Normal Free T4 Research Articles

12265 Isolated Adrenocorticotropic Hormone Deficiency In The Setting Of Anti-PD1 Immunotherapy

Abstract Disclosure: J. Poncelet: None. Q. Wang: None. A.J. Montero: Advisory Board Member; Self; AstraZeneca, Gilead. Other; Self; Medical Advisor for Paragon Infusion Services. L. Tranchito: None. Isolated Adrenocorticotropic Hormone Deficiency in the Setting of Anti-PD1 Immunotherapy Introduction: Immune checkpoint inhibitors have been associated with endocrine immune-related adverse events, such as secondary adrenal insufficiency with isolated ACTH deficiency in rare instances. Case Presentations: We present two different cases of isolated ACTH deficiency (IAD) while on anti-PD1 therapy with pembrolizumab. Patient A is a 66-year-old woman with history of tobacco use, hypertension, and COPD diagnosed with stage IV lung adenocarcinoma. After completing 15 cycles of pembrolizumab, she reported symptoms of fatigue, weakness, lightheadedness, and was subsequently admitted to the hospital for symptomatic hyponatremia. Lab workup revealed a morning cortisol level of 0.6 ug/dL (n2.5-20 ug/dL) and ACTH <1.5 pg/mL (n7.2-63.3 pg/mL), both of which had previously been normal. Her TSH was mildly elevated with a normal free T4. Her FSH, LH, prolactin, and IGF levels were normal as was MRI of the pituitary. She therefore was diagnosed with IAD and started physiologic steroid replacement therapy with hydrocortisone with subsequent symptomatic improvement and normalization of her serum sodium. Patient B is a 60-year-old woman with a history of osteoporosis, aortic stenosis, and stage II triple negative breast cancer treated with neoadjuvant chemotherapy and pembrolizumab. Two months after starting immunotherapy, she presented to her oncology office with symptoms of fatigue, poor appetite, body aches, and dizziness. Her labs revealed mild hyponatremia, cortisol of 0.9 ug/dL (n2.5-20 ug/dL) and ACTH <1.5 pg/mL (n7.2-63.3 pg/mL). TSH, LH, FSH, and prolactin levels were normal. She started physiologic steroid replacement therapy with hydrocortisone for IAD, which led to improvement in her symptoms. Both patients continue pembrolizumab. Conclusions: Immune-related adverse events affecting endocrine pathways have been reported with immune checkpoint inhibitors. There is no method to predict which patients may be affected, and no guidelines exist on when or how often to monitor hormone levels in these patients. Importantly, patients can continue immune checkpoint inhibitors despite IAD if controlled by hormone replacement, though ACTH recovery should not be expected[1]. Recognition of symptoms can prompt earlier evaluation for secondary adrenal insufficiency and provide greater benefit to patients. 1.Schneider BJ, Naidoo J, Santomasso BD, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update [published correction appears in J Clin Oncol. 2022 Jan 20;40(3):315]. J Clin Oncol. 2021;39(36):4073-4126. doi:10.1200/JCO.21.01440 Presentation: 6/1/2024

8791 A Case of Hyperfunctioning Thyroid Nodules Evaluated for Thyroid Metastasis in the Setting of Oropharyngeal Squamous Cell Carcinoma

Abstract Disclosure: M. Alashoor: None. J. Gogineni: None. A. Bakar: None. Introduction: Identifying and evaluating hyperfunctioning thyroid nodules in the setting of metastatic head and neck cancers represents a diagnostic challenge that may result in inaccurate identification of perithyroidal lymph node metastasis as malignant or metastatic thyroid nodules with standard workup. Case presentation: A 72-year-old male with a history of stage IV metastatic oropharyngeal squamous cell carcinoma, metastasized to the lymph nodes, lungs, mediastinum, and bilateral iliac bones. He was diagnosed two years ago and received chemotherapy, maintenance immunotherapy with pembrolizumab, and targeted palliative radiation therapy, with good clinical response. Restaging PET-CT two years later revealed local progression. During his workup, he was noted to have persistently abnormal thyroid function test with low TSH (0.03​​µIU/mL, n 0.3-5.33), normal free T4 (0.97ng/dL, n 0.60 - 1.40), mildly elevated free T3 (3.91pg/mL, n 2.5-3.9), negative thyrotropin receptor antibodies levels, negative TSI, negative TPO antibody, noted evidence of subclinical hyperthyroidism consistent over the past year. Radioactive iodine uptake demonstrated multinodular gland, mildly elevated 24-hour uptake of 28% consistent with hyperthyroidism, with decreased activity in the left lobe. Thyroid ultrasound revealed multiple probable malignant thyroid nodules, a 1.8 cm TI-RADS 5 lesion of the deep margin of the lower pole of the right lobe, and a 1.6 cm TI-RADS 5 lesion of the upper pole on the right lobe. He was treated with methimazole 5 mg. Further workup with fine needle aspiration demonstrated the right upper lobe nodule sample was positive for squamous cell carcinoma, findings suspicious for metastasis. He subsequently proceeded with radical tonsillectomy, right neck dissection, and right hemithyroidectomy. Surgical pathology results noted, right neck metastatic HPV-associated squamous cell carcinoma involving the lymph nodes with extranodal extension, right oropharyngeal HPV-mediated squamous cell carcinoma. The thyroid gland biopsy was significant for incidental papillary microcarcinoma 2mm, thyroid follicular nodular disease, without evidence of squamous cell carcinoma or metastatic infiltration. Post-hemithyroidectomy, his thyroid function normalized, and methimazole was discontinued. Conclusion: Thyroid metastasis from head and neck cancers represent a rare entity. In patients with a history of malignancy, evaluation of new thyroid masses remains crucial. While FNA is a sensitive method for detecting thyroid metastases, inaccuracies may occur, impacting the identification of thyroid nodules in the presence of local metastatic lymphadenopathy. Identifying squamous cell carcinoma in the thyroid can significantly influence the treatment plan of patients with metastatic carcinomas, therefore careful consideration must be undertaken on evaluation. Presentation: 6/1/2024

8197 A Captivating Case Report of Teprotumumab Induced Hyperglycemic Hyperosmolar State

Abstract Disclosure: K.M. Tuna: None. J.P. Perdomo Rodriguez: None. Introduction: Teprotumumab, a monoclonal antibody targeting the IGF-1 receptor, is increasingly utilized for moderate to severe thyroid eye disease. Initial trials noted mild hyperglycemia in patients with diabetes, while recent trials revealed a significant elevation in Hemoglobin A1c (HbA1c) among those with diabetes or pre-diabetes post-infusion. Here, we discuss a case of a patient with diet-controlled diabetes who developed hyperglycemic hyperosmolar state (HHS) two months after Teprotumumab infusion. Case Presentation: A 43-year-old male, with class III obesity, obstructive sleep apnea, dyslipidemia, coronary artery disease, and diet-controlled diabetes (HbA1c 6.5%) presented with worsening proptosis, decreased color vision, severe visual field depression. Laboratory evaluation revealed elevated TSH (6.3 mIU/ml), normal free T4 (0.67 ng/dl, ref: 0.60-1.2 ng/dl), and undetectable Thyroid Stimulating Immunoglobulin (<0.1 IU/L). Blood cell count, renal and liver function tests were normal. Due to high clinical suspicion of thyroid eye disease, he was treated with timolol, dorzolamide, brimonidine, and methylprednisolone 1g daily for 3 days. Glycemic control was achieved with 30 units of daily insulin while on pulse steroids. On outpatient ophthalmology follow-up, Teprotumumab was initiated and he received 2 doses. Eight weeks later, the patient was hospitalized with altered mental status caused by HHS (glucose 617 mg/dl, serum osmolality 316 osm). HbA1c was found to be significantly increased to 12% and the patient required 150 units total daily insulin and metformin upon discharge. Of note, the patient did not have significant weight changes during this time. GAD, IA2, and Zinc Transporter-8 antibodies were obtained prior to discharge and results are pending. Discussion: The IGF-1 receptor, a partial homologue of the insulin receptor, plays a pivotal role in glucose homeostasis. Inhibiting this receptor can lead to hyperglycemia. Initial randomized controlled trials (RCTs) reported a 10% incidence of mild hyperglycemia. A recent RCT from a cohort of 42 patients demonstrated a 50% incidence of hyperglycemia, in which two-thirds of the patients remained in a dysglycemic state with one patient with pre-existing prediabetes developing diabetic ketoacidosis (DKA). Our patient mirrored this scenario with no identifiable confounding factors. Conclusion: Teprotumumab-induced hyperglycemia, though rare, can lead to life-threatening complications. Baseline glycemic assessment, identification of high-risk patients, and comprehensive discussions on risks and benefits are crucial before initiating therapy. Close monitoring, especially in those with prediabetes, is recommended. Patient education plays a pivotal role in early symptom recognition, averting delayed diagnoses, and subsequent hospitalization. Presentation: 6/3/2024

12372 A Rare Case Of Silicon Granulomatosis Induced Hypercalcemia In A Transgender Female

Abstract Disclosure: O.A. Aluko: None. I. Singh: None. Introduction: Hypercalcemia has been described in patients with most granulomatous disorders, of which sarcoidosis and tuberculosis are the most common. Granuloma formation is a rare, however well known complication of silicon implants and injections. We present a case of silicon granulomatosis induced hypercalcemia in a transgender female. Case Report 60-year-old transgender female, with past medical history of HIV on HAART was referred to Endocrinology for evaluation of hypercalcemia. She Bloodwork done a few weeks prior revealed elevated calcium 12.3 and low PTH of 9. Reported symptoms include worsening abdominal pain similar to prior gastritis flare, insomnia and significant weight loss. Denied any constipation, joint pain, mood changes, no history of bone fractures or kidney stones. Admitted to significant dairy intake - half a gallon of milk within 3 days and daily yogurt consumption. Endorsed inadequate daily fluid intake and she was not taking oral calcium or Vitamin D supplementation. Quit tobacco 9 years ago. Vitals were significant for tachycardia with HR 120/min, BP stable. Patient was referred to the ER for IV hydration and further evaluation with initial suspicion of malignancy. Repeat corrected calcium was 14.7, ionized calcium 6.8, PTHrP undetectable <2, borderline high 1,25 dihydroxyvitamin D 74.5, low vitamin D 17.9 and normal free T4 1.5. ACE, SPEP, UPEP levels within normal limits. Vitamin A low. CT chest/abdomen/pelvis revealed innumerable soft tissue foci in the subcutaneous adipose tissue of the flanks and lateral gluteal areas; nodular liver, suspected cirrhosis and portal hypertension. Imaging findings prompted further discussion regarding prior procedures. She endorsed history of silicone fillers in hips and breast implants 30 years ago. Images reviewed with radiology confirmed calcification around bilateral breast implants, with intracapsular rupture. Calcium improved with IV Fluids, bisphosphonates and steroids. The most probable cause of hypercalcemia was believed to be secondary to silicone granulomatosis. Innumerable granulomas were deemed irresectable, removal of the breast implants considered however not performed. She was later diagnosed with hepatitis B, cirrhosis and succumbed to sepsis and multiorgan failure. Conclusion Eliciting a detailed history, physical exam and correlating with imaging findings is imperative to establishing an uncommon diagnosis. PTHrP was low and there were no bony metastases making the possibility of malignancy related hypercalcemia less likely. FDG-PET if performed would reveal hypermetabolic nodules, often an initial indication to the underlying etiology. Presentation: 6/2/2024

7439 Mercury toxicity presenting as Pheochromocytoma

Abstract Disclosure: A. Ansar: None. K. McNerney: None. B.A. Marshall: None. Background: Mercury intoxication is a rare cause of hypertension in children and can mimic other endocrinopathies such as pheochromocytoma. Mercury affects catecholamine metabolism and can cause elevated catecholamine levels, thereby incorrectly suggesting a catecholamine-secreting tumor. Clinical Case: An 8-year-old girl presented to the ED with progressive night sweats, intractable migratory myalgias, hypertension and tachycardia. Patient was in her usual state of health until 2 weeks before presentation when she started to have worsening intermittent pains in her chest, arms, back, and knees. She also experienced restlessness and inability to sleep. On presentation she was hypertensive, with blood pressure of 146/116 mm Hg while calm, heart rate 125 bpm, afebrile. She was anxious, irritable, and seemed uncomfortable. Her skin was dry and rough with a scaly eczematous rash on the arms and legs. She had persistently elevated blood pressure in upper and lower extremities, unremarkable echocardiogram and electrocardiogram, and a normal result on fundoscopic examination. Her initial electrolytes, creatinine, and urinalysis were all normal and remained so on serial evaluations. Urine drug screen was negative. Thyroid function panel showed normal TSH with slightly elevated Free T4 2.28 ng/dL (0.9-1.7), but a normal Free T3 3.9 pg/mL (2.0-4.4) and Free T4 by equilibrium dialysis 1.8 ng/dL (0.8 - 2.0). CT of the chest, abdomen and pelvis was negative and did not show any lesions. Plasma renin activity was 4.6 ng/mL/hour, supine, (<2.0) and plasma aldosterone level < 4.0 ng/dL (< 40 supine) were normal. 24-hour urinary norepinephrine was 90 μg/24h (13-65), epinephrine 37 μg/24h (0.2-10), urine metanephrines 195 μg/24h (18-144), urine normetanephrines 305 μg/24h (29-145), all elevated. Further history taking revealed that patient was taking Ayurvedic supplements prepared by hand by medicinal personnel in India for 3 months prior to presentation. These were stopped 2 weeks prior to her presentation, when she first became symptomatic. Her blood mercury level was 11 ng/mL (n <9), and urinary mercury excretion 67 μg/24 hours (n<10), both obtained 3 weeks after stopping supplementation. She was started on oral chelation therapy with succimer 10 mg/kg/day. Her hypertension was controlled with doxazosin. One week after initiation of therapy, her symptoms improved, and she became normotensive. Her acrodynia and irritability resolved. Urine metanephrine levels will be repeated at upcoming clinic follow up. Conclusion: Mercury toxicity should be considered in the differential of pheochromocytoma to avoid extensive diagnostic testing and morbidity associated with it. Lead, mercury, and arsenic have been detected in traditionally prepared Ayurvedic supplements. A careful history of intake of supplements can be important in cases with unusual symptomatology. Presentation: 6/3/2024

7039 Isolated Gonadotropin Deficiency Transmitted From Mother to Daughter Conceived Through Assisted Reproduction Due Newly Identified, Autosomal Dominant Mutation Within the SOX10 Gene

Abstract Disclosure: S. Bakjaji: None. R.P. Hoffman: None. Title: Isolated gonadotropin deficiency transmitted from mother to daughter conceived through assisted reproduction due newly identified, autosomal dominant mutation within the SOX10 gene. Objectives: We report a case of genetic isolated gonadotropin deficiency occurring in a mother and in her daughter conceived through assisted reproductive technology using mother’s ovum. Methods Case report Results: The daughter was initially seen at 12 years 0 months for evaluation of short stature and concerns she had not grown in the last year. She was otherwise in good health and reported normal sense of smell. At the time of assessment, her height was 132.6 cm (0.61 percentile; Z=-2.5). The mother had been diagnosed with Kallmann’s syndrome and achieved pregnancy through ovarian stimulation. Her height was 152.4 cm, while the father's height was 177.8 cm. Two male siblings were born at the same time and were in normal health. Physical examination of the daughter was unremarkable. She had Tanner stage 1 pubic hair and Tanner stage 1 breasts. The growth chart displayed a notable deceleration in growth Laboratory results showed normal free T4 of (0.9 ng/dL) with slightly elevated TSH (8.348 uIU/mL), positive thyroid antibodies, normal IGFI at 164 ng/mL (normal range for Tanner I: 54 - 301) and IGFBP-3 at 5.8 ug/mL (2.4 - 8.4 ug/mL). The karyotype was 46 XX. Her peak growth hormone using glucagon-arginine stimulation was 12.8 ng/ml. When no pubertal development was seen over the next 6 months, GnRH stimulation testing revealed baseline LH of 0.04 mIU/ml and a peak of 1.78 and baseline FSH of 0.41 mIU/ml with a peak of 2.83. Bone age was 8 years 4 months.Over the next year her growth velocity was 4.8 cm/year and she remained prepubertal. Genetic testing done identified a new heterozygous sequence variant (c.226G>A) in the SOX10 gene which would lead to replacement of valine by isoleucine at position 76 and was thought to be damaging in silico. This variant was subsequently found to be shared with her mother but not her father. Conclusions: Most Kallmann’s syndrome or genetic isolated gonadotropin deficiency cases are due to autosomal dominant but spontaneous new mutations since infertility is usually present in those with the syndrome. This case emphasizes the importance of genetic counselling regarding inheritance risk when assisted reproduction technology using maternal ovum is used. Presentation: 6/2/2024

Association between Subclinical Hypothyroidism and Adverse Pregnancy Outcomes in Assisted Reproduction Technology Singleton Pregnancies: A Retrospective Study.

Background/Objectives: Women with subclinical hypothyroidism (SCH) were reported to be at an increased perinatal risk. We aimed to investigate the relationship between SCH and perinatal outcomes in singleton pregnancies resulting from assisted reproduction technology (ART). Methods: We retrospectively examined the perinatal outcomes of ART singleton pregnancies in women who underwent thyroid function screening before conception and delivered at our hospital from January 2020 to July 2023. We defined SCH as thyroid-stimulating hormone (TSH) levels > 2.5 mU/L and normal free T4 levels. The patients were categorized into three groups: normal thyroid function (group A), SCH without levothyroxine therapy (group B), and SCH with levothyroxine therapy (group C). The risks of preterm birth, preeclampsia, fetal growth restriction, manual placental removal, and blood loss at delivery were compared among the three groups. Results: Out of the 650 ART singleton deliveries, 581 were assigned to group A, 34 to group B, and 35 to group C. The preterm birth rate at <34 weeks was significantly higher in group B and significantly lower in group C than in group A. The rate of preterm delivery at <34 weeks increased in correlation with TSH levels. Levothyroxine therapy was the significant preventive factor for preterm birth at <34 weeks. Conclusions: The preterm birth rate before 34 weeks was significantly higher in the SCH group. Levothyroxine therapy is a significant protective factor against preterm birth before 34 weeks. Universal screening for thyroid function and appropriate hormone therapy in pregnant women may help reduce perinatal risks, including preterm birth.

The importance and prognostic effect of thyroid hormones in patients with transposition of the great arteries

Objectives: Transposition of the great arteries (TGA) is a rare congenital heart disease that occurs in 3 in 10,000 newborns and is rapidly fatal (90%) within one year if left untreated. The prognosis of this pathology changed after introducing an early arterial switch operation (ASO), while the left ventricle could still adapt to systemic high-pressure conditions. Appropriate regulation of thyroid hormones positively impacts metabolism, cardiac function, and postoperative recovery. Therefore, regular thyroid hormone monitoring and thyroid function monitoring of TGA patients may help to improve the health status and prognosis of this group of postoperative patients. Methods: In our study, 127 patients who underwent ASO at our pediatric cardiac surgery clinic between 01.01.2014 and 18.09.2021 were retrospectively analyzed and included. Among the patients, 43% (n=54) were females, and 57% (n=73) were males. Results: The coronary arteries were normal in 89.7% (n=114) and abnormal in 10.3% (n=13) of the patients. Twenty-one of the patients exited, and mortality was calculated to be 16.5%. There were no significant differences in mortality or thyroid stimulating hormone (TSH), free thyroxine (T4), or free triiodothyronine (T3) values (P=0.674, P=0.345, P=0.478). In our study, in which we investigated the effect of thyroid hormone levels on prognosis in neonatal patients with TGA with normal free T3, T4, and TSH values, we found that TSH levels were greater in the group with advanced aortic regurgitation and exitus, although the effect of thyroid hormones on postoperative results was not statistically significant. Conclusions: Congenital hypothyroidism is a common disease with cardiac effects. During the neonatal period, this disease may conceal itself. Careful, expert clinical follow-up and clinical trials are crucial to improve outcomes in the surgical treatment of transposition of the great arteries, a complex congenital heart disease.

Progression of Gestational Subclinical Hypothyroidism and Hypothyroxinemia to Overt Hypothyroidism After Pregnancy: Pooled Analysis of Data from Two Randomized Controlled Trials.

Background: To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Methods: Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies. SH was diagnosed with thyrotropin (TSH) ≥4.0 mU/L and normal free T4 (fT4) (0.86-1.9 ng/dL). HT was diagnosed with normal TSH (0.08-3.99 mU/L) but fT4 <0.86 ng/dL. Serum from initial testing was stored for later thyroid peroxidase (TPO) antibody assay; results were not returned for clinical management. At 1 and 5 years after delivery, participants were asked whether they had either been diagnosed with or were being treated for a thyroid condition. Maternal serum was collected at these visits and thyroid function measured. Subsequent overt hypothyroidism was defined as TSH ≥4.0 mU/L with fT4 <0.86 ng/dL. Results: Data for 1- and 5-year follow-up were available in 307 of the 338 participants with SH and 229 of the 261 with HT. Subsequent hypothyroidism was more common both at year 1 (13.4% vs. 3.1%, p < 0.001) and year 5 (15.6% vs. 2.6%, p < 0.001) for participants with SH compared with those with HT. This progression was more common in individuals with TSH values >10 mIU/mL. Baseline TPO level >50 IU/mL in participants with SH was associated with higher rates of hypothyroidism at year 1 (26.7% vs. 6.5%, odds ratio [OR] = 5.3 [confidence interval (CI) 2.6-10.7]) and year 5 (30.5% vs. 7.5%, OR = 5.4 [CI: 2.8-10.6]) compared with those with TPO levels ≤50 IU/mL. For participants with HT, no differences in overt hypothyroidism were seen at 1 year related to baseline TPO level >50 IU/mL (1/10 (10%) vs. 6/218 (2.8%), OR = 3.9 [CI: 0.43-36.1]), but more participants with TPO levels >50 IU/mL developed hypothyroidism by year 5 (2/10 (20%) vs. 4/218 (1.8%), OR = 13.4 [CI: 2.1-84.1]). Conclusion: SH is associated with higher rates of overt hypothyroidism or thyroid replacement therapy within 5 years of delivery than is HT when these conditions are diagnosed in the first half of pregnancy.

Peripartum Torpor: A Chilling Case Report and Review of the Literature

Purpose: To report a rare case of peripartum maternal hypothermia and bradycardia. Methods: Case report. Results: Torpor is a transient state of hibernation with hypothermia and bradycardia. Hypothermia is defined as an abnormally low core body temperature less than 36°C.1 Sinus bradycardia is defined as less than 60 beats/min. While occasionally hypothermia or bradycardia is seen in obstetric patients undergoing vaginal delivery, when combined together, it can be a rare, life-threatening state that requires prompt intervention to prevent adverse maternal and fetal outcomes. A 23 year-old G2P0102 at 33+3 weeks of gestation was admitted to the high risk obstetric service for preterm labor complicated by fetal growth restriction. She had a history of preeclampsia in a previous pregnancy, but otherwise denied any chronic medical problems. Upon arrival, her vital signs showed a temperature of 37°C, a pulse of 53 bpm, and blood pressure of 126/62 mmHg. Her white blood cell count was 12.4 x 109/L and hemoglobin was 11.3 g/dL. She received betamethasone for fetal lung maturity and penicillin for Group B streptococcus prophylaxis. As her cervix continued to dilate, she received an epidural for pain management. Once she was in active labor, she became bradycardic with a pulse in the 30s-40s bpm, as confirmed by EKG. She was completely asymptomatic at this time, and fetal heart tones were reassuring with a baseline between 110’s-130’s bpm. She delivered vaginally with 150 mL of estimated blood loss, and her bradycardia continued postpartum even after the epidural was discontinued. When she complained of feeling cold, multiple attempts with different oral and axillary thermometers could not obtain a reading. She was warmed with forced-air warming blankets, warmed blankets, and hot packs in her groin and axilla. During this time, discussion with the NICU staff revealed that her baby was also hypothermic at 33.3°C and hypoglycemic at 28 mg/dL at birth. Other than feeling cold, the patient continued to be asymptomatic despite hypotension and bradycardia. She appeared somnolent but was responsive to questions. Her uterus was firm with minimal vaginal bleeding and no purulent or foul-smelling vaginal discharge. Repeat laboratory testing revealed a white blood count of 19 x 109/L and lactate was 3.3 mmol/L. Her comprehensive metabolic panel was unremarkable. A chest x-ray was clear. A C-reactive protein was &lt; 0.3 mg/dL and sedimentation rate was 14 mm/h. A rectal continuous thermometer was placed, which eventually recorded a temperature at 33.3°C and upon recheck was 31.7°C. A multidisciplinary team, including Anesthesia, Internal Medicine, and Neurology, evaluated the patient due to concern for a central nervous system insult. She received fluid resuscitation and broad-spectrum antibiotics for sepsis protocol. Due to the concern for potential septic shock, the decision was made to transport her to the Medical ICU for further management. As she was leaving Labor &amp; Delivery, her temperature had increased to 36.9°C and her pulse to 61. Thyroid studies the next day revealed a normal Free T4 of 1.00 ng/dL and a high thyroid stimulating hormone level of 9.55 uIU/mL. However, despite an extensive workup, no clear etiology of her hypothermia and bradycardia was identified. Intervention with fluids and application of forced-air warming system resolved the hypothermia in less than 6 hours without relapse. Antibiotics were discontinued after one day due to low suspicion for systemic infection. She remained vitally stable and was discharged on postpartum day 2 without further complications. Conclusions: Maternal hypothermia is relatively common during cesarean delivery; however, very few cases report maternal hypothermia during vaginal delivery. An English language literature search for maternal hypothermia during vaginal delivery yielded less than 10 case reports – few of which identified a cause of the hypothermia – and none of which reported simultaneous maternal bradycardia. While our case is a very rare presentation and the etiology is still unknown, it highlights the importance of prompt recognition of vital sign derangements in peripartum patients as well as multidisciplinary attention.

Subclinical hypothyroidism predicts outcome in heart failure: insights from the T.O.S.CA. registry.

Subclinical hypothyroidism (SH), defined as increased serum thyroid-stimulating hormone (TSH) with normal free T4 (fT4) levels, is frequently observed in the general population. Prevalence ranges from 0.6% to 1.8% in the adult population, depending on age, sex, and iodine intake. Several studies reported a worse prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and SH, but they considered heterogeneous populations suffering mainly from severe SH. Aim of this study was to evaluate if SH was independently associated with the occurrence of cardiovascular death considering 30months of follow-up. 277 HFrEF patients enrolled in the prospective, multicenter, observational T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, were included in this analysis. Patients were divided into two groups according to the presence of SH (serum TSH levels > 4.5mIU/L with normal fT4 levels). Data regarding clinical status, echocardiography, and survival were analyzed. Twenty-three patients displayed SH (87% mild vs 13% severe), while 254 were euthyroid. No differences were found in terms of age, sex, HF etiology, and left ventricular ejection fraction. When compared with the euthyroid group, SH patients showed higher TSH levels (7.7 ± 4.1 vs 1.6 ± 0.9, p < 0.001), as expected, with comparable levels of fT4 (1.3 ± 0.3 vs 1.3 ± 0.3, p = NS). When corrected for established predictors of poor outcome in HF, the presence of SH resulted to be an independent predictor of cardiovascular mortality (HR: 2.96; 5-95% CI:1.13-7.74; p = 0.03). Since thyroid tests are widely available and inexpensive, they should be performed in HF patients to detect subclinical disorders, evaluate replacement therapy, and improve prognosis.

Patient-Reported Satisfaction with Thyroid Hormone Replacement Therapy for Subclinical Hypothyroidism in Older Adults: A Pooled Analysis of Individual Participant Data from Two Randomized Controlled Trials.

Background: The benefit of levothyroxine treatment of subclinical hypothyroidism (SCH) is subject to debate. This study compared treatment satisfaction between older adults with SCH using levothyroxine or placebo. Methods: We analyzed pooled individual participant data from two randomized, double-blind, placebo-controlled trials investigating the effects of levothyroxine treatment in older adults with SCH. Community-dwelling participants aged ≥65 years, with SCH (persistent thyrotropin levels 4.60-19.99 mIU/L for >3 months and normal free T4 level), were included. Intervention dose titration until thyrotropin levels normalized, with a mock dose adjustment of placebo. Treatment satisfaction was determined during the final study visit using the Treatment Satisfaction Questionnaire for Medication (TSQM), encompassing perceived effectiveness, side effects, convenience, and global satisfaction, along with the participants' desire to continue study medication after the trial. Results: We included 536 participants. At baseline, the median (interquartile range [IQR]) age was 74.9 (69.7-81.4) years, and 292 (55%) were women. The median (IQR) thyrotropin levels were 5.80 (5.10-7.00) mIU/L at baseline in both groups; at final visit, 4.97 (3.90-6.35) mIU/L in the placebo and 3.24 (2.49-4.41) mIU/L in the levothyroxine group. After treatment, the groups did not differ significantly in global satisfaction (mean difference [CI] -1.1 [-4.5 to 2.1], p = 0.48), nor in any other domain of treatment satisfaction. These results held true regardless of baseline thyrotropin levels or symptom burden. No major differences were found in the numbers of participants who wished to continue medication after the trial (levothyroxine 35% vs. placebo 27%), did not wish to continue (levothyroxine 27% vs. placebo 30%), or did not know (levothyroxine 37% vs. placebo 42%) (p = 0.14). In a subpopulation with high symptom burden from hypothyroid symptoms at baseline, those using levothyroxine more often desired to continue the medication after the trial than those using placebo (mean difference [CI]: -21.1% [-35.6% to -6.5%]). Conclusion: These pooled data from two RCTs showed no major differences in treatment satisfaction between older adults receiving levothyroxine or placebo. This finding has important implications for decision-making regarding initiating levothyroxine treatment for SCH. Our findings generally support refraining from routinely prescribing levothyroxine in older adults with SCH.

Thyroid dysfunction after immune checkpoint inhibitors in a single-centre UK pan-cancer cohort: A retrospective study

PurposeThis study investigated thyroid dysfunction with immune checkpoint inhibitors (ICIs) in terms of proportions affected, risk factors, thyroid sequelae, and overall survival (OS). MethodsAmong patients with normal baseline free T4 (fT4) and thyroid stimulating hormone (TSH) receiving ICIs at a large cancer centre, proportions of hyperthyroidism/hypothyroidism were determined (any, subclinical [normal fT4, abnormal TSH], overt [abnormal fT4, abnormal TSH], isolated hyperthyroxinaemia/hypothyroxinaemia and secondary) with onset times and subsequent thyroid statuses. Associations of overt dysfunction with OS were estimated using Cox regression and methods robust to immortal time bias (time-dependent Cox regression and 3- and 6-month landmark analyses). Associations of baseline variables with overt hyperthyroidism and hypothyroidism were estimated using Fine and Gray regression. ResultsOf 1349 patients, 34.2% developed hyperthyroidism (10.3% overt), including 54.9% receiving combination ICIs, while 28.2% developed hypothyroidism (overt 9.3%, secondary 0.5%). A third of overt hypothyroidism cases occurred without preceding hyperthyroidism. Subclinical thyroid dysfunction returned directly to normal in up to half. Overt hyperthyroidism progressed to overt hypothyroidism in 55.4% (median 1.6 months). Melanoma treatment in the adjuvant vs. advanced setting caused more overt hyperthyroidism (12.1% vs. 7.5%) and overt hypothyroidism (14.5% vs. 9.7%). Baseline eGFR < 60 mL/min/1.73 m2 (HR=1.68, 1.07–2.63) was associated with overt hyperthyroidism and sex (HR=0.60, 0.42–0.87) and TSH (4th vs. 1st quartile HR=1.87, 1.10–3.19) with overt hypothyroidism. Overt dysfunction was associated with OS in the Cox analysis (HR=0.65, 0.50–0.85, median follow-up 22.2 months) but not in the time-dependent Cox (HR=0.79, 0.60–1.03) or landmark analyses (3-month HR=0.74, 0.51–1.07; 6-month HR=0.91, 0.66–1.24). ConclusionThyroid dysfunction affects up to half of patients receiving ICIs. The association with OS is unclear after considering immortal time bias. The clinical courses include recovery, thyrotoxicosis and de novo overt hypothyroidism. Adjuvant treatment for melanoma, where longer-term harms are of concern, causes more frequent/aggressive dysfunction.

Impact of Subclinical Hypothyroidism on Pregnancy and Newborn

Objective: The normal free T4 level together with a high TSH level is called subclinical hypothyroidism. In this study, we investigated cases of subclinical hypothyroidism diagnosed in the first trimester for possible adverse effects. The study aims to show the pregnancy outcomes and neonatal effects. Material and Methods: The study we planned was conducted retrospectively as a record study based on diagnoses. Three hospitals; one city and two state hospitals, were included in our study. Pregnant women treated at these centers between 2019 and 2021 were included the screening of newborns was similarly performed by our pediatric colleagues, based on the diagnosis in the form of scanning the files. Results: It became statistically significant when prematurity (p: 0.005), fetal weight, and week of birth were evaluated. The T4 values of the pregnant women who taken part in the study were normal, and their TSH values were ≥ 2.5-4 mIU/L. The evaluation showed that preterm birth was statistically higher and fetal weight and week of birth were significantly lower. Conclusions: In the study of pregnant women diagnosed with subclinical hypothyroidism, it was found that the preterm delivery rate was higher than in the control group, and the delivery week was also lower than in the control group.

SAT495 Persistent Euthyroid State in a Patient with Biochemical and Imaging Evidence of Graves' Disease

Abstract Disclosure: M. Antony: None. S. Gundlapally: None. M. Joglekar: None. B. Fritz: None. S. Patel: None. V. Verma: None. R. Kant: None. INTRODUCTION: Elevated TSI antibody and/or diffuse uptake on radioactive Iodine-123 scan is diagnostic of Graves’ disease. Thyromegaly with increased blood flow on color doppler seen on thyroid USG can also aid in the diagnosis. Rare presence of positive TSI antibody without hyperthyroidism has been reported1. Rare co-existence of both Graves’ disease and Hashimoto’s thyroiditis in a patient causing a challenging clinical course has been reported2. Presence of a neutralizing or blocking antibody against the TSH receptor1 or a false positive TSI have been implicated in such rare cases. CLINICAL CASE: A 37-year-old Caucasian Female was seen at our endocrinology clinic for further evaluation of thyroid disorder. Patient initially experienced goiter during 1st pregnancy at age 18, followed by hypothyroidism during last pregnancy needing levothyroxine treatment. Due to goiter history, patient underwent work-up by her primary physician in 2021. Thyroid ultrasound (usg) showed bilateral hyperemia, heterogeneous echotexture, and 0.2 cm cystic nodule in the right upper lobe. Labs showed normal TSH 1.33 uIU/ml (0.3-4.0 uIU/ml), normal Free T4 0.99 ng/dl (0.8-1.8 ng/dl), normal total T3 140 ng/dl (71-180 ng/dl). Patient underwent further work-up by endocrinology in 2022. Thyroid ultrasound again revealed bilateral hyperemia with other similar findings. Labs showed normal TSH 2.02uUI/ml, normal free T4 0.93 ng/dl, normal total T3 138 ng/dl. Interestingly, TSI antibody and TPO antibody were significantly elevated at 66.70 IU/L (0.0-0.55 IU/L) and 517 IU/ml (0-34 IU/ml), respectively. Repeat labs in April 2022, again showed normal TSH 1.77 uIU/ml, normal free T4 0.90 ng/dl and normal free T3 2.94 (2.0-4.40 pg/ml). Thyroid uptake scan was not performed due to persistently normal TSH values. Patient denied the use of biotin supplementation. Patient continues to remain clinically and biochemically euthyroid without treatment. CONCLUSION: Our case supports the rare presence of TSI antibody without hyperthyroidism. Close monitoring is warranted due to possibility of future progression to overt hyperthyroidism. REFERENCE: 1. Alvin Mathew A, Papaly R, Maliakal A, et al.(November 10, 2021)Elevated Graves’ Disease-Specific Thyroid-Stimulating Immunoglobulin and Thyroid Stimulating Hormone Receptor Antibody in a Patient With Subacute Thyroiditis. Cureus 13(11): e19448. doi:10.7759/cureus.194482. Vipin Verma, MD, Mc Anto Antony, MD, PSAT346 Persistent Fluctuation Between Hypothyroidism and Hyperthyroidism in a Patient with Both Hashimoto's Thyroiditis and Graves’ Disease: Challenges in Diagnosis and Treatment Approach, Journal of the Endocrine Society, Volume 6, Issue Supplement_1, November-December 2022, Page A833, https://doi.org/10.1210/jendso/bvac150.1723 Presentation Date: Saturday, June 17, 2023

SAT496 Tobacco Smoking May Mimic Subclinical Hyperthyroidism

Abstract Disclosure: R. Alshantti: None. U. Rafat: None. B. Alkhaurri: None. C.P. Barsano: None. M. Siddiqui: None. Introduction: Studies have shown lower levels of TSH in smokers and a positive association of smoking with hyperthyroidism. The urinary nicotine level is reported to be negatively correlated with TSH. Moreover, smoking cessation have shown reversible effects on thyroid functions and risk of having overt hypothyroidism increased more than 6-fold in the first 2 years after cessation of smoking. Whether transient smoking cessation, prior to blood work would alter thyroid functions is unknown. We report the case of an elderly woman who had normalization of suppressed TSH after smoking abstinence prior to her blood work, suggestive of smoking-induced alteration of the TSH level. Clinical Case: A 77- year-old woman was referred to endocrinology clinic for an abnormal TSH level. She had a suppressed TSH &amp;lt;0.01 uIU/mL [Ref range: 0.45-5.33], with normal free T4 0.78 ng/dl [Ref range: 0.70-2.70], and free T3 3.66 pg/ml [Ref range: 2.5-3.9], consistent with subclinical hyperthyroidism. Thyroid auto-antibodies were negative. She had a long-standing history of multinodular goiter with mild tracheal deviation for which she had declined surgical management. She was an active smoker with 40 pack years smoking history. There was no preceding viral illness. She was not taking any biotin-containing supplements or medications that would interfere with thyroid hormones. The patient denied symptoms of overt hyperthyroidism. On physical examination she had a large multinodular goiter with negative Pemberton’s sign. There was no exophthalmos, lid lag, tachycardia, tremors or hyperreflexia. Her subsequent blood tests, 2 and 4 months apart, were also consistent with subclinical hyperthyroidism with TSH levels of 0.115 to 0.144 uIU/mL with normal free T4 0.72 ng/dl and total T3 136.3 to 153 ng/dl [Ref range 80-187]. Based on her age, she met the treatment threshold. However, as the patient continued to smoke 10 cigarettes daily, even on the days when thyroid labs were drawn, treatment was deferred considering the possibility of smoking-induced altered thyroid function. Blood work re-drawn after a smoking abstinence of 10-12 hours showed normalization of TSH 0.58 uIU/mL consistent with a euthyroid state. Conclusion: When evaluating patients with abnormal thyroid functions, it is important to address smoking status. Cigarette smoking may alter thyroid function tests in a pattern consistent with subclinical or overt hyperthyroidism and its effect on thyroid functions may be transient and reversible. Therefore, the possibility of smoking-induced alteration of thyroid functions should be considered in active, clinically euthyroid smokers. It may be judicious to hold treatment with thionamides in such patients and to re-evaluate thyroid functions after smoking abstinence. Presentation Date: Saturday, June 17, 2023

FRI557 Don’t Forget The Incidental Thyroid Nodule In Graves’ Disease. A Case of Marine-Lenhart Syndrome

Abstract Disclosure: K.N. Andino-Lebrón: None. A. Martinó-Morales: None. J.M. Colón-Castellano: None. Marine-Lenhart syndrome (MLS) was initially described by Charkes in 1972 as he observed patients with Graves’ disease (GD) and incidental functioning thyroid nodules. He named the disease Marine-Lenhart syndrome based on a paper published by Marine and Lenhart in 1911. MLS is a variant of GD now described as the coexistence of GD and autonomous functional thyroid nodules (AFTN); thus, patients present with thyrotoxicosis due to GD and AFTN. MLS is very rare, and prevalence is estimated to be around 0.8%-2.7%. Here, we present a case of MLS in a 79-year-old female. A 79-year-old Hispanic woman with history of breast metaplasia s/p chemoprevention with tamoxifen for 5 years, atrial premature contractions on metoprolol, among other medical conditions was referred to Endocrinology clinics by her primary care physician (PCP) because of abnormal thyroid function tests and ultrasound. She reported feeling anxious with associated palpitations, she denied weight loss. Physical examination was remarkable for regular rate and rhythm, no goiter, no palpable nodules, no proptosis, and deep tendon reflexes +1. Laboratory testing revealed a suppressed TSH of 0.224 uIU/mL, normal free T4 at 1.17 ng/dL, normal total T3 at 142.5 ng/dL, and positive thyroid stimulating immunoglobulins at 345%. Thyroid ultrasound showed a normal size gland with multiple complex nodules. In the right lobe there was a mixed cystic and solid nodule, measuring 1.48x1.21x1.71cm, wider than tall, with internal vascularity and punctate calcifications. In the left lobe there was an isoechoic and solid nodule measuring 0.7x0.5x0.7cm, wider than tall, without calcifications. Thyroid uptake scan with SPECT-CT demonstrated a focus of increased tracer uptake on the upper pole of the right thyroid lobe that corresponds to the one found on CT scan and a diminished and nonuniform uptake of the tracer in the reminders of the thyroid gland. The 24-hour radioactive iodine uptake was 17.5%. Diagnosis of MLS was made, and the patient was started on methimazole 5mg daily, which she has been tolerating well. Follow up laboratories show a biochemically euthyroid state. Marine-Lenhart syndrome is a rare entity of Graves’ disease which is currently defined as GD and accompanying functioning nodule(s). To establish the diagnosis, it is important the evaluation with scintigraphy and autoimmune testing. Multiple treatment options are available and patients with GD should be evaluated for the presence of thyroid nodules and their functional status to achieve optimal therapy. Patients with GD have a chance of remission when treated with antithyroid drugs. Due to the pathophysiology of AFTN, patients with MLS (concurrent GD and AFTN) have lower remission rates with antithyroid drugs and may require definitive management therapy with radioactive iodine or surgery. Presentation: Friday, June 16, 2023

SAT504 Thyroidal Pax de Deux: 2 Cases of Resistance to Thyroid Hormone and Coexisting Thyroid Disease

Abstract Disclosure: S.V. Ribeiro: None. T. Moreno: None. A. Varela: None. P. Freitas: None. D.M. Carvalho: None. Resistance to thyroid hormone (RTH) is a rare clinical syndrome defined by hyposensitivity to thyroid hormone (TH) and characterized by elevated TH levels in the absence of TSH suppression. In most subjects with RTH, treatment is not required as tissue resistance is adequately compensated for by an increase in the endogenous supply of TH. This is not the case in patients with limited thyroidal reserve. Here we describe the clinical features of two unrelated patients with RTH and coexisting thyroid disease. Patient 1 was an 18-year-old female medical student referred to our consultation from Pediatrics. She had been diagnosed with autoimmune thyroiditis at age of 7 following the development of an obvious goiter. By then her thyroid-function tests (TFT) showed elevated TSH (8.75 µIU/mL, NR 0.41-3.67) and a normal free T4 (1.3 ng/dL, NR 0.82-1.76). She tested positive for the presence of antibodies to thyroperoxidase and thyroglobulin. The cytological findings on aspiration biopsy were consistent with Hashimoto’s thyroiditis. Throughout the years, despite levothyroxine supplementation she displayed systematically elevated TSH and normal FT4. The results of a thyrotropin stimulation test were normal. The suspicious of erratic compliance to therapy was raised.Follow-up at our outpatient clinic confirmed requirement for unusually high replacement doses of levothyroxine in order to maintain TSH within normal limits at expense of elevated FT4 and FT3 levels, suggesting the possibility of RTH. She was found with a THRβ c.1292T&amp;gt;C p.(Iso431Thr) heterozygous mutation. She remains clinically euthyroid under supplementation. Patient 2 was an asymptomatic 54-year-old female who consulted us for further evaluation of a thyroid nodule. Thyroid-FT showed an elevated FT3, at 3.86 μg/dL (NR, 1.75 to 3.71), an elevated FT4 at 1.86 ng/dL (NR 0.70 to 1.48), and a normal TSH level at 1.55 µIU/mL (NR, 0.40 to 4.50). A diffuse goiter was revealed by scintigraphy and the ultrasound showed no relevant findings. A diagnosis of RTH was genetically confirmed (THRβ c.1707C&amp;gt;G p.(P453A)). After a 6-year follow-up, she was diagnosed with supraventricular tachyarrhythmia for which she was started on amiodarone. Shortly after, her TFT revealed elevated TSH that normalized a few months after amiodarone withdrawal. Three years later, she was admitted to the intensive care unit due to cardiogenic shock attributed to tachycardia-induced cardiomyopathy and restarted on amiodarone. Her subsequent TFT showed elevated TSH (42.07 µIU/mL), with decreasing levels of TH (FT3 2.02 μg/dL, FT4 1.06 ng/dL). A diagnosis of amiodarone-induced hypothyroidism was made and levothyroxine supplementation was initiated and adjusted considering the patient’s symptoms. These cases show that the coexistence of RTH with other thyroidal disease can make diagnosis and management challenging and requires awareness and long-term follow-up. Presentation Date: Saturday, June 17, 2023

FRI257 Adrenal Insufficiency Secundary Due Immune Checkpoint Inhibitors Therapy

Abstract Disclosure: S.R. Rivera: None. J. Valencia: None. E. Figueroa: None. J. Calisto: None. Background: Immune checkpoint inhibitors (ICIs) are new anticancer immunotherapies that can trigger a variety of immune related adverse events (irAEs) in different organs, including the endocrine system. Adrenal insufficiency is uncommon with a nonspecific clinical presentation that must be recognized in time due to its potential mortality. Clinical Case: 41 year old man diagnosed with papillary renal cell carcinoma. He underwent surgery, performing a ​​right radical nephrectomy plus bilateral lymphadenectomy. He started chemotherapy in March 2022 with ICIs, Nivolumab and Ipilimumab. Three months later he presents with myalgias, fatigue and 6 kilogram weight loss. Physical exam: in regular conditions, vital signs with blood pressure 70/40 mmHg, heart rate 84 bpm, with no signs of hyperpigmentation or dehydration. No evidence of clinical hyperthyroidism. Lab results: low ACTH levels: 6.4 pg/ml (9 - 69 pg/ml), low cortisol: 0.06 µg/dl ( 6.02-18.4 µg/dl), low TSH: 0.1 µU/ml ( 0.4- 4.2 µU/ml) and normal free T4: 1.01 ng/dl ( 0.93-1.7 ng/dl). Antibody tests were negative: anti thyroglobulin, anti TPO and TRAB. Normal thyroglobulin levels. Sellar MRI was requested: normal, metastasis were ruled out. Thyroid ultrasound: normal thyroid gland. Exclusion of exogenous use of corticosteroids and levothyroxine was done. Case was interpreted as an adrenal insufficiency due to hypophysitis with associated thyrotoxicosis. Treatment with hydrocortisone was started, while thyroid function progression was observed. In the following lab control, elevation of TSH was noted. Two months later, we documented elevation of TSH levels: 5 µU/ml and decline of free T4 levels: 0.58 ng/dl, starting levothyroxine supplementation. Patient had a favorable clinical evolution. Conclusion: Adrenal insufficiency due to hypophysitis is uncommon and is mostly linked to Ipilimumab use. In those cases pituitary gland MRI is often normal most of the time. Thyroid involvement, which is frequently seen with Nivolumab therapy, varies from thyrotoxicosis, hyperthyroidism and hypothyroidism. Usually produces chronic damage and needs permanent treatment. The potentially lethal nature of these events makes it essential for oncologists and endocrinologists to be aware of these manifestations in order to achieve early treatment. Presentation: Friday, June 16, 2023

SAT343 Nicotinamide Nucleotide Transhydrogenase (NNT)-related Familial Glucocorticoid Deficiency: More Than Adrenal Insufficiency

Abstract Disclosure: A. Shanker: None. H.L. Calero: None. K. DeCarlo: None. Background: Familial glucocorticoid deficiency (FGD) is a rare cause of primary adrenal insufficiency, with an estimated prevalence of fewer than 5,000 cases in the United States. Patients often present as infants with signs including hypoglycemia, failure to thrive, seizures, and recurrent infections. Clinical Case: A 25-year-old woman with a history of intellectual disability was admitted with MIS-A due to COVID-19. Her presenting symptoms were lethargy and fever for several days. Her vitals were significant for a heart rate of 122 with atrial flutter and blood pressure of 90/50. Her initial labs showed elevated TSH (24.07 mcIU/mL [0.35-4.00]), normal free T4 (0.7 ng/dL [0.6-1.7]), hyponatremia (133 mmol/L [135-145]), and low alkaline phosphatase (25 U/L [40-125). Her physical exam was notable for hyperpigmentation, macrognathia, and oral mucositis. Her parents report she has limited daily activities and recalls recurrent illnesses as a child. She has been amenorrheic for the past 5 years; menarche was at age 12. Further chart review revealed that ketotic hypoglycemic seizure was diagnosed during hospitalization at 11 months of age. . Pediatric Endocrinology diagnosed Addison’s disease, which was treated until age 12 when she was lost to follow-up. On this admission, ACTH was elevated (756.5 pg/mL [7.2 - 63.3]), 8 AM cortisol was 1.2 ug/dL, and peak cortisol obtained after high dose co-syntropin stimulation was abnormal at 1.1 ug/dL upon high dose. Primary adrenal insufficiency was confirmed, and stress-dose steroids were initiated; her clinical condition improved. She was discharged with prednisone and fludrocortisone maintenance therapy. As an outpatient, TSH was persistently elevated (17.9 mcIU/mL [0.35-4.00]) and weight-based levothyroxine was initiated. Secondary amenorrhea testing demonstrated normal FSH, LH, and estradiol levels and discussions began regarding progesterone withdrawal testing (pending given patient again lost to follow up). The nutritional screening revealed deficiencies in vitamins A, C, and D, and supplementation was initiated. A unifying diagnosis was reached with microarray and whole exome sequencing showing nicotinamide nucleotide transhydrogenase (NNT) -related FGD. Conclusions: In FGD, several causative genes have been identified. One of these, NNT is expressed in most tissues, including cardiac, renal, thyroid, gastrointestinal, and gonadal tissue. This may predispose patients to organ dysfunction outside of the prominent effect on the adrenal glands. Since NNT is widely expressed, routine screening can include nutritional, renal, and hepatic labs and patients should receive reproductive counseling due to the risk of gonadal dysfunction. Therefore, patients with NNT-related glucocorticoid FGD require significant care coordination to ensure that patients receive uninterrupted therapy and appropriate multispecialty follow-up. Presentation: Saturday, June 17, 2023