Cyproheptadine in Cushing's syndrome.
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Evidence for the role of androgens in the male aggressive and sexual behavior is reviewed. Medroxyprogesterone acetate (MPA; Provera, Upjohn) has a marked antiandrogen property; it is effective in lowering the testosterone level and controlling certain otherwise intractable sex deviations. The finding in 6 patients treated for sex deviation are summarized. The effects of MPA in the treatment of 11 temporal lobe epileptics and 5 other patients with severe angry-aggressive behavior disorder are reported. Most temporal lobe epileptics responded well to MPA. Weight gain and earlier sleep were consistent side effects. The values of plasma testosterone, serum luteinizing hormone, and urinary 17-ketosteroids were decreased by the treatment. Four patients were XYY individuals with lack of control over their sexual-aggressive or angry-aggressive impulses.
Heparin and the heparinoid Ro 1-8307 inhibited the secretory rate of aldosterone in physiological or pathological aldosteronism to the level found in normal subjects on liberal sodium intake. In addition, these compounds inhibited corticosterone biosynthesis, although less markedly than that of aldosterone. Indications of interference with cortisol production have not been found. During drug treatment angiotensin, in doses of 5-10 ng/kg b.wt./min, did not stimulate aldosterone secretion. ACTH responsiveness of the adrenals--indicated by the fractional increases of both aldosterone and corticosterone secretory rates--remained unchanged. In two studies heparin had no consistent effect on plasma renin activity.
1 The elimination and metabolism of diazepam in man was investigated following the induction of the liver microsomal enzyme system by antipyrine. 2 Seven healthy volunteers were given 1200 mg antipyrine as an inducing agent for a period of 14 days. Before and after the induction period the elimination of diazepam and desmethyldiazepam was measured in the plasma by gaschromatography. As parameters of liver microsomal enzyme activity, antipyrine elimination and gamma-glutamyl-transpeptidase in the plasma, D-glucaric acid and 6-beta-hydroxycortisol urinary excretion were measured on both occasions. 3 Following the induction period most parameters of microsomal enzyme activity measured were significantly changed indicating an increase of the microsomal enzyme system. The elimination of diazepam was significantly altered having a half-life of 37 h before and 18 h afterwards combined with a significant increase in total body clearance after the induction period, although the volume of distribution remained unaltered. The formation of the main metabolite N-desmethyldiazepam was not changed, but its elimination was increased having a half-life of 139 or 58 h respectively. 4 The elimination of unchanged diazepam and desmethyldiazepam is significantly increased by the induction of the liver microsomal enzyme system using antipyrine as an inducing agent in healthy volunteers, which might be important under certain clinical conditions.
Two brothers showed ichthyosis, bilateral cryptorchidism, hypogenitalism and mental retardation. In addition, the younger brother had short stature associated with disorders of secretions of insulin, ACTH and GH. This is the third reported case of the syndrome of ichthyosis and hypogonadism.
The glucose tolerance curve in alcoholics in delirium tremens was similar to that seen in hepatogenic diabetes. The secretion of immunoreactive insulin and somatotropin after glucose was similar in patients with delirium tremens and alcoholic hallucinosis.
The determinations carried out on 12 divers during the immersion into the sea to a depth between 7 and 29 m, as well as on controls in immersions at 4 m revealed a significant prolongation of the visual reaction time and a marked tachycardia. The changes were more marked at great depths and if exercise was superimposed over hyperbaric stress. A rise in the urinary excretion of 17-HOCS and vanillylmandelic acid and an impairment of the manual dexterity were also found during immersions. The results stress the importance of divers' monitoring during their underwater activity and the necessity of improving their physical training.
Urinary unconjugated cortisol, total 17-oxogenic steroids and cortisol metabolites (THF, allo-THF, THE, cortol and cortolone) were measured in 90 normal women and in 90 women with idiopathic hirsutism of comparable age group. After carrying out Student's "t"-test, the mean steroid excretion values in hirsute women were significantly higher than those from normal females. The results indicate that, due to stress, these hirsute women do have altered adrenocortical function, as assessed by the estimation of these corticosteroids of which urinary unconjugated cortisol was found to be the most sensitive index.
On the basis of clinico-laboratory examination of 500 patients suffering from diabetes mellitus a comparison was made of the influence of treatment with insulin and sulfanilamides on disturbed metabolic processes promoting development of vascular affections. There were found no differences in the action of insulin and oral agents on the indices of lipid, protein and mucopolysaccharide metabolism and on activity of the enzymes of the pentose-phosphate cycle. Corticosteroid excretion normalized with the compensation of diabetes, irrespective of the type of the sugar-reducing preparations. A more pronounced increase in catecholamine excretion was seen in insulin therapy apparently in connection with greater variations in glycemia level. A conclusion was drawn on analogous effect of insulin and sulphanilamides on the metabolic changes under study in diabetes. In difference from the action of insulin, a marked allergization of the of the organism accompanying the action of sulphanilamides, and their normalizing effect on the vascular permeability should be referred to the positive aspects of sulphanilamide action.
Thirty-four cases of corticosurrenaloma with clinical onset before 15 years of age have been studied. Higher frequency in girls (65 percent of the cases) and in young age (80 percent before 5 years of age, 43 percent before 2 years), association with personal or familial other tumors and malformations, are noticeable features. Virilism is the major manifestation in children (83 percent of the cases), either isolated or associated with hypercortisolism and/or feminization. Hormonal assays are of little value, and the dynamic adrenal tests are of some help only in small tumors or isolated hypercortisolism. Radiological diagnosis by urography with cavography, arteriography, is easy in most cases. Evaluation of prognosis is very difficult. Clinical and biological data are not significant, histological data are often of little help. Only a very large mass, and occurrence of metastases (liver, lungs) evidence malignancy. This series does not allow to assess definitely the best therapeutic regimen. Surgery has to be performed as soon as possible. The effects of radiations have not yet been ascertained. High doses of op'DDD have led to a sustained remission of the tumor or metastases in 2 patients, and perhaps to a longer survival in 4 others.
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The circadian rhythm of plasma cortisol and urinary 17-hydroxy-corticosteroids has been studied in 6 normal volunteers both in basal conditions and after the administration of a single dose of 30 mg of a banthine derivative (the beta methyl-beta-isopropylaminoethyl ester bromide of xantene-9-carbonic acid, "Pervagal") given orally once a day at different hours (midnight, 4 AM, 8 AM, noon, 4 PM, 8 PM). The vagolytic drug inhibits the cortisol secretion only when administered at 4 PM, 8 PM or midnight, whereas it is ineffective when given at different hours. If don't exist circadian variations of the bio-availability of the drug employed, our results suggest that also in human beings as well as in experimental animals, the cholinergic mechanisms are effective, over all if not exclusively, in starting the circadian activation of the hypothalamo-pituitary-adrenal system.
The concentration of the fractions of corticosteroids, aldosterone, catecholamines, and cyclic nucleotides (cAMP and cGMP) in blood of the adrenal veins and the activity of renin in blood of the renal veins were studied in 22 patients with stages IIA and IIB hypertensive disease. At the same time the content of these substances in the peripheral blood was determined and compared with the level of steroid and catecholamine excretion in the daily urine. An increase in the content of free 11 OCS and F fractions in the peripheral blood and blood of the adrenal veins was revealed in all patients examined.
The authors determined the level of neuraminic acid in the serum of 50 patients with encephalomalacia and 25 patients with cerebral haemorrhages on the 1st, 3d and 7th days of the disease. Twenty healthy subjects served as controls. A statistically significant rise in the concentration of this substance was observed in both groups of patients throughout the whole period of observations.
Chronic investigations (up to 3 years) conducted in dogs have evidenced that periodic disturbances of vascular permeability produced by using dicoumarin with a long-term blocking of the thyroid function greatly aggravate pathological manifestations induced by the action of 6-methylthiouracil. They result in the development in the animals of endogenous hypercholesterinemia, elevated content in the blood of beta-lipoproteins and in a periodic rise of the arterial pressure. These changes were particularly spectacular at the final stage of the experiment in animals with marked manifestations of atherosclerosis and were accompanied by reduced stand-by potentialities of the adrenal gland, disruption of metabolic processes in the myocardium along with the slowed down resorption of NaI131 from the heart muscle. The sensitivity of the heart to adrenalin was down too.
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