In non-functioning pituitary macroadenoma (NFMA), hyperprolactinaemia (hyperPRL) is considered to be a sign of hypothalamic-pituitary dysregulation, but it is unknown whether hyperPRL is associated with an increased frequency of pituitary hormone deficiencies. Forty consecutive patients with histology-proven NFMA were studied and hyperPRL was defined as serum prolactin (PRL) > 200 mIU/l in men and > 600 mIU/l in women. The pituitary-adrenal axis was evaluated by measurement of urinary free cortisol (N = 38), peak cortisol to insulin-induced hypoglycaemia (IIH, N = 36) and to human corticotrophin-releasing hormone (hCRF, N = 40) and by urinary tetrahydrol 11-deoxycortisol (H4S, N = 39), plasma androstenedione increment (N = 39) and serum 11-deoxycortisol (N = 1) after metyrapone. Central hypothyroidism, gonadotrophin deficiency and growth hormone (GH) reserve were also assessed. Twenty patients had hyperPRL (serum PRL 331 (223-1120) mIU/l (median, range) in men and 932 (660-3927) mIU/l in women): urinary free cortisol excretion (p < 0.03) and peak serum cortisol in response to IIH (p < 0.02) were lower in hyperPRL than in normoPRL patients; peak serum cortisol after hCRF was not different between groups but occurred later in hyperPRL patients (at 60vs 30 min, p < 0.03); urinary H4S excretion and androstenedione response after metyrapone were lower in hyperPRL than in normoPRL patients (p < 0.05 for both): 60% of hyperPRL patients and 15% of normoPRL patients had an abnormal H4S response (p < 0.025): central hypothyroidism (overt + subclinical) was present in 74% of hyperPRL and in 60% of normoPRL patients (NS); 78% of hyperPRL and 55% of normoPRL patients had gonadotrophin deficiency (NS): growth hormone (GH) deficiency was present in 83% of hyperPRL and in 89% of normoPRL patients (NS); 73.3% of 75 evaluable pituitary hormone axes were abnormal in hyperPRL patients compared to 53.8% of 78 hormone axes in normoPRL patients (by metyrapone test to examine adrenal function, p < 0.025); and no significant differences in tumour grade and stage distribution were found between hyperPRL and normoPRL patients. It is concluded that hyper-prolactinaemia in NFMA is associated with a higher prevalence of pituitary-adrenal dysfunction, which is likely to be explained at least in part by functional hypothalamic-pituitary interruption.

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Five phenotypic female patients with primary amenorrhoea, mild hypertension, and hypokalaemia are described. The condition originates from 17-hydroxylase deficiency in both adrenals and gonads. Two cases had a XY chromosome pattern, two cases were familial. It is suggested to determine serum potassium in all cases with unexplained primary amenorrhoea.

Plasma levels of ACTH, 11-deoxycortisol, androstenedione and testosterone and urinary tetrahydro-11-deoxycortisol were determined during a two day oral metyrapone test using doses of 1.5 g every 6 h. The level of 11-deoxycortisol 48 h after the start was distinctive regarding the assessment of pituitary ACTH secretory capacity. The rise of androstenedione concentration after 48 h is distinctive in a similar way, whereas ACTH determination is of little diagnostic value in this respect.Further, an increase in testosterone level can be observed in cases of low basal testosterone production. This increase is probably the result of peripheral conversion of androstenedione to testosterone. Where the basal testosterone concentration was high, no change could be measured.Metyrapone, a compound structurally related to DDT, has been frequently used in the assessment of the secretory capacity of adrenocorticotrophic hormone (ACTH) since 1958 (Liddle et al. 1959).Metyrapone inhibits adrenal corticosteroid 11-hydroxylase, resulting in a decrease in cortisol synthe¬ sis followed by an increase in ACTH secretion and a rise of the plasma 1 l-deoxycortisol (S) level. The increase of S in plasma is accompanied by an augmented urinary excretion of tetrahydro-11-deoxycortisol (H4S). Short metyrapone tests (usually consisting of one dose of metyrapone) have been described (Jubiz et al. 1970b;Zachmann et al. 1974;Blichert-Toft 1975;Leisti 1977), but the conventional oral mety¬ rapone test is still widely used.Oral administration of metyrapone for three consecutive days results in a 95% inhibition of the 11-ß-hydroxylase, at a daily dose of 4.5 g (Cope et al. 1966).The relative increase of urinary H4S after mety¬ rapone administration exceeds the relative rise in plasma S considerably (Zachmann et al. 1974).However, in order to eliminate the troublesome collection of urine that can be a source of error, we investigated the diagnostic value of several plasma hormone assays in the assessment of ACTH secre¬ tory capacity. For this purpose we measured plasma ACTH, 11-deoxycortisol, androstenedione and testosterone in combination with urinary H4S. Androstenedione and testosterone measurementswere included because of the data of Nilsson & Hökfelt (1971) and of Schaison et al. (1977), indi¬ cating a five-fold rise of androstenedione during metyrapone administration in normal persons. Materials and MethodsThe metyrapone test was performed in the following groups of individuals : a. normal women (n = 6) and normal men (n = 8, in¬ cluding 5 cases of delayed puberty) ranging in age from 18 to 77 years (normal controls).b. Twenty-two men and 17 women with a pituitary tumour or a suspected process in the region of the sella turcica; of these 8 men and 4 women had undergone pituitary surgery.

The differential diagnosis between hypogonadotropic hypogonadism and delayed puberty is facilitated by comparing the response of gonadotropins to LH-RH stimulation before and after administration of clomiphene citrate 200 mg daily during 7 days. Premedication of clomiphene citrate depresses peak values of LH and FSH on LH-RH in delayed puberty. In hypogonadotropic hypogonadism clomiphene citrate raises LH-RH induced peak LH while FSH does not change.