24 patients with an extrasellar prolactinoma (mean prolactin 4,722 ng/ml), 8 of whom had previously had surgery, received 5–40 mg bromocriptine daily for 13–252 weeks. The mean prolactin level had fallen 89% at 2 days, 95% at 6 weeks, and 15 patients achieved normal values. Tumor shrinkage occurred in all 9 patients rescanned within 2 weeks and later was documented in 23; in 18 the extrasellar tumour disappeared. 12 patients had visual abnormalities; 7, including 2 who had been completely blind, improved within 1 week. 2 patients had normal prolactin levels after withdrawal of bromocriptine, 1 following radiotherapy and the other during two uncomplicated pregnancies. Bromocriptine is safe and effective. We conclude that medical treatment should always precede surgery unless pituitary apoplexy causes sudden deterioration of vision. Most patients will subsequently require radiotherapy or surgery for permanent cure.

A 6-year-old boy, of consanguinous parents, presented with severe rickets and alopecia; he was found to have hypocalcaemia and elevated circulating 1,25-dihydroxyvita-min D [1,25-(OH)₂D] levels. He showed no calcaemic response to 1,25-(OH)₂D₃ or ergocalciferol given for 3 or more months in daily doses as high as 48 µg and 6 × 10⁶ IU, respectively. Analyses with cultured skin fibroblasts revealed a normal capacity and affinity for 1,25-(OH)₂D₃ in soluble extracts (‘cytosol’) and in nuclei of intact cells but no detectable response of 25-(OH)D3 24-hydroxylase to 1,25-(OH)₂D₃ in high concentration. Treatment with high doses of calcium (3–4 g elemental calcium orally per day) produced a striking clinical and radiological improvement. We conclude that high oral doses of calcium can replace many of the actions of calciferols. Therapy with high doses of calcium should be tried in similarly affected cases that appear totally or partially unresponsive to calciferols.

Eight patients with large prolactinomas (serum prolactin > 900 ng/ml) were studied before and during bromocriptine treatment (5-10 mg/d). The mean fall in serum prolactin was 56% at 24 hours, 82% at 72 hours, and 93% at 3 weeks. Five of the six patients with extrasellar extension on CT scanning had visual abnormalities, which in three patients improved dramatically within 2 weeks, coincident with reduction in tumor size. Five patients, four with extrasellar extension, were treated with bromocriptine alone (7.5-22.5 mg/d) for 3 or more months. Clinical improvement was maintained, prolactin levels became normal or near normal, and three patients became pregnant. The extrasellar extension disappeared in three patients, two of whom developed partially empty sellas, and was much reduced in the fourth. No patient deteriorated on treatment. We conclude that bromocriptine is the initial treatment of choice for all patients with large prolactinomas, regardless of visual defects.

5 female patients with isolated hypothalamic hypogonadism were given subcutaneous pulses of gonadotrophin-releasing hormone (GnRH), 2.5–15 µg every 90 min, for 2–6 months by means of an automated pump. This treatment produced an increase in serum LH, FSH, and estradiol levels in 4 patients, all of whom became pregnant. The estradiol levels failed to rise in 1 patient, in spite of an adequate LH and FSH response, and a subsequent biopsy showed evidence of primary ovarian failure in addition to the hypothalamic deficit. We conclude that subcutaneous pulsatile GnRH administration is a simple, safe, and relatively inexpensive way to induce ovulation in patients with hypothalamic hypogonadism.

Six male patients (aged 21-34 years) with isolated hypothalamic hypogonadism were given subcutaneous pulses of gonadotrophin-releasing hormone every 90 min for 14-74 weeks. The therapy produced an increase in testicular volume (4 patients) and a rise in serum luteinizing hormone, follicle-stimulating hormone, and testosterone levels in every patient. Motile sperm developed in 3 patients after a mean of 17 weeks, but were not seen in other patients who were less sexually developed after a mean of 31 weeks of therapy. Computerized tomography scans of the pituitary fossa revealed an empty sella in 4 patients and a partially empty sella in 2. Subcutaneous pulsing of gonadotrophin-releasing hormone is a simple and safe way of inducing spermatogenesis, but it is more likely to be successful in patients whose pubertal development is otherwise near completion. Previous human chorionic gonadotro-phin and/or testosterone treatment does not interfere with and may benefit subsequent gonadotrophin-releasing hormone therapy.