Jan Kvetny

Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years.

objective  Mild thyroid failure is associated with an increased risk for development of atherosclerosis, but whether subclinical hypothyroidism is related to risk for cardiovascular disease is controversial. The purpose of the present study was to examine a possible association between subclinical hypothyroidism and cardiovascular disease.

Prevalence of depression, quality of life and antidepressant treatment in the Danish General Suburban Population Study

Abstract Background: The Danish General Suburban Population Study (GESUS), the objective of which is to facilitate epidemiological and genetic research, has included the Major Depression Inventory (MDI) and the WHO-Five Well-Being Index (WHO-5) among the medical health questionnaires. We were thus in a position to compare the 2-week prevalence of ICD-10 depression in the period from 2010 to 2012 with our previous Danish general population study from 2003, in which the MDI was also included. Aims: The aim of our analysis was not only to evaluate the point prevalence of ICD-10 depression but also to describe the prevalence of antidepressants received by the respondents in the GESUS study and the correspondence to their subjective well-being on the WHO-5 questionnaire. Methods: To evaluate the validity (scalability) of the MDI and the WHO-5 in the GESUS study we performed the non-parametric Mokken analysis. The scalability of the MDI and the WHO-5 was quite acceptable. Results: In total, 14,787 respondents were available from a response rate of 50%. The 2-week prevalence of ICD-10 depression was 2.3%, which is rather similar to the 2.8% in our 2003 study. The rate of people receiving antidepressants increased consistently with increasing severity of ICD-10 depression. Conclusion: This study has confirmed that the use of the MDI to obtain an ICD-10 depression diagnosis gives rather conservative estimates of the 2-week prevalence of depression in the Danish general population. The prescription of antidepressants depends on the severity of the ICD-10 depression diagnosis.

TSH, thyroid hormones and nuclear-binding of T3 in mononuclear blood cells from obese and non-obese women

The specific nuclear-binding of T3 (NBT3) in mononuclear blood cells, and the concentrations of TSH, thyroid hormones, and binding proteins were measured after overnight fasting in 12 obese and in 14 non-obese women, none of the subjects were taking any medicine. The concentrations of TSH and free plus bound-T3 (TT3) were significantly higher in the obese (p less than 0.05), concentrations of T4 and binding proteins did not differ. The NBT3 was significantly lower in the obese women; the maximal binding capacity (MBC) was 34.5 +/- 11.6 fmol/mg DNA in the obese subjects and 50.0 +/- 11.6 fmol/mg DNA in the non-obese subjects (p less than 0.02). The binding affinities did not differ. We have previously shown that increasing T3 concentrations within the physiological range down-regulates NBT3. Therefore, the reduced NBT3 in the obese women was probably secondary to the increased TT3 concentration and was not caused by a primary tissue resistance. The higher TSH and TT3 in the obese women could be caused by a greater caloric intake.

Subclinical hypothyroidism affects mitochondrial function.

The aim of the present study was to examine mitochondrial function in cells from persons with subclinical hypothyroidism and euthyroid controls. The participating persons were examined clinically and had basal oxygen consumption (VO(2)) determined. The concentrations of thyroid hormones and thyrotropine stimulating hormone were determined, and mitochondrial function in isolated mononuclear blood cells was examined by enzymatic methods [citrate synthase activity (CS)] and by flow cytometry (mitochondrial membrane potential by TMRM fluorescence and mitochondrial mass by MTG fluorescence). The ratio of T(4)/T(3) was lowered in subclinical hypothyroidism patients compared to controls (2.5+/-0.5 vs. 2.9+/-0.4, p=0.005). VO(2) was increased in persons with subclinical hypothyroidism compared to controls (adolescents: 134+/-27 ml O(2)/min*m(2) vs. 119+/-27 ml O(2)/min*m(2), p=0.006, adults: 139+/-14 ml O(2)/min*m(2) vs. 121+/-17 ml O(2)/min*m(2), p=0.001). The mitochondrial function, represented by citrate synthase activity, MTG, and TMRM fluorescence were all increased (CS in subclinical hypothyroidism vs. controls: 0.074+/-0.044 nmol/mg*min vs. 0.056+/-0.021 nmol/mg*min, p=0.005; MTG fluorescence in subclinical hypothyroidism vs. controls: 7,482+/-1,733 a.u. vs. 6,391+/-2,171 a.u., p=0.027; TMRM fluorescence in subclinical hypothyroidism vs. controls: 13,449+/-3,807 a.u. vs. 11,733+/-4,473 a.u, p=0.04). Our results indicate an increased mitochondrial stimulation, eventually caused by increased deiodination of T(4) to intracellular bioactive iodothyronines in adults and adolescents with subclinical hypothyroidism.

Well-being and depression in individuals with subclinical hypothyroidism and thyroid autoimmunity—A general population study

Abstract Background: The association between subclinical hypothyroidism (SCH), with and without raised thyroid peroxidase antibodies (anti-TPO), and well-being or depression is still controversial, in spite of many studies on the topic. Aims: In this large general population study of 8214 individuals, we aim to clarify the significance of elevated levels of anti-TPO as a marker of poor well-being and depression in euthyroid individuals and individuals with SCH. Methods: In participants from the Danish General Suburban Population Study (GESUS), serum thyroid stimulating hormone (TSH), total triiodothyronine (tT3), free thyroxine (fT4) and anti-TPO was measured. Prevalence of poor well-being and depression was measured using the WHO-5 Well-being questionnaire and WHO MDI [Major (ICD-10) Depression Inventory] questionnaire. Results: Raw score for well-being or depression overall and stratified for sex was not more significantly different in euthyroid individuals than in individuals with SCH, with or without high anti-TPO, except that euthyroid women with elevated anti-TPO had better well-being (P = 0.03) compared with euthyroid women with anti-TPO within the reference range. Conclusion: Elevated anti-TPO levels cannot be used as a general marker of poor well-being or depression in the general population.

The influence of caloric deprivation and food composition on TSH, thyroid hormones and nuclear binding of T3 in mononuclear blood cells in obese women

In vivo changes in thyroid-stimulating hormone (TSH), thyroxin (T4), triiodothyronine (T3) and nuclear binding of T3 (NBT3) in mononuclear blood cells were studied in obese women during seven days of caloric deprivation (maximum 1,100 kcal/d). In seven women given a high protein diet (80% protein, 7% carbohydrates, 7% fat) and in two women who fasted (group 1), total T3 (TT3) decreased from 1.66 +/- 0.43 nmol/L to 1.11 +/- 0.32 nmol/L (P less than .01), free T3 (FT3) decreased from 5.7 +/- 1.1 pmol/L to 4.3 +/- 1.6 pmol/L (P less than .01), and free T4 (FT4) increased from 17.8 +/- 2.3 pmol/L to 21.1 +/- 2.0 pmol/L (P less than .01). In five women given a carbohydrate diet (Dextrin-maltose 100%) (group 2), thyroid hormones were unchanged, TT3 was at start 1.66 +/- 0.24 nmol/L and after seven days 1.43 +/- 0.26 nmol/L (NS), FT3 changed from 6.4 +/- 1.8 pmol/L to 6.0 +/- 2.1 pmol/L (NS) and FT4 changed from 20.4 +/- 5.1 pmol/L to 20.6 +/- 3.1 pmol/L (NS). The caloric intake and the weight reduction was the same in the two groups. Basal TSH and TSH after thyrotropin-releasing hormone (TRH) (TSH+30min) declined in both groups. In group 1, basal TSH declined from 1.88 +/- 1.07 microU/mL (P less than .03), and TSH+30min declined from 12.44 +/- 7.49 microU/mL to 9.38 +/- 5.97 microU/mL (P less than .03). In group 2, basal TSH declined from 2.09 +/- 0.87 microU/mL to 1.66 +/- 0.92 microU/mL (P less than .03), and TSH+30min declined from 15.63 +/- 7.90 microU/mL to 11.93 +/- 7.20 microU/mL (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid hormone resistance in blood monocyte cells and elevated serum T3 in patients with autosomal dominant osteopetrosis

Seven patients with autosomal dominant osteopetrosis from three different families were investigated. They all had the roentgenological type I disease, characterized by universal, symmetrical osteosclerosis and enlarged thickness of the calvarium vault. Serum concentrations of thyroid hormones and the specific nuclear binding of triiodothyronine (T3) in mononuclear blood cells were studied. All patients appeared clinically euthyroid. The serum level of T3 was significantly elevated (serum T3 = 1.89 nmol/l) compared with normal age and sex-matched controls (serum T3 = 1.44 nmol/l, p less than 0.05). The specific maximal nuclear binding capacity of T3 was significantly decreased (MBC = 0.51 fmol T3/mg DNA) in these patients compared with controls (MBC = 1.8 fmol/mg DNA, p less than 0.05) whereas no difference in the equilibrium association constant (Ka) was observed. The decreased specific nuclear binding of T3 and the slightly elevated serum level of T3 might indicate a modest peripheral resistance to T3 in patients with autosomal dominant osteopetrosis type I.

NUCLEAR BINDING AND CELLULAR METABOLISM OF THYROXINE IN A EUTHYROID PATIENT WITH HYPERTHYROXINAEMIA

The receptor mechanism and intracellular T4 deiodination were studied in a patient, who was euthyroid despite high T4 levels. Serum T3 and serum reverse T3 levels were normal and the TRH tests produced a normal rise in TSH. Protein binding capacities for T4 in serum were found to be normal. The T4 bound to a single set of binding sites in the patients lymphocyte nuclei with a Ka which was depressed as compared with that of normals (Ka= 2·8 × 1010 l/mol) and a maximum specific binding capacity (MSBC = 1·9 fmol T4/10 μg DNA) which was increased as compared with normals (msbc = 1 × 10−16 mol/l T4/10 μg DNA). The cellular deiodination of T4 was found to be normal, whereas T3 accumulation was increased and the nuclear T3 concentration raised. In conclusion, these results suggest that in this patient the syndrome of peripheral tissue resistance to thyroid hormone action is due to a defect at the level of the nuclear receptor and not to a defective intracellular T4 to T3 conversion.

Impaired Fertility Associated with Subclinical Hypothyroidism and Thyroid Autoimmunity: The Danish General Suburban Population Study

Introduction. The aim of this study was to estimate the significance of TSH, thyroid peroxidase antibody (TPOAb), and mild (subclinical) hypothyroidism in women from The Danish General Suburban Population Study (GESUS) on the number of children born, the number of pregnancies, and the number of spontaneous abortions. Methods. Retrospective cross sectional study of 11254 women participating in GESUS. Data included biochemical measurements and a self-administrated questionnaire. Results. 6.7% had mild (subclinical) hypothyroidism and 9.4% prevalent hypothyroidism. In women with mild hypothyroidism TPOAb was significantly elevated and age at first child was older compared to controls. TSH and TPOAb were negatively linearly associated with the number of children born and the number of pregnancies in the full cohort in age-adjusted and multiadjusted models. TSH or TPOAb was not associated with spontaneous abortions. Mild (subclinical) hypothyroidism was associated with a risk of not having children and a risk of not getting pregnant in age-adjusted and multiadjusted models. Prevalent hypothyroidism was not associated with the number of children born, the number of pregnancies, or spontaneous abortions. Conclusion. Impaired fertility is associated with TSH, TPOAb, and mild (subclinical) hypothyroidism in a Danish population of women.

Peripheral markers of thyroid function: the effect of T4 monotherapy vs T4/T3 combination therapy in hypothyroid subjects in a randomized crossover study

Background A recent randomized controlled trial suggests that hypothyroid subjects may find levothyroxine (l-T4) and levotriiodothyronine combination therapy to be superior to l-T4 monotherapy in terms of quality of life, suggesting that the brain registered increased T3 availability during the combination therapy. Hypothesis Peripheral tissue might also be stimulated during T4/T3 combination therapy compared with T4 monotherapy. Methods Serum levels of sex hormone-binding globulin (SHBG), pro-collagen-1-N-terminal peptide (PINP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (representing hepatocyte, osteoblast, and cardiomyocyte stimulation respectively) were measured in 26 hypothyroid subjects in a double-blind, randomized, crossover trial, which compared the replacement therapy with T4/T3 in combination (50 μg T4 was substituted with 20 μg T3) to T4 alone (once daily regimens). This was performed to obtain unaltered serum TSH levels during the trial and between the two treatment groups. Blood sampling was performed 24 h after the last intake of thyroid hormone medication. Results TSH remained unaltered between the groups ((median) 0.83 vs 1.18 mU/l in T4/T3 combination and T4 monotherapy respectively; P=0.534). SHBG increased from (median) 75 nmol/l at baseline to 83 nmol/l in the T4/T3 group (P=0.015) but remained unaltered in the T4 group (67 nmol/l); thus, it was higher in the T4/T3 vs T4 group (P=0.041). PINP levels were higher in the T4/T3 therapy (48 vs 40 μg/l (P<0.001)). NT-proBNP did not differ between the groups. Conclusions T4/T3 combination therapy in hypothyroidism seems to have more metabolic effects than the T4 monotherapy.