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Biomedical subjects

D M Large

Publications and source records attributed to D M Large.

26 records · Page 2Linked to original sources
PubMed1984

Hyperkalaemia in diabetes mellitus--potential hazards of coexisting hyporeninaemic hypoaldosteronism.

Two patients with insulin-dependent diabetes mellitus (Type I), developed severe, life-threatening hyperkalaemia, the first following treatment with spironolactone, the second during treatment for staphylococcal septicaemia when glucose-induced hyperkalaemia occurred. Investigations demonstrated co-existing hyporeininaemic hypoaldosteronism. Prompt recognition of this combined hormone-deficiency syndrome led to appropriate treatment and recovery. The biochemical features and clinical importance of hyporeninaemic hypoaldosteronism are discussed.

Adult↗
PubMed1984

High dose androgen therapy in male pseudohermaphroditism due to 5 alpha-reductase deficiency and disorders of the androgen receptor.

We describe the clinical and biochemical features of six men with male pseudohermaphroditism due to androgen resistance. Each of the subjects had male-gender behavior but incomplete virilization. The underlying defects in androgen metabolism were defined by studies of the 5 alpha-reductase enzyme and the androgen receptor in fibroblasts cultured from biopsies of genital skin. Four of the six have 5 alpha-reductase deficiency, and two have defects of the androgen receptor (the Reifenstein syndrome). The responses of these men to androgen treatment were assessed by monitoring nitrogen balance, plasma luteinizing hormone (LH) values, and clinical parameters of virilization including penile growth, potency and ejaculatory volume, muscle bulk, and growth of body and facial hair. In all of the subjects with 5 alpha-reductase deficiency and one man with the Reifenstein syndrome significant response occurred, as evidence by nitrogen retention, lowered plasma LH levels, and improved virilization, with doses of parenteral testosterone esters that raised plasma testosterone levels above the normal male range and brought plasma dihydrotestosterone levels into the normal male range. The subject who did not respond with clinical virilization nevertheless showed nitrogen retention in response to acute testosterone administration. This patient had a profound deficiency of the androgen receptor, whereas the man with a receptor defect who did respond clinically to therapy had normal amounts of a qualitatively abnormal receptor. We conclude that high dose androgen therapy may be of benefit in improving virilization, self-image, and sexual performance in subjects with 5 alpha-reductase deficiency who have male-gender behavior and in some subjects with defects of the androgen receptor.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1983

Basal steroid production by the zona reticularis of the guinea-pig adrenal cortex.

The zonae glomerulosa and fasciculata (ZG/ZF) have been separated by microdissection from the zona reticularis (ZR) of the guinea-pig adrenal cortex. Using non-proliferative organ culture and specific radioimmunoassay the basal secretion of 12 steroids from each zone have been studied. The ZG/ZF secreted 9 times more cortisol (in pmol/mg dry weight 5 h culture) than the ZR. In contrast the androgens (androstenedione, 5-androstenediol, dehydroepiandrosterone, dehydroepiandrosterone-sulphate and testosterone) were preferentially produced (by a factor of 3) by the ZR which also secreted more of all the other steroids studied, with the exception of progesterone and 17-hydroxyprogesterone. The mean molar ratios of total androgen output to cortisol secretion were 1:1.7 and 1:45 for the ZR and ZF respectively. Using computerised image analysis the relative volumes of the ZG/ZF and ZR in the cortex were calculated to be 65 and 35% respectively. The medulla occupies 4.6% of the total gland. From the zonal composition of the cortex, the relationship between wet and dry weight for each zone and the basal secretion rate of each steroid/mg dry weight/5 h culture, we calculated that the ZR could be responsible for 7 and 66% of the cortisol and total androgen secretion respectively from the guinea-pig adrenal gland. It is concluded that the ZF and ZR are functionally as well as morphologically distinct.

Adrenal Cortex↗
PubMed1983

Gynaecomastia complicating the treatment of myeloma.

The hormonal mechanisms involved in the development of gynaecomastia accompanying the treatment of multiple myeloma in adult men have been investigated by studying levels of circulating testosterone (T), oestrone (EI), oestradiol (E2), sex-hormone binding globulin (SHBG), prolactin (PRL) and the gonadotrophins LH and FSH, before, during and after development of gynaecomastia in 4 men. These have been compared with 5 closely matched men who did not develop gynaecomastia during similar treatment for myeloma. Levels of circulating T fell, and levels of E1 and E2 rose during treatment periods in all subjects, and the changes were statistically significant in subjects developing gynaecomastia, which resolved as levels of sex steroid returned towards normal following cessation of treatment. We conclude that treatment of adult men for myeloma results in testicular dysfunction with a reduction in circulating T and a rise in circulating oestrogens. These changes are most marked in subjects developing gynaecomastia in whom the normal breast tissue is stimulated by a subtle, transient oestrogen:androgen imbalance in favour of oestrogens.

Aged↗
PubMed1981

Familial hypocalciuric hypercalcaemia and acute pancreatitis.

Four families with familial hypocalciuric hypercalcaemia were studied. The probands presented with abdominal pain, which in three was due to acute pancreatitis; in two the condition was life threatening. Serum concentrations of calcium, magnesium, phosphate, and immunoassayable parathyroid hormone, urinary calcium excretion, and the rate of renal tubular reabsorption of phosphate were measured; the findings were compared with results in 10 patients with primary hyperparathyroidism matched for serum calcium concentration to establish differences between the diseases. Familial hypocalciuric hypercalcaemia should be suspected in patients with hypercalcaemia in whom daily urinary calcium excretion is below 5 mmol (200 mg) provided renal insufficiency, vitamin D deficiency, and ingestion of drugs that reduce calcium excretion have been excluded. Most cases appear to run a benign course, but some may suffer considerable morbidity. Surgical treatment should be reserved for patients with severe complications, when all parathyroid tissue should be removed.

Acute Disease↗
PubMed1980

Twenty-four hour profiles of serum prolactin during male puberty with and without gynaecomastia.

Twenty-four hour profiles of circulating prolactin have been documented in eight boys with simple delayed puberty, eleven with gynaecomastia, three of whom were retested following its spontaneous resolution, and two normal adult men. Mean 24 h prolactin levels in four boys with delayed puberty and ten with gynaecomastia exceeded the mean levels for the two adult men. A sleep-associated rise in prolactin levels occurred at all stages of puberty irrespective of the presence or absence of gynaecomastia, and in some subjects peaks also occurred during the daytime. Boys with gynaecomastia had higher 24 h means levels of prolactin (P less than 0.05), higher daytime levels (P less than 0.05) and higher sleep-associated levels (P less than 0.05) than did control subjects. These were not related to the degree or duration of the gynaecomastia, but 24 h mean levels of prolactin and oestradiol were positively correlated. In one subject who had had transient galactorrhoea, high levels of circulating prolactin, oestrone and oestradiol fell following spontaneous resolution of the gynaecomastia. We believe that oestrogen: androgen imbalance during the daytime is the major cause of pubertal gynaecomastia, with hyperprolacinaemia (which may cause galactorrhoea) sometimes occurring as a response to relative hyperoestrogenaemia.

Adolescent↗
PubMed1979

Twenty-four hour profiles of circulating androgens and oestrogens in male puberty with and without gynaecomastia.

The possible mechanisms involved in the development of transient gynaecomastia during male puberty have been investigated by studying 24 h profiles of circulating androstenedione (Ao) and testosterone (T) and their oestrogen pairs oestrone (E1) and oestradiol(E2), in eight boys with simple delayed puberty, eleven boys with pubertal gynaecomastia (three of whom were re-tested after its spontaneous resolution), and two normal adult men. No differences were observed between the 24h T and Ao profiles of pubertal boys with or without gynaecomastia; we confirmed that the initial T rise was nocturnal, associated with sleep. Late in puberty daytime T levels also rise. A small rise in 24 h Ao was seen, but this was not closely related to the stage of puberty. The major new finding was that E2 and to a lesser extent E1 levels are high relative to T for prolonged periods of the afternoon and evening (when T levels are lowest) in male puberty. A frequent finding, seen only in boys with gynaecomastia and one who later developed it, was of elevated and markedly fluctuating levels of plasma E2, and an absolute increase in the area under the 24 h E2 profile and between the E2 and T profiles. These fell towards normal in three boys who were re-tested after resolution of gynaecomastia. In a minority of subjects T and E2 were quite closely correlated, suggesting that in them rapid aromatization of T was occurring within or outside the testis. We conclude that normal male puberty is associated with relative oestrogen dominance particulary in the daytime. In boys with gynaecomastia there is in addition often an absolute elevation of E2 with or without E1, while 24 h T levels are submaximal. Normal men probably require sustained adult circulating T levels to prevent their oestrogens from stimulating breast development.

Adolescent↗