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Biomedical subjects

Peter C Hindmarsh

Publications and source records attributed to Peter C Hindmarsh.

20 records · Page 2Linked to original sources
PubMed2002

Oral hydrocortisone administration in children with classic 21-hydroxylase deficiency leads to more synchronous joint GH and cortisol secretion.

In humans, GH and cortisol are secreted in a pulsatile fashion and a mutual bidirectional interaction between the GH/IGF-I axis and hypothalamic-pituitary-adrenal axis has been established. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in the synthesis of glucocorticoids and often mineralocorticoids, and adrenal hyperandrogenism. Substitution therapy is given to prevent adrenal crises and to suppress the abnormal secretion of androgens and steroid precursors from the adrenal cortex. However, treatment with twice or three times daily oral hydrocortisone does not mimic physiological adrenal rhythms and may influence the activity of the GH/IGF-I axis. We investigated the pattern of GH and cortisol secretion and the synchrony of joint GH-cortisol secretory dynamics in 15 children with classic 21-hydroxylase deficiency (5 males and 10 females; median age 9.5 yr, range 6.1-11.0 yr) and 28 short normal children (23 males and 5 females; median age 7.7 yr, range 4.9-9.3 yr). All subjects were prepubertal. Serum GH and cortisol concentrations were determined at 20-min intervals for 24 h. The irregularity of GH and cortisol secretion was assessed using approximate entropy (ApEn), a scale- and model-independent statistic. The synchrony of joint GH-cortisol secretion was quantified using the cross-ApEn statistic. Cross-correlation analysis of GH and cortisol secretory patterns was computed at various time lags covering the 24-h period. Children with CAH had significantly lower mean 24-h serum cortisol concentrations (6.4 +/- 2.2 vs. 10.4 +/- 2.6 microg/dl, P < 0.001), ApEn (GH) (0.64 +/- 0.13 vs. 0.74 +/- 0.17, P = 0.04), ApEn (cortisol) (0.54 +/- 0.13 vs. 1.08 +/- 0.18, P < 0.001) and cross-ApEn values of paired GH-cortisol secretion (0.78 +/- 0.19 vs. 1.05 +/- 0.12, P < 0.001) than normal children. There was no difference in mean 24-h GH concentrations between the two groups (4.5 +/- 2.9 vs. 4.5 +/- 1.9 mU/liter). In children with CAH, a significant positive correlation between GH and cortisol was noted at lag time 0 min (r = 0.299, P < 0.01), peaking at 20 min (r = 0.406, P < 0.0001), whereas in normal children, a significant negative correlation between the two hormones was noted at lag time 0 min (r = -0.312, P < 0.01). The above findings suggest that children with classic CAH have a more regular pattern of GH secretion and a more synchronous joint GH-cortisol secretory dynamics than their normal counterparts. These differences reflect bidirectional interactions between the GH/IGF-I axis and hypothalamic-pituitary-adrenal axis in humans, and are likely to evolve as a result of the exogenous administration of hydrocortisone at fixed doses and at specific time intervals, which leads to a more regular pattern in circulating cortisol concentrations, independent of variations in CRH and ACTH concentrations.

Administration, Oral↗
PubMed2002

The use of somatropin (recombinant growth hormone) in children of short stature.

The availability of somatropin [recombinant human growth hormone (GH)] has revolutionized the treatment of short stature resulting from GH deficiency. It is also widely used as an adjunct in the treatment of other disorders which do not fit the definition of classic GH deficiency, such as intrauterine growth restriction, Turner syndrome, healthy children with short stature and skeletal dysplasias. The widespread use and ready availability of GH treatment has prompted questions about its tolerability, rationality, and the psychological effects of long-term treatment, leading to several trials. Early treatment of GH deficiency will allow the child to reach his or her genetic potential, although there continues to be marked variability in the criteria used to diagnose the deficiency, and in the treatment schedule, especially during puberty. Treatment has also been shown to have a beneficial effect on growth in children with chronic renal failure, with no adverse effects on the renal function. There are, however, no long-term data to determine final height, or randomized controlled studies to justify routine use of GH in conditions such as intrauterine growth restriction. It remains controversial in conditions such as Turner syndrome and achondroplasia, where the response to treatment is only moderate. Healthy children with short stature have not been shown to have a psychological disadvantage, again proving difficult to justify prolonged GH treatment for idiopathic short stature. Meticulous monitoring, long-term follow-up to adult or near-adult final height, and well-defined endpoints of treatment need to be better clarified. The metabolic effects of treatment on the patient's lipid profile, bone mineral density, and muscle mass need careful documentation, especially with the high doses used in an already susceptible population such as low birthweight children and those with Turner syndrome. Lastly, the psychosocial impact of GH treatment, financial implications, and cost efficacy of treatment in an ever-increasing list of indications should be taken into consideration for rationalizing its use in future.

Body Height↗