COVID-19, a multi-system disease, could potentially play a role in thyroid dysfunction. New reports show a prevalence of COVID-related thyroiditis. Recent studies suggest that there may be a higher risk of thyroiditis in the setting of SARS-CoV-2, and several cases of Graves' disease have been reported in individuals with SARS-CoV-2, although the incidence of such findings and their relationship to COVID-19 is unknown. In this report, we present Graves' hyperthyroidism in a 48-year-old African American male who was admitted to the hospital for complaints of cough, fatigue, and palpitations. He tested positive for SARS-CoV-2 and was found to have suppressed thyroid-stimulating hormone (TSH) and an elevated free T4. The patient had no prior history of thyroid disease. Initially, it was thought to be a case of viral thyroiditis, and he was discharged on prednisone. However, he was found to have positive thyroid-stimulating immunoglobulin (TSI) and a diffuse increase in flow on doppler ultrasound of the thyroid. Subsequently, he was started on anti-thyroid medications with significant improvement. What is unique about this case is that, unlike other described cases in the literature where there was a relapse of a known Graves' disease after COVID-19 disease, our patient did not have a history or symptoms of thyroid disease prior to this event, which should raise the concern about possible activation of Graves' disease after SARS-CoV-2 infection through an autoimmune pathway. In our opinion, physicians, particularly endocrinologists, must be aware of this condition and keep it in mind as a potential differential diagnosis when encountering a similar clinical scenario.

Background Congenital Adrenal Hyperplasia (CAH) is classically attributed to defective 21-hydroxylase, caused by mutations in CYP21A2, impairing the production of mineralocorticoids and glucocorticoids and subsequently shifting steroidogenesis towards androgen production. This produces a classic constellation of neonatal symptoms, including genital virilization, salt-wasting, and adrenal crisis. A rare cause of CAH is a defect in 11β-hydroxylase from a mutation in CYP11B1, preventing production of cortisol and corticosterone, resulting in hypertension, hypokalemia, and androgen excess. Reports of combined mutations in CYP21A2 and CYP11B1 in the literature and the clinical manifestations of such a case are not well described. Here we present a case report wherein a pair of heterogenous mutations in CYP2A12 and CYP11B1 were detected in a new diagnosis of nonclassic Congenital Adrenal Hyperplasia, including a previously undescribed mutation in CYP11B1. Clinical Case The patient is a 30-year-old female who presented to her primary care clinic with teenage-onset irregular menses occurring every 2-3 months. She also reported hirsutism, but never had acne, changes in thirst or urination, or breast discharge. Primary evaluation revealed prolactin of 34.7 ng/mL, prompting a pituitary MRI which revealed a 2×3mm lesion. At this point, referral was made to endocrinology for endocrinological. PCOS was felt to be the top differential for her hirsutism and irregular menses but further workup to rule out CAH revealed a 17-OH-Progesterone of 554 ng/dL and a Testosterone of 83 ng/dL. Subsequently, a 250 mcg cosyntropin test increased 17-OH progesterone to 837 ng/dL and resulted in a cortisol of 24.7 mCg/dL after 60 minutes. Subsequent CAH gene sequencing was performed and revealed a heterogeneous pathogenic CYP21A2 variant (c.332_339 del; p.Gly111Valfs*21) and a heterogeneous previously undescribed variant of undetermined significance in CYP11B1 (c.1123C>T; p.Leu375Phe). Conclusion At least 100 mutations of CYP11B1 have been found to cause CAH due to 11β-Hydroxylase deficiency. Our case adds to the growing database of described mutations in CY11B1 and suggests that heterogenous mutations in two different genes may present phenotypically as nonclassic CAH in a potentially epistatic fashion. This enriches earlier conclusions that broader genetic analysis beyond CYP21A2 deletions is needed to identify the genotypes of those with CAH due to the complex diversity of genetic mutations, and ought to remind clinicians to consider it as a diagnosis, particularly in young women whose hyperandrogenism or menstrual irregularities cannot be explained by common endocrinological abnormalities or do not have an appropriate response to traditional treatment. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Introduction: Aromatase excess syndrome is a rare disorder with gynecomastia being the main symptoms. Its prevalence is unknown with approximately twenty cases reported. We describe an unusual case of Aromatase excess syndrome. It was diagnosed incidentally at a much older age than expected while evaluating for hypersomnia. Case presentation: A 28 year old male with no significant past medical history, presented with complaint of hypersomnolence, developed during puberty. He had multiple evaluations with no apparent etiology; sleep study and all his other laboratory tests were normal including testosterone levels, normal IGF-1 and cortisol. When patient was evaluated in the Endocrine clinic, he was found to have bilateral gynecomastia, which he had for many years. His estradiol was 150 pg/ml (Normal <50 pg/ml). Repeat was 137 pg/ml with normal DHEA-S Subsequent concomitant estradiol of 204 pg/ml with an estrone of 35.7 pg/ml (9–36). Total testosterone was normal at 588 ng/dl. Evaluation for a tumor with abdominal CT, testicular ultrasound, and HCG was negative. As his symptoms of fatigue and hypersomnolence were not improving and his estradiol to testosterone ratio was >10, he was started on an aromatase inhibitor and his ratio dropped from 1:40 to 1:24, as his estradiol went down to 75 pg/ml. Discussion: Gynecomastia is the benign proliferation of breast tissue due to imbalance between estrogen and testosterone. It could be caused by medications or medical illnesses. Occasionally its presence can harbor a serious endocrine issue especially if presenting in the prepubertal period. Thus, evaluation is often necessary. Among the pathological causes is the Aromatase excess syndrome. In this syndrome there are three types of cryptogenic genomic rearrangements identified. Those rearrangement affect the aromatase gene CYP19 and results in gain of function of the aromatase enzyme. Patients will have high estradiol and estrone level, lower FSH and LH levels that will normalize after treatment with aromatase inhibitor. Their testosterone levels could be low or normal. For the clinical diagnosis, there are four criteria; bilateralgynecomastia, pre or peripubertal onset, exclusion of other causes of gynecomastia and having a genetic trait. The first three criteria are indispensable for diagnosis while fourth one is not obligatory, but rather pathognomonic. An elevated estradiol to testosterone ratio above 1:10 is a supportive finding, as well as having a low FSH with low to normal LH. Genetic identification of the CYP19 A1 mutation remains the definitive method of diagnosis. Our patient met the first three criteria and also had estradiol to testosterone ratio is > 1:10. Genetic confirmation is challenging. Consequently, whole genome sequencing may be required. Though unusual, this case highlights the importance of looking deep in the differential when evaluating gynecomastia.

Introduction: Empty Sella syndrome (ESS) is characterized by subarachnoid space herniating into the Sella turcica, causing displacement or flattening of the pituitary gland. Primary ESS has an unknown etiology, secondary ESS may be caused by trauma, infection, adenoma, ischemia, surgery, pharmacological or radiological Rx. It has been noted in 5-23% of the population, usually found incidentally in autopsies or imaging. 25% to 50% of patients have endocrine abnormalities (panhypopituitarism, DI, DM type 2, irregular menses). Headache or ophthalmological symptoms may be seen. Case summary: 55-year-old AAF with Hx of anemia, presented with lethargy and acute encephalopathy after several months of progressively worsening dizziness, muscle weakness, and fatigue. For the past few days, her appetite was poor. She also complained of cold intolerance, brittle hair, dry skin, and occasional constipation. Denied headache, blurry vision, neck pain, palpitation, previous head imaging, trauma or surgery. Remote history included an uncomplicated pregnancy; menopause occurred several years ago. Found to be hypoglycemic with blood glucose 35 mg/dl. Six D50 ampules initially improved her hypoglycemia but blood glucose quickly dropped thereafter. Placed on D5 drip; with the same results. A&O to place and person only, lacked a goiter. Lab work revealed low morning serum cortisol <1.2 mcg/dl (10-20 mcg/dl),high TSH 37.1 mU/L (0.4-4.5Mu/L), low free T4 0.2 mcg/dl (4.5-11.2 mcg/dl), low insulin 1.6 mcU/ml (4-30 mcU/dl), low C peptide 0.48 ng/ml (1.1-22 ng/ml), elevated prolactin 31 ng/ml (2-29 ng/dl), and low FSH 10 mlU/ml (26-134 mlU/ml). ACTH stimulation test revealed adrenal insufficiency. Started on IV Dexamethasone 2mg BID, hypoglycemia resolved (later weaned to prednisone 5mg BID). In view of hypothyroidism, adrenal insufficiency, and low FSH in post-menopause, hypopituitarism was suspected. MRI brain revealed empty sella without micro- or macroadenoma. Discussion & Conclusion: PES is usually asymptomatic but can present with endocrine, neurologic, or visual symptoms. A fraction of patients present with nonspecific headache, dizziness, or cranial nerve disorders. Others may have ophthalmological symptoms such as blurry or decreased vision, or mild papilledema. Though mild hyperprolactinemia and various levels of hypopituitarism have been noted, it is rare that adult patients are hospitalized for undiagnosed hypopituitarism with refractory hypoglycemia or severe hyponatremia. Panhypopituitarism is noted in only 2% of ESS patients. Our case represents a rare clinical presentation of primary ESS, with no known trauma, surgery, or ischemia. As clinicians, we should include ESS in our differential when assessing patients presenting with hypopituitarism, refractory hypoglycemia, or neurological/visual symptoms. MRI brain should be obtained if ESS is suspected. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts ar...