triiodothyronine--reverse and Diabetes-Mellitus--Type-1

This article reviews our current knowledge on the effects of diabetes mellitus on thyroid function at the level of the pituitary-thyroid-peripheral tissue axis and attempts to determine its clinical importance.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Hypothalamo-Hypophyseal System; Pituitary Gland, Anterior; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

In 129 children, aged 12.6 +/- 3.8 years, affected by type 1 diabetes mellitus, the levels of dehydroepiandrosterone sulfate (DHEAS), cortisol, T3, fT3, T4, fT4, rT3, TSH, cholesterol, and triglycerides were evaluated and compared with those of a control group of 458 healthy age-matched children. The results were also correlated with hemoglobin HbA1C. The DHEAS-standard deviation score (DHEAS-SDS; -0.36 +/- 0.77) was significantly different from zero in diabetic children, while the cortisol serum level was higher than in control subjects (485 +/- 94 vs 359 +/- 132 nmol/l). Moreover, the DHEAS-SDS and DHEAS-SDS/cortisol ratio correlated negatively with HbA1c. Diabetic patients also showed lower T3 values (2.22 +/- 0.4 vs 2.32 +/- 0.3 nmol/l) and a higher rT3/T3 ratio (0.17 +/- 0.09 vs 0.15 +/- 0.05) than controls. There was a negative correlation between T3 and HbA1C. Cholesterol (4.77 +/- 1.08 vs 4.51 +/- 0.76 mmol/l) and triglycerides (0.82 +/- 0.53 vs 0.63 +/- 0.37 g/L) levels were higher in diabetic children and positively correlated with HbA1c, but not with DHEAS-SDS. We can therefore conclude that diabetes, particularly if poorly controlled, tends to induce a dissociation of cortisol and DHEAS secretion and a low T3 syndrome, similar to that seen in other illnesses.

Topics: Adolescent; Adrenal Glands; Age Factors; Blood Glucose; Child; Child, Preschool; Cholesterol; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Diabetes Mellitus, Type 1; Female; Humans; Hydrocortisone; Male; Reference Values; Thyroid Gland; Thyrotropin; Thyroxine; Triglycerides; Triiodothyronine; Triiodothyronine, Reverse

Thyroid hormone (TH) abnormalities are common in patients with diabetes mellitus (DM). These thyroid hormone abnormalities have been associated with inflammatory activity in several conditions but this link remains unclear in DM. We assessed the influence of subclinical inflammation in TH metabolism in euthyroid diabetic patients. Cross-sectional study involving 258 subjects divided in 4 groups: 70 patients with T2DM and 55 patients with T1DM and two control groups of 70 and 63 non-diabetic individuals, respectively. Groups were paired by age, sex, and body mass index (BMI). We evaluated the association between clinical and hormonal variables [thyrotropin, reverse T3 (rT3), total and free thyroxine (T4), and triiodothyronine (T3)] with the inflammation markers C-reactive protein (hs-CRP), serum amyloid A (SAA), and interleukin-6 (IL-6). Serum T3 and free T3 were lower in patients with diabetes (all P < 0.001) compared to the control groups. Interleukin-6 showed positive correlations with rT3 in both groups (P < 0.05). IL-6 was independently associated to FT3/rT3 (B = -0.193; 95% CI -0.31; -0.076; P = 0.002) and FT4/rT3 (B = -0.107; 95% CI -0.207; -0.006; P = 0.039) in the T1DM group. In the T2DM group, SAA (B = 0.18; 95% CI 0.089; 0.271; P < 0.001) and hs-CRP (B = -0.069; 95% CI -0.132; -0.007; P = 0.03) predicted FT3 levels. SAA (B = -0.16; 95% CI -0.26; -0.061; P = 0.002) and IL6 (B = 0.123; 95% CI 0.005; 0.241; P = 0.041) were related to FT4/FT3. In DM, differences in TH levels compared to non-diabetic individuals were related to increased subclinical inflammatory activity and BMI. Altered deiodinase activity was probably involved. These findings were independent of sex, age, BMI, and HbA1c levels.

Topics: Adult; Asymptomatic Diseases; C-Reactive Protein; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Serum Amyloid A Protein; Thyroid Diseases; Thyroid Function Tests; Thyroid Hormones; Triiodothyronine, Reverse; Young Adult

The response of the pituitary- thyroid axis, reverse triiodothyronine (rT3), prolactin, and growth hormone (GH) levels following TRH stimulus (Relefact TRH 200 microg 2 amp. i.v.) was examined in patients with autoimmune diabetes type 1 (DM1, n=30), with autoimmune thyroiditis (AT, n=25), and with concurrent DM1 and AT (n=22) to evaluate the influence of DM1 and AT of autoimmune pathogenesis on the above-mentioned hormonal parameters. Statistical analysis (ANOVA) showed that: a) the response of TSH did not differ from control groups (C); b) free triiodothyronine (fT3), free thyroxine (fT4) and their ratio in DM1, DM1+AT and C rose in 120 and 180 min, while a similar increase was not seen in AT (p<0.000001); c) rT3 was not present in any group, with rT3 levels higher in AT (p<0.00002) and lower in DM1 (p<0.02); d) the response of GH had a paradoxical character in some patients in all groups, most often in DM1 (52 %, DM1 vs C, p <0.01). The characteristic response difference was not in the peak GH level, but the delayed return to basal levels in DM1 (p<0.0001) and an abrupt one in AT (p<0.0001). The major findings in DM1 were the differences in GH response, while significant impairment of pituitary-thyroid axis and PRL response to TRH was absent. AT was associated with impairment of TRH stimulated fT3, fT4, fT3/fT4 response and changes in rT3 levels, in spite of preserved TRH-stimulated TSH secretion. GH response in AT patients was also altered.

Topics: Adult; Diabetes Mellitus, Type 1; Female; Hormones; Human Growth Hormone; Humans; Male; Middle Aged; Pituitary Gland; Prolactin; Thyroid Gland; Thyroiditis, Autoimmune; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Associated autoimmune phenomena might influence metabolic control in children and adolescents with Type 1 diabetes mellitus. A retrospective case control study was performed in order to explore the effect of subclinical hypothyroidism on metabolic control in Type 1 diabetes mellitus.. For this purpose each patient with Type 1 diabetes and subclinical hypothyroidism (cases) was matched for age, duration of disease and, if possible, for sex, with two to three diabetic patients without hypothyroidism (controls). Parameters of metabolic control such as HbA1c, total insulin requirement and frequency of symptomatic hypoglycaemia were retrieved for 12, 6 and 3 months before and after diagnosis of hypothyroidism.. Thirteen patients (two male/11 female) patients were diagnosed with subclinical hypothyroidism and were matched with 31 controls (nine male/22 female). There was no difference (mean and range) in terms of age (11.9 years (4.4-18.1) vs. 11.7 years (3.5-18.1), P = 0.9) and duration of disease (5.1 years (1.2-10.5) vs. 4.38 years (0.9-10.8), P = 0.6) between the two groups. There was no difference in HbA1c and total insulin requirement between the two groups at any time point of assessment (anova P = 0.8 and P = 0.1, respectively). Patients with hypothyroidism had significantly more symptomatic hypoglycaemic episodes during the 12 months before diagnosis (anova P = 0.05), increasing progressively during this time period and reaching a peak at time 0 (5.5+/-0.4 vs. 1.6+/-0.1 episodes/month, P = 0.01). No difference could be detected within 6 months of starting substitution therapy (2.4+/-0.2 vs. 1.6+/-0.1 episodes/week, P = 0.8).. These data suggest that subclinical hypothyroidism is associated with an increased risk of symptomatic hypoglycaemia. The prompt introduction of substitution therapy is recommended as it reduces its frequency.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Female; Humans; Hypothyroidism; Male; Prevalence; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Serum concentrations of thyroxine (T4),3,5,3'-triiodothyronine (T3),3,3',5'-reverse triiodothyronine (rT3),T3-binding capacity (TBC) and TSH were measured in 10 children with diabetes mellitus (mean age: 12.8 +/- 2 yr). The children were without ketoacidosis and serum glucose concentrations were 10.64 +/- 1.68 mmol/l (SD). The mean concentrations of serum T4, T3, rT3, TBC and TSH were 116.35 +/- 10.68 nmol/l (SD), 2.81 +/- 0.33 nmol/l, 0.27 +/- 0.04 nmol/l, 1.087 +/- 0.031 and 3.16 +/- 0.9 mu IU/ml, respectively, which were not significantly different from values of 10 normal control subjects (mean age: 11.6 +/- 2 yr). It seems therefore that the thyroid hormones and TSH levels between well controlled diabetic and healthy subjects of pediatric age do not differ significantly.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Female; Humans; Male; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

We have evaluated the thyroid function in 30 children and adolescents (average age 13 2/12 +/- 3 10/12 years) suffering from type 1 insulin-dependent diabetes (average duration of illness 5 +/- 3 3/12 years). We divided them into group A (good control) and group B (poor control), according to whether they had presented an HbA1C value lower or higher than 10%. The results obtained have been compared with a group of 30 normal patients of the same age. Both groups of diabetics presented T4 values which were notably lower than the control group (P less than 0.05). T3 was appreciably diminished both in group A (P less than 0.05) and in group B (P less than 0.01) and presented a negative correlation with HbA1C, only in group A however. The rT3/T3 ratio, on the other hand, was significantly increased in group B with respect to the controls. No significant differences were found with regard to FT3 and FT4, nor any correlations among thyroid hormones, C peptide, duration of illness, and daily insulin requirement. Our results indicated that the tendency to the low T3 syndrome, already described in adult diabetics, is also identifiable in young diabetics, particularly if poorly controlled.

Topics: Adolescent; Adult; Child; Child, Preschool; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The serum levels of thyroid hormones and thyroid stimulating hormone were compared in 64 type I diabetic children and adolescents without ketosis and in 28 age matched normal subjects. Only T3 levels were significantly different in the diabetic patients (2.38 +/- 0.41 nmol/l) than in controls (2.64 +/- 0.52 nmol/l) (p less than 0.01) confirming the existence of the 'low T3 syndrome' in diabetic children. A negative correlation was found between T3 and blood glucose as well as glycosylated haemoglobin suggesting that short-term hyperglycaemia could regulate T3 concentration. Thyroid function was not different in diabetic children with or without thyroid antibodies. We conclude that serum T3 level is influenced by the degree of metabolic control and that thyroid function in diabetic children should be assessed by the measurement of the serum concentration of T4, FT4 and TSH.

Topics: Adolescent; Age Factors; Autoantibodies; Child; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Male; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Male; Syndrome; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The influence of diabetic metabolic control on indices of thyroid function was studied in 9 euthyroid, insulin-dependent (Type 1) diabetics. During chronic poor metabolic control (mean fasting blood glucose 13 mmol/l and HbA1 concentrations 14.7%) serum T3 concentrations were low (P less than 0.01) while serum T4 and basal TSH concentrations were normal. After 6-8 weeks of improved metabolic control, mean HbA1 concentrations had fallen to 10.7% (P less than 0.01) and serum T3 concentrations had increased into the normal range. Serum T4 and basal TSH concentrations were unchanged. The serum TSH response to iv TRH remained normal throughout the study. In Type 1 diabetics, with chronic poor metabolic control, the serum T4 concentration and the TSH response to TRH are therefore appropriate indicators of thyroid function.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Comprehensive evaluation of thyroid hormone indices was performed in 58 children with insulin-dependent diabetes mellitus (IDDM) at the time of diagnosis and prior to insulin therapy. Two patients were found to have primary hypothyroidism, with markedly elevated TSH and very low T4, free T4, T3, and reverse T3 concentrations. The remaining 56 patients had the transient alterations in thyroid hormone indices that are characteristic of "euthyroid sick" or "low T3" syndrome. Mean TSH and reverse T3 values were significantly higher and the mean T3, T4, and free T4 levels were significantly lower than those observed in the control population. Ten of the diabetic patients had elevated TSH concentrations and normal or low free T4 values; eight had normal TSH levels and low T4 and free T4 values. The remainder of the group had thyroid indices compatible with abnormal peripheral metabolism of thyroid hormones. Elevated titers of antimicrosomal antibodies were found in 16% of the children with IDDM. We conclude that abnormal peripheral metabolism and altered hypothalamic-pituitary function are responsible for the transient changes in thyroid hormone indices in patients with untreated IDDM. The most reliable indicators of concomitant primary hypothyroidism in untreated IDDM are markedly elevated TSH and low reverse T3 values.

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Humans; Hypothyroidism; Infant; Male; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine, Reverse

Several parameters of thyroid function were studied in 112 non-ketoacidotic youngsters with insulin-dependent diabetes mellitus (IDDM). Levels of thyroxine (T4), reverse triiodothyronine (rT3), thyroxine-binding globulin (TBG) and T3 were lower than in controls, whereas FT4, and FT3 were normal. T4 levels in IDDM patients were positively related to T3, rT3 and TBG, and inversely related to haemoglobin A1 (HbA1). However, only 4 patients showed biochemical hypothyroidism (T4 less than 5 micrograms/100 ml), whereas their FT4, FT3 and thyroid-stimulating hormone (TSH) levels were normal. Concurrent variations of T3 and rT3 levels were found in IDDM patients; thus, their T3/rT3 ratios were stable or higher than in controls, indicating that peripheral deiodination of T4 is preferentially oriented to production of rT3 only during ketoacidosis. Although changes in thyroid function may reflect the degree of metabolic control of diabetes in a large population, the clinical usefulness of serum thyroid hormone measurements in an individual case still appears to be limited.

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Humans; Male; Thyroid Hormones; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Measurements of T4, T3, rT3, and TSH were done in 27 children with newly diagnosed type I diabetes mellitus prior to institution of treatment. Serum T4 concentrations were low in 18%, serum T3 concentrations were low in 37%. Serum rT3 concentrations were elevated in 59%; the ratio rT3/T3 was elevated in 78%. The ratio rT3/T3 was significantly higher in the group of patients with the low pH, the low bicarbonate levels, the high blood glucose, and the high serum osmolality values than in the group of patients with the high pH, the high bicarbonate levels, the low blood glucose, and the low serum osmolality values.

Topics: Adolescent; Bicarbonates; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Hemoglobinometry; Humans; Hydrogen-Ion Concentration; Iodide Peroxidase; Male; Osmolar Concentration; Thyroxine; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

Alterations in circulating iodothyronines were studied in 15 juvenile type diabetic patients during the development of metabolic derangement after withdrawal of insulin. By means of measurements of circulating C peptide, one group of patients with and one without residual beta-cell function had been selected. In both groups there was a gradual decrease in serum T3 during the 12-hour period studied after withdrawal of insulin, while an increase in serum rT3 was observed after 4-6 hours. The alterations in serum T3 and the metabolic derangement were significantly more pronounced in patients without than with residual beta-cell function.

Topics: C-Peptide; Diabetes Mellitus, Type 1; Humans; Insulin; Islets of Langerhans; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Circadian Rhythm; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Male; Middle Aged; Myxedema; Somatostatin; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Serum T3, rT3, T4 and TSH were measured in ten healthy subjects, in nine juvenile diabetic outpatients in fair metabolic control (fasting plasma glucose 6.5 mmol/1, 2.6-9.5 mmol/1 (mean, range), HbA1 10.1%, 8.1-12.2%), and in ten juvenile diabetic outpatients in poor metabolic control but without ketonuria (fasting blood glucose 15.1 mmol/l, 11.1-22.4 mmol/l, HbA1, 13,8% 10.8-16,2%. Serum T3 was identical in normal subjects and in diabetics in fair metabolic control. Diabetics in poor metabolic control had 13.0% lower serum T3 than normal subjects (2 p less than 0.05). No difference between groups was observed in serum rT3, T4 and TSH. These findings indicate that in diabetic patients, metabolic derangement induces alterations in serum T3 more easily than in serum rT3. However, alteration in serum T3 is not a sensitive indicator of moderate metabolic derangement in diabetic patients.

Topics: Adult; Diabetes Mellitus, Type 1; Female; Humans; Male; Reference Values; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse