Gender, age, puberty, and BMI related changes of TSH and thyroid hormones in schoolchildren living in a long-standing iodine replete area.

The aim of the work was to assess thyroid function in children and adolescents in an iodine replete area and to explore possible effects of age, gender, puberty, and adiposity. Thyrotropin (TSH), total triiodothyronine (T (3)), total thyroxine (T (4)), free thyroxine (FT (4)), and the T (4)/T (3) ratio were determined for 440 schoolchildren (200 boys and 240 girls), aged 5-18 years, living in an iodine replete region. Body Mass Index (BMI), BMI standard deviation score (BMI-SDS), and Body Surface Area (BSA) were calculated. In girls there was a negative correlation of TSH, T (3), and FT (4) values with age. In boys there was a negative correlation only of T (3) values with age. Girls had lower TSH, T (4), and T (3) values, whereas boys had only lower T (3) values at puberty compared to the prepubertal stage. Girls had lower TSH values than boys (p<0.03) only at puberty. BMI-SDS in boys and girls were 0.21 and 0.03, respectively. BMI-SDS was not related to TSH, T (4), or T (3) in either gender, whereas it was negatively related to T (4)/T (3) ratio in boys and to FT (4) in girls. We conclude that estrogens may exert a suppressive effect on the pituitary-thyroid axis after puberty. TSH values are not correlated with BMI-SDS, whereas T (4)/T (3) ratio in boys and FT (4) in girls are negatively correlated with BMI-SDS.

Obesity and attenuated adiposity rebound in children with congenital hypothyroidism. Normalization of BMI values in adolescents.

An earlier adiposity rebound, suggestive of adult obesity, has been reported in children with congenital hypothyroidism. We undertook this study to evaluate the effect of congenital hypothyroidism on: 1) the timing of adiposity rebound, 2) the long-term prognosis of BMI status, and 3) the factors potentially affecting adiposity in subjects with congenital hypothyroidism. We found that in children with congenital hypothyroidism the BMI values were higher during the first years of life compared to normal population, but subsequently normalized. After the initial rise of BMI, the decline (nadir) and subsequent rise (adiposity rebound), usually occurring in normal children at an age greater than 30 months, was less evident in our group of children with congenital hypothyroidism. The severity of hypothyroidism affected BMI values at 6 and 12, but not at 36 months of age. In conclusion, in children with congenital hypothyroidism, 1) the high BMI values in early childhood normalize in adolescence, and 2) the normally expected BMI fluctuations during the first years of life are attenuated. These findings constitute indirect evidence that thyroid function during fetal and neonatal life affects BMI status during the first years of life.

Scintigraphic evaluation of primary congenital hypothyroidism: results of the Greek screening program.

The Greek screening program for primary congenital hypothyroidism was initiated in 1979. By early 2000, thyrotropin measurements had been performed in 1,976,719 newborns, using dried blood spots obtained by heel prick. Among these children, 584 were diagnosed with congenital hypothyroidism (incidence: 1/3,384 births) and were given L-thyroxine (L-T4) replacement therapy. In order to further evaluate and classify the children as having either an aplastic (AT) or an ectopic thyroid gland (ET) or as showing thyroidal dyshormonogenesis (DN, with a nomotopic gland), scintigraphic studies were performed at the age of 2-3 years. In 413 children of this age group (including 24 subsequently diagnosed as having had transient hypothyroidism, in whom L-T4 therapy was not resumed), thyroid hormones were measured and scintigraphic studies were done after withdrawal of L-T4 replacement treatment for 3 weeks. Given the long duration of the study, we used various scintigraphic modalities. In 96 children (group A), scintigraphy was performed using technetium-99m pertechnetate (99mTcO4-; 18.5 MBq given i.v.) and a rectilinear scanner. Seventy-three children (group B) were studied with 99mTcO4- (18.5 MBq given i.v.) and a gamma camera equipped with a pinhole collimator. In these groups, atropine was administered 30 min prior to the study (0.02 mg/kg i.v. or i.m.) in order to reduce the secretion of saliva from the salivary glands. Finally, in the remaining 220 children (group C) iodine-123 sodium iodide (123I-Na) (0.74-1.85 MBq i.v.) and the same gamma camera were used. Between-group comparisons of scintigraphic findings were done with the chi square test. In 191 children from group C, thyroglobulin (Tg) was measured and in 49 children ultrasound (US) was performed (categorising the gland as AT or ET/DN). Comparison of these modalities was done with the kappa statistic. In group A, 61.5% of children had AT, 26.0% had ET and 12.5% had DN; in group B, 28.8% of children had AT, 52.0% had ET and 19.2% had DN; in group C, 23.2% of children had AT, 63.2% had ET and 13.6% had DN. Statistically significant differences in group A versus groups B and C were noted for AT and ET. The implementation of newer scintigraphic modalities, and especially the use of 123I-Na, indicates that the commonest finding in congenital hypothyroidism is ET. Scintigraphy was more concordant with Tg measurements (though at a moderate level) than with US. The latter was even less concordant with Tg values. These results show that the most appropriate approach for the evaluation and classification of congenital hypothyroidism is 123I-Na scanning.

Bone mineral status in children with phenylketonuria under treatment.

Bone mineral status was assessed in 48 children with phenylketonuria (PKU) (20M, 28 F, aged 2.5-17 y). Bone density was measured in the distal third of the right forearm using single photon absorptiometry and was expressed as +/-SD with respect to age- and gender-matched controls. Serum calcium (Ca), magnesium (Mg), phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone and 25-hydroxyvitamin D were measured in morning samples. The ratios of urinary Ca/creatinine (UCa/UCr), UP/UCr, UMg/UCr and hydroxyproline (OH-Pr)/UCr were calculated in urine samples collected over a period of 3 h. Patients' data were compared with those of 50 controls (22 M, 28 F, aged 3-15 y). The data showed severe osteopenia (below -2SD) in 22/48 patients. Bone loss was more prominent in patients over 8 y old. Bone density correlated significantly with age (r=-0.56,p < 0.001) and with Phe (r=-0.49, p < 0.007) but did not correlate with the other biochemical indices studied. Comparing PKU children with controls, significantly higher serum calcium and magnesium (p=0.04, p < 0.001, respectively), lower ALP (p=0.01), higher UCa/UCr ratio (p < 0.001), lower UP/UCr (p < 0.001) and lower UOH-Pr/UCr (p < 0.001) were found. Dietary compliance was poor in patients over the age of 8y, as only 3/22 of < or = 8y had mean serum phenylalanine >10mgdl(-1), in contrast to 21/26 in the older group. It is clear from the data that osteopenia is commonly found in PKU patients from early life. The biochemical data indicate a metabolic state of low bone turnover in PKU patients. In conclusion, a better, more restricted diet may correct osteopenia.

Effect of growth hormone therapy on bone metabolism of growth hormone deficient children.

UNLABELLED: The effects of human growth hormone (hGH) therapy on biochemical markers of bone metabolism were studied in 17 children (10 boys and 7 girls, aged 3.7-13.1 years old) with idiopathic GH deficiency, before and 1 and 6 months after GH therapy (0.5 0.7 IU/kg weekly SC). Serum levels of calcium, phosphate, alkaline phosphatase osteocalcin, parathyroid hormone, 1,25 dihydroxyvitamin D, insulin-like growth factor I (IGF-I) and renal phosphate per 100 ml glomerular filtrate (TPO4/GFR) were assessed. During therapy with hGH a significant decrease of serum calcium levels and increases of phosphate, osteocalcin, parathyroid hormone 1,25 dihydroxyvitamin D and IGF-I were observed. TPO4/GFR was also significantly increased. Growth response (increment in HV) was positively related with changes in alkaline phosphatase and IGF-I levels after 6 months of hGH therapy. There was also a significant positive correlation between increment in HV and increment in TPO4/GFR after 1 month of GH therapy, whereas no correlation between HV and changes in osteocalcin levels was found. CONCLUSION: GH treatment significantly influences mineral metabolism and the measurement of TPO4/ GFR after 1 month of GH therapy may serve as a useful predictor of growth response to hGH therapy in GH-deficient children.

Prolactin levels in febrile and afebrile seizures.

Transient hyperprolactinaemia has been reported to follow unprovoked seizures, a finding proposed to be useful in the differential diagnosis of epilepsy. There is also evidence that patients with unprovoked seizures may have high baseline prolactin levels, which could be of value in detecting those predisposed to epilepsy after a first convulsive attack. The purpose of this study was to examine whether prolactin levels are elevated: (1) postictally in febrile seizures and (2) interictally in afebrile seizures. In 17 children with simple febrile seizures, mean postictal prolactin value (370 +/- 160 mU/l, mean +/- SD) was significantly higher (approximately 0.001) than the mean baseline value of 18 seizure-free controls (202 +/- 136 mU/l). The mean baseline prolactin values were not significantly different: (1) in ten children with afebrile versus ten seizure-free controls and (2) in 18 children with febrile seizures associated with high risk for subsequent afebrile seizures versus 23 children with febrile seizures but unlikely to suffer from afebrile seizures. CONCLUSION. Postictal prolactin levels may be a useful marker of recent febrile seizures, while baseline prolactin levels do not appear to have any prognostic significance in afebrile seizures.

The screening programme for congenital hypothyroidism in Greece: evidence of iodine deficiency in some areas of the country.

Newborn screening for Congenital Hypothyroidism, using TSH measurement in dried blood spots, was started in Greece in 1979. A total of 1,274,000 neonates have been screened and 377 cases of Congenital Hypothyroidism were detected, for an incidence of 1:3370. Employing a cut-off point of 30 mU/L of TSH in whole blood, 0.3% of the infants were recalled for repeat examination. The sensitivity of the screening test was 0.99 and the predictive value of a positive test 0.1. The frequency of "false positive" cases in the different geographic regions of Greece showed wide variation between the south and the north areas of the country. We suggest that these differences reflect the degree of iodine deficiency in the population and may be used as an epidemiological indicator of this deficiency.

Effect of hydrochlorothiazide on renal hypercalciuria.

The long-term effect of hydrochlorothiazide (HCT) was studied in 30 children (17 boys and 13 girls), aged 4-13 years (mean 7.6 +/- 3.4), with renal hypercalciuria (HCU) for a period of 2.5 +/- 0.95 years. The purpose of the study was to evaluate the effect of HCT mainly on renal calcium excretion, but also on serum K+, Ca, P, Mg, cPTH, nephrogenic cAMP (ncAMP) and bone mineral content (BMC). In addition to the above-mentioned parameters, oxalate, uric acid, citrate and cystine levels in 24-hour urine collections were also measured, and UCa/UCr, UP/UCr, UMg/UCr in 3-hour urine collections were assayed. The results of the study showed that 1 mg/kg/day of HCT caused a rapid and long-lasting correction of HCU, a decrease in serum cPTH and ncAMP, a significant increase in BMC and prevention of the formation of new urinary stones or of the increase in size of stones already present. No side effects were observed.

Alpha-fetoprotein in congenital hypothyroidism.

alpha-Fetoprotein (alpha-FP) was measured in dried blood spots from normal, congenital hypothyroid (CH) and transient hyperthyrotropinemic (TH) newborns as well as in serum from CH and TH babies together with thyroxine, triiodothyronine and thyrotropin. The half-life of alpha-FP had a median value of 12 days in the CH cases and 4.9 days in the TH cases. alpha-FP was significantly higher in the CH group before treatment and showed a significant rise after discontinuation of thyroxine therapy. It would appear that thyroid hormones influence alpha-FP metabolism and that a hypothyroid environment results in increased alpha-FP levels.

The diagnosis of hypercalciuria in children.

Calcium loading tests were performed in 21 children with hypercalciuria, haematuria and/or nephrolithiasis and 10 control subjects. Comparisons of 24-h calcium excretion before and after loading were evaluated rather than fasting urinary calcium to urinary creatinine ratio. The differences in calcium excretion before and after loading clearly distinguished absorptive from renal hypercalciuria. A difference higher than 0.035 mmol/kg indicated absorptive hypercalciuria in 6 of 21 patients, whereas in the remaining 15 much lower differences indicated renal hypercalciuria. Resorptive hypercalciuria caused by low serum values of 25-hydroxyvitamin D was considered in 6 of the 15 patients with renal hypercalciuria. These patients had low values of phosphate reabsorption (TmP/GFR) and could be clearly separated by high values of calcium reabsorption (TmCa/GFR), in contrast to patients with renal hypercalciuria who had normal values of TmP/GFR and low values of TmCa/GFR. The correct treatment and prevention of nephrolithiasis caused by hypercalciuria in children should be based on accurate diagnosis; this can be achieved by using the calcium loading test described in this report.

Psychomotor development in congenital hypothyroidism. The Greek screening programme.

In 1979 a national screening programme for congenital hypothyroidism (CH) was introduced in Greece. Treatment with L-thyroxine was started immediately after confirmation of the diagnosis, at a median age of 28 days. A standardized development test (Griffiths) was given to a group of CH infants and to healthy controls at the ages of 5-7, 11-13, 17-19, and 23-25 months. Thirty-three infants with CH were also studied at the age of 35-37 months. The mean developmental quotient of CH infants was 103.8 +/- 12.0, 100.9 +/- 10.1, 103.3 +/- 7.1 and 99.8 +/- 10.2 from the ages of 5-7 to 23-25 months, and was not statistically different from those of the controls. Statistical analysis showed no significant differences between athyreotic children and those with an ectopic gland. Our findings show that the prognosis for psychomotor development of children with CH is quite good, provided that treatment starts in the first 6 weeks of life.

Hypothyroidism and sex chromosomes.

The observation of Campbell and Price in 1979 that their Unit had diagnosed four subjects with both Klinefelter's syndrome and congenital hypothyroidism raised the suspicion of an association between the two conditions. This, and the published reports of an XX male, five XXY males, and one mosaic XY/XXY with congenital or acquired forms of hypothyroidism, together with the higher incidence in women and the absence of sex difference among inherited congenital cases, suggested a possible sex chromosome effect in the aetiology of sporadic hypothyroidism. Various hypotheses can be tested either by examining the frequency of hypothyroidism in sex chromatin positive males or by establishing a higher frequency of sex chromatin positive males among hypothyroid cases than in normal males. We examined 57 boys with hypothyroidism for the presence of sex chromatin and found all to be negative. From this relatively small sample we can only exclude the possibility of a very large (100 fold) difference in frequency between the two populations and therefore more data are needed.

Neonatal screening for hypothyroidism in Greece.

One year's experience in screening for congenital hypothyroidism in Greece is reported. Thyroid stimulating hormone (TSH) determination by a radioimmunoassay on dried blood spots was selected as the screening method. During the first year of screening 75,879 newborn infants were tested from Guthrie blood spots taken on the 5th day of life. Eighteen cases of primary congenital hypothyroidism with serum TSH levels over 100 microIU/ml were detected, giving an incidence of 1: 4200. One case had already been diagnosed clinically. Replacement treatment was started between the 22nd and the 50th days of life.