Abstract Disclosure: S. Ghaith: None. A. Ramachandran: None. C. Alcorn: None. F. Amer: None. A. Thompson: None. A. Ramachandran: None. Background: Bexarotene, an antineoplastic agent used for the treatment of cutaneous T cell lymphoma, is associated with a rapid and profound suppression of thyrotropin, which may lead to central hypothyroidism. Case: A Seventy-four-year-old female with a recent diagnosis of Cutaneous T cell lymphoma presented with a 1-week history of progressive fatigue, lightheadedness, and night sweats. She was found to have hypotension and hypothermia. She was started on oral Bexarotene chemotherapy 225 mg daily five days prior to admission. The physical exam was unremarkable except for sinus bradycardia and hypothermia. Labs were significant for TSH 0.48 [0.4-4.2 uIU/mL] dropped from 3.3 uIU/mL one week prior, FT4 0.5 [0.8-1.7 ng/dL] and Total T3 111 ng/dL [87- 187 ng/dL] consistent with central hypothyroidism. Bexarotene was held during her hospitalization per hematology recommendations. The patient was started on Levothyroxine 50 mcg, which was later advanced to 75 mcg daily based on free T4 levels. At one month follow up, free T4 level normalized while on Levothyroxine and Bexarotene was restarted again by her hematologist. Discussion: Bexarotene, an antineoplastic agent approved for treating cutaneous T cell lymphoma, can rapidly suppress TSH levels by directly inhibiting its secretion and affect thyroid hormone metabolism, leading to central hypothyroidism. The degree of suppression of TSH increases with higher doses of Bexarotene while reduction in free T4 and TSH are reversible. Patients already receiving thyroid hormone therapy may require increased thyroid hormone doses to achieve therapeutic levels. If bexarotene is permanently discontinued, levothyroxine can either be stopped or can be resumed to doses used prior to bexarotene therapy. Recovery of thyroid function usually occurs within weeks of Bexarotene discontinuation. Conclusion: Oral Bexarotene can cause central hypothyroidism therefore, thyroid function tests should be measured at baseline and treatment. Thyroid hormone replacement should be considered if central hypothyroidism is suspected. Presentation: Friday, June 16, 2023

Abstract Disclosure: A. Ramachandran: None. S. Ghaith: None. A. Ramachandran: None. Background: Ritonavir, a potent inhibitor of the CYP3A4 enzyme, can lead to high systemic concentrations of even intranasal steroids causing Cushing’s syndrome. Case: A fifty-seven-year-old man with history of HIV on HAART presented with a 3-month history of fatigue, weight gain and easy bruising. History was negative for heat/cold intolerance, hair loss, constipation, erectile dysfunction. Medications included emtricitabine-tenofovir-alafenamide and ritonavir at stable doses for several years. He denied taking any oral or topical steroids, but reported using over the counter (OTC) fluticasone propionate (FP) for the past 6 months for seasonal allergies. Physical examination was significant for moon facies and abdominal striae. Labs were remarkable for low serum morning cortisol of 0.6 µg/dl (0.4-22.6 µg/dl), and low serum ACTH of <5 pg/ml (7-69 pg/ml). A diagnosis of exogenous steroid induced Cushing’s syndrome, as a result of ritonavir induced increase in FP levels was made. FP was gradually tapered and stopped. Serum cortisol and ACTH levels normalized at 15 µg/dl and 13 pg/ml respectively and his symptoms resolved completely after three months. Discussion: Ritonavir, a protease inhibitor (PI), is one of the strongest known inhibitors of CYP3A4 and is generally used to boost the plasma levels of other PIs. FP, a potent glucocorticoid, is generally used as monotherapy or as a combination inhaler in the treatment of asthma. It is rapidly metabolized by CYP3A4 and hence produces minimal side effects. However, its concurrent use with ritonavir results in increased serum concentration of FP leading to systemic adverse effects of glucocorticoids. Due to emerging awareness about this drug-drug interaction among physicians, prescription of inhalational steroids in patients on ritonavir is avoided. However, FP is an OTC intranasal glucocorticoid that is easily accessible, and its self-use is often times not reported by patients which makes it difficult for physicians to track on their patient’s medication list. A thorough review of OTC medications/supplements needs to be done when Cushing’s syndrome from exogenous steroids is suspected. It is also imperative that patients on ritonavir be counseled about the risks of taking any form of steroid formulations by any route. Conclusion: Educating patients on ritonavir about steroids being a component of many OTC medications/supplements, and a careful medication history and drug-drug interaction assessment is important in preventing steroid related adverse effects. Presentation: Saturday, June 17, 2023

Abstract Disclosure: F. Amer: None. S. Ghaith: None. S. Kadiyala: None. M. Xhikola: None. Background: Thionamides can lead to agranulocytosis in 0.1 - 0.5% of patients. This is a severe adverse reaction due to inhibition of myelopoiesis. The proposed mechanism of bone marrow suppression is thought to be due to direct toxicity and/or immune mediated. For methimazole this side effect is seen with doses > 30 mg/day. This is a case of isolated thrombocytopenia in a patient treated with low dose methimazole. Clinical case: 69-year-old man diagnosed with Graves’ disease about 8 years ago was initially started on methimazole 20 mg/day. Later it was decreased to 10 mg/day or lower based on the thyroid function. Baseline platelet count was 140k/µl (130k - 440k/µl). Three years post initiation of methimazole, platelet count decreased compared to baseline but stayed stable between 80k - 115k/µl. Later, from 2018 - 2022 the platelet counts progressively decreased below 80k (as low as 25k/µl). In June 2022 patient was euthyroid on methimazole 10 mg/day but platelets had decreased to 51k/µl, almost half of what they were 6 months prior when the methimazole dose was averaging at 6.4 mg/day but was increased to 10 mg/day due to patient being biochemically hyperthyroid. Different doses of methimazole were attempted including 5 - 10 mg/day. Patient was able to become euthyroid only with 10 mg/day but with each methimazole dose escalation, platelet count would drop. Clinically there was no indication of bleeding. Further work up included unremarkable bone marrow aspirate, normal karyotype, normal flow cytometry, negative antiplatelet antibodies. A screen for antinuclear antibodies was negative, serum protein electrophoresis showed no monoclonal protein. Serum IgG and IgA were normal, but serum IgM was elevated to 499 mg/dl (57 – 359). Immunological studies show a decrease in C3 and C4, suggesting activation of the classical complement pathway. Alternative treatments for hyperthyroidism were discussed including radioactive iodine (RAI) and/or total thyroidectomy. At that time patient categorically refused to undergo any alternative option other than medical therapy. In late 2022 platelet count decreased to 25k/µl, but patient again refused RAI or thyroidectomy, and the decision was made to stop methimazole and start prednisone and cholestyramine to decrease free T4 and prevent further platelet decline. In 2 weeks, platelets improved to 93,000/µl. Currently, patient has agreed to proceed with RAI and will be treated soon. Of note, patient had mild degree of leukopenia with white cell count (WBC) of 4400-5000 /µL. Correlation between the WBC and the methimazole dose was not noted.Conclusion: This case shows selective significant thrombocytopenia in a patient treated with low-dose methimazole (5 - 10 mg/day). The underlying mechanism could be direct toxicity due to dose accumulation over the years in addition to immune mediated mechanisms considering the low C3 and C4 complements and serum IgM increase. Presentation: Friday, June 16, 2023

Abstract Disclosure: C. Alcorn: None. P. Subarajan: None. S. Ghaith: None. K. Jordan: None. Introduction: Megestrol, a progestin derivative, is a common drug used for anorexia or cachexia. Chronic use of megestrol can lead to suppression of the pituitary-adrenal axis, causing secondary adrenal insufficiency (SAI). Case: A 93-year-old female with a history of dementia presented with one-week history of confusion and weakness. She was found to have hyponatremia with a sodium of 134meq, consistent with her baseline. CT head and infectious workup were negative. She received 600cc of normal saline and repeat sodium decreased to 124meq/l. Nephrology was consulted due to concern for SIADH. She remained altered and was given a short course of hypertonic saline, 25cc for 4 hours. Repeat sodium after hypertonic saline was 118meq/l. TSH was normal but 8 am cortisol was 1.3 mcg/dL and ACTH level was <1.5 pg/ml. Endocrinology was consulted for evaluation of adrenal insufficiency. Cosyntropin stimulation test was performed with inadequate response, consistent with secondary adrenal insufficiency (SAI). The patient was subsequently given 50mg IV hydrocortisone with improvement in sodium to 125meq/l. The patient had been prescribed megestrol 200mg at home for cachexia. Upon discussion with her family, she was receiving multiple extra doses of megestrol per day for further appetite stimulation. She was only started on 200mg daily dose on admission. It was determined the patient had SAI secondary to megestrol use. This medication was discontinued, and she was initiated on hydrocortisone therapy with endocrinology follow-up. Conclusion: SAI is defined by deficiency of ACTH in setting of hypocortisolemia. SAI is often associated with prolonged glucocorticoid use but can also be seen in patients with pituitary tumors, pituitary surgery, or granulomatous disease. SAI can cause hyponatremia, hypoglycemia, and fatigue but is not typically associated with hypotension or hyperkalemia as the mineralocorticoid function of the adrenals remains intact. Though rare, there have been case reports of patients developing SAI while taking megestrol. Megestrol acts as a progestin and is used for appetite stimulation in patients with cachexia. Megestrol is believed to have cross-affinity for glucocorticoid receptors which leads to suppression of the pituitary-adrenal axis. This suppression leads to decreased ACTH production, inducing SAI. In this case, the patient was receiving higher than prescribed doses of megestrol at home. When her dose was reduced on admission it precipitated her adrenal insufficiency, accounting for the worsening of her hyponatremia. Identification of SAI in patients taking megestrol is imperative as early recognition and diagnosis can prevent severe complications such as adrenal crisis. These patients should have megestrol discontinued and be placed on appropriate hydrocortisone therapy. Close follow-up is required as it can take 2-3 months for pituitary-adrenal axis recovery. Presentation: Saturday, June 17, 2023

Abstract Background Hyperinsulinemic-hyperammonemia, a rare form of congenital hyperinsulinemia, can seldom present in adulthood if failed to be diagnosed during infancy, enabling it to be difficult to identify, and predisposing affected individuals to neurological complications. Case A 20-year-old female with intellectual disability, seizure disorder and ornithine transcarbamylase deficiency was admitted for recurrent episodes of asymptomatic hypoglycemia. Her medications included risperidone, fluoxetine, levetiracetam, lacosamide, ferrous sulphate and acetaminophen. Physical examination including vital signs was unremarkable. Relevant labs included a fasting glucose of 46mg/dl [70-99]. Further work up of hypoglycemia revealed an IGF-1 of 215ng/dl [85-350] and AM Cortisol of 6.5mcg/dl [5-25]. Given a low AM cortisol level under stress, an ACTH stimulation test was done with appropriate response of cortisol of 24 following cosyntropin administration, ruling out adrenal insufficiency. The patient continued to have h ypoglycemia noted on several glucometer checks every 4 hours where she remained asymptomatic. She was further evaluated with a mixed meal study where no hypoglycemia was noted. A 72 -hour fast was performed which was terminated based on a venous blood sample glucose reading of 50 mg/dl confirmed after hypoglycemia was noted on a glucometer check. The labs showed elevated C-peptide levels of 4ng/ml [0.4-2], insulin of 4mIU/L [<25] and proinsulin level of 2.3pmol/l [3-20]. Levels of insulin and proinsulin were noted to be inappropriately normal in the setting of hypoglycemia. Beta hydroxybutyrate was low at 0.1mmol/L [<0.5] and glucagon inappropriately normal at 36pg/ml [50-100]. Sulfonylurea, meglitinide and autoimmune antibody screen were negative. CT abdomen and pelvis was negative for pancreatic abnormality. In the absence of evidence for acquired causes of hyperinsulinemic hypoglycemia, congenital cases were investigated. Based on that, further labs were obtained including ammonia levels which was elevated at 177.2 u/dl [15-45]. Accordingly, GLUD-1 gene mutation was sent, given high suspicion for hyperinsulinemic hyperammonemia syndrome, which resulted positive and confirmed the diagnosis. She was started on a protein restricted diet and diazoxide which regulated her blood glucose levels effectively. Discussion Hyperinsulinism/hyperammonemia (HI/HA) syndrome is a form of congenital hyperinsulinism caused by activating mutations of the GLUD 1 gene which encodes Glutamate Dehydrogenase, a key enzyme in the beta cell pathway of amino acid-stimulated insulin secretion. The resultant syndrome is characterized by fasting and protein induced hypoglycemia, elevated serum ammonia levels without typical hyperammonemic symptoms. Management includes effective blood glucose control with an insulin inhibitor such as diazoxide and a protein restricted diet with consideration to predominantly include carbohydrates and fat. Conclusion Hyperinsulinemia hyperammonemia is a rare form of congenital hyperinsulinemia typically diagnosed during infancy and should be considered as a possible differential diagnosis in patients presenting with new onset hypoglycemia, as timely diagnosis and intervention can prevent forthcoming neurological complications. Presentation: No date and time listed

OBJECTIVE:We aimed to determine the prevalence and clinical characteristics of self-reported hyperthyroidism in patients with sarcoidosis.METHODS:A national registry-based study investigating 3836 respondents to the Sarcoidosis Advanced Registry for Cures questionnaire in the period between June 2014 and August 2019 was conducted. This registry is generated from a web-based questionnaire that is self-reported by patients with sarcoidosis. We compared patients with sarcoidosis who had hyperthyroidism with those who did not. We used multivariate logistic regression analysis to study the association between hyperthyroidism and different cardiac manifestations in patients with sarcoidosis.RESULTS:Three percent of the study respondents self-reported having hyperthyroidism and were generally middle-aged Caucasian women. Compared with patients without hyperthyroidism, patients with hyperthyroidism had more sarcoidosis-related comorbidities (59% vs 43%, P = .001) and more steroid-related comorbidities (56% vs 44%, P = .01), but there was no difference in the sarcoidosis-specific treatments they received, which included corticosteroids. Patients with hyperthyroidism reported sarcoidosis involvement of the heart (26.6% vs 14.9%, P = .005), kidneys (14.9% vs 8%, P = .033) and sinuses (17.7% vs 10.2%, P = .030) more frequently. Cardiac manifestations that were more frequently reported in patients with hyperthyroidism included atrial arrhythmias (11.3% vs 6.3%, P = .046), ventricular arrhythmias (17.2% vs 7.5%, P < .001), congestive heart failure (10.4% vs 5%, P = .017), and heart block (9.4% vs 4.7%, P = .036).CONCLUSION:Hyperthyroidism is infrequent in patients with sarcoidosis but is potentially associated with different cardiac manifestations. We suggest considering routine screening for hyperthyroidism in patients with sarcoidosis, especially in those with cardiac involvement. Further studies are needed to investigate the impact of identifying and treating hyperthyroidism in patients with sarcoidosis.

SESSION TITLE: Diffuse Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: We aimed to determine the prevalence rate and clinical characteristics of hyperthyroidism and investigate its association with cardiac manifestations in patients with sarcoidosis METHODS: We conducted a national registry-based study investigating 3,836 respondents to the Sarcoidosis Advanced Registry for Cures Questionnaire in the period between June 2014 and August 2019. This registry is generated from a web-based questionnaire that is self-reported by sarcoidosis patients and provides data related to demographics, diagnostics, sarcoidosis manifestations and treatment. We compared sarcoidosis patients with and without hyperthyroidism. We used multivariate logistic regression analysis adjusted for gender, race, age at time of sarcoidosis diagnosis and comorbidities (cancer, diabetes mellitus, obesity, hypertension and sleep apnea) to study the association between hyperthyroidism and different cardiac manifestations in patients with sarcoidosis. RESULTS: Three-percent of US sarcoidosis patients self-reported having hyperthyroidism and were generally middle-aged Caucasian women. When compared to patients with no hyperthyroidism, patients with hyperthyroidism had more sarcoidosis related comorbidities (59% vs 43%, p=0.001) and more steroids-related comorbidities (56% vs 44%, p=0.01) but there was no difference in the sarcoidosis-specific treatments they received including corticosteroids. Hyperthyroidism patients more frequently reported sarcoidosis involvement of the heart (18.4% vs 10.1%, p=0.023), muscles (10.5% vs 6.4%, p=0.029), sinuses (12.3% vs 6.7%, p=0.026) and the gastrointestinal system (6.1% vs 4.9%, p=0.032). Cardiac manifestations that were more frequently reported in hyperthyroidism patients included atrial arrhythmias (11.3% vs 6.3%, p=0.046), ventricular arrhythmias (17.2% vs 7.5%, p<0.001), congestive heart failure (10.4% vs 5%, p=0.017) and heart block (9.4% vs 4.7%, p=0.036). There was no difference in placement of pacemakers or implantable cardioverter defibrillator (ICD) between the two groups. However, the hyperthyroidism patients reported ICD shock delivery more frequently (5.3% vs 2.2%, p=0.030). On multivariate logistic regression analysis adjusting for gender, race, age, cancer history, diabetes mellitus, obesity, hypertension and sleep apnea, hyperthyroidism patients were more likely to have ICD or pacemaker placed (aOR=1.89, 95% CI 1.02-3.51), heart block (aOR=2.20, 95% CI 1.05-4.63) and ventricular arrhythmias (aOR=2.52, 95% CI 1.42-4.46). CONCLUSIONS: Hyperthyroidism is common in patients with sarcoidosis and is potentially associated with different cardiac manifestations including cardiac arrhythmias. CLINICAL IMPLICATIONS: We suggest considering routine screening for hyperthyroidism in sarcoidosis patients especially with cardiac involvement. Further studies are needed to investigate the impact of identifying and treating hyperthyroidism in sarcoidosis patients. DISCLOSURES: No relevant relationships by Tamara Al-Hakim, source=Web Response No relevant relationships by Bashar Alzghoul, source=Web Response Own stock relationship with American airline, United Airlines and Delta Airlines Please note: $1001 - $5000 Added 06/01/2020 by Bara Alzghoul, source=Web Response, value=Own stock No relevant relationships by Farah Amer, source=Web Response My spouse/partner as a Own stock relationship with AMerican airlines, united airlines and delta airlines Please note: $1001 - $5000 Added 06/01/2020 by Sarah Ghaith, source=Web Response, value=Own stock No relevant relationships by Diana Gomez Manjarres, source=Web Response No relevant relationships by Johnny Jaber, source=Web Response No relevant relationships by Saminder Kalra, source=Web Response No relevant relationships by Divya Patel, source=Web Response No relevant relationships by Noopur Singh, source=Web Response

Background: Myxedema coma is a rare, but severe form of hypothyroidism with a high mortality rate. Case: An eighty-nine-year-old female with a history of hypothyroidism and hypertension presented from a nursing home with lethargy, bradycardia, and hypothermia. She was oriented to self only, minimally verbal requiring assistance for activities of daily life at baseline. Medications included cardizem, lisinopril, and levothyroxine 150 mcg at stable doses for a year. Physical examination was significant for hypothermia (35.4°C) and bradycardia (heart rate of 40); the patient was obtunded. Initial labs were significant for AKI, hyperkalemia, and transaminitis. Echo showed an EF of 60% with impaired LV relaxation. A temporary pacemaker was placed and the patient was started on an isoproterenol drip. TSH was drawn due to the history of hypothyroidism and was elevated at 270 (0.5-5 mU/L). Serum cortisol was drawn and a dose of hydrocortisone 100 mg was given intravenously followed by an IV dose of levothyroxine 100 mcg and liothyronine 20 µg. Serum cortisol level was high at 54.2 µg/dl (0.4-22.6 µg/dl). Her mental status improved the following day, bradycardia resolved and the isoproterenol drip was stopped. She was started on IV levothyroxine 50mcg daily. Subsequently, hyperkalemia and transaminitis resolved, but her renal function continued to deteriorate. Due to her poor baseline functional status, her spouse decided against dialysis and the patient was transitioned to inpatient hospice. Discussion: Myxedema coma is defined as severe hypothyroidism leading to decreased mental status, hypothermia and other symptoms related to slowing of function in multiple organs. Nowadays, due to the wide availability of TSH assays that are performed routinely, hypothyroidism is detected and treated early and rarely leads to myxedema coma. However, it can present itself in hypothyroid patients with poor compliance and comorbid conditions. Since it is associated with a high mortality rate, treatment should be initiated without waiting for lab results. Glucocorticoids are given until the possibility of co-existing adrenal insufficiency has been excluded. A dose of IV T₃ and T₄ is administered followed by maintenance IV T₄ daily until the patient is able to take PO.T₃ is continued until clinical improvement and stabilization of the patient. Clinical and biochemical improvement is usually seen within a week. Despite treatment, it has a 30-50% mortality rate. Conclusion: Myxedema coma is a rare endocrine emergency with a high mortality rate that requires a high index of suspicion and warrants early treatment.

Background: Hungry bone syndrome is a life-threatening complication focused on prevention following parathyroidectomy in ESRD patients, requiring pre-operative optimization of serum calcium levels Case: A 35-year-old male with a past medical history of HTN, polycystic kidney disease and ESRD on peritoneal dialysis presented with numbness around the mouth and fingers, diffuse body aches and generalized weakness. He underwent total parathyroidectomy for tertiary hyperparathyroidism three days prior to presentation at another medical facility. Physical exam was unremarkable. Labs were significant for profound hypocalcemia of 5.8mg/dl [8.6-10.3mg/dl] and ionized calcium of 0.59mmol/L [1.12-1.32mmol/L]. The diagnosis of hungry bone syndrome was made based on the clinical setting. He received massive doses of IV and oral calcium along with IV calcitriol. Calcium was also added to each bag of peritoneal dialysate. Serum calcium levels remained low for three days despite optimal therapy with improvement after day four of admission. On the day of discharge, the serum calcium level was 7.8mg/dl [8.6-10.3mg/dl] with complete resolution of symptoms. He was discharged on calcitriol and calcium carbonate. Discussion: Hungry bone syndrome is a life-threating complication of parathyroidectomy. It is characterized by a severe drop in serum total calcium concentration and prolonged hypocalcemia for more than four days post parathyroidectomy. Hypocalcemia is generally transient because the degree of bone disease is typically mild but in some cases, the postoperative hypocalcemia is severe and prolonged. This most often occurs in patients who have developed bone disease preoperatively due to a chronic increase in bone resorption induced by high levels of PTH. The focus of hungry bone syndrome should be on prevention with pre-operative management of serum calcium and vitamin D levels. IV Calcitriol 2mcg is administered at the end of dialysis beginning three to five days prior to surgery, continued post-operatively as well. 2-3g of oral calcium is started two days prior to surgery. Once the serum calcium levels are within the reference range, IV calcitriol can be switched to an oral formulation. Despite adequate pre-op management, the risk of developing hungry bone syndrome in ESRD patients is high, requiring aggressive calcium supplementation Conclusion: Correction of serum calcium levels within the reference range prior to parathyroidectomy in ESRD patient is imperative to reduce the incidence of hungry bone syndrome.