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SAT-LB85 Use of Weekly Levothyroxine Regimen for Rapid Normalization of Thyroid Hormone Levels: A Case Report

Abstract Background: Hypothyroidism affects around 4.6% of the U.S. population1. Non-adherence with thyroid hormone replacement is one of the biggest challenges in treating hypothyroidism1. The half-life of T4 and T3 in hypothyroidism is about 7.5 and 1.4 days respectively2. A large dose once-weekly administration of levothyroxine (Lt4) is possible3, 4. Recent publications suggest that once-weekly Lt4 does not increase the risk of cardiovascular events and is well tolerated by most of patients4. Once weekly Lt4 produces similar results as daily Lt4 as evidenced by thyroid function tests3,4, and potentially improves patient compliance and satisfaction with the treatment4. Clinical Course: A 29-year-old female with a history of Hashimoto’s hypothyroidism, polycystic ovarian syndrome, depression, presented with irregular menses. Her symptoms included depression, fatigue, increased appetite. Her TSH was grossly elevated at 217 uIU/mL (0.27-4.20 uIU/mL). However upon re-visit, after increasing Lt4 to 100 mcg daily her TSH increased to 280 uIU/mL. She admitted to non-adherence with her daily Lt4 prescription. Physical exam was notable for sinus bradycardia and slow mentation, otherwise unremarkable. Blood count, basic metabolic panel and hemoglobin A1C were within normal limits. Liver function tests showed mild transaminitis, ALT 46 U/L (10-45 U/L). Lt4 was started at 875 mcg per week. At five weeks, her TSH was 6.31 uIU/mL and at seven weeks, the patient was euthyroid with a TSH of 2.53 uIU/mL. Her periods have since normalized. Conclusion: The current discourse on weekly dosing mainly focuses on its use for non-adherent patients. This case provides a clear time course also demonstrating rapid normalization of TSH using weekly dosing. Weekly Lt4 dosing as first-line therapy in noncompliant depressed patients with severe hypothyroidism should be considered. 1.Hepp, Z., Wyne, K., Manthena, S., Wang, S. and Gossain, V. (2018). Adherence to thyroid hormone replacement therapy: a retrospective, claims database analysis. Current Medical Research and Opinion, 34(9), pp.1673-1678.2.Colucci, P., Yue, C., Ducharme, M. and Benvenga, S. (2010). A Review of the Pharmacokinetics of Levothyroxine for the Treatment of Hypothyroidism. European Endocrinology, 9(1), p.40.3.Jayakumari, C., Nair, A., Puthiyaveettil Khadar, J., Das, D., Prasad, N., Jessy, S., Gopi, A. and Guruprasad, P. (2019). Efficacy and Safety of Once-Weekly Thyroxine for Thyroxine-Resistant Hypothyroidism. Journal of the Endocrine Society, 3(12), pp.2184-2193.4.Rajput, R. and Pathak, V. (2017). The Effect of Daily versus Weekly Levothyroxine Replacement on Thyroid Function Test in Hypothyroid Patients at a Tertiary Care Centre in Haryana. European Thyroid Journal, 6(5), pp.250-254.

and 2) GH receptor knockout (GHR-/-) mice (GH resistance). Intestines from GH-/-and GHR-/-mice and their respective littermate controls at adult (12-13 mo.) and older adult (19 mo. and 24 mo., respectively) were used for this study. Both length and weight of small and large intestines were measured at the time of dissection. Six sections for the small intestine and four sections for the large intestine were prepared using a swill roll technique. Images were taken at 100x magnification with a Nikon Eclipse E600 microscope, and villus height, crypt depth, and muscle thickness were measured using ImageJ. All measurements were analyzed using Student t-test, and Cohen's d effect size was used to compare the intestinal phenotype between lines. Both GHR-/-and GH-/-displayed altered intestinal gross anatomy and morphology. GHR-/-mice at 13 mo. of age had significantly shorter small and large intestines compared to controls. Morphologically, GHR-/-mice also showed significantly decreased villus height in the duodenum and decreased villus height and crypt depth in the jejunum. Likewise, GHR-/-mice at 24 mo. of age had significantly decreased intestinal length, and circumference in both small and large intestines with significantly decreased crypt depth in the ileum. Similar to GHR-/-mice, GH-/-mice at both 12 mo. and 19 mo. of age exhibited significantly shorter small and large intestines compared to controls with significantly smaller circumferences. Duodenum and jejunum of GH-/-mice also had a significant decrease in villus height in the duodenum and jejunum. In this study, decreased GH action is apparent in significantly affecting intestinal morphology and gross anatomy. GHR-/-and GH-/-mice had similar changes in gross anatomy (i.e. length and circumference) and villus height of the duodenum and jejunum. Similar changes to intestinal gross anatomy and morphology were also seen across the different ages in the mice. These findings suggest that decreased GH action influences the gross anatomy of both small and large intestines, and yet has a distinctive section-dependent impact on intestinal morphology. Research needs to be conducted to understand how these structural changes relate to gut function and assess intestinal phenotype at a younger ages in these mouse lines.

SUN-LB111
Familial partial lipodystrophy (FPLD), a rare autosomal dominant disorder, is characterized by marked loss of subcutaneous (sc) fat from the extremities, and predisposition to insulin resistance, diabetes mellitus, dyslipidemia and hepatic steatosis. FPLD2 and FPLD3 due to causal variants in LMNA and PPARG, respectively, are the two most common subtypes. Due to extremely rare prevalence of FPLD3 and limited reports in the literature, whether there are phenotypic differences between the two subtypes remain unclear. Therefore, we compared the anthropometric measurements and prevalence of metabolic abnormalities among 32 FPLD3 subjects (4 M, 28 F; mean ± SD age, 41 ± 17.2 y; body mass index (BMI), 26 ± 4.0 kg/m 2 ) with 271 FPLD2 subjects (66 M, 205 F; age, 37.4 ± 17.0 y; BMI, 26 ± 5.0 kg/m 2 ) from two referral centers in the United States. As compared to those with FPLD2, FPLD3 subjects had borderline higher prevalence of hypertriglyceridemia (66% vs 84%; P = 0.063), but significantly higher prevalence of diabetes (44% vs 72%; P = 0.004), past history of acute pancreatitis (13% vs 52%; P <0.001), and polycystic ovarian syndrome (26% vs 52%; P = 0.011). As compared to FPLD2, FPLD3 subjects had similar fasting triglyceride levels (median 208 vs 255 mg/ dL; P=0.15), but lower high-density lipoprotein cholesterol levels (median 37.5 vs 30 mg/dL; P = 0.001), higher fasting glucose (median 95 vs 115 mg/dL; P = 0.05) and HbA1c (median 5.7 vs 7.0 %; P = 0.005) levels. Regional body fat was measured by dual energy X-ray absorptiometry in 19 FPLD3 and 105 FPLD2 subjects. In comparison to FPLD2, FPLD3 subjects had higher total fat (median 21.6% vs 26.1 %; P = 0.018); upper limb fat (median 20.3% vs 27.3%; P = 0.003) and lower limb fat (median 16.0% vs 20.8%; P = 0.007). Skinfold thickness measurements by calipers also revealed less severe fat loss from both the upper and lower extremities in FPLD3 subjects compared to FPLD2 subjects. As compared to FPLD2, FPLD3 subjects had significantly higher triceps skinfold thickness (median 5.5 mm vs 7.5 mm; P = 0.015); and thigh skinfold thickness (median 5.8 mm vs 11.3 mm; P = 0.001). There were no significant differences in the prevalence of fatty liver, plasma alanine aminotransferase and aspartate aminotransferase levels in the two subtypes. We conclude that compared to FPLD2 subjects, those with FPLD3 have milder lipodystrophy phenotype but paradoxically present with more severe metabolic complications, especially diabetes, dyslipidemia and polycystic ovarian syndrome. It is likely that this discrepancy could be due to early recognition of FPLD2 because of severe fat loss versus initial diagnosis of FPLD3 subjects due to severe metabolic complications leading to discovery of milder fat loss.

SAT-LB85 Use of Weekly Levothyroxine Regimen for Rapid Normalization of Thyroid Hormone Levels: A Case Report
Jose Martinez, Johnathan Kirupakaran, Giovanna Rodriguez, Gül Bahtiyar Background: Hypothyroidism affects around 4.6% of the U.S. population 1 . Non-adherence with thyroid hormone replacement is one of the biggest challenges in treating hypothyroidism 1 . The half-life of T4 and T3 in hypothyroidism is about 7.5 and 1.4 days respectively 2 . A large dose once-weekly administration of levothyroxine (Lt4) is possible 3, 4 . Recent publications suggest that once-weekly Lt4 does not increase the risk of cardiovascular events and is well tolerated by most of patients 4 . Once weekly Lt4 produces similar results as daily Lt4 as evidenced by thyroid function tests 3,4 , and potentially improves patient compliance and satisfaction with the treatment 4 . Clinical Course: A 29-year-old female with a history of Hashimoto's hypothyroidism, polycystic ovarian syndrome, depression, presented with irregular menses. Her symptoms included depression, fatigue, increased appetite. Her TSH was grossly elevated at 217 uIU/mL (0.27-4.20 uIU/mL). However upon re-visit, after increasing Lt4 to 100 mcg daily her TSH increased to 280 uIU/mL. She admitted to non-adherence with her daily Lt4 prescription. Physical exam was notable for sinus bradycardia and slow mentation, otherwise unremarkable. Blood count, basic metabolic panel and hemoglobin A1C were within normal limits. Liver function tests showed mild transaminitis, ALT 46 U/L (10-45 U/L). Lt4 was started at 875 mcg per week. At five weeks, her TSH was 6.31 uIU/mL and at seven weeks, the patient was euthyroid with a TSH of 2.53 uIU/mL. Her periods have since normalized.

Conclusion:
The current discourse on weekly dosing mainly focuses on its use for non-adherent patients. This case provides a clear time course also demonstrating rapid normalization of TSH using weekly dosing. Weekly Lt4 dosing as first-line therapy in noncompliant depressed patients with severe hypothyroidism should be considered. 1.Hepp, Z., Wyne, K., Manthena, S., Wang, S. and Gossain, V.  Mo M. Mai,MD 1 ,Jocelyne G. Karam,MD 2 ,Nyein Lynn,MBBS 1 ,Gurbaj Singh,MD,FACP 3

SAT-LB87
Background: Subacute thyroiditis is caused by an inflammation and a destruction of the thyroid cells, leading to hyperthyroidism due to leakage of thyroid hormones, followed by possible hypothyroidism and/or full recovery of thyroid function. This is a case report describing a rare occurrence of druginduced thyroiditis secondary to golimumab. Clinical Case: A 79-year-old female with HTN, hyperlipidemia, dementia and rheumatoid arthritis was brought to the ER for abnormal behavior including visual hallucinating and insomnia.Initial ER evaluation showed UTI for which antibiotic therapy was initiated. Dementia workup was performed including a negative head CT, nonreactive RPR, and borderline low vitamin B12 level. TFT obtained showed low TSH of 0.2mlU/L, elevated serum FT4 of 1.72ng/ml (n=0.58-1.64ng/ml) and elevated serum FT3 4.38pg/ml (n=2.5-3.9pg/ml), suggestive of hyperthyroidism. The patient reported no heat intolerance, hyperdefecation, or weight changes, but had intermittent palpitations. She denied any history of thyroid problem and did not take thyroid medication, amiodarone, biotin, or any new drug. She reported no fever or URI symptoms within the few weeks prior to admission. In addition to prednisone and methotrexate, she was taking golimumab 50mg every 30 days for the last 22 months for RA. The patient had a family history of hypothyroidism of two daughters and sister. She denied smoking, alcohol, or any other recreational drug use. Her home medications included prednisone 5mg daily, methotrexate, folic acid, lisinopril, simvastatin, and golimumab. On physical examination, she did not appear thyrotoxic and had no exophthalmos, thyroid tenderness, thyroid enlargement or thyroid nodules. Her HR range was 80bpm.Further analysis revealed normal TSI, TPO, and TgAb levels. The thyroglobulin level was very high at 2505ng/ml (n=1.6-59.9ng/ml). Her thyroid sonogram revealed bilateral thyroid nodules, largest at 1.9cm in the right mid pole. A 24-hr RAIU scan showed very low uptake (1.8%) consistent with thyroiditis (hyperthyroid phase).Endocrinology team did not recommend any antithyroid medications. In addition, she did not warrant NSAIDs or beta blockers as she was not symptomatic or tachycardic. In the absence of an autoimmune or an obvious viral process, her subacute thyroiditis was thought to be induced by golimumab. Conclusion: TNFɑ inhibitors used to treat chronic inflammatory diseases, have been rarely associated with subacute thyroiditis as described in case reports with adalimumab and