Prematurity may be a risk factor for thyroid dysfunction in childhood.

CONTEXT: Children born prematurely and/or small for gestational age (SGA) frequently show disturbances in thyroid function. OBJECTIVE: The objective of the study was to determine the role played either by size or gestational age on subsequent thyroid function. DESIGN AND SETTING: This cross-sectional study was conducted at a tertiary referral hospital. PATIENTS: A total of 117 children, 88 of whom were SGA (mean age 7.8 +/- 2.5 yr) and 29 appropriate for gestational age (AGA) (mean age 8.1 +/- 1.9 yr), were selected for the study. MAIN OUTCOME MEASURES: We evaluated TSH, free T(4), free T(3), urinary iodine, and antithyroid antibodies, and all patients underwent a thyroid ultrasound. Insulin sensitivity was assessed with the quantitative insulin sensitivity check index. RESULTS: TSH and free T3 were not significantly different in the two groups, whereas free T4 was higher in the AGA group (P < 0.005). Interestingly, four AGA (13.8%) and 17 SGA (19.3%) patients had TSH levels above the upper limit of normality. Thyroid volume was normal and thyroid autoimmunity was excluded. Urinary iodine was also similar in the two groups (115 +/- 66 vs. 143 +/- 87); however, in both groups there were some children [15 AGA (51%) and 13 SGA (14.7%) (P < 0.001)] with a mild to moderate iodine deficiency. By multiple regression analysis, gestational age was found to be the only determinant of TSH serum levels. Insulin sensitivity was the same in both groups of children and similar to controls. CONCLUSIONS: Some children born prematurely, independently from their birth size, frequently have disturbances of the hypothalamus-pituitary-thyroid axis later in life.

The natural history of euthyroid Hashimoto's thyroiditis in children.

OBJECTIVE: To study the natural history of Hashimoto's thyroiditis (HT) in children and identify factors predictive of thyroid dysfunction. STUDY DESIGN: We evaluated 160 children (43 males and 117 females, mean age 9.10 +/- 3.6 years, with HT and normal (group 0; 105 patients) or slightly elevated (group 1; 55 patients) serum thyroid-stimulating hormone (TSH) concentrations. The patients were assessed at presentation and then followed for at least 5 years if they remained euthyroid or if their TSH did not rise twofold over the upper normal limit. RESULTS: At baseline, age, sex, thyroid volume, free thyroxine, free triiodothyronine, thyroid peroxidase antibody (TPOab), and thyroglobulin antibody (TGab) serum concentrations were similar in the 2 groups. During follow-up, 68 patients of group 0 remained euthyroid, and 10 patients moved from group 0 to group 1. In 27 patients, TSH rose twofold above the upper normal limit (group 2), and 9 of these patients developed overt hypothyroidism. Sixteen patients of group 1 ended up in group 0, 16 remained in group 1, and 23 moved to group 2. A comparison of the data of the patients who maintained or improved their thyroid status with those of the patients whose thyroid function deteriorated revealed significantly increased TGab levels and thyroid volume at presentation in the latter group. However, none of these parameters alone or in combination were of any help in predicting the course of the disease in a single patient. CONCLUSIONS: The presence of goiter and elevated TGab at presentation, together with progressive increase in both TPOab and TSH, may be predictive factors for the future development of hypothyroidism. At 5 years of follow-up, more than 50% of the patients remained or became euthyroid.

Altered thyroid and adrenal function in children born at term and preterm, small for gestational age.

Intrauterine growth retardation may permanently influence the endocrine system by affecting its programming during development. The aim of this study was to evaluate thyroid and adrenal function together with insulin sensitivity in a group of children born small for gestational age (SGA). Forty SGA children (mean age, 6.7 +/- 1.7 yr) and 35 children born appropriate for gestational age (mean age, 6.5 +/- 2.2 yr) were selected for the study. TSH, free T4, free T3 (fT3), rT3, antithyroid antibodies, cortisol, and dehydroepiandrosterone sulfate (DHEAS) were assessed. Insulin sensitivity was evaluated with the quantitative insulin sensitivity check index (QUICKI). A thyroid ultrasound was also performed in the SGA children. We found that TSH was significantly higher in SGA than in children born appropriate for gestational age [2.9 +/- 1.1 vs. 1.7 +/- 0.7 microU/ml (mIU/liter); P < 0.001]; furthermore, eight SGA children (20%), seven born preterm and one at term, had TSH levels above the upper limit of normality. fT3 was also higher in SGA children (4.2 +/- 0.4 vs. 3.6 +/- 0.6 pg/ml; 6.4 +/- 0.6 vs. 5.5 +/- 0.9 pmol/liter; P < 0.0001), whereas no difference was found for free T4, rT3, and the fT3/rT3 ratio. Urinary iodine was normal, and antithyroid antibodies were absent. Thyroid ultrasound showed a normal echographic pattern with a normal volume in SGA children. Serum cortisol was similar in both groups, whereas DHEAS was significantly lower in SGA subjects (43 +/- 18 vs. 65 +/- 50 microg/dl; 1.1 +/- 0.4 vs. 1.7 +/- 1.3 micromol/liter; P < 0.05). There was no difference in insulin sensitivity between the two groups. Birth length and birth weight were the main determinants of TSH and DHEAS serum levels, respectively. In conclusion, functional thyroid and adrenal changes have been found in children who suffered from intrauterine growth retardation. A larger survey with an appropriate follow-up is, however, required to confirm these findings and to assess their natural evolution.

Insulin sensitivity in growth hormone-deficient children: influence of replacement treatment.

OBJECTIVE: In adults, excessive GH secretion may lead to secondary diabetes mellitus, while prolonged GH treatment may accelerate the onset of type 2 diabetes mellitus in predisposed children. The aim of the study was to evaluate insulin sensitivity (IS) and glucose tolerance (GT) in a group of GH-deficient children treated with GH for a period of 6 years. PATIENTS AND DESIGN: One hundred and twenty-eight children (40 females, 88 males) were included in the study. At the beginning of treatment chronological age was 8.9 +/- 3.2 years, height standard deviation score (SDS) -2.43 +/- 0.90 and body mass index (BMI) SDS 0.18 +/- 1.60. At the end of the study chronological age was 13.0 +/- 2.9 years, height SDS -1.24 +/- 1.27 and BMI SDS 0.23 +/- 1.54. GH was administered at a mean weekly dosage of 0.3 mg/kg, injected subcutaneously over 6-7 days. GT was assessed according to the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. IS was evaluated with the quantitative insulin sensitivity check index (QUICKI). RESULTS: No cases of impaired GT or diabetes were recorded during the follow-up period. IS, already lower than in controls before starting treatment with GH, decreased significantly during the first year of therapy (QUICKI: 0.346 +/- 0.033 vs. 0.355 +/- 0.044, P < 0.05), with no further decrease in the following years. No correlation was found between QUICKI, BMI, years of treatment and onset of puberty. CONCLUSIONS: GH treatment in GH-deficient children does not lead to an impaired GT or type 2 diabetes mellitus, although it does significantly decrease IS.

Insulin sensitivity in Turner's syndrome: influence of GH treatment.

OBJECTIVE: Excessive GH secretion may lead to secondary diabetes mellitus, while prolonged GH treatment may accelerate the onset of type 2 diabetes mellitus in predisposed individuals. Turner's syndrome (TS) patients are a population at risk since they have reduced glucose tolerance (GT) spontaneously and because they are usually treated with high doses of GH. DESIGN AND METHODS: The aim of the study was to evaluate insulin sensitivity (IS) and glucose tolerance (GT) in a group of TS patients treated with GH for a period of 6 years. Forty-seven TS girls were included in the study. GH was administered at a mean weekly dosage of 0.35 mg/kg, injected subcutaneously over 6-7 days. GT was assessed according to the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. IS was evaluated with the quantitative insulin sensitivity check index (QUICK-I). RESULTS: No significant increase of impaired GT was observed in the patients during the follow-up period, while a reduced IS was detected. IS in TS patients was already lower than in prepubertal controls (P<0.001) before starting treatment and further decreased during the first year of therapy (P<0.05), and then remained stable over the following years. No correlation was found between QUICK-I, body mass index, years of treatment, onset and duration of puberty. One patient became diabetic during the course of treatment. CONCLUSIONS: GH treatment in TS girls does not significantly increase the prevalence of impaired GT or type 2 diabetes mellitus, while it does, however, decrease IS.