Clinics in Endocrinology and Metabolism最新文献

The shape of the human growth curve is described and illustrated. Growth studies may be longitudinal, cross-sectional, mixed longitudinal or linked-longitudinal; each has advantages and disadvantages, and each requires appropriate statistical methods for handling the data. Standards for height and height velocity for use in a clinical setting wherein follow-up over several years is presumed are described and illustrated. Such standards have to take into account tempo of growth at ages over nine years. Cross-sectionally derived standards do not do this and are not suitable for clinical use.

The techniques of measurement of height, sitting height and skinfolds are described and illustrated.

Growth and development during puberty is described; there are changes in body composition as well as in body size and shape. Standards for pubertal stages of breasts, pubic hair and genitalia are given and emphasis of these pubertal changes.

Measurement of developmental age is discussed. The Greulich—Pyle and Tanner-Whitehouse methods for skeletal age are described. These methods can be used for predicting adult height which is useful both in diagnosis and in following the effects of treatment. In diagnosis the predicted adult height is compared to the range of expected heights in the children of the particular pair of parents concerned (the so-called ‘target’ range of heights) to see if smallness is simply due to delay. Change in Tanner-Whitehouse predicted height occurs on successful treatment of, for example, growth hormone deficient short stature, and is thus a guide to the success of treatment. Standards are also given for height of children from age two to nine inclusive, with allowance for height of their parents.

The basis for understanding clinical disorders in the neuroregulation of GH secretion is derived from the complexity of the CNS—hypothalamic-pituitary axis. Studies in animals and humans demonstrate an anatomic, physiological and pharmacological evidence for neurosecretory control over GH secretion including neurohormones (GRH, somatostatin), neurotransmitters (dopaminergic, adrenergic, cholinergic, serotonergic, histaminergic, GABAergic), and neuropeptides (gut hormones, opioids, CRH, TRH, etc). The observation of a defect in the neuroregulatory control of GH secretion in CNS-irradiated humans and animals led to the hypothesis of a disorder in neurosecretion, GHND, as a cause for short stature. We speculate that in this heterogeneous group of children a disruption in the neurotransmitter-neurohormonal functional pathway could modify secretion ultimately expressed as poor growth velocity and short stature.

Short stature may complicate the treatment during childhood of brain tumours and, to a lesser extent, ALL. A number of factors may be responsible, including spinal irradiation, malnutrition, recurrent tumour, chemotherapy, precocious puberty and radiation-induced GH deficiency. GH is always the first pituitary hormone to be affected by radiation damage to the hypothalamic-pituitary axis but larger radiation doses may result in panhypopituitarism.

Some children retain normal GH responses to certain provocative stimuli, although physiological GH secretion is reduced. Nonetheless, in children suspected of radiation-induced GH deficiency, pharmacological tests of GH secretion remain useful, the ITT being the test of choice because of the marked radiation sensitivity of the GH response to hypoglycaemia.

The hypothalamus is more radiosensitive than the pituitary. In many patients with radiation-induced GH deficiency, the damage appears to be at the hypothalamic level resulting in a deficiency of endogenous GRF. Treatment with synthetic GRF may provide an alternative to GH therapy in such children.

Finally, there is no evidence to suggest that GH therapy given to a child with radiation-induced GH deficiency might induce a brain tumour recurrence or a relapse of ALL.

The growth of hair, except that on the scalp, and the secretion of sebum are, in general, under the major influence of androgens. However, the responses of the hair follicles and their associated glands vary greatly between sites and between individuals.

On the face, trunk and extremities the most important role of testosterone is to increase the period of activity, the anagen phase, of the hair follicle, though it also increases the rate of growth, thickness, extent of medullation and pigmentation of the hair. These effects involve high levels of hormone and its conversion to 5α-dihydrotestosterone in the target organ. In contrast, the lower pubic triangle develops luxuriantly even in absence of 5α-reductase.

In the sebaceous glands, cell replication and lipid synthesis do not seem to be identically controlled, since they respond differently to inhibitors. The response of the sebaceous glands to androgens involves the interaction at the target site of pituitary factors, for which growth hormone, prolactin, and melanocyte stimulating hormone are all putative candidates.

The most important scientific and clinical question is whether, in any particular circumstances, the degree of response of the hair follicles or sebaceous glands is determined by the level of available androgen or by the sensitivity of the target organ. While it is true that some patients with hirsutism or acne have above normal levels of plasma androgens or below normal levels of SHBG, a substantial proportion are normal in all respects. Moreover, the rates of hair growth on the extremities or of sebum excretion on the forehead do not seem to be correlated either positively with plasma androgens or negatively with SHBG, though they each have been shown to be correlated with circulating 5α-dihydrotestosterone. The conclusion must be that, although male-type hair growth and high sebaceous secretion may be caused by, or at least accompanied by, high levels of free testosterone, the critical factor is more likely to be the peripheral response.

The pathophysiology of glandular androgen hypersecretion must be regarded as a continuous process without sharp borderlines from normal to non-tumorous conditions, such as polycystic ovaries and hyperthecosis, to neoplastic disease. Hirsutism and related symptoms are most often caused by excess androgens of ovarian and/or adrenal origin, i.e. testosterone, dihydrotestosterone, Δ⁴-androstenedione, dehydroepiandrosterone and its sulphate. As demonstrated by selective catheterization of glandular effluents, combined hypersecretion occurs more frequently than either purely gonadal or adrenal overproduction. No correlation can be found between the type, frequency and extent of hormonal changes and the clinical, laparoscopic, angiographic, or histological findings. Dynamic function tests do not reliably discriminate between the various aetiological subgroups due to extremely variable and even non-specific individual responsiveness. Selective catheterization is presently the most sensitive method for the preoperative identification and localization of androgensecreting neoplasms.