Journal of Thyroid Research
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Iodine Deficiency in Patients with Hypothyroidism: A Pilot Study

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Journal of Thyroid Research publishes articles on the molecular and cellular biology, immunology, biochemistry, physiology and pathology of thyroid diseases, with a specific focus on thyroid cancer.

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Research Article

Subclinical Hypothyroidism in Advanced Chronic Kidney Disease Patients: Prevalence and Associated Factors

Introduction. Renal function and thyroid metabolism are tightly related. However, evidence about subclinical hypothyroidism prevalence in patients with chronic kidney disease and its related factors is scarce. Objectives. Our aim is to analyze subclinical hypothyroidism prevalence and its related factors in patients with advanced chronic kidney disease. Materials and methods. Nondialysis-dependent patients with chronic kidney disease at stages 3 to 5 were included. Other inclusion criteria were age above 18 years and clinical stability. Patients with diagnosed thyroid illnesses were excluded. Subclinical hypothyroidism was defined as thyroid stimulating hormone (TSH) > 5.3 mU/L, with free thyroxine 4 (FT4) between 0.54 and 1.24 ng/dl. Filiation data, comorbidities, and routine blood and urine test results were registered. Results. A total of 299 patients were included. Of them, 184 (61.5%) were men. The mean age was 71 ± 13 years old. The mean glomerular filtration rate (CKD-EPI) was 22 ± 9 ml/min/1.73 m2. According to chronic kidney disease stages, global distribution of patients was as follows: Stage 3, 67 patients (22.4%); Stage 4, 155 patients (51.8%); and Stage 5, 77 patients (25.8%). We found subclinical hypothyroidism in 54 (18.1%) patients. According to chronic kidney disease stages, distribution of affected patients was as follows: Stage 3, 9 patients (13%); Stage 4, 25 patients (16.1%); and Stage 5, 20 patients (26%). Differences among stages were statistically significant. By univariate analysis, factors related with subclinical hypothyroidism were as follows: age RR 1.048 (95% CI 1.019–1.078; ), hypertension RR 2.705 (95% CI 1.026–7.130; ), glomerular filtration rate RR 0.962 (95% CI 0.929–0.996; ), and proteinuria higher than 1 gram/day RR 2.387 (95% CI 1.303–4.374; ). By multivariate analysis adjusted by age, hypertension, glomerular filtration rate, proteinuria, diabetes, and cardiovascular disease history, only age RR 1.016 (95% CI 1.009–1.028; ) and glomerular filtration rate RR 0.963 (95% CI 0.930–0.997; ) preserved their independent association with subclinical hypothyroidism. Conclusions. Subclinical hypothyroidism prevalence in patients with chronic kidney disease is high and increases with renal disease severity. Factors independently related to subclinical hypothyroidism are age and glomerular filtration rate.

Research Article

Thyroid Signaling Biomarkers in Female Symptomatic Hypothyroid Patients on Liothyronine versus Levothyroxine Monotherapy: A Randomized Crossover Trial

Background. Levels of thyroid-stimulating hormone (TSH) are believed to reflect degree of disease in patients with hypothyroidism, and normalization of levels is the treatment goal. However, despite adequate levels of TSH after starting levothyroxine (LT4) therapy, 5–10% of hypothyroid patients complain of persisting symptoms with a significant negative impact on quality of life. This indicates that TSH is not an optimal indicator of intracellular thyroid hormone effects in all patients. Our aim was to investigate different effects of LT3 and LT4 monotherapy on other biomarkers of the thyroid signaling pathway, in addition to adverse effects, in patients with residual hypothyroid symptoms. Methods. Fifty-nine female hypothyroid patients, with residual symptoms on LT4 monotherapy or LT4/liothyronine (LT3) combination therapy, were randomly assigned in a non-blinded crossover study and received LT4 or LT3 monotherapy for 12 weeks each. Measurements, including serum analysis of a number of biochemical and hormonal parameters, were obtained at the baseline visit and after both treatment periods. Results. Free thyroxine (FT4) was higher in the LT4 group, while free triiodothyronine (FT3) was higher in the LT3 group. The levels of reverse triiodothyronine (rT3) decreased after LT3 treatment compared with LT4 treatment. Both low-density lipoprotein (LDL) and total cholesterol levels were reduced, while sex hormone-binding globulin (SHBG) increased after LT3 treatment compared with LT4 treatment. The median TSH levels for both treatment groups were within the reference range, however, lower in the LT4 group than in the LT3 group. We did not find any differences in pro-B-type natriuretic peptide (NT pro-BNP), handgrip strength, bone turnover markers, or adverse events between the two treatment groups. Conclusion. We have demonstrated that FT4, FT3, rT3, cholesterol, and SHBG show significantly different values on LT4 treatment compared with LT3 treatment in women with hypothyroidism and residual symptoms despite normal TSH levels. No differences in general or bone-specific adverse effects were demonstrated. This trial is registered with NCT03627611 in May 2018.

Research Article

Short-Term Adverse Pregnancy Outcomes in Women with Subclinical Hypothyroidism: A Comparative Approach of Iranian and American Guidelines

Introduction. Subclinical hypothyroidism during pregnancy can be associated with numerous adverse outcomes. The purpose of this study was to compare short-term adverse pregnancy outcomes in treated versus nontreated patients who fall within the numerical range of thyroid-stimulating hormone (TSH) between the Iranian and American reference ranges. Materials and Methods. Eighty pregnant women with a known level of antithyroid peroxidase (anti-TPO) and TSH levels of 2.5–3.9 mIu/L in the first trimester and 3–4.1 mIu/L in the second and third trimesters were enrolled in the study and randomly assigned into two groups including 41 patients in the intervention group and 39 in the control group. The intervention group was treated with levothyroxine at least 50 μg/day and the control group received no treatment. The data were analyzed by SPSS software version 23. Results. The only significant findings were a correlation between pregnancy loss frequency (p − 0.011) and/or increased TSH level in the follow-up period (p = 0.008) with anti-TPO antibody positivity. Forty-four percent of mothers with positive anti-TPO Ab needed treatment initiation with levothyroxine, based on Iranian guidelines, due to increased TSH level during the follow-up period. Conclusion. Untreated pregnant women with subclinical hypothyroidism, who were placed in the intermediate range of TSH, recommended by Iranian and American guidelines, did not show any significant difference in short-term adverse pregnancy outcomes compared to the treated patients. Positive anti-TPO Ab may play a role in the development of short-term complications in mothers with subclinical hypothyroidism or it may increase the likelihood of an increase in TSH level during pregnancy.

Research Article

Clinicopathological Profile of Thyroid Carcinoma in Young Patients: An Indonesian Single-Center Study

Introduction. Thyroid cancer is the third most common cancer that occurs in children and adolescents. Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy. Although the mortality rate of thyroid malignancy in children is usually low, the disease recurrence is higher in children with more severe clinical presentation than in adults. This study aimed to determine the demographic and clinicopathological characteristics and outcome of pediatric and adolescent patients with thyroid malignancy in Indonesia. Methods. The retrospective study included all patients diagnosed with thyroid carcinoma aged <20 years, from January 1, 2015, to December 31, 2019. Twenty-nine subjects fulfilled the inclusion and exclusion criteria. We retrieved baseline characteristics, pathology features, TSH and fT4 status, radioactive iodine therapy data, and patients’ outcomes. Then, data were analyzed using the chi-square or Fisher’s exact method. Results. We identified 29 eligible subjects, including 3 boys and 26 girls. The most common type of thyroid carcinoma was PTC (96.5%), and follicular type (31%) was the predominant variant of PTC. Lymph node involvement occurred in 24% of patients, while distant metastasis occurred in 17.2% of patients with PTC. Twenty-four (82.7%) patients had stage 1 disease. Disease recurrence was recorded in 31% of patients during the study period with a median follow-up time of 24 months. Conclusion. PTC is the most frequent type of thyroid carcinoma among children and adolescents. This malignancy has a low mortality rate, but the recurrence rate remains high among younger patients than adults even during a short-term follow-up analysis. Distant metastasis and lymph node involvement are commonly found in this age group.

Research Article

RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant

Background. The aim of this study was to identify germline mutation of the RET (rearranged during transfection) gene in patients with medullary thyroid carcinoma (MTC) and their first-degree relatives to find presymptomatic carriers for possible prophylactic thyroidectomy. Methods/Patients. We examined all six hot spot exons (exons 10, 11, 13, and 14–16) of the RET gene by PCR and bidirectional Sanger sequencing in 45 Iranian patients with MTC (either sporadic or familial form) from 7 unrelated kindred and 38 apparently sporadic cases. First-degree relatives of RET positive cases were also genotyped for index mutation. Moreover, presymptomatic carriers were referred to the endocrinologist for further clinical management and prophylactic thyroidectomy if needed. Results. Overall, the genetic status of all of the participants was determined by RET mutation screening, including 61 affected individuals, 22 presymptomatic carriers, and 29 genetically healthy subjects. In 37.5% (17 of 45) of the MTC referral index patients, 8 distinct RET germline mutations were found, including p.C634R (35.3%), p.M918T (17.6%), p.C634Y (11.8%), p.C634F (5.9%), p.C611Y (5.9%), p.C618R (5.9%), p.C630R (5.9%), p.L790F (5.9%), and one uncertain variant p.V648I (5.9%). Also, we found a novel variant p.H648R in one of our apparently sporadic patients. Conclusion. RET mutation detection is a promising/golden screening test and provides an accurate presymptomatic diagnostic test for at-risk carriers (the siblings and offspring of the patients) to consider prophylactic thyroidectomy. Thus, according to the ATA recommendations, the screening of the RET proto-oncogene is indicated for patients with MTC.

Research Article

Effect of Micronutrients on Thyroid Parameters

Micronutrients are involved in various vital cellular metabolic processes including thyroid hormone metabolism. This study aimed to investigate the correlation between serum levels of micronutrients and their effects on thyroid parameters. The correlation of serum levels of micronutrients and thyroid markers was studied in a group of 387 healthy individuals tested for thyroid markers (T4, T3, FT4, FT3, TSH, anti-TPO, RT3, and anti-Tg) and their micronutrient profile at Vibrant America Clinical Laboratory. The subjects were rationalized into three groups (deficient, normal, or excess levels of micronutrients), and the levels of their thyroid markers were compared. According to our results, deficiency of vitamin B2, B12, B9 and Vit-D25[OH] () significantly affected thyroid functioning. Other elemental micronutrients such as calcium, copper, choline, iron, and zinc () have a significant correlation with serum levels of free T3. Amino acids asparagine (r = 0.1765, ) and serine (r = 0.1186, ) were found to have a strong positive correlation with TSH. Valine, leucine, and arginine () also exhibited a significant positive correlation with serum levels of T4 and FT4. No other significant correlations were observed with other micronutrients. Our study suggests strong evidence for the association of the levels of micronutrients with thyroid markers with a special note on the effect of serum levels of certain amino acids.

Journal of Thyroid Research
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