Adequacy of thyroid hormone replacement for people with hypothyroidism in real-world settings: A systematic review and meta-analysis of observational studies.

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 DESIGN: Four electronic databases (Embase [Ovid], Medline [Ovid], PubMed and SCOPUS) were searched for published and unpublished observational studies until 12 December 2022.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.

Predictors of Prolonged Euthyroidism After Radioactive Iodine Treatment for Graves' Disease: A Pilot Study.

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.

TSH levels within the normal range and risk of cardiovascular and all-cause mortality among individuals with diabetes.

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.

Use of thyroid hormones in hypothyroid and euthyroid patients: a 2020 THESIS questionnaire survey of members of the Czech Society of Endocrinology.

BACKGROUND: Inconsistencies in the management of hypothyroidism have been reported among endocrinologists in different European countries. Aim of this study was to explore Czech endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients. METHODS: We used a web-based survey containing 32 questions regarding the use of thyroid hormones. Four-hundred thirty-two members of the Czech Society of Endocrinology received an e-mail invitation to participate in the survey. RESULTS: We received and analysed 157 responses (112 females and 45 males) from the 432 members (36.3%). According to 99.4% of the respondents, levothyroxine (LT4) is the primary drug of choice for the treatment of hypothyroidism. Liothyronine (LT3) was used in clinical practice by 29.9% of responders. According to 90.5% of respondents, thyroid hormones may be indicated in biochemically euthyroid patients. Female physicians prescribe thyroid hormones in euthyroid infertile women with high antibody levels more frequently than male physicians (P = 0.003). Most Czech endocrinologists (76.4%) consider combined therapy with LT4 and LT3 in various clinical scenarios, but only 1 of 29 hypothyroid physicians (3.5%) would recommend it to their patients, and only 4 out of 128 respondents (3.1%) would consider LT3 or desiccated thyroid for themselves, if diagnosed with hypothyroidism. CONCLUSION: LT4 is the primary thyroid hormone used in the Czech Republic for treatment of hypothyroidism. At variance with thyroid guideline recommendations, Czech endocrinologists are quite liberal when prescribing thyroid hormones to euthyroid patients and in the use of LT4/LT3 combination treatment for hypothyroid patients with persisting symptoms.

Time to Normalization and Sustainable Normal Serum Thyrotropin Concentrations in Patients with Hyperthyroidism: Comparison of Methimazole and Radioactive Iodine Treatments.

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.

Natural history of subclinical hypothyroidism and prognostic factors for the development of overt hypothyroidism: Tehran Thyroid Study (TTS).

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.

Normalisation of serum TSH doesn't represent true euthyroidism for patients on levothyroxine treatment.

OBJECTIVE: To evaluate whether normalisation of serum thyroid-stimulating hormonelevels with levothyroxine is related with metabolic parameters and psychologic wellbeing. METHODS: The observational, case-control study was conducted from to May to July 2019 in the outpatient thyroid clinics of Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey, and comprised of hypothyroid patients in the euthyroid state with levothyroxine treatment and euthyroid controls. Psychological wellbeing was assessed using the General Health Questionnaire-12, and metabolic parameters with lipid levels and body composition were analysed for both the groups. Data was analysed using SPSS 25. RESULTS: Of the 159 subjects, 110(69%) were cases with a mean age of 50.1±11.7 years, and 49(31%) were controls with a mean age of 47.3±15.2 years. There was no significant difference related to thyroid-stimulating hormone levels between the groups (p=0.191). Free throxine levels were significantly higher in the cases, while free triiodothyroinine levels were higher in the controls (p<0.001). Total cholesterol and triglycerides levels were significantly higher in the cases than the controls (p<0.05). The cases had lower basal metabolic rate and fat free mass than the controls, but the difference was not significant (p>0.05). The cases scored higher in terms of wellbeing than the controls, but the difference was not significant (p>0.05). CONCLUSIONS: Thyroid hormone replacement needs to be adjusted to provide a satisfactory treatment for hypothyroid patients with normal thyroid-stimulating hormone levels who remain clinically and biochemically asymptomatic. In symptomatic patients, peripheral parameters of hypothyroidism, such as lipid levels, physiological symptoms and quality of life, might be useful in determining the levothyroxine dose and bringing the thyroid-stimulating hormone level within the normal range.

Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society.

PURPOSE: The standard treatment of hypothyroidism is levothyroxine (LT4), which is available as tablets or soft-gel capsules in Denmark. This study aimed to investigate Danish endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients. METHODS: An e-mail with an invitation to participate in an online survey investigating practices about substitution with thyroid hormones was sent to all members of the Danish Endocrine Society (DES). RESULTS: Out of 488 eligible DES members, a total of 152 (31.2%) respondents were included in the analysis. The majority (94.1%) of responding DES members use LT4 as the treatment of choice. Other treatment options for hypothyroidism are also used, as 58.6% prescribe combination therapy with liothyronine (LT3) + LT4 in their clinical practice. LT4 + LT3 combination is preferred in patients with persistent symptoms of hypothyroidism despite biochemical euthyroidism on LT4 treatment. Over half of the respondents answered that thyroid hormone therapy is never indicated for euthyroid patients, but 42.1% will consider it for euthyroid infertile women with high antibody levels. In various conditions that could interfere with the absorption of LT4, most responding Danish endocrinologists prefer tablets and do not expect a significant difference when switching from one type of tablet formulation to another. CONCLUSION: The treatment of choice for hypothyroidism is LT4. Combination therapy with LT4 + LT3 is considered for patients with persistent symptoms. Even in the presence of conditions affecting bioavailability, responding Danish endocrinologists prefer LT4 tablets rather than newer LT4 formulations, such as soft-gel capsules.

Free triiodothyronine is associated with the occurrence and remission of nonalcoholic fatty liver disease in euthyroid women.

BACKGROUND: The association between nonalcoholic fatty liver disease (NAFLD) and free triiodothyronine (FT3) in euthyroid subjects was in dispute. We aimed to investigate this issue in a population-based cohort study. MATERIALS AND METHODS: A total of 3144 euthyroid subjects at baseline from the Shanghai Nicheng Atherosclerosis Study were selected for the cross-sectional analysis, and 2089 subjects being followed up after 2.2 years were selected for the longitudinal analysis. NAFLD was diagnosed by ultrasound. The cut-off point of elevated alanine aminotransferase (ALT) level was 40 U/L. The FIB-4 index was used to assess the risk of advanced liver fibrosis. RESULTS: Age-adjusted mean levels of FT3 and FT3/free thyroxine (FT4) ratio were higher in subjects with NAFLD than those without NAFLD and linearly increased with a higher risk of NAFLD progression (assessed by levels of ALT and FIB-4 index) in euthyroid women but not in men. After adjustment for confounding variables, FT3 levels significantly increased with the presence of NAFLD (ß = 0.1, P < 0.001) and linearly increased with a higher risk of NAFLD progression in euthyroid women. After a 2.2-year follow-up, FT3 levels increased with the occurrence of NAFLD (mean change percentage: 1.4%) and decreased with the remission of NAFLD (mean change percentage: -2.7%) in euthyroid women. CONCLUSIONS: There are positive associations of FT3 levels with NAFLD and the risk of NAFLD progression in euthyroid women. The changes in FT3 levels with the alteration of NAFLD status may be an adaptive response to maintain energy and metabolic homeostasis.

Thyroid hormones, metabolic syndrome and Vitamin D in middle-aged and older euthyroid subjects: a preliminary study.

AIM: To explore the relationship between thyroid hormones, Vitamin D (Vit.D) serum concentrations and metabolic syndrome (MetS) in euthyroid subjects. METHODS: 123 community-dwelling subjects were enrolled. According to thyroid-stimulating hormone (TSH) values the sample was divided into: (1) group 1 (TSH ≤ 2 mU/L); (2) group 2 (TSH > 2 mU/L). RESULTS: Group 2 showed higher percentage of subjects with MetS (p = 0.003) and hypertension (p = 0.031), higher values of waist circumference (WC) (p = 0.007), parathyroid hormone (p = 0.016), glycaemia (p = 0.045), triglycerides (p = 0.034) and free T4 (fT4) (p = 0.013). Correlation analysis showed several weak significant correlations: MetS with TSH (r = 0.202, p = 0.031) and fT3 (r = - 0.206, p = 0.028); THS with body mass index (r = 0.187, p = 0.047) and hypertension (r = 0.199, p = 0.034); Vit.D with WC (r = - 0.185, p = 0.04). CONCLUSIONS: Our results showed a possible association between thyroid hormones and MetS. Visceral fat and insulin resistance may be an interesting link between Vit.D and TSH levels.

Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence.

BACKGROUND/AIMS: Thyroid hormones have been recently linked to senescence and longevity. Given the recent description of TSHB mRNA in human adipose tissue (AT), we aimed to investigate the relationship between local AT TSH and adipose tissue senescence. METHODS: TSHB mRNA (measured by real-time PCR) and markers of adipose tissue senescence [BAX, DBC1, TP53, TNF (real-time PCR), telomere length (Telo TAGGG Telomere Length Assay) and lipidomics (liquid chromatography mass spectrometry)] were analysed in subcutaneous (SAT) and visceral (VAT) AT from euthyroid subjects. The chronic effects of TSH were also investigated in AT from hypothyroid rats and after recombinant human TSH (rhTSH) administration in human adipocytes. RESULTS: Both VAT and SAT TSHB gene expression negatively correlated with markers of AT cellular senescence (BAX, DBC1, TP53, TNF gene expression and specific glucosylceramides) and positively associated with telomere length. Supporting these observations, both rhTSH administration in human adipocytes and increased TSH in hypothyroid rats resulted in decreased markers of cellular senescence (Bax and Tp53 mRNA) in both gonadal and subcutaneous white adipose tissue. CONCLUSION: These data point to a possible role of TSH in AT cellular senescence.

A single-center retrospective study of factors related to the effects of intravenous glucocorticoid therapy in moderate-to-severe and active thyroid-associated ophthalmopathy.

BACKGROUND: Intravenous glucocorticoids (ivGC) have been recommended as a first-line treatment of moderate-to-severe and active thyroid-associated ophthalmopathy (TAO). However, not all patients are responsive to ivGC. The identification of potential factors used to predict their efficacy and the selection of suitable patients have both been lacking. METHODS: It was a single center retrospective study. Potential factors related to the effects of ivGC were analyzed using logistic regression in 90 consecutive patients with moderate-to-severe and active TAO, who received 4.5 g ivGC therapy. Response was defined as the achievement of at least three points of the overall response. RESULTS: Fifty-two (57.8%) patients showed a positive response to ivGC therapy. Significant correlations were observed between the effects of ivGC and pretreatment clinical activity score (CAS), duration of eye symptoms, and restoration of euthyroidism. The two latter factors were both independent. The duration of eye symptoms was negatively correlated with the effects of ivGC, with an odds ratio (OR) of 0.984 (p = 0.012). Restoration of euthyroidism (OR = 3.282, p = 0.039) and pretreatment CAS (OR = 1.653, p < 0.01) were both positively correlated with the effects of ivGC. The diagnostic accuracy of the duration of eye symptoms was ≤13 months (p = 0.000), with a specificity of 76.9%, and sensitivity of 65.8%. The diagnostic accuracy of the pretreatment CAS was more than 2.5 (p = 0.000), with a specificity of 61.5% and sensitivity of 80.5%. Besides, a multi-variables prediction model were established as well, which was better in the forecasting aspect with an area under curve of 0.784 (p = 0.000). CONCLUSIONS: The duration of eye symptoms and restoration of euthyroidism are independent factors that are associated with the effects of ivGC. The following practical implications were inferred: firstly, the shorter the duration of eye symptoms, the more favorable the effects of ivGC therapy. Thus, prompt diagnosis and treatment (within 13 months) is important. Secondly, the restoration of euthyroidism improves the efficacy of ivGC. Thirdly, hope the multi-variables prediction model can be applied to clinical therapy in the future.

The association between subclinical hypothyroidism and erectile dysfunction.

OBJECTIVES: Erectile dysfunction (ED) is highly prevalent among males, and hypothyroidism is previously reported to be related with ED. However there have been rare studies to investigate the association between subclinical hypothyroidism (SCH) and ED, hence our objective was to fill this gap. METHODS: ED patients who visited the Urology Outpatients Clinic owere recruited consecutively, and males from the Health Manage Center were included as the controls. Serum thyroid and sexual hormones were estimated, and the International Index of Erectile Function (IIEF-5) questionnaires were evaluated as well. Subjects with normal sexual hormones were included for statistical analysis. RESULTS: One hundred nine ED patients and 32 healthy controls were included in this study. The ratio of SCH and euthyroidism in ED males was 29.36% and 66.06% respectively. The IIEF-5 scores in ED patients with SCH were significantly lower than the controls with euthyroidism (P<0.05). The serum concentrations of TSH and prolactin were significantly higher and free thyroxine lower in ED patients with SCH when compared with the controls with euthyroidism (all p<0.05), and no significant differences of estradiol and total testosterone were found between those two groups. However the IIEF-5 scores were not significantly different between males with SCH and euthyroidism among ED patients (P>0.05). CONCLUSIONS: SCH is common in ED patients and may be associated with ED, whereas the severity of ED is not related to SCH. Screening for thyroid dysfunction in men presenting with ED is recommended.

Remission of Graves' disease is not related to early restoration of euthyroidism with high-dose methimazole therapy.

UNLABELLED: Introduction and aims: The most recent hypothesis postulated that early restoration of euthyroid state in patients with Graves' disease changes the course of the disease and leads to better disease control. Therefore, we analyzed the efficacy of methimazole therapy and the course of disease in patients with restored euthyroidism and in patients with active disease on first control visit. PATIENTS AND METHODS: We included 63 patients with total T4 level >190 nmol/L or T3 >7 nmol/L and diffuse goiter with no previous episodes of hyperthyroidism. All patients received initially high doses of methimazole (60-80 mg) followed by a rapid dose reduction. RESULTS: Ten percent of patients were excluded from the study due to side effects. Two different groups emerged after 5 weeks of treatment with same dose of methimazole: group 1 with active disease (48%) and group 2 with restored euthyroidism. Further controls on 12th, 24th and 68th weeks of treatment showed no difference in remission rates, number of iatrogenic hypothyroid episodes, and number of exacerbations between the two groups, regardless of methimazole dose. There was no association between age, gender, thyroid hormone levels, and remission and exacerbation rates. CONCLUSIONS: Initially, higher methimazole doses with rapid progressive decrease to maintenance dose result in similar remission rates and are followed by similar incidence of adverse side-effect as fixed low dose therapy. Our results indicate that neither an early restoration of euthyroidism nor the difference in methimazole doses influence the course of Graves' disease.

[Age characteristics of the cardiovascular system, depending on the thyroid function in type 2 diabetes mellitus].

To study the features of cardiovascular system in patients with diabetes mellitus type 2 considering the thyroid pathology and age, 264 patients were examined. They were divided into three groups: 1st - patients with diffuse-nodular changes in the thyroid gland, 2nd - patients with autoimmune thyroid disease, 3rd - a control group of patients without thyroid disease. The patients of different ages were examined in each of these groups. All patients were in euthyroid state. It was established that identified in diabetes mellitus type 2 thyroid pathology and the thyroid disease contribute special features to the clinical picture for combined diabetic and cardiovascular pathology even in a euthyroid state including the age features. The laboratory and instrumental researches showed that the patients with combined diabetes and thyroid pathology have a higher incidence of atrial fibrillation, ischemic heart disease, and ventricular arrhythmias of high grades. They also were noticed to have a more adverse form of the left ventricle remodeling, also the combination of diastolic and systolic dysfunctions were found to be more frequent. It was concluded about the necessity of early diagnosis and correction of the cardiovascular disorders and thyroid systems in type 2 diabetes mellitus patients, including euthyroid patients.

Graves' Disease in Hypopituitarism Due to Pituitary Apoplexy.

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.

Relationship between bisphenol A and autoimmune thyroid disease in women of childbearing age.

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.

Thyroid dysfunction in Hashimoto's thyroiditis: a pilot study on the putative role of miR-29a and TGFß1.

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.

Thyrotropin and body mass index, are they related?

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.

Thyroid-stimulating hormone within the normal reference range has a U-shaped association with the severity of coronary artery disease in nondiabetic patients but is diluted in diabetic patients.

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.