Defining the normal cortisol response to the short Synacthen test: implications for the investigation of hypothalamic-pituitary disorders.

OBJECTIVE: To define the normal cortisol response to the Short Synacthen Test using four different cortisol immunoassays and to assess the implications for the investigation of hypothalamic-pituitary disorders. DESIGN AND PATIENTS: The cortisol response to 250 micrograms im ACTH1-24 (Synacthen, Ciba Geigy) in 100 healthy volunteers using four different cortisol immunoassays has been measured. In 44 newly diagnosed and untreated patients with pituitary disease, basal and 30 minute post-ACTH cortisol results were also determined using the four immunoassays. RESULTS: The distribution of cortisol results at all time points and for all methods were non-Gaussian and significant differences in the absolute values of the 5th-95th percentiles were found between methods (P < 0.01). At 30 min post-Synacthen in normals the 5th percentile of the cortisol response ranged from 510 to 626 nmol/l with the different methods. Similarly the relationship between assay results differed at different time points. No effect of age on the cortisol response was found but for stimulated cortisol values and the incremental responses females showed significantly higher responses than males (P < 0.05) for most methods. Although there was a significant positive linear correlation (P < 0.001) between stimulated and basal cortisol values for all methods, no significant relationship was found between the incremental response and basal cortisol values. In the pituitary disease patients basal and 30 minute post-ACTH cortisol results were significantly lower (P < 0.05 and < 0.001) than the control group using the same cortisol assay. When the results were compared to the 5th percentile of the gender and assay specific control group 33.3% of male and 17.4% of female patients failed the Synacthen test at 30 min. CONCLUSIONS: The definition of the 'normal' response to Synacthen should be both gender and method related at all time points. The data suggest that up to one-third of untreated patients with pituitary disease may have subtle defects in the hypothalamic-pituitary-adrenal axis.

Hypothalamic hypogonadism following major head injury.

Endocrine studies, using the four hypothalamic releasing hormones, gonadotrophin releasing hormone, thyrotrophin releasing hormone, corticotrophin releasing hormone and growth hormone releasing hormone, were performed in 33 males after admission with a major head injury. The test was repeated 7 days later in all 33 patients and after 3-6 months in 21 patients. All patients had a period of unconsciousness followed by post-traumatic amnesia of greater than 24 h. The results obtained from investigating the gonadal axis are reported in this paper. The levels of total and free testosterone, basal FSH and basal LH fell significantly during the first 3 days after injury, when the LH and FSH responses to GnRH achieved their highest peak levels. This hormone pattern has not previously been reported in the gonadal axis and may be a consequence of hypothalamic dysfunction. The severity of the injury was negatively correlated to the testosterone concentration on admission and to the basal and peak FSH concentrations 1 week later. Persistent hypogonadism was found in five of the 21 patients retested after 3-6 months, with low testosterone concentrations and three continued to have an exaggerated LH response to GnRH. Thus major head injury frequently results in hypogonadism shortly after injury, with an increased gonadotrophin response to GnRH. In addition, a substantial minority of patients continue to be hypogonadal after 3-6 months. In view of these findings we strongly suggest that all patients should be endocrinologically assessed at intervals following severe head injury.

Thyroid stimulating hormone measurement by an ultrasensitive assay during thyroxine replacement: comparison with other tests of thyroid function.

Serum thyroid stimulating hormone (TSH) was measured using a highly sensitive enzyme-amplified immunoassay in 37 clinically euthyroid patients receiving thyroxine replacement therapy and compared with other biochemical tests of thyroid function. A highly significant correlation (P less than 0.001) was found between the basal serum TSH and the increase in serum TSH concentration 20 min after the administration of thyrotropin releasing hormone (TRH). The basal serum TSH was negatively correlated with the serum total thyroxine (P = 0.05). When patients results were classified as abnormal or normal many discrepancies were noted between the various thyroid tests. A suppressed serum TSH was found in 65% of patients with a normal serum total thyroxine. However, in patients on thyroxine replacement therapy a basal TSH measured by enzyme-amplified immunoassay provides the same information as a TRH test.

Undescended testis and hormone levels in early pregnancy.

A case-control study was carried out on mothers of boys with undescended testis to investigate the hypotheses that raised maternal levels of oestrogen or reduced levels of human chorionic gonadotrophin in early pregnancy might be factors in the environment of the fetus associated with this condition. No significant difference in the levels of either of these hormones was found, though, if anything, levels of oestrogen may have been lower in cases than in controls, and not higher as previously postulated.