1426

lithium, in

common with many other antidepressants, reduced the accumulation of 5-H.I.A.A. in the c.s.F. of probenecid-treated patients. Furthermore, it is difficult to reconcile the beneficial effects of lithium in recurrent depressive illness with the deterioration in mental function which may result from phenytoin therapy."

Department of Neurology, Institute of Psychiatry, De Crespigny Park, Denmark Hill,

D. CHADWICK P. JENNER E. H. REYNOLDS.

London SE5 8AF.

SOMATOSTATIN AND INSULINOMA

SiR,-Somatostatin’s remarkable suppressive effect

on

the secretion of several hormones is well established. Besides inhibiting secretion from normal endocrine tissue, somatostatin has also been shown to inhibit hormone secretion from two kinds of endocrine tumours-eosinophil pituitary adenoma 12 and glucagonoma.13We have examined the effect of somatostatin in two patients with nonmalignant insulinoma in the fasting state and during intravenous glucose stimulation, in order to determine whether the absolute or relative hypersecretion of insulin

..

..

.. :1’-----

- 30 0

60

120

180

240min.

250;;g a..;.. 250;;g

Somatostatm

-30i;

60

120

180

240min.

250)jg L.;;. 250 P9

Somatostatin

Fig. 2-Effect of glucose intravenously alone and with statin in two patients with insulinoma.

somato-

The effects of prolonged somatostatin infusion are shown in fig. 1. In both patients the overall hormone pattern was the same: immediately after somatostatin, plasma-insulin and plasma-glucagon fell sharply, and after the infusion both hormones rose again. However, the glucagon patterns were quantitatively different in the two patients: in patient A plasma-glucagon was suppressed to below 10 pg. per ml., and the rise after the infusion was barely appreciable. In patient B plasma-glucagon was suppressed to between 20 and 60 pg. per ml., and the postinfusion rise was very

z I

Somatostohn

know 1000Ng

250Ng Somatostatin

. 2iO)1g

Fig. I-Effect of somatostatin infusion in

striking. Plasma-glucose behaved differently in the 1000µg 1000 ug

two

patients with

insulinoma.

found in this disease is also suppressible by somatostatin. Somatostatin was infused into the fasting patients as a bolus of 250 mg., followed by 1000 mg. over 225 minutes. Venous blood-samples were drawn every 15 minutes from 60 minutes before the infusion until 60 minutes after the cessation of the infusion. On another day two intravenous glucose-tolerance tests In the first test 25 g. of glucose was were performed. injected. The second test was made 120 minutes after the first one, and this time somatostatin was injected as a bolus of 250 mg. together with the glucose and followed by an infusion of 250 mg. during the next 60 minutes. Bloodsamples were taken every 15 minutes from 60 minutes before the first glucose injection until 120 minutes after the second

injection. Plasma-glucose was determined by a glucose-oxidase method, plasma-insulin and plasma-pancreatic-glucagon by radioimmunoassay using wick chromatography.14 For the glucagon determination plasma was ethanol-extracted," and an antiglucagon specific for pancreatic glucagon was used (kindly supplied by Lise Heding, Novo Research Institute, Copenhagen). 11. 12.

13.

14. 15.

Reynolds, E. H., Travers, R. D. Br. J. Psychiat. 1974, 127, 440. Hall, R., Besser, G. M., Schally, A. V., Coy, D. H., Evered, D., Goldie, D. J., Kastin, A. J., McNeilly, A. S., Mortimer, C. H., Phenekos, C., Tunbridge, W. M. G., Weightman, D. Lancet, 1973, ii, 581. Mortimer, C. H., Tunbridge, W. M. G., Carr, D., Yeomans, L., Lind, T., Coy, D. H., Bloom, S. R., Kastin, A., Mallinson, C. N., Besser, G. M., Schally, A. V., Hall, R. ibid. 1974, i, 697. Ørskov, H., Thomsen, H. G., Yde, H. Nature, 1968, 219, 193. Heding, L. G. Diabetologia, 1971, 7, 10.

two

patients.

In A there was a fall from 50 mg. to 30 mg. per 100 ml. during the first 30 minutes of infusion, and after that a rise to a plateau of 55 mg. per 100 ml. After the infusion plasma-glucose fell again. In B glucose rose from 20 to 45 mg. per 100 ml. during the infusion and fell to 25 mg. per 100 ml. again afterwards. The results of the intravenous glucose-tolerance tests (fig. 2) showed a large insulin rise and a very fast glucose disappearance in the control tests. When the tests were repeated during somatostatin infusion, plasma-insulin fell despite the glucose stimulus, and the glucose disappearance was much slower than in the control experiments. In patient A the change in plasma-insulin 15 minutes after glucose was +37 microunits per ml. and -3 microunits per ml. in the two tests, and the K values for glucose disappearance were 3-85 and 1-10, respectively. In patient B the plasma-insulin changes were +32 and -4 microunits per ml. The K values were 3-30 and 0-91. The results demonstrate that insulin secretion from nonmalignant insulinomas can be suppressed by somatostatin, just as hormone secretion from some other autonomous tumours (pituitary adenoma and glucagonoma) can be inhibited. Intravenous glucose infusions are needed in many patients in preoperative management of insulinomas. The infusion raises the blood-glucose, but at the same time it increases insulin secretion. Addition of somatostatin to the glucose infusions, suppressing the secretion of insulin, may be of value in this situation.

2nd University Clinic of Internal

Medicine, Aarhus, Denmark.

S. E. CHRISTENSEN AA. P. HANSEN K. LUNDBÆK H. ØRSKOV K. SEYER-HANSEN.