Hypercalcemia in infants with congenital hypothyroidism and its relation to vitamin D and thyroid hormones.

The circulating concentrations of calcium, phosphorus, and vitamin D metabolites were measured in 25 infants (fifteen to 30 days of age) with congenital hypothyroidism before treatment or during the first 6 months of thyroxine therapy. Five of the children before treatment and four during the early 3 months of treatment had mild hypercalcemia (10.8 to 12.4 mg/dl). Hypercalcemia before treatment did not appear to be related to the vitamin D status of the infant nor to an alteration in vitamin D metabolism, but to the presence of a residual thyroid secretion. In contrast, hypercalcemia during thyroxine therapy was related to vitamin D supplementation, even though the serum calcium concentration could not be correlated with the circulating concentration of any of the vitamin D metabolites assayed and obvious changes in vitamin D metabolism could not be demonstrated.

[Analysis of failures of screening for congenital hypothyroidism by the assay of TSH in capillary blood]. / Analyse des échecs du dépistage de l'hypothyroïdie congénitale par dosage de la TSH sur sang capillaire.

Screening for congenital hypothyroidism was started in France in 1979. The system was rapidly extended to the whole country and works very efficiently. The number of children who escaped the system is very small. However, these children represent a severe failure of the system. From 1980 to 1983, 32 cases escaped the screening. Retrospective analysis of these cases should help in improving the present system.

Diabetes insipidus in children. III. Anterior pituitary dysfunction in idiopathic types.

Seventeen patients with idiopathic diabetes insipidus occurring in childhood were observed from 4 to 26 years (mean duration 15 1/2 years). The diagnosis of idiopathic diabetes insipidus was based on routine clinical examination and careful, repeated neuroradiologic investigations. Anterior pituitary dysfunction was present in some of these patients. Growth hormone deficiency was present in six children, insufficient thyroid stimulating hormone secretion after thyrotropin-releasing hormone stimulation was demonstrated in one, and abnormal response to a metyrapone test in two. Elevated prolactin and TSH values were present in three and two patients, respectively. Some of these abnormalities were transitory. The presence of anterior pituitary dysfunction in idiopathic diabetes insipidus indicates that the destructive process is not localized to vasopressin synthesizing cells but may also involve other parts of the hypothalamus.

Twenty-four hour variations of thyroid hormones and thyrotrophin concentrations in hypothyroid infants treated with L-thyroxine.

The 24 hour plasma profile of T4, FT4, T3 and TSH was measured in a group of infants treated for congenital hypothyroidism with an oral aqueous preparation of L-T4 (5-7.5 micrograms/kg) given as a single dose at 0800 h. Mean basal plasma T4 was 8.4 +/- 2.0 micrograms/dl (mean +/- SD) and remained constant during the study while mean serum FT4 increased significantly from 1.64 +/- 0.50 ng/dl to a maximum of 2.08 +/- 0.63 ng/dl 4 h after medication. Plasma T3 decreased significantly from 241 +/- 48 ng/dl to 202 +/- 36 ng/dl 6 h after drug administration. Finally, plasma TSH decreased significantly from a mean of 24.2 +/- 18.8 microU/ml to 14.8 +/- 10.5 microU/ml 6 h later. Therefore during treatment of congenital hypothyroidism with L-T4 no specific schedule for T4 sampling is required. However, TSH determination 4 to 8 h after medication could slightly underestimate mean levels. In addition, any attempt to monitor treatment by FT4 determination should take into consideration variations of plasma values in the hours following L-T4 absorption.

[Effect of hematologic treatment on the growth and puberty of children with thalassemia major]. / Effet du traitement hématologique sur la croissance et le développement pubertaire des enfants atteints de thalassémie majeure.

This study reports on the endocrine abnormalities associated with delayed growth and puberty, observed in 10 children presenting with thalassemia major. Hormonal changes were followed up during treatment with regular transfusions and efficient chelating agents. Recovery of growth and onset of puberty were observed in most cases. When puberty was delayed, an associated substitutive treatment with sexual hormones was useful. In one case only, an isolated gonadotropic deficiency could be proven. In all cases STH, TSH and PRL secretions were normal. Without efficient and early treatment, the main consequence of the disease with respects to growth seems to be the risk of delayed puberty, mainly functional, or rarely hypogonadotropic due to definite LH and FSH deficiency.

Incidence of anterior pituitary deficiency after radiotherapy at an early age: study in retinoblastoma.

Thirty-one patients treated for retinoblastoma in the first few years (3 months to 3 years and 6 months) of life were studied 2 to 15 years later. Radiotherapy delivered 1 300 to 6 500 rads to the hypothalamo-pituitary area. Growth deficiency was documented in 30% of all cases. Other pituitary deficiencies were the exception. The critical dose for GH insufficiency is between 2 000 and 3 000 rads, as in older children or adults. Our study does not support the hypothesis that the hypothalamo-pituitary area is more sensitive to radiation at an early age. Furthermore, conservative therapy of retinoblastoma leads to double lateral irradiation and will increase the number of GH deficient children after retinoblastoma.

Germinoma in a boy with precocious puberty: evidence of hCG secretion by the tumoral cells.

The present report concerns a 10-year-old boy in whom diabetes insipidus and short stature were the first manifestations of a suprasellar germinoma. Neuroradiological investigations performed when these symptoms appeared were negative. 2 years later, a rapid and early pubertal development was observed and related to secretion by the germinoma of human chorionic gonadotropin (hCG) identified immunohistochemically. This clinical evolution is unusual and indicates that plasma hCG measurements in patients with so-called idiopathic diabetes insipidus can be of clinical value in predicting the presence of an hCG-secreting tumor.

Plasma thyroglobulin measurements help determine the type of thyroid defect in congenital hypothyroidism.

Plasma thyroglobulin (Tg) measurements were conducted in infants with congenital hypothyroidism to determine their value in the classification of the thyroid defect. Twenty hypothyroid patients were examined before 50 days of age. Plasma T4, T3, TSH, and Tg were measured and a thyroid scan was performed on all the infants. On the basis of clinical evaluation and the thyroid scans, patients were divided into three groups: group I, ectopic or eutopic hypoplastic glands (n = 11); group II, goiters (n = 3); group III, athyreosis (n = 6). There were no differences among the mean (+/- SD) TSH values of the three groups (377 +/- 291, 402 +/- 202, and 757 +/- 421 microU/ml for group I, II and III respectively). The mean (+/- SD) plasma T4 and T3 levels were lower in group III patients than in the other groups [T4, 0.55 +/- 0.12 vs. 5.0 +/- 3.5 micrograms/100 ml (group I) and 2.7 +/- 1.9 micrograms/100 ml (group II); T3, 29.3 +/- 23 vs. 165 +/- 83 ng/100 ml (group I) and 220 +/- 150 ng/100 ml (group II). Plasma Tg was undetectable in all six infants with athyreosis, and varied from 15-600 ng/ml in group I patients (mean +/- SD, 125 +/- 171 ng/ml). Tg was undetectable in one infant with congenital goiter. We conclude that tg measurements are of value in the classification of infants with congenital hypothyroidism to help clarify the nature of the thyroid abnormality once hypothyroidism has already been diagnosed.

[Precocious puberty. Comment on the diagnostic conditions and etiological aspects]. / Pubertés précoces. Réflexion sur les conditions de diagnostic et les aspects étiologiques.

The present review is based on the retrospective study of 124 children with precocious puberty, 92 girls and 32 boys. In girls, the analysis of the clinical initial presentation has shown that premature pubarche (n = 18), premature adrenarche (n = 2) or isolated menstruations (n = 3) must be ruled out, as these symptoms can remain isolated for more than a year. However, in most cases the presence of growth acceleration and vaginal estrogenisation was of major diagnostic value. Bone maturation, although generally accelerated, can be normal in recently developed puberty. Precocious puberty may proceed by steps, with complete disappearance of physical signs in the intervals. Organic causes were found in 31% of the girls, and 44% of the boys with some characteristic features as rapid progression, and elevated LH response to LRF stimulation. Main causes were glioma of the optic chiasma (n = 11), 3rd ventricule invasive tumors, hamartoma (n = 8). The latter should be looked for by a non invasive procedure as the CT scan. In girls, precocious puberty with very high circulating estrogen levels was observed as part of a McCune-Albright syndrome. As the effect of precocious puberty on the final adult height is variable, the evaluation of therapeutic results remains uncertain. Medroxyprogesterone as well cyproterone acetate have not been fully efficient in controlling bone maturation. More recently, and still controversial, the treatment with long acting LRF analogues might provide a more satisfactory statural prognosis.

Endocrine aspects and tumoral markers in intracranial germinoma: an attempt to delineate the diagnostic procedure in 14 patients.

This work outlines the endocrine abnormalities associated with intracranial germinomas (14 patients before treatment). Diabetes insipidus of various intensity was present in all cases. Adipsia is often present as well. In six patients, the first neuroradiologic examination after the onset of DI was normal. Growth hormone secretion was deficient in 11 of 13 patients. Abnormalities of TSH response to TRH were present in nine of ten (four insufficient and five exaggerated responses to TRH). Anterior pituitary dysfunction could not be predicted by the tumor site as determined by radiologic criteria. Tumoral markers have also been studied. Elevated plasma tumoral markers were found in four patients of 11 studied. Tumoral germinoma cells were present in CSF in five patients of ten, in one of them before radiologic confirmation. Pertinent endocrine evaluation and search for tumoral markers was of great value in systematic follow-up of patients with central diabetes insipidus, and could lead to early diagnosis and treatment of the tumor.

[Genetic of the 21 hydroxylase deficiency]. / Génétique du déficit en 21-hydroxylase.

A dose genetic linkage exist between the HLA complex (especially HLA-B), and the 21 hydroxylase deficiency form of adrenal hyperplasia. By their polymorphisms HLA antigens can be used as "markers" to follow the segregation of 21-OH deficiency in families, to diagnose the heterozygous offspring and eventually to offer a prenatal diagnosis to couples at risk. In late onset forms of 21-OH deficiency the same genetic linkage has been demonstrated with a high frequency of HLA-B14 antigen.

[Thalassaemia intermedia. Clinical and laboratory study. Therapeutic suggestions (author's transl)]. / La thalassémie intermédiaire. Etude clinique et biologique. Propositions thérapeutiques.

The clinical and laboratory criteria which distinguish thalassaemia intermedia (T.I.) from thalassaemia major were analyzed in a series of 30 patients with homozygous beta- thalassaemia, 8 of whom had T.I. The appearance of the first symptoms after the age of 2 years, the moderate spleen enlargement, the haemoglobin levels approaching 8 g/100 ml and the response to moderate transfusions over 1-year observation period were in favour of T.I. Since patients who had transfusions were clinically better than those who had none, it is suggested that T.I. patients should be treated with regular transfusions and iron chelating agents.

[ADH-deficient diabetes insipidus in children. A study of 93 cases (author's transl)]. / Le diabète insipide pitresso-sensible de l'enfant. II. Etude de 93 cas observés entre 1955 et 1978.

Ninety three cases of diabetes insipidus are reviewed after 1 to 20 years follow-up. A codified water deprivation test realized in 50 cases revealed 31 severe cases and 19 partial forms. Apart from surgical causes of diabetes insipidus (16%), tumors represent the most frequent etiology (33.5%), essentially craniopharyngiomas and pinealomas. Histiocytosis X (16%) is also an important cause. In one third no cause could be found. Decreased secretion of anterior pituitary hormones is very common in association with surgical and tumoral causes and can also be found in idiopathic forms. Thus, in our experience, detection of a pituitary deficit is not necessarily associated with a tumor. It can be pointed out that when an etiology is found it is always discovered during the four years following the onset of diabetes insipidus. This implies that very careful neurological and neuroradiological follow-up is necessary during this period.

Diabetes insipidus in children. I. Arginine-vasopressin determination in plasma during short dehydration test.

Plasma vasopressin as well as plasma and urinary osmolality are measured during an overnight dehydration test in vasopressin is undetectable. It is present in plasma from patients with partial diabetes insipidus but the level is not appropriate for plasma osmolality. In patients with polyuria of renal origin plasma vasopressin was significantly higher than in patients with neurogenic diabetes insipidus. Plasma vasopressin measurement is of diagnostic values in partial neurogenic diabetes insipidus and may be of considerable help to distinguish this group of patients from children with polyuria of renal origin.

[Plasma vasopressin in premature infants on mechanical ventilation]. / Etude de la vasopressine plasmatique chez les enfants prématurés soumis à la ventilation artificelle.

A systematic study has been undertaken to improve the understanding of water regulation in premature babies who are artificially ventilated. Thirty nine premature babies, 16 normal (Group N, GA 31.4 weeks, B/W 1622 g) and 23 with respiratory distress syndrome who were ventilated with or without continuous positive pressure (Group V, GA 31 weeks, BW 1505 g) have been studied. Plasma osmolalities were the same in both groups (284 and 282 mosM/Kg H2O) but there were significant differences (p less than 0.001) between the urine osmolalities N = 150.6 +/- 19.6 V = 294 +/- 25.9 mosM/Kg H2O) and the plasma ADH levels of the two groups (N = 2.9 +/- 0.4 pg/ml, V = 12.2 +/- 2.4 pg/ml). There was a significant correlation between the urine osmolality and the plasma ADH level but not between plasma osmolality and the plasma ADH level. Several hypotheses can be proposed but none are satisfactory.