Thyroid function and obesity in children and adolescents

The aim of this retrospective study was to investigate the frequency of thyroid dysfunction as assessed by TSH, T3 and T4 in a large cohort of 290 obese and 280 healthy children. In addition, thyroid autoantibodies were measured in random subgroups of 123 obese and 80 control children, iodine excretion in 50 and thyroid volume in 23 of the obese children. Elevated TSH levels (>4 U/l) were found in 22 obese children (7.5%), but only in one control (0.3%). The medians of TSH and T3 concentrations were normal, but significantly higher in the obese group than in the controls, while T4 levels did not differ. The prevalence of positive thyroid autoantibodies was increased in the obese children, for the most part in those with elevated TSH. There was no evidence for iodine deficiency as a cause of the average increase of TSH. We conclude that in childhood obesity TSH and T3 levels are significantly increased; in most cases, however, these increases are not accounted for by thyroid autoimmunity or iodine deficiency. As a consequence, TSH elevations with normal thyroid hormone levels in obese children don't need any thyroxine treatment, if thyroid disorders were definitely excluded beforehand.     

Destructive Thyroiditis Followed by Hypothyroidism Associated with Infliximab Therapy

ObjectiveTo present the rare case of a patient who developed destructive thyroiditis accompanied by transient thyrotoxicosis resulting from infliximab therapy for the treatment of psoriasis.MethodsThe clinical presentation and management of a case with infliximab-associated thyroiditis is described with a brief review of the literature.ResultsA 57-year-old male who suffered from psoriasis was treated with infliximab therapy for 4 years. Thyroid function tests were normal before infliximab therapy. When the patient presented in our clinic, he had thyrotoxicosis and was using propylthiouracil. A 99m Technetiumpertechnetate thyroid scintigraphy scan showed no visualization of either thyroid lobe or decreased thyroid iodine uptake. Thyroid-stimulating hormone (TSH) receptor antibody, thyroid peroxidase antibody (anti-TPO Ab) and thyroglobulin antibody (anti-Tg Ab) were negative. Thyroid ultrasonography revealed a heterogeneous thyroid gland without nodules. After stopping propylthiouracil therapy, we advised monitoring of his thyroid function tests in the following weeks, and infliximab therapy for psoriasis was continued. Four weeks later, his thyroid function tests showed an elevated TSH level with normal levels of free triiodothyronine and thyroxine (FT3 and FT4, respectively), and levothyroxine treatment was administered to the patient. Thyroid function tests normalized after levothyroxine treatment. One year later, infliximab therapy was stopped because of clinical remission. Simultaneously, levothyroxine treatment was also stopped. His thyroid function tests were normal 6 weeks after the cessation of levothyroxine treatment.ConclusionTo our knowledge, the present report is the third infliximab-associated thyroid disorder case. Periodic follow-up of thyroid function tests is necessary during infliximab therapy. (Endocr Pract. 2014;20:e207-e210)     

Screening of geriatric patients for thyroid dysfunction with thyrotropin-releasing-hormone test, sensitive thyrotropin and free thyroxine estimation

Hospitalized geriatric patients (N = 354) from an iodine-deficient area were screened with sensitive thyrotropin (TSH), free and total thyroxine (FT4, T4) and total triiodothyronine (T3) to determine the occurrence rate of clinical and subclinical thyroid dysfunction. The diagnostic value of the tests was compared to each other and to that of the thyrotropin-releasing-hormone test (TRH-test) in order to find the optimal first line screening test in geriatric patients. Clinical hyperthyroidism was found in 13, subclinical hyperthyroidism in 10, overt hypothyroidism in 6 and subclinical hypothyroidism in 8 cases. 20.6% of the patients were euthyroid but had subnormal TSH response to TRH, as a sign of possible thyroid autonomy. The low occurrence rate of clinical thyroid disorders (4.8%) does not justify the screening of geriatric patients in general, but the high probability of thyroid autonomy makes reasonable the investigation of every geriatric patient before iodine administration. Suppressed basal TSH and high FT4 were found to be both sensitive and specific in diagnosing clinical hyperthyroidism, but the predictive value was insufficient; elevated T4 and T3 are specific, but not sensitive. Basal TSH is sensitive, specific and has a good predictive value in diagnosing euthyroidism, whereas normal T4, FT4 or T3 are not specific enough for euthyroidism. Basal TSH is better as a first line test of thyroid function than FT4. A normal basal TSH confirms euthyroidism by itself. Other tests (TRH test, T4, FT4, T3) are necessary to elucidate the clinical importance of a subnormal or suppressed basal TSH.     

Thyroid Function in Patients Treated with Radioactive Iodine for Thyrotoxicosis

A series of 105 patients treated at least two years earlier with radioactive iodine for thyrotoxicosis have been surveyed. Eighty-five patients (81%) were euthyroid clinically and on the basis of routine thyroid function tests. Of the euthyroid patients 46 (54%) had normal thyroid-stimulating hormone (TSH) levels and 39 (46%) had raised TSH levels. There was no difference in serum triiodothyronine levels between these two groups but the serum protein bound iodine and serum thyroxine, though still well within the normal range, were significantly lower in the group with raised TSH levels. The serum cholesterol was also significantly higher in this latter group.Most of the euthyroid patients were seen again a year later. None had become hypothyroid and neither those with normal nor those with raised TSH levels showed any evidence of a decline in the level of serum thyroxine.It is concluded that raised serum TSH levels in patients treated with iodine-131 are not necessarily indicative of hypothyroidism. There is no indication that patients who have this abnormality become overtly hypothyroid over a 12-month follow up.     

A sensitive immunoradiometric assay for serum thyroid stimulating hormone: a replacement for the thyrotrophin releasing hormone test?

The value as a thyroid function test of a new, rapid, and highly sensitive immunoradiometric assay for thyroid stimulating hormone (TSH) was assessed in 188 consecutive new patients with suspected hyperthyroidism. The diagnosis was made on clinical grounds and on the basis of serum total triiodothyronine and thyroxine concentrations and the response of TSH to thyrotrophin releasing hormone (TRH) as measured by radioimmunoassay. In all except one patient the basal TSH concentration by immunoradiometric assay predicted the response of TSH by radioimmunoassay to TRH, an undetectable value being recorded in patients with a subnormal response and a measurable value in those with a normal test result. This clear relation was not observed for basal TSH concentrations as measured by radioimmunoassay. In a series of 39 hospital inpatients with acute or chronic non-thyroidal illness, of whom 11 had low concentrations of total thyroxine or triiodothyronine, or both, basal TSH concentrations were detectable by both radioimmunoassay and immunoradiometric assay in all cases and were associated with normal responses to TRH. The immunoradiometric assay for TSH, which is commercially available, may therefore obviate the need for the more time consuming TRH test and simplify the approach to thyroid function testing in patients with suspected hyperthyroidism.     

Significant fluctuation of thyroid function in children with chronic lymphocytic thyroiditis

In order to investigate the degree of pituitary reserve of TSH secretion and the fluctuation of thyroid function in children with chronic lymphocytic thyroiditis, TSH response to TRH was examined in 42 patients, and the thyroid function was carefully followed up in two patients retrospectively and in four prospectively. Increased basal TSH levels were revealed in seven patients (16.8%), and an exaggerated response of TSH to TRH loading in 15 (35.8%). We retrospectively observed spontaneous recovery of thyroid function in two cases. In one of them, two episodes of a transient decrease in thyroid function over a period of several years were noted. Prospectively, low normal T4, elevated TSH and normal T3 were detected in two cases at the first visit. Thereafter, TSH levels decreased to the normal range and the exaggerated response of TSH to TRH became normal. In two other cases, typical transient hypothyroidism occurred during the observation period. These fluctuations lasted for only a few months, and concomitant changes in the size of the thyroid gland were observed. No signs or symptoms suggesting viral infection were noted during the study period. Nor were changes in titers of thyroid auto-antibodies detected. These results show that the secretion of TSH is exaggerated and the thyroid function is decreased in adolescents with chronic lymphocytic thyroiditis, but the thyroid function may fluctuate from euthyroid to hypothyroid within a short period. The causes of these changes, especially of the transient hypothyroidism remain to be classified.     

Subclinical Hypothyroidism in Obese Patients: Relation to Resting Energy Expenditure,Serum Leptin,Body Composition,and Lipid Profile

Objective: To evaluate whether subclinical hypothyroidism (SH) affects resting energy expenditure (REE) as well as body composition, lipid profile, and serum leptin in obese patients. Research Methods and Procedures: A total of 108 obese patients with SH defined as normal free thyroxine levels and thyroid‐stimulating hormone (TSH) values of >4.38 μU/ml (mean ± 2 SD of the values of our reference group of obese patients with normal thyroid function) were compared with a group of 131 obese patients matched for age, sex, and body mass index (BMI) but with normal TSH levels. We assessed estimated daily caloric intake by 7‐day recall, REE by indirect calorimetry, body composition by bioelectrical impedance analysis, serum leptin by radioimmunoassay, and lipid profile (i.e., total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, and triglycerides). Results: All of the variables measured were not different between the euthyroid obese patients and those with SH. In a multiple regression model with REE expressed for kilograms of fat free mass (REE/kgFFM) as a dependent variable and percentage of fat mass, BMI, waist‐to‐hip ratio, age, TSH, free thyroxine, serum leptin, and caloric intake as independent variables, only percentage of fat mass was significantly correlated with REE/kgFFM in both groups. In the SH group only, BMI, waist‐to‐hip ratio, age, and TSH were related to REE/kgFFM and explained 69.5% of its variability. After dividing the patients with SH using a cutoff TSH value of 5.7 μU/ml, which represents 3 SD above the mean of TSH levels of the group of obese patients with normal thyroid function, only REE/kgFFM was significantly different and lower in the group of more severely hypothyroid patients. Discussion: In patients with obesity, SH affects energy expenditure only when TSH is clearly above the normal range; it does not change body composition and lipid profile. We suggest that, at least in obese patients, evaluation of TSH levels may be useful to rule out a possible impairment of resting energy expenditure due to a reduced peripheral effect of thyroid hormones.     

Selenium Status Is Positively Associated with Bone Mineral Density in Healthy Aging European Men

ObjectiveIt is still a matter of debate if subtle changes in selenium (Se) status affect thyroid function tests (TFTs) and bone mineral density (BMD). This is particularly relevant for the elderly, whose nutritional status is more vulnerable.ResultsThe overall Se status in our population was low normal with only 0.5% (2/387) of subjects meeting the criteria for Se deficiency. SePP and Se levels were not associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3) or reverse triiodothyronine (rT3) levels. The T3/T4 and T3/rT3 ratios, reflecting peripheral metabolism of thyroid hormone, were not associated with Se status either. SePP and Se were positively associated with total BMD and femoral trochanter BMD. Se, but not SePP, was positively associated with femoral neck and ward''s BMD. Multivariate linear analyses showed that these associations remain statistically significant in a model including TSH, FT4, body mass index, physical performance score, age, smoking, diabetes mellitus and number of medication use.ConclusionOur study demonstrates that Se status, within the normal European marginally supplied range, is positively associated with BMD in healthy aging men, independent of thyroid function. Thyroid function tests appear unaffected by Se status in this population.     

Erythrocyte carbonic anhydrase I concentration in patients receiving thyroxine.

We recently reported that the red blood cell (RBC) carbonic anhydrase I (CAI) concentration in patients with hyperthyroidism is reduced and reflects the patient's mean thyroid hormone level over the preceding months. In this study, RBC CAI concentrations were measured in patients with thyroid nodules who were receiving suppressive doses of thyroxine (group I) and compared with those obtained in patients with primary hypothyroidism receiving replacement doses of thyroxine (group 2). Of the 17 patients in group 1, 16 (94%) had elevated plasma free T4 levels, but all 17 had normal free T3 levels. Of the 17 patients in group 2, 16 (94%) had normal free T4 levels and all 17 had normal free T3 levels. Plasma TSH concentrations in group 1 were all below the lower limit of sensitivity of 0.04 mU/l. In group 2, 11 had normal and 6 had slightly elevated plasma TSH concentrations. The mean (+/- SD) RBC CAI concentration in group 1 (300 +/- 53 nmol/g Hb) was significantly lower than that in group 2 (340 +/- 57 nmol/g Hb). The RBC CAI concentration was significantly correlated with both the concentration of plasma free T4 and free T3. These observations indicate that in patients receiving suppressive doses of thyroxine a slight increase in the plasma free T4 concentration produces a slight but significant decrease in RBC CAI levels.     

An investigation of the prolactin-thyroxine synergism in newt limb regeneration

The use of hormone replacement to support limb regeneration in hypophysectomized newts has been the subject of many investigations. Growth hormone, as well as prolactin (PL) in combination with exogenously supplied thyroxine, have all been shown to he effective. However, the bovine growth hormone used to support limb regeneration was contaminated by prolactin and thyroidstimulating hormone (TSH). The present investigation evaluates the significance of (1) prolactin contamination and (2) endogenous thyroxine synthesis resulting from TSH contamination on limb regeneration in hypophysectomized newts. The effect of supplying exogenous thyroxine was also evaluated. Our studies showed that when hypophysectomized newts were injected with contamination levels of PL and TSH, regeneration occurred, suggesting that the newt's thyroid synthesized sufficient thyroxine to support a prolactin-thyroxine synergism. The endogenous thyroxine was synthesized by thyroid glands that were indistinguishable from those of saline-injected, hypophysectomized controls.     

Further data supporting episodic degenerative discharge of thyroid hormone from nodular goiters

To elucidate the features of thyroid hormone secretion under conditions of impaired circulation, blood samples were withdrawn at operation from thyroid and peripheral veins of 23 patients with thyroidal and non-thyroidal diseases. They were taken from the respective veins simultaneously, when the arterial supply to the thyroid tissue was partially occluded by surgical manipulation. It was found that triiodothyronine was preferentially, as compared with thyroxine, secreted from the thyroid, irrespective of the disease. Serum levels of thyroglobulin were also markedly elevated in the thyroid vein. These results suggest that episodic degenerative discharge of thyroid hormone from nodular goiters may be a cause of impaired or blunted TSH response to TRH, frequently observed in patients with common nontoxic nodular goiters.     

Treatment of inappropriate secretion of thyrotropin with somatostatin analog SMS 201-995

Inappropriate thyrotropin secretion (IST) may originate from either neoplastic disease (nIST) or non-neoplastic resistance to thyroid hormone (nnIST). An inhibitory effect of somatostatin on TSH secretion has been documented. In an attempt to elucidate the possible therapeutic effect of this peptide on nIST and nnIST, a study was conducted in 7 such patients. Sandostatin (SMS 201-995) was administered in daily doses of 100 micrograms for several days to 1 month. Four patients with nIST responded with a fall in circulating TSH as well as alpha-subunit with concomitant normalization of free thyroxine and clear symptomatic improvement. In the 3 nnIST patients this effect was considerably less apparent and a partial TSH escape was observed on long-term treatment in 2 cases. The importance of somatostatin and its analogs in the management of thyroid malignancy is stressed.     

Transient thyrotoxicosis associated with infarction of a large thyroid adenoma

We report a 46-year-old male patient with a transient thyrotoxicosis that seems to have been caused by hemorrhagic infarction of a cold thyroid nodule. The serum level of triiodothyronine was markedly but transiently elevated, while the serum thyroxine level remained within the normal range. The resected nodule, measuring 8 x 7 x 5 cm, showed extensive degeneration and necrosis with viable follicles left only at the margin of the nodule. A transient thyrotoxicosis due to acute hemorrhagic infarction of autonomously functioning thyroid nodules has already been reported. This case showed that the phenomenon could occur even in cold thyroid nodules. Its implications were discussed in relation to the high incidence of impaired TSH response to TRH in patients with nodular goiter.     

Effects of chronic hemodialysis on thyroid function in chronic renal failure

Thyroid function was studied in 54 patients undergoing chronic hemodialysis. Serum thyroxine, triiodothyronine and free thyroxine and the free thyroxine index were significantly lower than normal. The levels of both serum thyroxine and the free thyroxine index tended to fall progressively the longer the patients were on hemodialysis. These findings, in association with low serum TSH levels and normal increase in radioactive iodine uptake by the thyroid after TSH injection, suggest that a defect in pituitary secretion of TSH may be responsible. Although some patients experienced symptomatic improvement after treatment with L-thyroxine the efficacy of this form of treatment in patients on chronic hemodialysis has not yet been established.     

Changes in thyroid function caused by continuous treatment with thiouracil in rats

Serum concentration evolution of thyroxine and triiodothyronine, and thyrotropin (TSH), have been studied in rats while they were given 6-propylthiouracil (PTU) as antithyroid drug, and during the recovery period after suppression of treatment. In the same way thyroid hypertrophy and plasmatic levels of thyrotropin were correlated. Animals received orally a daily dose of 1 mg/100 g body weight during thirty-five days and had a two week recovery period. Thyroid hormone concentrations in plasma were determined by immunoenzymatic assay ELISA with peroxidase as labelled enzyme. From the results obtained, it can be stated that chronic administration of PTU implies a continuous decrease in thyroid hormone concentrations in plasma, reaching nearly zero values, while after treatment, levels recover their normal values in a week's time. A parallelism exists between thyroid hypertrophy and pituitary TSH hypersecretion, due to a decrease in thyroid hormone levels.     

Hormonal regulation of thermogenesis in goslings. Possible role of the thyroid gland.

The experiments performed on 90 male goslings showed that 6 h cold exposure (5 +/- 1 degree C) of the specimens 3, 10 and 21-day-old increases considerably 131I uptake by their thyroid gland. After single subcutaneous injection of thyroxine (100 mug/kg) no significant alterations of the metabolic rate, during 4 h measurements, in comparison with the pre-injection value were observed. Since, in control birds about 17% decrease of the metabolic rate within the same time occurred, as the effect of fasting, it was concluded that thyroxine does have the calorigenic effect. The metabolic rate of the goslings 5 to 7-day-old treated with thyroxine for four consecutive days (100 mug/kg daily) and the control ones was very similar. In the older goslings (22--24 days) thyroxine treatment significantly elevated the metabolic rate. Direct (extrathyroid) effect of TSH on heat production, did not occur in goslings.     

Changes in serum T4, T3 and TSH concentrations in newborns and infants with congenital goiter from the Mazovia region.

Thyroid function was investigated in a group of 61 newborns with congenital goiter before starting the therapy with thyroid hormones. The group included 19 girls and 42 boys, of which 27 were of age not exceeding one week (group I), 19 were between the first and the second week (group II), and 15 were between the second week and the third month of life (group III). The concentrations of the thyroid hormones were determined by radioimmunoassay. The values obtained have been compared with the local reference range obtained for the newborns of the Mazovia region. The values remaining outside the reference range were found in 47.5% of the newborns studied. The elevated values of TSH were observed mainly in group I newborns (12 from 27); among group II newborns there was only one with the elevated values, and none among the newborns of group III. thyroxine (T4) values were lowered in 14 among 27 newborns of group I, and in 2 among 19 newborns of group II; all T4 values were normal in group III. The percentage of the elevated values of triiodothyronine (T3) was higher in older newborns (group III). The elevated level of T3 accompanied by the lowered level of T4 with the normal or moderately elevated level of TSH is characteristic for the adaptation to the deficiency of iodine. There is preferential secretion of T3 aimed at maintaining euthyreosis. The elevated levels of T3 found in 30% of newborns with untreated goiter suggest an intrauterine deficit of iodine as a cause of the goiter appearance.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case with isolated ACTH deficiency accompanying chronic thyroiditis

An unusual case of isolated ACTH deficiency with coexisting chronic thyroiditis in a 53-year-old man is reported. The patient was admitted with a 2-year history of generalized fatigue, a 13-kg weight loss, muscular weakness, and frequent hypotensive and hypoglycemic attacks. On admission serum thyroxine and triiodothyronine were significantly elevated. Basal TSH concentration was not detected and TSH showed no response to TRH, but one month after replacement therapy with hydrocortisone it was shown that serum T3, T4 and TSH response were all within normal limits. Thyroid antibodies were positive and biopsy of the thyroid gland showed chronic thyroiditis. Arginine and 1-Dopa provoked a subnormal rise in GH with a maximum of 5.6 ng/ml and 5.0, respectively. One month after treatment with hydrocortisone, GH response to 1-Dopa and arginine increased to the normal range. Prolactin response to TRH was normal and FSH response to LHRH was also normal. LH showed an exaggerated response to LHRH, although a normal response was revealed after treatment with hydrocortisone. We also presented a summary of 44 Japanese cases, 23 males (mean age; 46 yrs old) and 21 females (mean age; 48 yrs old), with isolated ACTH deficiency.     

Is there a link between blastomere contact surfaces of day 3 embryos and live birth rate?

Background

Limitations in our current knowledge of normative physiologic changes in thyroid function during the periconception window narrow our ability to establish an optimal approach to screening and diagnosis of thyroid disease in pregnant women. The objective of this study was to characterize changes in thyroid function during the transition from the pre-pregnant to pregnant state in normal fertile women.

Methods

Women (N = 60) ages 30-42 years without a history of thyroid disease, who were planning pregnancy, were observed prospectively before and during early pregnancy. Thyroid function (thyroid stimulating hormone, TSH and free thyroxine, FT4) was measured before conception and between 6 and 9 weeks gestation. Pre-pregnancy samples were analyzed for thyroid antibodies. Bivariate analyses and longitudinal curves (general estimating equation models) were used to analyze changes in thyroid function during the periconception window by antibody status.

Results

Pre-pregnancy TSH values were significantly higher than early pregnancy TSH (p < 0.001), but FT4 values did not differ (p = 0.53). TSH declined as gestational age increased (P < 0.01). Thyroid antibody positive women had a higher pre-pregnancy TSH compared to antibody negative women (p < 0.01). Periconceptional change in thyroid function was more variable among women with antibodies (p < 0.001). 50% of women with elevated pre-pregnancy TSH values (TSH > 3.0 mIU/L) had normal TSH values (TSH < 2.5 mIU/L) in pregnancy.

Conclusions

TSH values decline during the transition from pre-pregnancy to early pregnancy. The change in TSH appears to be less predictable in women with thyroid antibodies. Periconceptional changes in thyroid function should be considered in formulating prenatal thyroid screening guidelines.     

Acute thyroid dysfunction (thyroiditis) after therapy with interleukin-2.

Interleukin-2 (IL-2) is frequently incorporated in antineoplastic therapy: While the effect of interferon on the thyroid has been extensively studied the impact of other cytokines on thyroid function is less well understood. We monitored the thyroid function in six patients who received IL-2 in combination with tumor necrosis factor-alpha (TNF) or alpha-Interferon (alpha IFN). Hyperthyroxinemia with suppressed TSH developed within the first four weeks of IL-2 administration; during this phase, there was no technetium or iodine uptake by the thyroid gland. During the following few weeks, serum thyroxine decreased and serum TSH rose, consistent with the development of primary hypothyroidism; during this phase, thyroidal isotope incorporation was normal. All hypothyroid patients received thyroxine replacement therapy upon documentation of hypothyroidism; in several cases thyroxine was successfully discontinued after 2-3 months. None of the patients had detectable antithyroidal antibodies and none experienced thyroid-related pain, although two patients developed thyroid enlargement. We conclude that IL-2 administration is associated with the development of transient, subacute, painless thyroiditis. The frequency and severity of this complication requires further elucidation through systematic, prospective study.