Making a rational diagnosis of growth-hormone deficiency.

Growth hormone (GH) has been available for therapeutic use for more than 30 years, but there is still considerable debate about the best way to diagnose GH deficiency. This can be attributed to the existence of a variable degree of GH insufficiency in most cases and the fact that assays vary considerably between laboratories in terms of sensitivity and epitope specificity. These difficulties are compounded by the episodic nature of GH secretion and our reliance on a variety of provocative tests. A workshop and consensus report held in Portland, Oregon, in 1995 highlighted these issues and suggested a rational diagnostic approach that emphasizes good auxologic evidence, followed by assays of insulin-like growth factor I and insulin-like growth factor binding protein 3 to identify abnormalities in the GH axis. Actual assays of GH, during some provocative tests, are relegated to confirming that an identified abnormality in the GH-insulin-like growth factor axis is related to GH insufficiency rather than to GH resistance.

The mechanism of low testosterone levels in homozygous sickle-cell disease.

Significantly lower testosterone levels are common in male patients with homozygous sickle-cell (SS) disease and have been attributed to either abnormalities of the hypothalamo-pituitary axis or primary testicular failure. The mechanism has now been investigated by observing the response to gonadotropin-thyrotropin releasing hormones (GnRH-TRH) in 10 male patients with SS disease and in 10 matched male sibling controls without sickle-cell disease. Mean basal levels of luteinizing hormone (LH), follicular stimulating hormone (FSH) and thyrotropin (TSH) were significantly elevated but prolactin (PRL) levels were within the normal range in the SS group. All hormones increased following GnRH-TRH, and proportionate increases over baseline were similar for FSH and TSH in SS and AA subjects, but SS patients showed a lesser percentage increase in LH at 30 minutes, and a higher percentage increase in PRL at 60 minutes. These observations are more consistent with primary testicular failure than with abnormalities of the hypothalamic-pituitary-testicular axis.

The mechanism of low testosterone levels in homozygous sickle-cell disease

Significantly lower testosterone levels are common in male patients with homozygous sickle-cell (SS) disease and have been attributed to either abnormalities of the hypothalamo-pituitary axis or primary testicular failure. The mechanism has now been investigated by observing the response to gonadrotropin-thytotropin releasing hormones (GnRH-TRH) in 10 male patients with SS disease and in 10 matched male sibling controls without sickle-cell disease. Mean basal levels of luteninizing hormone (LH) follicular stimulating hormone (FSH) and thyrotropin (TSH) were significantly elevated but prolactin (RL) levels were within the normal range in the SS group. All hormones increased following GnRH-TRH, and proportionate increases over baseline were similar for FSH and TSH in SS and AA subjects, but SS patients showed a lesser percentage increase in LH at 30 minutes, and a higher percentage increase in PRL at 60 minutes. These observations are more consistent with primary testicular failure than with adnormalities of the hypothalmic-pituitaty-testicular axis (AU)

The mechanism of low testosterone levels in homozygous sickle-cell disease

Significantly lower testosterone levels are common in male patients with homozygous sickle-cell (SS) disease and have been attributed to either abnormalities of the hypothalamo-pituitary axis or primary testicular failure. The mechanism has now been investigated by observing the response to gonadrotropinthytotropin releasing hormones (GnRH-TRH) in 10 male patients with SS disease and in 10 matched male sibling controls without sickle-cell disease. Mean basal levels of luteninizing hormone (LH) follicular stimulating hormone (FSH) and thyrotropin (TSH) were significantly elevated but prolactin (RL) levels were within the normal range in the SS group. All hormones increased following GnRH-TRH, and proportionate increases over baseline were similar for FSH and TSH in SS and AA subjects, but SS patients showed a lesser percentage increase in LH at 30 minutes, and a higher percentage increase in PRL at 60 minutes. These observations are more consistent with primary testicular failure than with adnormalities of the hypothalmic-pituitaty-testiculat axis.

Pulsatile growth hormone secretion in peripubertal patients with chronic renal failure. Cooperative Study Group on Pubertal Development in Chronic Renal Failure.

The pubertal growth spurt has been associated with changes of physiologic pulsatile growth hormone (GH) secretion, and abnormalities of the central regulation of GH release have been found by pharmacologic testing in patients with chronic renal failure. To assess the characteristics of GH pulsatility in chronic renal failure and their relationship to pubertal growth, we studied spontaneous nighttime GH plasma profiles in 80 patients (61 boys) aged 10 to 20 years receiving conservative treatment (n = 29) or dialysis (n = 18) or after renal transplantation (n = 33). Tanner genital stages 1 to 4 in boys and breast stages 1 to 3 in girls were represented. Growth hormone pulse analysis was performed by the PULSAR algorithm. Growth hormone concentration profiles were pulsatile in each patient. Growth hormone mean and baseline levels and pulse amplitudes were higher in patients receiving conservative or dialysis treatment than in patients who had undergone renal transplantation. Peak frequency was similar in all treatment groups in boys but higher in girls who had undergone transplantation than in girls receiving conservative or dialysis treatment. Growth hormone peak amplitude and mean levels were lowest in patients in late puberty. The physiologic elevation of GH amplitudes around midpuberty was observed in boys receiving conservative and dialysis treatment but not after transplantation. Growth hormone mean and baseline levels were positively correlated with plasma androgen levels in boys. Growth hormone peak amplitude was correlated with 6-month height velocity after transplantation but not in patients receiving conservative treatment or dialysis. A strong inverse relationship was observed between GH peak amplitude and corticosteroid dosage in patients undergoing transplantation. The lack of relationship between circulating GH levels and growth in patients receiving conservative or dialysis treatment is compatible with end-organ hyporesponsiveness to GH. Pubertal growth failure despite successful transplantation appears to be related to steroid-induced GH hyposecretion.

Evaluation of the nutritional status of 1st-year school children in Campinas, Brazil.

We present findings from a study of nutritional status amongst 1st year primary school children in Brazil. The study was based on a 10% stratified random sample of children in Campinas, Sao Paulo State. The primary schools in the city were grouped into four socio-economic strata (high, medium, low and very low) based on the type of school maintenance (private or maintained by the local or by the State government) and the socio-economic characteristics of the school's catchment area. The nutritional status of 1942 children was assessed by looking at the distributions of z-scores of weight-for-age, height-for-age and weight-for-height in relation to growth charts of the National Center for Health Statistics reference population. In the overall population, 22% of the children were found to be stunted (z-score of height-for-age less than -1.0), 15% wasted (z-score of weight-for-height less than -1.0), 22% underweight (z-score of weight-for-age less than -1.0) and 5% overweight (z-score of weight-for-height greater than 2.0). These figures represent an excess of 6% of stunted children and also 6% of underweight children in comparison with the expected values in the NCHS reference population, and an excess of 2% overweight. The data were analysed by age, sex, ethnic group and socio-economic level. Both stunting and low weight-for-age were observed in 32% of children from the very low socio-economic level, with the highest percentages amongst the oldest children. A total of 11.6% of children from the high socio-economic stratum were obese. These results emphasize the need for different programmes to deal with nutritional problems in different groups of the population.

Ovarian ultrasound appearances in Turner syndrome.

We performed pelvic ultrasound assessment in 104 patients with Turner syndrome aged 0.2 to 17.4 years; 69 had the 45,X karyotype and 35 had variant karyotypes. Ovarian appearances were classified as "streak" (n = 70, including 30 patients in whom no ovary could be seen) or "nonstreak" (n = 34). The nonstreak ovaries ranged from small glands, sometimes containing minute cysts, to ovaries indistinguishable from those which are normal for age. Nonstreak ovaries retained a range of function, as evidenced in some cases by spontaneous breast development and uterine enlargement. The proportion of nonstreak ovaries followed a U-shaped pattern, with a nadir from 4 to 10 years; this follows the known biphasic pattern of luteinizing hormone and follicle-stimulating hormone secretion. Only those patients with karyotype variants in which the long arm of the X chromosome was retained fared better than those with the 45,X karyotype.

Impaired pituitary responsiveness to luteinizing hormone-thyrotropin releasing hormone: a possible sickle-cell disease - abstract

Homozygous sickle-cell(SS) disease is associated with delayed development and reduced fertility in both men and women. The results of an initial pilot study indicated significantly lower (p<0.01) serum levels of testosterone in male SS patients. This study is a further attempt to evaluate pituitary responsiveness to exogenous administration of luteinizing-thyrotropin releasing hormone (LHRH-TRH) in a group of 10 male SS patients, each matched with a brother without SS disease to determine whether a defect exists in the central regulation of pituitary secretions in these patients. The mean serum testosterone levels were significantly lower (p < 0.025), whereas basal levels of luteinizing hormone (LH) and thyrotropin (TSH) were significantly higher (p < 0.05) at 20 minutes in the SS patients. Mean LH responses were consistently higher in SS patients but the differences only reached significantly (p<0.05) at 120 minutes after LHRH-TRH administration. We concluded that subnormal levels of serum testosterone in SS disease are not solely attributable to primary testicular failure, but also result from defect(s) in LH-negative feed back operation (AU)

Clinical and subclinical vitamin D deficiency in Bradford children.

A survey of the vitamin D status of Bradford schoolchildren was carried out in April 1973, employing conventional biochemistry, radiology, and measurement of 25-hydroxycholecalciferol levels. Biochemical evidence of rickets was present in 45% of the Asians. When re-examined in September, several children showed spontaneous biochemical resolution; nevertheless, radiological abnormalities were present in 12% of the original sample. No evidence of rickets was detected in the smaller White sample. Minor biochemical abnormalities were present in 9 of the 40 West Indian children. A study of admissions of Bradford hospitals in the 4 years 1969-1972 inclusive confirmed that clinical vitamin D deficiency was confined to Asians except for a few cases of infantile rickets in White children. The probability that one Asian child in 40 may require admission during the period from birth to adolescence emphasizes the urgent need for the introduction of prophylactic measures.