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PURPOSE: The study aims to investigate the relationship between thyroid-stimulating hormone (TSH) and remnant cholesterol (RC) in euthyroid adults. METHODS: The adults who were recruited for the study had undergone physical examination at Beijing Chao-Yang Hospital. High RC levels were defined as the upper quartile of RC levels in males and females, respectively. The relationship between TSH and RC was assessed using the logistic and linear regression models. RESULTS: A total of 29,708 adults (14,347 males and 15,361 females) were enrolled in this study. RC ≥ 0.77 mmol/L in males and RC ≥ 0.60 mmol/L in females were defined as high RC levels. With increasing serum TSH levels, the percentage of adults with high RC levels increased. The odds ratios (ORs (95% confidence intervals (CIs)) for high RC levels increased as TSH quartiles (Q) rose after full adjustments [males: Q2 1.11 (1.00-1.24), P < 0.05; Q3 1.03 (0.92-1.15), P > 0.05; Q4 1.25 (1.12-1.40), P < 0.001; and females: Q2 1.07 (0.96-1.20), P > 0.05; Q3 1.17 (1.05-1.31), P < 0.01, Q4 1.33 (1.20-1.48), P < 0.001, all P for trend < 0.001], using Q1 as the reference. CONCLUSION: Higher TSH levels were independently associated with higher RC levels in euthyroid adults, this underscoring the significance of regulating TSH levels appropriately.

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PURPOSE: Hashimoto's thyroiditis (HT) is one of the most common causes of thyroid dysfunction in iodine sufficient worldwide areas, but its molecular mechanisms are not completely understood. To this regard, this study aimed to assess serum levels of miRNA-29a (miR-29a) and transforming growth factor beta 1 (TGFß1) in HT patients with different patterns of thyroid function. METHODS: A total of 29 HT patients, with a median age of 52 years (21-68) were included. Of these, 13 had normal thyroid function (Eu-HT); 8 had non-treated hypothyroidism (Hypo-HT); 8 had hypothyroidism on replacement therapy with LT4 (subst-HT). All patients had serum miR-29a assayed through qRT-PCR and serum TGFß1 assayed by ELISA. RESULTS: Serum miR-29a levels were significantly down-regulated in patients with Hypo-HT compared to Eu-HT patients (P < 0.01) and subst-HT patients (P < 0.05). A significant negative correlation was detected between serum miR-29a levels and TSH levels (r = -0.60, P < 0.01). Serum TGFß1 levels were significantly higher in Hypo-HT than both Eu-HT (P < 0.01) and subst-HT patients (P < 0.05). A negative correlation was observed between serum miR-29a and TGFß1 (r = -0.75, P < 0.01). CONCLUSIONS: In conclusion, Hypo-HT patients had lower levels of serum miR-29a and higher levels of TGFß1 in comparison with Eu-HT patients. Worthy of note, subst-HT patients showed restored serum miR-29a levels compared with Hypo-HT group, associated with lower serum TGFß1. These novel findings may suggest a possible impact of replacement therapy with levothyroxine on serum miR-29a levels in HT.

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BACKGROUND: Central hypothyroidism and autoimmune hyperthyroidism are contrasting pathologies requiring careful hormone monitoring for restoring euthyroidism. Their coexistence is rare and challenging for clinicians [1, 2]. CASE REPORT: We have, herein, presented the case of a 41-year-old female patient with an unremarkable clinical history except for chronic autoimmune thyroiditis in euthyroidism. At the 21st week of gestation, she experienced a spontaneous abortion. The patient underwent an assessment of the uterine cavity, which was complicated by bleeding and hypotensive shock. In the postoperative course, the patient presented worsening headache, and after an MRI, the diagnosis of pituitary apoplexy due to an ischemic-hemorrhagic base was made. Laboratory tests showed anterior panhypopituitarism. Multiaxial replacement therapy was initiated with hydrocortisone, levothyroxine (LT4), and subsequently estrogen-progestin and GH. After two years of good recovery with stable LT4 dosage, the patient experienced palpitations and fine tremors; blood tests showed hyperthyroidism with suppressed Thyroid-stimulating Hormone (TSH) levels and elevated free thyroid fractions and anti-TSH receptor antibodies. Diagnosis of Graves' disease was made, and therapy with methimazole was initiated. During antithyroid therapy, TSH remained persistently suppressed, consistent with the underlying central hypothyroidism. This condition required close follow-up, with monitoring based solely on free thyroid hormone levels. After six months of antithyroid therapy, disease remission was achieved, with negative antibodies and mild hypothyroxinemia. Therefore, methimazole was discontinued and replacement therapy gradually resumed until optimal hormone levels were reached. CONCLUSION: This case is unique demonstrating autoimmune hyperthyroidism to coexist with central hypothyroidism, rendering TSH a misleading disease progression indicator. Consequently, managing Graves' disease has become more complex and challenging.

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Background: Autoimmune thyroid disease (AITD) is the main cause of hypothyroidism in women of childbearing age. Bisphenol A (BPA) is an environmental factor affecting AITD. This study aims to investigate relationship between BPA and AITD in women of childbearing age, thereby contributing novel evidence for the prevention of hypothyroidism in this specific demographic. Methods: A total of 155 women of childbearing age were enrolled in this study, including the euthyroid group comprised 60 women with euthyroidism and thyroid autoantibodies negativity and the AITD group consisted of 95 women with euthyroidism and at least one thyroid autoantibody positivity. The general information, thyroid function, thyroid autoantibodies, and thyroid ultrasound results of the two groups of women of childbearing age were recorded. Urinary BPA and urinary BPA/creatinine were detected. The difference of BPA levels between the two groups was compared. logistic regression was used to analyze the correlation between BPA and AITD. Results: The proportion of multiparous and serum thyroid stimulating hormone levels were significantly higher in the AITD group compared to the euthyroid group. Logistic regression analysis revealed that BPA levels did not exhibit a statistically significant association with AITD. Spearman correlation analysis revealed a statistically significant correlation between BPA and urinary iodine levels (r=0.30, P < 0.05), as well as a correlation between urinary BPA and free tetraiodothyronine (FT4) levels (r=0.29, P < 0.05). Conclusion: This study revealed a correlation between urinary BPA levels and FT4 levels. However, it did not establish a relationship between BPA and AITD in women of childbearing age.

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OBJECTIVE: Thyroid hormone under-replacement and over-replacement are associated with adverse health outcomes. This systematic review aimed to evaluate the extent of thyroid hormone replacement adequacy for patients with known hypothyroidism in real-word settings, excluding those receiving thyroid hormone suppressive therapy as thyroid cancer treatment. DESIGN: Four electronic databases (Embase [Ovid], Medline [Ovid], PubMed and SCOPUS) were searched for published and unpublished observational studies until 12 December 2022. The results of the studies were meta-analysed to calculate pooled prevalence estimates for thyroid hormone supplementation adequacy, over-replacement and under-replacement. Quality assessment of studies was performed using the Joanna-Briggs appraisal tool for prevalence studies. RESULTS: Seven studies with a total of 4230 patients were eligible for quantitative synthesis. The pooled prevalence estimates of adequate thyroid replacement, over-replacement and under-replacement were 0.55 (95% confidence interval [CI]: 0.49-0.60, p = .001), 0.20 (95% CI: 0.14-0.27, p = .001) and 0.24 (95% CI: 0.13-0.36, p = .001), respectively. Four studies subclassified hypothyroidism and hyperthyroidism into overt and subclinical. The pooled prevalence of overt and subclinical hyperthyroidism was 0.04 (95% CI: 0.00-0.11, p = .01) and 0.17 (95% CI: 0.09-0.27 p = .001), respectively. For overt and subclinical hypothyroidism, the pooled prevalence was 0.02 (95% CI: 0.01-0.03, p = .001) and 0.20 (95% CI: 0.12-0.29, p = .001), respectively. CONCLUSIONS: On average, approximately half of patients with hypothyroidism are only treated to target euthyroidism. In real-world practice, a significant number of patients are over-treated or under-treated, leading to adverse healthcare outcomes. It is imperative that more effective thyroid monitoring strategies be implemented, with an emphasis on primary care thyroid function monitoring, to minimise inappropriate thyroid replacement treatments and optimise healthcare outcomes at a population level.

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Background Thyroid hormone replacement (THR) in athyreotic patients post-thyroidectomy due to thyroid cancer might seem like a straightforward clinical issue to address. To investigate the impact of THR on enhancing thyroid-stimulating hormone (TSH) levels, we conducted a clinical audit, tailoring the dosage based on patient weight and aligning with the standards outlined by the National Institute for Health and Care Excellence and the American Thyroid Association guidelines. Methodology This retrospective and prospective audit analyzed outpatient clinic records for hormone replacement therapy (HRT) post-total thyroidectomy. Retrospective data from March to May 2022 were collected, followed by prospective data after interventions adjusting HRT based on patient weight to digitize clinic notes. The second phase involved changes for 20 scheduled thyroidectomy patients among the total 37 included in the study. Results The thyroid profiles of both groups in the initial and subsequent cycles, treated with adjusted doses of THR, exhibited normal levels of thyroid hormones and calcium. No substantial differences were observed between the groups. On multivariate logistic regression analysis, we found that older age, male sex, body mass index, and preoperative TSH level were the only significant predictors of the need for hormonal therapy. Conclusions Optimal dose of THR after total thyroidectomy had a positive effect on TSH levels in hypothyroidism patients. Hence, THR should be prescribed according to patient weight based on standards and guidelines.

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BACKGROUND: Little is known about the association of dietary patterns with thyroid function. Since thyroid function and cardiometabolic variables are inter-related, we investigated whether cardiometabolic-related dietary patterns are associated with thyroid function. METHODS: This cross-sectional study included 3520 Tehran Lipid and Glucose Study participants. Reduced rank regression was used to find dietary patterns with body mass index, serum fasting glucose, triglycerides, HDL-C, and systolic and diastolic blood pressures as response variables. Two patterns were retained, one based on 35 food groups (native-based pattern) and the other based on the European Prospective Investigation into Cancer and Nutrition Germany (EPIC) food grouping (n = 33). A confirmatory cardio-metabolic dietary pattern was also created according to the weight of food groups proposed by the Framingham Offspring Study (FOS). The association of each pattern with thyroid-stimulating hormone (TSH), free thyroxine, and thyroid peroxidase antibody (TPOAb) and the odds of thyroid dysfunction was examined by linear and logistic regression, respectively. RESULTS: The two exploratory dietary patterns were highly correlated and associated with greater TSH levels in euthyroid participants. The adjusted odds ratio (95% CI) of subclinical hypothyroidism per one standard deviation was 1.14 (1.01, 1.28) for the native-based pattern and 1.16 (1.03, 1.31) for the EPIC-based pattern. The odds of subclinical hypothyroidism was significantly greater in the second and third tertiles of the native-based pattern compared to the first tertile in the adjusted model (p-trend = 0.005). The odds of subclinical hypothyroidism increased across the tertiles of the EPIC-based pattern, but the odds was significantly higher only in tertile 3 compared to tertile 1, with an OR (95% CI) of 1.44 (1.07, 1.94) in the adjusted model. The adjusted odds of clinical hypothyroidism were greater in tertile 3 of the native-based pattern compared with tertile 1 (OR = 1.65, 95% CI 1.04, 2.62). The patterns were unrelated to hyperthyroidism or TPOAb positivity. The FOS-based confirmatory score was unrelated to thyroid function. CONCLUSIONS: A diet high in fast foods, soft drinks, and legumes and low in confectionery, potatoes, butter, and jam and honey was associated with higher TSH levels in euthyroidism and higher odds of subclinical hypothyroidism.

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PURPOSE: Inconsistencies in the medical management of hypothyroidism have been reported between endocrinologists in different countries. This study aimed to identify the attitudes of Latin America thyroid specialists towards the use of thyroid hormones. METHODS: Online survey of members of the Latin America Thyroid Society. RESULTS: 81/446 (18.2%) completed the questionnaire. Levothyroxine (LT4) was the initial treatment of choice for all respondents. 56.8% would consider LT4 use in biochemically euthyroid patients: infertile women with elevated anti-thyroid antibodies (46.9%), resistant depression (17.3%) and growing goiter (12%). Most respondents preferred tablets (39.5%) over liquid formulations (21.0%) or soft gel capsules (22.2%) and would not consider switching formulations in patients with persistent symptoms. 39.5% would never use LT4 + liothyronine (LT3) combination therapy in symptomatic euthyroid patients, due to low quality evidence for benefit. 60.5% reported that persistence of symptoms despite normal TSH is rare (below 5% of patients) and its prevalence has been stable over the last five years. Psychosocial factors (84.0%), comorbidities (86.4%) and the patient unrealistic expectation (72.8%) were considered the top three explanations for this phenomenon. CONCLUSION: LT4 tablets is the treatment of choice for hypothyroidism. A significant proportion of respondents would use LT4 in some groups of euthyroid individuals, contrasting the recommendations of the major clinical practice guideline indications. LT4 + LT3 combination treatment in euthyroid symptomatic patients was considered by nearly 50%. Practices based on weak or absent evidence included use of thyroid hormones for euthyroid subjects by 56.8% of respondents and use of LT4 + LT3 treatment by 60.5% of respondents for patients with persistent symptoms. In contrast to many European countries, LATS respondents report a low and unchanged proportion of dissatisfied patients over the last five years.

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Too high or too low thyroid-stimulating hormone (TSH) has been associated with the progress and prognosis of coronary artery disease (CAD). However, whether TSH within its normal reference range plays a role in the severity of CAD remains unclear. In this observational study, we explored the potential relationship of hypersensitive TSH (hs-TSH) with the severity of CAD in euthyroid patients with or without diabetes mellitus. A total of 7357 CAD patients with euthyroidism were enrolled in this study. Of those, 1997 had diabetes mellitus. The severity of CAD was evaluated through the presence of myocardial infarction (MI) and the severity of coronary lesions, which was calculated using the Gensini score (GS). Logistic regression models treating hs-TSH as a categorical variable and restricted cubic spline analyses treating it as a continuous variable were used to evaluate the associations of hs-TSH with the severity of CAD. The propensity score matching method was used to further validate the differences between diabetic and nondiabetic patients. CAD patients with diabetes mellitus had lower levels of hs-TSH (1.6 (0.97-2.53) vs 1.67 (1.00-2.64)) in serum compared with CAD patients without diabetes mellitus. Meanwhile, hs-TSH was independently related to the severity of CAD. In CAD patients with vs without diabetes mellitus, the U-shaped relationship between hs-TSH and MI was more prominent in patients without diabetes mellitus, and the significant U-shaped association between higher GS and hs-TSH remained only in nondiabetes. Therefore, hs-TSH within the normal reference range has a U-shaped association with the severity of CAD in nondiabetic patients, which is markedly diluted in diabetic patients.

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OBJECTIVE: Patients with Graves' disease who remain hyperthyroid under the treatment of antithyroid drugs (ATD) or cannot tolerate ATD usually receive radioactive iodine (RAI) to control disease activity. This pilot study aimed to identify predictors of prolonged euthyroidism > 12 months after receiving RAI. METHODS: Demographic, clinical, and laboratory data from 117 patients receiving RAI were retrospectively collected, including age, gender, body surface area, smoking status, free thyroxine, thyrotropin, thyrotropin binding inhibiting immunoglobulin, microsomal antibody, thyroglobulin antibody, medication history, and thyroid volume. Only 85 patients without missing values were included in statistical analysis. The calculated RAI dose was the estimated thyroid volume × 0.4. The difference and ratio between the actual and calculated RAI doses were examined. A stepwise logistic regression analysis was conducted to identify important predictors of prolonged euthyroidism > 12 months. The cut-off values for discretizing continuous covariates were estimated by fitting generalized additive models. RESULTS: Among the 85 patients on RAI, 18 (21.2%) achieved prolonged euthyroidism > 12 months, 38 (44.7%) remained hyperthyroid with decreased ATD doses, but 29 (34.1%) suffered permanent hypothyroidism and needed long-term levothyroxine. Logistic regression analysis revealed that patients with age > 66 years, 33 < age ≤ 66 years, quitting smoking vs nonsmoking or current smoking, 600 < micorsomal antibody ≤ 1729 IU/mL, 47% < thyrotropin binding inhibiting immunoglobulin ≤ 81%, 7 < thyroglobulin antibody ≤ 162 IU/mL, 0.63 < ratio between actual and calculated RAI doses ≤ 1.96, or taking hydroxychloroquine would have a higher chance of reaching prolonged euthyroidism > 12 months after receiving RAI. Its area under the Receiver Operating Characteristic (ROC) curve was 0.932. CONCLUSION: Patients with Graves' disease who received an actual RAI dose close to the calculated RAI dose achieved prolonged euthyroidism > 12 months if they also took hydroxychloroquine during RAI treatment.

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BACKGROUND: Sleep plays a critical role in maintaining human health. This study aimed to explore the association between sleep status and thyroid nodules. METHODS: A total of 2414 individuals aged 18 or older with euthyroidism were enrolled in this community-based survey. Sleep status was self-reported. Thyroid ultrasonography was performed to measure nodules. Multiple logistic analyses were applied to adjust for confounding factors. RESULTS: The percentages of thyroid nodules among individuals who slept <5 hours, 5-8 hours, and >8 hours per night were 57.79% (115/199), 44.19% (833/1885) and 42.73% (141/330), respectively (p = 0.001). Individuals who slept <5 hours per night had a significantly higher percentage of thyroid nodules than those who slept 5-8 hours per night (57.79% vs. 44.19%, p = 0.001) or >8 hours per night (57.79% vs. 42.73%, P < 0.001). However, no similar result was shown between individuals who slept >8 hours and 5-8 hours per night (42.73% vs. 44.19%, p = 0.621). Multiple logistic analysis showed that a sleep duration of <5 hours per night was significantly associated with thyroid nodules (odds ratio (OR) 1.643, 95% confidence interval (CI) 1.084-2.490, p = 0.019) when compared to a sleep duration of >8 hours per night. However, a sleep duration of <5 hours per night was not associated with thyroid nodules compared to a sleep duration of 5-8 hours (OR 1.294, 95% CI 0.918-1.824, p = 0.141). Similarly, no significant differences were seen among sleep duration per day, time of falling asleep, habit of daytime napping or thyroid nodules in multiple logistic analyses (all p > 0.05). CONCLUSIONS: Short nighttime sleep duration was associated with thyroid nodules in our community-based population. Screening for thyroid nodules among these individuals is recommended.

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OBJECTIVES: It is well recognized that overt thyroid dysfunction is associated with changes in body mass index (BMI). However, there is ongoing debate regarding the influence of thyroid stimulating hormone (TSH) on BMI, in euthyroid subjects. The aim of this study is to examine the association of TSH with BMI in an outpatient population without evidence of thyroid disease. METHODS: Cross-sectional study conducted in an Endocrinology Department. We identified the latest TSH and BMI measurements in 923 patients from the reference euthyroid population. All patients with positive thyroid autoimmunity and nodules were excluded. We performed a linear regression analysis using SPSSv.025. RESULTS: 923 adult patients were evaluated. 79.4% were males, with a mean age of 67.6 years old. Mean TSH level was 1.78 mIU/L and mean BMI was 29.2 kg/m2. A significant negative correlation between serum TSH concentration and BMI was evident (p=0.04; r=-0.067). Statistical significance was lost when performing subgroup analysis, for males and females (p=0.19 and p=0.075), elderly (≥65 years) and non-elderly (p=0.55 and p=0.32) and also obese (BMI ≥30 kg/m2) and non-obese (p=0.39 and p=0.13). CONCLUSIONS: The relationship between BMI and TSH is not consensual in the literature. This study included a large cohort sample of euthyroid patients, majority men and with negative autoimmunity. Our results support the hypothesis that variation in thyroid status within the normal range, could have a negative effect on BMI, contrary to most published studies.

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【Objective】 To investigate the correlation between body composition and thyroid function indicators in type 2 diabetic patients with euthyroidism of different genders. 【Methods】 Type 2 diabetic patients with euthyroidism who were hospitalized in the Endocrinology Department of The Second Affiliated Hospital of Xi’an Jiaotong University from February 2016 to September 2018 were enrolled in this study. Bioelectric impedance analysis was used to measure body composition, and the thyroid function indicators (FT3, FT4, and TSH) were tested. The male and female subjects were matched according to the ratio of 2:1 using the propensity score matching method, and the correlation between body composition and thyroid function indicators was studied in different genders by correlation analysis. 【Results】 The basal metabolic rate, trunk fat mass, fat-free mass, fat-free mass index, bone mass, water mass, total body muscle mass, skeletal muscle mass, and skeletal muscle index were positively correlated with FT3 in male patients (P<0.05). The percentage of body fat mass and fat mass index were positively correlated with FT3 and TSH (P<0.05), and the percentages of lean mass, water mass, and total body muscle mass were negatively correlated with FT3 and TSH (P<0.05), and the basal metabolic rate was negatively correlated with FT4 (P<0.05) in female. 【Conclusion】 In euthyroid type 2 diabetic patients, the correlation between body composition and thyroid function indicators are different between males and females. In males, only FT3 is positively correlated with basal metabolic rate, trunk fat mass, and fat free-related composition; while in females, both FT3 and TSH are positively correlated with fat-related composition, but negatively correlated with fat-free-related composition.

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PURPOSE: To estimate the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and to evaluate the associations between thyroid parameters, MAFLD and liver fibrosis in euthyroid patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: Overall, 776 patients with newly diagnosed T2DM and 120 subjects without diabetes were included. All the participants were euthyroid, and were categorized as non-MAFLD and MAFLD. Demographic information, biochemical parameters, and serum thyroid hormones were collected. The thyroid hormone sensitivity indices were calculated. MAFLD was defined according to abdominal ultrasound and clinical manifestations. Noninvasive fibrosis indices were calculated to identify advanced liver fibrosis. RESULTS: The prevalence of MAFLD was significantly higher in patients with T2DM than in subjects without diabetes. Levels of free triiodothyronine (FT3) and FT3 to free thyroxine (FT4) ratio were significantly higher in subjects with MAFLD. In patients with T2DM, levels of thyroid stimulating hormone (TSH), Thyroid feedback quantile-based index (TFQIFT3) calculated using FT3 and TSH, thyrotroph T3 resistance index (TT3RI) and thyrotroph T4 resistance index (TT4RI) were significantly higher in subjects with MAFLD. The prevalence of MAFLD increased with the rise of FT3, FT3/FT4, TSH, and sensitivity to thyroid hormone indices (TFQIFT3, TT3RI, and TT4RI). But significant correlations were not found between thyroid hormones, sensitivity to thyroid hormones and MAFLD, after adjustment for BMI and HOMA-IR. The incidence of advanced fibrosis tended to increase as the rise of TSH and sensitivity to thyroid hormone indices (TFQIFT3, TT3RI, TT4RI, and TSHI). CONCLUSION: MAFLD was prevalent in euthyroid patients with newly diagnosed T2DM. Higher normal FT3, TSH and impaired sensitivity to thyroid hormones are associated with increased incidence of MAFLD, being dependent on other metabolic factors.

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Objectives: The study assessed gustatory functions in patients with primary hypothyroidism who are euthyroid on supplemental hormone therapy with levothyroxine over six months' duration and to evaluate the association of gustatory dysfunction, if any, with the serum TSH levels. Design: This analytical community-based cross-sectional study was conducted in April 2021, following participants' ethical approval and written informed consent. Setting: The study was conducted in a tertiary health care centre in Bangalore, Karnataka, India. Participants: Sixty-eight subjects participated in this study: 34 primary hypothyroid patients and an equal number of healthy controls. Interventions: Gustatory sensations were assessed by the triple drop test, and scores were given depending on the identification of the tastants (sweet, sour, salty, and bitter). The taste scores were compared, and the association between TSH levels and gustatory parameters were evaluated. Results: Overall taste scores were lesser in hypothyroid patients. This finding depicted that their taste thresholds were increased and were statistically significant (p < 0.001), though the association between the degree of hypogeusia and TSH levels was not statistically significant. Conclusion: Patients with primary hypothyroidism can suffer from hypogeusia, which may revert to normal once they achieve euthyroid status with levothyroxine supplementation. However, this has not been conclusively shown in studies. Our study concluded that hypogeusia was present in primary hypothyroidism despite patients being euthyroid on hormone supplementation, and it was not dependent on the serum TSH levels. Funding: None declared.

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BACKGROUND: Evidence regarding thyroid-stimulating hormone (TSH) levels within the normal range and mortality in adults with diabetes is scarce. This study aimed to identify the association between TSH levels and cardiovascular disease (CVD) and all-cause mortality among euthyroid patients with diabetes. METHODS: This prospective cohort study included 1830 adults with diabetes from the Third National Health and Nutrition Examination Survey III. Mortality outcomes were ascertained by linkage to National Death Index records through December 31, 2019. Participants were categorized by tertiles of TSH levels (low-normal, 0.39-1.30 mIU/L; medium-normal, 1.30-2.09 mIU/L; high-normal, 2.09-4.60 mIU/L). Multivariable Cox proportional hazards models were used to explore the association between TSH levels within the normal range and overall and CVD mortality. Furthermore, restricted cubic spline analyses were used to determine the nonlinear relationship between TSH levels and mortality. RESULTS: During a median follow-up of 17.1 years, 1324 all-cause deaths occurred, including 525 deaths from CVD. After multivariate adjustment, a U-shaped relationship was observed between TSH levels in euthyroid status and all-cause or CVD mortality among patients with diabetes (both P < 0.05 for nonlinearity). Compared with participants with medium-normal TSH levels, those with high-normal TSH levels had a significantly higher risk of all-cause (hazard ratio, 1.31; 95% confidence interval, 1.07-1.61) and CVD (1.52; 1.08-2.12) mortality. Similarly, low-normal TSH levels also increased all-cause (1.39; 1.12-1.73) and CVD (1.69; 1.17-2.44) mortality risk. In stratum-specific analyses, we found that high-normal TSH levels were associated with higher mortality risk in younger (< 60 years) patients with diabetes but not in older (≥ 60 years) participants. CONCLUSION: Low- and high-normal serum TSH levels were associated with increased all-cause and CVD mortality in euthyroid adults with diabetes. Further studies are needed to confirm the present observation in a wider population.

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Thyrotoxicosis can cause acute chest pain without ST changes in EKG due to coronary artery spasm. Its diagnosis can be particularly challenging as the symptoms may mimic acute coronary syndrome. The diagnosis of coronary artery spasm is confirmed by coronary angiography. The use of intracoronary nitroglycerin can relieve spasms and reveal the true extent of coronary artery disease. We present a case of a perimenopausal woman with newly diagnosed hyperthyroidism who presented with chest pain. Coronary angiography showed spasm of the left anterior descending artery which was relieved by intracoronary nitroglycerin.  Hyperthyroidism is associated with a spectrum of cardiovascular manifestations ranging from relatively benign palpitations to cardiac arrest. Rarely, it has been associated with episodic angina which indicates myocardial ischemia secondary to coronary artery spasm. Thyrotoxicosis-induced coronary artery spasm is a rare condition. Coronary artery spasm might masquerade as acute coronary syndrome, and coronary angiography is usually necessary to rule out myocardial infarction. In patients with risk factors for developing thyrotoxicosis-induced coronary artery spasm, any stenosis found on coronary angiography must not be assumed to be coronary artery disease only, and the possibility of coronary artery spasm must be explored. Our case emphasizes the use of intraprocedural nitroglycerin in these patients, which can relieve the spasm and reveal the true extent of coronary artery disease. Restoration of euthyroidism is the cornerstone of management and abates the need for long-term coronary vasodilator medications. Early diagnosis and optimal management have a favorable prognosis in these patients.

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OBJECTIVE: The significance of subclinical hypothyroidism (SCH) is largely due to its potential risk for developing overt hypothyroidism (OH). Investigations are still exploring predictive factors contributing to the progression of SCH to OH, particularly in patients with mildly elevated serum thyrotropin (TSH). We aimed to clarify the natural history of SCH and the predictive factors of its progression, based on the grade of SCH severity. METHODS: This study was conducted within the framework of the Tehran Thyroid Study (TTS), in which 5783 individuals aged ≥ 20 years were followed. After applying exclusion criteria, data of 270 SCH subjects remained for the analysis. Thyroid function tests were assessed at baseline and every 3 years. RESULTS: Of 270 participants with SCH, 239 (88.5%) had TSH level between 5.06 and 10 mU/L, and 31 (11.4%) had TSH ≥ 10 mU/L. During a median follow-up of 10 years, 40% had TSH within the reference range, 44% maintained elevated TSH, and 16% had added low T4 to the elevated TSH. The annual incidence rate of progression to OH was 22.3 (16.5-101.9) per 1000 person-years [18 (12.6-25.6) for those with TSH 5.07-9.9 mU/L and 57.8 (22.8-101.9) for patients with TSH ≥ 10 mU/L per 1000 person-years (P = 0.001)]. After adjusting age, sex, body mass index (BMI), thyroid peroxidase antibody (TPOAb), and serum TSH, only TPOAb positivity (HR: 2.31; 95% CI 1.10-4.83, P = 0.026) and baseline TSH level ≥ 10 mU/L (HR: 5.14; 95% CI 2.14-12.3, P < 0.001) remained as predictors for development of OH. In patients with TSH 5.07-9.9 mU/L, TPOAb positivity was associated with an increased risk of OH (HR: 2.41; 95% CI 1.10-5.30, P = 0.027). However, in patients with TSH ≥ 10 mU/L, TPOAb positivity was not a predictor (P = 0.49). CONCLUSION: TPOAb and not TSH are associated with the development of OH in individuals with serum TSH below 10 mU/L, and follow-up at regular intervals is recommended in TPOAb-positive individuals with TSH between 5 and 10 mU/L.

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OBJECTIVE: The aim of this study was to compare the "time to euthyroidism" and "time spent in euthyroidism" following methimazole (MMI) and radioactive iodine (RAI) treatments. METHODS: Three hundred fifty-eight patients with hyperthyroidism, 178 who underwent long-term MMI treatment and 180 patients who underwent RAI treatment, were analyzed. The time to normalization of increased serum values of free thyroxine and triiodothyronine and suppressed serum thyroid-stimulating hormone (TSH) values as well as the percentage of time that the thyroid hormone levels remained within normal ranges during a mean follow-up time of 12 years were compared. RESULTS: The mean time to euthyroidism was 4.59 ± 2.63 months (range, 2-16 months) in the MMI group and 15.39 ± 12.11 months (range, 2-61 months) in the RAI group (P < .001). During follow-up, the percentage of time spent in euthyroidism was 94.5% ± 7.3% and 82.5% + 11.0% in the MMI and RAI groups, respectively (P < .001). Serum TSH values above and below the normal range were observed in 5.3% and 0.2% of patients, respectively, in the MMI group and 9.8% and 7.7% of patients, respectively, in the RAI group (P < .001). The time to euthyroidism and the percentage of time spent in euthyroidism in 40 RAI-treated patients with euthyroidism were similar to those in the MMI group and significantly shorter than those in the RAI-treated hypothyroid and relapsed subgroups. In patients who continued MMI therapy for >10 years, the percentage of time spent in euthyroidism was >99%. CONCLUSION: In our cohort of selected patients, MMI therapy was accompanied by faster achievement of the euthyroid state and more sustained normal serum TSH levels during long-term follow-up compared with RAI therapy.

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