most commonly revealed pituitary gland enlargement, enhancement, or stalk thickening on brain/pituitary MRI. Treatment included glucocorticoid replacement in 92.6%, thyroid replacement in 40.7%, and testosterone in 7.4% of patients. All patients remained on glucocorticoid therapy indefinitely after hypophysitis was diagnosed. ICIs were momentarily held in 22.2% and discontinued in 51.86% of patients, while 25.9% of patients did not experience treatment interruptions. Conclusions: Immune-related hypophysitis is an uncommon irAE that presents with variable clinical and diagnostic findings. Nonetheless it is a cause of permanent glucocorticoid dependence. Healthcare professionals should be aware of this entity so treatment can be promptly started.

Increased pituitary volumes in patients with Sanfilippo syndrome (mucopolysaccharidosis type 3, MPS III).

To evaluate apparent pituitary gland enlargement in patients with Sanfilippo syndrome observed at our institution. Twelve patients with Sanfilippo syndrome with brain MRI were studied. Anterior, posterior, and whole pituitary volumes were estimated using the prolate ellipsoid volume calculation method (π/6 × L × W × H). Convexity along the upper pituitary margin (Elster's grade) was also measured. These values were compared to two age- and sex-matched groups (normal controls and patients with Hurler syndrome) using one-way ANOVA followed by Tukey's post hoc analysis for multiple comparisons. In the Sanfilippo cohort, the mean whole pituitary volume was 529.9 mm, the mean anterior pituitary volume was 333.4 mm, and the mean posterior pituitary volume was 59.1 mm with Elster's grade of 4.2. In the control cohort, the mean whole pituitary volume was 217.4 mm, the mean anterior pituitary volume was 154.8 mm, and the mean posterior pituitary volume was 28.4 mm with Elster's grade of 2.5. In the Hurler syndrome cohort, the mean whole pituitary volume was 310.0 mm, the mean anterior pituitary volume was 178.2 mm, and the mean posterior pituitary volume was 35.4 mm with Elster's grade of 3.5. In our cohort of patients with Sanfilippo syndrome, whole, anterior, and posterior pituitary volumes and degree of convexity along the upper pituitary border were all significantly greater than controls. The cause of these morphological changes is unclear, as is clinical correlation of the findings.

Teaching Neuro Images : Intracranial hypotension in a patient with Marfan syndrome

An 18-year-old man with Marfan syndrome and migraine headaches presented with acute worsening of headaches with postural changes following spinal fusion surgery for scoliosis. Lumbar spine MRI done before surgery showed diffuse dural ectasia (figure 1). Brain MRI after surgery showed distended transverse and sagittal dural venous sinuses1 and an enlarged pituitary gland suggesting intracranial hypotension (figure 2). He was treated conservatively with rest, fluids, and caffeine. Patients with Marfan syndrome frequently have dural ectasia2 and are at risk of CSF leaks after spinal surgery leading to intracranial hypotension. Our case highlights subtle changes on brain MRI suggesting intracranial hypotension.

Hypophysitis and Secondary Adrenal Insufficiency From Immune Checkpoint Inhibitors: Diagnostic Challenges and Link With Survival.

Hypophysitis is a serious adverse event stemming from immune checkpoint inhibitor (ICI) therapy for malignancy. This study aimed to characterize ICI-induced hypophysitis, identify diagnostic challenges, and evaluate an association with survival in a large cancer cohort. We performed a retrospective cohort study of adult patients with cancer who received ICIs between December 1, 2012, and December 31, 2019. We identified 839 patients who received CTLA-4, PD-1, or PD-L1 inhibitors or a combination thereof who were followed for a median of 19.4 months. Hypophysitis was defined as MRI evidence of pituitary gland and/or stalk enlargement or biochemical evidence of hypopituitarism if not explained by another etiology. A total of 16 (1.9%) patients developed hypophysitis a median of 7 months after ICI initiation, with most patients having melanoma (9/16; 56.2%) or renal cell carcinoma (4/16; 25%). Two patients also had exogenous glucocorticoid exposure but exhibited secondary hypothyroidism and secondary adrenal insufficiency (AI). Median age at the start of ICI was 61.3 years and 57% were men. Patients who developed hypophysitis were younger compared with those who did not develop hypophysitis (median age, 57 vs 65 years; P=.011). Hypophysitis occurred most frequently after combination therapy (13.7%) compared with CTLA-4 monotherapy (1.9%), PD-1 monotherapy (1.2%), and PD-L1 monotherapy (0.8%) (P<.0001). Pituitary gland enlargement on MRI occurred more frequently after CTLA-4 inhibitor monotherapy or combination therapy (5/7; 71.4%) compared with PD-1/PD-L1 inhibitor monotherapy (1/6; 16.7%). The survival benefit of hypophysitis was not apparent after addressing immortal time bias and adjusting for other variables affecting patient outcomes. Secondary AI occurred in all patients, and secondary hypothyroidism occurred in half. Classic pituitary gland enlargement is usually absent in PD-1/PD-L1 inhibitor-induced hypophysitis. Further pituitary evaluation must be conducted to differentiate secondary AI resulting from exogenous glucocorticoids and hypophysitis in patients with cancer receiving ICIs. The link between hypophysitis and ICI efficacy needs further investigation.

TEST ARTICLE: Hypophysitis and Secondary Adrenal Insufficiency From Immune Checkpoint Inhibitors: Diagnostic Challenges and Link With Survival.

Hypophysitis is a serious adverse event stemming from immune checkpoint inhibitor (ICI) therapy for malignancy. This study aimed to characterize ICI-induced hypophysitis, identify diagnostic challenges, and evaluate an association with survival in a large cancer cohort. We performed a retrospective cohort study of adult patients with cancer who received ICIs between December 1, 2012, and December 31, 2019. We identified 839 patients who received CTLA-4, PD-1, or PD-L1 inhibitors or a combination thereof who were followed for a median of 19.4 months. Hypophysitis was defined as MRI evidence of pituitary gland and/or stalk enlargement or biochemical evidence of hypopituitarism if not explained by another etiology. A total of 16 (1.9%) patients developed hypophysitis a median of 7 months after ICI initiation, with most patients having melanoma (9/16; 56.2%) or renal cell carcinoma (4/16; 25%). Two patients also had exogenous glucocorticoid exposure but exhibited secondary hypothyroidism and secondary adrenal insufficiency (AI). Median age at the start of ICI was 61.3 years and 57% were men. Patients who developed hypophysitis were younger compared with those who did not develop hypophysitis (median age, 57 vs 65 years; P=.011). Hypophysitis occurred most frequently after combination therapy (13.7%) compared with CTLA-4 monotherapy (1.9%), PD-1 monotherapy (1.2%), and PD-L1 monotherapy (0.8%) (P<.0001). Pituitary gland enlargement on MRI occurred more frequently after CTLA-4 inhibitor monotherapy or combination therapy (5/7; 71.4%) compared with PD-1/PD-L1 inhibitor monotherapy (1/6; 16.7%). The survival benefit of hypophysitis was not apparent after addressing immortal time bias and adjusting for other variables affecting patient outcomes. Secondary AI occurred in all patients, and secondary hypothyroidism occurred in half. Classic pituitary gland enlargement is usually absent in PD-1/PD-L1 inhibitor-induced hypophysitis. Further pituitary evaluation must be conducted to differentiate secondary AI resulting from exogenous glucocorticoids and hypophysitis in patients with cancer receiving ICIs. The link between hypophysitis and ICI efficacy needs further investigation.

A detailed pituitary profile always matters

Abstract 29-year-old female with known hypothyroidism and positive thyroid auto antibodies, followed up throughout pregnancy for adjusted doses of thyroid replacement therapy, presented 2 months post-partum with gradually increasing fatigue, repeated pre-syncope experience, inability to cope with daily home and family needs and headache. Adequacy of thyroid replacement therapy was questioned, TSH has been performed: 0.18 mIU/ml. Checking the blood pressure in lying and standing position has showed Postural hypotension. An urgent measurement of Cortisol (am) showed a result of1.06 ug/dl. Preliminary Differential Diagnoses have been suggested; Pituitary apoplexy, Pituitary adenoma, Autoimmune adrenalitis (Autoimmune Polyglandular Syndrome) or Others. On further detailed history, the patient affirmed dizziness and fainting liability on standing from lying position, bitemporal headache more in the morning. However, she denied frequent urination throughout the day, neither repeated times at night. In addition, she confirmed efficient breast feeding. Continued Lab investigations: ACTH (am) (Low); FT4 (Low; on replacement therapy); IGF1 (Normal) Serum osmolality (Normal); Urine osmolality (Normal); E2 / LH / FSH (normal physiological levels) Prolactin (normal for breast feeding) MRI pituitary and sella: Diffuse isointense enlargement of anterior pituitary gland. Homogenous and strong diffuse pituitary enhancement with gadolinium contrast. History and investigations were not fully matching with any of the previously proposed differential diagnoses, especially in regards of selective corticotroph and thyrotroph affection, sparing other pituitary cell types. Moreover, the autoimmune predisposition, the nature of the clinical presentation and its timing during early postpartum period, together with the laboratory and imaging investigations were all matching with the diagnosis of Lymphocytic Hypophysitis. The Patient got pregnant again 14 months post-partum, reflecting spared gonadotroph function and highlighting the importance to identify this uncommon diagnosis and to notify the patient about normal gonadal function and the normal possibility of pregnancy. However, she remained on hydrocortisone and thyroxine replacement. Finally, it is important that this condition should not be misdiagnosed in the first place as postpartum thyroid disturbance and TSH results, especially during and after pregnancy, shall always be interpreted in the clinical context and with the overall thyroid profile.

ODP317 Hypophysitis or No? A Rare Case of Bipolaris Fungal Sinusitis Causing Severe Pituitary Inflammation.

Abstract Clinical case: A 28 year old male with uncontrolled diabetes mellitus presented to the hospital with severe, worsening holo-cephalic headache associated with fevers, light sensitivity which was unresponsive to pain medications. Initial CT of the brain showed severe paranasal sinus disease. Lumbar puncture was significant for elevated protein and cell count with neutrophilic predominance and negative CSF culture. Patient was empirically treated for meningitis. Due to no improvement in his symptoms, MRI brain with contrast was done that showed complete opacification of the left sphenoid sinus with partial opacification of the ethmoid sinus. Of note, heterogeneous enlargement and enhancement of pituitary gland including portion of distal infundibulum was seen with mild compression of optic chiasm. High dose dexamethasone was initiated. Pituitary workup revealed preservation of all axes including AM cortisol 36.5 mcg/dL (6.6mcg/dl- 33 mcg/dl), prolactin 2.9 ng/ml (2.1ng/ml-17.7ng/ml), TSH 1.4 uIU/mL (0.34-5.6 uIU/mL), FT4 0.99 uIU/mL (0.80-1.80 uIU/mL) with normal serum chemistry and hemodynamics. Repeat MRI brain showed sphenoid pyomucocele with infection extending to the sella, cavernous sinuses and anterior/middle cranial fossas. ENT surgery was emergently performed with surgical debridement of the sphenoid and ethmoid sinuses revealing green cement like debris causing posterior septal perforation from the pressure. Interestingly, ethmoid sinus fluid culture grew Bipolaris fungal species. Patient's condition gradually improved and he was discharged on oral itraconazole with steroid taper. The patient did not develop signs or symptoms of hypophysitis during his hospital course. Presentation: No date and time listed

PSAT328 Primary Hypothyroidism Presenting with Galactorrhea and Pituitary Hyperplasia

Abstract Introduction Pituitary Hyperplasia (PH) refers to diffuse enlargement of pituitary gland and is most commonly physiological as in pregnancy and lactation. PH can also be associated with end organ hormone deficiencies like primary hypothyroidism, Addison's disease and some neuroendocrine tumors. Primary hypothyroidism is a known cause of prolactin elevation however hyperprolactinemia in the presence of pituitary enlargement can often be mistaken for pituitary adenoma. We report a case of PH caused by primary hypothyroidism presenting with galactorrhea and hyperprolactinemia and successfully treated with thyroid hormone replacement. Case presentation 21-year-old female presented to the Primary Care Provider's office with galactorrhea from bilateral breasts for 2 months. Pregnancy was ruled out and prolactin levels were checked and noted to be elevated at 51.3 ng/mL. Subsequently MRI of Pituitary was done which showed diffusely enlarged, homogenously enhancing anterior pituitary gland with convex superior margin, measuring 12 mm in superior to inferior dimension, contacting and slightly elevating optic chiasm. Further testing showed TSH &amp;gt;100µIU/mL, and undetectable Free T4. She was started on Levothyroxine and then referred to Endocrinology for evaluation of Pituitary mass. Upon further questioning she reported headaches for few weeks associated with intermittent dizziness, fatigue, weight gain of 30-40 pounds, irregular menstrual periods, cold intolerance, and low libido for several months. Physical exam was remarkable for bradycardia, dry skin. Thyroid was normal on exam. Pituitary hyperplasia was thought to be secondary to primary hypothyroidism and patient was continued on Levothyroxine. At 3 month follow up visit, patient reported improvement in her symptoms of fatigue, menstrual periods and lost few pounds of weight. Her galactorrhea resolved completely. Repeat labs showed normal prolactin levels and her thyroid levels normalized after few dose adjustments. Follow up MRI done 1 year from initial presentation showed decrease in the anterior pituitary enlargement, now measuring 8 mm, and the superior margin was no longer contacting the optic chiasm. Conclusion Primary hypothyroidism is common, but often under recognized cause of Pituitary hyperplasia. The underlying pathophysiology is lack of negative feedback of Thyroid hormones on Hypothalamus resulting in elevated levels of Thyrotropin releasing hormone (TRH). Excess TRH leads to thyrotroph cell hyperplasia in anterior pituitary and elevated TSH levels, TRH also leads to lactotroph hyperplasia and can result in hyperprolactinemia. Neurological symptoms related to PH and symptoms related to hyperprolactinemia, can sometimes be the initial presenting symptoms of primary hypothyroidism. It is important to recognize primary hypothyroidism as the cause for pituitary hyperplasia and hyperprolactinemia (especially those with TSH &amp;gt; 50-100 microIU/mL) as the primary treatment is thyroid hormone replacement and not surgery. These patients should be followed closely with repeat MRI to document the resolution of pituitary hyperplasia. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.