bluuebunny/crossref_metadata_2025 huggingface dataset:
FRI292 Asymptomatic TSH Secreting Pituitary Macroadenoma
Authors: Gautam Bharat , Hossain Md Shajjad , Liao Huijuan , Mandal Kaushik , Rosenthal David S , Kumar Salini Chellappan
Published: October 2023

Disclosure: B. Gautam: None. M.S. Hossain: None. H. liao: None. K. Mandal: None. D.S. Rosenthal: None. S.C. Kumar: None.

Introduction: TSH-producing adenoma is a rare disorder accounting for 0.5-2% of all pituitary adenomas with prevalence of 1-2 cases/million, often diagnosed at the stage of invasive macroadenoma hence challenging to manage. Case Presentation: A 36 years old male with no PMH referred to endocrine clinic for the evaluation of insomnia with abnormal thyroid panel for last 4 years. He denied skin or hair changes, diaphoresis, tremor, change in appetite, weight or bowel habits, cold/heat intolerance, palpitations, recent use of biotin or x-ray contrast exposure. Patient denied headache, visual or hearing impairment, galactorrhea, sexual dysfunction, change in facial appearance or size of gloves & shoes. Patient also denied childhood history of developmental delay, learning disability and family history of thyroid disorder. Unremarkable physical exam with normal vitals. Thyroid was normal without palpable nodule. No thyroid bruit. Normal visual field by confrontation. No tremors, gynecomastia or galactorrhea noted. Laboratory results showed normal CBC, CMP, TSH 5.2 (0.55-4.78 uIU/ml) with FT4 2.1 (0.8-1.8 ng/dl), FT3 5.4 (2.3-4.2 pg/ml), FT4 by dialysis 3.1 (0.9-2.2 ng/dl), FT3 by dialysis 433 pg/dl, Thyroglobulin ab <1 (<1 IU/ml), TPO ab 3 (<9 IU/ml), TSI <89 (<140%), TBII <1 (<2 IU/L), HAMA <6 (<74 ng/ml). Normal ACTH 17 (6-50 pg/ml), serum cortisol level 10.5 (5.2-22.4 ug/dl), prolactin 9.2 (2-18 ng/dl), GH 0.1 (<7.1 ng/ml), IGF-1 183 (53-331 ng/ml), LH 4.7 (1.5-9.3 mIU/ml), FSH 5.9 (1.6-8 mIU/ml), free testosterone 120 (35-155 pg/ml) and total testosterone 1100 (250-1100 ng/dl), SHBG 82 (10-50 nmol/L), alpha-subunit 0.8 (0.1-0.5 ng/ml) & alpha/TSH molar ratio 1.5. MRI brain with pituitary protocol showed an expansile round enhancing soft tissue mass filling the sellar cavity measuring 1.5 x 1.5 x 1.3 cm tenting the optic chiasm without cavernous sinus involvement. Patient was diagnosed with TSH secreting pituitary adenoma and referred to Neurosurgery. Patient had successful trans-sphenoidal adenectomy. Post-surgery TFTs: TSH 2.18 (0.55-4.78 uIU/ml), FT4 1.2 (0.8-1.8 ng/dl). Pathology report showed pituitary adenoma, IM stains positive for FSH, GH patchy and TSH (patchy and weak), negative for prolactin and ACTH. Rare tumor cells positive for LH Discussion: Our case highlights the importance of early diagnosis and appropriate treatment of TSH secreting adenoma to prevent complications such as hyperthyroidism, visual field defect and pan-hypopituitarism. Diagnosis in our case was particularly challenging as the patient was completely asymptomatic, therefore emphasize the importance of correlating TSH level with FT4 and early evaluation of central cause in the presence of biochemical evidence suggesting central thyroid disorder.

Presentation: Friday, June 16, 2023
FRI293 Phoenixin As A Novel Autocrine/Paracrine Factor Mediating Prolactin Regulation By Functional Interaction Of LH And IGF-I/-II In Carp Pituitary Cells
Authors: Ye Cheng , Qin Xiangfeng , He Mulan , Wong Anderson On-Lam
Published: October 2023

Disclosure: C. Ye: None. X. Qin: None. M. He: None. A.O. Wong: None.

Phoenixin (PNX), a novel peptide identified by bioinformatics, is known to have pleiotropic functions mediated by its receptor GPR173. At present, very little is known for PNX regulation and the intracellular signaling for PNX expression is still unclear. Recently, PNX and GPR173 were cloned in grass carp and found to be co-expressed in carp lactotrophs. In carp pituitary cells, PNX was also confirmed to be a novel autocrine/paracrine factor maintaining/stimulating prolactin (PRL) synthesis & secretion. To unveil the functional role of PNX in PRL regulation, a systematic screening of >40 neuroendocrine factors/local growth factors was conducted in the same cell model to look for regulators with modulatory functions for both PNX and PRL in carp pituitary. Based on our study, IGF-I & -II were shown to elevate PNX mRNA level with parallel rise in PRL gene expression in carp pituitary cells whereas the opposite was true for the functional agonist of LH, namely hCG. In parallel experiment, PRL mRNA expression induced by IGF-I was negated by removing endogenous PNX using immunoneutralization with PNX antiserum. Besides, hCG inhibition on PNX & PRL gene expression could be mimicked by parallel treatment of LH but not FSH, whereas removal of endogenous LH by LH antiserum immunoneutralization could lead to the opposite effects. Of note, hCG co-treatment not only attenuated the PNX and PRL responses induced by IGF-I but also triggered notable suppression of IGF-I receptor (IGF1R) gene expression at pituitary cell level. In our study, IGF1R & insulin receptor (InsR) expressed in carp pituitary cells were both activated by IGF-I treatment, but IGF-I induced PNX and PRL mRNA expression could be blocked only by the inactivators for IGF1R but not InsR. Using a pharmacological approach, the gene expression of PNX and PRL induced by IGF-I was confirmed to be mediated through the PI3K/Akt and MEK1/2/ERK1/2 but not P38MAPK pathways. Our findings, as a whole, suggest that (i) IGF signals can induce PRL gene expression in carp pituitary via IGF1R coupled to PI3K/Akt & MAPK cascades and this stimulatory effect is mediated via local production of PNX, and (ii) LH released in the pituitary can act locally to inhibit both basal & IGF-induced PRL expression and these inhibitory actions are mediated by blocking pituitary expression of PNX & IGF1R.

Presentation: Friday, June 16, 2023
SAT676 Severe Recurrent Pancreatitis In A Familial Partial Lipodystrophy Patient On Metreleptin
Authors: Sargin Pinar , Vinicky Mark , Biglione Alejandro
Published: October 2023

Disclosure: P. Sargin: None. M. Vinicky: None. A. Biglione: None.

Lipodystrophy syndromes are congenital or acquired disorders characterized by either total or partial lipoatrophy and often unrecognized by clinicians due to their rarity. Patients with lipodystrophy may demonstrate severe complications of metabolic syndrome since lipids are deposited in non-adipose organs where they induce lipotoxicity resulting in insulin resistance, diabetes mellitus, hypertriglyceridemia, and hepatic steatosis. Familial Partial Lipodystrophy (FPLD) syndromes are one of the four major subtypes of lipodystrophy syndromes. These are heterogeneous, mostly autosomal dominant, and characterized by site-specific subcutaneous adipose tissue loss. The management of patients with FPLD can be challenging with life-threatening complications, heavy dependence on lifestyle modifications, limited treatment options and medication availability. One of the important complications seen in these patients is pancreatitis, related to high triglyceride levels. It can be recurrent and the episodes can be more severe compared to the general patient population. Metreleptin, the human leptin analogue, is the only disease-specific treatment for lipodystrophy syndromes and it has been shown to reduce the complications of leptin deficiency, but it is not currently approved for FPLD in the USA. Previous studies showed improvement of the complications of FPLD with its use. Our case is a 29-year-old woman who has Dunnigan type FPLD with a history of numerous bouts of pancreatitis while on fenofibrate, statin and omega-3-acid ethyl esters, later was on metreleptin for almost 3 years, presented to our hospital with typical symptoms of acute pancreatitis incited by severe hypertriglyceridemia (>1,500 mg/dL). Lipase levels were high at 27,501. Patient was treated with vigorous intravenous hydration, insulin and home metreleptin was continued at the hospital. Despite the initial improvement of the symptoms, on the 6th day of hospitalization, she developed worsening abdominal pain, nausea, and vomiting. CT angiogram of the abdomen showed 2.0 cm splenic artery pseudoaneurysm. Coiled embolization of the superior segmental branch of the splenic artery performed by interventional radiologist which was further complicated by splenic infarction. Her condition improved eventually, she was able to be discharged home. Importance of adherence to medications and special diet was discussed with the patient in length. This case report aims to bring attention to this rare disease and urgent need for further treatment options for these patients to prevent serious complications in this young patient population. Metreleptin is a daily injection which could be challenging to adherence and the consequence can be relapse of pancreatitis. Lack of other treatment options, treatment availability, physician awareness are barriers to optimize the treatment for these complex patients.

Presentation: Saturday, June 17, 2023
FRI307 Gigantism Due To Transcriptional Activation Of GHRH: The First Case Of Hormone-encoding Gene Overexpression Underlying A Congenital Disorder
Authors: Hattori Atsushi , Katoh-Fukui Yuko , Zhang Ruogu , Terao Miho , Takada Shuji , Nakabayashi Kazuhiko , Hata Kenichiro , Yamada Yutaka , Matsuura Nobuo , Fukami Maki
Published: October 2023

Disclosure: A. Hattori: None. Y. Katoh-Fukui: None. R. Zhang: None. M. Terao: None. S. Takada: None. K. Nakabayashi: None. K. Hata: None. Y. Yamada: None. N. Matsuura: None. M. Fukami: None.

Background: Pituitary gigantism is characterized by tall stature due to GH overproduction. To date, known genetic causes of pituitary gigantism are invariably associated with predispositions to tumors producing GH or GHRH. Clinical and genetic findings of the patient: The patient was a Japanese woman who was born mildly large for gestational age. Her overgrowth started in her first year of life. Despite radiation and pharmacotherapy starting at age three years, she reached an adult height of 197 cm (+7.4 SD). She developed panhypopituitarism associated with empty sella in adulthood and was deceased during sleep at age 53 years. Exome sequencing identified no pathogenic variant causing acromegaly or gigantism. Chromosomal microarray analysis detected a 752-kb deletion upstream of GHRH. This deletion was predicted to create a chimeric gene consisting of the 5´-UTR of TTI1, a ubiquitously expressed gene, and the coding region of GHRH. Reverse transcription PCR (RT-PCR) using mRNA of immortalized lymphoblastoid cells detected the chimeric transcript. Analysis of model mice: We established a mouse model harboring a 676-kb deletion upstream of Ghrh using the CRISPR/Cas9 system. RT-PCR detected a chimeric transcript consisting of the 5´-UTR of Tti1 and the coding region of Ghrh, which mimicked the patient’s chimeric transcript. Mutant mice started to overgrow at two weeks of age and showed high serum GH levels and long tibia at 12-13 weeks of age. Quantitative RT-PCR showed that the median level of Ghrh expression in the hypothalamus of the mutant mice was three-fold higher than that of the wildtype mice. Furthermore, the mutant mice had ectopic Ghrh expression in all analyzed tissues (the pituitary, thymus, heart, liver, and gonad). Discussion: Our findings propose a novel etiology of gigantism. In the present case, the GHRH gene obtained a constitutively active promoter through germline genomic microdeletion. The newly acquired promoter likely led to the constant expression of GHRH in various tissues including the hypothalamus. Possible explanations for GH overproduction in the present case include (1) GHRH overproduction in the hypothalamus, (2) paracrine and autocrine effects of GHRH secreted from the pituitary, and (3) endocrine effects of GHRH produced outside the hypothalamic-pituitary unit. The patient’s clinical course suggests that prenatal GHRH overproduction only mildly affects human growth. More importantly, this is the first case in which transcriptional activation of a hormone-encoding gene caused a human congenital disorder.

Presentation: Friday, June 16, 2023
FRI314 Prolactinoma And Macroprolactin; A Diagnostic Dilemma
Authors: Farooqi Aneeba , Dewan Sandesh , Jun John
Published: October 2023

Disclosure: A. Farooqi: None. S. Dewan: None. J. Jun: None.

Prolactin is a 199 amino acid, 23 (Kilo Dalton) kDa protein secreted by pituitary lactotroph cells. The two other major forms of prolactin present in circulation are big prolactin, the dimeric 40-60 kDa prolactin and big-big prolactin or macroprolactin, 100-150 kDa complexes of 23 kDa prolactin and IgG autoantibodies. Hypothalamic dopamine is the primary regulator of prolactin secretion through its inhibitory effect. Prolactinoma accounts for ∼40% of pituitary tumors with clinical presentations of hypogonadotropic hypogonadism and tumor-related mass effects.  A 77-year-old female with a past medical history of hypertension and hyperlipidemia was admitted after a mechanical fall. She underwent a computed tomography (CT) of the brain which incidentally showed a pituitary mass. Magnetic resonance imaging (MRI) of pituitary showed a homogenously enhanced 3.0 x 3.5 x 2.8 cm mass centered in the Sella turcica, invading the supra-seller cistern, left cavernous sinus, and orbital apex abutting the optic chiasm and optic tracts. The patient did not report headache, nausea, vomiting, visual changes, or abnormal milky nipple discharge. Physical examination was unremarkable without any neurologic deficit. Formal ophthalmology evaluation showed intact extra ocular movements, visual field-testing using octopus 24-2 and Humphrey test showed few missed points, though not suggestive of pituitary related loss. Serum prolactin was measured at 1432 ng/ml (reference range, 0-25). The presence of macroprolactin was considered due to the absence of clinical features of hyperprolactinemia. The monomeric prolactin was found to be 68.7% (<40%) at 867.5 ng/ml of the total prolactin at 1259.7 ng/ml with 31.3 % of other prolactin forms are present. Evaluation for other pituitary functions was unremarkable with thyroid stimulating hormone (TSH) of 0.72 uIU/ml (0.49-4.76l), morning serum cortisol of 52.9 ug/dl (6.7-22.4), and insulin like growth factor (IGF-1) 73 ng/ml (20-214). Cabergoline 0.5 mg twice weekly was prescribed. This case illustrates a menopausal state as a probable explanation for lack of clinical features of hyperprolactinemia with macro adenoma while macroprolactin should be considered.

Presentation: Friday, June 16, 2023
FRI321 Aggressive Prolactinoma Empirically Treated With Cabergoline Leading To Rapid CSF Leak
Authors: Yau Alice , Reisman Tamar
Published: October 2023

Disclosure: A. Yau: None. T. Reisman: None.

Over two-thirds of pituitary tumors are prolactinomas. These are discovered as a result of symptoms of hypogonadism, menstrual irregularities, infertility or galactorrhea, as well as symptoms of mass effects including visual field deficit or acute severe headaches.1 A more rare subgroup, aggressive prolactinomas, in which the tumors are radiographically invasive and show resistance to dopamine agonist treatment as well as surgery, account for 10% of all hypophyseal neoplasia. 2 During medical treatment of prolactinomas, there is a known rare complication of CSF rhinorrhea; recorded time of onset of leak following treatment ranges from 14 days to 5 years.3 We present a case in which a patient with an aggressive prolactinoma rapidly developed a CSF leak within 48 hours of starting cabergoline treatment. Case: A 36-year-old male with type 2 diabetes, erectile dysfunction and infertility presents to Endocrine clinic after initial evaluation by Urology revealed elevated prolactin. He reported headaches, gynecomastia associated with liquid discharge from nipples, and minor issues with peripheral vision. He was started empirically on cabergoline for probable prolactinoma and within 48 hours developed worsening frontal headache, cough and clear fluid leakage from his right nostril. Labs revealed prolactin over 2600 ng/ml. MRI pituitary showed evidence of pituitary adenoma as well as likely CSF leak. Cabergoline was stopped and the patient was sent to the emergency room. The patient was underwent urgent neurosurgical transsphenoidal endoscopic surgery and CSF leak repair with resolution of rhinorrhea and cough. Post-operative MRI was consistent with minimal residual tumor. He was monitored in the NICU with no obvious post-operative pituitary hormone imbalance, diabetes insipidus, adrenal insufficiency or syndrome of inappropriate ADH. Months after discharge, the patient’s prolactin remained elevated to the 600’s ng/ml and repeat MRI showed a mass occupying the entire sella and suprasellar cistern, compressing the optic chiasm. Conclusion: In this case of a patient with the subtype of aggressive prolactinoma, there seems to be a more rapid presentation of complications. When treating these rare subtypes, physicians need to stay vigilant of developing complications or even consider nonstandard therapies as first-line management. 1. Molitch ME, Drummond J, Korbonits M. Prolactinoma Management. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. South Dartmouth (MA): MDText.com, Inc.; January 6, 2022.2. Lasolle H, Ilie MD, Raverot G. Aggressive prolactinomas: how to manage?. Pituitary. 2020;23(1):70-77. doi:10.1007/s11102-019-01000-73. Arimappamagan A, Sadashiva N, Kandregula S, Shukla D, Somanna S. CSF Rhinorrhea Following Medical Treatment for Prolactinoma: Management and Challenges. J Neurol Surg B Skull Base. 2019;80(6):620-625. doi:10.1055/s-0039-1677686

Presentation: Friday, June 16, 2023
FRI323 Prolactinoma Recurrence With Testosterone Treatment In Transgender Male
Authors: Arnouk Nelly , Schroeder Pamela Rose
Published: October 2023

Disclosure: N. Arnouk: None. P.R. Schroeder: None.

Introduction: We present a case of recurrent hyperprolactinemia due to testosterone treatment for gender-affirming hormonal therapy in a transgender male after being controlled on cabergoline for more than a year. Case: A 27-year-old female with history of HTN and polycystic ovary syndrome was diagnosed with pituitary microadenoma after hospital admission for headache and blurry vision. MRI brain showed a mass in the sella and right parasella measuring 36 mm W x 36 mm D x 44 mm H. Hormonal workup showed prolactin (PRL) >999 ng/mL in the diluted assay. The patient was treated medically with cabergoline and discharged home. PRL level improved to 22 ng/mL on treatment. Cabergoline was continued at 0.5 mg twice weekly. The patient was lost to follow-up but returned to clinic after 8 months with PRL level of 58 ng/mL. Cabergoline 0.5 mg twice weekly was continued. PRL level monitoring every ∼6 weeks showed an increase to 184 ng/mL and then 199 ng/mL. Cabergoline was increased to 1 mg twice weekly. PRL level 1 month later was 222 ng/mL. Repeat brain MRI showed markedly decreased microadenoma 4.8 X 2.6 mm. The patient was asymptomatic with no headache, blurry vision, or galactorrhea. On further questioning, the patient reported starting transgender female to male testosterone cypionate 200 mg/mL once weekly for the past 6 months. After discussion with the primary care provider who was managing testosterone treatment, he was started on 60 mg weekly, and the dose was gradually increased to 80 mg weekly to stop the menstrual period. With the 60-mg weekly cypionate dose, the testosterone level was 346 pg/mL, and PRL level was 184 ng/mL. With the cypionate dose of 80 mg weekly, PRL increased to 194 ng/mL and 222 ng/mL. The cypionate dose was decreased to 60 mg weekly, based on literature noting elevated PRL level with testosterone replacement in patients with prolactinoma and hypogonadism. Based on repeat blood work showing elevated testosterone 366 pg/mL with PRL 318 ng/mL, the plan is to start an aromatase inhibitor. Discussion: Testosterone treatment as hormonal affirming therapy in some transgender female to male patients may exacerbate pre-existing hyperprolactinemia or induce PRL secretion, thus close monitoring is required. Testosterone is aromatized to estradiol, which then stimulates the release of PRL from the pituitary gland. The serial measurement of estradiol may serve as an index of aromatization. Hyperprolactinemia in this setting is resistant to dopamine agonist therapy, as noted in multiple case reports. There are no established reference ranges for PRL levels for transgender patients on gender-affirming hormone therapy and no current guidelines regarding routine imaging or biochemical assessment during follow-up. Transgender patients with prolactinoma may require additional treatment with non-aromatizable androgens or the concomitant administration of aromatase inhibitors.

Presentation: Friday, June 16, 2023
FRI331 Autoimmune Hypophysitis Secondary To Ipilimumab And Nivolumab Combination Therapy In A Patient With Advanced Renal Cell Carcinoma
Authors: Ibrahim Eiman Y , Hulinsky Ilja , Regelmann David
Published: October 2023

Disclosure: E.Y. Ibrahim: None. I. Hulinsky: None. D. Regelmann: None.

Introduction: Ipilimumab and nivolumab combination therapy is an effective immune checkpoint inhibitor regimen indicated for advanced stages of renal cell carcinoma. Autoimmune hypophysitis is a rare adverse event from this therapy that occurs in only 3-6% of patients. The mechanism underlying immune checkpoint inhibitor-induced hypophysitis is not fully understood but involves immune, inflammatory, and genetic factors. Clinical Case: A 65-year-old male with a history of hypertension and type 2 diabetes mellitus, recently diagnosed with renal cell carcinoma with metastasis to the lungs presents to the emergency department with three days of generalized weakness and worsening confusion, accompanied by 2 weeks of headache. Two months prior to presentation, the patient began chemotherapy with four cycles of nivolumab and ipilimumab. The emergency department team initiated a stroke code for right facial droop and right-sided weakness seen on his physical exam. The CT of the patient’s head was unremarkable. The patient was also hypotensive (BP 90/40 mmHg) and tachycardic (140 bpm). He received 3 liters of crystalloid as well as diltiazem injection without improvement. Random cortisol on admission at 11:00 am was 1 ug/dl (3.4-22), ACTH was 7 pg/mL (6-50), Na was 135 mEq/L (137 - 145) and K was 5.1 mEq/L (3.5 - 5.0). Furthermore, TSH 0.02 μIU/ml (0.47-4.70), ILGF 39 ng/mL (41-279), and total testosterone levels <3 ng/dL (139-740) were low. The free thyroxine level was measured at 1.00 ng/dL (0.8-1.9), and MRI revealed a normal sella tursica. Based on these findings, we diagnosed the patient with hypopituitarism, likely due to hypophysitis as an immune-related adverse event of immune checkpoint inhibitor therapy. Consequently, we discontinued the administration of Ipilimumab-Nivolumab combination therapy and started oral dexamethasone 8 mg and fludrocortisone 0.1 mg for mineralocorticoid supplementation. The patient’s symptoms resolved, and laboratory data showed improvements in hyponatremia, hyperkalemia, and hypoglycemia. The care team transitioned the patient’s steroid regimen to prednisone 25 mg daily maintenance dose, and the patient was discharged with stress dosing instructions. Conclusion: Diagnosis of hypophysitis as an immune-related adverse event is challenging due to its vague presentation. However, a delayed diagnosis can be life-threatening. As a result, clinicians must maintain a high index of suspicion for presentations of weakness and headache in consistent clinical contexts, in order to provide optimal management and minimize morbidity. Additionally, early management of hypophysitis can reduce the interval of immune checkpoint inhibitor therapy, which in turn affects the course of cancer.

Presentation: Friday, June 16, 2023
FRI336 A Case Of Pituitary Apoplexy In Late Pregnancy
Authors: Abdelrahman Houda , Rasiah Stephen , Braunthal Stephanie , Mahoney Lindsey , Carneiro Raquel M , Chen Kenneth K
Published: October 2023

Disclosure: H. Abdelrahman: None. S. Rasiah: None. S. Braunthal: None. L. Mahoney: None. R.M. Carneiro: None. K.K. Chen: None.

Case: A 20-year-old primigravida presented at 36 weeks gestation due to persistent left-sided headache of 4 weeks duration. MRI brain demonstrated pituitary enlargement (15x17x14 mm) with hemorrhage as well as suprasellar extension and mass effect upon the optic chiasm, consistent with pituitary apoplexy (PA). She has no known medical history or prior endocrinopathies. Serum prolactin was appropriately elevated for pregnancy (299 ng/mL). She was started on levothyroxine for secondary hypothyroidism (TSH 3.4 mcg/dL, free T4 0.8ng/dL (0.7-1.5 ng/dL)) and hydrocortisone for prevention of adrenal insufficiency. She was admitted for semi-urgent induction of labor following the discovery of visual field defects on formal perimetry testing by ophthalmology. After discussion with neurosurgery and maternal fetal medicine, she was permitted to have a trial of vaginal delivery with a brief period of Valsalva but she ended up requiring an emergency C-section due to failure to progress. Her delivery was complicated by significant blood loss (∼5000ml), resulting in bilateral uterine artery embolization followed by an emergency hysterectomy. Repeat MRI brain with contrast following delivery demonstrated a cystic pituitary lesion, possibly a Rathke’s cleft cyst. She underwent endoscopic transnasal exploration and resection two days following delivery. Discussion: Pituitary apoplexy is a rare cause of acute headache in pregnancy. The majority of PA occurs in the setting of undiagnosed pituitary adenomas. Rapid treatment of possible adrenal insufficiency is imperative. Conservative versus surgical treatment plans are tailored to the patient’s obstetric care and neurological status. The earliest reported PA occurrence is at 7 weeks gestation (associated with subsequent miscarriage). Coordination of care between different specialists is paramount especially in late pregnancy. It is theoretically possible that Valsalva during vaginal delivery may increase intracranial pressure and exacerbate hemorrhage. Women with pituitary adenomas are recommended to undergo standard obstetric care with close surveillance, as C-section deliveries can also be associated with increased blood loss. Timing of surgery in gestational pituitary apoplexy is variable; it may be up to one month after delivery. Dopamine agonist therapy may be started during pregnancy for confirmed prolactinomas. The European Society of Endocrinology recommends transsphenoidal surgery in the second trimester for symptomatic adenomas. In the third trimester, preterm delivery may be considered. Post-operative adverse events are not uncommon due to the high risk nature of these pregnancies. After surgery, most patients should experience some degree of vision improvement but many will continue to need hormone replacement.

Presentation: Friday, June 16, 2023
FRI341 Nothing Great Comes Without Its Risks; A Rare Case Of Pembrolizumab Induced Hypophysitis
Authors: Fernando Ashen Kavinda , Cheema Rashid
Published: October 2023

Disclosure: A.K. Fernando: None. R. Cheema: None.

Introduction: Immune checkpoints are proteins expressed by immune cells and are crucial for maintaining self-tolerance. Immune checkpoint inhibitors (ICIs) are antibodies that inhibit these checkpoints and enhances T-cell activation and antitumor activity. This emerged as a powerful tool in treating cancer, however its use is jeopardized by various immune related adverse events (IRAEs). Secondary hypophysitis, although rare, is associated with immunotherapy. The incidence of hypophysitis is considerably lower with PD-1 inhibitors such as pembrolizumab (0.5-1.5%) than with CTLA-4 inhibitors. We present a case of hypophysitis following initiation of pembrolizumab for NSCLC.

Case: A 64-year-old Caucasian male was seen in Endocrinology for evaluation of abnormal TFTs with nonspecific symptoms of fatigue and malaise. He was recently diagnosed with poorly differentiated lung carcinoma with metastasis to brain. After completing XRT, he was started on pembrolizumab/trastuzumab. TFTs prior to initiation of treatment were unremarkable. He developed a mild rash and fatigue post treatment but otherwise treatment was well tolerated. TFTs at week 8 after starting ICIs showed TSH 0.09 uIU/mL (0.27-4.2), T4 0.8 ng/dL (0.9-1.7) and T3 2.2 pg/mL (2.5-4.3). MRI Sella showed enlargement of the pituitary gland and stalk suggestive of hypophysitis. Pembrolizumab was discontinued. Additional studies showed low total testosterone 19.5 ng/dL (193-740) and free testosterone 4.5 pg/mL (35-130) with inappropriately normal gonadotropins suggestive of central hypogonadism. Other pituitary axis were intact. Cosyntropin stimulation test confirmed intact HP Adrenal axis. He was started on levothyroxine and hydrocortisone (20 mg AM and 10 mg PM) for hypophysitis. His symptoms improved. He is closely being monitored with plan to repeat MRI Sella in 3 months and to re-evaluate his HP adrenal prior to weaning off steroids. Discussion: IRAEs from ICIs typically present within 6 to 12 weeks but can present several months to years later. The non-specific nature of symptoms in patients on PD-1 inhibitors can delay clinical recognition with dire consequences. Treatment involves hormone replacement and stopping immunotherapy. Though benefit of GC in patients with grades 1-2 hypophysitis is unclear, low dose corticosteroids have been used to mitigate pituitary inflammation. High dose GC although commonly used in patients with critical illness (grades 3-4), its use remains controversial as they have not shown to significantly alter overall survival. Some degree of pituitary function may recover 4-12 weeks following withdrawal of ICIs. Given the increase in use of ICIs and the serious nature of IRAEs, it is critical to be aware of clinical manifestations, diagnosis, and management of this entity.

Presentation: Friday, June 16, 2023
FRI371 Serum Androstenedione As An Additive Biomarker In Ectopic Cushing’s Syndrome Evaluation
Authors: Zhang Sherry , Lo Joan C , Jaffe Marc G , Arzumanyan Hasmik
Published: October 2023

Disclosure: S. Zhang: None. J.C. Lo: None. M.G. Jaffe: None. H. Arzumanyan: None.

Background: Ectopic Cushing’s syndrome (ECS) results from glucocorticoid excess secondary to ectopic ACTH or CRH producing tumors. Although ECS identification can be challenging when presentation lacks classic Cushing’s features, ectopic ACTH secretion can result in a key constellation of findings that facilitate early clinical recognition. We describe a case of ECS from an ACTH-producing carcinoid tumor of the lung presenting with resistant hypertension, severe hypokalemia, and muscle weakness. In addition to significant hypercortisolism, laboratory findings were notable for high androstenedione levels without concomitant increase in DHEAS and testosterone levels. Case: A 59-year-old female athlete with history of well-controlled hypertension developed difficult to control hypertension, requiring escalation to triple antihypertensive therapy within 3 months. During this time, she had multiple emergency department visits for progressive muscle weakness, hypertension, and persistent hypokalemia despite potassium supplementation. She was hospitalized for further evaluation. Physical examination was notable for bruising, muscle wasting, thin extremities, facial fullness, and disproportionate abdominal adiposity. Workup for Cushing’s syndrome demonstrated ACTH-dependent hypercortisolism and markedly elevated androstenedione 398 ng/dL (normal 20-75 ng/dL) despite normal DHEAS 48 mcg/dL (normal <430 mcg/dL) and total testosterone 11 ng/dL (normal <45 ng/dL) levels. A chest CT identified a 3.8 cm right lower lobe lung mass and transbronchial biopsy confirmed atypical carcinoid tumor. She underwent a right middle and lower lobe bilobectomy with complete tumor resection. Cortisol, androstenedione, and potassium levels rapidly normalized postoperatively, and blood pressure returned to baseline, well-controlled on monotherapy. The patient only required 3 days of hydrocortisone therapy for transient steroid withdrawal symptoms. Conclusions: Our case illustrates a difficult to diagnose uncommon disease presenting with resistant hypertension, hypokalemia and marked androstenedione elevation despite normal DHEAS and testosterone levels. This steroidogenic profile has been reported in other ECS cases and attributed to differential effects of ectopic ACTH production on adrenal androgen biosynthesis (1). Although ECS is rare and the primary lesion can be difficult to identify, disproportionate elevation in androstenedione may prompt recognition of ECS and support early detection and management.

Reference: (1) Barbetta L, Dall’Asta C, Re T, Colombo P, Travaglini P, Ambrosi B. Androgen secretion in ectopic ACTH syndrome and in Cushing’s disease: modifications before and after surgery. Horm Metab Res Horm Stoffwechselforschung Horm Metab. 2001;33(10):596-601

Presentation: Friday, June 16, 2023
OR13-03 Assessment Of Skeletal Health Including Bone Density, Turnover, Microarchitecture And Osteoporosis In Patients With Sheehan’s Syndrome: A Prospective, Multicentric Study In Asian Indians
Authors: Das Liza , Laway Bashir , Sahoo Jayaprakash , Bhadada Sanjay K , Dutta Pinaki
Published: October 2023

Disclosure: L. Das: None. B. Laway: None. J. Sahoo: None. S.K. Bhadada: None. P. Dutta: None.

Introduction: Sheehan’s syndrome (SS) is a rare cause of hypopituitarism. Evidence on skeletal health in patients with this condition is limited, and data on bone geometry, structure and volumetric bone mineral density (BMD) are lacking. We aimed to comprehensively explore skeletal fragility in a multicentric cohort of treated SS. Patients and Methods: Patients with SS were recruited for analysis of demographic, clinico-biochemical and hormonal profile including bone turnover markers. Areal BMD, T- and Z-scores and trabecular bone score (TBS) were evaluated using DXA. In a subset of patients (n=29) as well as age-and BMI-matched controls (n=34), high-resolution peripheral quantitative computed tomography (HRpQCT, XtremeCT II, Scanco Medical AG, Switzerland) was performed to assess bone geometry and microarchitecture. Results: There were a total of 105 patients with SS with a mean age 45.2 ± 10.5 years and a lag of 7.4 ± 5.5 years from disease onset to diagnosis. Regular levothyroxine replacement was ongoing in 91.2% and glucocorticoid replacement in 86.1% of the cohort. Past HRT replacement was done in 66.7% patients. Bone turnover markers (P1NP, CTX) were not significantly different between cases and controls. The T- score [-2.3 (-3.0 to -1.6) vs -1.5 (-3.0 to -0.7)] and Z-score [-1.4 (-2.1 to -1.2) vs -0.6 (-2.1 to -0.1)] at the lumbar spine (LS) and the T- score [-1.8 (-2.3 to -1.3) vs -0.8 (-2.1 to -0.1)] and Z-score [-1.1 (-1.7 to -0.4) vs -0.4 (-1.0 to 0.2)] at the femoral neck (FN) were lower in cases as compared to controls (trend towards significance). Osteopenia or osteoporosis was prevalent in significantly greater proportion of the cases as compared to controls, at LS (96.3% vs 64.7%), FN (91.7% vs 47%) and ultradistal radius (65.2% vs 11.8%). Bone microarchitectural assessment showed no significant differences between TBS, or bone geometry. However, trabecular volumetric bone mineral density was higher at both tibia (p<0.05) and radius (p>0.05) in cases as opposed to age-and BMI-matched controls. There was a weak negative correlation between glucocorticoid and levothyroxine replacement duration and BMD at both LS and FN (p<0.05), but not with replacement dose. Conclusion: Osteopenia-osteoporosis is highly prevalent in SS. BMD at both LS and FN is negatively correlated with duration of glucocorticoid and levothyroxine exposure. There are no significant differences in bone microarchitecture or geometry but tibial trabecular volumetric BMD is greater in treated SS.

Presentation: Friday, June 16, 2023
THU602 A Comprehensive Review Of Incidence, Demographics, Laterality And Survival Analysis Of Adrenal Malignancies.
Authors: Desai Krishna , Pereira Kristal , Iqbal Sabah , Baralo Bohdan , Vidhi Mehta , Renzu Mahvish , Rather Manzoor , Thirumaran Rajesh
Published: October 2023

Disclosure: K. Desai: None. K. Pereira: None. S. Iqbal: None. B. Baralo: None. M. Vidhi: None. M. Renzu: None. M. Rather: None. R. Thirumaran: None.

Background: Adrenal malignancy is extremely rare in the United States with only ∼200 new cases/per year. Adrenocortical carcinoma is the most common histologic subtype, followed by pheochromocytoma and neuroblastoma. In this study, our aim is to evaluate the incidence rate and compare the survival analysis based on race, laterality, and histologic tissue involvement. Method: The data were collected from Surveillance, Epidemiology, and End Result database 17 Registries, Nov 2021 Sub (2000-2019). We included patients above 20 years with a primary diagnosis of an adrenal malignant tumor. Neuroblastomas were excluded due to low incidence in the adult population. We analyzed incidence rates using linear regression with t-test and compared overall survival (OS) curves using the Log-rank test (GraphPad Prism). Result: 3323 cases were identified with the majority being female (54.68%). 50.29% were adrenal cortical tumors, followed by pheochromocytoma (14.44%) & neuroblastoma (0.51%). 48.03% were left-sided, 39.54% were right-sided, 3.64% were bilateral & the rest were unspecified. The incidence rate for adrenal tumors is 2.77 per 1 million. The highest incidence was among Caucasians (2.98), followed by African American (2.63, p=0.09), which is higher than Asians (2.03, p<0.0001) and Hispanics (2.42, p=0.0002). A review of the incidence trends showed that only African-American patients had rising incidence rates from 1.46 in 2000 to 2.48 in 2019 (p=0.02). Patients with adrenal cortical tumors had worse survival compared to patients with pheochromocytoma (19 vs 98 months) HR 2.236 [1.988-2.232]. No significant statistical difference was noticed in the survival of left vs. right-sided tumors or racial groups when subdivided based on histology. However, there was a difference in the median survival of the women with pheochromocytoma (123m), compared to men (75m) HR 1.397 [1.064 - 1.834]. Conclusion: The incidence rate of adrenal malignancies remained stable and is higher among Caucasians compared to Hispanics and Asians. We noticed concerning rising incidence among African American patients. Patients with adrenocortical tumors had worse survival compared to patients with pheochromocytoma. Laterality of the tumor and race of the patients plays no role in survival in adrenal malignancies, unlike the colon and kidneys. However, there is a noticeably lower survival of the male population with pheochromocytoma.

Presentation: Thursday, June 15, 2023
SAT589 A Case Of Lymphocytic Hypophysitis In A Young Female With Unilateral Abducens Nerve Palsy
Authors: Yu Jeremy H , Nguyen Michael L , Horani Mohamad Hosam , Shahlapour Mahmood
Published: October 2023

Disclosure: J.H. Yu: None. M.L. Nguyen: None. M.H. Horani: None. M. Shahlapour: None.

Lymphocytic hypophysitis is a neuroendocrine disorder characterized by autoimmune inflammation of the pituitary gland. Lymphocytic hypophysitis is the most common form of hypophysitis with the cause usually unknown. It often occurs in late pregnancy or in the postpartum period with affected individuals presenting with symptoms of headaches of an intensity out of proportion to the size of the lesion and with hypopituitarism. Other manifestations include visual field defects and ocular motility disturbances. We present a case of a 24 year old Female who presents with headache, diplopia, and left-sided CN6 nerve palsy of 4 day duration. She has a known history of amenorrhea for the past year and obesity. She also presents with polydipsia and polyuria. Further workup included MRI of the brain showing a sellar mass with mass effect on optic chiasm and left cavernous sinus lesion. Pituitary hormonal workup showed ACTH 13, LH 0.42, FSH 2.1, TSH 0.442, free T4 1.0, random cortisol 6.3, and prolactin 78. Lumbar puncture with basic CSF studies showed glucose 56, protein 48, nucleated cells 38 (lymph 91%, poly 4%, mono 5%), and RBC 4. ACE, AFP, IgG4, ANA, ANCA, and CEA workup was negative. Biopsy of the mass was performed with results suggesting lymphocytic hypophysitis. Additional immunohistochemistry stains will be performed to evaluate for IgG4 related diseases. The patient would later develop diabetes insipidus and central hypothyroidism weeks later. Discussion: The lymphocytic infiltration causes inflammation, enlargement and fibrosis of the pituitary gland which can produce a mass effect on surrounding tissues. The definitive diagnosis is made via histopathology staining of biopsied sellar or suprasellar tissue. The condition predominantly affects women more than men at a ratio of 8:1.Treatment involves evaluation of pituitary function with management of any hormone deficiencies and alleviating any mass effects due to pituitary inflammation and enlargement. First line treatment usually involves high dose corticosteroids with refractory cases being treated with immunosuppressive medications. Surgery or fractionated radiotherapy can be used if medical therapy fails. In our patient, a biopsy was performed that confirmed lymphocytic hypophysitis with unmasked diabetes insipidus and hypothyroidism presenting weeks after starting on high-dose corticosteroids. Conclusion: This case highlights the unique presentation of lymphocytic hypophysitis including left-sided CN6 nerve palsy, headaches, and hypogonadotropic hypopituitarism. From our knowledge, it is one of the first presentations with unilateral CN6 nerve palsy as a mass effect from lymphocytic hypophysitis.

Presentation: Saturday, June 17, 2023
SAT593 Mechanism Of Kisspeptin Neuron Synchronization In Acute Brain Slices From Female Mice
Authors: Morris Paul G , Herbison Allan Edward
Published: October 2023

Disclosure: P.G. Morris: None. A.E. Herbison: None.

Arcuate kisspeptin (ARNKISS) neurons, which co-express glutamate, neurokinin B and dynorphin, intermittently synchronize their activity to drive pulsatile hormone secretion. However, the mechanisms underlying such network behaviour remains unclear in females. Using an acute Kiss1-Cre GCaMP6 brain slice preparation which maintains spontaneous synchronized ARNKISS neuron burst firing, we were able to both characterise this behaviour and reveal the neurotransmitter receptors contributing to it. Results in diestrous female mice revealed that the order individual neurons took part in synchronizations was only mildly consistent, with a mean Spearman correlation coefficient of 0.43. Spontaneous ARNKISS neuron synchronizations were found to be highly dependent on glutamate transmission via AMPA receptors, as well as Neurokinin B transmission. Inhibition of NMDA receptors did not alter rates of synchronization, and similarly inhibition of kappa opioid receptors had no effect on rate of synchronization or duration of spontaneous events. Combined with previously published data in male mice, these data underscore the importance of AMPA receptors in synchronizing the ARNKISS neuron network, but additionally suggest a sex difference in the relative contribution of neurokinin B to synchronizations.

Presentation: Saturday, June 17, 2023
SAT596 Evidence That Corticotropin-releasing Hormone Receptor 2 Activation Mediates Stress-induced Hyperglycemia
Authors: McCosh Richard B , Kreisman Michael J , Jang Jessica , Jung Jacklyn , Breen Church Kellie M
Published: October 2023

Disclosure: R.B. McCosh: None. M.J. Kreisman: None. J. Jang: None. J. Jung: None. K.M. Breen Church: None.

Stress-induced hyperglycemia refers to the transient increase in blood glucose (BG) levels during stress, which occurs in healthy and diabetic patients. In critically ill patients, stress-induced hyperglycemia is associated with a 2-fold increase in risk of incident diabetes. Thus, stress-induced hyperglycemia is a predictor of or may contribute to glucose dysregulation. In mice, activation of catecholamine neurons in the rostral ventral lateral medulla (rVLM) is necessary for stress-induced hyperglycemia; however, the mechanism by which these cells become activated during stress is not clear. Here, we tested the possibility that corticotropin-releasing hormone receptor 2 (CRHR2) signaling mediates stress-induced hyperglycemia in adult, ovariectomized mice. First, BG levels and rVLM cell activation were examined in two stress models. For psychosocial stress, BG levels were not altered by control treatment. In contrast, placement in a restraint device increased BG levels ∼2-fold, within 30 min, from pretreatment values and BG remained elevated for an additional 90 min. For immune stress, BG was significantly elevated (21% increase) at 30 min post IP injection of lipopolysaccharide (LPS, 10ng/g bw), then returned to baseline levels whereas BG levels were not altered from pretreatment levels in saline injected mice. In tissue collected 2 hr after initiation of restraint stress, the percentage of tyrosine hydroxylase (TH, marker of catecholamine cells) neurons in the rVLM that contained c-Fos (a marker of neural activation) was significantly greater than control mice. Next, we assessed the sufficiency of CRHR2 activation to induce hyperglycemia using the CRHR2 agonist urocortin 2 (UCN2), injected intracerebroventricular (ICV). BG was significantly increased 30 min after injection of both saline and UCN2 (60-80%); however, BG subsequently returned to baseline in saline-treated mice, but remained elevated in mice that received UCN2, similar to restraint stress. To test necessity of CRHR2 activation to induce hyperglycemia, we delivered ICV either the specific CRHR2 antagonist Astressin 2B (A2B) or saline 1 hr before psychosocial or immune stress. In no stress controls, A2B did not alter BG levels compared to saline, yet, BG levels in both groups decreased over time. BG levels were elevated in saline-treated controls 30 min after restraint stress; and, this increase was delayed, although not prevented, by 30 min by A2B pre-treatment. Following LPS injection, BG was increased at 30 min then decreased relative to baseline in saline-treated controls; yet, A2B pre-treatment blocked these changes. Together these data support the hypothesis that CRHR2 signaling is an important mediator of stress-induced hyperglycemia. Assessment of rVLM TH cells is ongoing.

Presentation: Saturday, June 17, 2023