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An investigation of the calcium metabolism has been carried out in 16 patients with Cushing's syndrome of various types and degrees, before and after either uni- or bilateral adrenalectomy, or implantation of the pituitary gland with 90 Y, and in 2 cases of adrenogenital syndrome.In all the cases of Cushing's syndrome a disturbance of calcium metabolism was observed. A negative trend of calcium metabolism was frequently found, both in cases with and without radiographic signs of osteoporosis. This was revealed by an increase of the urinary calcium, both spontaneously and after a calcium tolerance test. However, an opposite metabolic condition was found in 3 cases. A rapid change of the calcium metabolism, consisting of a marked decrease of both spontaneous and induced calciuria to values below the normal range, together with a normalisation of the hormonal picture was always recorded after the surgical treatment.A normal or positive calcium metabolism was found in the 2 cases of adrenogenital syndrome.The relationship between the metabolic and hormonal picture is thoroughly discussed.

Renal phosphate excretion was measured in 23 cases of Cushing's syndrome using the phosphate excretion index (PEI) described by Nordin & Fraser(1960). The majority of the patients had an increased PEI associated with a tendency towards hypophosphoraemia. Regression of the syndrome due to intrasellar implantation of 90Y or to removal of an adrenal neoplasm led to prompt correction of both the PEI and the phosphoraemia. In patients with adrenal insufficiency the PEI values fell below the lower limit of the normal.

1. The effect of propranolol on adrenaline- and insulin-induced hypophosphataemia was studied in man. 2. ß-Adrenergic blockade with propranolol almost completely abolished and significantly inhibited adrenaline- and insulin-induced hypophosphataemia respectively; in addition, the drug clearly prevented the normally observed rise in plasma lactate, while causing only a slight change in blood glucose levels. 3. It is suggested that the fall in blood phosphate values induced by adrenaline and, in part, that caused by insulin, is mediated by ß-adrenergic receptors.

A study of calcium and phosphorus metabolism has been carried out on 13 acromegalic patients, in various stages of the disease. This study was repeated in nine patients following implantation of the pituitary gland with 90Y and in another two patients after deep X-ray therapy and suction removal of a pituitary adenoma respectively.Increased urinary calcium and phosphorus excretion was found in all the patients in whom the disease was in an active phase of evolution. The calcium tolerance test revealed a marked decrease of calcium retention in certain subjects, while in others, calcium retention was found to be increased. Such changes were not found in patients in whom the disease was in a quiescent phase. The blood calcium, phosphorus and alkaline phosphatase were found to be either normal or slightly increased.The implantation of the pituitary gland with 90Y and deep X-ray therapy induced a marked decrease of hypercalciuria, both spontaneous and induced, and of hyperphosphaturia, together with a definite improvement, of the clinical picture and glucose metabolism. It is concluded that the changes in calcium and phosphorus metabolism described above depend either directly or indirectly on a pituitary factor. They may therefore prove a reliable index for assessing pituitary growth hormone activity.

Recently it has been demonstrated that the alkaloids of »Rauwolfia serpentina« cause depletion of catechol amines from the adrenal medulla in animals of different species (Holzbauer & Vogt, 1956; Carlsson & Hillarp, 1956; Kroneberg & Schümann, 1957; Molinatti et al., 1958).Considering separately the behaviour of the two main catechol amines of the medulla, it has been demonstrated by our previous studies (Camanni et al., 1958) that reserpine in relatively small doses causes in rats an almost complete depletion of the content of noradrenaline, while it causes no changes in the adrenaline content. These observations were recently confirmed by Eränkö & Hopsu(1958) in the adrenal medulla of rats but not of mice. In this animal they observed a parallel loss of both adrenaline and noradrenaline after reserpine administration.Since the functional response of the adrenal medulla to reserpine appears to be different from one species to another, we extended

The effects of various adrenergic substances, either alone or in association with alpha and beta blocking agents, on human plasma growth hormone (GH) were studied in 36 normal volunteers.Plasma GH levels were unaffected by i.v. adrenaline (10 μg/min for 30 min) or by propranolol (1·5 mg/min for 10 min). Given together at the same doses, these drugs provoked sharp increases in plasma GH (from 8·5 to > 100 ng/ml; a mean increase of 30±8·02 (s.e.m.)). Reduction of the adrenaline dose to 7 μg/min produced a positive response in four out of six cases.The GH response to propranolol plus adrenaline was suppressed by simultaneous administration of phentolamine, but not significantly altered by glucose and aminophylline. Noradrenaline (7–14 μg/min for 30 min) produced no changes in plasma GH levels in six cases, while its association with propranolol was followed by an increase in only one out of four cases. Phenylephrine and tyramine were without effect, with or without propranolol.In five out of six cases, GH values gradually increased after oral administration of 1 g l-DOPA (from 4·2 to 85 ng/ml; mean, 30·2). This response was totally suppressed by phentolamine.It is considered that stimulation of GH by propranolol plus adrenaline and l-DOPA is mediated by alpha-adrenergic receptors. The possible role of a beta-inhibiting effect is discussed.

An attempt was made to determine whether 6α-methyl-17α-acetoxyprogesterone (MAP) was as active as a glucocorticoid in man, as in experimental animals. This steroid was administered as a substitute for cortisone to 5 patients with definite signs of adrenal insufficiency. The subcutaneous administration of MAP in doses of 100 mg per day caused the prompt and complete disappearance of the symptoms attributable to glucocorticoid insufficiency which had developed when cortisone had been replaced by 9α-fluoro-hydrocortisone. When substitution treatment was carried out with MAP only, compensation was practically the same as with the daily administration of 50 mg cortisone. The glucose-tolerance and the insulin tests demonstrated that MAP administered subcutaneously displayed a marked glycogenetic activity.

A study has been made of the inorganic serum phosphorus pattern in twenty-one acromegalic subjects during the 'augmented insulin tolerance test'.The serum phosphorus curve differed from normal in an elevated fasting level and, more especially, a reduction in the maximum fall. The latter anomaly is far more marked and constant than those found in the blood-sugar curve, and would thus seem to be a reliable criterion for the 'activity' of acromegaly.

A study on steroid hormone metabolism in 24 cases of blood dyscrasias has been performed through chemical determination of urinary 17-ketosteroids and 17-hydroxycorticosteroids and chromatographic analysis of the former.Corticoids appeared to be preferentially decreased in acute leukemia, chronic myelogenous leukemia and polycythemia, while in chronic lymphatic leukemia and in Waldenstrom's disease 17-ketosteroids were affected as well.The chromatographic analysis of 17-ketosteroids showed that fractions IV and V, corresponding to androsterone and etiocholanolone, are decreased in almost all cases. High and bifid peaks III are constantly found in polycythemia and haemophilia; changes of peak III of a minor importance are occasionally found in all types of leukemia.The significance of the data observed is discussed from the point of view of steroid metabolism and a hypothesis is presented to explain the mechanism of the changes occurring in pattern of the various chromatographic fractions of 17-ketosteroids.