bluuebunny/crossref_metadata_2025 huggingface dataset:
6419 Cushing’s Syndrome due to Metastatic Pancreatic Neuroendocrine Neoplasm With Incidental Pituitary Microadenoma
Authors: Ibrahim A , Esper L , Jain R , El Asmar N
Published: October 2024

Disclosure: A. Ibrahim: None. L. Esper: None. R. Jain: None. N. El Asmar: None.

Introduction: Pancreatic neuroendocrine neoplasms (PNENs) are rare with a reported incidence of 1-2/100,000. While the majority are non-functional, insulinomas and gastrinomas are the most common functional PNENs. Our case of ACTH-producing PNENs is extremely rare. Case presentation: A previously healthy 47-year-old female was hospitalized for worsening dyspnea. Her symptoms included rapid weight gain, skin hyperpigmentation, and lower extremity edema. Her exam was notable for elevated blood pressure of 181/120 mmHg, moon facies, purple abdominal striae, and proximal myopathy. Her lab analysis showed a cortisol level of 42 mcg/dL (6.2-19.4), ACTH of 254 pg/ml (7.2-63), DHEA sulfate of 171 mcg/dl (41-243), HbA1C 7%, K of 3 mmol/l and 24H urine cortisol >2100 mcg/24hrs. A post low-dose DST cortisol level was 42.7 mcg/dl. CT chest demonstrated an ill-defined hypodense lesion in the region of the pancreatic head. MRI abdomen revealed a 3 x 2.3 x 2.3 cm mass in the pancreatic head and many small enhancing lesions within the right lobe of the liver. Adrenal glands appeared normal. Subsequent PET CT scan with GA 68 DOTOTATE showed increased uptake in the pancreatic head mass and in the right hepatic lobe. Her pituitary MRI revealed a right pituitary gland 6 mm hypointense lesion, possibly a microadenoma. A high dose DST resulted in a cortisol level of 80 mcg/dl mostly consistent with ectopic ACTH secretion. EUS-guided biopsy of the pancreatic mass showed a well-differentiated neuroendocrine tumor that stained positive for ACTH, chromogranin, synaptophysin, and CD56. Treatment with Ketoconazole 600mg q6h and Octreotide 50mg q6h was started 3 days before surgery to control acute hypercortisolism as she developed acute psychosis. The patient subsequently underwent a Whipple procedure with successful resection of the pancreatic mass. Post-op, her ACTH levels dropped to 19 pg/ml with a cortisol level of 6 mcg/dl. Final pathology showed a well-differentiated grade 3 neuroendocrine tumor with a KI-67 labeling index greater than 20%. After surgery, the patient received a short course of stress dose hydrocortisone which was tapered off over the following 2 months. The patient is being followed for planning further intervention given the aggressive grade of the tumor and hepatic metastases. Conclusion: Ectopic ACTH-producing PNENs are rare. An accurate and timely diagnosis, while challenging, is key. Patients usually present with rapidly progressing symptoms that could cause life-threatening complications such as thrombosis and sepsis. We demonstrated the importance of utilizing a multidisciplinary team approach and starting cortisol-lowering medications early given the complexity of the disease, requiring rapid intervention and lifelong follow-up.

Presentation: 6/3/2024
9272 Diagnostic utility of 11C-Methionine PET-CT imaging in persistent or recurrent Cushing’s disease after transsphenoidal surgery
Authors: Furnica Raluca Maria , Devuyst France , Mathey Céline , Constantinescu Stefan Matei , De Herdt Carlien , Renaud Lhommel , Maiter Dominique M
Published: October 2024

Disclosure: R. Furnica: None. F. Devuyst: None. C. Mathey: None. S. Constantinescu: None. C. De Herdt: None. L. Renaud: None. D.M. Maiter: None.

Introduction: Equivocal or negative pituitary magnetic resonance imaging (MRI) findings pose a significant challenge in the management of persistent or recurrent Cushing’s disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of [1][1]C-methionine (MET) positron emission tomography coupled with computerized tomography (PET-CT) in localizing the residual corticotroph adenoma. Methods: We retrospectively analyzed the results of all MET-PET-CT performed between May 2002 and November 2023 in patients with a CD persisting or relapsing after TSS, and equivocal (n=14) or negative pituitary MRI findings (n=8). In 15 cases, images obtained from MET-PET were also co-registered with a high-resolution 3D pituitary MRI. All patients had a pathologically confirmed corticotroph tumor, and/or biochemical evidence of early postoperative remission after the first TSS, and/or proven ACTH-dependent Cushing’s syndrome with positive bilateral inferior petrosal sinus sampling. Results: Twenty-two patients were included (18 females and 4 males), with a mean age of 35.5 years at diagnosis. Initial tumors were mostly microadenomas with a mean tumor volume of 15 mm3. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A significant MET standardized uptake value (SUV) in the suspected area of the tumor residue was defined as a ratio ≥ 1.80 relative to cerebellum SUV and was found in 12/22 patients (55%; 4 patients with negative pituitary MRI and 8 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 10 patients and was successful in 6, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate: 8/12). Among the 4 patients not cured by TSS, the presence of corticotroph adenoma in the resected tissue was found in 3 cases. Exploratory TSS was performed in 4 of the 10 PET negative patients, with no remission. Two patients were treated with GKRS, with remission in 1 case. Among the 4 other patients, bilateral adrenalectomy was performed in one case and adrenal steroidogenesis inhibitors were used in the remaining patients. Conclusions: [1][1]C-Methionine PET-CT imaging can provide valuable diagnostic information to detect a residual active corticotroph adenoma in about half of patients with a persistent or recurrent CD and equivocal or negative MRI results, thereby allowing targeted TSS or radiosurgery with a global success rate of 67% in this selected subpopulation.

Presentation: 6/1/2024
8365 Bilateral Adrenal Hemorrhage Unveiling Adrenal Metastases In A Patient With Retroperitoneal Sarcoma
Authors: Jatin Shah Rutu , Carol Goldberg Anne , Itani Malak , Jasim Sina
Published: October 2024

Disclosure: R.J. Shah: None. A.C. Goldberg: None. S. Jasim: None.

Introduction: Metastatic disease to the adrenal gland is the most commonly occurring malignancy of the adrenal glands. Adrenal hemorrhage (AH) however is a rare but potentially fatal manifestation of malignancy. This case report highlights the unusual presentation of retroperitoneal sarcoma, manifesting as bilateral adrenal hemorrhage in the context of underlying metastases. Case Presentation: A 53-year-old man presented with a 4-week history of fatigue, intermittent abdominal pain radiating to the back, and vomiting. CT revealed bilateral adrenal masses measuring up to 8.5cm on the left side, with Hounsfield units (HU) 27, and 5.9cm on the right, HU 27, consistent with large areas of bilateral adrenal hemorrhage later confirmed on MRI. Biochemical evaluation included ACTH-stimulated cortisol, which was borderline at 17.4mcg/dl (recommended above 18-20mcg/dl), with a significantly elevated ACTH level of 103.8pg/nl (reference range 7.0-63.0pg/ml). Plasma metanephrines, electrolytes, aldosterone, and DHEA-S were normal. Although hemodynamically stable, he was started on prednisone 5mg daily as he was at high risk for primary adrenal insufficiency (AI). He was referred to endocrine surgery and further workup with PET/CT demonstrated a new FDG-avid periaortic retroperitoneal mass, with an interval increase in the size of the adrenal masses and development of hypoattenuating lesions in the kidneys and pancreas favoring aggressive metastatic disease. He underwent biopsy of the retroperitoneal mass, and pathology was consistent with high-grade sarcoma. Oncology started treatment with dexrazoxane and doxorubicin. His adrenal masses remained unchanged in size, and the patient died related to rapid progression of disease. Discussion: Spontaneous bilateral adrenal hemorrhage is rare with a reported incidence of 0.14 to 1.8%. Although most cases have been associated with sepsis, anticoagulation, hematologic disorders and trauma, it is important to maintain a high level of suspicion for underlying adrenal tumors and metastatic disease. AH can be a diagnostic challenge because of its non-specific presentation, and imaging is vital for timely recognition. Patients with bilateral AH should be managed with corticosteroids to avert AI-related fatalities.

Presentation: 6/1/2024
8411 Ectopic ACTH-dependent Cyclical Cushing’s Syndrome- the Art of Hide-and-seek
Authors: Mon Hla Myat , Kapoor Ashutosh , Qureshi Sheharyar , Martineau Marcus , Meeran Karim
Published: October 2024

Disclosure: H. Mon: None. A. Kapoor: None. S. Qureshi: None. M. Martineau: None. K. Meeran: None.

Case report: A 72-years-old lady was admitted with hypokalaemia, hyperglycaemia with metabolic alkalosis with background hypertension, type2 diabetes, osteoporosis and right-sided breast cancer treated with chemotherapy and radiotherapy 3years ago. She was previously seen in Endocrinology Clinic for similar episode and deemed not having Cushing’s or Conn’s syndrome on workup. During this admission, although there was no obvious Cushingoid appearance, there was refractory hypokalaemia. On further exploration, there were previous admissions with similar episodes in UK and in her home country, within the same year, a few months apart. Therefore, endocrinology workup was conducted for suspected cyclical Cushing’s syndrome. It demonstrated raised 24-hour urinary free cortisol of 5643 nmol/24hour (reference range 0-164 nmol/24hours), unsuppressed low dose dexamethasone suppression test with cortisol level of 800 nmol/L and increased ACTH level of 429 ng/L. MRI (pituitary) showed no pituitary lesion with probable empty sella and CSF filled. However, CT (thorax) showed enlarging lesion (previously from 1cm to 1.6cm) in the left lower lobe, concerning lung metastasis or primary lung malignancy. PET scan showed left lower lobe nodule having low-grade activity with likelihood of indolent malignancy and appearances of physiologic adrenal hyperplasia. Management: Given persistently high cortisol levels during admission with ongoing hyperglycaemia and refractory hypokalaemia, metyrapone was started and titrated accordingly. Her clinical condition including potassium and cortisol levels effectively responded to metyrapone. Gallium scan was booked for detail localization with ongoing lung MDT (multidisciplinary team meeting) and neuroendocrine tumour MDT.However, after starting metyrapone, she had type 1 respiratory failure, not responding to initial antibiotics. After excluding other possible respiratory aetiologies, empirical treatment for Pneumocystosis pneumonia (PCP) was initiated, after which blood test for Beta-D-glucan was found out to be significantly raised, supporting the presumptive diagnosis. Conclusion: Our case highlighted the following interesting points 1. diagnostic challenges, due to the fluctuating nature of cyclical Cushing’s syndrome, presenting with recurrent hypokalaemia. 2. the interesting nature of likely ACTH-dependent cyclical Cushing’s syndrome, progressing into florid Cushing’s syndrome, with efficacy to metyrapone 3. rare and compelling combination of 3 conditions of Cyclical Cushing’s syndrome, being ectopic ACTH-dependent and complicated by Pneumocystosis pneumonia (PCP).

Presentation: 6/1/2024
6728 Bilateral Adrenal Hemorrhage: Cause Or Consequence?
Authors: Natasha Rayan Melanie , Horner Robert , Valenciaga Anisley , Ryan Laura E
Published: October 2024

Disclosure: M.N. Rayan: None. R. Horner: None. A. Valenciaga: None. L.E. Ryan: None.

Introduction: Before the advent of the CT scan, bilateral adrenal hemorrhage was primarily discovered post-mortem in patients who had succumbed to sepsis, burns, or anticoagulant therapy. Today, non-traumatic hemorrhage is recognized as an infrequent, yet potentially lethal diagnosis causing clinical deterioration in acutely ill patients. Clinical Case: Our patient is a 64-year-old-male with a medical history of Myelodysplastic Syndrome initially presented to an external ED with abdominal pain. CT abdomen revealed hepatomegaly, splenomegaly, and new bilateral adrenal masses—absent in an MRI conducted a year earlier. He was treated conservatively and subsequently discharged. Two weeks later, he returned to the hospital with severe right sided flank pain. His hemoglobin and platelet counts dropped from 11.5 g/dL and 309 K/uL during the previous ED visit to 7.7 g/dL and 80 K/uL, respectively. Additionally, his PT/INR, PTT, fibrinogen, and D-Dimer levels were elevated. A repeat CT scan indicated a significant enlargement of the right adrenal mass, raising suspicion of adrenal hemorrhage. He was appropriately transfused, and a BM biopsy was performed to evaluate for acute transformation of underlying MDS. Cortisol levels were monitored daily for adrenal insufficiency. A complicated hospital course ensued marked by worsening anemia, thrombocytopenia, and coagulopathy, accompanied by high fevers and new-onset atrial fibrillation. Mixing studies showed absence of a factor inhibitor ruling out acquired forms of Hemophilia. Infectious workup including fungal and viral serologies returned negative. A PET scan revealed several small hypermetabolic hypodense liver lesions, and hypermetabolic activity diffusely in the spleen, and adrenal glands leading to suspicion of metastasis. Results of the BM biopsy returned revealing hypercellularity, with aggregates of hemosiderin-laden macrophages replacing the bone marrow space with associated necrosis. Worsening abdominal pain with hematochezia prompted an endoscopy, confirming a diagnosis of metastatic melanoma. Concurrently, seizure activity and altered mentation led to a head CT, revealing new metastatic lesions that confirmed the rapid progression of the disease. Subsequently, the patient was transitioned to comfort care and passed away. Clinical Lesson: It is crucial to review the various causes of adrenal hemorrhage, understand the challenges associated with interpreting adrenal imaging, emphasize the need to monitor adrenal function, and consider the occasional necessity for tissue sampling. In this clinical scenario, metastases with hemorrhage were the most likely etiology. The causes of adrenal hemorrhage are not always apparent; in this presentation, the consequence of the underlying disease state ultimately led to the initial presenting symptom of abdominal pain.

Presentation: 6/2/2024
12516 Bilateral Adrenalectomy And Bariatric Surgery For Hormonal And Metabolic Control Of Classic Congenital Adrenal Hyperplasia
Authors: Palú Gabriele , Maria Rodrigues Adriane
Published: October 2024

Disclosure: G. Palú: None. A.M. Rodrigues: None.

Background: Hyperandrogenism is sometimes difficult to control in female patients with classic congenital adrenal hyperplasia (CAH), requiring supra-physiologic glucocorticoid dose with its metabolic consequences. Clinical Case: A 25-year woman with salt-losing CAH has been followed since she was born, requiring high glucocorticoid dose (hydrocortisone dose equivalent 50-75 mg), in addition to fludrocortisone (0.1-0.15 mg/day), without control of hyperandrogenism (testosterone and androstenedione levels more than 3 times ULN). She progressively gained weight, reaching 116 kg (256 pounds) and BMI of 46 kg/m2 when she was 17 years old. Bilateral adrenalectomy was performed in 2016 for disease control and to lower glucocorticoid dose. Androgen levels were supressed, glucocorticoid dose was reduced to 5mg prednisone (hydrocortisone dose equivalent 20mg) and she lost 10 kg of weight, but she remained in class III Obesity (BMI 42.5 kg/m2). Serious adrenal crises were not reported after bilateral adrenalectomy. Pharmacologic obesity treatment was done (sibutramine plus topiramate) and she lost 16 kg of weight, reaching 90 kg and a BMI of 36 from April 2017 to February 2020. She stopped treatment during the COVID- 19 pandemic and regained weight, reaching 106 kg again. She was lost to follow-up and returned in November 2023. In May 2022, she was submitted to a gastric bypass in a country town. She achieved 71 kg with a BMI of 28. She was feeling very well, taking post-bariatric vitamins and minerals, combined oral contraceptive, prednisone 5 mg/day (hydrocortisone dose equivalent 20 mg/day) and fludrocortisone 0.1 mg/day. Until now, she did not have any adrenal crises requiring parenteral glucocorticoid use. Conclusion: Even though treatment was aggressive with two surgeries that could lead to increased risk of adrenal crises, the patient had a benign course. New medicines that block CRH or ACTH action in CAH patients could prevent excessive glucocorticoid doses and weight gain and would be a better alternative to bilateral adrenalectomy in cases such as this one.

Presentation: 6/1/2024
7178 Human loss-of-function variants in the TRPC5 associated with Postpartum Depression
Authors: Li Yongxiang , Farooqi Ismaa Sadaf , Xu Yong
Published: October 2024

Disclosure: Y. Li: None. I.S. Farooqi: None. Y. Xu: None.

Postpartum depression is a serious psychiatric disorder that is understudied and underdiagnosed. Postpartum depression, the most common complication of childbirth negatively impacts the mother, with suicide accounting for approximately 20% of postpartum deaths. Further, postpartum depression also has adverse effects on infant behavioral, emotional, and cognitive development. However, the neurobiological mechanisms underlying postpartum depression remain to be comprehensively elucidated. Transient receptor potential channel 5 (TRPC5/Trpc5), an ion channel that conducts calcium inward currents, as a critical regulator of many behaviors. Here, we found that microdeletions on chromosome Xq23 disrupting TRPC5 gene in humans and identified seven rare TRPC5 variants in mothers who exhibited postpartum depression and reduced bonding with their infants. Heterozygous females with TRPC5 deletions had postpartum depression and anxiety after delivery. We then generated a knock-in mouse model of a human severe loss-of-function mutation, K34del (Trpc5K34del). Our study showed that Trpc5K34del/+ heterozygous dams abandoned their pups after delivery. The Trpc5K34del/+ dams also showed inefficient retrieval and increased the time to retrieve pups, which is associated with abnormal pup care. Importantly, Trpc5K34del/+ dams exhibited severe depression-like and anxiety-like behaviors during the postpartum period. Oxytocin (OXT), a polypeptide comprised of 9 amino acids, is primarily synthesized by neurons in the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON). We found that endogenous Trpc5 protein is abundantly expressed by OXT neurons in PVH but not by SON. Further, the Trpc5K34del/+ dams reduced OXT expression in the PVH but does not affect OXT expression in the SON. Deletion of Trpc5 in OXTPVH neurons recapitulated phenotypes in Trpc5K34del/+ dams, including inefficient retrieval, abnormal pup care, depression-like and anxiety-like behaviors during the postpartum period. We then bilaterally injected AAV-DIO-Trpc5 into the PVH of virgin female Trpc5K34del/+/OXT-Cre mice to result in restoration of Trpc5 only in OXTPVH neurons in these mutant mice. Restoration of Trpc5 in OXTPVH neurons in Trpc5K34del/+/OXT-Cre mutant mice significantly improved pup retrieval behavior and indices of maternal care. After weaning, Trpc5K34del/+/OXT-Cre dams with Trpc5 restoration in OXTPVH neurons showed reduced depression-like and anxiety-like behaviors. Our study indicates that the postpartum depression and impaired maternal behavior of Trpc5 deficient female mice are mediated by impaired function of OXTPVH neurons. This revelation not only offers crucial insights into the pathogenesis of postpartum depression but also provides a foundation for potential therapeutic interventions.

Presentation: 6/2/2024
8231 Hyperprolactinemia Post-Brain Radiation
Authors: Kalas R , Manohar V , Bapat N S , Kim Y
Published: October 2024

Disclosure: R. Kalas: None. V. Manohar: None. N.S. Bapat: None. Y. Kim: None.

Hormonal dysfunction in adults is common after brain radiotherapy, especially when the hypothalamus or the pituitary gland is within the field of radiation. Following cranial radiotherapy, it is crucial to routinely monitor the emergence of hormonal imbalances, with particular attention to the somatotroph-GH axis, which is most frequently affected. Notably, hyperprolactinemia may manifest in 5%-50% of individuals following radiation. The degree and extent of the hormonal disorder can depend on radiation dose and technique, and the length of time after radiation. We report a case of hyperprolactinemia occurring five years after radiotherapy for cavernous sinus schwannoma. A 44-year-old woman with a history of cavernous sinus schwannoma status post right pterional craniotomy and radiation therapy 5 years prior presented with a 4-month-history of secondary amenorrhea. She underwent pencil beam scanning proton radiation to the right orbital apex and cavernous sinus for a dose of 5040 cGy in 28 fractions. Review of systems was negative for hot flashes, breast tenderness, or galactorrhea. Labs revealed: diluted prolactin 118 (4.8-23.3 ng/mL), monomeric prolactin 99.6 (4.79-23.3 ng/ml), estradiol 184 pg/ml, LH 10.5 mIU/mL, FSH 2.9 mIU/mL, serum beta-HCG <5 mIU/mL, TSH 2.630 (0.450-4.500 mIU/L), free T4 0.85 (0.82-1.77 ng/dL), IGF-1 104 ( 74-239 ng/mL), and ACTH 17.8 (7.2-63.3 pg/mL) with morning cortisol 14.0 (6.2-19.4 ug/dL). A brain MRI with and without contrast revealed stable mass with postsurgical changes in the right cavernous sinus extending to the orbital apex and no abnormalities of the pituitary gland when compared to 2 years ago. The patient was started on cabergoline 0.5 mg twice a week. Her menses resumed four weeks after starting treatment, and the prolactin level repeated one month after was <1.0 ng/mL. The proposed mechanism for radiation-induced hyperprolactinemia is damage to the hypothalamus resulting in reduction of dopamine, an inhibitory neurotransmitter. It is typically dose dependent, and for the majority, it is subclinical occurring years after radiation. It can develop in both sexes and all ages but most commonly amongst young women. Hyperprolactinemia can sometime self-resolve, potentially due to evolving damages to lactotrophs. We emphasize that while brain radiotherapy can frequently lead to hormonal deficiencies, hyperprolactinemia can occur and eventually lead to dysfunction in the LH/FSH axis. Pituitary function should be routinely checked for many years post-radiation, as the likelihood of developing hormonal dysfunction tends to increase with time.

Presentation: 6/1/2024
8144 Hypertension in Sheehan Syndrome: A Diagnostic Challenge
Authors: Ahsan E , Foo F F , Lesniak C , Akula M , Hu K , Ong R , Chalasani K , Cheng J , Holland S
Published: October 2024

Disclosure: E. Ahsan: None. F.F. Foo: None. C. Lesniak: None. M. Akula: None. K. Hu: None. R. Ong: None. K. Chalasani: None. J. Cheng: None. S. Holland: None.

Introduction: Postpartum pituitary necrosis, commonly known as Sheehan syndrome (SS), is the term used to describe the necrosis of anterior pituitary gland cells that occurs after significant postpartum bleeding, hypovolemia, and shock. This typically occurs after delivery, during which the mother suffers significant blood loss. The pituitary gland fails to produce hormones due to this blood loss. Depending on the degree of tissue damage, SS can have an acute or chronic course, and patients may present with a wide range of clinical symptoms at diagnosis. Acute SS is associated with postpartum pituitary infarction, which can result in hypotension, shock, hypoglycemia, hyponatremia, headache, vision disturbances, unconsciousness, and an inability to lactate. We present a rare case of SS where the patient experienced hypertension instead of classic hypotension due to postpartum preeclampsia. Clinical Case: A 40-year-old female with no significant medical history presented to the hospital for scheduled induction of labor for polyhydramnios and underwent vacuum-assisted vaginal delivery and postpartum hysterectomy due to severe postpartum hemorrhage secondary to DIC. The postpartum course was also complicated by preeclampsia with severe features. Patients developed features like excessive fatigue, hypoglycemia, hyponatremia, hypothyroidism, polyuria, and failure of lactation, which were consistent with panhypopituitarism secondary to Sheehan syndrome. However, the patient was hypertensive to 145/91 before steroids were given. Labs were significant for serum sodium 116 mmol/L (135-145 mmol/L), FSH <0.7 mIU/mL (Follicular Phase: 2.5-10.2, Mid-cycle Peak: 3.1-17.7, Luteal Phase: 1.5-9.1, Postmenopausal: 23.0-116.3), LH <0.2 mIU/m (Follicular Phase: 1.9-12.5, Mid-Cycle Peak: 8.7-76.3, Luteal Phase: 0.5-16.9, Postmenopausal: 10.0-54.7), Prolactin: 2.4 ng/mL (Non-pregnant: 3.0-30.0, Pregnant: 10.0-209.0, Postmenopausal: 2.0-20.0), PM Cortisol on admission: 1.10 ug/dL (3.44-16.76 ug/dL), plasma ACTH 7 pg/mL( 6 - 50 pg/mL), TSH 0.430 uIU/mL (0.550 - 4.780 uIU/mL), FT4 0.59 ng/dL - 1.76 ng/dL). MRI of the brain pituitary showed- A 1.5 cm region of hypoenhancement and an additional 2 mm focus of hypoenhancement in the sella, findings represent evolving pituitary necrosis. The patient received 24 units of blood transfusion and hormone replacement therapy, followed by outpatient endocrinology follow-up. Clinical lessons: Although considerable blood loss causes hypotension in patients with SS, additional postpartum medical issues can sometimes result in atypical presentations. In our patient, postpartum preeclampsia caused hypertension. Identifying the atypical symptoms of SS is just as vital as identifying its typical features to prevent potentially fatal consequences.

Presentation: 6/2/2024
12623 Hypopituitarism Secondary To Empty Sella Syndrome Post Motor Vehicle Accident
Authors: Fawcett D , Ceballos S , Livasky C
Published: October 2024

Disclosure: D. Fawcett: None. S. Ceballos: None. C. Livasky: None.

Introduction: Empty sella is a pituitary disorder characterized by the herniation of the subarachnoid space within the sella turcica. It can be further classified as primary empty sella (PES), considered an idiopathic disease or secondary empty sella (SES) which may result after pituitary tumor treatment, spontaneous necrosis, infection, autoimmune disease or brain trauma. Case Description: 47-year-old female with no medical history, who presented to emergency due to a 2-week history of fatigue associated with persistent heart pounding sensation and intermittent holocranial headache. On admission, the patient had sinus tachycardia with a normal blood pressure, and a non-focal neurologic exam. Her initial labs were significant for elevated lactic acid and low TSH. Initially a hyperthyroid etiology was considered, however, thyroid panel obtained on admission showed low T4 level. On further interrogation patient recalled a recent motor vehicle accident (MVA) a month prior to symptoms developing, without medical evaluation at the time. Brain MRI was completed as part of a central etiology work up demonstrating an empty sella with enlargement of the sella turcica measuring 1.6 cm. No contrast enhancing lesions were seen. Endocrinologic work up was consistent with a secondary adrenal insufficiency. Patient was discharged with hormonal thyroid and hydrocortisone supplementation. Discussion: Empty sella is a pituitary disorder in which a herniation of the subarachnoid space within the sella turcica occurs. There are two types: Primary empty sella (PES) which is considered idiopathic and is seen in patients with no history of previous pituitary pathology, and Secondary empty sella (SES) which may result after pituitary tumor treatment such as surgery or radiation, spontaneous necrosis, infection, autoimmune disease or brain trauma. The patient we presented did not have medical history consistent with autoimmune diseases or prior procedures. However, she did report an MVA with head trauma, that did not receive medical attention with subsequent development of headache and rest of previously described symptoms, highly concerning for a possible traumatic etiology. A high level of suspicion is required for diagnosis, particularly in patients with unspecific symptoms in order to improve patient’s prognosis.

Presentation: 6/1/2024
8043 IgG4-related disease with isolated involvement of the pituitary gland: case report
Authors: Ramos Jayme Mendonça
Published: October 2024

Disclosure: J.M. Ramos: None.

Female patient, 36 years old, presented to our service complaining of a headache lasting five weeks, mainly in the frontal and left periorbital region, radiating to the occipital region. The pain was intense and intermittent, lasting about 40 minutes. No nausea or vomiting was reported, but the patient experienced dizziness and double vision. During the symptomatic interview, the patient mentioned increased thirst and urinary volume. In her medical history, she denied comorbidities, with only frequent episodes of tension-type headaches. She had no continuous medication use and no known drug allergies. The patient had undergone two cesarean sections, with the last one in December 2021. On physical examination, she had horizontal binocular double vision in all three gazes to the left, accompanied by pain during eye movement. Increased facial sensitivity on the left in branches V1 and V2 was observed. The rest of the physical examination showed no abnormalities. Initial general laboratory tests were normal. Evaluation of pituitary function was mostly normal, except for slightly elevated prolactin. A cranial MRI revealed an expansive lesion with sellar and suprasellar components measuring 1.2x1.1x1.2cm. Additional imaging of the sella turcica showed an intra- and suprasellar expansive lesion, predominantly isointense on T1, hyperintense on T2, with discreetly heterogeneous enhancement with gadolinium. In consultation with the neuroradiology team, a hypointensity on T2 at the left margin of the pituitary was noted, suggesting an inflammatory etiology. Based on this, laboratory tests were conducted, and treatment with methylprednisolone 1g per day for 7 days was initiated. After treatment completion, the IgG4 level was found to be 146.7 mg/dL (upper limit of reference: 86 mg/dL). A follow-up MRI, five days after the steroid pulse therapy, showed a reduction in lesion size to 0.8 cm in the cranio-caudal dimension, with a preserved appearance of the optic chiasm. The patient experienced considerable symptom improvement and was discharged with oral corticosteroids and a scheduled initiation of rituximab. The patient meets criteria confirming the diagnosis of IgG4-related hypophysitis, a rare condition representing 30% of hypophysitis cases. Isolated pituitary involvement is even rarer, and its association with diabetes insipidus has been described. Treatment involves corticosteroids, and rituximab can be considered, especially in recurrent cases.

Presentation: 6/3/2024
8565 Impact of Mild Blast Traumatic Brain Injury on Pituitary Hormone Secretion Trajectory in Male and Female Mice in Response to Restraint
Authors: Donaldson H , Wu T Y J
Published: October 2024

Disclosure: H. Donaldson: None. T.J. Wu: None.

Over 10 million people suffer from traumatic brain injury (TBI) annually. Mild blast TBI (mbTBI) account for about 80% of TBIs in service members. One third of people exposed to mbTBIs have prolonged neuroendocrine defects, particularly anterior pituitary dysfunction. Previous studies in our laboratory have shown that male and female mice demonstrate different neuroendocrine defects in response to mbTBI. Specifically, male mice with mbTBI have an increase (p<0.05) in corticosterone (CORT) response at 30 min after the initiation of restraint. Conversely, female mice show attenuated (p<0.05) levels of CORT at the same timepoint after the initiation of restraint. It is not known, however, what the trajectory of anterior pituitary hormone changes is in response to mbTBI. Our project aims to characterize the temporal relationship of peripheral anterior pituitary hormones in male and female mice in response to mbTBI and restraint. Male and female mice were randomly assigned to undergo sham or mbTBI injury using the Advanced Blast System (ABS). At 1 week after mbTBI, mice within each group were randomly assigned to be killed at 0-, 5-, 10-, 20-, 30-, or 90-min after the initiation of a 20-min restraint. At the appropriate timepoint, tissue was collected after the mice were euthanized. Prolactin (PRL) and adrenocorticotropin hormone (ACTH). were measured using commercially available ELISA. Analysis of the data show that the peak response to restraint was altered in mice exposed to the ABS. PRL increased (p<0.05) starting at 5 min in both males and females after the initiation of restraint and returned to baseline by 90 min. ACTH increased (p<0.05) starting at 10 min and 20 min after the initiation of restraint and returned to baseline by 90 min in males and females, respectively. Peak PRL was delayed in both males (20 min vs 5 min) and females (10 min vs 5 min) whereas peak ACTH advanced in both males (10 min vs 30 min) and females (20 min vs 30 min). Area under the curve analysis show that ABS decreased overall PRL in both males and females whereas ACTH was lower in males and higher in females. The results of the current study showed that mice of both sexes have different serum PRL and ACTH trajectories in response to restraint when exposed to mbTBI.

Presentation: 6/2/2024
7940 Insulinoma as a Rare Manifestation of MEN4
Authors: Han Hye Jeong , Moalem Jacob , Shih Angela R , Gigliotti Benjamin J
Published: October 2024

Disclosure: H. Han: None. J. Moalem: None. A.R. Shih: None. B.J. Gigliotti: None.

Background/Objective: Multiple endocrine neoplasia 4 (MEN4) is a rare syndrome that is caused by germline mutations in CKDN1B. Its phenotypic expression is similar to multiple endocrine neoplasia 1 (MEN1). Manifestations include primary hyperparathyroidism (PHPT), pituitary adenomas, and pancreatic neuroendocrine tumors (NET). Prevalence of MEN4 is less than one per million. Case Report: A 55-year-old female with history of hypercalcemia presented with symptomatic hypoglycemia. She had a fasting plasma glucose of 41mg/dL, proinsulin of 84.3 pmol/L, insulin level of 24 uIU/mL, c-peptide of 5.2 ng/mL, and beta hydroxybutyrate level of 0.34 mmol/L, consistent with endogenous hyperinsulinism. She was incidentally noted to have PHPT. CT abdomen showed a 1.5 x 1.1 x 1.0 cm pancreatic lesion consistent with an insulinoma. Pathology from subsequent Whipple surgery showed that it was a well-differentiated neuroendocrine tumor with no metastasis. She became normoglycemic after surgery. Germline testing revealed a variant of unknown significance in CDKN1B (p.R93W). Discussion: Increasing evidence suggests that MEN4 exhibits subtle differences in penetrance and natural history compared to MEN1. A recent systemic review of MEN4 cases showed that most gastrointestinal NETs in MEN4 are non-functional NETs and gastrinomas; to date, no insulinomas have been reported. PHPT in MEN4 may exhibit a lower risk of recurrence after parathyroidectomy. This case highlights the importance of germline genetic testing when a patient presents with clinical manifestations of MEN1. Conclusion: This is the first reported case of insulinoma in MEN4.

Presentation: 6/3/2024
7044 It Is Back, Three Decades Later! When To Stop Glucagonoma surveillance?
Authors: Wahba A T , Dillon J S
Published: October 2024

Disclosure: A.T. Wahba: None. J.S. Dillon: Advisory Board Member; Self; Crinetics Pharmaceuticals, CA.

A 76-year-old woman presented to the Neuroendocrine Tumor (NET) Clinic for evaluation of sore mouth, perianal area and itchy ankles. She had a medical history notable for glucagonoma, status post distal pancreatectomy and splenectomy in 1988, 32 years prior to her current presentation. She recalled that she had CT imaging post operatively for a few years, but no more recent imaging. She was diagnosed with diabetes mellitus in approximately 2002, with highly variable glucose control. She developed a left leg DVT with pulmonary emboli one year prior to presentation. Shortly after her thromboembolic events, she noted her current presenting complaints. A CT abdomen scan with contrast was reported as normal. Three months later, an abdomen ultrasound for evaluation of right upper quadrant pain and intractable vomiting, showed a liver mass. MRI revealed a contrast enhancing 3.1x2.1x1.8 cm lesion in liver segment 6 and 7. Her plasma Glucagon concentration, which had been undetectable when last checked in 2007, was 382 (N: < 80 pg/ml). CT-guided needle biopsy of the liver lesion confirmed a well differentiated neuroendocrine tumor, immunohistochemically positive for somatostatin receptor 2 (SSTR2A), Islet-1 and PAX6, with low mitotic count and Ki-67 proliferation index of 0.45%. Gallium-68 DOTATATE-PET scan showed a single avid hepatic metastasis, with no other evidence of somatostatin receptor expressing tumor. She was initially started on a combination of short-acting Octreotide 100 mcg TID and monthly 20 mg Sandostatin LAR injections for symptomatic relief. Zinc copper 100 mg capsules were prescribed with significant improvement of skin rash and glossitis within 2-4 months. Repeat MRI abdomen at 3 months and 6 months showed a stable single liver lesion without evidence of additional metastasis. She has continued annual clinic visits and abdomen MRI follow up with stable imaging findings at 3 years. Percutaneous ablation, trans hepatic arterial embolization and surgical resection were discussed, but the patient preferred a more conservative approach of monthly octreotide LAR, which she tolerated well, and which resolved her symptoms. Glucagonoma syndrome presents classically with 5D’s: Dermatitis (Necrolytic Migratory Erythema), DVTs, Diabetes mellitus, Depression, Diarrhea. The National Comprehensive Cancer Network guidelines recommend monitoring glucagonoma patients post-resection for up to 10 years with clinical evaluation, glucagon levels every 6-12 months and imaging studies as clinically indicated. Our case illustrates that recurrence can occur after 30 years from initial resection and that longer surveillance should be considered.

Presentation: 6/3/2024
9281 Menopause Has a Beneficial Influence on the Evolution of Prolactinomas: a Study in 95 Patients
Authors: Constantinescu Stefan Matei , Nava Caterina , Chasseloup Fanny , Chanson Philippe , Alexopoulou Orsalia , Maiter Dominique M
Published: October 2024

Disclosure: S. Constantinescu: None. C. Nava: None. F. Chasseloup: None. P. Chanson: Consulting Fee; Self; Eli Lilly & Company, Recordati, Ipsen, Novo Nordisk. O. Alexopoulou: None. D.M. Maiter: Consulting Fee; Self; Ipsen, Recordati, Pfizer, Inc.

The natural occurrence of menopause is considered to have beneficial effects in women with a prolactinoma and represents a window of opportunity for successful dopamine agonist (DA) withdrawal. Strong evidence for these effects remains however scarce. We retrospectively analyzed data from 95 women undergoing menopause (Mp) (FSH>35 U/L) while still treated with DA (cabergoline (CAB) in 82) for a prolactinoma diagnosed at a mean age of 38.0 ± 8.0 years. The pituitary tumor was a microadenoma in 66 and a macroadenoma in 29 (invasive in 12). Our objectives were to identify the influence of menopause on the evolution of treated prolactinomas and on the risk of recurrence after DA withdrawal. In post-menopausal women still treated with DA (median dose of 0.50 mg CAB/week or equivalent), a significant decrease in median prolactin (PRL) was observed from a premenopausal value of 15.1 µg/L to 10.7 µg/L 3-6 months after Mp (n=64, P=0.05) and to 7.7 µg/L 24 months after Mp (n=43, P < 0.001). There was also a significant reduction in median coronal tumor surface at 24 months, from 12.6 to 7.1 mm² (p < 0. 01). DA treatment was withdrawn in 53 women (56%) after a median interval of 26 months after menopause (range: 3-262). Strict criteria for discontinuation were fulfilled in 52 of them: a normal PRL for at least 24 months under a cabergoline dose ≤ 0.50 mg/week and a more than 50%-reduction in tumor surface area for macroadenomas. Among them, 37 women (71%) remained in remission during a median follow-up period of 26 months (range: 6-176), while 15 (29%) had an asymptomatic biological recurrence after a median duration of 6 months (range: 2-47). Only one woman showed minimal tumor regrowth. 12/15 of the biological recurrences of hyperprolactinemia occurred within the first year after withdrawal and the estimated probability of remission at 5 years was 66%. Multivariate analysis showed that the only independent predictor of recurrence was the PRL value observed 3 to 6 months after DA discontinuation (p = 0.028). Estrogen-progestin replacement therapy, given in 21 women, did not influence these outcomes. In conclusion, we confirm that menopause has a beneficial effect on the evolution of treated and untreated prolactinomas. When using strict criteria for DA withdrawal in the post-menopausal period, a sustained clinical and biological remission can be expected in two-thirds of women, and when recurrence occurs, it is usually mild and asymptomatic.

Presentation: 6/2/2024
7220 Menopause Has a Beneficial Influence on the Evolution of Prolactinomas: a Study in 95 Patients
Authors: Constantinescu Stefan Matei , Nava Caterina , Chasseloup Fanny , Chanson Philippe , Alexopoulou Orsalia , Maiter Dominique M
Published: October 2024

Disclosure: S. Constantinescu: None. C. Nava: None. F. Chasseloup: None. P. Chanson: Consulting Fee; Self; Eli Lilly & Company, Recordati, Ipsen, Novo Nordisk. O. Alexopoulou: None. D.M. Maiter: Consulting Fee; Self; Ipsen, Recordati, Pfizer, Inc.

The natural occurrence of menopause is considered to have beneficial effects in women with a prolactinoma and represents a window of opportunity for successful dopamine agonist (DA) withdrawal. Strong evidence for these effects remains however scarce. We retrospectively analyzed data from 95 women undergoing menopause (Mp) (FSH>35 U/L) while still treated with DA (cabergoline (CAB) in 82) for a prolactinoma diagnosed at a mean age of 38.0 ± 8.0 years. The pituitary tumor was a microadenoma in 66 and a macroadenoma in 29 (invasive in 12). Our objectives were to identify the influence of menopause on the evolution of treated prolactinomas and on the risk of recurrence after DA withdrawal. In post-menopausal women still treated with DA (median dose of 0.50 mg CAB/week or equivalent), a significant decrease in median prolactin (PRL) was observed from a premenopausal value of 15.1 µg/L to 10.7 µg/L 3-6 months after Mp (n=64, P=0.05) and to 7.7 µg/L 24 months after Mp (n=43, P < 0.001). There was also a significant reduction in median coronal tumor surface at 24 months, from 12.6 to 7.1 mm² (p < 0. 01). DA treatment was withdrawn in 53 women (56%) after a median interval of 26 months after menopause (range: 3-262). Strict criteria for discontinuation were fulfilled in 52 of them: a normal PRL for at least 24 months under a cabergoline dose ≤ 0.50 mg/week and a more than 50%-reduction in tumor surface area for macroadenomas. Among them, 37 women (71%) remained in remission during a median follow-up period of 26 months (range: 6-176), while 15 (29%) had an asymptomatic biological recurrence after a median duration of 6 months (range: 2-47). Only one woman showed minimal tumor regrowth. 12/15 of the biological recurrences of hyperprolactinemia occurred within the first year after withdrawal and the estimated probability of remission at 5 years was 66%. Multivariate analysis showed that the only independent predictor of recurrence was the PRL value observed 3 to 6 months after DA discontinuation (p = 0.028). Estrogen-progestin replacement therapy, given in 21 women, did not influence these outcomes. In conclusion, we confirm that menopause has a beneficial effect on the evolution of treated and untreated prolactinomas. When using strict criteria for DA withdrawal in the post-menopausal period, a sustained clinical and biological remission can be expected in two-thirds of women, and when recurrence occurs, it is usually mild and asymptomatic.

Presentation: 6/2/2024
7239 Natural history of cystic pituitary lesions
Authors: Graner Brian , Erickson Dana Z , Donegan Diane
Published: October 2024

Disclosure: B. Graner: None. D.Z. Erickson: None. D. Donegan: None.

Introduction: Pituitary lesions are a common incidental finding on brain MRI, the majority of which are cystic. The natural history and management of cystic pituitary lesions have not been clearly established. Purpose: The purpose of this study is to determine the natural history of incidentally identified cystic pituitary lesions, risk factors for growth and the proportion of patients who develop clinically significant symptoms requiring surgical intervention. Methods: Pituitary MRI reports between 01/01/2015 and 12/31/2022 in patients aged 18 years and older were searched for using Dig Our Radiology Information System (DORIS) using the words “cyst” or “cystic.” Additional inclusion criteria included a follow-up pituitary MRI of at least one year duration, clinical evaluation by Endocrinology, and the presence of a cystic pituitary lesion. Patients with non-contrast exams, excessive pituitary hormone secretion, and surgery within 1 year of presentation were excluded. Patient demographics, imaging characteristics of the lesion and clinical outcomes were collected. All pituitary MRI exams were reviewed by a single neuroradiologist. Results: A total of 157 MRIs in 56 patients with a mean age of 48 ±15 years were included, 39 (70%) were female. The mean follow-up was 2.3 ± 1.4 years. The most common indication for MRI was headache (n= 18, 32%). There was no significant difference in mean maximum (max) diameter at last follow-up compared to baseline (7.45 ±4.23 vs 7.04 ±4.35 mm, p=0.06) or mean cyst volume (197.08 ±252.68 vs 201.43 ±326.18 mm3). Nine (16%) of the lesions increased in volume with a mean change in volume of 105 ±133.64 mm3/yr, note 11 (20%) decreased volume and 36 (64%) remained the same size. Using univariate logistic regression, the odds of cyst growth was greater the larger the max diameter (p= 0.03) or volume was at baseline (p= 0.02)/ Female sex (p=0.32), age at diagnosis (p=0.70) or whether the lesion was thought to be a Rathke cleft cyst or a cystic adenoma (p=0.80) were not associated with increased odds of growth. The risk of growth was higher (42 vs 9%, p=0.016) and the volume change per year was greater (67.2 ±134 vs -7 ±28 mm3, p=0.04) in those with a baseline max diameter of >10 mm. Surgery was performed in 4 patients (7%), 3 of which demonstrated lesion growth (baseline size 12-15 mm and growth rates of 59-341mm3/yr). Pathology revealed one Rathke cleft cyst, one cystic adenoma and fibrotic pituitary changes. The fourth surgical patient opted for resection at an outside facility without a demonstrated increase in size (Rathke cleft cyst). Conclusion: The majority of incidentally found cystic pituitary lesions do not increase after an average follow-up 2-3 years. Growth necessitating surgical intervention was only required in 5% of patients over the study period. A pituitary cyst >10 mm at diagnosis was associated with an increased risk of growth and therefore warrants closer follow-up.

Presentation: 6/1/2024