Bailliere's clinical endocrinology and metabolism最新文献

The prevalence of non-insulin-dependent diabetes mellitus dramatically increases with age. Older diabetic subjects have an increased frequency of complications from diabetes compared with their younger counterparts and higher morbidity and mortality rates compared with age-matched non-diabetic controls. Elderly patients with diabetes are generally treated following the same approach as in younger patients: dietary therapy first, followed by oral hypoglycaemic agents and ultimately insulin. However, several specificities should be pointed out. Changes associated with ageing may affect the pharmacokinetics and pharmacodynamics of both sulphonylureas (increasing the risk of severe hypoglycaemia) and biguanides (increasing the risk of lactic acidosis). The best insulin regimen in old age is not known, but a twice-daily injection of a pre-mixed insulin preparation is usually recommended. Goals of therapy must be realistic and not cause disabling side-effects. The general practitioner plays a crucial role in the care of elderly diabetic patients, but access to a multidisciplinary specialized team may be necessary.

Ageing alters the metabolism of calcium and vitamin D in a number of ways. Intake of calcium and vitamin D, exposure to sunlight, cutaneous production of vitamin D₃, renal production of 1,25-dihydroxyvitamin D (1,25(OH)₂D₃), intestinal absorption of calcium and the ability to adapt to a low calcium diet may all be reduced in elderly subjects. As a consequence, secondary hyperparathyroidism often occurs with ageing and can contribute to accelerated bone loss. In fact, alterations in calcium and vitamin D metabolism may be widespread in the ageing population and play a central role in the pathogenesis of senile (age-related) osteoporosis. From a preventive point of view, recent intervention studies have indicated the need to optimize calcium intake and to maintain serum 25(OH)D₃ levels within the normal range in elderly people.

Characteristic of the normal ageing process are changes in the renal, hormonal and thirst regulatory systems involved in the control of sodium and water balance. In the presence of disease or drug use, the ageing changes put the elderly person at increased risk of either sodium retention or loss and of water retention or loss. Clinically, these alterations in water and sodium balance are commonly expressed as either hyponatraemia or hypernatraemia with central nervous system dysfunction as the symptomatic expression. Thus, the impaired homeostasis of the many systems affecting fluid balance in the elderly is readily influenced by many of the disease states and medications which are often present in the elderly with resultant adverse clinical consequences. Awareness of these age-associated circumstances can allow the physician to anticipate the impact of illnesses and drugs and to implement a rational approach to therapeutic intervention and management.

The ageing thyroid is associated with a number of morphological and functional changes, such as decreased serum T, and mean thyroid-stimulating hormone concentrations, that are to some extent independent of intercurrent non-thyroidal illnesses. All thyroid diseases, including clinical and subclinical hypo- and hyperthyroidism, non-toxic nodular goitre and thyroid cancer, are encountered in the elderly, but their prevalence and clinical expression differ from those observed in younger patients. In the elderly, autoimmune hypothyroidism is particularly prevalent, hyperthyroidism is mainly characterized by cardiovascular symptoms and is frequently due to toxic nodular goitres, and differentiated thyroid carcinoma is more aggressive. The interpretation of thyroid function tests is difficult in old individuals, because of age-associated changes in thyroid function and frequent alterations secondary to non-thyroidal illnesses and/or drugs. Treatment of thyroid disease deserves special attention in old patients because of the increased risk of complications.

Ageing in men is accompanied by a progressive decline of gonadal function with, in particular, a decline of total and free testosterone (T) plasma levels resulting in a significant proportion of elderly men over age 60 years presenting with subnormal T levels compared with the levels in young adults. A great interindividual variation in T levels is observed in elderly men, a variability explained in part by physiological variables and differences in life style, while associated acute or chronic diseases may accentuate the age-related decline of T levels. The progressive decrease of plasma T levels has been shown to result from both primary testicular changes and altered neuroendocrine regulation of Leydig cell function. At present, little is known about the clinical relevance of the relative hypoandrogenism of elderly men and there is an urgent need for more longitudinal studies, which may clarify a possible role of decreased T levels in the modulation of the clinical consequences of ageing in men. In view of the lack of relevant controlled clinical trials having careful assessment of the risks and benefits of androgen replacement therapy in elderly men, this treatment should be reserved for selected patients with clinically and biochemically manifest hypogonadism, after careful screening for contraindications.

From the endocrine point of view, menopause is considered a deficiency state and oestrogen therapy regarded as restoring the pre-menopausal endocrine milieu. Oestrogen therapy alleviates acute climacteric symptoms and also reduces the risk of cardiovascular disease, osteoporosis and Alzheimer's disease. Cardiovascular protection seems to be the major benefit of oestrogen replacement: it reduces morbidity and mortality from coronary heart disease by approximately 50%. The mechanisms are complex and not fully understood. In this review we discuss currently available data on the effects of hormone replacement therapy on serum lipids and lipoproteins, the vessel wall (endothelium dependent and endothelium independent), blood flow, cardiac function, blood pressure, haemostasis, insulin sensitivity and direct anti-atherosclerotic effect as possible mechanisms of cardioprotection. Oestrogen therapy reduces the rate of post-menopausal bone loss, increases bone mineral density (BMD) and decreases fracture rate. Recent evidence suggests that initiation of oestrogen therapy in older women produces larger increases in BMD which might provide a significant protective effect at the time when fracture is common. The incidence of Alzheimer's disease is reduced by 50% in post-menopausal women taking oestrogen replacement. Limited clinical trials of oestrogen treatment in women with this disease have documented beneficial effects on cognitive function. The results of epidemiological studies of the effects of oestrogens on breast cancer risk are conflicting but recent evidence suggests that the risk is increased in current users after 5 years of use and among older women. In contrast, increase in the risk of venous thromboembolism is most significant within the first 12 months of therapy, strongly suggesting the importance of individual susceptibility.

Pituitary tumours in the elderly are a neglected topic in the literature of endocrinology and gerontology. Data from autopsy studies in the elderly show that the commonest tumours are microadenomas, which are either immunocytochemically negative or stain for prolactin. Prolactin-secreting pituitary tumours, however, appear rarely in clinical series of patients in this age group and non-functioning adenomas are the commonest tumour seen, although pituitary metastasis and craniopharyngiomas also occur. Diagnosis can be difficult, but the commonest presentation is visual field loss. Hypopituitarism may be diagnosed late and incidental radiological diagnosis is not uncommon. There are few data which specifically answer the question, but there is a suggestion that the syndromes associated with hormonal hypersecretion may be milder in this age group. Conventional treatment with drugs, surgery and radiotherapy should be decided on an individual basis as these therapies appear to be well tolerated and beneficial in selected patients.