Low-dose Levothyroxine Research Articles

8145 Type 2 Diabetes In A Patient With IMAGe Syndrome

Abstract Disclosure: N. Mulpuri: None. S. Mirfakhraee: None. J. Abramowitz: None. Background: Individuals with mutations that lead to deficiency of POLE1 (a catalytic subunit of polymerase epsilon) may have clinical features of IMAGe syndrome (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenital, and genitourinary anomalies) in addition to distinctive facial features and variable immunodeficiency. Of 15 reported cases in the literature, none were previously characterized with type 2 diabetes mellitus (T2DM). Clinical case: This is a 25-year-old woman with a history of IMAGe syndrome (confirmed mutation in the POLE gene). With regards to IMAGe syndrome history, during the prenatal period, she had growth restriction in the third trimester with delivery at 38 weeks. At 4 years-old, she presented with adrenal crisis and was started on glucocorticoid and mineralocorticoid therapy, now taking hydrocortisone 2.5mg three times daily (8.6 mg/m2/day) and fludrocortisone 0.05mg daily. Initial labs in the adult endocrine clinic were notable for serum glucose 339 mg/dL (65-99 mg/dL), undetectable estradiol (< 15 pg/ml) with FSH 6.8 mIU[JA1] /mL and LH 2.0 mIU/mL, TSH 1.25 mIU/L (0.40-4.50 mIU/dL), FT4 0.7 ng/dL (0.8-1.8 ng/dL). The patient denied any history of T2DM. She also denied polyuria, polydipsia, or weight loss. There was no stigmata of peripheral insulin resistance on exam. Subsequent labs included HbA1c 8.9%, fructosamine 417 mcmol/L (200-285 mcmol/L), insulin 18.4 mcIU/mL (2.6-24.9 mcIU/mL), and C-peptide 3.9 ng/dL (1.1-4.4 ng/dL) with serum glucose 164 mg/dL. Islet cell, insulin, and GAD-65 antibodies were undetectable. CT abdomen/pelvis did not show any pancreatic mass or anomalies. Initially, prandial insulin (lispro 3 units prior to each meal) was initiated given post-prandial hyperglycemia noted on continuous glucose monitoring. Low-dose levothyroxine, 25 mcg daily, was initiated given concern for secondary hypothyroidism, with subsequent normalization of serum thyroxine. HbA1c improved to 7.4% six months later. Ultimately, she transitioned to sitagliptin 25 mg daily and her latest HbA1c was 6.2% three years after initial diagnosis of T2DM. Conclusion: Of the 15 cases of IMAGe syndrome with mutations in POLE described in Logan et al, none were noted to have diabetes. The patient described above was diagnosed with new-onset diabetes at age 21, presumably T2DM in the context of undetectable antibodies and high-normal C-peptide. Interestingly, she did not have any typical stigmata of peripheral insulin resistance. Glucocorticoids used for the treatment of adrenal insufficiency in patients with IMAGe syndrome can contribute to development of T2DM. Patients with IMAGe syndrome on chronic glucocorticoids should be monitored for hyperglycemia and diabetes. Additionally, glucocorticoid doses should be optimized to balance mitigating side effects such as hyperglycemia and osteoporosis while preventing adrenal crisis. Presentation: 6/3/2024

The effect of low- and high-dose levothyroxine on the expression, protein level, and function of P-glycoprotein in mice

The study was investigated the effect of different doses of levothyroxine on the mRNA expression, protein level and function of Pgp. Mice were divided into 6 groups as control, low dose levothyroxine, high dose levothyroxine, fexofenadine, low dose levothyroxine+fexofenadine and high dose levothyroxine+fexofenadine. Mice received levothyroxine at doses of 8 and 80 µg/kg daily for 21 days. Fexofenadine was administered at dose of 40 mg/kg at the 24 h following the last administration of levothyroxine. The mRNA levels and protein level of Pgp in liver and small intestine were determined by RT-PCR and western blot analysis, respectively. Plasma concentrations of fexofenadine were determined using HPLC. Levothyroxine at low and high doses caused an insignificant increase intestinal mRNA expression of mdr1a, while high dose levothyroxine+fexofenadine caused a significant increase. Levothyroxine caused a dose-dependent decrease in intestinal mRNA expression of mdr1b. In liver, levothyroxine caused a dose-dependent increase in the mRNA expression of mdr1a. Fexofenadine significantly reduced the effect of levothyroxine on mRNA expression of mdr1a in liver. Levothyroxine increased the protein level of Pgp in liver and decrease in intestines. Low dose levothyroxine significantly increased the plasma concentration of fexofenadine. The effects of levothyroxine on the mRNA expression of mdr1a and b in small intestine and liver and protein level of Pgp varied depending on the dose, tissue type, and fexofenadine administration.

SAT347 Surprising Turn Of Events In A Patient With Weight Gain: Simultaneous Diagnosis Of Macroprolactinoma And Polycystic Ovary Syndrome

Abstract Disclosure: A.N. Keskinkilic: None. D. Sistla: None. Background: The differential diagnoses of excess weight gain are broad and endocrinopathies constitute a small proportion of these etiologies. A pattern of associated symptoms, classical exam findings and hormonal testing can signal some endocrine causes. However, diagnosis can still be challenging due to overlapping clinical and biochemical features and concurrent presentations of endocrine disorders. Here, we present a diagnostically challenging rare case of a young female with weight gain who had simultaneous diagnosis of macroprolactinoma and PCOS. Clinical Case: A 34-year-old healthy female presented with one year of weight gain despite lifestyle changes. She also reported headaches, acne, hirsutism, stretch marks, excessive sweating, and had 10 years of amenorrhea while on oral contraceptives (OCs). Labs revealed mildly low free T4 of 0.72 ng/dl (n: 0.70-1.48 ng/dl) and significantly elevated prolactin (PRL) of 259.8 ng/ml (n: 1.2-29.9 ng/ml); normal FSH, LH, GH, IGF, TSH, ACTH, 1 mg dexamethasone suppression test, and 24-hour urinary cortisol. HbA1c, lipid panel, plasma metanephrine and androgen levels were normal. MRI pituitary revealed a 2.1 x 1.9 x 1.5 cm macroadenoma with mild compression to the optic chiasm. A low dose levothyroxine and cabergoline 0.25 mg twice weekly was started with dose increment to 0.5 mg twice weekly. At 6-month follow-up, PRL decreased to 30 ng/ml. Repeat MRI showed a decrease in size of the pituitary adenoma (1.5 x 1.4 x 1.3 cm). However, she could not tolerate cabergoline due to persistent headaches and depression. Hence, she elected to undergo transsphenoidal pituitary resection. Tumor pathology showed sparsely granulated lactotroph adenoma. Post op PRL level normalized, and MRI showed radiological cure of the adenoma. Headaches improved but amenorrhea persisted despite discontinuation of OCs for 6 months. Progesterone challenge tests resulted in withdrawal bleed suggesting anovulation. Repeat work-up ruled out nonclassical CAH, Cushing’s, and androgen-secreting tumors. However, subsequent pelvic ultrasound confirmed polycystic ovarian morphology, suggesting PCOS. The patient preferred to avoid OCs and could not tolerate metformin. She elected progesterone IUD placement for endometrial protection in combination with lifestyle changes with notable improvement in her symptoms. Conclusion: PCOS is a diagnosis of exclusion. Thorough evaluation of symptoms like weight gain, amenorrhea, clinical hyperandrogenism is recommended to rule out serious pathology like prolactinoma. Dual diagnosis of PCOS and macroprolactinoma is rare and should be suspected if menstrual abnormalities persist even after treatment of hyperprolactinemia. Presentation: Saturday, June 17, 2023

THU667 Severe Hypothyroidism With Paradoxically Elevated Direct Free T4 Due To Anti-thyroxine Antibodies

Abstract Disclosure: O. Magvanjav: None. M.J. McPhaul: None. I. Choucair: None. E. Holt: None. Introduction Laboratory interference may cause abnormal thyroid function test (TFT) results, leading to misdiagnosis and inappropriate patient care. There are several major types of interference. Here, we describe a hypothyroid patient with an elevated thyroid stimulating hormone (TSH) level with a paradoxically elevated direct free thyroxine (FT4) level caused by interference from anti-thyroxine autoantibodies (THAAB). Clinical Case Our patient is a 38-year-old man who was found to have markedly elevated TSH and FT4 levels during an outpatient workup for Lyme disease. The patient was overall well-appearing but reported some symptoms suggestive of hypothyroidism including excessive fatigue, non-pitting edema, and dry skin. Physical exam was notable elevated blood pressure (systolic blood pressure of 150 mmHg and diastolic blood pressure of 95 mmHg), normal temperature, normal heart rate (72 bpm), regular heart rhythm, and normal body mass index. He had non-tender thyromegaly without nodules, non-pitting edema of bilateral hands and legs, decreased leg hair over bilateral shins, and coarse, dry skin of his hands. Initial TSH level was >150 mIU/ml, with a paradoxically elevated direct FT4 of 10 ng/dl (normal range 0.80-1.70 ng/dL). The FT4 level by equilibrium dialysis was <0.2 ng/dl. Outside laboratory testing to eliminate the effect of heterophile antibodies using two different assays again returned with elevated FT4 levels. Screening for macro TSH confirmed the markedly elevated TSH level. Further investigations at a second outside laboratory revealed that he had THAAB. A repeat FT4 level by dialysis confirmed the markedly low FT4 levels. He was empirically started on low dose levothyroxine and after increasing the levothyroxine dose, he showed improvement in clinical symptoms and the expected decline in TSH. Conclusions Here we present a rare case of THAAB that caused laboratory interference during thyroid function testing, leading to falsely elevated thyroid hormone levels on immunoassays. This case shows the importance of suspecting interference when there is a discrepancy between clinical symptoms and laboratory results or between results obtained from different testing methods. Our patient likely had a genetic predilection for autoimmunity, and Lyme disease is a known trigger for various autoimmune conditions. Our case also emphasizes the importance of taking a systematic approach to investigate the cause of the laboratory interference. This will help prevent misdiagnosis of thyroid disorders that may lead to additional unnecessary testing and treatment. Presentation: Thursday, June 15, 2023

THU664 Discontinuation Of Low-dose Levothyroxine Therapy For Patients With Subclinical Hypothyroidism Is Feasible: A Pilot, Randomized, Double-blind, Placebo-controlled Trial

Abstract Disclosure: S. Maraka: None. R. Owen: None. N.M. Singh Ospina: None. M. Knox: None. T. Dodds: None. H. Spencer: None. A. Albashaireh: None. A. Shah: None. S. Syed: None. S. Naqvi: None. H. Motahari: None. S. Thumma: None. E. Ambrogini: None. J.P. Brito: None. Objective: Levothyroxine (LT4) therapy has not been shown to improve quality of life (QoL), thyroid-related symptoms, cardiovascular events, or mortality for patients with subclinical hypothyroidism (SCH) in clinical trials. We conducted this pilot, double-blind, placebo-controlled clinical trial to evaluate the effects of LT4 discontinuation among adults with SCH. Methods: We aimed to randomize 50 adults 1:1 to continue receiving LT4 (25-75 mcg/day) for SCH or discontinue it (switch to placebo). The primary outcome was feasibility. Secondary outcomes included changes in QoL measures (Thyroid-specific QoL Patient-Reported Outcome [ThyPRO]-Hypothyroid Symptoms and Tiredness scores, EuroQoL 5-Dimension Self-Report Questionnaire [EQ-5D]) assessed at baseline and 6 months post-randomization, and incidence of adverse events (overt hypothyroidism, hyperthyroidism, atrial fibrillation, stroke, acute coronary syndrome, heart failure, fracture, mortality). Higher scores for ThyPRO indicate more symptoms and tiredness and for EQ-5D, better health state. Data are reported as mean (standard deviation). Analysis of covariance model adjusting for age and baseline measure of the variable was performed for the outcomes based on the intention-to-treat principle. Results: Fifty participants were enrolled (33% recruitment rate); 24 were randomized to the LT4 and 26 to the discontinuation group. Five patients were excluded post-randomization due to lack of ascertainment of SCH diagnosis (final N=45; 21 LT4, 24 discontinuation). There was no statistically significant difference at baseline between the discontinuation and LT4 groups in age [65.7 (10.6) vs. 71.0 (7.9) yrs], gender (male 75 vs. 86%), LT4 dose (25 mcg; 29.2 vs. 33.3%, 50 mcg; 54.2 vs. 47.6%, 75 mcg; 16.7 vs. 19.0%), TSH [3.1 (1.0) vs. 3.2 (1.4) mIU/L], TPOAb positivity (17 vs. 19%), ThyPRO-Hypothyroid Symptoms [27.1 (20.4) vs. 21.1 (18.4)] and Tiredness score [33.2 (23.7) vs. 31.1 (23.9)], and EQ-5D [0.746 (0.229) vs. 0.758 (0.193)]. A patient in the discontinuation group withdrew for personal reasons (98% completion rate). Two patients in the discontinuation group met study criteria to restart LT4 (TSH>10 mIU/L; n=1, fatigue; n=1). At final visit, 34.8% of patients in the discontinuation group had mild SCH compared to 9.5% of patients on LT4 (p=0.07). There was no statistically significant difference between the discontinuation and LT4 groups in ThyPRO-Hypothyroid Symptoms [28.3 (22.8) vs. 22.9 (19.5)], Tiredness [27.6 (22.8) vs. 32.8 (22.1)], and EQ-5D score [0.750 (0.232) vs. 0.741 (0.180)]. A patient suffered rib fracture (placebo); no other adverse event of interest was reported. Conclusion: This pilot clinical trial showed the feasibility and safety of discontinuing LT4 in patients with SCH. These findings support proceeding with a larger multi-site clinical trial to fully assess the effects of LT4 discontinuation. Presentation: Thursday, June 15, 2023

Relationship between thyroid hormone levels in euthyroid patients before HSCT and time to achieve neutrophil and platelet engraftment: an analytical cross-sectional study

Introduction. The time to reach neutrophil (NE) and platelet engraftment (PE) in hematopoietic stem cell transplantation (HSCT) is one of the most important factors indicating transplantation survival. The aim of this study was to investigate the relationship between thyroid hormone levels before HSCT and the time to achieve NE and PE. Material and methods. The relationship between thyroid hormone levels before HSCT, age, gender, type of HSCT, type of disease and cluster of differentiation 34+ (CD34+) cell count and the number of days to reach NE and PE was examined in 37 clinically and laboratorially euthyroid patients. Results. An odds ratio (OR) of > 6 was observed in the probability of time to NE > 10 days in patients with thyroid-stimulating hormone (TSH) > 2.89 mU/L in the upper normal range (UNR) and male patients, also in the probability of time to PE > 15 days in patients with TSH > 2.89 mU/L in the UNR. Statistically significant p -value and confidence interval were found in the probability of time to NE > 10 days in male patients (OR = 8.58, p -value = 0.036) and time to PE > 15 days in patients with TSH > 2.89 mU/L in the UNR (OR = 14.32, p -value = 0.041). Conclusions. Treatment with low dose levothyroxine can be cautiously recommended to achieve TSH to ≤2.8 mU/L in the lower normal range before performing HSCT in euthyroid patients, which will reduce the times to NE and PE and help earlier discharge of patients.

ODP635 A rare case of metastatic papillary thyroid carcinoma on NTRK inhibitor with thyrotoxicosis

Abstract We present a case of 26-year-old Hispanic female with neck enlargement and worsening dyspnea. She was noted to have enlarged thyroid nodules; biopsy revealed papillary thyroid carcinoma (PTC) with ETV6-NTRK fusion by next-generation sequencing (NGS). Further work up revealed extensive bilateral milliary pulmonary metastases and Graves’ disease with elevated thyrotropin receptor antibodies and thyroid-stimulating immunoglobulin titers. Tuberculosis work up was negative and bronchoalveolar lavage revealed metastatic PTC. The patient was initiated on larotrectinib (100mg administered twice daily) as well as block-and-replace regimen with levothyroxine and methimazole. Her dyspnea improved and she successfully underwent total thyroidectomy as well as bilateral neck dissections; methimazole and thyroid hormones were discontinued thereafter. Interestingly, patient developed thyrotoxicosis post-surgery even without being on levothyroxine with elevated free T3 at 18 pg/mL (normal range 2.3–4.2), compared to 5.8 pg/mL prior to surgery. Despite discontinuation of levothyroxine, patient continued to be biochemically and clinically hyperthyroid. She was treated with methimazole for 4 months after surgery, and subsequently underwent radioactive iodine (RAI) ablation with 30 mCi of I-131 of sodium iodide. After RAI, thyroid function started to improve, prompting re-initiation of very low dose levothyroxine about 5 months after surgery. Since then, she has remained clinically stable. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Rapid Resolution of Megaesophagus by Low-dose Levothyroxine in a Hypothyroid dog with Mitral Valve Degeneration

A 14-year-old intact female Maltese dog weighting 4.84kg was presented with acute regurgitation. At presentation, the dog was diagnosed with megaesophagus and primary hypothyroidism based on the radiography and thyroid-stimulating hormone stimulation test, respectively. Treatment was initiated with oral low-dose levothyroxine (0.0025 mg/kg b.w., orally, SID) considering underlying myxomatous mitral valve disease. Ten days after the management, the clinical and radiographic signs of megaesophagus were completely resolved. The dog was managed by levothyroxine administration with a gradual increase of the dose along with the monitoring of serum thyroxine concentrations since the dog was diagnosed with hypothyroidism. At 10 months after presentation, the dog continued to do well clinically. This is first case report describing rapid resolution of generalized megaesophagus after low-dose levothyroxine administration considering underlying cardiac disease in a hypothyroid dog.

Clinical Effect of Low Dose Levothyroxine in the Treatment of Benign Thyroid Nodules

Clinical Effect of Low Dose Levothyroxine in the Treatment of Benign Thyroid Nodules

A systematic review on the prevalence and management of subclinical hypothyroidism in patients with Type 2 Diabetes Mellitus

Background: Subclinical hypothyroidism (SCH) remains one of the most common biochemical manifestations of thyroid dysfunction.1 Similarly, type 2 diabetes mellitus (T2DM) is considered the most common metabolic disorder in clinical practice.2Methods: This is a systematic review to ascertain the prevalence and optimum management approach for thyroid dysfunction in patients with T2DM. We conducted a search on PubMed and Google scholar (Figure 1) for articles published between 2010-2020 using the following keywords: subclinical hypothyroidism, type 2 diabetes mellitus, thyroid diseases, diabetic retinopathy, diabetic nephropathy, and diabetic complications. Results: The prevalence of SCH in T2DM patients ranges from 7.8% to 23 % (average around 13.4%). In comparison, the prevalence of SCH in the general population ranges from 6% to 10%. SCH has a higher prevalence in females, older age >60 years old, long duration of T2DM, positive thyroid autoantibodies, glycated hemoglobin (Hba1c) 8%, and obese patients (risk factors).3 The prevalence of SCH in patients with diabetic retinopathy (DR) ranges from 17.3% to 43.3%. Also, the prevalence of SCH among patients with diabetic nephropathy (DN) ranges from 18.1% to 36%. Screening for thyroid dysfunction in T2DM at diagnosis is recommended and justified (Table 1). If patients with SCH have a risk of cardiovascular disease (CVD), DR, DN, symptomatic, presence of goiter, pregnant women, and continuous sustained increases of thyroid-stimulating hormone (TSH) on follow-up, it is recommended to start low dose levothyroxine which improves morbidity. Conclusion: The prevalence of SCH is relatively high in T2DM patients. This supports routine screening of such patients for thyroid dysfunction especially in patients with risk factors and diabetic complications (DR, DN), and consideration of thyroxine replacement wherever warranted although more evidence from randomized controlled trials is needed to explore the possible causal relationships.

IMPENDING PERICARDIAL TAMPONADE AS THE INITIAL PRESENTATION OF AUTOIMMUNE POLYGLANDULAR SYNDROME 3B

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Autoimmune polyglandular syndromes (APS) are rare polyendocrinopathies characterized by loss of immune tolerance to self-antigens leading to autoimmune destruction of endocrine glands and other tissues. APS is classified into APS types 1, 2, 3 and 4. APS Type 3 is recognized by absence of adrenal insufficiency. APS type 3b (APS3b) specifically comprises of the association of autoimmune thyroid disease with pernicious anemia. CASE PRESENTATION: A 66-year-old female with history of pernicious anemia presented to the emergency department with shortness of breath and lethargy which started on day of arrival. She was diagnosed with pernicious anemia 2 years ago and was receiving intramuscular cyanocobalamin injections. In the emergency department, she was found to be hypoxic with oxygen saturation of 90%. Her physical exam was notable for muffled heart sounds. Her labs on admission were: Hb 11.8 g/dl, HCT 35.8 %, WBC 6.3 K/ul, PLT 166 K/ul, Glucose 106 mg/dl, Sodium 143 mmol/l, BUN 13 mg/dl, Creatinine 1.13 mg/dl, pro-BNP 171 pg/ml, TSH 44.6 UIU/ml, Free T4 0.2 ng/dl, Free T3 0.5 pg/ml and positive thyroid peroxidase antibody >1300 u/ml. Serial troponins were unremarkable. Chest x-ray showed an enlarged cardiac silhouette concerning for pericardial effusion. EKG showed normal sinus rhythm with low voltage QRS complexes. 2D Echo showed a large circumferential pericardial effusion with end diastolic RV collapse suggestive of impending pericardial tamponade. LV ejection fraction was 60%. Pericardiocentesis drained 1700 cc of fluid with relief of patient's symptoms. This was followed by placement of pericardial drain. Her pericardial effusion was attributed to her new diagnosis of hypothyroidism. She was started on low dose levothyroxine given her age above 60 with plan for slowly increasing her dose with close outpatient follow up. DISCUSSION: Pernicious anemia is the most common association with thyroid autoimmune disease in APS type 3 seen in 39% of cases. APS3 is more commonly seen in females. The diagnosis of this condition requires the presence of multiple autoimmune diseases in the same individual, diagnosed in any order and at any age. CONCLUSIONS: A high index of suspicion is required whenever one autoimmune disease is diagnosed to prevent morbidity and mortality from other associated conditions. Here, we describe a patient with known history of pernicious anemia presenting with impending tamponade who was subsequently diagnosed with Hashimoto's thyroiditis. The constellation of these findings represent APS Type 3b. REFERENCE #1: Betterle, Corrado et al. "A rare combination of type 3 autoimmune polyendocrine syndrome (APS-3) or multiple autoimmune syndrome (MAS-3)." Auto- immunity highlights vol. 5,1 27-31. 11 Feb. 2014, doi:10.1007/s13317-013-0055-6 REFERENCE #2: Lahner E, Centanni M, Agnello G, et al. Occurrence and risk factors for autoimmune thyroid disease in patients with atrophic body gastritis. Am J Med. 2008;121(2):136-141. doi:10.1016/j.amjmed.2007.09.025 DISCLOSURES: No relevant relationships by Sana Fatima, source=Web Response No relevant relationships by Shumail Syed, source=Web Response

Subclinical hypothyroidism or isolated high TSH in hospitalized patients with chronic heart-failure and chronic renal-failure

Sub-clinical hypothyroidism (SCH) is common in heart failure (HF) and advanced renal failure (RF), but it is unclear whether there is a thyroid disease or a transient increase in TSH level. This is a retrospective study of hospitalized patients in medical departments. All patients with SCH and a TSH level up to less than 12 mIU/L were identified. Those who had at least one recurring admission within at least 6 months were included. A change in thyroid function during the last re-admission was determined and classified as an improvement, no change, or worsening of thyroid function. Overall, 126 cases of SCH met the inclusion criteria for re-admission. Analysis of the most recent hospitalization showed that in 100 (79.4%) patients thyroid function improved, in 15 (11.9%) patients thyroid function remained unchanged and only in 11 (8.7%) patients did thyroid function worsen. In most cases, worsening of hypothyroidism was determined by initiation of a low dose levothyroxine treatment. Of the 126 participants, 43 (34.1%) and 22 (17.5%) had a diagnosis of HF and RF (CKD stages 4 and 5), respectively. There was no association between HF or advanced RF and worsening of SCH. No association was found between worsening of hypothyroidism and gender, age, TSH, or creatinine levels in the first hospitalization. A borderline association between elevated CRP levels at first hospitalization and hypothyroidism worsening was found (p = 0.066). Mildly elevated TSH in hospitalized patients with HF and advanced RF is transient and most probably not related to thyroid disease and not associated with age or gender.

Palpitations and Fatigue Post COVID: A Harbinger of Silent Thyroiditis!

Background: Subacute thyroiditis is a self-limiting condition brought about by an inflammatory reaction often linked to a recent viral infection. SARS-COV2 (COVID-19), an RNA coronavirus that started a global pandemic in December 2019 has been linked mostly to severe acute respiratory distress syndrome. However, there have been increasing reports of its effect on other organ systems. We present a case of a 32-year-old female recovering from COVID-19, only to develop silent thyroiditis afterwards. Clinical Case: A 32-year-old female with anxiety disorder but otherwise in excellent health was diagnosed with COVID-19 via nasal swab RT-PCR after experiencing low grade fever and cough. She quarantined at home and was on her way to recovery when, a few weeks later, she began to experience increasing bouts of chest pain with no relation to activity, intermittent headaches and lower extremity edema. This prompted her to visit the emergency department. Work-up done at that time was unremarkable and her symptoms were attributed mostly to anxiety. She was advised to follow-up as an outpatient with a cardiologist. One month later, due to the persistence of her fatigue, low exercise tolerance and tremors, she decided to seek consult with a cardiologist. An electrocardiogram done during that visit showed normal sinus rhythm with poor-R wave progression and early repolarization changes. Both the echocardiogram and 24-hour Holter monitoring, which were subsequently done, were unremarkable. Blood work-up, however, revealed a significantly low thyroid stimulating hormone (TSH) level of 0.17 mU/L, for which she was referred to an endocrinologist. A month later, she sought consult with an endocrinologist. Thyroid gland was non-tender on palpation. Repeat blood work-up showed an elevated TSH level (23.50 mU/L) with a low Free T4 (0.42 ng/dL) and an elevated thyroid peroxidase antibody (TPO-Ab) level (900 mU/mL), indicative of subacute thyroiditis, but without associated neck pain. Thyroid sonography done showed diffusely heterogeneous thyroid lobes with no evidence of a dominant mass or nodule. A decision was made to start her on low dose levothyroxine. Two months into treatment, she underwent repeat thyroid hormone levels. Normal TSH and normal free T4 were observed. However, TPO-Ab was still elevated. It was decided to continue her therapy for one more month before gradually tapering her levothyroxine dose. She was told to follow-up in a month for further monitoring. Conclusion: Subacute thyroiditis associated with COVID-19 infection has become a more common occurrence as more cases of COVID-19 are noted worldwide. Our patient followed the usual course of subacute thyroiditis, initially presenting with a thyrotoxicosis phase which typically lasts 4-10 weeks, then subsequently developing hypothyroidism, inadvertently needing thyroid hormone replacement. What made this case more intriguing was that she did not have severe anterior neck pain, the classic clinical presentation of subacute thyroiditis. While there is a very strong association between COVID-19 and respiratory failure, there is paucity of evidence linking COVID-19 to dysfunction of other body systems. This case of thyroiditis presenting post COVID-19 illness, buttresses the versatility of COVID-19. Physicians should keep this in mind when evaluating a COVID-19 survivor who continue to present with persistent tachycardia or palpitations with or without anterior neck pain even after a month or two from infection. Routine follow-up TSH assay on COVID-19 survivors may be a valuable consideration.

Pituitary Macroadenoma: A Case of Balanced Deficiencies

Abstract Introduction: Diabetes insipidus (DI) rarely occurs in pituitary tumors although some patients may develop DI following pituitary tumor resection. However DI is known to occur in patients with tumors metastatic to the pituitary or in infiltrative disorders of the pituitary gland. We are reporting a patient with a 2 cm pituitary macroadenoma whose DI was unmasked by glucocorticoid therapy. Case Presentation: A 61-year-old male with a history of non-functioning pituitary macroadenoma, incidentally discovered on imaging in 2015 and stable at 1.6cm for 4 years, was referred to endocrinology for interval enlargement of his macroadenoma. He had presented to primary care due to new headache during extreme physical exertion, but otherwise denied any symptoms such as vision loss, fatigue, decreased libido, weight loss, or urinary frequency. Repeat MRI indicated growth to 2.1cm in the suprasellar component, no cavernous sinus involvement, and abutting the optic chiasm. Laboratory results revealed new onset central hypothyroidism (FT4 0.21 ng/dL (ref 0.78-2.19) with triiodothyronine 68 ng/dL (ref 80-200) and TSH 1.61 mIU/L (ref 0.47-4.68), central hypogonadism (Testosterone Free 1.3 pg/mL (ref 6.6-18.1)) and concern for adrenal insufficiency with a cortisol of 4.4 mcg/dL. He was empirically started on hydrocortisone replacement until an ACTH stimulation test could be completed, and after 3 days instructed to begin low dose levothyroxine replacement. At close followup, patient revealed that he developed new hourly nocturia causing significant distress. An overnight water deprivation test yielded a serum sodium 152 mmol/L with a urine osmolality 191 mOsm/kg, both rapidly improving with intravenous desmopressin. Copeptin was 4.6 pmol/L. Discussion Diabetes insipidus occurring in pituitary tumors including macroadenomas is extremely rare. Secretion of AVP occurs in the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei, and the superior portion of the supraopticohypophyseal tract. AVP deficiency is most commonly due to damage to these areas either through neurosurgery or trauma, and more rarely tumors or infiltrative disease. However, glucocorticoid and thyroid replacement each may precipitate the development of diabetes insipidus. Well described in literature, glucocorticoid deficiency and hypothyroidism each independently impairs free water excretion. Low cortisol stimulates release of antidiuretic hormone, but this secretion is then inhibited by exogenous steroid replacement. Cortisol interferes with AVP signaling through unclear mechanisms either at the V2 receptor or post-receptor level, decreasing translocation of type 2 aquaporins and therefore reducing free water reabsorption. It is important to recognize that CDI can be unmasked after glucocorticoid or thyroid hormone replacement.

SUN-516 Unplanned Pregnancy Post Thyroid RAI Ablation

A patient’s pregnancy and fetus are at an increased risk for complications secondary to history of recent RAI ablation and maternal secondary hypothyroidism.A 31 year old female with a recent history of miscarriage presented with abnormal thyroid function tests and was history of low dose levothyroxine use. She complained of a 3 month history of extreme fatigue, palpitations and 18 pound weight loss at the time of presentation. Her thyroid stimulating immunoglobulin was 9.21 IU/L (0-0.55), free thyroxine 6.2ng/dL (0.9-1.8), free triiodothyronine 20.04 pg/mL (1.8-4.6) with a suppressed TSH 0.01 uIU/ml (0.27 - 4.2). She was started on methimazole. Her 24 hour radioactive iodine uptake was 60% and she subsequently underwent radioactive iodine-131 ablation in capsule form. She failed the ablation after 7 months and remained on methimazole during that duration. Her second radioactive iodine uptake was 58% and she underwent a second RAI ablation. Her TSH was 50 uIU/ml and her free thyroxine was 0.1 ng/dl. She was started on levothyroxine for replacement. Patient unexpectedly became pregnant approximately six weeks after her radioactive iodine treatment.Studies have shown that with the exception of miscarriages, there is no evidence that exposure to radioiodine affects the outcome of subsequent pregnancies and offspring. Although the number of children born of mothers exposed to radioiodine is relatively small, the present data indicates that there is no reason for patients exposed to radioiodine to avoid pregnancy. The only adverse effect observed in the study series is an increased incidence of miscarriages in women exposed to therapeutic radioiodine during the year which preceded conception. The fetus would be at risk due to maternal hypothyroidism.Discussion: Radioactive iodine exposure does not appear to be associated with an increased risk of miscarriage or abnormal subsequent pregnancies.Conclusion: Pregnancies achieved after exposure to radioactive iodine treatment do not appear to be at increased risk for negative outcomes. Nevertheless, it is recommended that pregnancy be avoided for 1 year following radioactive iodine therapy to allow reproductive function to normalize.

SUN-622 Graves Disease Triggered by Lobectomy for Thyroid Cancer

Background: The incidence of Hashimoto thyroiditis as well as Graves disease in patients with thyroid cancer has been observed however molecular and pathophysiological basis of this association has only been hypothesized. Cases of new onset severe thyrotoxicosis and Graves ophthalmopathy shortly after lobectomy for thyroid cancer have not been described to our knowledge. Case: The patient is a 46-year-old woman who had a 2.5cm thyroid nodule. Fine needle aspiration showed atypia of undetermined significance and subsequent thyroid genomic classifier test Thyroseq confirmed positive for fusions involving THADA and IGF2BP3. Since THADA positive nodules are usually associated with low risk thyroid carcinoma and non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), thyroid lobectomy was advised. Prior to surgery the patient had positive thyroid peroxidase antibodies and was treated with low dose levothyroxine only during two pregnancies. Surgical pathology confirmed 2.5 cm NIFTP and 2 foci of papillary thyroid microcarcinoma of 0.5mm and 1mm with the background of chronic lymphocytic thyroiditis (Hashimoto). No further therapy was advised. At 6 weeks after left thyroid lobectomy the patient presented for a follow up clinically euthyroid with thyroid stimulating hormone (TSH) of 3 mcIU/mL. Two weeks after this regular follow up visit she started having severe periorbital swelling, double vision and bulging of her eyes that was followed by shortness of breath, palpitations, anxiety, sweating and weight loss. She presented to emergency room and was found to have suppressed TSH and positive TSI and TBII antibodies with high titer. After stabilization of hyperthyroidism with methimazole completion thyroidectomy was performed on patient request. Surgical pathology of the right thyroid lobe showed scattered papillary hyperplasia, chronic inflammation, focal atrophy and lymphoid follicles. Six weeks after completion thyroidectomy the patient is clinically euthyroid on levothyroxine and with significantly improved ophthalmopathy. TSI and TBII antibodies remain positive and continue to downtrend. Conclusion: As partial thyroidectomy for low-risk thyroid carcinoma is becoming increasingly convenient method of therapy we may encounter more surgically triggered autoimmune thyroid disorders in the future.

Short Call Abstracts

Short Call Abstracts

Clinical Profile of Subclinical Hypothyroidism:A Retrospective Study

Background: Subclinical hypothyroidism occurs due to an under functioning thyroid gland and presents with varied symptoms and signs. Thyroid disorders are common in Indian population and the prevalence of subclinical hypothyroidism is high. Objective: This study intended to assess the clinical profile of patients presenting with subclinical hypothyroidism. Materials and Methods: This was a retrospective study that analyzed the medical records of adult patients diagnosed with subclinical hypothyroidism for a period of three years. Results: 71 patients within the age range of 18 years to 77 years were diagnosed with subclinical hypothyroidism. Among these 53 (75%) patients had various clinical symptoms. Body pains were the most common symptom (38 %) followed by weight gain(27%) and tiredness (20%). A significant number of patients were obese (25%). Enlarged thyroid(14%) and dyslipidemia (25%) were also recorded. 63 (75%) patients were initiated on low dose levothyroxine. Conclusion: Patients with subclinical hypothyroidism present with varied non-specific clinical symptoms. Treatment with low dose levothyroxine resulted in lowering of serum TSH to normal range and relief of symptoms.

Clinical Profile of Subclinical Hypothyroidism:A Retrospective Study

<p><strong>Background:</strong> Subclinical hypothyroidism occurs due to an under functioning thyroid gland and presents with varied symptoms and signs. Thyroid disorders are common in Indian population and the prevalence of subclinical hypothyroidism is high.</p><p><strong>Objective:</strong> This study intended to assess the clinical profile of patients presenting with subclinical hypothyroidism.</p><p><strong>Materials and Methods:</strong> This was a retrospective study that analyzed the medical records of adult patients diagnosed with subclinical hypothyroidism for a period of three years.</p><p><strong>Results:</strong> 71 patients within the age range of 18 years to 77 years were diagnosed with subclinical hypothyroidism. Among these 53 (75%) patients had various clinical symptoms. Body pains were the most common symptom (38 %) followed by weight gain(27%) and tiredness (20%). A significant number of patients were obese (25%). Enlarged thyroid(14%) and dyslipidemia (25%) were also recorded. 63 (75%) patients were initiated on low dose levothyroxine.</p><p><strong>Conclusion:</strong> Patients with subclinical hypothyroidism present with varied non-specific clinical symptoms. Treatment with low dose levothyroxine resulted in lowering of serum TSH to normal range and relief of symptoms.</p>

Early Initiation of Low-Dose Levothyroxine After Radioactive Iodine Appears Safe

Initiating low-dose levothyroxine at 4 weeks after radioactive iodine therapy for Graves disease appears safe and did not increase the risk of hyperthyroidism in this interim safety analysis of 20 patients.