bluuebunny/crossref_metadata_2025 huggingface dataset:
7518 A Case of Delayed Diagnosis of Acromegaly Associated with Uncontrolled Diabetes
Authors: Mahmoudabadi A , Patel S
Published: October 2024

Disclosure: A. Mahmoudabadi: None. S. Patel: None.

Background: Acromegaly is a rare disorder characterized by an excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) levels, typically due to a GH-secreting pituitary adenoma. This consequently leads to complications such as acral and soft tissue overgrowth, visual disturbance, insulin resistance, and dyslipidemia. In this case, we describe a patient who presented to the endocrinology clinic for uncontrolled diabetes and was subsequently diagnosed with acromegaly. Clinical Case: This is a 47-year-old male with a history of heart failure, hypertension, and type 2 diabetes mellitus (DM) who presented to the clinic with uncontrolled DM. He had failed to achieve adequate blood sugar control despite being compliant with metformin, dapagliflozin, and insulin degludec. Physical examination revealed frontal bossing, prognathism, macroglossia, and a deep voice. On further questioning, he had noticed these changes since five years prior. Anthropometry and laboratory tests were as follows: Height, 180 cm; body weight 107.5 kg; body mass index (BMI), 33.05 kg/m2 and A1c level of 15.0%. Suspicion of acromegaly was confirmed based on biochemical and imaging findings. Fasting growth hormone (GH), at 58 mU/L (reference range 0-10), and insulin-like growth factor 1 (IGF-1), at 857 nmol/L (reference range 81-263), were markedly elevated. Pituitary magnetic resonance imaging (MRI) showed a sellar and suprasellar mass (2.6 × 2.2 × 2.2 cm) extending and compressing the optic chiasm. He eventually underwent a transsphenoidal adenomectomy with neurosurgery. Following surgery, his insulin requirements went from a total daily dose of about 100 units to an inpatient dose of 30 units by his last day of admission. Conclusion: Acromegaly is prevalent in less than 3% of patients with DM, but higher rates of DM are seen in acromegalic patients with higher IGF-1 levels and longer duration of disease. The diagnosis of acromegaly can often be delayed due to missed findings on routine physical examination. This can lead to increased morbidity, mortality, and complications such as uncontrolled DM, witnessed in our patient. Surgical management of acromegaly is the mainstay of treatment and can lead to improvement of glycemic control and insulin sensitivity. Fortunately, our patient could undergo surgery, but delayed diagnosis can prevent patients from surgery if the pituitary tumor becomes too large or unresectable. Ultimately, this case highlights the importance of a thorough physical examination and keeping a wide differential diagnosis when evaluating patients with uncontrolled DM, as failure to diagnose acromegaly at an early stage may have devastating consequences on patient outcomes.

Presentation: 6/3/2024
8774 An Uncommon Presentation Of A Large Silent Pheochromocytoma
Authors: Lozano M , Pinero-Pilona A
Published: October 2024

Disclosure: M. Lozano: None. A. Pinero-Pilona: None.

Background: The reported estimated incidence of pheochromocytoma is approximately 2-8 cases per 1 million people per year. Of those, silent pheochromocytomas will make up about 8%. Thus, biochemically silent and non-secreting pheochromocytomas are a very rare phenomenon. Clinical Case: A 74-year-old Caucasian female with significant past medical history of primary hypothyroidism, hypercholesterolemia, and nasal sinus carcinoma s/p surgery (in remission) presented to the clinic for endocrine evaluation of a right adrenal mass. The patient was asymptomatic and denied headaches, tachycardia, sweating, severe hypertension, diabetes, muscle weakness, easy bruising, or striae. The mass was initially diagnosed as an incidental finding after a contrast CT scan of the abdomen was performed for diverticulitis. The right adrenal enhancing mass was 2.3 x 3.9 x 4.1 cm in diameter. Subsequent MRI abdomen with and without contrast ordered by the referring physician showed that the adrenal mass had grown to 4.9 x 3.8 x 5.4 cm and was hyperenhancing in nature with central T2 hyperintense signal. Notably, multiple “parasitized and arborealized” vessels were detected within the mass. Such findings led us to suspect metastatic versus primary adrenal neoplasm such as cortical carcinoma as a working diagnosis. Other laboratory studies including plasma free metanephrines (<10 pg/mL, normal 0-88 pg/mL), plasma normetanephrines (29.2 pg/mL, normal 0-285.2 pg/mL) and 24-hour urine collections (24 hr urine epinephrine - 3 ug/24 hr [normal 0-20 ug/24 hr]; 24 hr urine norepinephrine - 75 ug/24 hr [normal 0-135 ug/24 hr]; 24 hr urine VMA - 3 mg/24 hr [normal 0-7.5 mg/24 hr]) were negative for pheochromocytoma. As her mass was greater than 4 cm in diameter, surgical referral was then recommended to the patient. Right adrenalectomy was performed. Pathology report was consistent with pheochromocytoma as supported by immunohistochemistry. Ki-67 proliferation index was 0-10% (average 3-4%, rare hotspots 10%). Atrophy and vascular ectasia were present in residual non-neoplastic adrenal cortex and medulla. Histology showed a nested growth pattern, absence of composite tumor elements, absence of necrosis, and no atypical mitoses. The incidence of non-secreting pheochromocytomas has been quoted to be 0.000064% (1). Conclusion: The case illustrates an uncommon presentation of a large, silent pheochromocytoma with negative plasma metanephrines accompanied by negative urine studies, which have a negative predictive value close to 100% in ruling out a pheochromocytoma. Our case emphasizes the importance of considering pheochromocytoma on the differential of adrenal masses with high attenuation or high enhancement even when biochemical studies suggest otherwise. Reference: (1) Radojkovic, D., et al. "CLINICALLY" SILENT GIANT PHEOCHROMOCYTOMA. CASE REPORT." Acta Endocrinologica (1841-0987) 9.1 (2013).

Presentation: 6/1/2024
7743 A Case Study of Ectopic Adrenocorticotropic Hormone Secretion from Pancreatic Neuroendocrine Tumor
Authors: Wei K S , Huang J
Published: October 2024

Disclosure: K.S. Wei: None. J. Huang: None.

Introduction: Pancreatic neuroendocrine tumors (PanNETs) are uncommon cancers that account for less than 2% of pancreatic malignancies. Even rarer are ACTH-producing NETs which may only become symptomatic until after metastasis. This case study examines the distinct presentation and diagnostic complexities associated with ectopic adrenocorticotropic hormone (ACTH) secretion from a PanNET. Clinical Case:A 42 year-old male with hypertension and type 2 diabetes initially presented to the hospital with increased abdominal girth for one month, bilateral lower extremity edema for two weeks, and generalized abdominal pain. He had unremarkable surgical, family, and social histories. Patient was afebrile, normotensive, saturating well on room air, with exam notable for a distended abdomen and 2+ bilateral pitting edema. Admission labs were notable for potassium of 2.4 (ref: 3.5-5.1 mmol/L). MRI abdomen showed hepatomegaly with numerous heterogeneously enhancing masses and an ill-defined pancreatic tail mass with involvement of the spleen. Liver biopsy showed well-differentiated neuroendocrine tumor, grade 2. He was started on octreotide 20mg q4weeks and capecitabine/temozolomide q4weeks. Two months later, the patient was readmitted after presenting with back pain for two days, found to have acute compression fractures of T9-L1 without spinal PET activity. At follow-up visit with endocrinology, he endorsed easy bruising and muscle weakness and had hypertension (161/96 mmHg) with hypokalemia. Random cortisol was 43.7 (ref: 2.5-11.9 mcg/dL). ACTH was 124 (ref: 6-50 pg/mL) despite receiving chemotherapy. 24-hour urine cortisol was 3,049 (ref: 4-50 mcg/24 hrs). He was diagnosed with ectopic Cushing’s disease from ACTH-producing PanNET leading to osteoporosis and fracture of the vertebral bodies. For the ectopic Cushing’s disease, he was started on ketoconazole 200mg BID with plan to start osilodrostat once approved. For the fracture, he is scheduled for Zometa infusion and IR kyphoplasty. Conclusion: This case offers several important clinical insights. In patients with PanNET with Cushingoid exam findings, ACTH-producing PanNET should be high on the differential. Most ACTH NETs are aggressive often with liver metastases, whereby metastatic disease will have already occurred by the time the Cushingoid features develop. The initial severe hypokalemia and hypertension should have prompted investigation for mineralocorticoid excess from hypercortisolism, which may have led to an earlier diagnosis of ectopic ACTH Cushing’s disease, thereby decreasing the possibility of developing vertebral fractures, uncontrolled diabetes and hypertension. Ketoconazole or osilodrostat may be used to treat Cushing’s disease from ACTH NETs.

Presentation: 6/1/2024
7025 Acute Psychosis and the Diagnosis of Cushing’s Syndrome: Lessons Learned from a Patient with a Long History of Obesity
Authors: Modi Saman , Maria Belalcazar L
Published: October 2024

Disclosure: S. Modi: None. L. Belalcazar: None.

Background: Although the association of hypercortisolism and psychosis is well established, acute psychosis remains a very rare manifestation of Cushing’s syndrome, especially in the absence of previous psychiatric history. We present lessons learned from a patient in whom the diagnosis of Cushing’s syndrome was missed until the onset of acute psychosis helped identify his underlying endocrine disorder. Clinical Case: A 31-year-old male presented to the Emergency Department after being found down on the street. The patient had superficial lacerations that were suspected to be self-inflicted due to a suicide attempt, but later found to be the result of auditory hallucinations. He had no previous psychiatric history and no history of suicidal ideation. His medical history was positive for obesity since adolescence and a recent diagnosis of hypertension. His family noted that for the past several months he had been experiencing headache, fatigue, muscle weakness and, more recently, insomnia, restlessness, and confusion. Weight gain was noted, but of unknown magnitude. On admission, he was agitated and hallucinating. He was initially sedated with dexmedetomidine and started on quetiapine. Physical examination revealed Cushingoid features with truncal obesity (body mass index of 35 kg/m2), facial plethora, and dorsocervical fat pad; no abdominal striae were present. Labs showed mild hypokalemia. His AM cortisol was markedly elevated at > 123 ug/dL (normal 4.5-23.0 ug/dL) with an ACTH level at 144 pg/mL (normal 7.2-63.3 pg/mL). MRI Brain showed a 1.9 cm pituitary macroadenoma with small suprasellar extension. With a diagnosis of Cushing’s disease, later confirmed by pathology, he underwent transsphenoidal resection. AM cortisol on post-operative day 3 was 3.2 ug/dL (normal 4.5-23.0 ug/dL). Maintenance-dose steroids were started due to evidence of post-surgical corticotroph suppression. Notably, there was marked improvement in his anxiety, paranoia, and confusion post-operatively. Quetiapine and blood pressure medications were discontinued after discharge. Conclusion: In this patient, the diagnosis of Cushing’s syndrome was missed when initially presenting with new onset hypertension in the setting of long-standing obesity. Despite months of symptoms compatible with the diagnosis, it was not until he developed acute psychosis and a careful history was obtained, that the diagnosis of Cushing’s syndrome was entertained. Psychosis is present in only 3-8% of reported cases of Cushing’s syndrome. This case illustrates the importance of including Cushing’s syndrome in the differential diagnosis of acute psychosis, especially in patients without previous psychiatric history. It also highlights the need of excluding secondary causes of hypertension in young adults, with particular attention to Cushing’s syndrome in those who present with obesity, even if long-standing.

Presentation: 6/1/2024
12224 Addressing Blood Glucose Fluctuations and Fasting Challenges in Sheehan Syndrome: A Case Study
Authors: Awadalla Huyam Awadalla Hassan , Kiani Amna Nadeem , Taha Wael , Solanki Naisargee Nilesh , Lattouf Ali , Shermetaro Angela , Taweel Adrianna
Published: October 2024

Disclosure: H.A. Awadalla: None. A.N. Kiani: None. W. Taha: None. N.N. Solanki: None. A. Lattouf: None. A. Shermetaro: None. A. Taweel: None.

Introduction: Sheehan's syndrome (SS) is a rare condition characterized by hypopituitarism resultingfrom ischemic necrosis of the pituitary gland due to severe postpartum hemorrhage.Patients may have hormonal insuﬃciencies, ranging from single pituitary hormoneinsuﬃciency to total hypopituitarism. The diagnosis of SS is often delayed due to itsnonspeciﬁc signs and symptoms, leading to many undiagnosed and untreated cases. Case Presentation:A 33-year-old African American female with a history of panhypopituitarism secondaryto Sheehan Syndrome presented with syncope, lightheadedness, and severehypoglycemia (blood glucose 12mg/dL). Despite regular food intake, she struggled withglycemic control, experiencing recurrent hypoglycemic episodes associated withnausea, vomiting, unintentional weight loss (25kg), and polydipsia/polyuria. Laboratoryﬁndings revealed low ACTH, sodium, cortisol, and elevated liver enzymes, consistentwith hypopituitarism. Cosyntropin stimulation test conﬁrmed adrenal insuﬃciency. MRIshowed an empty sella. Initially treated with high-dose hydrocortisone, then transitionedto lower maintenance doses, she continued to experience glycemic ﬂuctuations.Intravenous dextrose and insulin sliding scale were initiated. Upon discharge, she wasprescribed hydrocortisone and levothyroxine. Despite adjustments, hypoglycemiapersisted, managed with dietary modiﬁcations. This case underscores the challenges inmanaging Sheehan Syndrome-associated panhypopituitarism and the need for tailoredtreatment approaches to achieve metabolic stability. Conclusion: This case underscores the complexities of managing panhypopituitarism secondary toSheehan syndrome, emphasizing the importance of comprehensive hormonalreplacement therapy and thorough monitoring to achieve symptom control andmetabolic stability. Tailored treatment regimens and continuous assessments arecrucial to addressing individual hormone deﬁciencies and preventing associatedcomplications effectively in these patients.

Presentation: 6/1/2024
7460 An Atypical Presentation of a Nonfunctional Pituitary Macroadenoma Found in a Patient with Chronic Sinusitis
Authors: Patel A A , Mai V Q
Published: October 2024

Disclosure: A.A. Patel: None. V.Q. Mai: None.

Non-functioning pituitary adenomas (NFPAs) are benign pituitary tumors that account for up to one third of all pituitary adenomas. The vast majority of NFPAs are incidentally found on head or brain imaging performed to evaluate for other medical problems. We present a unique case of a NFPA incidentally found via biopsy during a sphenoid sinus endoscopy. A 56-year-old female was evaluated initially by otolaryngology for two year duration of persistent post-nasal drip, retro-orbital pressure and frontal headaches despite trials of antibiotics and allergy medications. A CT of the sinuses showed soft tissue opacification of the midline sphenoid sinus with erosion of the sellar floor. Nasopharyngeal endoscopic evaluation showed copious purulent material and granulation tissue from the floor of the sphenoid sinus which was drained and biopsied. Surgical pathology was consistent with pituitary adenoma. Immunohistochemical staining showed strong reactivity in the cells with chromogranin A, CD56, INSM1, and synaptophysin and scattered positivity with AE1/AE3 and FSH. E-cadherin staining was retained and p53 negative. ACTH, CD31, CD68, GH, LH, prolactin, and TSH were non-reactive. Biochemical evaluation demonstrated that the lesion was hormonally non-functioning. An MRI of the sella subsequently showed a pituitary macroadenoma measured 1.7 x 0.7 x 1.4 cm extending into the right cavernous sinus and inferiorly into the right sphenoid sinus and wrapping around the right internal carotid artery without compressing it. The patient was initially thought to have Ectopic Sphenoid Sinus Pituitary Adenoma (ESSPA) which is rare and accounts for only 2% of all pituitary adenomas. By strict definition, ESSPA does not often have direct anatomic connection with the pituitary and imaging studies usually show a normal pituitary gland. In our patient, MRI shows a direct communication and extension into the sphenoid sinus potentially following the migratory embryonic path during the Rathke's pouch development. Therefore, although not truly an ESSPA, this case may still be a unique variant where there is not a complete separation of the path between the pituitary and pharynx. Management options of NFPAs include observation, surgical resection if symptomatic or compressive, medical therapy with dopamine agonists and/or somatostatin agonists, or radiation therapy. Our patient was particularly unique as the endoscopy also resulted in surgical removal of part of the adenoma from the sphenoid sinus. She will be monitored for development of compressive symptoms and growth of her macroadenoma on subsequent imaging to determine the need for further surgery. In conclusion, it is important to broaden our differential diagnoses to include intracranial pathology particularly the pituitary gland when evaluating for common symptoms and chronic diseases of the sinuses.

Presentation: 6/2/2024
5086 Approaching the Enigma: Unveiling a Pituitary Stalk Lesion with Imaging and Hormonal Patterns
Authors: Rodriguez-Morales N , Guido P
Published: October 2024

Disclosure: N. Rodriguez-Morales: None. P. Guido: None.

Background: Pituitary stalk lesions (PSL) pose a diagnostic dilemma for endocrinologists. Multiple studies have attempted to associate hormonal imbalances and imaging patterns to a specific etiology (1,2). However, the diagnosis remains a mystery on many occasions. We describe a case of secondary hypogonadism and central DI attributed by a PSL. Clinical Case: A 39-year-old male presented with symptoms of hypogonadism and polyuria. Initial workup was consistent with secondary hypogonadism; decreased free and total testosterone levels (1.8 pg/dL and 9 ng/dL, n>35 pg/dL, n>250 ng/dL), LH (0.2 mIU/mL, n>1.5 mIU/mL), and FSH (<0.7 mIU/mL, n>1.6 mIU/mL). The remaining anterior pituitary hormones were within normal limits. The patient was also polyuric (6.5L urine output in 24hr). HgbA1c was normal. Urine Na, urine Osm demonstrated water diuresis (13 mmol/L and 54 mOsm/kg, respectively). A water deprivation test was performed. Initial urine Osm after water restriction was 119 mOsm/kg, which more than tripled to 575 mOsm/kg after administration of desmopressin, diagnostic of central DI. Pituitary MRI showed a well-circumscribed thickening of the pituitary stalk (6x6x5mm), with uniform enhancement. Evaluation for etiology to rule out germ cell tumor, lymphoma, sarcoidosis, opportunistic infection, tuberculosis, Langerhans cell histiocytosis showed a normal serum hCG, HIV, ACE, LDH, AFP. A lumbar puncture demonstrated normal cytology and was negative for AFB. Whole body bone scintigraphy and chest X-ray were normal. Pituitary deficits were treated with hormone replacement (testosterone and desmopressin), and a repeat MRI showed a stable lesion. Conclusion: Noninvasive testing is key to the evaluation of a pituitary stalk lesion. Careful consideration of inflammatory, infectious, and neoplastic etiologies along with attention to pituitary deficits is very important. Our patient most likely has a craniopharyngioma based on data from other case series (1,2). This case serves to bring additional data to the body of literature on this complicated clinical scenario. References: 1. Turcu AF, Erickson BJ, Lin E, et al. Pituitary stalk lesions: The mayo clinic experience. Journal of Clinical Endocrinology and Metabolism. 2013;98(5):1812-1818. doi:https://doi.org/10.1210/jc.2012-41712. 2. Sbardella E, Joseph R, Bahram Jafar-Mohammadi, Isidori AM, Cudlip S, Grossman A. Pituitary stalk thickening: the role of an innovative MRI imaging analysis which may assist in determining clinical management. European journal of endocrinology. 2016;175(4):255-263. doi:https://doi.org/10.1530/eje-16-0455

Presentation: 6/1/2024
8407 Baseline Clinical Factors Associated with Cessation of Growth Hormone Therapy in Patients with Severe Growth Hormone Deficiency: Real World Evidence
Authors: Ssemmondo Emmanuel , Nadarajah Nageswary , Brooks Shani , Akinyombo Remi , Adeleke Kazeem A , Deshmukh Harshal , Sathyapalan Thozhukat
Published: October 2024

Disclosure: E. Ssemmondo: None. N. Nadarajah: None. S. Brooks: None. R. Akinyombo JNR: None. K.A. Adeleke: None. H. Deshmukh: None. T. Sathyapalan: None.

Introduction: Growth hormone replacement is indicated in adults with severe growth hormone (GH) deficiency, adult growth hormone deficiency assessment (AGHDA) score of at least 11 and are receiving treatment for other pituitary hormone deficiencies. GH is administered as a daily subcutaneous injection. There are no data looking at the cessation of GH replacement in adult patients with severe GH deficiency and the factors that predict the likelihood of patients continuing or stopping growth hormone replacement. Methods: We audited patients on the GH register between January 2006 and January 2023 in Hull Teaching Hospital NHS foundation Trust, a UK tertiary hospital. Baseline characteristics, the cause of GH deficiency, AGHDA score at diagnosis and the reason for stopping GH were collected. Proportions were compared between patients adhering to GH replacement and those who had ceased it using the Fisher exact test. Logistic regression was employed to explore factors correlated with the cessation of GH replacement. Results: The study comprised 141 adult patients with a mean age of 52 years, of which 75 (53%) were female. Notably, 54 (38%) individuals had discontinued GH replacement therapy. Predominant reasons for discontinuation were cited as lack of therapeutic benefit (46%) and a shift in clinical indication (26%). Among patients off GH therapy, the most frequent cause of GH deficiency was idiopathic (57%), while for those on GH replacement, pituitary surgery was the leading cause (53%). Upon adjusting for covariates, gender emerged as significantly associated with the cessation of GH therapy. Females exhibited an 8.8 times higher likelihood of discontinuing GH therapy compared to males (P-value=0.02). However, no other baseline factors displayed a statistically significant correlation with the cessation of GH replacement. Conclusion: In this real-world investigation of patients with severe GH deficiency, over two in five individuals who discontinued GH therapy cited the absence of perceived benefits. Notably, gender is a predictive factor for the cessation of GH replacement, with females displaying a higher tendency to discontinue this therapy.

Presentation: 6/1/2024
12450 Beyond the Surface: A Deep Dive into Pancreatic Insulinoma
Authors: Bhandari S , Elhag R , Singh J , Rastogi N
Published: October 2024

Disclosure: S. Bhandari: None. R. Elhag: None. J. Singh: None. N. Rastogi: None.

Background: Pancreatic neuroendocrine tumors (NET) are rare lesions that are typically sporadic, solitary and usually <2cm in diameter, with reported incidence of 4 cases per 1 million patients per year[1]. The most common hormone secreting NET are insulinomas. The hallmark of insulinomas is hypersecretion of insulin, leading to neuroglycopenic symptoms and uncontrolled sympathoadrenal activity. Clinical case: 51 years old female with no significant past medical history was referred to endocrine clinic by her primary care physician for hypoglycemia with a blood glucose level of 48 mg/dl. She reported an increased frequency of headaches and dizziness which began with intermittent fasting (10-12 hours) for past 6 months. These symptoms improved upon increasing meal frequency. Initial laboratory investigations revealed glucose of 54 mg/dl, normal HbA1c, and negative sulfonylurea panel. The patient had normal liver and kidney function with no malnutrition or malabsorption issues. Further work up showed C-peptide level 1.56 ng/ml (n 0.80-3.85ng/ml), insulin level 7.9 uIU/mL (n <18.4 uIU/mL), pro-insulin level significantly elevated at 77.6 pmol/L (n </= 18.8pmol/L) and beta hydroxybutyrate of 0.12 mmol/l (n 0.02-0.27mmol/l). Insulin like growth factor was normal. Insulin antibodies were negative, and pituitary hormones were within normal limits. Pancreatic ultrasound was normal. CT abdomen/pelvis showed a 0.8x1.1 cm homogenously hypervascular anterior pancreatic body soft tissue lesion consistent with NET. Patient was started on diazoxide and continuous glucose monitoring (CGM). She was referred to general surgery and underwent successful tumor resection. Insulinoma is suggested by Whipple's triad, which is presence of hypoglycemic symptoms, documented hypoglycemia and resolution of hypoglycemic symptoms after glucose administration. As clinical manifestations are non-specific, diagnosing an insulinoma is challenging and depends on collateral history and a high index of suspicion. The gold standard of diagnosis is supervised 72-hour fasting test with plasma glucose, insulin, C-peptide, and proinsulin level measurements. Medical management of insulinoma includes the use of diazoxide, calcium channel blockers, propranolol, and glucocorticoids. Surgery is definitive treatment for insulinomas, with cure rates ranging from 77 to 100%. Conclusion: Insulinomas are benign and curable in most cases but can be fatal if misdiagnosed. Incidental findings of hypoglycemia should warrant thorough diagnostic workup to facilitate timely diagnosis and management. References:1.Service FJ, McMahon MM, O'Brien PC, Ballard DJ. Functioning insulinoma--incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin Proc. 1991 Jul;66(7):711-9. doi: 10.1016/s0025-6196(12)62083-7. PMID: 1677058.

Presentation: 6/1/2024
8623 Atypical VHL Genetic Variant Causing Paraganglioma
Authors: Mangu Goutami , Faria Briceno Judith Jackelyn , Kanth Yatavelli Rajini
Published: October 2024

Disclosure: G. Mangu: None. J.J. Faria Briceno: None. R. Yatavelli: None.

Abstract: Pheochromocytomas and paragangliomas (PPGLs) are rare chromaffin cell tumors that originate from the adrenal medulla and extra-adrenal paraganglia respectively. Previous studies have shown that incidental PPGLs are seen in older patients with mild symptoms. They have lower levels of plasma catecholamines and lower incidence of malignancy than patients with nonincidental PPGLs. We report a case of an incidental paraganglioma in a young female with atypical pathogenic variant in the VHL gene which is known to cause familial erythrocytosis but NOT VHL syndrome or PPGL. Case Presentation: A 33-year-old African American female with no significant medical history presented to the emergency room with the chief complaint of right lower quadrant pain for 2 days, which started with her menstruation. The vitals were BP 128/67, pulse 67 and physical examination was unremarkable. CT showed a 4.0 x 3.0 cm heterogenous enhancing left adrenal mass and MRI with adrenal protocol revealed 3.4 x 3.1 cm mass consistent with pheochromocytoma. Labs revealed elevated plasma nor metanephrines and 24-hour urine normetanephrines were 1020 mcg. She was asymptomatic without hypertension, palpitations, or chest pain. She underwent laparoscopic left adrenalectomy after appropriate alpha blockade. The pathology report showed left periadrenal paraganglioma with immunohistochemistry staining significant for Carbonic anhydrase IX (CAIX) membranous expression which is mostly seen in paragangliomas associated with von Hippel-Lindau syndrome. Clinically, she did not have any stigmata for hereditary PPGL syndrome. Her genetic testing revealed a pathogenic heterozygous variant in the VHL gene, Exon 3, c.598C.T (pArg200Trp), which is a missense variant expected to disrupt VHL protein function. Although she has a germline mutation in VHL, it is not the garden variant which is associated with classic VHL syndrome. It has been reported to cause autosomal recessive erythrocytosis but not PPGL. Conclusion: The pathogenic heterozygous variant in VHL gene, Exon 3, c.598C.T (pArg200Trp) is known to cause autosomal recessive familial erythrocytosis type 2 in the Chuvash population, termed as Chuvash Polycythemia. Our patient did not have polycythemia but had iron deficiency anemia from menorrhagia. Several studies have reported that this variant does not cause VHL syndrome, however it has been reported in a single family with VHL syndrome but WITHOUT pheochromocytoma. To our knowledge, incidental adrenergic paraganglioma associated with this mutation has not been reported in the literature.

Presentation: 6/3/2024
7173 Cabergoline Induced Psychosis in a Patient with no Previous History of Psychiatric Disorder
Authors: Aryal Badri , Kim Keun Young , Shafi Amtul , Ganesh Malini
Published: October 2024

Disclosure: B. Aryal: None. K. Kim: None. A. Shafi: None. M. Ganesh: None.

Introduction: Cabergoline is a dopamine agonist (DA) used to treat prolactinomas. It is well established that DAs may cause psychotic symptoms. However, very few cases report cabergoline-associated psychosis in patients without personal or family history of psychiatric disorders. We report a rare case of cabergoline-induced psychosis in a patient with a prolactinoma without any underlying psychiatric disorder, which was managed with the addition of olanzapine. Case: A 41 year old male with no history of psychiatric disorder was started on cabergoline 0.5mg twice a week for a newly diagnosed prolactinoma. 4 weeks later, he presented to the emergency room for aggressive behavior and confusion for the past 2 weeks. He endorsed visual and auditory hallucinations. Cabergoline was discontinued. During hospitalization, he attempted suicide and required 1:1 observation. He was started on olanzapine per the inpatient psychiatry team. Surgical resection of the prolactinoma was considered given his acute psychosis associated with cabergoline. However, complete resection of the tumor was deemed impossible given encasement of the internal carotid arteries. After discussion with the patient, he underwent re-challenge with cabergoline 0.25mg weekly while on olanzapine under 1:1 observation in the ICU. He was monitored for 2 weeks and eventually discharged home on cabergoline 0.25mg twice a week and olanzapine with improvement in prolactin levels to 4973.7 ng/mL after 4 weeks. He continued to remain free of psychotic symptoms upon follow up as an outpatient. Discussion: Psychosis is a rare side effect of DA mediated via D2/D3 receptors in the mesocortical and mesolimbic pathways. Several cases report psychosis associated with cabergoline in patients with a history of psychiatric disorders. However only one case reports de novo psychosis. Our patient developed severe psychosis while on low-dose cabergoline for 4 weeks. This rare case of de novo cabergoline-associated psychosis re-emphasizes that psychosis may occur regardless of previous history of psychiatric disorder and independent of the dose or duration of cabergoline. Treatment of a prolactinoma in the setting of cabergoline-associated psychosis requires a multidisciplinary approach. Alternative treatment of surgical resection was considered for our patient. However surgical resection was not plausible given difficult surgical anatomy. Therefore he was monitored closely to re-initiate cabergoline while on olanzapine. Several cases report successful use of clozapine, aripiprazole, and quetiapine for patients with psychiatric symptoms while on cabergoline. Patients who are on cabergoline should be closely monitored for any psychotic symptoms. Further studies are warranted to identify patients at risk of developing psychosis while on cabergoline to tailor an individualized approach to therapy and monitoring.

Presentation: 6/2/2024
8705 Autoimmune Polyglandular Syndrome Type 2 Presenting As Recurrent Cardiac Tamponade
Authors: Marta Niedzialkowska Ewelina , Shelden Daniel
Published: October 2024

Disclosure: E.M. Niedzialkowska: None. D. Shelden: None.

Introduction: Autoimmune polyglandular syndrome type 2 (APS2) is a rare endocrinopathy with co-occurrence of autoimmune adrenal insufficiency, autoimmune thyroiditis and/or type 1 diabetes. In rare cases, APS2 can predispose patients to recurrent pericardial effusion and tamponade. Case presentation: 32 y.o male with medical history of hypothyroidism on replacement therapy diagnosed 2 weeks prior to admission presented with progressive dyspnea and hypotension. The patient was found to have pericardial effusion with tamponade requiring pressor support. Initial lab tests showed TSH 148.7 uIU/ml (N 0.4-4.5), free t4 0.7 ng/dl(N 0.7-1.5 ), free t3 2 pg/ml (N 1.7-3.5), Hb a1c 4.7% (N <5.6%), thyroglobulin antibody 851 IU/ml (N <20), TPO antibody >1 000 IU/ml (N<=35), TSI 0.1 IU/l (<0.1), sodium 127 mmol/l (N 135-145), and a negative adrenal antibody panel. The patient was started on IV levothyroxine (400 mcg daily) and stress dose steroids in the setting of shock requiring 4 pressors. Shock resolved after pericardiocentesis and the patient was weaned off pressor support. Pericardial fluid showed neutrophil predominance and was negative for an infectious process, lab tests showed negative ANA, ANCA and GBM. The day following admission lab tests showed TSH of 23.86 uIU/ml, ft4 1.3 ng/dl, the patient was transitioned to oral levothyroxine 125 mcg and the steroid regimen was tapered and discontinued. Follow up tests showed normal TSH and resolution of pericardial effusion. Four weeks after initial admission the patient was readmitted due to hypotension. Laboratory tests showed random cortisol <1.0 ug/dl (N 2.9-19.4), ACTH 17 pg/ml (N 6-48), adrenal antibody titers 1:20 (N < 1:10), cosyntropin stimulation test was positive for adrenal insufficiency and the patient was started on steroid regimen with symptomatic improvement. He was diagnosed with APS type 2 based on his constellation of endocrinopathies. Repeat echocardiogram was negative for pericardial effusion. Two months later, the patient presented with chest pain. Imaging was positive for recurrent pericardial effusion requiring pressor support and pericardiocentesis. The patient was subsequently started on colchicine. Infectious and rheumatologic workup continued to be negative. The patient did not exhibit symptoms of connective tissue disease. Seven months after the initial presentation the patient was readmitted with COVID-19 infection complicated by hypotension and a small pericardial effusion. Symptoms improved after initiation of stress dose steroids. Conclusion: Cardiac tamponade is a rare presentation of APS2 with 9 cases reported in the literature up to date. Increased incidence of pericardial effusion is presumed to be a result of autoimmune inflammation leading to fluid accumulation. The patients are prone to tamponade due to intravascular volume depletion, decreased vascular tone and impaired stress response.

Presentation: 6/3/2024
6372 Changes in Blood Steroid Hormone Profile after Switching from Metyrapone to Osilodrostat
Authors: Yokozeki K , Kameda H , Miya A , Nomoto H , Nakamura A , Jin S , Matoba K , Atsumi T
Published: October 2024

Disclosure: K. Yokozeki: None. H. Kameda: None. A. Miya: None. H. Nomoto: None. A. Nakamura: None. S. Jin: None. K. Matoba: None. T. Atsumi: None.

Background: The new steroidogenesis inhibitor osilodrostat has recently been approved for use in Cushing's syndrome. However, there are limited studies on changes in blood steroid hormone profiles after switching from existing drugs including metyrapone. Purpose: To study the changes in steroid hormone profiles with switching from metyrapone to osilodrostat in patients with Cushing's disease and to examine the differences in clinical efficacy. Case 1: A woman in her 40s underwent transsphenoidal pituitary tumor surgery (TSS) for Cushing's disease in X-12, but was not in remission and was treated with 1000 mg/day of metyrapone and oral hydrocortisone. In X-3, the patient complained of masculinization and was started pasireotide LAR 10 mg per month, which was subsequently increased to 30 mg. Despite the addition of 240 mg/day of trilostane in X-2, the patient did not show improvement. Switched the steroidogenesis inhibitors to osilodrostat 4 mg/day in year X, blood cortisol and testosterone levels decreased and the symptoms of virilization disappeared.Case 2: A woman in her 40s experienced edema in her face and limbs, increased appetite and weight gain since Y-13. After endocrinological examination, she was diagnosed with Cushing's disease. TSS was performed and she was in remission. However, she suffered a relapse in Y-4 and was started on metyrapone, which was titrated up to 4,000 mg/day. Due to gastric discomfort, metyrapone was switched to osilodrostat 52 mg/day in year Y, leading to an improvement of her gastric symptoms and stabilized blood cortisol level. Case 3: A woman in her 70s underwent TSS for Cushing's disease in Z-6, but the tumor remained and she was prescribed metyrapone 1,500 mg/day. The disease was stable and complications were under control with metyrapone. In Z-1, the patient developed elevated blood pressure and worsening leg edema, and metyrapone was switched to osilodrostat 3 mg/day in year Z, resulting decreased blood cortisol level and blood pressure. Results: Liquid chromatograph mass spectrometry (LC-MS) analysis of blood steroid hormone profiles in above three cases demonstrated a decrease in 17-OH pregnenolone, 17-OH progesterone, and 11-deoxycorticosterone after switching the steroidogenesis inhibitors. Discussion and Conclusion: It has been noted that osilodrostat lowers serum cortisol in a shorter period of time compared to metyrapone and may also decrease the number of antihypertensive medications used. Under metyrapone administration, hypertrichosis, hypertension, and hypokalemia are often observed with increased mineralocorticoid precursors, but osilodrostat may have a different clinical effect as a result of its different pattern of steroid hormone synthase inhibition.

Presentation: 6/2/2024
8602 Classical progesterone signaling in kisspeptin neurons is not required for negative feedback regulation of the GnRH pulse generator in mice
Authors: Dillon Kendra M , Lohr Dayanara B , Novak Alyssa G , Petriv Anna-Maria V , Neifert Nicole T , Moore Aleisha M
Published: October 2024

Disclosure: K.M. Dillon: None. D.B. Lohr: None. A.G. Novak: None. A.V. Petriv: None. N.T. Neifert: None. A.M. Moore: None.

Mammalian reproductive function depends on the ability of progesterone to suppress pulsatile gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion in a homeostatic negative feedback loop. Impairments in progesterone negative feedback are associated with the development of polycystic ovary syndrome (PCOS), the leading cause of infertility for people with ovaries. Although previous research indicates cells upstream from GnRH neurons expressing the classical progesterone receptor (PR) are required for negative feedback, the identity of these cells and the mechanism by which they reduce GnRH/LH pulsatile secretion remain unclear. In this study, we aimed to address the hypothesis that PR expressed by a neuronal population in the arcuate nucleus expressing Kisspeptin, Neurokinin B, and Dynorphin, recently defined as the GnRH pulse generator, is required for negative feedback regulation of LH pulses. To achieve this, we utilized Cre-lox technology in mice to conditionally delete PR from kisspeptin cells (KPRKO mice) and assessed fecundity, LH pulsatility, and the mRNA expression of KNDy neuropeptides. Female KPRKO mice paired with B6 stud males for 3 months produced significantly fewer litters (p<0.05, n=5) and pups per litter (p<0.05) compared to WT controls (n=5) (students t-tests), recapitulating a previously reported subfertile phenotype in this model. In a separate cohort of animals, serial blood samples were collected every 6 minutes for 2 hours from the tail-tip of habituated WT and KPRKO mice in diestrus (n=6/group) and estrus (n=6/group), and an ultra-sensitive ELISA was used to detect LH pulses. However, compared to WT controls, KPRKO mice did not exhibit any significant changes in total and baseline LH release, pulse frequency or pulse amplitude in either cycle stages (p>0.05, students t-tests). At the completion of serial blood sampling, brains were collected from WT and KPRKO mice and RNAscope in situ hybridization was used to quantify mRNA for kisspeptin (KISS1) and dynorphin (PDYN), which are excitatory and inhibitory to GnRH/LH secretion, respectively. No differences in the number of KISS1- and PDYN-expressing cells or the number of KISS1 and PDYN mRNA transcripts were observed between WT and KPRKO mice (n=4/group, p>0.05, students t-tests). These data suggest that progesterone signaling in kisspeptin cells through PR is not essential for negative feedback regulation of LH pulses and is unlikely to contribute to the infertile phenotype of KPRKO mice. These results suggest that negative feedback may be maintained via non-classical mechanisms or an unidentified PR-positive neuronal population.

Presentation: 6/1/2024
7476 Clinical, Pathological and Biochemical Characteristics of patients with Neuroendocrine Neoplasms (NENs) at a University Hospital in Belo Horizonte, Brazil
Authors: Romanowski R d , Ribeiro F P , Mello T T , Soares B S , Drummond J B
Published: October 2024

Disclosure: R.D. Romanowski: None. F.P. Ribeiro: None. T.T. Mello: None. B.S. Soares: None. J.B. Drummond: None.

Neuroendocrine neoplasms (NENs) are a group of rare, heterogeneous, and potentially aggressive neoplasms, whose incidence is on the rise, largely due to advances in diagnostic methods that allow for more precise and early identification. A recent comprehensive review focusing on the epidemiology, incidence and prevalence of NENs described global findings, however, it did not include any data from Latin America, particularly after WHO 2019 digestive system tumours classification. Methods: We carried a retrospective analysis in a single center aiming to evaluate different clinical, pathological and biochemical characteristics of a cohort of patients with NENs followed at the Neuroendocrinology Outpatient Clinic of the Federal University of Minas Gerais, Brazil, who were diagnosed between the years of 2004 and 2023. Results: The study sample (n=30) included 13 female patients (43%). The median (range) age at diagnosis was 42 (19-73) years old. The most common primary sites observed in the studied population were the pancreas (38%) and the stomach (24%). Twenty three percent of the patients had MEN1 associated NENs. Fourteen tumors (45%) were classified as G1 NENs, 7 tumors (23%) were classified as G2 NENs and two tumors (6,7%) were classified as neuroendocrine carcinomas, while tumor grade classification was not feasible in 7 patients (23%). One third of the patients had functional tumors and metastatic disease was present in 60% of the cases at the time of diagnosis. Conclusion: In general, the epidemiological characteristics here described for our patients align with the global trend. Concerning gender, we observed a higher prevalence of these tumors in men (57%), consistent with the male predominance of up to 3 times over females described around the world. Our patient population seems to be younger than the mean age reported in different case series. Tumoral grade classification was not feasible in a high proportion of patients and despite the high prevalence of well differentiated and low-grade NENs, metastases were commonly seen at diagnosis, in accordance with the literature.

Presentation: 6/2/2024
8539 Curcumin a Double Edged Sword: A Case of Curcumin Induced Pituitary Macroadenoma Apoplexy
Authors: Balozian P , Alfakara D , Linz M
Published: October 2024

Disclosure: P. Balozian: None. D. Alfakara: None. M. Linz: None.

<Curcumin, the active component of turmeric, exerts numerous beneficial anti-inflammatory, antiplatelet, and anticoagulant effects. Recent literature has shown however that curcumin inhibits proliferation and induces apoptosis of pituitary cells. Despite these findings, there are limited clinical cases reporting an association between curcumin and pituitary adenoma apoplexy.We report the case of a 39-year old G9P6A3 female with Hashimoto’s disease and class II obesity who presented with a constant bifrontal excruciating headache, blurry vision, photophobia, and nausea. She also had fatigue and amenorrhea for two years. Her exam showed normal vitals, decreased visual acuity, diplopia, and bitemporal hemianopsia. Data showed a serum prolactin of 69 ug/L , plasma IGF-1 of 133 ng/ml (Z score -0.4), TSH of 2.58 with a free T4 of 0.47 ng/dl [0.61-1.12 ng/dL], a random cortisol of 12.7 mcg/dl despite her stress and pain, ACTH of 27 pg/ml, DHEA-S of 46 mcg/dl, an LH of 0.5 IU/L, and an FSH of 4mIU/ml with an estradiol of 25 pg/ml. MRI of the pituitary revealed a 1.8 cm macroadenoma with a mass effect on the overlying optic chiasm and a T1 intrinsic hyperintense signal indicative of a hemorrhagic component. She was given IV dexamethasone for 24 hours then underwent transsphenoidal resection of the hemorrhagic tumor that resulted in rapid resolution of headaches and visual symptoms. She was not given any glucocorticoids during or after surgery. Labs immediately after surgery revealed a prolactin of <1ug/L and a cortisol of 26.7 mcg/dl. Pathology showed corticotroph tumor with hemosiderin deposition with a 4.2% Ki67 and negative ACTH immunostaining. On medication review, patient had been taking large doses of curcumin. In the absence of other recent precipitating factors, it was highly likely that she had curcumin-triggered apoplexy of a pituitary macroadenoma. Most recent bloodwork, about 20 months from presentation, revealed a serum prolactin of 5.0 ug/L, IGF-1 of 123ng/mL (Z score -0.6), TSH of 0.97 mIU/L with a free T4 of 0.85 ng/dL, a random cortisol of 5.3 ug/dL, ACTH of 18.2 pg/mL, DHEA-S of 94 ug/dL, LH of 2.5 IU/L, FSH of 4.3 IU/L, and an estradiol of 45 pg/mL. Regular menstrual cycles had resumed. Headaches, nausea, and vision abnormalities completely resolved.The case illustrates the need to identify any herbal remedies and supplements a patient is taking, particularly turmeric, as supplements may contribute to increased bleeding tendency of an already existing adenoma. The case also emphasizes the potential rapid recovery of pituitary function after surgical resection of an apoplectic pituitary tumor.>

Presentation: 6/3/2024