The aim of the present study was to evaluate the activity of opiate receptors involved in the control of LH secretion during pubertal development, as determined by the LH response to naloxone. Normal children (n = 28) of both sexes, subdivided according to breast (girls) or testicular (boys) development, and patients with idiopathic precocious puberty (n = 7), delayed puberty (n = 8), or hypergonadotropic hypogonadism (n = 4) were studied. Plasma LH levels were measured after the administration of naloxone (NLX; 0.08 mg/kg BW, iv), GnRH (50 micrograms, iv) or placebo. In healthy subjects, NLX significantly increased plasma LH levels only in girls and boys at the most advanced stage of gonadal maturation. NLX was ineffective in prepubertal and early pubertal children, and it did not significantly alter LH levels in children with delayed puberty or hypogonadism or in most of the children with precocious puberty. GnRH injection consistently increased plasma LH levels in healthy subjects as well as in the children with pubertal disturbances. These results indicate that the LH response to NLX occurs only at the most advanced stages of pubertal maturation when normal or precocious and is absent in early puberty or in children with pubertal disturbances. Furthermore, the results suggest that opioid regulation of LH secretion in humans changes during puberty, reaching an adult-like functional state with maturation of the hypothalamus-pituitary-gonadal axis.

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Patients with insulin-dependent diabetes mellitus (IDDM) have a 6-20% incidence of thyroid autoantibodies, depending upon the population studied /1-5/.It has been reported that 45% of IDDM patients with antimicrosomal antibodies (MCHA) may develop thyroid dysfunction /4/. In adult diabetics there is an increased prevalence of subclinical hypothyroidism, unrelated to the presence of autoantibodies, diagnosed by basal TSH and T 4 values /6/ and an exaggerated response of TSH to TRH /7/.The aims of the present investigation were to study children with IDDM for a) the evolution of the anti-thyroid antibodies during a 12-18 month follow-up period and b) changes in thyroid function as assessed by T 4 and T 3 levels and the TSH response to TRH. SUBJECTS AND METHODSNone of the patients had a goiter or clinical signs of thyroid dysfunction at the diagnosis of diabetes. Each patient was treated with at least 2 injections of insulin per day, and none was in ketoacidosis at the time of the test. The patients were randomly divided into two groups. Group 1 consisted of 77 patients with IDDM (41 females and 36 males) with a mean age of 12.3 years (range 4-18.9 years) and a mean duration of the disease of 59.4 months. In this group, we investigated the presence of antithyroglobulin (TGHA) and MCHA antibodies and measured the basal values of T 4 , T 3 , Free T 4 (FT 4 ), TSH and the TSH response to i.v. TRH.All patients were re-examined clinically 12-18 months after the first test. In 19 of them the antibody titer and the TSH response to TRH were again determined.Group 2 consisted of 23 patients with IDDM (13 females, 10 males) with a mean age of 13.4 years (range 5.8 to 18.1 years) and with a mean duration of the disease of 73.8 months. In these patients, basal blood values of T 4 , T 3 and Hb A] were longitudinally (2-3 times) monitored during 12-18 months. Five Mg/kg TRH (Roche, Basel) was intravenously injected as a bolus: blood samples were withdrawn just before the TRH injection (time 0) and 20, 30, 60 and 90 min. afterwards.TGHA and MCHA were detected in the plasma with the method of passive hemoagglutination (thymune-T -Wellcome, Beckenham, UK and Fujizoki, Tokyo, Japan respectively). TSH, T 4 , T 3 , FT 4 and HbAiwere determined in the blood respectively by RIA and by microchromatography as previously reported /8/. RESULTS Group 1:MCHA were present in 11.7% and TGHA in 5.2% of the patients. In a control study carried out in 197 normal subjects, age and sex matched with our patients, MCHA were present in 3% and TGHA in 0.5% of the subjects. The nine patients with MCHA (Table I) (6 females and 3 males) were older than 10 years. In the patients with MCHA both basal TSH levels (3.3 ± 1.3 μΙΓ/πι1;Χ ± SD 9) and peak levels of TSH after TRH (21.3+7.0 μυ/ml) were statistically not different from the patients without VOL. 1, NO. 2&3, 1985 185 Brought to you by | University of Arizona Authenticated Download Date | 7/29/15 7:31 PM