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Introduction: Hypothyroidism requires lifelong thyroid hormone replacement with levothyroxine. For most hypothyroid patients fasting during Ramadan, compliance with the administration procedure is a challenge. This study aimed to determine the impact of different administration times of levothyroxine on thyroid-stimulating hormone (TSH) and free T4 (FT4) levels before and after the holy month of Ramadan. Materials and Methodology. Hypothyroid patients taking levothyroxine were randomized to 3 groups during Ramadan: group 1, 30 minutes before the iftar meal; group 2, 3-4 hours after the iftar meal, with no food taken for at least 1 hour after the meal; group 3, they were not given specific instructions for taking levothyroxine during Ramadan. Thyroid function tests were performed within 2 weeks before Ramadan and within 2 weeks after Ramadan. Pre- and post-Ramadan TSH and free T4 levels were compared. Mixed-effects analyzes were performed to identify factors associated with changes in TSH and FT4 levels. Results: Compliance was lower in patients taking levothyroxine 3-4 hours after iftar. In addition, the majority of patients who had not received a specific recommendation took levothyroxine 30 minutes before iftar. There was a statistically significant increase in TSH (P=0.006) and FT4 (P=0.044) levels after Ramadan. In multivariate analysis, the cause of hypothyroidism (Hashimoto's; postthyroidectomy; compared to postradioactive iodine) and levothyroxine dose significantly affected FT4 levels. In contrast, no variable was significantly associated with TSH level. The timing of levothyroxine intake during Ramadan did not significantly affect TSH or FT4 levels. Conclusion: TSH and FT4 significantly increased after Ramadan. However, the timing of levothyroxine intake per se had no influence on TSH or free T4 levels. Therefore, hypothyroid patients might take levothyroxine either 30 minutes or 3-4 hours after iftar with no meal for 1 hour, depending on preference.
RESUMEN
CONTEXT: Dyshormonogenesis due to genetic defect in thyroglobulin (Tg) synthesis and secretion can lead to congenital hypothyroidism. OBJECTIVES: The aim of the study was to analyze the TG gene for the presence of mutations and to study the underlying mechanisms leading to dyshormonogenesis. CASES: Two siblings aged 25 and 31 yr presented with recurrent goitrous hypothyroidism with undetectable serum Tg. The older sibling was diagnosed with follicular variant of papillary thyroid carcinoma (FVPTC) at age 21 and metastatic FVPTC 8 yr later. METHODS: The entire coding region of TG gene was sequenced. BRAF, RAS, and P53 mutations or PAX8/PPAR-gamma rearrangement were screened in the FVPTC. Tg expression was studied by immunohistochemistry. RESULTS: Biallelic c.6725G>A (p.R2223H) and c.6396C>T (p.S2113L) sequence variations were detected in both patients and monoallelic variations in their family members. The c.6396C>T (p.S2113L) sequence variation was found in 14% of 100 population controls, whereas c.6725G>A variation was not present in the controls. Two previously reported polymorphisms (c.2200T>G and c.3082A>G) were present in all the family members. Strong cytoplasmic immunostaining of Tg was observed in the hyperplastic thyroid epithelial cells and weak or no staining in the follicular lumen. Cytoplasmic staining was localized in the endoplasmic reticulum. Reduced staining was found in the FVPTC. Neither RAS, BRAF, or P53 gene mutation nor a PAX8/PPAR-gamma rearrangement was detected in the tumor tissue. CONCLUSIONS: Biallelic c.6725G>A (p.R2223H) mutation causes Tg retention in the endoplasmic reticulum, resulting in dyshormonogenesis. Prolonged TSH stimulation may promote malignant transformation and development of thyroid cancer. The c.6396C>T (p.S2113L) is a novel polymorphism.
