Journal of Thyroid Research

Background. Bone turnover markers (BTMs) have emerged as a useful tool for monitoring bone remodeling activity in the skeleton, and their serum levels correlate with bone loss rates in osteoporotic and normal individuals. Whether the same holds for other metabolic bone diseases is still subject to discussion. Methods. We analyzed the relation between levels of BTMs and TSH in 79 females on thyroid hormone substitution therapy for hypothyroidism. Based on the reference range for TSH (0.2–4.0 mU/L) in our lab, we assessed BTMs in five different groups of patients based on the following criteria: (1) hypothyroidism (TSH >4.0); (2) TSH in the high normal range (1.0–4.0); (3) TSH in the low normal range (0.2–1.0); (4) TSH below the normal range (0.01–0.2); (5) TSH undetectable (<0.01). We studied the relationship between TSH and four different bone markers: procollagen type 1 N-terminal propeptide (PINP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin (OC), and bone specific alkaline phosphatase (BSAP). In a subgroup of patients, bone mineral density was assessed by a DXA scan. Results. PINP emerged as the most sensitive and dynamic BTM for assessment of bone turnover in this patient group, achieving significant rho values on nonparametric correlation analysis for both TSH (rho −0.47; ) and FT4 (rho 0.27; ). CTX and OC also revealed significant correlations to TSH, albeit with lower rho values (−0.37 and −0.24, respectively). Categorical analysis showed that bone turnover increased significantly, albeit with pronounced interindividual variability for TSH values below the lower limit of normal (0.2 mU/l), with the most severe affected being women exhibiting suppression of TSH. Further analysis of loss rates by DXA in a limited subgroup of patients showed that this was accompanied by accelerated bone loss. Conclusion. PINP is the most sensitive marker of bone turnover in thyroid disorders. TSH values below the lower limit of normal are associated with increased bone turnover and accelerated bone loss, however, with pronounced interindividual variations. Assessment of PINP may be a valuable tool in cases where there is concern about possible adverse effects of thyroid hormone substitution therapy on bone.

Objective. To evaluate whether thyroid nodule depth correlates with nondiagnostic results in ultrasound-guided fine needle aspiration cytopathology. Background. Many factors correlate with nondiagnostic ultrasound-guided fine needle aspiration cytology (FNAC) results, including older age, macrocalcification, small-sized nodules, aspirin medication, and cystic portion in more than 50% of the thyroid nodules. However, there are few studies which have examined whether there is a relationship between the depth of nodules and the percentage of nondiagnostic results in cytology (Bethesda category I). We conducted this study in order to investigate if such a correlation exists. Materials and Methods. FNAC was performed on 283 thyroid nodules between January 2019 and December 2020. Cytological analyses of the nodules were reviewed and sorted as nondiagnostic and diagnostic according to the Bethesda score. Patient files and ultra sound (US) scans were reviewed for clinical information (such as age, sex, and ethnic group) and sonographic features of nodules (such as depth, size, cystic portion, type of calcification, and echogenicity) and were compared between the nondiagnostic and diagnostic nodule results. The depth of a nodule was calculated as the shortest distance from the skin to the most superficial border of the nodule in the axial plane, using our medical center’s computer program, which allows reviewing all saved shots of the US scan. Results. Age, sex, and ethnicity were not significantly different between the nondiagnostic group and the diagnostic group (). Nodule diameter, cystic portion, calcification, and echogenicity were also not associated with the frequency of nondiagnostic results. The depth of nodules ≥9 mm was correlated with nondiagnostic US-guided FNA cytological results (OR = 2.55, ). Conclusions. Deep thyroid nodules correlated with nondiagnostic US-guided FNA cytological results. Further studies are needed for optimizing the approach to deep thyroid nodules in order to improve the efficacy of FNA in deep thyroid nodules.

Objective. Worldwide, 21 countries have insufficient iodine in their diets. Persistent iodine deficiency may result in hypothyroidism. The aim of this study is to determine whether iodine measurements can be used to determine the prevalence of iodine deficiency in patients with (subclinical) hypothyroidism compared to a control group. Design. A prospective cohort pilot study was performed at the Internal Medicine Outpatient Clinic of Isala, a large teaching hospital in Zwolle, the Netherlands. Patients. This study consisted of two groups of 24 adult patients each: a group of consecutive patients presenting with overt or subclinical hypothyroidism and a control group of euthyroid patients with type 1 diabetes mellitus. Measurements. All patients collected 24-hour urine. Iodine status was determined using urinary iodine concentration (UIC), urinary iodine excretion (UIE), and iodine creatinine ratio (I : Cr). Iodine deficiency was defined as an iodine concentration <100 µg/L for UIC, iodine level <125 µg for UIE, and <0.13 µmol/mmol for I : Cr. Results. According to UIE and UIC measurements, 54.2% of hypothyroid patients were iodine-deficient compared to 41.7–45.8% in the control group. According to the I : Cr measurement 91.7% of hypothyroid patients were iodine-deficient compared to 87.5% in the control group. No significant difference was seen between the two groups. No correlation was found between thyroid-stimulating hormone (TSH) level and iodine deficiency. Conclusions. Iodine deficiency is prevalent in both hypothyroid patients and euthyroid patients. Because there is no significant difference between the groups, a single 24-hour urine or spot urine sample to determine UIC, UIE, and I : Cr, seems not suitable to determine iodine status in an individual participant.

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.

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.

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.