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Biomedical subjects

G M Besser

Publications and source records attributed to G M Besser.

At least 433 records · Page 24Linked to original sources
PubMed1979

Psychiatric manifestations of Cushing's syndrome: response to lowering of plasma cortisol.

The incidence of psychiatric abnormalities has been assessed in 38 patients with Cushing's syndrome and two with alcohol-induced pseudo-Cushing's syndrome. Twenty-six patients were examined by one of us using a standardized psychiatric interview, and this group included all those with severe to moderate psychiatric disorders. Depression was the commonest symptom: five patients (13%) were markedly or severely depressed, four (10%) were moderately depressed and 13 (32%) were mildly depressed. Four patients exhibited other, non-depressive psychiatric symptoms and only 14 (35%) were judged free from psychiatric abnormality. The first line of treatment was to reduce the circulating cortisol level either by adrenalectomy or by treatment with oral metyrapone; both patients with alcohol-induced pseudo-Cushing's syndrome were treated by alcohol withdrawal. Once the plasma cortisol level was successfully controlled, depressive symptoms were relieved in all five patients with marked or severe depression and in three of the four who were moderately depressed. Mild depressive symptoms were relieved in six of the 13 affected. It is concluded that metyrapone may be of considerable value in the management of the acute psychiatric states which may occur in Cushing's syndrome and these findings are discussed in the light of their possible pathogenesis.

Adolescent↗
PubMed1978

Hormonal and metabolic responses to an enkephalin analogue in normal man.

An enkephalin analogue [D-Ala2, MePhe4, Met(o)-ol] enkephalin (DAMME), given intravenously to normal subjects raised serum prolactin and growth-hormone levels but lowered serum levels of luteinising hormone, follicle-stimulating hormone, cortisol, and corticotrophin. There was also a small fall in total glucagon and gastric inhibitory peptide (G.I.P.) and a rise in thyrotrophin. beta-Lipotrophin, motilin, vasoactive intestinal peptide, insulin, gastrin, and pancreatic glucagon were unchanged. Blood-glycerol increased, and blood lactate, alanine, and glucose fell. Prior administration of the opiate antagonist, naloxone, attenuated the hormonal responses to DAMME. This enkephalin analogue produces endocrine and metabolic changes in man which may be mediated through opiate-binding receptors both within and outside the brain. The enkephalins and related substances may provide an important link between perception, behaviour, and neuroendocrine regulation of hormone secretion and metabolism.

Adrenocorticotropic Hormone↗
PubMed1978

Medical management of acromegaly with bromocriptine. Effects of continuous treatment for over three years.

Eighty-seven patients with active acromegaly were treated with bromocriptine for periods of up to 42 months. On treatment, 82 of these patients noted a rapid alleviation of one or more symptoms of their disease. In 67 patients, the mean growth hormone level of four values taken through the day fell by 14 mu/L or more, or became undetectable. Eighty patients have been treated for over 12 months and this suppression was maintained. Improvement in abnormal glucose tolerance occurred in 25 out of 29 diabetics and tolerance became normal in 19. Bromocriptine is of great value in cases in which surgery or radiotherapy has not been completely effective or as interim treatment until the full effect of other therapy has taken place. However, the long-term effect of high doses of bromocriptine is not yet known.

Acromegaly↗
PubMed1978

beta-Endorphin in human cerebrospinal fluid.

beta-endorphin is a brain peptide with potent morphine-like activity structurally related to the anterior pituitary hormone beta-lipotrophin (beta-L.P.H.). We have developed a radioimmunoassay for human beta-endorphin in plasma and cerebrospinal fluid (C.S.F.). Since the antiserum also reacts with beta-L.P.H., beta-endorphin was distinguished by using a second antiserum which measures beta-L.P.H. alone. With these two immunoassay systems and gel chromatography, we found beta-endorphin in all 20 C.S.F. samples tested at a concentration always higher than, but with no other relationship to, that in plasma. beta-endorphin was found in C.S.F. of patients who had hypopituitarism and undetectable plasma-beta-endorphin, suggesting that it is synthesized in the brain rather in the pituitary.

Adult↗
PubMed1978

The relationship between circadian variations in circulating thyrotrophin, thyroid hormones and prolactin.

Half-hourly blood samples were taken from six clinically euthyroid men over a continuous period of 24 h. Their concentrations of total thyroxine (T4), total triiodothyronine (T3), thyrotrophin (TSH) and prolactin (PRL) were assessed together with the degree of unsaturation of thyroid hormone binding proteins as determined by the thyroid hormone uptake test (THUT). Both T3 and T4 were also measured in urine samples collected serially during the same 24 h period. Significant circadian changes in serum TSH, THUT, serum and urine T4 and serum PRL were demonstrated in all subjects. TSH showed a reciprocal pattern to serum T4, with higher levels during the evening and at night than the daytime. This TSH pattern did not coincide with PRL secretion. Further studies on the same subjects did not show any significant effect of posture, corticosteroid or T4 administration upon circadian changes in TSH. There appeared to be no consistent circadian changes in serum or urinary T3. It seems likely that the TSH circadian rhythm is centrally determined and that free T3 levels are maintained more or less constant by variation in peripheral conversion from T4.

Adult↗
PubMed1978

A specific radioimmunoassay for human beta-lipotropin.

A homologous RIA for human beta-lipotropin (beta hLPH) has been developed. At a final dilution of 1:24,000, the antiserum employed shows cross-reaction with beta hLPH but none with human beta-MSH (beta hMSH), and it is concluded that the antigenic determinant lies within the N-terminal 1-36 region of beta hLPH. With extraction of 3-ml plasma samples, the assay is sufficiently sensitive to measure circulating beta hLPH levels in normal individuals at 0900 h (25-200 pg/ml). There is a circadian variation with levels falling to (less than 20-80 pg/ml) at 2300 h. beta hLPH levels rise after metyrapone and after insulin-induced hypoglycemia, and fall after administration of dexamethasone. In patients with a variety of diseases of the pituitary-adrenal axis, levels of beta hLPH follow immunoreactive ACTH levels, although the two are not always secreted on a 1:1 molar basis.

Humans↗
PubMed1978

Effect of the dopamine agonist, lergotrile mesylate, on circulating anterior pituitary hormones in man.

The effects of the ergoline derivative, lergotrile mesylate, on the serum levels of PRL, GH, TSH, LH, FSH, cortisol, and blood sugar were studied in six normal males. The effects of lergotrile mesylate on the serum levels of GH and PRL were also studied in eight patients with acromegaly and in two with idiopathic hyperprolactinemia. In the normal subjects, 2 mg oral lergotrile lowered basal PRL levels after 90 min and markedly impaired the PRL response to TRH (200 micrograms iv); the mean peak value +/- SE was 8.3 +/- 1.1 micrograms/liter, compared to the control value of 66.6 /+- 11.3 micrograms/liter. Lergotrile raised serum GH levels in five of the six subjects to peaks of 8-49 micrograms/liter, compared to 2-8 micrograms/liter after placebo. In three subjects, the GH response to lergotrile was attenuated by the prior administration of the dopamine antagonist, metoclopramide (10 mg orally). Lergotrile had no effect on FSH and LH levels under basal conditions or after the gonadotrophin-releasing hormone (GnRH; 100 micrograms iv). Circulating TSH levels were unaltered basally but impaired after TRH. Blood sugar levels were unaltered; serum cortisol was elevated in five of six subjects; there was a brief depression of diastolic blood pressure, but no change in pulse rate. The side effects after lergotrile were variable, with drowsiness as a consistent feature. These actions are similar to those of bromocriptine (an ergot derivative treatment of hyperprolactinemia and acromegaly, to suppress PRL and GH secretion, and in parkinsonism. Therefore, it may be expected that lergotrile could fulfill these clinical uses; however, in the studies comparing the effects of single oral doses of lergotrile (2 mg) and bromocriptine (2.5 mg) on GH and PRL secretion in patients with acromegaly and hyperprolactinemia, lergotrile in the dose used has been found to have an earlier onset and shorter duration of action.

Acromegaly↗
PubMed1978

Hypothalamic regulatory hormones: physiological and clinical implications.

The hypothalamic regulatory hormones used for clinical studies are TRH, Gn-RH and somatostatin. In addition, as dopamine appears to be a physiological PIF, the dopamine agonists such as bromocriptine, could be considered as functional analogues of PIF. Gn-RH can be used to study the hypothalamic-pituitary gonadal relationship and to test the secretory reserve capacity of the gonadotrophs in disease states. Unfortunately Gn-RH testing discrimulates between pituitary and hypothalamic diseases only poorly. However gonadotrophin deficient men or women may be successfully treated with long-term Gn-RH with induction of puberty, potency, spermatogenesis and ovulation. Somatostatin has multiple actions in inhibiting endocrine and exocrine secretion but its actions are still being explored in diabetes. Bromocriptine, a long acting dopamine agonist (a functional analogue of PIF), suppresses prolactin and is highly effective in treating many hypogonadal states since hyperprolactinaemia is common. It also lowers growth hormone in acromegaly. TRH has provided a major, accurate, sensitive and safe test of thyroid function.

Dopamine↗
PubMed1978

Bromocriptine treatment of hyperprolactinaemic hypogonadism.

Results of bromocriptine therapy of 70 women and 25 men with hyperprolactinaemia are reported together with those of 8 normoprolactinaemic and 3 post menopausal women. Galactorrhoea was present in 79% and 28% of the hyperprolactinaemic women and men respectively. 34 of the hyperprolactinaemic women had suspected pituitary tumours. Bromocriptine therapy resulted in lowering of prolactin levels to normal in 85 of the 95 patients, and in the remainder prolactin levels were lowered in all but one patient. Gonadal function was restored in all but seven of the hyperprolactinaemic women, and potency in all but 4 of the men. Normal cyclical function was restored or pregnancy was achieved in 5 of 6 normoprolactinaemic women with irregular cycles or amenorrhoea. Basal circulating LH and FSH levels and their responses to GnRH were normal or exaggerated in the majority of the women, but the LH responses to GnRH were impaired in 12 of 21 men. The results of 37 pregnancies in 31 women, 11 of whom had suspected pituitary tumours, are discussed together with the problems of possible tumour growth during pregnancy.

Adolescent↗
PubMed1978

Acromegaly--results of long term treatment with bromocriptine.

Bromocriptine, a long acting dopamine agonist, has been used to treat 73 patients with active acromegaly for between 3 and 25 months. Clear clinical improvement occurred in 71 patients (97%). This included improvement in facial appearance, reduction in hand and foot size and sweating, relief of headaches and increased energy and libido. Abnormal visual fields became normal in two patients, but one of these was given concomitant radiotherapy. A significant reduction in growth hormone occurred in 58 patients (79%), but only 15 patients had levels persistently below 5microgram/l. Carbohydrate tolerance improved with the reduction in growth hormone and of 23 patients with diabetes mellitus before treatment, glucose tolerance became normal in 15 and improved in a further 5. Administration of bromocriptine should begin slowly in order to minimise early side effects. Long term side effects have been minor to date and the deaths of two patients whilst taking the drug were not considered to have been caused by it. Bromocriptine offers a major advance in the management of acromegaly, but further careful follow-up is required to determine whether serious side effects will be a problem with the long term use of high doses.

Acromegaly↗
PubMed1977

Metyrapone in long-term management of Cushing's disease.

Metyrapone was used in the long-term management of 13 patients with pituitary-dependent bilateral adrenal hyperplasia (Cushing's disease). The total length of treatment ranged from two to 66 months, with a mean of 21 months. The clinical features of the disease rapidly improved on metyrapone and this improvement was maintained. Although plasma ACTH concentrations rose in all patients, the increase was insufficient to overcome the adrenal blockade induced by the drug. Eight of the 13 patients had additional external pituitary irradiation as definitive treatment of their disease and one underwent a transfrontal hypophysectomy. Radiotherapy cured one patient, and after three years metyrapone was withdrawn. Slight hirsuties was noted in four of the seven women who received the drug for six months or more. A fifth woman had more severe hirsuties and this led to bilateral adrenalectomy. Other than hirsuties, side effects were few and the routine use of metyrapone is recommended as an adjunct to more definitive treatment in all patients who present with Cushing's syndrome, irrespective of aetiology.

Adolescent↗
PubMed1977

Plasma immunoreactive corticotrophin and lipotrophin in Cushing's syndrome and Addison's disease.

Plasma immunoreactive corticotrophin (ACTH) and lipotrophin (LPH) were measured in patients with raised circulating concentrations from a pituitary or an ectopic source. They were measured again in seven patients after they had received hydrocortisone. Plasma ACTH concentrations were higher than LPH concentrations in patients with a pituitary source of their hormones, whereas this relation was reversed when the source was ectopic. After hydrocortisone administration the half life of immunoreactive ACTH was 40 minutes and that of LPH 95 minutes, resulting in a reversal of the normal relation of ACTH to LPH. The use of two antisera with different specificities for measuring LPH has further shown that pituitary LPH differs from ectopic LPH. Relatively less gamma-LPH than beta-LPH was produced from ectopic sources, the relation being reversed in patients with a pituitary source for their raised concentrations. Measuring plasma LPH as well as ACTH might therefore help in deciding whether a patient with Cushing's syndrome has a pituitary or ectopic source of ACTH, which sometimes presents a difficult clinical problem.

Addison Disease↗