181 of fibrinolysis of normal pregnancy, and there is much evidence that many of the vascular complications of diabetes represent a low-grade consumptive coagulopathy, so pregnancy for the diabetic woman could represent a calculated pathological as well as a clinical risk. In the first instance it would be of interest to know whether there is evidence of deterioration in the retinal circulation of pregnant diabetics. Secondly, an attempted correlative study between lactogen levels and fibrinolytic activity in pregnancy has yet to be done.
the test could not be carried out because of postural hypotension. His retinopathy, assessed photographically, did not alter significantly during the 8 weeks of treatment.
We report this
case to
draw attention
Department of Medicine, Hammersmith Hospital, London W12 0HS.
E. N. WARDLE.
NE3 3DE.
BROMOCRIPTINE AND SERUM-GROWTHHORMONE LEVELS IN DIABETES MELLITUS
dopamine-receptor stimulant,! SIR,-Bromocriptine, growth-hormone secretion in some acromegalics.2-4 Since growth-hormone secretion may play a role in the evolution of diabetic retinopathy,ó,6 we tried to suppress growth-hormone secretion with bromocriptine in a male juvenile diabetic with severe proliferative retinopathy. a
suppresses
The patient, a man aged 31, presented in diabetic ketoacidosis the age of 4 years, and he has been treated with insulin ever since. Currently he is well controlled on two injections of soluble and isophane daily and a 180 g. carbohydrate diet. He was referred to this hospital for management of severe proliferative retinopathy. His blood-pressure was 145/60 mm. Hg and he had no postural hypotension. It was decided to start treatment with bromocriptine in February of this year because of deteriorating retinopathy despite extensive treatment with photocoagulation, and to assess growth-hormone levels monthly at rest and during an exercise test consisting of 20 minutes on a bicycle ergometer at 45% of working capacity.7 Bromocriptine was worked up to a dose of 5 mg. thrice daily over a period of a month. The serum-growthhormone levels in this patient before and 4 weeks after the start of the treatment are shown in the accompanying table. For comparison, the levels in four normal males and four insulintreated male juvenile diabetics are shown. Bromocriptine did not suppress the serum-growth-hormone levels at rest or during exercise. Blood-glucose levels were similar during the two tests. The patient felt generally unwell and complained of some nausea and dizziness while on bromocriptine. He also felt slightly faint after the second exercise test, and a month later at
Corrodi, H., Fuxe, K., Hökfelt, T., Lidbrink, P., Ungerstedt, U. J. Pharm. Pharmac. 1973, 25, 409. 2. Liuzzi, A., Chiodini, P. G., Botalla, L., Cremascoli, G., Müller, E. E., Silvestrini, F. J. clin. Endocr. Metab. 1974, 38, 910. 3. Liuzzi, A., Chiodini, P. G., Botalla, L., Silvestrini, F., Müller, E. E. ibid. 1974, 39, 871. 4. Thorner, M. O., Chait, A., Aitken, M., Benker, G., Bloom, S. R., Mortimer, C. H., Sanders, P., Stuart Mason, A., Besser, G. M. Br. med. J. 1975, i, 299. 5. Lundbæk, K. in Blood Vessel Disease in Diabetes Mellitus (edited by K. Lundbæk and H. Keen). Acta diabet. lat. 1971, 8, suppl. 1, 1.
the fact that
renorted.8e
33 Hawthorn
Gardens, Kenton, Newcastle upon Tyne
to
bromocriptine increased growth-hormone secretion’ in a diabetic and that side-effects were significant. Bromocriptine has been found to increase growth-hormone secretion in normal subjects but no side-effects were J. CASSAR R. EDWARDS K. MASHITER EVA M. KOHNER.
HYPOTENSION DURING ANGIOTENSIN BLOCKADE WITH SARALASIN Sirwas interested to read Dr Pettinger and Dr Keeton’s account (June 21, p. 1387) of hypotension during saralasin (sarl-ala8-angiotensin n) infusion in a patient with resistant hypertension on multiple drug therapy. It was not clear why Dr Pettinger and Dr Keeton started their infusion at a rate of 1 {g. per kg. per min. and increased the infusion-rate from 1 to 3 {j!.g. per kg. per min. when the lying blood-pressure was less than 100/70 mm. Hg. They themselves state that similar patients’ blood-pressures were in some instances controlled with an infusionrate of 0-15 (Jt.g. per kg. per min. Whilst I agree with their conclusion that angiotensin-n blockade with saralasin may lead to hypotension in patients on multiple hypotensive drugs, I think this can be avoided by careful adjustment of the infusion-rate, which should be started at a maximum of 0.100 g. per kg. per min., and by measuring the standing
blood-pressure. The standing blood-pressure appears to be a more sensitive index of angiotensin-n dependency in these relatively volume-depleted patients. The other advantage of measuring standing blood-pressure is that, if hypotension occurs on standing, the patient only needs to lie down to restore a reasonable blood-pressure. In 3 of our patients similar to the one that they describethat is, uncontrolled hypertension on multiple hypotensive therapy-standing blood-pressure fell at a lower rate of infusion and to a greater extent than lying blood-pressure. In all 3 patients, the blood-pressure was lowered to less than 160/100 mm. Hg lying at a maximum infusion-rate of 1 g. per kg. per min. This is illustrated by the following case.
A 46-year-old man with severe hypertension, uncontrolled by combination of propranolol, frusemide, hydrallazine, and methyldopa, was infused with saralasin, starting at a rate of 0-100 jj.g. per kg. per min. The standing blood-pressure started to fall at this rate, and fell progressively as the infusion-rate was a
p. 344. 6. 7.
Luft, R., Guillemin, R. Diabetes, 1974, 23, 783. Hansen, A. P. J. clin. Invest. 1970, 49, 1467.
8.
Camanni, F., Massara, F., Belforte, L., Molinatti, G. M. J. clin. Endocr. Metab. 1975, 40, 363.
SERUM-GROWTH-HORMONE LEVELS AT REST AND DURING EXERCISE
the test could not be carried out because of postural hypotension. His retinopathy, assessed photographically, did not alter significantly during the 8 weeks of treatment.
We report this
case to
draw attention
Department of Medicine, Hammersmith Hospital, London W12 0HS.
E. N. WARDLE.
NE3 3DE.
BROMOCRIPTINE AND SERUM-GROWTHHORMONE LEVELS IN DIABETES MELLITUS
dopamine-receptor stimulant,! SIR,-Bromocriptine, growth-hormone secretion in some acromegalics.2-4 Since growth-hormone secretion may play a role in the evolution of diabetic retinopathy,ó,6 we tried to suppress growth-hormone secretion with bromocriptine in a male juvenile diabetic with severe proliferative retinopathy. a
suppresses
The patient, a man aged 31, presented in diabetic ketoacidosis the age of 4 years, and he has been treated with insulin ever since. Currently he is well controlled on two injections of soluble and isophane daily and a 180 g. carbohydrate diet. He was referred to this hospital for management of severe proliferative retinopathy. His blood-pressure was 145/60 mm. Hg and he had no postural hypotension. It was decided to start treatment with bromocriptine in February of this year because of deteriorating retinopathy despite extensive treatment with photocoagulation, and to assess growth-hormone levels monthly at rest and during an exercise test consisting of 20 minutes on a bicycle ergometer at 45% of working capacity.7 Bromocriptine was worked up to a dose of 5 mg. thrice daily over a period of a month. The serum-growthhormone levels in this patient before and 4 weeks after the start of the treatment are shown in the accompanying table. For comparison, the levels in four normal males and four insulintreated male juvenile diabetics are shown. Bromocriptine did not suppress the serum-growth-hormone levels at rest or during exercise. Blood-glucose levels were similar during the two tests. The patient felt generally unwell and complained of some nausea and dizziness while on bromocriptine. He also felt slightly faint after the second exercise test, and a month later at
Corrodi, H., Fuxe, K., Hökfelt, T., Lidbrink, P., Ungerstedt, U. J. Pharm. Pharmac. 1973, 25, 409. 2. Liuzzi, A., Chiodini, P. G., Botalla, L., Cremascoli, G., Müller, E. E., Silvestrini, F. J. clin. Endocr. Metab. 1974, 38, 910. 3. Liuzzi, A., Chiodini, P. G., Botalla, L., Silvestrini, F., Müller, E. E. ibid. 1974, 39, 871. 4. Thorner, M. O., Chait, A., Aitken, M., Benker, G., Bloom, S. R., Mortimer, C. H., Sanders, P., Stuart Mason, A., Besser, G. M. Br. med. J. 1975, i, 299. 5. Lundbæk, K. in Blood Vessel Disease in Diabetes Mellitus (edited by K. Lundbæk and H. Keen). Acta diabet. lat. 1971, 8, suppl. 1, 1.
the fact that
renorted.8e
33 Hawthorn
Gardens, Kenton, Newcastle upon Tyne
to
bromocriptine increased growth-hormone secretion’ in a diabetic and that side-effects were significant. Bromocriptine has been found to increase growth-hormone secretion in normal subjects but no side-effects were J. CASSAR R. EDWARDS K. MASHITER EVA M. KOHNER.
HYPOTENSION DURING ANGIOTENSIN BLOCKADE WITH SARALASIN Sirwas interested to read Dr Pettinger and Dr Keeton’s account (June 21, p. 1387) of hypotension during saralasin (sarl-ala8-angiotensin n) infusion in a patient with resistant hypertension on multiple drug therapy. It was not clear why Dr Pettinger and Dr Keeton started their infusion at a rate of 1 {g. per kg. per min. and increased the infusion-rate from 1 to 3 {j!.g. per kg. per min. when the lying blood-pressure was less than 100/70 mm. Hg. They themselves state that similar patients’ blood-pressures were in some instances controlled with an infusionrate of 0-15 (Jt.g. per kg. per min. Whilst I agree with their conclusion that angiotensin-n blockade with saralasin may lead to hypotension in patients on multiple hypotensive drugs, I think this can be avoided by careful adjustment of the infusion-rate, which should be started at a maximum of 0.100 g. per kg. per min., and by measuring the standing
blood-pressure. The standing blood-pressure appears to be a more sensitive index of angiotensin-n dependency in these relatively volume-depleted patients. The other advantage of measuring standing blood-pressure is that, if hypotension occurs on standing, the patient only needs to lie down to restore a reasonable blood-pressure. In 3 of our patients similar to the one that they describethat is, uncontrolled hypertension on multiple hypotensive therapy-standing blood-pressure fell at a lower rate of infusion and to a greater extent than lying blood-pressure. In all 3 patients, the blood-pressure was lowered to less than 160/100 mm. Hg lying at a maximum infusion-rate of 1 g. per kg. per min. This is illustrated by the following case.
A 46-year-old man with severe hypertension, uncontrolled by combination of propranolol, frusemide, hydrallazine, and methyldopa, was infused with saralasin, starting at a rate of 0-100 jj.g. per kg. per min. The standing blood-pressure started to fall at this rate, and fell progressively as the infusion-rate was a
p. 344. 6. 7.
Luft, R., Guillemin, R. Diabetes, 1974, 23, 783. Hansen, A. P. J. clin. Invest. 1970, 49, 1467.
8.
Camanni, F., Massara, F., Belforte, L., Molinatti, G. M. J. clin. Endocr. Metab. 1975, 40, 363.
SERUM-GROWTH-HORMONE LEVELS AT REST AND DURING EXERCISE
