Subclinical hypothyroidism (SCH) is defined by increased thyrotropin (TSH) and normal free thyroxine (fT4) levels. Controversial data are available regarding the effects of SCH on adipose tissue. Adiponectin and leptin are two major adipokines secreted from adipose tissue. We aimed to determine the levels of adiponectin and leptin in women with SCH and potential effects of L-thyroxine therapy on those levels. Forty three women with SCH and 53 age- and BMI-matched healthy euthyroid control women were included. Adiponectin and leptin levels, total cholesterol (TC), triglycerides (TG), HDL-, and LDL cholesterol, fat mass (FM) and fat-free mass (FFM) were determined in all participants. Patients received L-thyroxine treatment for 6 months after which all measurements were repeated. Patients with SCH and controls had similar baseline values for adiponectin, leptin, lipids, FM and FFM. All patients reached euthyroid status after 6 months of replacement therapy. Treatment resulted in an increase in adiponectin (p <0.01) and a decrease in leptin levels (p <0.05). Lipid levels, FM and FFM did not show a significant change. Achievement of euthyroid status by replacement therapy increases adiponectin and decreases leptin levels in women with SCH in this prospective study independent of a change in body fat mass.

INTRODUCTION:

Hyperthyroidism is characterized by increased synthesis and release of thyroid hormones by the thyroid gland. Thyrotoxicosis refers to the clinical syndrome resulting from excessive circulating thyroid hormones, secondary to hyperthyroidism or due to other causes. This article describes evidence-based guidelines for the clinical management of thyrotoxicosis.

OBJECTIVE:

This consensus, developed by Brazilian experts and sponsored by the Department of Thyroid Brazilian Society of Endocrinology and Metabolism, aims to address the management, diagnosis and treatment of patients with thyrotoxicosis, according to the most recent evidence from the literature and appropriate for the clinical reality of Brazil.

MATERIALS AND METHODS:

After structuring clinical questions, search for evidence was made available in the literature, initially in the database MedLine, PubMed and Embase databases and subsequently in SciELO - Lilacs. The strength of evidence was evaluated by Oxford classification system was established from the study design used, considering the best available evidence for each question.

RESULTS:

We have defined 13 questions about the initial clinical approach for the diagnosis and treatment that resulted in 53 recommendations, including the etiology, treatment with antithyroid drugs, radioactive iodine and surgery. We also addressed hyperthyroidism in children, teenagers or pregnant patients, and management of hyperthyroidism in patients with Graves' ophthalmopathy and various other causes of thyrotoxicosis.

CONCLUSIONS:

The clinical diagnosis of hyperthyroidism usually offers no difficulty and should be made with measurements of serum TSH and thyroid hormones. The treatment can be performed with antithyroid drugs, surgery or administration of radioactive iodine according to the etiology of thyrotoxicosis, local availability of methods and preferences of the attending physician and patient.

INTRODUCTION:

Subclinical hypothyroidism (SCH), defined as elevated concentrations of thyroid stimulating hormone (TSH) despite normal levels of thyroid hormones, is highly prevalent in Brazil, especially among women and the elderly. Although an increasing number of studies have related SCH to an increased risk of coronary artery disease and mortality, there have been no randomized clinical trials verifying the benefit of levothyroxine treatment in reducing these risks, and the treatment remains controversial.

OBJECTIVE:

This consensus, sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism and developed by Brazilian experts with extensive clinical experience with thyroid diseases, presents these recommendations based on evidence for the clinical management of SCH patients in Brazil.

MATERIALS AND METHODS:

After structuring the clinical questions, the search for evidence in the literature was initially performed in the MedLine-PubMed database and later in the Embase and SciELO - Lilacs databases. The strength of evidence was evaluated according to the Oxford classification system and established based on the experimental design used, considering the best available evidence for each question and the Brazilian experience.

RESULTS:

The topics covered included SCH definition and diagnosis, natural history, clinical significance, treatment and pregnancy, and the consensus issued 29 recommendations for the clinical management of adult patients with SCH.

CONCLUSION:

Treatment with levothyroxine was recommended for all patients with persistent SCH with serum TSH values > 10 mU/L and for certain patient subgroups.

To discuss the effect and mechanism of Platycladi Cacumen Carbonisatum (PCC) on rats with blood heat and hemorrhage syndromes.Rats were fed with 15 g x kg(-1) water decoctions of Zingiberis Rhizoma and 5% alcohol for 15 days to establish the blood-heat and hemorrhage syndrome model. Yunnan Baiyao was taken as the positive control drug, and PCC decoctions (5.0, 10.0 g x kg(-1)) were given simultaneously, in order to detect changes in general physical signs of rats, such as body weight, daily diet, volume of daily drinking and urine and stool, and rectal temperature. Automatic hematology analyzers was used to determine white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), and hematocrit (HCT), blood time by docking (BT). Blood rheometers was used to detect whole blood and plasma viscosities, thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen content (FIB). Indexes related to thyroid functions, such as triiodothyronine (T3), tetraiodothyronine (T4), reverse triiodothyronine (rT3) and thyroid stimulating hormone (TSH) were measured by radio-immunoassay, and changes in lung tissues were observed by hematoxylin-eosin (HE) stain.After modeling, rats witnessed slow-down in weight growth rate, significant increase in daily diet, volume of daily drinking, urine and temperature, significant decrease in stools and their water content (P < 0.05, P < 0.01), rise in plasma T4 level, notable growth in T3 and rT3 concentrations (P < 0.05), decline in TSH concentration. Additionally, their WBC, RBC, HGB and HCT remarkably increased (P < 0.05, P < 0.01), with significant increase in high, middle and low whole blood viscosities and plasma viscosity (P < 0.01); their BT, TT, APTT were notably prolonged (P < 0.01), with significant increase in FIB content (P < 0.01). After oral administration of Yunnan Baiyao or PCC, rats of all groups showed significant improvement in blood heat syndromes (P < 0.05, P < 0.01), and their blood coagulation indexes including BT, TT, APTT, FIB, thyroid function indexes including T4, T3, rT3, TSH, WBC, RBC, HGB, HCT, whole blood viscosity and plasma viscosity were getting normal (P < 0.05, P < 0.01).PCC can ameliorate blood heat symptoms and pathologic hemorrhage among rats with blood heat and hemorrhage syndromes by inhibiting thyroid functions and correcting hemorheological and coagulation disorders.

There is no consensus on the optimal treatment of multinodular goiter (MNG), but in the past few years, the use of radioiodine has increased. This study's objective was to evaluate adjuvant methimazole (MMI) therapy to increase and standardize radioiodine uptake (RAIU) with a fixed therapeutic (131)I dose of 1110 MBq (30 mCi).Our study included 5 women with MNG treated with MMI, 10 - 15 mg/day for 2 to 4 months, prior to the administration of 1110 MBq (131)I (30 mCi); none of the patients developed hypothyroidism during MMI therapy and had average basal TSH levels of 0.32 ± 0.39 mIU/L that increased to 2.6 ± 0.9 mIU/L (P = 0.07).RAIU increased from 25.6 ± 8.7% to 49.2 ± 8.3% (P = 0.003). All patients were followed for 12 months: median thyroid volume (TV) decreased from 77.2 mL (32.9 - 124.2) to 48.8 ml (12.4 - 68.9) with an average decrease of 46.4 ± 14.8% (P = 0.01). All patients developed hypothyroidism during the first 6 months after radioiodine therapy.This new therapeutic protocol using MMI as adjuvant therapy is effective in increasing RAIU as well as the deleterious effects of (131)I, without increasing the required dose, but leading to thyroid volume decreases similar to those reported with the use of recombinant human thyrotropin (rhTSH) or higher radioiodine doses.

Context:

The relationship between TSH and T4 is thought to be inverse log-linear, but recent studies have challenged this. There are limited data regarding age and gender differences in the TSH-T4 relationship.

Objective:

To evaluate the TSH-free T4 relationship in a large sample.

Methods:

In a cross-sectional, retrospective study we analyzed TSH and free T4 results from 152,261 subjects collected over 12 years by a single laboratory. For each free T4 value (in pmol/L), the median TSH was calculated and analyzed by gender and age (in 20 year bands).

Results:

The relationship between log TSH and free T4 was nonlinear. Mathematical modeling confirmed that it was described by two sigmoid curves with inflexion points at free T4 concentrations of 7 and 21 pmol/L. For free T4 within the reference range (10 - 20 pmol/L), median TSH was higher in males than females (p<0.001) and increased across age bands with the highest values in those aged over 80 years (p<0.001). By contrast, in overt hypothyroidism (n= 4403), TSH was lower in older age groups compared with those aged 20 to 39 years (p<0.001).

Conclusions:

The TSH-free T4 relationship is not inverse log-linear but can be described by two overlapping negative sigmoid curves. At physiological free T4 concentrations, TSH is higher in males and in older people, whereas the TSH response to hypothyroidism is more robust in younger people. These results advance understanding of the TSH-free T4 relationship, which is central to thyroid pathophysiology and laboratory diagnosis of thyroid disease.

AIMS/

HYPOTHESIS:

The aim of this work was to investigate, in children newly diagnosed with type 1 diabetes: (1) the prevalence of autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb); and (2) the association between TPOAb, TGAb or both, with either islet autoantibodies or HLA-DQ genes.

METHODS:

Blood samples from 2,433 children newly diagnosed with type 1 diabetes were analysed for TPOAb and TGAb in addition to autoantibodies against arginine zinc transporter 8 (ZnT8RA), tryptophan zinc transporter 8 (ZnT8WA), glutamine zinc transporter 8 (ZnT8QA), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), HLA-DQA-B1 genotypes, thyroid-stimulating hormone (TSH) and free thyroxine (T4).

RESULTS:

At type 1 diabetes diagnosis, 12% of the children had thyroid autoantibodies (60% were girls; p < 0.0001). GADA was positively associated with TPOAb (p < 0.001) and with TGAb (p < 0.001). In addition, ZnT8A was associated with both TPOAb (p = 0.039) and TGAb (p = 0.015). DQB1*05:01 in any genotype was negatively associated with TPOAb (OR 0.55, 95% CI 0.37, 0.83, p value corrected for multiple comparisons (p c) = 0.012) and possibly with TGAb (OR 0.55, 95% CI 0.35, 0.87, p c = 0.07). Thyroid autoimmunity in children newly diagnosed with type 1 diabetes was rarely (0.45%) associated with onset of clinical thyroid disease based on TSH and free T4.

CONCLUSIONS

/

INTERPRETATION:

GADA and ZnT8A increased the risk for thyroid autoimmunity at the time of clinical diagnosis of type 1 diabetes, while HLA-DQB1*05:01 reduced the risk. However, the associations between thyroid autoimmunity and HLA-DQ genotype were weak and did not fully explain the co-occurrence of islet and thyroid autoimmunity.

Our previous study reported that thyroid-stimulating hormone (TSH) promotes cholesterol synthesis via the cyclic adenosine monophosphate/protein kinase A/cAMP regulatory element-binding protein (cAMP/PKA/CREB) pathway after binding to TSH receptors in the liver. The hepatic cAMP/PKA/CREB pathway also plays an important role in maintaining fasting glucose homeostasis. These findings implied a possible role for TSH in hepatic glucose metabolism. In this study, we used TSH receptor knockout mice (Tshr-ko mice) to clarify the effect of Tshr deletion on hepatic glucose metabolism, and investigated whether the effects of TSH directly regulate hepatic gluconeogenesis in HepG2 cells. Tshr-ko mice exhibited decreased fasting blood glucose levels, increased insulin sensitivity but normal level of fasting plasma insulin. Tshr deletion impaired hepatic glucose production by down-regulating the expression of glucose-6-phosphatase (G6P) and phosphoenolpyruvate pyruvate carboxylase (PEPCK) mRNA, two rate-limiting enzymes in hepatic gluconeogenesis, and enhancing the abundance of hepatic glucokinase (GK), the first enzyme regulating glycogen synthesis. Moreover, Tshr deletion inhibited the protein expression of hepatic phospho-CREB and increased the protein expression of hepatic phospho-AMP-activated protein kinase (p-AMPK), two up-stream regulators of PEPCK and G6P mRNA. In HepG2 cells, TSH increased the expression of G6P and PEPCK at mRNA level. These results indicated the simulative effects of TSH on hepatic glucose production in vivo and in vitro, suggesting a novel role for TSH in hepatic glucose metabolism.

It has been commonly recognized that circadian rhythm and sleep/wake cycle are causally involved in bipolar disorder. There has been a paucity of systematic research considering the relations between sleep and mood states in bipolar disorder. The current study examines the possible influences of sleep deprivation on mood states and endocrine functions among first-degree relatives of patients with bipolar disorder and healthy controls. Blood samples were taken at two time points in the consecutive mornings at predeprivation and postdeprivation periods. Participants simultaneously completed the Profiles of Mood States at two time points after giving blood samples. Plasma T3 and TSH levels increased after total sleep deprivation in both groups. Sleep deprivation induced TSH levels were reversely associated with depression-dejection among healthy controls. A paradoxical effect was detected for only the first-degree relatives of the patients that changes in plasma cortisol levels negatively linked to depression-dejection and anger-hostility scores after total sleep deprivation. Plasma DHEA levels became correlated with vigor-activity scores after sleep deprivation among first-degree relatives of bipolar patients. On the contrary, significant associations of depression-dejection, anger-hostility, and confusion-bewilderment with the baseline plasma DHEA levels became statistically trivial in the postdeprivation period. Findings suggested that first-degree relatives of patients with bipolar disorder had completely distinct characteristics with respect to sleep deprivation induced responses in terms of associations between endocrine functions and mood states as compared to individuals whose relatives had no psychiatric problems. Considering the relationships between endocrine functions and mood states among relatives of the patients, it appears like sleep deprivation changes the receptor sensitivity which probably plays a pivotal role on mood outcomes among the first-degree relatives of patients with bipolar disorder.

Background:

Thyroid disease during pregnancy may be associated with increased risk of various pregnancy complications. It is known that serum thyroid stimulating hormone (TSH) is suppressed by human chorionic gonadotrophin (hCG) in early pregnancy, and that higher hCG levels in twin pregnancies may cause a more pronounced physiologic suppression, this is important to avoid unnecessary concern and facilitate the diagnosis of overt thyroid disease in twin pregnancy. The aim of this study is to establish normal ranges of maternal serum TSH, and free thyroxine (FT4) at 11-13 weeks' gestation in twin pregnancy.

Methods:

This was a case series of 177 dichorionic and 58 monochorionic twin pregnancies with normal outcome and 19 monochorionic pregnancies complicated by severe twin-to-twin transfusion syndrome (TTTS). Maternal serum concentrations of TSH, FT4, anti-thyroperoxidase and anti-thyroglobulin antibodies were measured at 11-13 weeks' gestation. The measured TSH and FT4 were converted to multiple of median (MoM) of normal singleton pregnancy and MoM values in the different groups were compared.

Results:

In the antithyroid antibody negative twin pregnancies with normal outcome, compared to singletons, serum TSH MoM was lower (median 0.62, IQR 0.16-1.18 vs. 1.01, IQR 0.61-1.51; P<0.0001), FT4 MoM was not significantly different (median 0.98, IQR 0.91-1.08 vs. 0.99, IQR 0.91-1.09; P=0.975) and free ß-hCG MoM was higher (median 1.91, IQR 1.33-2.59 vs. 0.98, IQR 0.66-1.50; P<0.0001). In the antibody-positive group (n=37), compared to the negative group (n=198), the median TSH was higher but FT4 and free ß-hCG were not significantly different. In the TTTS group, compared to normal twin pregnancies, TSH, FT4 and free ß-hCG were not significantly different.

Conclusion:

In twins, compared to singleton pregnancies, TSH is lower but FT4 is not significantly different. These normal ranges of thyroid hormones in twins can form the basis for the study of early thyroid function in pathological pregnancies and the investigation of the consequences of overt and subclinical hypothyroidism on twin pregnancy outcome.