Rad, Mona Vahidi

Abstract Immune checkpoint inhibitors (ICI) have transformed cancer therapy but can induce a spectrum of endocrine complications. Acquired generalized lipodystrophy (AGL) is a rare adverse effect, leading to severe metabolic derangements including insulin-resistant diabetes, dyslipidemia, and hepatic steatosis. Marked hypoleptinemia is noted in these patients, and leptin-replacement therapy is known to be beneficial in patients with other forms of AGL. Though rare, T-cell lymphoma has been reported in patients with AGL on leptin therapy, and there has been much debate on the association between hyperleptinemia and cancer. The safety and efficacy of leptin therapy in patients with ICI-induced AGL and cancer are therefore not clear. We report a 66-year-old woman with metastatic lung adenocarcinoma who developed multiple endocrine disorders including AGL with metabolic abnormalities following pembrolizumab therapy. Initiation of daily metreleptin led to marked improvement in dyslipidemia, glycemic control, and hepatic steatosis, with no evidence of cancer recurrence after 2 years of leptin-replacement therapy. While further studies are warranted to establish the long-term efficacy and safety of leptin in ICI-induced AGL patients with a history of malignancy, this case report provides useful information for the management of these rare, challenging patients.

Abstract Disclosure: J. Arguinchona: None. N. Allen: None. M. Vahidi Rad: None. K. Doshi: None. Background: Thyrotoxic periodic paralysis (TPP) is a distinct disorder characterized by episodic, generalized muscle weakness due to hypokalemia, occurring predominantly in young adult males (20-40 years) with hyperthyroidism, particularly Graves' disease. TPP is common in East Asian populations, affecting approximately 2% of individuals with hyperthyroidism, but is rare in Western populations (0.1-0.2%) and often underrecognized in the United States. Herein, we present three cases of TPP in young Hispanic and Caucasian males with Graves’ disease, underscoring the importance of diagnostic vigilance. Clinical Cases: Case 1: A 21 y.o. Hispanic male presented to endocrine clinic following multiple hospitalizations for severe hypokalemia and myopathy. During admission, labs showed a potassium (K) 1.2 mmol/L (3.6-5.2), undetectable thyroid stimulating hormone (TSH), and free thyroxine (FT4) 2.8 ng/dL (0.9-1.7). K was replaced and Graves’s disease was confirmed by positive TSH receptor antibodies. He was started on methimazole and subsequently underwent radioactive iodine (I-131) therapy. Following development of hypothyroidism, he was placed on levothyroxine replacement, with no further recurrence of paralysis. Case 2: An 18 y.o. Caucasian male with a history of Graves’ disease presented after multiple hospitalizations for hypokalemia and lower extremity weakness. Hospitalization labs showed a suppressed TSH, FT4 2.2 ng/dL, free triiodothyronine (FT3) 7.9 pg/mL (2.3-4.1), and K 2.8 mmol/L. His weakness improved with K replacement. Methimazole was initiated and the patient subsequently opted for total thyroidectomy for definitive therapy. No recurrence of TPP was observed after thyroidectomy. Case 3: A 29 y.o. Hispanic male with Graves’ disease, non-adherent to methimazole was hospitalized due to symptoms of diffuse upper and lower extremity weakness. Labs showed K 1.6 mmol/L, undetectable TSH, and T4 >7.7 ng/dL. Symptoms resolved with K replacement. He was restarted on methimazole as well as atenolol and advised on medical adherence. Unfortunately, he was lost to follow up, and re-hospitalized 7 months later with similar symptoms and labs, again due to nonadherence with thionamide medication. After aggressive K replacement and methimazole resumption, he was discharged with urgent endocrine follow-up for definitive management of Graves’ disease. Conclusion: These cases highlight the under recognition of TPP in non-Asian populations in the United States, leading to delayed diagnosis and recurrent hospitalizations. Clinicians should maintain a high index of suspicion for TPP in young males with hypokalemia, and generalized weakness, particularly in the setting of undiagnosed or untreated hyperthyroidism. Prompt recognition and definitive treatment of hyperthyroidism is critical to preventing recurrent episodes and associated morbidity. Presentation: Saturday, July 12, 2025

Abstract While adrenal androgen production is primarily regulated by ACTH, some data suggest a less common association between hyperprolactinemia and elevated dehydroepiandrosterone sulfate (DHEA-S). We describe 2 patients with this underrecognized connection. Patient 1, a 60-year-old male, was incidentally found to have bilateral adrenal masses on computed tomography during evaluation of gastrointestinal complaints. Further workup revealed elevated levels of DHEA-S and prolactin, with pituitary macroadenoma identified as the cause, given normalization of both prolactin and DHEA-S on cabergoline therapy. Patient 2, a 38-year-old male, presented with visual field defects, and subsequent pituitary magnetic resonance imaging confirmed a macroadenoma. He also had markedly elevated levels of DHEA-S and prolactin. Both patients were treated with cabergoline, leading to rapid normalization of both prolactin and DHEA-S levels. These cases demonstrate an association between hyperprolactinemia and elevated DHEA-S, supported by the normalization of levels with medical treatment of prolactinoma. Although hyperprolactinemia in the context of a prolactinoma is an uncommon cause of elevated DHEA-S, it should be considered once other etiologies have been excluded.

Abstract Disclosure: S. Ahmed: None. M. Vahidi Rad: None. S.A. Westphal: None. M.D. Whitaker: None. Introduction: Painful Hashimoto thyroiditis is a rare variant of Hashimoto thyroiditis that mostly affects women. Most cases are empirically treated as subacute thyroiditis with corticosteroids, levothyroxine, or nonsteroidal anti-inflammatory drugs. However, no medical treatment may provide sustained pain resolution, so optimal treatment remains unclear. We describe the case of a 40-year-old female with longstanding throbbing anterior neck discomfort that failed medical therapy and her symptoms completely resolved with total thyroidectomy. Case Report: A 40-year-old lady with anterior neck pain centered over the thyroid for more than 16 years, shortly after she delivered her last child. The pain is described as intense, it tends to wax and wane but there is a constant throbbing with occasional radiation to the angle of the jaw. Over the years the pain has gradually worsened and during its flares, the thyroid itself is very tender to the point where she experiences difficulty in swallowing and hoarseness of voice. Complicating the issue is her underlying diagnosis of fibromyalgia, as she tends to experience discomfort in many other areas of her body. However, the neck pain appears to be of a different character. No symptoms of hyper or hypothyroidism. The anterior neck pain has been difficult to alleviate, she has used chronic opioids for it which seems to have helped to some extent, in the past she was on prednisone for 1 month however this made no difference to it. On examination, the thyroid is tender and somewhat firm without lymphadenopathy. Thyroid levels have been consistently normal and the most recent of which was a TSH: 1.48, FT4: 1.4, FT3: 3.5 with negative TPO and thyroid stimulating antibodies. ESR and CRP were unremarkable. Thyroid ultrasound showed mildly heterogeneous parenchyma with no solid nodules or lymphadenopathy. Interestingly she had an elevated thyroid uptake in her scan dated April 1st 2022, 4 hour and 24-hour uptakes were abnormal at 23% and 49% respectively which can be seen with Hashimoto's. She underwent total thyroidectomy and her surgical pathology showed benign thyroid tissue with multiple foci of chronic lymphocytic thyroiditis and hyperplastic nodules. Her pain completely resolved after total thyroidectomy. Discussion: Painful Hashimoto thyroiditis is a rare diagnosis and optimal treatment remains unclear. The painful variant of Hashimoto's thyroiditis should be considered in the differential diagnosis of pain and tenderness of the thyroid which can be managed successfully by surgical treatment. Thyroidectomy not only can lead to alleviation of symptoms but also provides the definitive diagnosis. The risks of surgical intervention must be taken into consideration, especially because painful Hashimoto thyroiditis can be associated with a small fibrous gland; hence, the importance of access to highly skilled, experienced surgeons cannot be overemphasized. Presentation: 6/1/2024

Abstract Disclosure: M. Vahidi Rad: None. S. Ahmed: None. A. Kumar: None. Introduction: Granulomatous disease can cause hypercalcemia due to increased production of 1,25 dihydroxyvitamin-D. Mycobacterium avium complex (MAC) infection is an AIDS (acquired immunodeficiency syndrome)-defining illness and a granulomatous disease that can lead to hypercalcemia. We report a case of severe hypercalcemia from Immune Reconstitution Inflammatory Syndrome (IRIS) in a patient with AIDS and disseminated MAC which developed several months after initiation of appropriate antibiotic and antiviral therapy. Clinical Case: A 30-year-old female with HIV on anti-retroviral therapy and disseminated MAC infection on antibiotics developed PTH independent mild hypercalcemia in the 10.9-11.5 mg/dL range about 4 months after initiation of antiviral and antibiotic therapy. 1,25 dihydroxyvitamin D level was normal at 50 pg/mL (reference range 18-78 pg/mL). The hypercalcemia worsened and about 8 months after initiation of antimicrobial therapy, she had a hospitalization for severe hypercalcemia with corrected calcium of 15.2 mg/dL and acute kidney injury. PTH was suppressed at 6.9 pg/mL and repeat 1,25 dihydroxyvitamin D level was elevated at 129 pg/mL (reference range 18-78 pg/mL). Other testing for PTH independent hypercalcemia including PTH- Related Peptide, serum protein electrophoresis (SPEP) and TSH were normal. She was diagnosed with hypercalcemia from increased calcitriol production in the setting of IRIS secondary to disseminated MAC. Hypercalcemia secondary to increased production of calcitriol in patients with MAC and HIV infection might happen or worsen months after starting the antimicrobial treatments and has been reported as a potential manifestation of immune reconstitution. MAC-associated IRIS has been reported to be associated with a T-helper cell response with increased number of interferon-gamma-producing T-cells and Th1-cytokines that can potentially cause a granulomatous reaction. These granulomas will have increased macrophage 1-alpha-hydroxylase activity that can further result in more production of 1,25 dihydroxyvitamin D3 and cause more hypercalcemia. Prednisone was started with resultant improvement in hypercalcemia. Conclusion: Severe hypercalcemia due to worsening of subclinical granulomatous infections such as MAC can be a manifestation of IRIS in patients with HIV infection or AIDS who are on antiretroviral treatments. This responds to glucocorticoids. Presentation: 6/2/2024