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We studied insulin-like growth factors (IGF) I and II, prolactin, and the insulin response to arginine in 19 children with craniopharyngioma and documented growth hormone deficiency. Patients were divided into three groups according to their growth rate during the first postoperative year. Seven patients with excessive growth (Group A) had hyperinsulinism, normal IGF values, elevated basal prolactin levels, and a delayed thyrotropin response to thyrotropin-releasing hormone, which was compatible with hypothalamic lesions. In the six patients with normal growth (Group B), the insulin level was low; all other hormone values were similar to those of Group A. In the six patients with decreased growth (Group C), levels of IGF I, insulin, prolactin, and thyrotropin were low, indicating the presence of severe pituitary damage and explaining the failure to grow. Patients in all groups had low or undetectable basal levels of growth hormone. We conclude that in Group B, normal IGF permitted normal growth, and prolactin hypersecretion may have been responsible for normal IGF I values. Excessive growth in Group A may have been caused by hyperinsulinism associated with hyperphagia and obesity of hypothalamic origin.

Because of the high incidence of antibodies after HGH therapy in our hypopituitary patients, we have studied the plasma of all HGH-treated children with a sensitive radioimmunological method. We found antibodies to HGH in 12 out of 21 children who were initially treated with a cloudy preparation of HGH Raben, and in only 2 out of 14 children treated with HGH Roos. Growth was not inhibited in 4 children with low and in 2 out of 4 children with medium-high antibody titers. In one patient, antibodies in medium-high concentrations inhibited the growth response to administered HGH and seemed to suppress also the effect of endogenous GH. Replacement of the cloudy preparation by a clear solution of HGH Raben or by HGH Roos led to a decrease or the disappearance of antibodies, and, in the absence of antibodies, growth response to therapy returned. Thus, the quality of the HGH preparation might account for the appearance of antibodies in low and medium-high titers. In 6 children with isolated GH deficienc...

Intelligence quotient (IQ), school and professional performance were reviewed in 33 patients with idiopathic hypothalamo-pituitary hypothyroidism. Diagnosis was based on low T4 values and clinical signs. All were treated with growth hormone (HGH). In some, hypothyroidism became manifest only after HGH therapy. Birth history revealed breech delivery in 24 and perinatal asphyxia in 15 of them. Thyroid treatment was started at a mean age of 9.8 (range 4-18 years). The mean IQ was 103.4 +/- 16.7 (SD). 9 patients had IQs below 90, 8 of them were born by breech delivery, 3 had severe perinatal asphyxia, one recurrent symptomatic hypoglycemia, and one a micropenis. Of those patients who have reached the respective age, 7 attended college, 3 university, and 9 had skilled professions. Only 7 required special education. For comparison, 52 patients with primary hypothyroidism were studied. Their mean IQ was with 89.3 +/- 18.1 (SD) significantly lower (p0.001) than the mean IQ of patients with hypothalamo-pituitary hypothyroidism. The best IQ (96.8 +/- 16.9) was attained when thyroid treatment was started before the age of 4 months, the lowest IQ (78.2 +/- 19.2) was found in the group of patients in whom thyroid substitution was initiated between 5 and 12 months. Patients who were treated after one year of age, had a mean IQ of 90.0 +/- 15.7. This group includes patients with ectopic thyroid glands or acquired hypothyroidism such as Hashimoto's thyroiditis.

Stimulation with LH-RH (luteinizing hormone-releasing hormone) was performed in 29 children and adolescents with Turner's syndrome (15 less than 13 years old), and in 11 patients with Klinefelter's syndrome (7 before puberty). Synthetic LH-RH was injected intravenously in a dose of 25 mug/m2; plasma LH and FSH were determined radioimmunologically. The results show that patients with Turner's syndrome had pathologically elevated LH and FSH values at all ages. Normal LH and FSH results before and after LH-RH were found in 3 patients with X0/XX karyotype who had spontaneous menstruation. The 2 adult patients with Klinefelter's syndrome showed an exaggerated LH response and excessively high FSH levels before and after LH-RH, consistent with hypergonadotropic hypogonadism. Six out of 7 prepubertal boys with Klinefelter's syndrome, had a normal LH and FSH response to LH-RH. Only 1 prepubertal boy with cryptorchidism and genital maliformation in addition to the Klinefelter's syndrome had pathological values. The normal gonadotropin results in prepubertal patients with Klinefelter's syndrome show that their testes apparently loose the negative feedback activity on gonadotropin secretion only during puberty, at a time when tubular hyalinization appears. This is in contrast to Turner patients with gonadal dysgenesis who have hypergondadotropic hypogonadism already early in childhood.

The case of a 6-year-old mentally retarded boy is described, who was delivered by breech presentation and who was later found to have adrenal calcifications. He presented with severe hypoglycemia during infancy and early childhood. Subsequent examinations revealed the coexistence of pituitary growth hormone and ACTH-deficiency and of adrenal medullary insufficiency. The hypothalamus-pituitary-thyroid and -gonadal axes were apparently normal. It is concluded that both, the pituitary and adrenal medullary insufficiency are probably due to the same complications at birth (hypothalamic or pituitary asphyxia and adrenal hemorrhage) and that both conditions contributed to the development of hypoglycemia.

Although newborn screening for congenital hypothyroidism was introduced into Europe as late as 1975, its high acceptance rate has quickly led to its wide use in most European countries. One would expect early diagnosis with early onset of treatment to result in normalization of previously impaired mental development. One may conclude from results obtained in 790 children up to the age of seven years that normal mental development is assured if levothyroxine is administered within the first four weeks of life. This also applies to children with athyroidism: their mental development is not different from that of children with an ectopic thyroid.

The effect of intranasal luteinising-hormone releasing hormone (L.H.R.H.) in 84 boys with unilateral or bilateral cryptorchidism was evaluated in a double-blind controlled trial. Boys with retractile testes were not studied. L.H.R.H. caused no side-effects; plasma antibodies to L.H.R.H. were never demonstrated. Four weeks' therapy with intranasal L.H.R.H. administered in six doses daily (1.2 mg/day) led to complete descent in 38% of a total of 61 testes, an improved position in 28%, and no response in 19%; 15% of testes were never palpated. After placebo the position of 25% of testes was improved; there was no response in 75% of a total of 51 testes. The success-rate seemed to be independent of age, but was related to the initial testicular position, with complete descent in only 11% of testes not previously palpated compared with 48% of testes found in the inguinal region.

In a girl with latent diabetes mellitus, glucose tolerance and insulin release were regularly examined from 6 to 12 years of age. Under diet height and weight increased normally, the glucose intolerance disappeared, and the hypoinsulinism turned into hyperinsulinism with reactive hypoglycemia. This observation demonstrates that in a longitudinal study, the same patient may present in one period with glucose intolerance (latent diabetes) and insulin deficiency and in another period with normal glucose tolerance (prediabetes) and insulin excess.

Head circumference, height, bone age and weight were studied in 103 children with congenital hypothyroidism before and up to 8 years of thyroid replacement therapy. The patients were divided into 4 groups according to the age at start of treatment: group I (diagnosed by neonatal screening): less than 2 weeks (n = 55); group II: 1-3 months (n = 7); group III: 4-12 months (n = 15); group IV: greater than 1 year of age (n = 26). Before treatment, group I showed a head circumference significantly larger than normal and a delay in bone maturation in the presence of normal length and weight. In the other groups length as well as bone age were significantly lower than normal, head circumference, in contrast, was normal (groups II and III) or even increased (group IV). During therapy, head circumference and bone age of group I became normal as were length and weight from the beginning. In the other groups, therapy led to a further increase of head size resulting in a mean head circumference significantly larger than normal during 8 years of observation in group IV. There was a catch-up of height, bone age and weight in groups II, III and IV; mean height of late treated children (group IV), however, remained significantly lower than normal even after 8 years of therapy. - Our study shows that congenital hypothyroidism is associated with increased head circumference, either absolutely or in relation to stature. Thyroid hormone therapy resulted in a normalization of head growth when treatment was initiated early, and in a further increase when treatment was started late. There was a catch-up of height, bone age and weight; complete normalization, however, occurred only in those children treated before one year of age.

The action of luteinizing hormone-releasing hormone (LH-RH) was studied in 200 children and adolescents in a general dose of 25 mcg/sq m of body surface. Results lead to the following conclusions. Testosterone in a physiological dose suppresses the LH response in delayed adolescence where LH is at normal levels, but only partially with primary testicular failure where levels of LH are increased. Young children with idiopathic hypopituitarism have a decreased response and 2 prepubertal patients with primary testicular failure had an increased response. This indicates that the hypothalamo-pituitary-gonadal axis is active even before puberty. The LH-RH test was shown to be a valuable diagnostic aid in identifying hypogonadotropic and hypergonadotropic hypogonadism and in distinguishing primary gonadal failure from primary pituitary failure. This allows one to distinguish, even before puberty, between benign delayed adolescence , primary hypothalamo-pituitary insufficiency, and primary testicular insufficiency.