SUMMARY A personal series of 256 cases of acromegaly/gigantism seen over a 20‐year period from 1963 is described. The insidious nature of the condition resulted in delay in diagnosis which was often made by a doctor when seeing the patient for an unrelated problem. Other features which commonly led to the diagnosis being made were headache, change in appearance, carpal tunnel syndrome, amenorrhoea and diabetes. The Hardy system for grading the radiological appearance of the pituitary tumour was used. Widely invasive tumours were not common but tended to occur in patients with younger age of onset and high GH levels. The occurrence of various symptoms and clinical features was noted and the changes resulting from reducing the GH level to normal. The incidence of hypertension, but not of coronary artery disease, is increased and the blood pressure may be reduced following successful treatment. The effects on the upper and lower respiratory tract are reported as well as sleep apnoea and problems associated with anaesthesia. Skin manifestations included sweating, pigmented skin tags, acanthosis nigricans and cutis verticis gyrata. In the skeletal system the incidence of kyphoscoliosis and osteoarthritis especially of the hip is reported: the question of hip replacement is discussed. Diabetes mellitus disappeared in most cases if the acromegaly was cured. In men but not in women the incidence of colloid nodular goitre was increased as was hyperthyroidism in middle‐aged women. In two patients a parathyroid adenoma was present: hypercalcaemia was present in five additional patients, but the cause was not determined. The common occurrence of amenorrhoea in the younger women was noted, it was not always associated with hyperprolactinaemia, and often responded to successful treatment of the acromegaly. The association of acromegaly with hirsutism and galactorrhoea is confirmed. The incidence of impotence and loss of libido in the men is discussed: in a proportion of those in whom the acromegaly was cured, potency returned, but in a number depression occurred and what was believed to be psychogenic impotence persisted. Hyperprolactinaemia was found in 49 out of 151 patients with active acromegaly in whom the prolactin level was measured. Previous reports have indicated a doubling of death rates in acromegalics. In this series there were 47 deaths observed compared to 37.2 expected. The increased death rate was in women of all ages and in men under the age of 55. The increased deaths in the women were from cardiovascular and cerebrovascular causes and from breast cancer. To demonstrate cure it is emphasized that not only must the GH level be reduced to normal, but that suppression following a glucose load must be demonstrated and disappearance of abnormal responses for example to TRH, that would mark the persistence of adenoma cells, confirmed. Even so, late relapse may occur and GH levels should be checked regularly. Long‐term follow up (mean 9.4 years) of 102 patients after transsphenoidal surgery is reported. Eighteen pat...

1. The metabolism of unlabelled monocomponent human insulin and porcine proinsulin was studied in ten normal subjects (five males and five females) by using a priming dose-constant-infusion technique. In each subject, the metabolic clearance rate (MCR) was measured at four separate steady-state hormone concentrations averaging 16-21 6 punitslml (insulin) and 4-2-42.8 ng/ml (proinsulin).2. For insulin the MCR fell progressively from 34 ml kg-' min-' at a mean fasting insulin concentration of 3.8 punitslml to 11.4 ml kg-' min-' at the highest concentration achieved (280 punits/ml); for proinsulin MCR averaged 3.7 ml kg -' min-' at a mean plasma concentration of 4.2 ng/ml and fell to 2.71 ml kg-' min-' at 10.7 ng/ml, remaining constant thereafter at concentrations up to 71 ng/ml.3. The half-disappearance time (T+) from the plasma, after the end of the infusion, averaged 4.3 min for insulin and 25.6 min for proinsulin.4. The apparent distribution space (DS) was similar for both hormones (83 ml/kg of insulin and 98.9 ml/kg of proinsulin).5. There was a direct correlation between T+ and DS for both hormones. 6. Although the higher MCR of insulin was reflected in its shorter T+, there was, for each hormone, no relationship between MCR and T+.7. The biological potency of porcine proinsulin, as judged by its effect on plasma glucose, was approximately 5% of that of insulin.8. The responses of serum growth hormone and cortisol were shown to be directly related to the degree of hypoglycaemia induced.

The mechanism of age-related glucose intolerance was investigated by comparing forearm glucose uptake (FGU) during 100-g oral glucose tolerance tests (GTTs) in healthy men of different ages: group Y, 19-24 yr (n = 11); group M, 30-45 yr (n = 12); and group E, 70-83 yr (n = 9).Progressive elevation of the glucose tolerance curve occurred with increasing age, the curve of each group differing from the others at all points from 60-180 min. Although with age absolute levels of FGU were not reduced, the rise in FGU per incremental change in arterial plasma glucose concentration was significantly decreased, whereas the corresponding relationship between FGU and serum insulin was less marked. Early insulin responses were similar in all age groups, but after 60 min the curves diverged in a pattern corresponding to the respective glucose responses and differed significantly from 150-180 min. The relative changes in insulin levels corresponded to those observed in C-peptide concentrations in all groups. C-peptide to insulin ratios were not influenced by age. Similar proportions of proinsulin in total immunoreactive insulin were found in elderly subjects and men from group M.No difference in monocyte insulin receptor numbers or affinity was observed in elderly men and subjects from group M. Basal FFA levels were significantly higher in the elderly than in group Y and fell rapidly after glucose loading in all groups.Arterial lactate concentrations increased after glucose loading in all groups, but in the elderly the rise was significantly delayed.In order to compare FGU in these groups at similar arterial glucose levels rather than at the differing concentrations observed after glucose loading, GTTs were repeated in five subjects from group M. During these studies additional glucose was infused intermittently from 30-180 min in order to simulate the raised arterial glucose concentrations noted in the elderly. This required a mean infusion of 62.3 g (range, 33.4-97.7 g) and increased FGU to a level 3-fold greater than that observed in the elderly. To determine whether any reserve for further increasing overall glucose disposal is retained in the elderly, GTTs were repeated in three older men, in each of whom additional glucose infusions raised the 60-min concentrations by 50 mg/dl. In each of these subjects the subsequent fall in arterial glucose levels was accelerated.The results suggest that impaired peripheral glucose uptake is an important mechanism resulting in age-related glucose intolerance. At similar glucose and insulin concentrations, peripheral glucose uptake in the elderly is only one-third that in younger men. Since insulin receptor binding was not reduced in the elderly, this impairment may be a postreceptor phenomenon. (J Clin Endocrinol Metab 55: 840, 1982)

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