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Height and sitting height were measured in all the 28 patients (19 females and 9 males) of our Thalassaemic Centre who exhibited evidence of cessation of growth. Their average final stature, which had been spontaneously achieved at an age ranging from 15.0-21.5 years (mean 17.9), was slightly lower with respect to the mean standards for women (159.1 +/- 8.4 vs 160.0 +/- 6.0 cm) and men (167.8 +/- 6.4 vs 172.5 +/- 6.0 cm). Height deficiency exceeded 2 SD scores in only 3/28 patients. If compared to the familial target height, patients' stature fell within the familial range in 19/24 cases and in only one case was it below the lower limit. In the whole sample the patients' height was positively related to their familial target height (r = 0.72, P less than 0.0002) and also to mid-parental stature (r = 0.45, P less than 0.05). Heights of both females and males were superimposable on those of their own mothers and fathers respectively. Average values of either SH (76.4 +/- 3.8 vs 79.9 +/- 3.4 cm, 2 P less than 0.02) or SH/H ratio (48.9 +/- 2.5 vs 51.5 +/- 1.0, 2 P less than 0.005) were significantly lower in the female thalassaemics than in the sex-matched controls. Three females and one male showed subnormal values of both SH and SH/H ratio. Two out of these patients with eunochoid body proportions and another one with a decreased SH/H ratio have hypogonadotropic hypogonadism and are undergoing a chronic substitutive treatment with sexual hormones, which was instituted after the achievement of final stature.

Significant high titres (1:400-1:25,600) of circulating thyroid microsomal antibodies (MCHA) were found in the sera of 5 out of 59 non-ketoacidotic, insulin-dependent diabetic (IDDM) patients (mean age 14.5 years). Among these five patients (four females, one male), all of whom were over 11 years, two also had thyroglobulin antibodies. Increased thyrotropin (TSH) response to TRH was found in 3/5 MCHA positive patients and in 3/54 without circulating MCHA. Serum thyroxine (T4) and free T4 (FT4) average values were significantly lower (P less than 0.01 and P less than 0.001) in diabetics (7.1 +/- 1.8 micrograms/dl and 10.2 +/- 3.1 pg/ml, means +/- SD) as compared to normal sex and age matched controls (8.9 +/- 1.9 micrograms/dl and 12.2 +/- 2.2 pg/ml, respectively). T4 and FT4 values were inversely related to the duration of the disease. Subnormal T4 values were found in six (five females and one male) patients, four of whom had subnormal FT4 values. No patient had low triiodothyronine (T3) and high reverse T3 (rT3) values, i.e. none displayed the biochemical pattern of the 'low T3 syndrome' described with ketoacidotic status. This indicates also a satisfactory compensation of IDDM in all the patients. At the time of study no patient (including also those with circulating MCHA and TGHA and with TSH hyper-response to TRH) showed either thyroid size enlargement or clinical features of thyroid dysfunction including impaired growth and bone age retardation.

Several parameters of thyroid function were studied in 112 non-ketoacidotic youngsters with insulin-dependent diabetes mellitus (IDDM). Levels of thyroxine (T4), reverse triiodothyronine (rT3), thyroxine-binding globulin (TBG) and T3 were lower than in controls, whereas FT4, and FT3 were normal. T4 levels in IDDM patients were positively related to T3, rT3 and TBG, and inversely related to haemoglobin A1 (HbA1). However, only 4 patients showed biochemical hypothyroidism (T4 less than 5 micrograms/100 ml), whereas their FT4, FT3 and thyroid-stimulating hormone (TSH) levels were normal. Concurrent variations of T3 and rT3 levels were found in IDDM patients; thus, their T3/rT3 ratios were stable or higher than in controls, indicating that peripheral deiodination of T4 is preferentially oriented to production of rT3 only during ketoacidosis. Although changes in thyroid function may reflect the degree of metabolic control of diabetes in a large population, the clinical usefulness of serum thyroid hormone measurements in an individual case still appears to be limited.

The effects of an iv thyrotropin releasing hormone (TRH) bolus on serum growth hormone (GH) and cortisol levels were evaluated in 59 children and adolescents with insulin dependent diabetes mellitus (IDDM) and in 24 healthy, age-matched control subjects. In the IDDM group GH baseline levels sharply rose within 30 min after TRH and successively normalized. On the contrary, TRH injection failed to affect GH serum concentrations in the control group. The GH increase after TRH in IDDM patients was positively correlated to age, but unrelated to other variables, such as sex, pubertal stage, duration of disease, glycemia, glycosylated hemoglobin, thyrotropin and T4 concentrations. Twenty-one out of 59 diabetics and only 1/24 controls exhibited a paradoxical GH response to TRH, arbitrarily defined as a precocious increase (within 30 min), of more than 100% with respect to the baseline value, associated with a GH peak greater than 10 ng/ml. Eighteen IDDM patients underwent a second TRH test 12 to 24 months later and substantially exhibited the same GH pattern documented the first time. The mechanism responsible for such anomalous GH responsiveness to TRH in IDDM is unclear. However, it cannot be attributed to a nonspecific stress reaction, as proven by the lack of a concomitant increase of cortisol serum levels in the same subjects.

In five L-thyroxine-substituted hypothyroid children with partial epilepsy serum total thyroxine (T4) and free T4 (FT4) significantly (P less than 0.01) decreased following 2 months of carbamazepine (CBZ) administration (20 mg/kg per BW per day) from mean (+/- SD) values of 12.7 +/- 1.1 micrograms/dl and 15.5 +/- 1.8 pg/ml to mean values of 7.5 +/- 2.3 and 10.1 +/- 1.7, respectively. In all but one patient important changes in both serum total and free triiodothyronine (T3, FT3) were not observed; consequently T3:T4 and FT3:FT4 ratios significantly (P less than 0.05) increased in the whole series. Three subjects had post-treatment serum TSH that rose to hypothyroid levels parallel to a T4 decrease. The negligible thyroid hormone secretion and the unmodified T3-uptake (T3U) or T4-binding globulin (TBG) exclude direct effects of CBZ on thyroid gland and on carrier serum proteins, respectively. The findings observed, instead, might be due to accelerated T4 metabolic clearance together with augmented T4 to T3 conversion rate, as previously demonstrated for diphenylhydantoin. The sharp reduction in T4 and FT3 concentrations is the peripheral display of this event, which is associated with a decompensation of the metabolic status, as indicated by serum TSH enhancement. In all cases a supplement of L-thyroxine by itself was able to restore euthyroid TSH serum concentrations, suggesting that hypothyroidism in patients with partial epilepsy to whom CBZ had been administered requires a higher L-T4 substitutive regimen.