To evaluate the effect of human growth hormone (hGH) on the growth of children with achondroplasia, three patients with achondroplasia and one patient with hypochondroplasia were treated with 0.5 IU/kg/W of pituitary‐extracted hGH for 6–12 months. Mean height velocity was significantly increased from 4.0 0.4 to 7.5 0.7 cm/year (P0.05) by hGH. The tibial index, defined as the length/width ratio of left tibia, did not change during the treatment, indicating that hGH promotes growth without exaggeration of tubular bone deformity. Case 2, who had atlantoaxial dislocation, developed sleep apnea and neurological deficits during the second hGH treatment, but these were cured by operation. Thus, hGH therapy is effective in promoting growth in patients with achondroplasia, but the complication of atlantoaxial dislocation should be explored and corrected before the treatment.

The echo patterns of diffuse thyroid lesions in children are not yet well known. We present here the ultrasound findings of 32 children aged 5 to 15 years with a newly diagnosed diffuse thyroid disease. 23 patients had thyromegaly by palpation, 9 had hypothyroidism but no goiter. Of the 23 goitrous patients 9 were hypo-, 3 hyper-and 11 euthyroid. The 9 with hypothyroidism had all autoimmune thyroiditis as judged by antithyroid antibodies, and confirmed cytologically in 5. They had all 9 a hypoechogenic patchy, partly nodular thyroid by ultrasound.2 of the 3 with Graves disease had initially a similar pattern than in thyroiditis, the 3rd showed hypoechogenity later. Of the 11 euthyroid patients 8 had antithyroid antibodies and the ultrasound suggested thyroiditis in 5 of them, 3 were judged normal (2 and 1 became later hypothyroid). Of the 3 patients with euthyroid goiter but without antithyroid antibodies the ultrasound finding was normal in 1, showed multicystic thyroid in 1 and suggested thyroiditis in 1 who later had antithyroid antibodies. Of the 9 hypothyroid patients without thyromegaly one had an unusually small hit otherwise normal thyroid by ultrasound. The others had an echopoor thyroid, but the patchy and nodular pattern was often less marked than in goitrous hypothyroidism. We conclude that autoimmune thyroiditis gives a typical ultrasound pattern, and ultrasonography gives useful information especially of euthyroid goiter and nongoitrous hypothyroidism. PERICARDIAL EFFUSION IN CONGENITAL HYPOTHYROID/ ; A 1NFANTS:AN AETIOLOGICAL CORRELATION. Gianfili~po -" ...~e h children positive at the newborn screen'ing program for congenital hypothyroidism were studied. Confirmlng diagnosis was made in 8/10 infants,while 2/10 were false positive. Moreover we have considered in the study a patient clinically diagnosed at 19 months (he did not undergo the screening prograrn),in which was demonstrated an ectopic g1and.A complete thyroid function evaluation (FT3,FT4,T3,T4,TBG,TRH test),scintlgraphy (TC99),echocardiography (B-mode)were carried out in all the babies (scintigraphy was not performed in the 2 false positive children). Pericardial effusion was demonstrated in 4/9 patients (44%); complete resolution occurred after a variable period of L-T4 therapy (15 days to 5 months).None of the patients showed clinical symptoms nor electrocardiographrc signs of cardiac failure. Data collected in Zaire suggested that severe iodine deficiency resulted in neonatal hypothyroidism and its longterm consequence, endemic cretinism. In order to further evaluate this possibility, we initiated neonatal thyroid screening in an endemic goiter area in Algeria (area A) with a high prevalence of goiter (51.3 %) and cretinism (1.1 %) and a low dietary supply of iodine (I)(Mean urinary I : 16.2 uglg creatinine) and in a non goitrous area (B) with no cretinism and a normal iodine supply (urinary 1:73.9 ug/g creat.). Serum TSH levels in 3135 newborn infants of area A were shifted towards high values as compared to the results obtained in a...

SummaryChanges in the regulatory mechanisms of hepatic thyroxine (T4) 5'-monodeiodination during maturational process were studied in rats aged 1,3, and 6 wk andin adults. ~e s d i t e low T4 5'-deiodinase activity in the neonates, a similar degree of activation in older rats was obtained with graded doses of dithiothreitol. Lineweaver-Burk plot analysis showed that Vmax increased 1-3 wk of age, decreasing with age thereafter, whereas a high Km value in young rats (7.0-7.8 x M) fell to a level of 4.8 x lo-* M by 6 wk of age.T4 5'-deiodiiase at 3 wk of age was relatively resistant to iodoacetamide, a S H blocking agent (11% inhibition at M versus 47% in adult). Furthermore, it was markedly enhanced with 3 mM EDTA (125% versus 10-2Wo in older rats). Among various bivalent cations tested, Cu++ and Zn++ had a strong inhibitory effect on the reaction, whereas livers from 3-wk-old rats were less sensitive to Zn++ (7% inhibition at M versus 40% in adult). Responses to graded doses of reduced glutathione (GSH) or to its blocker, diamide, suggest that GSH exerts its promoting effect through preservation of protein S H radicals in reduced form. In contrast, NADPH stimulates the reaction directly, and a marked increase in the sensitivity to NADPH was observed 1-3 wk of age. Doseresponse relation to methylene blue (MB), inhibitor of NADPH, exhibited a biphasic effect on the reaction: stimulatory at smaller dose and inhibitory at larger dose. The critical dose of MB producing this reversal shifted to a lower level with advancing age, which appears to be due to the content of endogenous NADPH as well as to the reactivity of the enzyme to it. These results indicate that (1) protein S H radicals appear to change from a relatively inactive to an active state with age, in which an interaction with Zn++ might be involved; (2) GSH is probably associated with the conversion of S H groups; (3) NADPH enhances directly the --enzyme activity, playing a pivotal role in the regulation of the reaction; and (4) maturation of T4 5'-deiodination includes changes in the protein SH groups and GSH-NADPH generating system.

Abstract. To elucidate the mechanism by which TRH and its metabolite, histidyl-proline diketopiperazine (cyclo(His-Pro)), act on the maturation of homoiothermy, the chronic effects of intrathecal administration of the peptides on body temperature, serum thyroid hormone levels, and mitochondrial energy-producing enzyme activities were examined in neonatal rats. The two peptides or an equimolar mixture of both were injected intrathecally at a dose of 3, 6 and 9 nmol for 7 consecutive days during the 1st, 2nd or 3rd week of life, respectively. Control rats were treated with saline and they were sacrificed at 6 weeks of age. Although food and water intake were not decreased, body weight gain was slightly reduced in the rats treated with TRH or cyclo(His-Pro) during the 1st and 2nd week of life, whereas the mixturetreated rats showed normal weight gain. Body temperature at 25°C was not different in the TRH- and cyclo(HisPro)-treated groups, whereas after cold exposure (5°C for 3 h), the groups treated with TRH during the 1st and 2nd week of life had an impaired thermoregulation at 5 weeks of age. Serum T4 and T3 concentrations were similar in all groups, except in the rats treated with TRH during the 2nd week of life; their thyroid hormone levels were slightly reduced. The TRH treatment suppressed mitochondrial cytochrome c reductase and glucose-6-phosphatase activities, whereas cyclo(His-Pro) reduced cytochrome c reductase and malic enzyme activities. In contrast, α-glycerophosphate dehydrogenase was enhanced by both treatments. These results suggest that TRH and cyclo(His-Pro) modulate the central thermoregulatory mechanism and produce particular changes in the mitochondrial respiratory chains in peripheral thermogenic tissues.

Nine patients with Turner's syndrome aged 7 to 13 years were treated with recombinant human growth hormone (hGH) at a dose of 0.5 or 1.0 U/kg/w for 1 year. In five of them the growth rate was accelerated from 3.3 +/- 0.6 (SD) to 6.5 +/- 0.5 cm/y (group A), whereas 4 had a reduced rate of growth promotion (3.4 +/- 0.3 to 4.6 +/- 0.4 cm/y) (group B). Analysis of factors affecting growth response to hGH revealed 3 major parameters: (1) age of initiating hGH therapy (A, 9.5 +/- 2.1 vs B, 13.3 +/- 0.4 yrs, P less than 0.01), (2) basal LH (A, 3.2 +/- 2.4 vs, B, 44.9 +/- 17.8 mIU/ml, P less than 0.001) and FSH levels (A, 14.7 +/- 15.4 vs B, 131 +/- 49 mIU/ml; P less than 0.01) and (3) somatomedin-C (SM-C) producing capacity: coefficient of correlation to growth rate, r = 0.80, P less than 0.01). No remarkable changes were observed in the results of glucose tolerance, thyroid state, calcium metabolism and liver function tests. These results indicate that patient's age is the most crucial factor in effective treatment with hGH, and in adolescent girls, gonadal failure with a limited increase in SM-C production attenuates the growth promoting potency of hGH.