G. F. Joplin

Abnormalities of growth hormone release in response to human pancreatic growth hormone releasing factor (GRF (1-44)) in acromegaly and hypopituitarism

Human pancreatic growth hormone releasing factor (GRF (1-44)) is the parent molecule of several peptides recently extracted from pancreatic tumours associated with acromegaly. A study was conducted to examine its effects on the release of growth hormone in normal volunteers and in patients with hypopituitarism and acromegaly. GRF (1-44) dose dependently stimulated the release of growth hormone in normal people and produced no appreciable side effect. This response was grossly impaired in patients with hypopituitarism and, although similar to the growth hormone response to hypoglycaemia, was of quicker onset and a more sensitive test of residual growth hormone function. Patients with acromegaly appeared to fall into (a) those with a normal response to GRF, whose growth hormone suppressed significantly with oral glucose, and (b) those who had an exaggerated response to GRF (1-44), whose growth hormone had not suppressed previously after oral glucose. Present methods for testing growth hormone deficiency entail using the insulin stress test, which is time consuming, unpleasant, and sometimes dangerous. A single intravenous injection of GRF now offers the possibility of an easier, safer, and more reliable routine test for growth hormone deficiency. It has the further advantage of being free of side effects and readily performed in outpatients. Hence it seems likely to become the standard test and take the place of the insulin stress test.

Florid Diabetic Retinopathy and its Response to Treatment by Photocoagulation or Pituitary Ablation

A group of 34 patients with florid diabetic retinopathy are reported. Nine of these had at least one eye untreated and of these only two maintained vision at one year—the others were blind. Ten patients had 11 florid eyes treated by photocoagulation. At one year six were blind and five had good vision. At two years only three could still see. Of 20 pituitary-ablated patients with 29 florid eyes, only three were blind at one year. Even at five years, 12 of 17 eyes could see and only two patients were blind. The one- and two-year visual acuities were significantly better in the pituitary ablated eyes than in the untreated and photocoagulated ones (p = 0.01 – 0.03). It is suggested that for this rare form of retinopathy pituitary ablation remains the treatment of choice if vision is to be maintained.

Pregnancy, prolactin, and pituitary tumours

Nine pregnancies are described in patients with pituitary tumours. All patients had definite radiological evidence of a pituitary tumour and no evidence of acromegaly or Cushings disease. In seven patients serum prolactin levels were estimated before pregnancy and found to be raised. Seven patients had been treated with pituitary implantation of yttrium-90. The remaining two developed complications of the tumour during pregnancy. One developed a bitemporal visual field defect in the second trimester which was successfully treated by emergency yttrium-90 implantation. The other developed diabetes insipidus in the third trimester which resolved spontaneously after delivery. Six patients were treated with drugs to achieve pregnancy. Four took bromocriptine to suppress raised prolactin levels, one was treated with human menopausal gonadotrophin, and one was treated with clomiphene.

Analgesic effect of somatostatin analogue (octreotide) in headache associated with pituitary tumours.

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Serum Growth Hormone Levels and the Response of Diabetic Retinopathy to Pituitary Ablation

Serum growth hormone levels were measured during insulin tolerance tests in 36 patients after yttrium-90 pituitary implantation for diabetic retinopathy. The response of the new blood vessels was more clearly related to loss of growth hormone function than was the improvement of retinal haemorrhages and microaneurysms. The overall response of the retinopathy was greatest when growth hormone function was lost. Since the loss of growth hormone function was related to the loss of other aspects of anterior pituitary function, a unique role of growth hormone in the response of diabetic retinopathy to pituitary ablation could not be established.

EFFECTIVE LONG‐TERM TREATMENT OF ACROMEGALY WITH A LONG‐ACTING SOMATOSTATIN ANALOGUE (SMS 201–995)

Nine acromegalic patients, six previously untreated, were studied before and after 3–15 months of treatment with a long‐acting somatostatin analogue (SMS 201–995; 100 μg injected s.c. three times daily). During treatment, the mean (± SEM) 24‐h GH concentration fell from 82 ± 22 mIU/1 to 33 ± 7 mIU/1 (P < 0.001), and eight of the 9 patients showed a reduction of at least 50% in GH levels in the fasting state and/or during a glucose tolerance test. There was a significant 30% fall in serum concentrations of insulin‐like growth factor (IGF‐1) with SMS. All patients showed rapid clinical improvement, with diminished sweating and headaches, and reduction in skinfold thickness, hand volumes and finger size. Computer tomographic scanning of the pituitary in eight patients showed no change in the size of the pituitary tumour during treatment. The only side‐effects of SMS noted were transient abdominal discomfort and loose stools in two patients on initiating therapy. Although fasting plasma glucose concentration did not change during treatment (5.4 ± 0.3 vs 5.5 ± 0.3 mmol/l), mean 24‐h plasma glucose concentration was higher with SMS (6.6 ± 0.5 mmol/l vs 6.0 ± 0.4 mmol/l; P < 0.02). Mean 24‐h plasma insulin concentration fell from 87 ± 11 mIU/1 before treatment to 39 ± 6 mIU/1 during treatment (P < 0005). No change in other anterior pituitary hormones was observed. SMS appears to be a safe, rapidly effective, long‐term treatment for certain patients with acromegaly.

Pregnancy in patients presenting with hyperprolactinaemia.

SIR,-Mr St C Hopper (27 October, p 1074) and Mr J P Calvert (28 July, p 274), both advocate midline uterine incisions to avoid trauma to the head by the contracting thick uterine wall at caesarean section. I would suggest that the administration of halothane will abolish uterine contractions and make the abdominal delivery of the premature fetus easier, especially when there is no liquor. Halothane is routinely used during caesarean section at this hospital and uterine haemorrhage is not a problem and when it occurs it responds to oxytocics. Halothane depresses the fetus but this is always temporary and responds to the usual remedies. M J JOHNSTONE

Bromocriptine treatment of acromegaly

Bromocriptine at a dose of 7.5-30 mg/day was given to 12 acromegalics for 6 mo. Mean serum growth hormone (GH) levels during a glucose tolerance test (GTT) were significantly lowered by the drug. In four patients the serum GH response during a GTT was suppressed to normal (i.e. less than or equal to 5 mlU/liter). If bromocriptine had not brought the serum GH response to a GTT to normal at a dose of 20 mg/day, this effect was not achieved by raising the dose to 30 mg/day. Bromocriptine was effective for the duration of treatment. On discontinuing therapy there was an increase in serum GH levels. No obvious clinical changes in the acromegalic features were noted. One patient with impaired glucose tolerance and one with established diabetes had normal glucose tolerance while on bromocriptine and another two patients with impaired glucose tolerance showed no obvious changes while on the drug. Side effects were minor. X-rays of the pituitary fossa before starting and at the end of treatment showed no significant change. We conclude that although bromocriptine is the most promising form of medical treatment for acromegaly to date, it is fully effective only in a minority of patients.

Paget's Disease in a 5-year-old: Acute Response to Human Calcitonin

A five-year-old boy presented with a three-and-a-half-year history of repeated bone fractures and progressive bone deformity. The excretion of hydroxyproline in the urine was greatly increased, and serum alkaline phosphatase and acid phosphatase levels were very high. These abnormalities together with the findings on bone histology and radiology suggested a diagnosis of juvenile Pagets disease. Human calcitonin reduced the bone turnover as evidenced by an immediate and sustained fall in urine hydroxyproline excretion, while calcium and phosphate balance became more positive. This treatment is therefore being continued on an outpatient basis.

Calcium metabolism in acromegaly.

A total of 78 acromegalic patients were studied before and after treatment by yttrium-90 needle implantation. Among the untreated patients 16% had a borderline or raised serum calcium. In half of these patients the serum calcium fell to normal after remission of their acromegaly. In the others the hypercalcaemia was due to associated proved or probable hyperparathyroidism. A downward trend of the serum calcium was noted even in the normocalcaemic patients with remission of their disease. Only 20% of untreated patients had a raised serum phosphate, and follow-up showed this measurement to be a poor index of disease activity. Net calcium absorption and calcium balances in five patients in this series and 12 others from the literature were essentially normal for their given level of calcium intake. No patient showed definite radiological evidence of osteoporosis and vertebral fractures. Bone uptake rate of calcium-47 and stable strontium was raised in the untreated state in all nine patients studied. The 24-hour strontium space was raised in 73% of untreated patients and fell to normal after treatment in all the retested patients in whom it was high initially.