The acute GH inhibitory effects of 50 micrograms SMS 201-995, a somatostatin analog, and 2.5 mg bromocriptine were compared in 17 acromegalic patients. SMS 201-995 suppressed plasma GH levels after 2-6 h to 5 micrograms/liter or less in 10 of these 17 patients, while bromocriptine did the same in only 5 of them. There was much variation in the responsiveness to both drugs in these patients, but the GH-lowering effect of 50 micrograms SMS 201-995 was significantly greater than that of 2.5 mg bromocriptine. SMS 201-995 and bromocriptine together significantly suppressed plasma GH levels in 2 of 3 acromegalic patients who were insensitive to both compounds when tested separately. We conclude that most acromegalic patients respond better to SMS 201-995, while a few patients are more sensitive to the GH-lowering effect of bromocriptine. In addition, the combination of SMS 201-995 and bromocriptine can be of value in a few acromegalic patients who do not respond to either drug alone.

The somatostatin analogue SMS 201-995 has recently been shown to be effective in suppressing GH secretion in most acromegalic patients. In the present study it was investigated whether PRL release in prolactinoma and acromegalic patients might also be sensitive to SMS 201-995 and whether co-secretion of PRL in acromegaly plays a role in determining the sensitivity of GH secretion to SMS 201-995. The s.c. administration of 50 micrograms SMS 201-995 did not affect high plasma PRL levels in four microprolactinoma patients. Therapy of one of these patients for 3 d with 50 micrograms three times a day also did not affect PRL levels. The single administration of 50 micrograms SMS 201-995 in 22 acromegalic patients lowered plasma GH levels for 2-6 h to less than 5 micrograms/l in 14 patients and to less than 50% of control values in 16 patients. In 18 of these 22 patients the immunohistochemical picture of the pituitary tumour was known. Eleven patients had pure GH-containing tumours and in seven patients there were mixed GH/PRL-containing tumours. In two of these latter patients there was evidence for GH and PRL being secreted by the same tumour cells. The sensitivity of GH secretion to SMS 201-995 did not differ between the patients with pure GH or mixed GH/PRL-containing adenomas. Plasma PRL levels were not affected by SMS 201-995 in the patients with pure GH-secreting tumours, but were significantly suppressed in four of the seven patients with mixed GH/PRL containing tumours. Chronic treatment for 16 weeks of one patient with a mixed GH/PRL-containing tumour with SMS 201-995 (100 micrograms three times a day) resulted in normalization of both the increased GH and PRL levels. It is concluded that SMS 201-995 does not affect tumorous PRL secretion in patients with pure prolactinomas. In acromegalic patients with mixed GH/PRL-containing tumours PRL secretion in some patients is sensitive to SMS 201-995, making these patients good candidates for chronic treatment with the analogue. The simultaneous presence of PRL in the GH-secreting pituitary tumour or the presence of hyperprolactinaemia in acromegalics does not play a role in the sensitivity of GH secretion to the somatostatin analogue.

A 26-yr-old woman presented with hirsutism, male pattern scalp baldness ("geheimratsecken"), and menstrual irregularities. She had no hypertension or other signs and symptoms of Cushing's syndrome. Plasma cortisol levels were greatly elevated and did not suppress normally in response to dexamethasone. Cortisol binding to transcortin was normal. Plasma androstenedione and testosterone levels were also increased, but 17-hydroxyprogesterone and aldosterone levels were normal. Further studies revealed an increased cortisol production rate, increased 24-h urinary cortisol excretion, increased plasma ACTH levels, a normal diurnal rhythm of cortisol at an elevated level, and normal increments of plasma ACTH, cortisol, GH, and PRL in response to insulin-induced hypoglycemia. The father and two brothers also had increased plasma cortisol levels, which did not suppress normally in response to dexamethasone. Chronic therapy with dexamethasone (at first 1 and later 0.5 mg, three times daily) for more than 30 weeks resulted in decreased hirsutism, normalization of scalp hair and menstrual cyclicity, and normal plasma testosterone and androstenedione levels. No signs or symptoms of Cushing's syndrome developed, and the central regulation of secretion of ACTH, cortisol, GH, and PRL (insulin test, diurnal rhythm) remained qualitatively normal at a lower set-point. We conclude that this patient had autosomal dominantly inherited hereditary (partial) cortisol insensitivity, which had resulted in increased adrenocortical cortisol and androgen secretion. The latter had not resulted in clinical symptoms in the three afflicted male members of the family, but had in the propositus. The results also indicate the potential usefulness of the insulin test in distinguishing this disorder from Cushing's disease.

Bone age was assessed in children with acute lymphoblastic leukaemia (ALL) using the Tanner-Whitehouse II method. X-rays of the left hand (wrist) were made at diagnosis and annually until 5 years after diagnosis. A total of 164 X-rays from 40 patients was available. During treatment bone age development as well as height growth was retarded in relation to calendar age. A catch-up of bone age and height was observed in the 2 years after cessation of treatment. No significant differences could be found between patients with and without cranial irradiation as central nervous system treatment. Therefore cranial irradiation alone is not responsible for the growth retardation of children with ALL; the causative role of cytostatic drug therapy and/or corticosteroids has to be investigated.