Thyroid function in thalassaemia major.

Serum concentrations of T4, T3, rT3, and TSH were measured by radioimmunoassay in 45 patients suffering from beta-thalassaemia. A TRH stimulation test was performed and the binding capacity of TBG and TBPA for T3 and T4 measured by reverse flow zone electrophoresis in a group of these patients. Mean T4 serum concentration was lower in thalassaemic patients than controls; T3, rT3, TSH levels, and the pituitary response to TRH were normal. TBPA binding capacity for thyroxine was greatly decreased, probably due to iron overload impairing the liver function. The decreased circulating total thyroxine might be explained by the reduced TBPA capacity, serum free thyroid hormone concentration total thyroxine might be explained by the reduced TBPA capacity, serum free thyroid hormone concentration values being normal. It is concluded that thalassaemic children are euthyroid, despite often having low-normal or subnormal thyroxine levels.     

Thyroid hormones before and after weight loss in obesity.

BACKGROUND: Little is known about changes in thyroid function in obese children. An influence of leptin on thyroid hormone synthesis has been proposed. AIMS: To examine thyroid function and leptin concentrations in obese children. METHODS: Triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), and leptin were measured in 118 obese children (aged 4.5-16 years); thyroid function was also determined in 107 healthy children of normal weight. T3, T4, and TSH were analysed in 55 obese children who had achieved weight reduction and in 13 obese children who had not achieved weight reduction after one year based on normal energy diet. RESULTS: TSH, T3, and T4 were significantly higher in obese children compared to those of normal weight. Twelve per cent of the obese children had TSH, 15% had T3, and 11% had T4 concentrations above the twofold standard deviation of normal weight children. The degree of overweight correlated with T3, T4, and TSH. Thyroid hormones did not correlate significantly with leptin. A reduction in overweight showed a significant decrease in T3, T4, and leptin serum concentrations, but there was no significant change in TSH. CONCLUSION: Peripheral thyroid hormones (T3, T4) and TSH are moderately increased in obese children; weight reduction leads to a long term decrease in the peripheral thyroid hormones but not in TSH. There is no necessity to treat the increased serum TSH.     

Thyroid hormones before and after weight loss in obesity

Background: Little is known about changes in thyroid function in obese children. An influence of leptin on thyroid hormone synthesis has been proposed. Aims: To examine thyroid function and leptin concentrations in obese children. Methods: Triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), and leptin were measured in 118 obese children (aged 4.5–16 years); thyroid function was also determined in 107 healthy children of normal weight. T3, T4, and TSH were analysed in 55 obese children who had achieved weight reduction and in 13 obese children who had not achieved weight reduction after one year based on normal energy diet. Results: TSH, T3, and T4 were significantly higher in obese children compared to those of normal weight. Twelve per cent of the obese children had TSH, 15% had T3, and 11% had T4 concentrations above the twofold standard deviation of normal weight children. The degree of overweight correlated with T3, T4, and TSH. Thyroid hormones did not correlate significantly with leptin. A reduction in overweight showed a significant decrease in T3, T4, and leptin serum concentrations, but there was no significant change in TSH. Conclusion: Peripheral thyroid hormones (T3, T4) and TSH are moderately increased in obese children; weight reduction leads to a long term decrease in the peripheral thyroid hormones but not in TSH. There is no necessity to treat the increased serum TSH.     

The importance of reverse triiodothyronine in hypothyroid children on replacement treatment.

Reverse triiodothyronine (rT3), triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) values were measured by radioimmunoassay in 40 children with congenital hypothyroidism who were being given levothyroxine (0.05-0.35 mg/day) and in 14 normal controls. In 15 of the children with hypothyroidism the treatment, judged by serum T4 and TSH values and thyrotrophin releasing hormone (TRH) test, seemed to be adequate and their mean rT3 value and rT3:T4 ratio were comparable with the controls. The remaining 25 children had a raised serum T4 and a low TSH value. Only 4 (16%) of these children had an abnormally high T3 concentration but the rT3 value was raised in 23 (92%) and their mean rT3 value and rT3:T4 ratio were significantly higher than in the control children. Less than 20% of this ''overtreated'' group, however, had clinical hyperthyroidism. We suggest that in patients on T4 replacement treatment the peripheral thyroid homeostatic mechanisms produce larger amounts of rT3, thereby preventing high T3 values where serum T4 values are raised. This may explain why the ''overtreated'' children showed no clinical evidence of hyperthyroidism. These findings emphasise the protective and selective role of peripheral monodeiodination.     

Evidence of hypothalamic-pituitary thyroid abnormalities in children with end-stage renal disease

Patients with end-stage renal disease may have abnormalities of growth and of gonadal and thyroid hormones, so we attempted to determine the mechanisms that may be involved in the altered thyroid function. We evaluated serum thyroid hormone levels, their changes immediately after hemodialysis, the serum thyrotropin (thyroid-stimulating hormone (TSH) response to thyrotropin releasing hormone, and the circadian pattern of serum TSH in nine children with end-stage renal disease who were between 7 1/2 years and 17 years 1 month of age. Seven patients had been receiving hemodialysis for a median of 3.3 years; the other two were receiving continuous ambulatory peritoneal dialysis. Four patients had low serum total thyroxine (T4) values, and all nine had low free T4 values. Mean concentrations of total T4, free T4, and total triiodothyronine (T3), which were significantly less than normal before hemodialysis, returned to normal levels immediately after dialysis. Postdialysis thyroid hormone increases did not correlate with the decrease in weight or the increase in hematocrit observed immediately after dialysis. All but one patient had basal TSH levels within the normal range. Three patients had a deficient TSH response to thyrotropin releasing hormone, and the TSH response was prolonged in all of them. The mean (+/- SD) nocturnal TSH surge was 50 +/- 68%. Five of the eight patients studied had a nocturnal TSH surge below the normal range (95% confidence limits 47% to 300%). Serum free T4 values correlated with the TSH nocturnal surge (r, 0.73; p less than 0.05). Our findings support the hypothesis that some patients with end-stage renal disease have central hypothyroidism.     

Thyroid hormone unresponsiveness in two siblings with intrauterine growth retardation and exophthalmos

Two cases of a brother and a sister with thyroid hormone unresponsiveness are described. They had large goiters and high levels of thyroid hormones in the face of clinical euthyroidism. The birth weight of the brother was low for his gestational age. He was also lean and exophthalmic, as is often seen in Graves' disease.Abbreviations used TSH thyrotropin - T4 thyroxine - PBI protein-bound iodine - BMR basal metabolic rate - T3 triiodothyronine - TRH thyrotropin releasing hormone - RT3U resin triiodothyronine uptake - TBG-C thyroxine binding capacity of thyroxine binding globulin - LATS long acting thyroid stimulator - hGH human growth hormone - LH luteinizing hormone - FSH follicle stimulating hormone - Gn-RH gonadotropin releasing hormone     

Effects of anticonvulsant drugs on thyroid hormones in epileptic children.

Serum total and free thyroid hormones, reverse T3 (rT3), thyroxin binding globulin (TBG) and thyroid stimulating hormone (TSH) concentrations were measured in 35 epileptic patients receiving anticonvulsants (phenobarbitone, phenytoin). There was a significant reduction found in total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3) and rT3 in the group treated with, phenytoin. The thyroid hormone levels were within normal limits in the group receiving phenobarbitone.     

Plasma thyroid hormones and prolactin in premature infants and their mothers after prenatal treatment with thyrotropin-releasing hormone.

We assayed TSH, triiodothyronine, free thyroxine, and prolactin (PRL) in plasma of women and infants participating in a trial of prenatal thyrotropin-releasing hormone (TRH) treatment for prevention of newborn lung disease. Women in labor at 26-34 wk of gestation received 400 micrograms of TRH i.v. every 8 h (one to four doses) plus 12 mg betamethasone (one or two doses); controls received saline plus betamethasone. Mean cord concentrations in control infants were TSH 9.7 mU/L, triiodothyronine 0.6 nmol/L (40.2 ng/dL), free thyroxine 14.4 pmol/L (1.13 ng/dL), and PRL 67.6 micrograms/L. TRH increased maternal plasma TSH by 100% at 2-4 h after treatment and decreased levels by 28-34% at 5-36 h. In cord blood of treated infants delivered at 2-6 h, TSH, triiodothyronine, and PRL were all increased about 2-fold versus control, and free thyroxine was increased 19%; the response was similar after one, two, three, or four doses of TRH. In treated infants delivered at 13-36 h, cord TSH and triiodothyronine levels were decreased 62 and 54%, respectively, and all thyroid hormones were lower after birth at 2 h of age versus control. We conclude that prenatal TRH administration increases thyroid hormones and PRL in preterm fetuses to levels similar to those normally occurring at term. Pituitary-thyroid function is transiently suppressed after treatment to a greater extent in fetus than mother, and infants born during the early phase of suppression do not have the normal postnatal surge in thyroid hormones.     

Hyperfunctioning thyroid nodules in children

We studied two cases of hyperfunctioning thyroid nodules in children. A 9-year-old girl and an 11-year-old girl had thyroid masses in otherwise nonpalpable thyroid glands. Scintiscan showed hyperfunctioning thyroid nodules. The former patient had elevated values for T4 and T3, and plasma thyrotropin (TSH) level failed to respond to stimulation with thyrotropin releasing hormone (TRH), whereas the latter patient had normal values for T4, and T3 and plasma TSH response to TRH was normal. After the surgical removal of nodules, scintiscan exhibited radioactivity in the contralateral lobe of the thyroid gland in the former and in the ectopic thyroid tissue in the latter. Results of microscopic examinations of thyroid nodules were consistent with adenomatous goiter.     

Hypothyroidism in children with cystinosis

Eight children with cystinosis (3 with renal transplants, 2 on maintenance haemodialysis, 2 with chronic renal failure, and one with normal renal function) were studied for evidence of hypothyroidism, and compared with a control group of children with chronic renal failure due to other causes. Abnormal thyroid function was present in all the cystinotic patients: thyroxine (T4) low in 1, free thyroxine index (FTI) low in 2, thyroid-stimulating hormone (TSH) raised in 6; all had a supranormal TSH response to thyrotrophin-releasing hormone (TRH) stimulation, indicating impaired thyroid reserve compared with patients in the control group who had a depressed or normal TSH response. Increased growth velocity with thyroid supplementation occurred in only 2 patients, and the onset of puberty may have contributed to this improvement. Hypothyroidism is a common finding in cystinosis, and it is suggested that thyroxine treatment be started when the TSH concentration becomes raised.     

Hypothyroidism in children with cystinosis.

Eight children with cystinosis (3 with renal transplants, 2 on maintenance haemodialysis, 2 with chronic renal failure, and one with normal renal function) were studied for evidence of hypothyroidism, and compared with a control group of children with chronic renal failure due to other causes. Abnormal thyroid function was present in all the cystinotic patients: thyroxine (T4) low in 1, free thyroxine index (FTI) low in 2, thyroid-stimulating hormone (TSH) raised in 6; all had a supranormal TSH response to thyrotrophin-releasing hormone (TRH) stimulation, indicating impaired thyroid reserve compared with patients in the control group who had a depressed or normal TSH response. Increased growth velocity with thyroid supplementation occurred in only 2 patients, and the onset of puberty may have contributed to this improvement. Hypothyroidism is a common finding in cystinosis, and it is suggested that thyroxine treatment be started when the TSH concentration becomes raised.     

Cyclical combination chemotherapy and thyroid function in patients with advanced hodgkin's disease

Clinical and biochemical assessment of thyroid function was undertaken in patients with Hodgkin's disease at designated points following diagnosis. At diagnosis, two of 20 patients had either abnormally low routine thyroid indices, or elevated thyroid stimulating hormone (TSH) levels that were not due to iodine-based investigations. Following lymphography, 76.5% of patients had TSH levels that remained elevated for a median period of 3 months. No detectable thyroid dysfunction was induced during chemotherapy. Fifty-four patients were studied at a median time of 35 months after chemotherapy. One euthyroid patient had a nodular goitre, and one had abnormal thyroid indices. TSH levels were elevated in 44% of patients, although the median TSH level for the group was normal. Half the patients had abnormal TRH stimulation tests. Sixty patients were studied after irradiation and chemotherapy. Four patients had clinical thyroid dysfunction, and 10% of routine thyroid indices were abnormal. TSH levels were abnormal in 80%, with a markedly elevated median level. All thyroid releasing hormone stimulation tests were abnormal.     

Familial hypothyroidism with autosomal dominant inheritance.

Three generations of a family with clinical and subclinical hypothyroidism caused by thyroid stimulating hormone (TSH) unresponsiveness are described. Findings were low to normal serum thyroxine, raised serum TSH, and low radioiodine uptake; goitre was notably absent. This family is the first evidence of an autosomal dominant mode of transmission of TSH unresponsiveness and may enable identification of the precise defect by genetic linkage study.     

THYROXINE-BINDING GLOBULIN DEFICIENCY IN EARLY CHILDHOOD

ABSTRACT. Jacobsen, B. B., Hansted, L. C, Brandt, N. J., Haahr, J., Hummer, L., Munkner, T. and Sorensen, S. S. (Department of Paediatrics, Viborg Hospital, Children's Hospital Fuglebakken, Department of Paediatrics, Section of Clinical Genetics and Department of Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark). Thyroxine-binding globulin deficiency in early childhood. Postnatal changes in serum concentrations of thyroid hormones and thyroid hormone-binding proteins. Acta Paediatr Scand, 70:155, 1981. –Serial determinations of serum thyroxine (T4), triiodothyronine (T3), thyrotropin(TSH), thyroid hormone-binding globulin (TBG), prealbumin (TBPA) and albumin were performed in a euthyroid girl with TBG deficiency and in her mother for a period of 22 months after delivery. At 8 days old the child had a serum TBG concentration around 50% of normal level which remained essentially unchanged during infancy. Total serum T4 and T3 concentrations were low, the free serum T4, free serum T3 and serum TSH concentrations were normal. The mother had received thyroid hormone from the age of 15 years. Her serum TBG level at 6 weeks post partum was similar to that of non-pregnant adults but decreased to about 50% of normal level, indicating a TBG deficiency. She remained euthyroid after withdrawal of T4 therapy. Serum TBPA and albumin concentrations were normal in mother and child. An X-linked inheritance of the TBG deficiency was suggested from a study of the family.     

Thyroid-stimulating hormone, prolactin, and growth hormone response to thyrotropin-releasing hormone in treated children with congenital hypothyroidism

The purpose of the present study was to assess thyroid-stimulating hormone (TSH), prolactin, and growth hormone responses to TRH stimulation in 12 congenitally hypothyroid children adequately treated with L-thyroxine from the first weeks of life. Although clinically euthyroid, six of these children were found to have abnormally high basal serum TSH concentrations despite clinical euthyroidism. Serum triiodothyroxine and L-thyroxine concentrations were normal and did not differ whether the children had elevated or normal basal serum TSH. All six of the children with high basal TSH had an exaggerated TSH response to TRH and 4 of them also had an augmented prolactin response to TRH. The children with normal basal TSH concentrations had normal TSH and prolactin responses to TRH. An abnormal ("paradoxical") elevation of growth hormone concentration in response to TRH was found in four of seven children in a separate group of patients who had prolonged, untreated primary hypothyroidism, but such responses were not found in any of the adequately treated children. These findings suggest the following conclusions: 1) the phenomenon of high serum concentrations of TSH in conjunction with normal L-thyroxine and triiodothyronine levels (and clinical euthyroidism), is prevalent in congenital hypothyroid patients. 2) These patients have an exaggerated response of their pituitary thyrotroph and lactotroph cells to TRH, presumably caused by selective and relative resistance of these cells to the inhibitory effects of thyroid hormones. 3) Congenital hypothyroidism is not associated with abnormal somatotroph cell responses to TRH.     

Thyroxine-binding globulin deficiency in early childhood. Postnatal changes in serum concentrations of thyroid hormones and thyroid hormone-binding proteins

Serial determinations of serum thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), thyroid hormone-binding globulin (TBG), prealbumin (TBPA) and albumin were performed in a euthyroid girl with TBG deficiency and in her mother for a period of 22 months after delivery. At 8 days old the child had a serum TBG concentration around 50% of normal level which remained essentially unchanged during infancy. Total serum T4 and T3 concentrations were low, the free serum T4, free serum T3 and serum TSH concentrations were normal. The mother had received thyroid hormone from the age of 15 years. Her serum TBG level at 6 weeks post partum was similar to that of non-pregnant adults but decreased to about 50% of normal level, indicating a TBG deficiency. She remained euthyroid after withdrawal of T4 therapy. Serum TBPA and albumin concentration were normal in mother and child. An X-linked inheritance of the TBG deficiency was suggested from a study of the family.     

Familial growth retardation with isolated thyroid-stimulating hormone deficiency

Three brothers with isolated thyroid-stimulating hormone (TSH) deficiency were observed at ages 17, 15, and 10 years. They suffered from severely retarded growth, with a marked retardation in bone maturation. Their serum T4, T3, and TSH levels were low. Serum thyrotropin-releasing hormone (TRH) concentration was normal. No increases in TSH levels were elicited during the TRH test. The other pituitary hormones, adrenocorticotropic hormone, growth hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin hormone, responded normally to stimulation. Thyroxin treatment triggered a growth acceleration. Genetic investigation revealed several instances of small stature on the father's side.     

Raised serum TSH in hypothyroidism.

It is desirable to detect early hypothyroidism of the mildest degree even before conventional tests of thyroid function become abnormal. Serum TSH levels (normal: undetectable to 4 muU/ml) rise in patients with mild hypothyroidism long before serum T4 and T3 levels fall. In the patient described the serum TSH level was 310 muU/ml, while other tests of thyroid function gave normal results. After treatment with thyroxine, serum TSH returned to normal. It should now be accepted that patients with mild hypothyroidism have a raised serum TSH and that thyroid insufficiency can be confidently excluded if the serum TSH concentration is normal. It is thus important to assay serum TSH when suspicion of hypothyroidism is aroused.     

Pseudohypoparathyroidism with hypothyroidism (author's transl)

This is a report about three children suffering from pseudo-hypoparathyroidism type I and moderate primary hypothyroidism. The thyroid dysfunction was characterised by slightly low plasma thyroxine and high basal TSH showing an increased response to TRH. T3 and rT3 were within normal limits, the size of the thyroid glands and also bone age were normal. The plasma concentrations of T4 and TSH and the response of TSH to TRH were no different during hypocalcemia from those obtained in normocalcemia during vitamin D treatment. Thyroxine treatment could normalize T4 and TSH. Moderate hypothyroidism is frequently present in pseudohypoparathyroidism. It has to be assumed that the same genetical defect of the second messenger, already proved to exist in the kidneys of patients with pseudohypoparathyroidism may also exist in the thyroid gland.     

Three-year follow-up of borderline congenital hypothyroidism

The purpose of this study was to determine whether children with borderline hypothyroidism in the neonatal period had persistent hypothyroidism after 3 years of levothyroxine replacement therapy. Fourteen term infants with slightly abnormal newborn screening results (thyroxine <10th percentile, thyroid stimulating hormone ?TSH <40 microU/mL) were identified. The subsequent serum confirmatory TSH results of 12 subjects were modestly elevated (5.3 to 18.8 microU/mL, normal 0.6 to 4.6), whereas 2 subjects who had borderline confirmatory TSH (4.6 and 4.7 microU/mL) had abnormal TSH responses to thyrotropin releasing hormone testing. After 3 years of therapy, levothyroxine was discontinued in 13 patients, and repeat thyroid function tests were obtained 1 month later. Levothyroxine was not discontinued in one patient because he had an elevated random TSH (10 microU/mL) while receiving therapy. At 3 years of age, 13 patients had persistently abnormal thyroid function tests (TSH >4.6 microU/mL or a thyroid releasing hormone test result consistent with primary hypothyroidism), and levothyroxine was reinitiated. Only one patient had normal thyroid function studies. Although prospective studies are still lacking, we recommend levothyroxine replacement in newborns with borderline hypothyroidism.