Low Normal Thyroid-stimulating Hormone Research Articles

8412 Resolution of Central Hypothyroidism shortly after Transsphenoidal Surgery For Cushing’s Disease

Abstract Disclosure: L. Esper: None. A. Ibrahim: None. N. El Asmar: None. Background: Cushing's disease is a rare endocrine disorder characterized by excessive cortisol production, resulting in various metabolic disturbances. Hypercortisolism is known to cause central hypothyroidism. The mechanism is complex and involves hypercortisolism mediated decreased TRH and TSH secretion in addition to inhibition of peripheral deiodination. This case details the successful management and recovery of a patient with Cushing's disease and reversal of central hypothyroidism after pituitary surgery.Case:A 43-year-old man was evaluated for central hypogonadism, 20 pound weight gain with central weight distribution, and the development of purple abdominal striae for the past year. He had a normal thyroid exam and appeared euthyroid. He was alsodiagnosed with hypertension and prediabetes in the past yearrequiring medical therapy.A low dose dexamethasone suppression test (DST) resulted in AM cortisol of 12.9 mcg/dl. Two adequate 24hr Urinary cortisol measurements showed elevated cortisol excretion at 458 and 378mcg/24. Lab evaluation revealed elevated cortisol levels along with elevated adrenocorticotropic hormone (ACTH) levels(ACTH of 172 pg/ml with a cortisol level of 23.9 mcg/dl). A high dose DST demonstrated suppression of cortisol to 3.4 mcg/dl. MRI pituitary was performed which showed a clearright sided 7mm pituitary adenoma.Thyroid function tests performed were consistent with central hypothyroidism, with low levels of free thyroxine (FT4) at 0.67ng/dl along with an inappropriately low normal thyroidstimulating hormone (TSH) at 0.596 uIU/ml. Total T4 was low at 4 ug/dl in addition to a low total T3 of 66 ng/dl. Remaining labs revealed central hypogonadism along with slightly elevated prolactin of 16 ng/ml. He was not started on thyroid hormone.He then underwent transsphenoidal surgery for tumor removal. He developed post-operative adrenal insufficiency (cortisol 2.12 mcg/dl) 16 hours post-op after which he was started on hydrocortisone replacement, indicating remission. 12 hours post-op, his TSH was 0.656 uIU/ml with a free t4 of 0.79 ng/dl, both in the normal range. 36 hours post-op, TSH was 0.524 uIU/ml and free t4 was 1.15 ng/dl. Histopathological examination confirmed the diagnosis of an ACTH-secreting pituitary adenoma.At 4 weeks post-op, thyroid labs showed normal FT4 (1.07ng/dl) and TSH (2.06uIU/ml). Conclusion: Hypercortisolism causes a global inhibition of the thyroid axis, with decreased levels of TSH, T4, and T3 (1). Previous studies suggest the monitoring of thyroid function at 6 and 12 months after surgical cure of hypercortisolism. Our case suggests that the resolution of hypothyroidism occurs shortly after surgery for Cushing’s disease and the need for earlier monitoring. Presentation: 6/3/2024

Are resting metabolic rate and clinical symptoms affected by variation of serum thyroid stimulating hormone levels within the normal range in healthy and women with hypothyroidism? A case–control study

BackgroundIt is unclear whether variation in thyroid stimulating hormone (TSH) levels within the reference range affect energy expenditure and clinical symptoms and even within the normal range of TSH levels, resting energy expenditure may alter. The aim of the present study was to determine whether treated hypothyroid subjects and healthy subjects with a low-normal TSH range (0.3–2.3 mIU/L) have better clinical outcomes and increased energy expenditure than those with a high-normal TSH range (2.3–4.3 mIU/L). MethodsThis was a case-control study of 160 overweight/obese women with TSH levels across the reference range of 0.3-4.3 mU/l. Subjects were paired in four groups: healthy subjects with low-normal target TSH (n =40), healthy subjects with high-normal target TSH (n =40), subjects with treated hypothyroidism with low-normal target TSH (n =40), and subjects with treated hypothyroidism with high-normal target TSH (n =40). Resting energy expenditure (RMR), dietary intake, body composition, physical activity, and biochemical markers were assessed. ResultsSubjects with low-normal (≤2.3 mU/L) and high-normal (>2.3 mU/L) TSH levels did not differ in terms of RMR, serum T3 levels, and clinical symptoms except fatigue (P=0.013). However, serum fT4 levels were found to be significantly different between the study groups (P=0.002). Serum fT4 concentration was the highest in subjects with treated hypothyroidism with low-normal target TSH. ConclusionVariation in serum TSH levels within the reference range did not significantly affect REE and clinical symptoms except fatigue in healthy and women with hypothyroidism.

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

BackgroundEvidence 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.MethodsThis 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.ResultsDuring 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.ConclusionLow- 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.

Comparison of reproductive outcomes in subclinical hypothyroidism women with high-normal versus low-normal thyroid-stimulating hormone levels after treatment with levothyroxine.

Reproductive outcomes in euthyroid women with high-normal thyroid-stimulating hormone (TSH) levels are comparable to those in euthyroid women with low TSH levels; however, few studies have investigated whether strictly controlled TSH levels after levothyroxine (LT4) treatment impair reproductive outcomes in infertile women with subclinical hypothyroidism (SCH). This study aimed to investigate the impact of high-normal versus low-normal TSH levels on reproductive outcomes in women undergoing their first in vitro fertilisation and embryo transfer (IVF-ET) cycle. This was a retrospective cohort study. Patients were divided into low-normal (TSH < 2.5 mIU/L, and ≥0.27 mIU/L) and high-normal (TSH ≥ 2.5 mIU/L, and <4.2 mIU/L) groups based on TSH levels after LT4 treatment. TSH levels after LT4 treatment and before ovarian stimulation were recorded. Reproductive outcomes were compared between the low-normal and high-normal TSH groups and between the euthyroid and LT4-treated groups. A total of 6002 women, 548 of whom were LT4-treated women, were finally included in this study. Among the LT4-treated women, 129 women had low-normal TSH levels, and 167 women had high-normal TSH levels. The clinical pregnancy rate, miscarriage rate, and live birth rate were comparable between the low-normal and high-normal groups (all p > .05). When adjusted by age, anti-Mullerian hormone (AMH) levels, infertility duration, transferred embryos, and dose and duration of LT4 treatment, high-normal TSH levels neither significantly decreased miscarriage (adjusted odds ratio [aOR] = 2.27, 95% confidence interval [CI] = 0.77-6.69, p = .14) nor increased clinical pregnancy (aOR = 1.15, 95% CI = 0.70-1.89, p = .57 or live birth (aOR = 0.97, 95% CI = 0.60-1.59, p = .92). Similar obstetric outcomes were observed between the low-normal and high-normal TSH groups after LT4 treatment and between the euthyroid and LT4-treated groups (all p ≥ .05). High-normal TSH levels did not have adverse effects on clinical and obstetric outcomes when compared with low-normal TSH levels after LT4 treatment. However, whether it is appropriate to set 2.5 mIU/L as the goal of treatment before IVF/ICSI remains to be determined in further well-designed studies.

Economic and Cardiometabolic Risk Factors Are Predictors of Lower Thyroid Stimulating Hormone (TSH) Levels in Hispanic/Latinx Adults with Euthyroidism-A Community-Based Study.

Thyroid hormone abnormalities are among the most common endocrine disorders comorbidly suffered alongside metabolic syndrome and type 2 diabetes mellitus (T2DM), and within the euthyroid range they may also impact other outcomes, such as mood disorders. This study aimed to observationally examine the relationship between TSH and social determinants of health and clinical measures in a euthyroid Hispanic/Latinx patient sample with a diagnosis of anxiety and/or depression disorders from a community health clinic. A needs assessment was completed using a random sample of 100 de-identified medical records of individuals who received free medical care, including mental health, at a community-based clinic. Those with low normal TSH (<2 mIU/L) compared with high normal TSH (≥2 mIU/L) had a greater odds of food insecurity (p = 0.016) and being at 100% of the federal poverty level (p = 0.015). The low normal TSH group had significantly higher fasting glucose (p = 0.046), hemoglobin A1c (p = 0.018), and total cholesterol (p = 0.034) compared with the high normal TSH group. In those with T2DM, individuals with low normal TSH had six-times greater odds of having high fasting glucose (p = 0.022) and high hemoglobin A1c (p = 0.029). These relationships warrant further study, to inform future public health policies and follow-up care for underserved and vulnerable communities.

Relationships between Glycemic and Lipid Control and TSH in Euthyroid Latinx Adults- a Community-Based Study

ObjectivesThyroid hormone abnormalities are among the most common endocrine disorders comorbidly suffered alongside metabolic syndrome and type 2 diabetes mellitus (T2DM). Thyroid hormones and their regulating hormone, thyroid-stimulating hormone (TSH), play a role in metabolism, obesity, insulin resistance and other disorders that share similar mechanisms. The aim of this study was to examine the associations between TSH and clinical measures of chronic disease markers in a Latinx population receiving free health care services at a community clinic. MethodsA needs assessment was conducted on euthyroid Latinx adult patients from a community clinic in south Florida. The medical records of 93 randomly selected patients were cross-sectionally reviewed to collect data on demographics, diagnoses of health conditions, and biomedical laboratory information. The cut-off point for high TSH was ≥2 mU/L and low TSH as <2 mU/L. Statistical analyses included descriptive statistics, independent t-test, chi-squared test, logistic regressions. ResultsThe mean age was 51.9 ± 11.8 years and 82.8% were female. There were no differences between low and high TSH groups on age, gender, BMI, hypertension, T2DM, CVD, or CVD risk factors. The low TSH group had significantly higher fasting glucose (194.0 mg/dL ± 86.2 vs 140 mg/dL ± 52.8, P = 0.046), hemoglobin A1c (9.6% ±2.8 vs 7.5% ±1.5, P = 0.018), and total cholesterol (200.5 mg/dL ± 32.8 vs 171.5 mg/dL ± 39.7, P = 0.034) compared with the high TSH group. Subgroup analysis of those with T2DM revealed that the low TSH group also had a greater proportion of patients with high fasting glucose (≥170 mg/dL) and high hemoglobin A1c (≥8.5%) compared with the high TSH group. Similarly, those with a low TSH had 6 times greater odds of having high fasting glucose (OR 6.66, 95% CI 1.31–33.69, P = 0.022) and high hemoglobin A1c (OR 6.11, 95% CI 1.19–31.16, P = 0.029). ConclusionsIn Latinx euthyroid patients receiving medical services at a community clinic, a relationship between low-normal TSH levels, fasting glucose and hemoglobin A1c was demonstrated. As the population ages and the risk of both obesity and multimorbidity increases, understanding how thyroid hormone dysfunction can influence chronic disease status may help address health disparities suffered in disadvantaged and vulnerable populations. Funding SourcesFIU RCMI/NIMHD

Effect of TSH levels during active surveillance of PTMC according to age.

We previously reported that high thyroid-stimulating hormone (TSH) levels are associated with papillary thyroid microcarcinoma (PTMC) progression during active surveillance. However, validation with multicenter, long-term data, and identification of appropriate age or TSH levels are needed. This multicenter retrospective study enrolled PTMC patients under active surveillance with TSH measurements and ultrasonography. The primary outcome was PTMC progression (volume increase ≥50%, size increase ≥3 mm, or new lymph node (LN) metastasis). PTMC progression according to time-weighted average of TSH (TW-TSH) groups was compared using survival analyses in overall patients and each age subgroups (<40, 40-49, 50-59, and ≥60 years). The identification of TW-TSH cutoff point for PTMC progression and trend analysis of PTMC progression rate according to LT4 treatment were also performed. During 1061 person-years of follow-up, 93 of 234 patients (39.7%) showed PTMC progression (90, 17, and 5 patients for volume increase ≥50%, size increase ≥3 mm, and new LN metastasis, respectively). The highest TW-TSH group was the risk factor most strongly associated with PTMC progression (hazard ratio 2.13 (1.24-3.65); P = 0.006), but the impact was significant only in patients aged <40 or 40-49 years (hazard ratio 30.79 (2.90-326.49; P = 0.004), 2.55 (1.00-6.47; P = 0.049)). For patients aged <50 years, TW-TSH cutoff for PTMC progression was 1.74 mU/L, and PTMC progression rates successively increased in the order of effective, no, and ineffective LT4 treatment group (P for trend = 0.034). In young PTMC patients (<50 years), sustained low-normal TSH levels during active surveillance might be helpful to prevent progression.

Thyroid function and age-related decline in kidney function in older Chinese adults: a cross-sectional study

BackgroundThyroid function may be a factor affecting kidney function in the general population. Kidney and thyroid function vary with age; therefore, the association between thyroid function and decreased kidney function in older adults may be different from that in younger adults and remains controversial. This study aimed to estimate the association between normal-range thyroid function and age-related decline in kidney function in older Chinese adults.MethodsA total of 15,653 adults, of whom 23.2% (N = 3624) were older adults (age≧65 years), were collected at the Health Management Center of the First Affiliated Hospital of Nanjing Medical University from January 2018 to January 2020. Basic demographic information was collected by a physician-administered questionnaire. The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. Trends in thyroid function with age were shown by means of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) in subgroups every ten years. The association between kidney function and thyroid function was estimated by multiple linear regression using β value and by multivariable logistic regression models using odds ratios (OR) after adjusting for age, gender, body mass index, and serum urine acid.ResultsIn the older population, TSH tended to increase with age and FT3 tended to decrease, whereas FT4 was relatively stable. eGFR decreased significantly with increasing TSH (β = -0.081) and decreasing FT3 (β = 0.083) concentrations. Compared with those in the lowest quartile of FT3 (3.10–4.47 pmol/L), the prevalence of eGFR < 75 ml/min/1.73m2 decreased significantly by 22.0% for those with FT3 of 4.47–4.81 pmol/L, 27.6% for those with FT3 of 4.82–5.20 pmol/L, and 34.9% for those with FT3 of 5.21–6.8 pmol/L in older individuals (P for trend < .001). The OR was 1.315 (P: 0.025) in subjects with high-normal TSH, using low-normal TSH as a reference. The prevalence of reduced kidney function was not significantly associated with FT4 within the reference range. Similar results were found in association between the prevalence of eGFR < 60 ml/min/1.73m2 and thyroid function.ConclusionsThis study demonstrated a significant association between kidney function and thyroid function, particularly FT3, in the older population. Clinicians may need to pay more attention to the assessment and follow-up of kidney function in older individuals with low-normal FT3 and high-normal TSH.

Thyroid function and IVF outcome for different indications of subfertility.

Graphical Studies evaluating pregnancy outcomes after assisted reproductive treatment (ART) in women with high-normal (2.5–4.5 mIU/L) thyroid-stimulating hormone (TSH) levels are conflicting, possibly due to different patient charactistics and subfertility indications. The aim of this study was to examine the hypothesis that high-normal compared to low-normal TSH levels are associated with adverse implications for pregnancy outcomes in conventional in vitro fertilization (IVF)-treated women. Therefore, we analyzed retrospectively the characteristics and pregnancy outcomes of 949 subfertile women with TSH 0.3–4.5 mIU/L, treated with conventional IVF between January 2008 and March 2012. Demographic and baseline characteristics were compared between groups of patients based on TSH quartiles, using one-way Anova, Kruskal–Wallis ANOVA and chi-square test. Women with high-normal quartile TSH were significantly more likely to be primary subfertile (P = 0.01), with a higher prevalence of unexplained subfertility and with 15% fewer live births after IVF compared to lower TSH quartiles (P = 0.02). In secondary subfertile women with high-normal TSH, male factor subfertility prevailed (P = 0.01), with more live births (P = 0.01). When analyzing primary and secondary subfertile women as one group, these differences failed to be observed, showing no differences in cumulative pregnancy outcomes of IVF between TSH quartiles (I: 0.3–1.21 mIU/L; II: 1.22–1.68 mIU/L; III: 1.69–2.31 mIU/L; IV: 2.32–4.5 mIU/L). In conclusion, primary subfertile women predominate in the high-normal TSH quartile, associated with significantly fewer live births in a subgroup of primary unexplained subfertile women (9%; n = 87/949), while in secondary subfertile women, dominated by male factor subfertility, high-normal TSH is associated with more live births.Lay summaryThyroid hormones are required for all cell processes in the body. An underactive thyroid gland, in which insufficient thyroid hormones are produced and thyroid-stimulating hormone (TSH) rises, is associated with a lower chance of pregnancy. It is not yet clear above which TSH level, 4.5 or also 2.5 mIU/L, this lower probability occurs. Therefore, in 949 couples treated with conventional IVF, we examined whether high-normal TSH levels (TSH: 2.5–4.5 mIU/L) compared to low normal TSH levels (0.3–2.5 mIU/L) affect the live birth rate. We found that women who were trying to become pregnant for the first time, especially without any other cause, that is unexplained subfertility, were more likely to have higher TSH levels. These women had a much lower chance of having a baby compared to women with low-normal TSH levels.

Фактори кардіоваскулярного ризику у хворих на артеріальну гіпертензію при різному рівні тиреотропного гормону

Метою роботи було встановити вплив рівня тиреотропного гормону (ТТГ) на частоту і вираженість факторів кардіоваскулярного ризику у хворих на артеріальну гіпертензію (АГ). Були обстежені 123 хворі із АГ I–II ступенів віком 45–70 років. Методи дослідження: визначення показників ліпідограми, ТТГ, вільного тироксину, ехокардіографія, вимірювання офісного артеріального тиску (АТ), дуплексне сканування судин шиї, тестування за госпітальними шкалами тривоги і депресії. Серед обстежених хворих 12,4 % мали не діагностований раніше субклінічний гіпотиреоз, що асоціювався з більшою частотою дисліпідемії, порушення вуглеводного обміну, гіпертрофії лівого шлуночка і атеросклеротичного ураження сонних артерій, більш високими значеннями пульсового АТ, а також зі зменшенням швидкості клубочкової фільтрації і тривожно-депресивними розладами. При аналізі групи з нормальною функцією щитоподібної залози (ЩЗ) було виявлено, що високонормальний рівень ТТГ (2–4 мОд/л) також пов’язаний зі збільшенням частоти факторів кардіоваскулярного ризику і погіршенням стану органів-мішеней порівняно з особами із низьконормальним рівнем ТТГ. Отже, функціональний стан ЩЗ впливає на частоту та вираженість факторів ризику і уражень органів-мішеней при АГ, що потребує ретельного його контролю у хворих із кардіологічною патологією.

Prognostic significance of low TSH concentration in patients with COVID-19 presenting with non-thyroidal illness syndrome

BackgroundLow free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI.MethodsPatients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality.ResultsOne hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42–5.552, P = 0.003).ConclusionsLow FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.

High-Normal Thyroid Function Predicts Incident Nonalcoholic Fatty Liver Disease Among Middle-Aged and Older Euthyroid Subjects

Thyroid hormones (THs) influence hepatic lipid homeostasis through multiple pathways, suggesting that THs may predict the risk of non-alcoholic fatty liver disease (NAFLD). However, prospective studies on the association between THs levels and incident NAFLD in euthyroid subjects are limited. This prospective cohort study aimed to explore whether THs were associated with the development of NAFLD in middle-aged and elderly euthyroid subjects. A total of 6,462 subjects without baseline NAFLD were included in the cohort study (~6-year follow-up period, median: 4.2 years). Chemiluminescence immunoassay was used to measure serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), and NAFLD was diagnosed by abdominal ultrasonography. Multivariable Cox proportional hazards regression models were used to assess the association between baseline THs, TSH, and the risk of NAFLD. During the follow-up period, 1,675 subjects developed NAFLD. The incidence rate of NAFLD was 85.0 per 1000 person-years. Compared with the lowest FT3, FT4, and TSH quartiles, the multivariable-adjusted hazard ratios (95% confidence interval) of incident NAFLD for highest quartiles were 1.30 (1.12, 1.51), 1.07 (0.93, 1.23), 0.82 (0.71, 0.95) (P <0.001, =0.56, =0.01, respectively), respectively. In middle-aged and elderly euthyroid subjects, high-normal FT3 and low-normal TSH are independently associated with a higher incidence of NAFLD.

Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Disease.

The prevalence of subclinical hypothyroidism (SH) is 3-10%. The prevalence of subclinical hyperthyroidism (SHr) is 0.7-9.7%. Thyroid hormones affect cardiac electrophysiology, contractility, and vasculature. SH is associated with an increased risk of coronary heart disease (CHD), especially in subjects under 65. SHr seems to be associated with a slightly increased risk of CHD and an increase in CHD-related mortality. Both SH and SHr carry an increased risk of developing heart failure (HF), especially in those under 65. Both SH and SHr are associated with worse prognoses in patients with existing HF. SH is probably not associated with atrial fibrillation (AF). SHr, low normal thyroid-stimulating hormone (TSH) and high normal free thyroxine (FT4) are all associated with the increased risk of AF. An association between endothelial dysfunction and SH seems to exist. Data regarding the influence of SHr on the peripheral vascular system are conflicting. SH is a risk factor for stroke in subjects under 65. SHr does not increase the risk of stroke. Both SH and SHr have an unfavourable effect on cardiovascular disease (CVD) and all-cause mortality. There is a U-shaped curve of mortality in relation to TSH concentrations. A major factor that modifies the relation between subclinical thyroid disease (SCTD) and mortality is age. SH increases blood pressure (BP). SHr has no significant effect on BP. Lipids are increased in patients with SH. In SHr, high-density lipoprotein cholesterol and lipoprotein( a) are increased. SCTD should be treated when TSH is over 10 mU/l or under 0.1 mU/l. Treatment indications are less clear when TSH is between normal limits and 0.1 or 10 mU/L. The current state of knowledge supports the understanding of SCTD's role as a risk factor for CVD development. Age is a significant confounding factor, probably due to age-associated changes in the TSH reference levels.

Strong Positive Correlation between TSH and Ghrelin in Euthyroid Non-Growth Hormone-Deficient Children with Short Stature.

The growth processes in children depend on the proper functioning of some hormones and growth factors. Recently, a positive correlation between ghrelin and TSH (thyroid stimulating hormone) in patients with hyper- and hypothyroidism was proved. Moreover, in hypothyroid rats with high ghrelin concentration, growth hormone (GH) and insulin-like growth factor I (IGF-I) secretion was suppressed. We analyzed these relationships in euthyroid prepubertal children with idiopathic short stature (ISS). The analysis comprised concentration of ghrelin, GH in stimulating tests and during the night, as well as IGF-I, TSH, free thyroxine (FT4) and free triiodothyronine (FT3) in 85 children with ISS (36 girls, 49 boys) aged 9.65 ± 3.02 years (mean ± SD). A strong positive correlation between ghrelin and TSH was confirmed (r = +0.44, p < 0.05). A higher ghrelin but lower nocturnal GH and lower IGF-I were observed in children with higher normal TSH concentration than those in children with lower normal TSH. Interestingly, alterations of TSH level were without any impact on FT4 and FT3 concentrations. Summing up, in ISS prepubertal euthyroid children, ghrelin and TSH secretion are closely related. On the other hand, the higher the TSH, the lower the nocturnal GH and IGF-I levels. The contribution of the above findings in deterioration of growth processes requires further studies.

Low Normal TSH Levels and Thyroid Autoimmunity are Associated with an Increased Risk of Osteoporosis in Euthyroid Postmenopausal Women.

Studies on the relationship of thyroid stimulating hormone (TSH) within the reference range and thyroid autoimmunity with osteoporosis have produced conflicting results. The objective of this study was to investigate the association of thyroid function and thyroid autoimmune bodies (TPOAb and TgAb) with osteoporosis in euthyroid postmenopausal women. A total of 174 subjects were retrospectively included. Serum TSH, total T3, total T4, TPOAb, TgAb, vitamin D, calcium and bone mineral density were measured. Correlation and logistic multivariate regression analysis were performed. Levels of TSH were lower in osteoporosis group (TSH: 2.03±1.08 vs 2.40±1.24 mIU/L, p=0.040) while TT3 and TT4 levels were similar between the two groups. The positive percentage of anti-TPO antibodies was higher in osteoporosis group (17.9% vs 6.7%, χ2= 5.13, p=0.024) while no significant difference was observed for anti-Tg antibodies (17.9% vs 8.9%, χ2=3.05, p=0.081). The Spearman correlation analysis showed that TSH levels were significantly correlated with lumbar spine BMD (r= 0.161, P=0.035) and femoral neck BMD (r = 0.152, P= 0.045). Logistical regression analysis revealed that low-normal TSH levels and positive TPOAb was an independent risk factor for osteoporosis (OR: 0.698, 95% CI: 0.505-0.965, p=0.030; OR: 3.961, 95% CI: 1.176-13.345, p=0.026 respectively). The results showed that low-normal TSH levels and anti-TPO antibodies were independently associated with the presence of osteoporosis in postmenopausal women.

SAT-447 Thyroid Function, Cardiovascular Disease, and Mortality: A Mediation Analysis

Background: Subclinical hypothyroidism is a common clinical entity among the United States (U.S) adults and has been associated with increased risk of cardiovascular disease (CVD) and mortality in some studies. However, the mediation effect of CVD from elevated serum thyroid stimulating hormone (TSH) to mortality has not yet been well established or sufficiently quantified. In this study, we aimed to elucidate the extent to which subclinical hypothyroidism or high-normal thyroid stimulating hormone [TSH] concentrations (i.e. upper normative-range TSH concentrations) contribute to mortality through its effect on CVD among U.S. adults. Methods: This study relies on the U.S. representative samples of 9,020 adults enrolled in the National Health and Nutrition Examination Surveys (NHANES) 2001-2002, 2007-2012 and their mortality data through 2015. We employed Cox proportional hazards regression models to investigate associations between the TSH concentration categories (subclinical hypothyroidism or tertiles of serum TSH concentrations within the reference range) and all-cause mortality. Utilizing mediation analysis within the counterfactual framework, we estimated the mediation effect of CVD on the association between TSH and all-cause mortality. Results: The median duration of follow-up for mortality ascertainment was 7.3 (interquartile range, 5.4–8.3) years, during which 435 deaths from all causes were identified. Subjects with TSH in the subclinical hypothyroidism and the high-normal TSH tertile concentrations were associated with increased all-cause mortality (subclinical hypothyroidism: hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.14–3.19; high-normal TSH: HR, 1.36; 95% CI, 1.07–1.73) compared with the middle-normal TSH tertile concentration. CVD mediated 14.3% and 5.9% of the effects of subclinical hypothyroidism and high-normal TSH on all-cause mortality, respectively, with the CVD mediation effect being most pronounced in women and subjects ≥60 years old. No mediation through CVD was found for low-normal TSH levels and all-cause mortality. Conclusion: CVD mediated the effects of subclinical hypothyroid and high-normal TSH concentrations on all-cause mortality in the U.S. general population. These findings may have potential implications for treatment, and early and more aggressive CVD screening for such at risk populations. Further studies are needed to examine the clinical impact of targeted therapy towards mid-normal TSH concentration.

Obese Women With Hypothyroidism Treated with Levothyroxine Have Reduced Resting Energy Expenditure

Obese Women With Hypothyroidism Treated with Levothyroxine Have Reduced Resting Energy Expenditure

High normal TSH is associated with lower mannan-binding lectin in women of childbearing age

BackgroundMannan-binding lectin (MBL) is a main component of the lectin pathway of the complement system. Lower MBL levels are associated with, among other conditions, hypothyroidism and adverse pregnancy outcomes. In turn, adverse pregnancy outcomes and infertility may result from hypothyroidism, even in patients with high normal Thyroid-stimulating hormone (TSH). The aim of this study was to determine if MBL level differs between women of reproductive age with low normal (< 2.5 mIU/l) and high normal (≥2.5 mIU/l) TSH. Associations with other parameters potentially affected by hypothyroidism were also evaluated.MethodsNinety five (95) patients with normal thyroid tests (TSH 0.27–4.2 mIU/l), aged 18–48 years, were prospectively enrolled. Several laboratory parameters were measured, including MBL level, thyroid tests and lipid profile.ResultsSerum MBL level was lower in women with TSH ≥ 2.5 mIU/l than with TSH < 2.5 mIU/l. This association was confirmed by univariate regression analysis. MBL level was significantly lower in patients with abnormally low HDLC/cholesterol ratio and a positive correlation was found between MBL level and HDL/cholesterol ratio.ConclusionIn women of reproductive age with normal thyroid tests, lower MBL is associated with high normal TSH and with less favourable lipid profile. Therefore treatment with L-thyroxine should be considered in women of reproductive age with TSH ≥ 2.5 mIU/l.

Assessment of subclinical hypothyroidism for a clinical score and thyroid peroxidase antibody: a comparison with euthyroidism grouped by different thyroid-stimulating hormone levels

Abstract Background Subclinical hypothyroidism (SCH) might have many symptoms of hypothyroidism. The controversy appears to lower the level of thyroid-stimulating hormone (TSH) and group subjects with TSH of more than 3 or even 2.5 mIU/L as SCH subjects. Objectives To assess SCH subjects both clinically using Zulewski clinical score and biochemically and to evaluate whether the euthyroid subjects with high-normal TSH (HNT) have any clinical symptom or subnormal biochemical finding. Methods A prospective cross-sectional study of 233 subjects, 67 with SCH and 166 euthyroidism, was conducted. Euthyroid subjects were divided according to the level of TSH as HNT (&gt;2.5 mIU/L) and low-normal TSH (0.5–2.5 mIU/L). The subjects were examined for clinical feature including Zulewski clinical score and biochemical evaluations including thyroid peroxidase antibody (TPO-Ab) titer. The comparisons between groups were assessed using independent sample t test, and correlations between variables were evaluated using Pearson correlation. Results A significantly higher clinical score and higher frequencies of symptoms were found in the SCH group compared to the euthyroid group. The most frequent symptom was fatigue. Euthyroid subjects with HNT were found to have higher TPO-Ab titers than those with low-normal TSH, P &lt; 0.05. The Zulewski clinical score was positively correlated with TSH and TPO-Ab titer but negatively correlated with the FT4 level, P &lt; 0.05. Conclusions Zulewski clinical score is higher in SCH subjects compared to euthyroid subjects and can aid in assessing SCH subjects. A significant correlation exists between Zulewski clinical score and each of the TSH, FT4, and TPO-Ab titer levels. The frequency of TPO-Ab positivity is high in SCH. Additionally, euthyroid with higher TSH levels has higher level of TPO-Ab titer but not higher clinical score.

Abstract P374: Thyroid-stimulating Hormone Levels and Coronary Artery Calcium Score. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Introduction: There is scarce information about the association between thyroid stimulating hormone (TSH) levels with subclinical atherosclerosis as the coronary artery calcium score (CAC). Hypothesis: we assessed the hypothesis that the extremes quintiles of TSH were associated with high values of CAC. Methods: We analyzed cross-sectionally baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a cohort of civil servants aged 35-74 years-old, in 4549 participants with CAC information. We excluded individuals using medications that affect thyroid function, with overt thyroid disorders and who self-reported cardiovascular disease. We included in the analysis TSH levels of subjects with euthyroidism and with subclinical thyroid disorders (subclinical hypothyroidism and hyperthyroidism). Logistic regression models evaluated increasing quintiles of TSH as the independent variables and CAC greater than 100 Agatston units as the dependent variable. Multivariate models were adjusted for age (continuous), sex, race (white, mixed, black, Asian, indigenous), body-mass index (continuous), hypertension (yes/no), diabetes (yes/no), dyslipidemia(yes/no), smoking (never/former/current), glomerular filtration rate (continuous, CKD-Epi formula) and C-Reactive Protein (log transformed). Results: From 3,836 subjects included (median age = 49 years;52.1%, women), 3,551 (92.6%) had euthyroidism, 239 (6.2%) subclinical hypothyroidism, and 46 (1.2%) subclinical hyperthyroidism. Frequencies of women, whites, never smokers, overweight/obesity and of reduced glomerular filtration rate increased according to TSH quintiles, but the frequency of diabetes decreased. Quintiles of TSH were from 1 st to 5 th respectively: TSH:0-0.99; 1.00-1.38; 1.39-1.85 (reference); 1.86-2.67; and 2.68-35.5 mIU/L. Using the 3 rd quintile as reference, the odds ratio OR (95% Confidence Interval) for CAC greater than 100 Agatston units were 1.57 (1.05-2.35) for the 1 st ; 0.95 (0.62-1.46) for the 2 nd ; 1.25 (0.81-1.87) for the 4 th ; and 1.18 (0.77-1.80) for the 5 th quintiles. Restricting analysis to the 3,551 euthyroid participants, quintiles of TSH in normal range were from 1 st to 5 th respectively: 0.40-0.99; 1.00-1.35; 1.36-1.75 (reference); 1.76-2.43 and 2.44-4.0. Using 3 rd quintile as reference, we also observed a significant association of the 1 st quintile with CAC: 1.70 (1.11-2.59) but not with 2 nd 0.95 (0.60-1.50), 4 th 1.46 (0.95-1.70) or 5 th 1.08 (0.69-1.70) quintiles. Conclusion: contrasting with previous studies that did not find any association between subclinical hypothyroidism and prevalent CAC, our results point to an association of low and low-normal TSH levels with prevalent CAC. Although one previous study showed an association between low normal TSH levels with CAC, our results also extended this association to low TSH levels.