No abstract

We describe a female newborn infant with McCune-Albright syndrome. In addition to the cutaneous pigmentation, she had apparent manifestations of hyperthyroidism and Cushing syndrome since birth. X-ray examinations showed many scattered lucencies in multiple bones. Endocrinological findings were as follows: serum T 4 276 nmol/l; free T 4 125 pmol/l; TSH less than 1 mU/l; serum cortisol greater than 2210 nmol/l; plasma ACTH less than 10 pg/ml; urinary free cortisol 865 nmol/day; estradiol 0.36 nmol/l. Regardless of treatment with antithyroid drugs and an inhibitor of 3 beta-hydroxysteroid dehydrogenase, the patient died of cardiac failure at the age of 4 months. Autopsy findings included a follicle cyst in the right ovary and multinodular hyperplasia in the thyroid and both adrenals. To our knowledge such a severe neonatal form of McCune-Albright syndrome has not been described in the literature.

To ascertain the molecular background of combined pituitary hormone deficiency, screening for mutations in the pituitary-specific transcription factor (Pit-1/GHF-1) gene (PIT1) was performed on a cohort of 15 children from Russia with combined growth hormone (GH)/prolactin (Prl)/thyroid-stimulating hormone (TSH) deficiency. The group of patients, suspected of PIT1 mutations, consisted of four familial cases (seven patients) and eight sporadic cases. All had complete GH deficiency and complete or partial Prl and TSH deficiency. Direct sequencing of all six exons of PIT1 and its promoter region showed a C to T transition mutation at codon 14 of exon 1 in a 3 8/12-year-old girl. This novel PIT1 mutation results in a proline to leucine substitution (P14L). The patient was heterozygous for mutant and normal alleles. The heterozygous P14L mutation was also present in her mother as well as in her maternal aunt and grandmother, all of whom were phenotypically normal. There was no mutation in the father's DNA, suggesting the need for reevaluation of genomic imprinting. In other children of our series, no mutation in PIT1 or in its promotor region was identified. This is the first report on the analysis of PIT1 and its promoter region in Russian children with GH/Prl/TSH deficiency. However, as the involvement of PIT1 mutation is rare in Russia, the other negative cases need to be analyzed for another candidate gene responsible for combined GH/Pr/TSH deficiency.

In this study we evaluated the pituitary-hypothalamic abnormalities of "idiopathic growth hormone (GH) deficiency" as demonstrated by MR imaging. Twenty-four patients were examined with a 1.5-T unit using spin echo T-1 weighted images. The patients were divided into two groups according to MR findings: those with ectopic posterior pituitary glands (12 patients), and those with normal posterior pituitary glands (12 patients). Ten patients in the former group and four in the latter group had small anterior pituitary glands. All patients in the former group but only four in the latter group had severe GH deficiencies. Multiple hormone deficiencies were found in eight patients in the former group, but in only two in the latter group. Among the 12 patients with posterior pituitary ectopia, 11 were males, 10 had been born by breech delivery, and four had a history of asphyxia. It is speculated that perinatal abnormalities can cause posterior pituitary ectopia and that there is a close correlation between breech delivery and the male disadvantage of posterior pituitary ectopia. Half of our patients with "idiopathic GH deficiency" had ectopic posterior pituitaries. GH deficiency with posterior pituitary ectopia should no longer be considered idiopathic because organic lesions can now be identified during life.

Keywords: radon inhalation; ascorbic acid; carbon tetrachloride; antioxidative function; liver 3