ABSTRACT. In 1985, a follow‐up investigation was performed of all patients with acromegaly (n = 166, 89 women and 77 men) seen over a 30‐year period (1955–1984) at our Endocrine Unit, referral centre for the western region of Sweden (population 1.5 million). At the end of 1984, the prevalence of the disease was 6.9 per 105 inhabitants, the average incidence per year was 3.3 per million people. Mean age at diagnosis was 46.3 years and at death (n=62) 64.1 years. About one‐third of the patients (50/153), in whom it had been possible to estimate the total duration of the disease, had survived for more than 25 years. Mortality was, however, increased compared to the normal population. The observed number of deaths from vascular and malignant disorders was 32 and 15, respectively, compared to the expected numbers 9.0 (p<0.001) and 5.6 (p<0.01).

The acromegalic state often is accompanied by an enlargement of the soft tissues of the body. The purpose of the present work was to determine whether these tissue changes are accompanied by changes in the content and distribution of water and electrolytes in the body. In this connection the administration of growth hormone was shown to induce an increase in the total body water of normal (1-4) and hypophysectomized (5) rats, and of normal dogs and cats (3). Similarly, growth hormone caused a retention of sodium and potassium in normal (6) and diabetic (7) rats, and a retention of sodium, potassium, and chloride in adrenalectomized rats (8). The thiocyanate space in normal and hypophysectomized rats (9) and the plasma volume in dogs (10) increased after injection of growth hormone.The present paper gives the results of measurements of the total body water, the extracellular water and the exchangeable sodium in 18 acromegalic patients. MATERIAL AND METHODSTotal body water was calculated from the volume of distribution of antipyrine (11). Total exchangeable sodium was calculated from the apparent volume of distribution of the radioactive sodium isotope Na' (12). The extracellular water was calculated from the volumes of distribution of inulin (13) Radioactive sodium, Nan, was injected intravenously, immediately after the determination of the extracellular water was completed. Urine was collected for the following 18 hours, and blood samples were taken at the end of the urine collection period.Antipyrine in plasma was analyzed according to Brodie, Axelrod, Soberman, and Levy (15). In our hands the time necessary for the completion of the reaction between antipyrine and sodium nitrite was different from day to day. Repeated readings, therefore, were taken every five to ten minutes after the addition of sodium nitrite. The maximal extinctions obtained were plotted on a semilogarithmic paper, and the extinction at zero time was obtained by extrapolation. The volume of distribution of antipyrine was calculated by dividing the given amount of antipyrine by its zero time plasma concentration.The inulin in plasma was analyzed by Roe's resorcinol method, as modified by Schreiner (16). The inulin space was obtained by dividing the total amount of inulin excreted after discontinuation of the infusion by the inulin concentration in plasma at equilibrium. The thiosulfate in plasma was analyzed by the indirect iodometricmacromethod of Newman, Gilman, and Philips (17). The thiosulfate concentration at zero time was obtained by extrapolation, and the volume of distribution calculated from this value and the amount of thiosulfate given.The concentration of'sodium in plasma was measured by a Beckman flame photometer.The conversion of the antipyrine, inulin, and thiosulfate spaces to total body water and extracellular water, respectively, was made by multiplying the values obtained by 0.93. The concentration of sodium in plasma water was calculated from the corresponding value in plasma, using the same figure, 0.93. The plasma wate...

Measurement of the volume of extracellular water (ECW) was performed simultaneously with determinations of glomerular filtration rate (GFR) and renal plasma flow (RPF) in 12 hypophysectomized patients (five cases of metastatic mammary carcinoma and seven diabetic subjects) and in 13 cases of acromegaly. Thirteen normal subjects served as controls. ECW was estimated from the volume of distribution of inulin, GFR and RPF from the renal clearances of inulin and para-aminohippurate, respectively. In the acromegalic group, an increased GFR and RPF was found together with an increased ECW, confirming earlier observations. In the hypophysectomized patients (who were all on cortisone replacement therapy), GFR and RPF were markedly decreased. However, the reduction in GFR and RPF was not associated with any significant changes in ECW.

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Determinations of cardiac output and oxygen consumption simultaneously with measurements of glomerular filtration rate and renal plasma flow were performed before and after hypophysectomy in two cases of acromegaly, two cases of metastatic mammary carcinoma, one case of diabetes mellitus and in one case of chromophobe adenoma. After hypophysectomy evidence of adrenocortical insufficiency was present in all but one subject and these patients were on substitution therapy with cortisone (17,21-dihydroxy-pregn-4-ene 3,11,20-trione) at the time of the postoperative studies. In two patients at least, postoperative hypothyroidism could not be demonstrated. In all cases, however, hypophysectomy was followed by a marked and roughly parallel reduction in cardiac output and oxygen consumption. A substantial decrease in glomerular filtration rate, renal plasma flow and renal blood flow following hypophysectomy was also found while no or only slight changes in mean brachial arterial blood pressure were observed. The changes in renal function did not always parallel the reduction in cardiac output.

Using 51Cr-labelled red cells, studies on the blood volume were performed before and after hypophysectomy in five patients (three cases of metastatic mammary carcinoma and two cases of acromegaly). In addition, studies were performed only after hypophysectomy in nine patients (two cases of metastatic mammary carcinoma and seven diabetic subjects). All patients were on replacement therapy with cortisone (17,21-dihydroxy-pregn-4-ene-3,11,20-trione) postoperatively, and several cases also received thyroid and sex hormones. Hypophysectomy was followed by a decrease in the red cell volume, the calculated total blood volume, and the total amount of haemoglobin in the patients studied before and after operation. The differences in calculated total blood volume and the total amount of haemoglobin between all hypophysectomized patients and a series of control subjects were analyzed on the basis of body weight. The total blood volume and total haemoglobin were significantly reduced in the hypophysectomized group.

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