Clinics in Endocrinology and Metabolism最新文献

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 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 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.

PSAs, with few exceptions, consist of a piliary and a sebaceous component. In androgen-sensitive areas, each has the capacity to develop into either a terminal hair follicle or a sebaceous follicle depending upon its location. Without androgen, there is no development of the sexual hair follicle or sebaceous gland. Androgens appear to promote sexual hair growth by recruiting a population of PSAs that have preset genetic sensitivity to initiate the production of terminal hairs. The site of action of androgens within the PSA is unclear. There are indications that androgens may act at more than one site in a system that requires two-way reciprocal interaction between dermal and epithelial cells for the generation of hair growth. Growth hormone appears to exert an important synergism with androgen in affecting the PSA, seemingly through the mediation of insulin-like growth factors.

Hirsutism is due to an increased density of growing terminal hairs. The majority of cases of moderately severe hirsutism in women are due to hyperandrogenaemia, as are half the cases of mild hirsutism and about one-quarter of the cases of mild acne vulgaris. We advocate reserving the term idiopathic hirsutism or idiopathic acne for those patients in whom excessive growth of terminal hair or acne is not explained by androgen excess. We believe that highly variable sensitivity to androgen within the population explains both idiopathic hirsutism and cryptic hyperandrogenaemia; that is, these disorders lie at opposite ends of the normal spectrum of sensitivity to androgen. The biological basis for the variations in responsiveness of PSAs to androgens is unknown. The regression of hirsutism induced by antiandrogen treatment is characterized by the growth of hairs that are more vellus in character, i.e. smaller and less medullated.