1/7. Endocrine studies in Fanconi's anaemia. Report of 4 cases.Four boys with Fanconi's anaemia and growth hormone (GH) deficiency are reported. Case 1 had isolated GH deficiency and responded to HGH and to oxandrolone treatment. Case 2, his brother, had milder haematological and dysmorphic manifestations and maintained a low-normal growth rate without treatment in spite of laboratory evidence of GH deficiency. Case 3 had multiple hypothalamopituitary defects, including deficiencies of GH, ACTH, and gonadotrophins. Case 4 had isolated GH deficiency and responded moderately well to HGH treatment. 3 of the 4 patients had bilateral cryptorchidism, 2 with increased plasma gonadotrophins, indicating primary testicular failure. We conclude that GH deficiency, isolated or combined with other hypothalamopituitary defects, and primary testicular failure with cryptorchidism are frequent but not constant features of Fanconi's anaemia.- - - - - - - - - - ranking = 1keywords = pituitary (Clic here for more details about this article) |
2/7. Unusual cause of short stature.A 24-year-old man evaluated for paresthesias and short stature was found to be hypocalcemic on initial presentation. Further evaluation showed that he had a low-normal parathormone level by amino-terminal assay, medullary stenosis of the long bones, and multiple ophthalmologic abnormalities. The remainder of his pituitary function, including growth hormone response to insulin-induced hypoglycemia, was normal. As no family history of similar findings was evident, a sporadic case of Kenny's or Kenny-Caffey syndrome was diagnosed. He became normocalcemic in response to vitamin d and calcium carbonate therapy. The results of testing in this patient and the findings in other patients previously described with the Kenny-Caffey syndrome are reviewed.- - - - - - - - - - ranking = 0.5keywords = pituitary (Clic here for more details about this article) |
3/7. Russell-silver syndrome and hypopituitarism. Patient report and literature review.Russell-silver syndrome (RSS) is a sporadic form of prenatal onset dwarfism with typical facial features, variable asymmetry, and linear growth 3 to 4 SDs below the mean. Endocrinologic studies are usually normal; however, six cases of RSS with growth hormone deficiency have been reported, three of which had additional pituitary abnormalities. We describe another case, a 7-year-old girl with RSS and deficiencies of growth hormone, corticotropin, and thyroid-stimulating hormone. Replacement therapy including growth hormone resulted in an improved growth velocity, though twice the usual dose of growth hormone was required and short stature persisted. Since growth hormone secretion is usually normal in RSS, the existence of individuals with RSS phenotype and hypopituitarism including growth hormone deficiency suggests etiologic heterogeneity. We recommend that those individuals with RSS phenotype and a continuous significant decline in height velocity be investigated for pituitary abnormalities. Unusually high replacement doses of growth hormone may be required to overcome deficiency.- - - - - - - - - - ranking = 1keywords = pituitary (Clic here for more details about this article) |
4/7. GH secretion in two siblings with Laron's dwarfism: the effects of glucose, arginine, somatostatin, and bromocryptine.The secretion of GH in two siblings with clinical dwarfism and high GH plasma levels (the mean of several basal values; 233.83 ng/ml in patient A and 178.16 in patient B has been studied with several dynamic tests. An arginine infusion increased GH levels in both cases ( 193.55% for A, 140.27% for B). No significant modifications were obtained with oral glucose tolerance test 18.70% for A, 24.32% for B). A bolus of somatostatin almost completely prevented the rise in GH levels in response to arginine. Pretreatment with bromocryptine clearly increased basal GH plasma levels (A, 58.66%; B, 56.03%) and the response to arginine. As in the case of a normal hypothalamus, the hypothalamus of Laron's syndrome responds to arginine and bromocryptine, with GH elevations. somatostatin suppresses GH levels. A lack of response to glucose can be considered as a nonspecific effect of the very low biological activity of the stimulus in a hyperstimulated hypothalamus. We suggest that GH secretion by the hypothalmo pituitary system in Laron's syndrome is normal, and that GH hyperproduction may be due to a generalized defect in GH receptors or to the low levels of somatomedin.- - - - - - - - - - ranking = 0.5keywords = pituitary (Clic here for more details about this article) |
5/7. Unique case of growth hormone (GH) deficiency accompanied by clinical anophthalmia, hypoplastic orbits, digital dysplasia, short stature, obesity, and diabetes mellitus.A 43-year-old female was admitted to our hospital for polydipsia and hyperglycemia. She had total blindness and globes were not recognized by inspection, indicating clinical anophthalmia. physical examination revealed short stature, obesity, prematurely gray hair, shortness of fingers and toes, syndactyly, and multiple dental caries. Laboratory examination showed hyperglycemia, increased glycosilated hemoglobin (HbA1c) and insulin resistance on euglycemic glucose clamp. Blunted growth hormone (GH) secretion was shown in response to insulin-induced hypoglycemia, arginine infusion, and GH-releasing hormone (GHRH) loading test, and in 24 h spontaneous GH profile. magnetic resonance imaging (MRI) and computed tomography (CT) showed dysostosis of orbit, defect of optic nerve, enlarged suprasellar cistern, and prolonged pituitary stalk. This may be the first report of a unique case with GH deficiency accompanied by clinical anophthalmia, hypoplastic orbits, digital dysplasia, short stature, obesity, and diabetes mellitus.- - - - - - - - - - ranking = 0.5keywords = pituitary (Clic here for more details about this article) |
6/7. Pituitary dwarfism in the R271W Pit-1 gene mutation.The Pit-1 gene encodes the POU-domain transcription factor pit-1 which is important for the differentiation of the anterior pituitary and regulation of the PRL, GH and TSH genes. As a member of the POU domain transcription factors, Pit-1 contains a dna-binding region, consisting of a POU-specific domain and a POU homeodomain. mutation of the Pit-1 gene causes hypoplasia of the pituitary gland and deficiencies of GH, PRL and TSH. In a dna sample from a 3-month-old girl with severe growth deficiency from birth, single stranded conformational polymorphism analysis of the Pit-1 gene identified a gel shift in exon 6. dna-sequencing disclosed a single base mutation in codon 271 (CGG to TGG) that changes arginine to tryptophan (R271W) in the POU homeodomain. The patient presented distinct facial features with prominent forehead, marked mid-facial hypoplasia with depressed nasal bridge, deep-set eyes and a short nose with anteverted nostrils. MRI examination showed a hypoplastic pituitary gland. Low serum GH did not respond to insulin-arginine provocation or GHRH tests. PRL levels below the detection limit did not increase in response to a TRH test. T4 and free T4 was below detection limit (< 20 nmol/l and < 4 pmol/l). TSH was 2.0 mU/l and showed a blunt response to 6.0 mU/l following TRH test. TBG was normal. In spite of inappropriately low TSH and very low T4, T3 was in the low normal range (1.4-1.6 nmol/l) and she was clinically euthyroid. The thyroid function tests are consistent with increased monodeiodination activity and increased conversion of T4 to T3, possibly related to the Pit-1 gene mutation. GH and T4 treatment resulted in catch-up growth continued during 5 years of therapy. Conclusion: Reports of nine other cases of R271W mutations of different populations as well as the present Norwegian patient suggest codon 271 of exon 6 to be a "hot spot" for Pit-1 mutations. To enable rapid and simple detection of this type of de novo mutation we have designed a specific amplification-created-restriction-site assay to check for the R271W mutation in patients suspected to have this rare form of genetic defect in growth hormone production.- - - - - - - - - - ranking = 1.5keywords = pituitary (Clic here for more details about this article) |
7/7. Megalencephaly, hydrocephalus and cortical dysplasia in severe dwarfism mimicking leprechaunism.This report concerns an autopsy case of megalencephaly exhibiting a unique combination of physical and brain malformations. A 4-year-old boy had a peculiar face, a severe reduction of subcutaneous adipose tissue, severe growth failure and frequent hypoglycemic episodes. These clinical features were compatible with leprechaunism; however, the absence of hyperinsulinemia and insulin resistance prevented the diagnosis of leprechaunism. The autopsy disclosed complex cardiac and brain malformations. Although hydrocephalus coexisted, the brain weight after complete removal of the cerebrospinal fluid was 2260 g, which was greater than the average brain weight of normal Japanese children of the same age. The neuronal density in the cerebral cortex was decreased, while the surface area of the cerebral cortex and white matter were greater than those in an age-matched control. There was cortical dysplasia in the frontal and parietal lobes. Endocrine tests and immunohistochemical analysis of the brain did not demonstrate any abnormalities in the hypothalamus-pituitary system. Megalencephaly can be associated with dwarfism, and this case is important for consideration of the interrelationship between neuronal proliferation and physical growth.- - - - - - - - - - ranking = 0.5keywords = pituitary (Clic here for more details about this article) |