Hasil untuk "Diseases of the endocrine glands. Clinical endocrinology"

Mary A Faragalla, Candice Holliday, N. Holliday

Purpose: To report a rare case of pituitary macroadenoma in pregnancy. Pituitary macroadenomas are benign tumors of the pituitary gland. Routine presentation may include endocrine abnormalities or visual field defects. The prevalence of pituitary macroadenomas in the general population is approximately 40.67 per 100,000 individuals. In pregnancy, the occurrence is even more rare, and diagnosis and management require a multidisciplinary approach to minimize potential complications. This case highlights the diagnostic process, management considerations, and potential impact on pregnancy outcomes. Method: Case Report Results: A 38-year-old G8P3043 female at 26+2 weeks of gestation presented with intractable headache. The patient stated she choked while drinking juice the night before, which led to a coughing spell. She reported that the headache began soon after the coughing spell. The headache was persistent, dull, and diffuse in nature and associated with photophobia, phonophobia, and two episodes of vomiting. She denied visual changes, dizziness, or weakness. The patient was administered a pain cocktail with minimal relief. Computed tomography (CT) and magnetic resonance imaging (MRI) of the head showed a 2.6 x 1.3 x 1.8 cm expansile mass in the sella with suprasellar extension, elevating and compressing the optic chiasm. The primary diagnosis was a pituitary macroadenoma. Neurology was consulted, and the patient was evaluated. Neurological physical exam was unremarkable, including cranial nerves, motor, sensation, coordination, and higher integrative functions. Neurology concluded there was no need for further neurological workup at this time and to follow up with the neurologist in 2 months. Her pregnancy has been complicated by fetal growth restriction (FGR), abnormal non-invasive prenatal testing (NIPT) with high suspicion for Trisomy 21, chronic hypertension, and advanced maternal age. Past medical history includes chronic hypertension on labetalol 100 mg twice a day and occasional migraines. She was never evaluated by a neurologist for the migraines because she reported only a few episodes a year. The patient was receiving twice weekly fetal testing for FGR with follow up ultrasounds every 3 weeks to assess fetal growth in the setting of highly suspected Trisomy 21. The patient remained asymptomatic throughout this time and did not require pain medication. The patient expressed a desire for a vaginal delivery. Due to the findings of pituitary adenoma and concerns for labor, an anesthesia referral was requested to determine if she was an appropriate candidate for regional anesthesia. She was evaluated by anesthesia, and they deemed her an appropriate candidate. At her 2 month follow-up visit with neurology, she denied any complaints, including headache or visual changes. Neurology referred her to neurosurgery for further evaluation. Neurology plans to follow up with her in 6 months. The team plans for delivery at 38 weeks pending continued normal antenatal testing. Conclusion: Pregnancy is a physiological state that induces significant changes in the endocrine system, particularly affecting the pituitary gland. These anatomical and functional changes make the management of pituitary disease more complex compared to the non-pregnant state. Due to hyperplasia and hypertrophy of lactotroph cells, the pituitary gland may increase in size by up to 40% in the second trimester and up to 70% in the third trimester, reaching two to three times its normal size. A pituitary adenoma greater than 10 mm in diameter, classified as a macroadenoma, has a 15-36 % chance of increasing in size during pregnancy. This growth risk necessitates close monitoring for symptoms such as headaches or visual disturbances, which may indicate tumor progression and could require neurosurgical evaluation. The treatment and surveillance of macroadenomas during pregnancy should be individualized. Patients should undergo close clinical follow-up with visual field testing during each trimester. In cases of non-functioning adenomas or hormone-secreting adenomas, surgery may be considered when there is significant visual impairment or life-threatening endocrine dysfunction. The second trimester is typically considered the safest period for surgical intervention, as it is associated with lower risks of congenital anomalies and preterm birth. The majority of women with macroprolactinomas or non-functioning adenomas experience favorable pregnancy outcomes. The primary goal of management is to ensure maternal and fetal safety while effectively controlling the tumor. Although rare, pituitary apoplexy, which involves infarction or hemorrhage within the pituitary gland often in the context of a pre-existing adenoma, can occur and may require emergency intervention. A collaborative, multidisciplinary approach involving obstetrics, endocrinology, neurology, neurosurgery, and maternal-fetal medicine is essential to optimize outcomes for both the mother and the fetus.

Nipith Charoenngam, Natapong Thaneerat, Pornlada Likasitwatanakul et al.

Kim Tunez, Sara Ringwald-de Meyer, Mohammed Barigou et al.

Although an increase in insulin resistance is frequently associated with liver cirrhosis, a condition sometimes referred to as hepatogenic diabetes (HD), the pathophysiology is still poorly understood. Moreover, the management of patients with HD, both diagnostically and therapeutically, is complex. In this article, we present the case of a cirrhotic patient, initially not known to have diabetes or prediabetes, who developed fulminant diabetes overnight, with massive resistance to subcutaneous insulin treatment. Management during hospitalization was extremely complicated, leading to significant staggering of the insulin doses until the liver transplant, which allowed complete normalization of the glycemic profile.

Liangliang Huo, Liangliang Huo, Tingting Zhao et al.

BackgroundIodine deficiency during pregnancy has been associated with various adverse outcomes; however, recent data on iodine status among women in Hangzhou, China, remain limited.MethodsBetween 2019 and 2022, this birth cohort study enrolled 290 eligible pregnant women at ≤12 weeks of gestation. A standardized, self-developed questionnaire was used to survey each participant, covering demographic information, pregnancy details, dietary iodine intake, and related topics. Physical examination findings of each participant and their offspring were collected. Maternal urinary iodine concentration was measured in the first, second, and last trimesters of pregnancy. Offspring outcomes were evaluated by measuring weight and length at birth, 1 month, 6 months, and 18 months, along with the recording of incidences of spontaneous premature birth, small for gestational age (SGA), and low birth weight.ResultsHigher maternal urinary iodine concentration (UIC) during the third trimester was found to be a protective factor against spontaneous premature birth and SGA. Similarly, elevated maternal UIC in the second trimester was identified as a protective factor against spontaneous premature birth. No significant association was observed between low birth weight and maternal UIC in the first, second, and last trimesters. However, offspring born to mothers with iodine insufficiency in the last trimester exhibited lower birth weight and length, as well as reduced length during follow-up. Additionally, offspring of mothers with iodine insufficiency in the first trimester showed lower long-term weight and length.ConclusionsThese findings highlight the importance of enhanced monitoring of iodine status in pregnant women to mitigate related adverse outcomes.

Maryam Sanoie, Farshad Teymoori, Raziyeh Abooshahab et al.

ABSTRACT Aim This study aimed to investigate the relationship between plasma fatty acids (FAs), FA‐derived factors and PPARγ expression in visceral and subcutaneous adipose tissues (VAT and SAT) of obese and nonobese adults. Methods This cross‐sectional study involved 167 adults aged 19 to 65. Samples of VAT and SAT were obtained during elective abdominal surgeries. Participants were divided into two groups: nonobese (BMI < 30 kg/m2) and obese (BMI ≥ 30 kg/m2). Anthropometric and biochemical measurements were taken, and plasma fatty acids (FAs) were analysed using gas chromatography flame ionisation detection (GC/FID). PPARγ mRNA levels were measured through real‐time RT‐qPCR. Results Obese individuals had higher PPARγ gene expression in both VAT and SAT compared to nonobese participants (p < 0.001). Eighteen FFAs and three new FA‐derived factors were identified in both groups, accounting for 69% of the variance in nonobese individuals and 71% in obese individuals. After adjusting for confounding factors, saturated FA (SFA) was associated with PPARγ expression in the SAT of the nonobese group (β = −0.12, p = 0.019). Additionally, total FAs (β = −0.02, p = 0.017), SFA (β = −0.06, p = 0.048), monounsaturated FA (MUFA) (β = −0.08, p = 0.020), polyunsaturated FA (PUFA) (β = −0.03, p = 0.039) and omega‐6 FA (β = −0.03, p = 0.040) were associated with VAT PPARγ expression among obese individuals. Conversely, an inverse correlation was observed between factor I of FAs and SAT PPARγ expression in nonobese individuals (β = −0.15; p = 0.027). Conclusion These findings suggest that alterations in plasma FA profiles are associated with PPARγ gene expression, particularly in obese individuals. This fact highlights the potential role of dietary FAs in metabolic regulation and health issues related to obesity.

Tyler N. Akonom, Mary A. Allen, Pei-San Tsai

Sexual interactions have previously been shown to improve reproductive health through unknown mechanisms. In this study, we used RNA-Seq to examine sex-induced gene expression changes in the preoptic area (POA), a critical reproductive brain region. Using a mouse model defective in fibroblast growth factor signaling (dnFGFR mouse), previously shown to disrupt the gonadotropin-releasing hormone (GnRH) system, we examined the impact of opposite sex (OS) housing on gene expression in the POA of a reproductively compromised animal. Bulk RNA-Seq followed by gene set enrichment analysis (GSEA) were used to analyze changes in gene expression and biological processes in control and dnFGFR mice after 300 days of cohabitation with a same sex or OS partner. OS housing of dnFGFR mice, but not control mice, significantly improved reproductive anatomy and gonadotropins in dnFGFR mice. These changes occurred concomitantly with novel biological processes related to estradiol metabolism and neuron excitation. Our results suggest a new role of neuron- or astrocyte-derived estradiol in the plasticity of the GnRH neuron population and offer a promising new direction for the treatment of reproductive disorders stemming from GnRH deficiency.

Karine Aouchiche, Thierry Brue, Emeline Marquant et al.

ABSTRACT Objective This study aimed to evaluate the experiences of patients who had a joint endocrinology consultation for transition to adult care at Marseille university hospitals between 2010 and 2020, focusing on patient follow‐up, satisfaction, difficulties, and expectations. Methods A healthcare transition questionnaire was designed and administered to patients several years after transition to adult care. Results One hundred and fifteen patients with rare endocrine disorders were included, with a mean age of 18.8 years at the transition consultation. Ninety‐six percent (110/115) continued adult care after the first joint consultation, and 75% were still in follow‐up when completing the questionnaire (mean follow‐up, 4.5 years). Of the 81 respondents, 89% were satisfied with the transition, and 64% reported no difficulties. The most common difficulties were psychological, logistical, and medical. Fifty‐three out of 74 respondents (72%) felt the transition occurred at the right time, 17 (24%) thought it was too early, and 4 (5%) felt it was too late. The main concern was the transmission of medical information between doctors. Suggestions for improvement included more joint consultations and personalized transition pathways. Conclusion In this group of rare endocrine disease patients, a transition pathway based on a joint pediatric‐adult consultation was associated with high patient satisfaction and long‐term follow‐up rates. Patients' suggestions and reported difficulties highlight issues to be addressed and complementary strategies to develop.

M. Lopez Baez, Ingrid Abarca, Gordon White et al.

Abstract Disclosure: M. Lopez Baez: None. I. Abarca: None. G. White: None. C. Sanchez Perez: None. S. Gra Menendez: None. Langerhans Cell Histiocytosis (LCH) is a rare systemic disorder characterized by clonal proliferation of Langerhans cells, with potential involvement of multiple organs, including the lungs and hypothalamic-pituitary axis. We present the case of a 29-year-old male with a history of spontaneous pneumothorax and a new diagnosis of LCH, complicated by transient central diabetes insipidus (DI).The patient initially presented with recurrent pneumothorax requiring thoracic intervention. He subsequently developed persistent polyuria and polydipsia, raising concern for an endocrine etiology. Brain MRI revealed scattered non-enhancing T2 hyperintense foci within the posterior fossa, partially empty sella, and absent T1 hyperintensity of the posterior pituitary gland, consistent with central DI secondary to LCH. A right lower lobe lung wedge resection confirmed small clusters of CD1a- and S100-positive cells, supporting the diagnosis of LCH. Laboratory findings showed hypernatremia, low urine osmolality, and symptomatic relief with desmopressin, confirming central DI. Surprisingly, at follow-up, the patient no longer required desmopressin therapy, suggesting potential resolution or stabilization of pituitary dysfunction. This case highlights the diagnostic complexity of LCH with multi-organ involvement and the importance of recognizing polyuria and polydipsia as red flags for central DI. A multidisciplinary approach integrating endocrinology, thoracic surgery, and radiology was critical in diagnosing and managing this multisystemic disease. Tailored interventions, including pleurodesis and transient desmopressin therapy, improved the patient’s clinical stability. The variability of endocrine dysfunction in LCH underscores the need for close monitoring and follow-up to optimize outcomes. Presentation: Sunday, July 13, 2025

Luyao Zhang, Luyao Zhang, Pai Wang et al.

There has been a major increase in Type 2 diabetes and obesity in many countries, and this will lead to a global public health crisis, which not only impacts on the quality of life of individuals well but also places a substantial burden on healthcare systems and economies. Obesity is linked to not only to type 2 diabetes but also cardiovascular diseases, musculoskeletal disorders, and certain cancers, also resulting in increased medical costs and diminished quality of life. A number of studies have linked changes in gut in obesity development. Dysbiosis, a deleterious change in gut microbiota composition, leads to altered intestinal permeability, associated with obesity and Type 2 diabetes. Many factors affect the homeostasis of gut microbiota, including diet, genetics, circadian rhythms, medication, probiotics, and antibiotics. In addition, bariatric surgery induces changes in gut microbiota that contributes to the metabolic benefits observed post-surgery. Current obesity management strategies encompass dietary interventions, exercise, pharmacotherapy, and bariatric surgery, with emerging treatments including microbiota-altering approaches showing promising efficacy. While pharmacotherapy has demonstrated significant advancements in recent years, bariatric surgery remains one of the most effective treatments for sustainable weight loss. However, access to this is generally limited to those living with severe obesity. This underscores the need for non-surgical interventions, particularly for adolescents and mildly obese patients. In this comprehensive review, we assess longitudinal alterations in gut microbiota composition and functionality resulting from the two currently most effective anti-obesity treatments: pharmacotherapy and bariatric surgery. Additionally, we highlight the functions of gut microbiota, focusing on specific bacteria, their metabolites, and strategies for modulating gut microbiota to prevent and treat obesity. This review aims to provide insights into the evolving landscape of obesity management and the potential of microbiota-based approaches in addressing this pressing global health challenge.

Adrian H. Heald, John Bassett, Nuria Puente‐Ruiz et al.

淼 张

Hyperthyroidism, the full name of hyperthyroidism, is a disease caused by the secretion of excessive thyroid hormone by the thyroid gland, clinically manifested as palpitation, goiter, bulging eyes, hyperhidrosis, irritability, etc., which belongs to the endocrine system disease. Patients with hyperthyroidism often experience a variety of complications, of which lack of sleep is the most common and intractable one, which has a great impact on the quality of life of patients. Modern medicine has a good clinical effect, but sleep disorders need to use sedatives to help patients sleep, resulting in long-term dependence and drug resistance. In recent years, with the development of traditional Chinese medicine, the clinical use of integrated traditional Chinese and Western medicine can effectively supplement the shortcomings of Western medicine, and play a certain effect in preventing and reducing complications such as hyperthyroidism combined with insomnia. The author has been engaged in the process of diagnosis and treatment of endocrine diseases for a long time. From the perspective of traditional Chinese medicine, gall disease combined with insomnia and spleen has a strong correlation, if the qi tonifies blood, spleen and heart as the treat-ment principle, the effect is exact. Based on this, this study expounds the experience of treating hyperthyroidism combined with sleep disorders from the perspective of differentiation of heart, liver and spleen. The author selects 60 cases of hyperthyroidism combined with insomnia treated in the Endocrinology Department of Urumqi Hospital of Traditional Chinese Medicine from January 2020 to January 2023 for syndrome differentiation analysis, and analyzes the experience of treating hyperthyroidism combined with insomnia from the perspective of differentiation of heart, liver and spleen of traditional Chinese medicine. In order to provide reference for future clinical work and scientific research work, it is summarized as follows.

Gia Fontanazza, A. Conforti, Kimberly Bird et al.

Abstract Disclosure: G. Fontanazza: None. A.R. Conforti: None. K. Bird: None. M. Caplan: None. Intro: Carney complex (CNC) is an autosomal dominant disorder characterized by multisystem neoplasia that primarily affects the thyroid, pituitary, and adrenal glands. Its prevalence is not well established, as only 750 cases have been reported worldwide. This condition arises when an inactivating PRKAR1A gene mutation results in dysregulated cell proliferation and tumorigenesis. Complications include the potential for malignant transformation and systemic manifestations, necessitating comprehensive management and ongoing surveillance of disease progression. Case: The patient is a 58-year-old woman who initially presented as a teenager with complaints of hirsutism, truncal obesity, and violaceous abdominal striae. Initial workup revealed a low-dose dexamethasone suppression test that resulted in a non-suppressed cortisol levels. She also had undetectable adrenocorticotropic hormone (ACTH) levels. Imaging revealed no pituitary masses and demonstrated slight bilateral adrenal enlargement without adenomas. Despite these results, she was empirically treated for presumed pituitary-dependent Cushing's disease and received external beam radiation. Despite treatment, she continued to have episodes of hypercortisolism that were apparent clinically and biochemically. Over time, she developed a cardiac myxoma with six cerebrovascular accidents and multiple benign tumors. As an adult, she underwent extensive endocrine evaluation, which revealed urine cortisol excretion that paradoxically rose in response to dexamethasone. ACTH levels were always undetectable, even when she was significantly hypercortisolemic. Genetic testing revealed a homozygous mutation in the melanocortin-2 receptor (MC2R). Accordingly, she elected to have a bilateral adrenalectomy and was started on hydrocortisone and fludrocortisone. Discussion: The patient exhibited ACTH-independent micronodular adrenal hyperplasia and its most frequent variant, primary pigmented nodular adrenocortical disease. Bilateral pigmented nodular hyperplasia is a finding which can occur in association with CNC and cause episodic hypercortisolism. These patients have been shown to respond to dexamethasone with a paradoxical increase in glucocorticoid excretion. While management requires ongoing surveillance, this patient had not been diagnosed until later in life and did not have regular screening. When speculating on the late detection, her story reflects the parable of the blind men and the elephant: endocrinology managed Cushing's disease, cardiology managed atrial myxoma, and oncology managed osteochondromyxomas. Limited perspective with specialized management and an inability to see the whole picture led to prolonged diagnosis with unfortunate sequelae. This report encourages physicians to develop perspective awareness and to consider the entire picture when treating patients. Presentation: 6/2/2024

William Lai, A. Turtz, Pamela Traisak et al.

Abstract Disclosure: W. Lai: None. A. Turtz: None. P. Traisak: None. F.H. Morgan: None. Introduction: Hypopituitarism is a rare disorder of decreased hormone secretion with a prevalence of 0.05% [1]. It is exceedingly rare to be caused by pituitary inflammation such as IgG4 mediated plasmacytic cell invasion hypophysitis which accounts for 4% of all hypopituitarism cases [2]. We present a challenging case of presumed IgG4 hypophysitis using Leporti criteria. Case: A 79 year old male with a medical history of hypertension, hypothyroidism, and mitral valve repair presented to the hospital for syncope, fatigue, and hypotension. Blood work done was significant for a low cortisol of 0.8 µg/dL (5-25 µg/dL), ACTH of 5 pg/mL (10-60 pg/mL), TSH of 0.120IU/mL (0.5-5IU/mL), and FT4 of 0.89ng/dL(0.7-1.9ng/dL). Prolactin and IGF1 were unremarkable. He was started on hydrocortisone 10 mg in the morning and 5 mg in the evening with improvement in symptoms. On follow up with Endocrinology, an MRI revealed an intrasellar/ suprasellar mass measuring 18 mm craniocaudal, sellar component of 11x9 mm, and suprasellar component 13x9mm with effacement and superior displacement of the optic chiasm raising the question of hypophysitis, and an incidental finding of a parotid mass. IgG4 testing was sent with results elevated at 377 mg/dL. PET scan showed uptake in the pituitary gland, right parotid gland, as well as mediastinal and hilar lymphadenopathy. Biopsy of the right parotid lesion showed pleomorphic adenoma. Patient deferred biopsy of hilar lymph nodes.The patient’s steroids were changed to prednisone to treat likely IgG4 mediated hypophysitis and repeat MRI after 4 weeks of treatment showed a reduction in the size of the pituitary lesion. He was subsequently referred to rheumatology for further evaluation of systemic disease. Additional work up including SPEP, Cryoglobulins, ANA IFA, ANCA, C3, C4, SSA, SSB, ACE, and immunoglobulin levels were negative. Conclusion: IgG4 related hypopituitarism is a rare diagnosis that is difficult to diagnose. In this case a definitive diagnosis with histological sampling was not obtained but a working diagnosis of IgG4 related hypophysitis was made based on clinical presentation, MRI findings, an elevated IgG4 > 140, and response to treatment. He ultimately fulfilled the diagnostic criteria proposed from Leporti et al [3]: MRI with sellar mass, IgG4 > 140mg, and steroid responsive decrease in size of the pituitary lesion, with concomitant improvement of symptoms. This case highlights the difficulty in diagnosis of IgG4 hypophysitis and the benefit of using non histological diagnostic criteria. Presentation: 6/1/2024

Emily Langnas, S. Chao, Kellyann M Gomes et al.

Abstract Disclosure: E. Langnas: None. S. Chao: None. K.M. Gomes: None. A. Bhan: None. Metastatic disease to the thyroid gland is uncommon with a reported incidence of up to 4% in post-surgical specimens. Lung cancer is the most common primary tumor site in autopsy series. Clinically, renal cell carcinoma is the most common primary tumor site. Metastatic melanoma to the thyroid gland is clinically rare, however, in autopsy series, it has been reported with incidence of up to 39%. A 61-year-old man presented to the endocrinology clinic for an incidentally detected thyroid nodule. He had recently presented with a chronic cough, prompting a chest x-ray that revealed pulmonary nodules. Subsequent computed tomography (CT) showed numerous bilateral lung nodules measuring up to 2.5 cm and an incidental thyroid nodule. Ultrasound of the thyroid identified a 2.7 cm mixed cystic-solid right thyroid nodule. No risk factors for thyroid cancer were identified. His TSH was 3.51uIU (0.45 - 5.33 uIU/mL). The thyroid nodule was biopsied, and pathology revealed atypical spindle cells with irregular nuclear membranes and scattered histiocytes. A further review with cytopathology suggested non-thyroidal origin of the cells. Molecular testing with AFIRMA reported a telomerase reverse transcriptase (TERT) promoter mutation at C228T. The sequencing was negative for TERT C250T, BRAF, RET, PETC1, PTC3 and MTC. Due to concerns about metastatic disease, a positron-emission tomography (PET)-CT was conducted, revealing hypermetabolic lesions in numerous bilateral lung nodules, right thyroid nodule, porta hepatis lymph node, and a soft tissue nodule within the greater curvature of the gastric body. Subsequent biopsies of the right lung and gastric body confirmed the diagnosis of metastatic melanoma. On further questioning, it was found that the patient had a history of a skin lesion on his back that was excised several years ago with pathology reporting tumoral melanosis. Malignant melanoma has a poor prognosis due to high recurrence and metastatic rates. In melanoma, TERT promoter mutations are the most common mutations in noncoding regulatory regions. TERT C228T mutations and C250T mutations are seen in malignant melanoma and studies have shown that TERT promoter mutations are associated with aggressive clinical behavior. These TERT promoter mutations can also be seen in various other cancers including primary thyroid cancers with a similar association with more aggressive thyroid tumor characteristics. Our case describes a patient with a thyroid nodule and molecular testing noting a TERT promoter mutation. Both primary thyroid cancer and metastatic disease to the thyroid should be considered in these cases. This case also highlights the importance of obtaining a thorough history of prior malignancy in patients with thyroid nodules to assess the risk of metastatic disease. Presentation: 6/1/2024

Isabella Marranzini Rodriguez, Michelle Lemelman, Lorraine E. Canham

Abstract Disclosure: I. Marranzini Rodriguez: None. M. Lemelman: None. L. Canham: None. Background: Medullary thyroid cancer (MTC) is a neuroendocrine tumor that originates from the parafollicular C cells of the thyroid gland. MTC accounts for approximately 5% of thyroid cancer in children, and the majority of MTC cases are associated with the autosomal dominant tumor predisposition syndrome Multiple Endocrine Neoplasia 2 (MEN2). Sporadic MTC is uncommon in the pediatric population and associated with somatic mutations of RET or RAS (1). Existing management options for metastatic disease have demonstrated some benefit, however, with systemic side effects. Selpercatinib, a highly selective RET kinase inhibitor, is FDA approved for patients >= 12 years of age. Here we present a case of a 10-year-old patient with metastatic MTC with encouraging results. Clinical Case: A previously healthy 10 year 2-month-old male presented with left-sided neck swelling. Imaging showed a 9.7 cm solid mass spanning nearly the entire left neck, occluding the left internal jugular vein, extending to the upper chest, and resulting in high-grade narrowing of the trachea near the thoracic inlet; the mass involved the left thyroid gland and engulfed the left common carotid. His initial lab evaluation showed an elevated TSH of 10.10 mcU/mL (0.6-5.5 mcU/mL) and Free T4 1.22 ng/dL (0.9-1.67 ng/dL). Tumor markers revealed a calcitonin of 32,264 pg/mL (normal range C, p.M918T somatic mutation. Evaluation for pheochromocytoma and hyperparathyroidism, given association of MTC with MEN2, was negative. Genetic testing was negative for germline RET mutations. He was started on selpercatinib, 120 mg every 12 hours. Follow up imaging after 2 months of therapy demonstrated a significant decrease in tumor burden. Approximately 5 months after starting he had a decrease in CEA to 14.8 ng/mL and calcitonin to 69 pg/mL, prior to surgery. Given the risk of locoregional recurrence he underwent total thyroidectomy with lateral neck dissection. However, the tumor was noted to be adherent to the trachea, encasing the left recurrent laryngeal nerve, and left carotid artery preventing full resection. He was started on levothyroxine at 62.5 mcg daily on POD#1 and re-started on selpercatinib approximately 2 weeks post-operatively. Conclusion: We present a case of RET-positive metastatic medullary thyroid carcinoma without germline RET mutation successfully treated with selpercatinib. Long-term follow-up for sustained response and tolerability is needed. Reference: 1. Bauer, Andrew J. “Pediatric Thyroid Cancer: Genetics, Therapeutics and Outcome.” Endocrinology and metabolism clinics of North America vol. 49,4 (2020): 589-611. doi:10.1016/j.ecl.2020.08.00 Presentation: 6/2/2024

Lara Frommer, Jochem König, Sofia Chatzidou et al.

Andrea M. Isidori, Valeria Hasenmajer, Francesca Sciarra et al.

J. Seidenberg, M. J. Uddin Ansari

Abstract Disclosure: J. Seidenberg: None. M.J. Ansari: None. Background: Resistant HTN, blood pressure remaining above goal despite concurrent use of three antihypertensives of different classes at maximum doses is a common presentation in both endocrinology and primary care settings. Patients can often be prescribed multiple max-dosed antihypertensives with varying results and adverse effects and still spend years with uncontrolled HTN leading to long term health concerns. Hyperaldosteronism is diagnosed for resistant HTN in 4% of primary care patients and 10% endocrinology-referred patients. Adrenal adenomas account for 40% of all cases characterized by high aldosterone/renin activity ratio, hypokalemia, mild hypernatremia and hypomagnesemia commonly diagnosed with a mass found in the adrenals on CT. Clinical Case: Patient is a 39 year old Female who presented to the endocrinology office due to elevated urine metanephrine levels, BP 159/100. Patient had resistant HTN since her early 20s treated currently with labetalol and nifedipine, and hypokalemia treated with potassium supplements. Lab results revealed potassium 3.4 mmol/L (3.6 -5.2 mmol/L), normetanephrines 787 mcg/g (0-145 mcg/g) , aldosterone 11 ng/dL (2-9 ng/dL) , renin 0.2 ng/mL/h (0.7- 3.3 ng/mg/hr), aldosterone/renin activity ratio 55 (30, and 15 years of potassium levels between 3.0 and 3.5. CT of the adrenals revealed no masses. Patient underwent IR guided venous sampling which indicated R adrenal gland producing 45x more aldosterone than the L adrenal gland. Patient underwent R sided adrenalectomy for definitive management of primary hyperaldosteronism. Pathology showed cortical adenoma. Patient was continued on chlorthalidone, losartan and nifedipine, and within 3 months her BP averaged 120/70 mmHg, with potassium within normal limits, Aldosterone 13 ng/dL, renin 1.25 ng/mL. Conclusion: Concurrent hyperaldosteronism with essential HTN is an uncommon but potential cause of resistant HTN. Patients with resistant HTN, prescribed multiple max-dosage antihypertensive medications while also having negative renal artery US result should undergo aldosterone and renin lab work. CT scans can have low sensitivity for adrenal adenoma. Concerning lab work should be followed up by IR-guided venous sampling for evaluation of an adrenal cortical adenoma, which can be treated surgically. Underlying essential HTN will still require treatment, but at significantly decreased medication dosages. Patients with resistant HTN should be evaluated for hyperaldosteronism early in their disease course regardless of a negative CT to prevent sequelae of untreated hyperaldosteronism including cardiac hypertrophy, arrhythmias, nephrogenic diabetes insipidus and neuromuscular symptoms. Presentation: Friday, June 16, 2023

Brigida Colon Barreto, Stephanie Patrick, H. Oktaei et al.

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

Zeynep Koçberber, Nienke Willemsen, Alexander Bartelt et al.

IntroductionBrown adipocytes produce heat through non shivering thermogenesis (NST). To adapt to temperature cues, they possess a remarkably dynamic metabolism and undergo substantial cellular remodeling. The proteasome plays a central role in proteostasis and adaptive proteasome activity is required for sustained NST. Proteasome activators (PAs) are a class of proteasome regulators but the role of PAs in brown adipocytes is unknown. Here, we studied the roles of PA28α (encoded by Psme1) and PA200 (encoded by Psme4) in brown adipocyte differentiation and function.MethodsWe measured gene expression in mouse brown adipose tissue. In cultured brown adipocytes, we silenced Psme1 and/or Psme4 expression through siRNA transfection. We then assessed impact on the ubiquitin proteasome system, brown adipocyte differentiation and function.ResultsWe found that Psme1 and Psme4 are expressed in brown adipocytes in vivo and in vitro. Through silencing of Psme1 and/or Psme4 expression in cultured brown adipocytes, we found that loss of PAs did not impair proteasome assembly or activity, and that PAs were not required for proteostasis in this model. Loss of Psme1 and/or Psme4 did not impair brown adipocyte development or activation, suggesting that PAs are neither required for brown adipogenesis nor NST.DiscussionIn summary, we found no role for Psme1 and Psme4 in brown adipocyte proteostasis, differentiation, or function. These findings contribute to our basic understanding of proteasome biology and the roles of proteasome activators in brown adipocytes.