In childhood the traditional diagnostic approach to thyroid nodules consists of clinical, laboratory, and imaging evaluations. A safe and accurate procedure is needed to promptly identify patients who require surgery.In regard to the usefulness of fine needle aspiration biopsy, the data in the literature concerning children and adolescents are scanty. The aim of this study was to evaluate and compare the diagnostic accuracies of clinical, laboratory, and imaging data collected retrospectively in a group of pediatric patients with thyroid nodules submitted to fine needle aspiration biopsy.Forty-two patients who underwent surgery for thyroid nodules, recruited in 9 Italian pediatric endocrine units, were retrospectively studied. According to histological diagnosis, they were divided into 2 groups, 22 patients with benign lesions and 20 patients with malignant lesions. From clinical records we obtained data about 1) symptoms of neck compression; 2) cervical adenopathy; 3) thyroid function, calcitonin level, and antithyroid antibody titers; 4) ultrasonography; 5) 99m Tc scintiscanning; and 6) cytology obtained with fine needle aspiration biopsy. Patients and nodule characteristics were analyzed statistically for associations with the presence of thyroid cancer.Among clinical findings, only adenopathy was significantly higher in the group with cancer (8 of 22 benign lesions vs. 16 of 20 malignant lesions; P ‫؍‬ 0.006). Thyroid function and antibody titers were similar in the 2 groups, whereas the serum calcitonin level was elevated only in 1 patient with malignant lesions. Among ultrasonography findings, no significant statistical difference was found between the 2 groups with regard to number, dimensions, growth progression, or hypoechogenic pattern of the nodules. Regarding scintigraphic findings, no significant difference was found between the 2 groups. However, a positive correlation (r ‫؍‬ 0.90; P < 0.0001) was found between fine needle aspiration biopsy cytological findings and histological diagnoses. The sensitivity, specificity, and accuracy of fine needle aspiration biopsy were 95%, 86.3%, and 90.4%, respectively. A multiple regression analysis showed that only fine needle aspiration biopsy (␤ coefficient ‫؍‬ 0.963; P < 0.0001) significantly contributed to detecting malignancy (multiple r ‫؍‬ 0.973; P < 0.0001).This study provides strong evidence that fine needle aspiration biopsy is a safe technique even in childhood and adolescence, offering the best sensitivity, specificity, and accuracy in detecting malignancy compared with conventional approaches. (J Clin Endocrinol Metab 86: 4644 -4648, 2001)

The human growth hormone gene (GH-N) is located in a cluster of five highly homologous genes that are coordinately expressed in pituitary (GH-N) and in placental tissues (the chorionic-somatomammotropin-like gene, the GH-variant gene and the two chorionic somatomammotropin genes). Sequence analysis from position -162 to position +100 of the GH-N gene has revealed eight nucleotide polymorphisms with no significant difference in frequency between patients affected by isolated growth hormone deficiency and controls. Remarkably, all these variations are located at positions where the GH-N differs from at least one of the other four homologous genes. The analysis of the twelve GH-N haplotypes originating from the combinations of the eight polymorphisms has revealed that not only single variations, but also nucleotide combinations are identical to those of the other placental genes. These findings suggest that whole stretches of the GH-N gene promoter have been replaced by homologous DNA stretches copied from one of the other four loci by repeated gene-conversion-like events, where the GH-N gene has acted as the recipient and the placental genes as donors of the converted sequences. The presence of a Chi-like element also indicates that the GH-N promoter represents a hot spot of gene conversion. Three of these variations cause, in addition, an amino-acid substitution in the GH-gene-derived transcriptional activator gene whose coding sequence overlaps the GH-N promoter. Thus, a DNA region that serves two distintic functions representing the proximal promoter of a gene and the 5' coding region of another gene displays an unusually high degree of polymorphism that has probably arisen because of gene conversion.

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CommentIn the elderly, changes in blood pressure relate to health. In those who remained healthy blood pressure continued to rise by 1.5 mm Hg per year but fell in those who developed disease (representing probable heterogeneous effects of different medical conditions). In the healthy group no rise was seen in retired blue collar workers. Possibly, retired manual workers have more unrecognised disease, consistent with a persistent effect of socioeconomic factors on health status in old age. For healthy individuals the most important predictor of blood pressure at follow up was baseline blood pressure, accounting for 24% of the variance of systolic, but only 6% of the variance of diastolic, pressure. In general, disease affected systolic more than diastolic pressure. Hence the poorer correlation between baseline and follow up diastolic pressure compared with systolic pressure is not easily explained by possible undetected disease in the healthy group and deserves further investigation.We thank the patients and general practitioners.

Leptin signals to the brain energy stores and balance while integrating neuroendocrine functions. Leptin levels in adults are higher in females than in males, while a gender-related difference in newborns is controversial. To clarify this point, in 202 healthy neonates we measured dynamic changes in leptin levels over the first month of life and looked for correlation between leptin levels and auxological and hormonal parameters. Cord leptin concentration in females was higher (p < 0.001) than in males. IGF-I, IGF-II, insulin, testosterone and 17beta-estradiol levels were similar in both sexes while insulin-like growth factor binding protein 3 (IGF-BP3) levels in females were slightly higher than in males. Leptin levels were positively associated to body weight, gestational age, IGF-BP3 levels, insulin levels and maternal body mass index (BMI) at time of delivery. In a subset of subjects (no. = 65), in comparison with cord levels, serum leptin levels were decreased on the 5th day of life (p < 0.0001) and then increased at 1 month (p < 0.0001). Positive association between leptin and weight was lost on the 5th day of life but present again at 1 month. In conclusion, our findings in a large population of neonates definitely show that leptin levels at birth are functions of gender, body weight and gestational age but not of length, cranial circumference, IGF-I and IGF-II levels. These findings, coupled with weight-independent prompt decrease after birth followed by weight-dependent increase at one month of life, suggest that leptin secretion in neonates as well as in adults mainly signals the nutritional state to the brain.

Administration of growth hormone in humans has been reported variably to affect arterial blood pressure and ventricular contractility. The present study was undertaken in anaesthetized pigs to establish whether increases in the blood levels of growth hormone primarily affect haemodynamic variables and to determine the mechanisms involved. In pigs anaesthetized with pentobarbitone sodium, left circumflex or anterior descending coronary blood flow was measured with an electromagnetic flowmeter. In a first group of 23 pigs, growth hormone administration (0.05 IU kg-1 i.v.) increased aortic blood pressure and reduced coronary blood flow when heart rate and aortic blood pressure were held constant. These responses were augmented by graded increases in plasma levels of growth hormone. The mechanisms of the above responses were studied in a second group of 29 pigs and involved beta2-adrenergic receptors since they were abolished by propranolol or butoxamine but not by atropine, phentolamine or atenolol. The present study showed that administration of growth hormone in anaesthetized pigs primarily increased aortic blood pressure and vasoconstricted the coronary circulation. The mechanisms of these responses involved beta2-adrenoceptor effects.

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This study was undertaken to confirm the importance of iodine excess in neonatal transient hypothyroidism. In 30 transient hypothyroid newborns at screening we measured urinary iodine excretion and TSH. They were divided into two groups: group A consisted of 21 newborns who had been exposed to iodine; group B of 9 non-exposed newborns. The two groups were significantly different only for median urinary iodine excretion (p = 0.001). In 61.5% of newborns of group A, iodine exposure caused iodine excess (urinary iodine excretion higher than 185 micrograms/l); this correlated with a higher prevalence of prematurity and a lower mean gestational age. Clinical records should reveal iodine exposure, but only urinary iodine excretion shows iodine excess. We suggest that evaluation at birth of urinary iodine excretion in every newborn with high TSH could help in predicting a good prognosis, since hypothyroidism due to the Wolff-Chaikoff effect is always spontaneously reversible, even if treatment may be suggested.