Atypical antipsychotic-induced diabetes mellitus: an update on epidemiology and postulated mechanisms.

Diabetic ketoacidosis and hyperglycaemic hyperosmolar syndrome are rare, but potentially fatal complications of antipsychotic-associated hyperglycaemia. The mechanisms for this remain unclear, but are probably multifactorial. The suggested reasons include drug-induced weight gain and adiposity, development of the metabolic syndrome, antagonism of serotonin (5-hydroxytryptamine) receptors, drug-induced leptin resistance, dyslipidaemia mediated pancreatic beta-cell damage and hepatocyte transcription factor dysregulation. Patients with schizophrenia are known to be at a higher genetic risk of developing diabetes mellitus and cardiovascular disease. This review emphasizes a rare case of hyperosmolar hyperglycaemic syndrome in a young man with schizophrenia and discusses proposed mechanisms for the development of antipsychotic-associated diabetes mellitus.

Variable androgen receptor levels in infertile men.

Labeled methyltrienelone was used to determine androgen receptor (AR) levels in cultured pubic skin fibroblasts in 40 infertile men with primary seminiferous tubule disorders and 18 normal men. LH pulse patterns and mean serum LH levels were also determined by blood sampling at 10-min intervals for 6 h. The infertile men and the normal men had similar mean receptor levels [mean, 28.1 +/- 2.0 (+/- SEM) and 24.8 +/- 1.8 fmol/mg protein, respectively]. However, 5 men with chromosomal disorders had a higher mean AR level (41.3 +/- 6.2 fmol/mg protein) than the normal men, and 5 of the remaining infertile men (14.2%) had receptor levels that were less than the minimum value in normal men. In men with idiopathic oligospermia, 19.0% had low receptor levels. Although mean serum FSH and testosterone levels were similar in the infertile men with low AR levels and in the normal men, mean LH levels were significantly elevated in this group (7.1 vs. 3.6 IU/L), the higher values being a result of increased LH pulse amplitude (mean, 5.6 vs. 2.8 IU/L). The LH-testosterone product (an index of androgen resistance) was also elevated in these men. When infertile men with low AR levels were matched with infertile men with normal receptor levels, the mean LH values were significantly elevated in the former, as was the LH-testosterone product. Testosterone values were similar in the two groups of men. After excluding subjects with chromosomal disorders, there were no significant correlations between AR levels and other indices of androgen action, such as semen volume, seminal fructose, or sex hormone-binding globulin levels. We conclude that AR levels are higher in patients with severe testicular failure associated with X-chromosome disorders. Also, AR defects were found in 19.0% of infertile men with idiopathic oligospermia. Finally, elevation of mean LH levels in men with seminiferous tubule disorders may reflect resistance to androgen action.

Partial gonadotrophin deficiency is infrequent in infertile men.

Hormone values and semen analyses were studied in 1761 men referred for evaluation of infertility to determine the frequency of isolated deficiency of either FSH, LH, or partial deficiency of both gonadotrophins. There were 17 men (1%) with oligospermia and FSH values at the lower end of the normal range. Without treatment, four pregnancies occurred in this group. Of the remainder, one was treated with gonadotrophin replacement therapy with no improvement in sperm concentration or motility. One man had possible isolated LH deficiency, but was subsequently found to have normal LH and testosterone values. No case of partial gonadotrophin deficiency was found. It was concluded that isolated deficiency of either FSH, LH, or partial deficiency of both gonadotrophins must be extremely rare as a cause of infertility.

Different testosterone and LH relationships in infertile men.

In both man and animals, changes in Leydig cell structure and function accompany seminiferous tubule damage. In this study of 1745 men attending an infertility clinic, 14% of men with elevated levels of FSH also had elevated LH levels. Groups with severe seminiferous tubule failure (eg, Sertoli Cell Only syndrome or high FSH levels) showed an inverse correlation between LH and testosterone levels. In contrast, groups with milder forms of seminiferous tubule disorders (mild hypospermatogenesis, or FSH levels in the low-normal range) showed a positive correlation between LH and testosterone. It is concluded that different mechanisms must be operative to explain the opposite relationships between LH and testosterone, and that their elucidation may point to the etiology of some forms of seminiferous tubule damage in man.