<jats:p>Tjeerdsma G, Sluiter WJ, Hew JM, Molenaar WM, de Lange WE, Dullaart RPF. Hyperprolactinaemia is associated with a higher prevalence of pituitary—adrenal dysfunction in non-functioning pituitary macroadenoma. Eur J Endocrinol 1996;135:299—308. ISSN 0804–4643 <jats:p>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 tetrahydro11-deoxycortisol (H<jats:sub>4</jats:sub>S, 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 (2231120)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 60 vs 30 min, p < 0.03); urinary H<jats:sub>4</jats:sub>S 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 5 3.8% 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 hyperprolactinaemia 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. <jats:p>RPF Dullaart. Department of Endocrinology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands