50 CIGARETTE SMOKING AND RISK OF RETINOPATHY
it may be an idiosynwith the XYY sex-chromosome complement, a possibility suggested by the raised levels of prolactin found in others who have not been treated with lactogenic drugs. We would be interested to hear of any patients with this chromosome abnormality who experience the same side-effect on phenothiazine treatment or who are found to have raised prolactin levels when not on any drug therapy. Men with a 47,XYY karyotype at maximum security hospitals are above average height and are admitted in greater than expected numbers. The possibility that prolactin secretion is abnormal in these patients is therefore of interest since it is a hormone known to stimulate growth in some species and its secretion may be related to behaviour. are
given simultaneously. Alternatively,
crasy in
(3.8%). In contrast to the results of Paetkau et al. we found in non-smokers a strong relationship between proliferative retinopathy and duration of diabetes. Among non-smokers who had had diabetes for fifteen years or more, 15% had proliferative lesions (10 of 66). In long-duration cases who were smokers this rate was 9% (3 of 33). Among the 447 nonsmokers there were 166 former smokers. Rates of retinopathy (24-1%) and proliferative retinopathy (3-0%) were the same as in those who had never smoked. Mean duration of known diabetes was seven years in both of these subgroups. More data are needed but our results lend no support to the hypothesis that smoking is a risk factor for diabetic retinopathy. Diabetics should not smoke, because they are already at risk of coronary and peripheral vascular disease. Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, U.S.A.
KELLY M. WEST JUDY A. STOBER
PROLACTIN SECRETION IN XYY MALES the clinical examination of patients with a at a maximum security hospital, a 27-yearold man was found to have marked gynxcomastial and galactorrhoea. He had been aware of breast enlargement for about two years and during that time he was treated with fortnightly injections of 50 mg fluphenazine decanoate. Intermittent lactation had been occurring for several months. Mild gynscomastia had been noted when the patient had been treated with cestrogens 7 years earlier, but it was not known if this had persisted when treatment was discontinued after about a year. He refuses to provide further blood-samples. Gynaecomastia was not noted in any others with the same karyotype but in three, aged 23, 29, and 43 years, who had not received any drugs, the prolactin levels were 394, 745, and 426 mU/1, respectively, all of which are abnormally high. Several factors such as exercise,2 sleep,3 stress,2 and even venepuncture may raise circulating prolactin levels, but in blood-samples obtained in an identical manner, under similar conditions, from men at the same institution who only had one Y chromosome the prolactin levels were normal. ’Most males with a 47,XYY karyotype are free from physical abnormality, and the patient reported here is the first we have seen with any breast enlargement. We believe that the gynaecomastia and the lactation are complications of treatment with fluphenazine, but the severity seems disproportional to the dose of the drug and raises the possibility of an increased sensitivity. This could be related to the previous oestrogen administration since phenothiazine-stimulated prolactin secretion is augmented by aestrogens,4 but usually when the drugs
SIR,-During
47,XYY karyotype
Price, W. H., Brunton, M , Buckton, K. E., Jacobs, P. A. Clin Genet. 1976, 9, 389. 2. Noel, G. L., Sug, H. K., Stone, J G., Franz, A. G. J. clin. Endocr. Metab 1.
1972, 35, 840. 3. Sassin, J. F., Frantz,
A.
G., Weitz, E. D., Kapen, S. Science, 1972, 177,
1205. 4.
Buckman, M. T., Peake, G. T. J. clin. Endocr. Metab 1973, 37, 977.
men
We thank Dr E. A. Cameron of the regional hormone laboratory for estimations of prolactin and the consultant psychiatrists in charge of the patients at the security hospitals for kind cooperation.
Department of Medicine and M.R.C. Clinical and Population
Cytogenetics Unit, Western General Hospital, Edinburgh EH4 2XU
W. H. PRICE W. B. RENTON W. A. CAMPBELL
PROPRANOLOL THERAPY FOR SECONDARY HYPERPARATHYROIDISM IN URÆMIA
SiR,—The description by Dr Caro and Dr Besarab (April 15, p. 827) of a patient in whom propranolol decreased both raised
raised plasma-parathyroid-horreport the preliminary results of two studies on the interference of antihypertensive drugs with the hormonal control of calcium-phosphate homoeostasis in ursemic patients. In a first study, thirteen hoemodialysed patients were successively treated for 6-week periods with equally antihypertensive regimens of metoprolol, methyldopa, and clonidine. P.T.H. and plasma concentrations of calcitonin, calcium, and phosphate were measured before the first dialysis in the sixth week of each period of treatment. Throughout the study other theraa
mone
plasma-calcium and (P.T.H.) prompts us to
a
peutic measures were kept constant. Variance analysis showed no significant differences between the three treatments except that the predialysis plasma-calcium was lower after metoprolol (8-5 ±0-2 mg/dl) than after clonidine (9-2±0-2). Because a higher P.T.H. was not observed after metoprolol despite the fall in plasma-calcium, metoprolol could have had a greater suppressive effect or a lower stimulating effect on P.T.H. secretion than clonidine. Because the study produced no denmuve conclusion about the absolute effect of these antihypertensive drugs on the hormonal control of calcium phosphate homceostasis, we began a second study to evaluate the acute effects of propranolol and metoprolol on P.T. H. and plasma-calcitonin. Propranolol (blocking &bgr;I and 32 receptors) was given intravenously (priming dose 1 mg given over 5 min and 1 p.g/kg/min given over 85 min) to nine uraemic patients not yet on dialysis and metoprolol (blocking only 31 receptors) was given intravenously (priming dose 1.2mg given over 5 min and 1.2 ug/ kg/min given over 85 min) 15 days later to six of these patients. Venous blood was taken before and 15, 30, 60, and 90 min after starting the injection. P.T.H. and plasma concentrations of total and ionised calcium, phosphate, and calcitonin were measured. The antibody used for P.T.H. was specific for the fragment 1-34 and the native human molecule. There was no significant change at any time in phosphate or total ionised calcium. The significant decrease in heart-rate was of the same magnitude with both drugs, suggesting equally effective 31 receptor blockade. P.T.H. decreased significantly (by 36%) at 30 min with propranolol but did not decrease with metoprolol. Calcitonin also decreased significantly at 60 min after propranolol (by 40%) but did not change after metoprolol. It appears, therefore, that propranolol acutely suppresses
it may be an idiosynwith the XYY sex-chromosome complement, a possibility suggested by the raised levels of prolactin found in others who have not been treated with lactogenic drugs. We would be interested to hear of any patients with this chromosome abnormality who experience the same side-effect on phenothiazine treatment or who are found to have raised prolactin levels when not on any drug therapy. Men with a 47,XYY karyotype at maximum security hospitals are above average height and are admitted in greater than expected numbers. The possibility that prolactin secretion is abnormal in these patients is therefore of interest since it is a hormone known to stimulate growth in some species and its secretion may be related to behaviour. are
given simultaneously. Alternatively,
crasy in
(3.8%). In contrast to the results of Paetkau et al. we found in non-smokers a strong relationship between proliferative retinopathy and duration of diabetes. Among non-smokers who had had diabetes for fifteen years or more, 15% had proliferative lesions (10 of 66). In long-duration cases who were smokers this rate was 9% (3 of 33). Among the 447 nonsmokers there were 166 former smokers. Rates of retinopathy (24-1%) and proliferative retinopathy (3-0%) were the same as in those who had never smoked. Mean duration of known diabetes was seven years in both of these subgroups. More data are needed but our results lend no support to the hypothesis that smoking is a risk factor for diabetic retinopathy. Diabetics should not smoke, because they are already at risk of coronary and peripheral vascular disease. Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, U.S.A.
KELLY M. WEST JUDY A. STOBER
PROLACTIN SECRETION IN XYY MALES the clinical examination of patients with a at a maximum security hospital, a 27-yearold man was found to have marked gynxcomastial and galactorrhoea. He had been aware of breast enlargement for about two years and during that time he was treated with fortnightly injections of 50 mg fluphenazine decanoate. Intermittent lactation had been occurring for several months. Mild gynscomastia had been noted when the patient had been treated with cestrogens 7 years earlier, but it was not known if this had persisted when treatment was discontinued after about a year. He refuses to provide further blood-samples. Gynaecomastia was not noted in any others with the same karyotype but in three, aged 23, 29, and 43 years, who had not received any drugs, the prolactin levels were 394, 745, and 426 mU/1, respectively, all of which are abnormally high. Several factors such as exercise,2 sleep,3 stress,2 and even venepuncture may raise circulating prolactin levels, but in blood-samples obtained in an identical manner, under similar conditions, from men at the same institution who only had one Y chromosome the prolactin levels were normal. ’Most males with a 47,XYY karyotype are free from physical abnormality, and the patient reported here is the first we have seen with any breast enlargement. We believe that the gynaecomastia and the lactation are complications of treatment with fluphenazine, but the severity seems disproportional to the dose of the drug and raises the possibility of an increased sensitivity. This could be related to the previous oestrogen administration since phenothiazine-stimulated prolactin secretion is augmented by aestrogens,4 but usually when the drugs
SIR,-During
47,XYY karyotype
Price, W. H., Brunton, M , Buckton, K. E., Jacobs, P. A. Clin Genet. 1976, 9, 389. 2. Noel, G. L., Sug, H. K., Stone, J G., Franz, A. G. J. clin. Endocr. Metab 1.
1972, 35, 840. 3. Sassin, J. F., Frantz,
A.
G., Weitz, E. D., Kapen, S. Science, 1972, 177,
1205. 4.
Buckman, M. T., Peake, G. T. J. clin. Endocr. Metab 1973, 37, 977.
men
We thank Dr E. A. Cameron of the regional hormone laboratory for estimations of prolactin and the consultant psychiatrists in charge of the patients at the security hospitals for kind cooperation.
Department of Medicine and M.R.C. Clinical and Population
Cytogenetics Unit, Western General Hospital, Edinburgh EH4 2XU
W. H. PRICE W. B. RENTON W. A. CAMPBELL
PROPRANOLOL THERAPY FOR SECONDARY HYPERPARATHYROIDISM IN URÆMIA
SiR,—The description by Dr Caro and Dr Besarab (April 15, p. 827) of a patient in whom propranolol decreased both raised
raised plasma-parathyroid-horreport the preliminary results of two studies on the interference of antihypertensive drugs with the hormonal control of calcium-phosphate homoeostasis in ursemic patients. In a first study, thirteen hoemodialysed patients were successively treated for 6-week periods with equally antihypertensive regimens of metoprolol, methyldopa, and clonidine. P.T.H. and plasma concentrations of calcitonin, calcium, and phosphate were measured before the first dialysis in the sixth week of each period of treatment. Throughout the study other theraa
mone
plasma-calcium and (P.T.H.) prompts us to
a
peutic measures were kept constant. Variance analysis showed no significant differences between the three treatments except that the predialysis plasma-calcium was lower after metoprolol (8-5 ±0-2 mg/dl) than after clonidine (9-2±0-2). Because a higher P.T.H. was not observed after metoprolol despite the fall in plasma-calcium, metoprolol could have had a greater suppressive effect or a lower stimulating effect on P.T.H. secretion than clonidine. Because the study produced no denmuve conclusion about the absolute effect of these antihypertensive drugs on the hormonal control of calcium phosphate homceostasis, we began a second study to evaluate the acute effects of propranolol and metoprolol on P.T. H. and plasma-calcitonin. Propranolol (blocking &bgr;I and 32 receptors) was given intravenously (priming dose 1 mg given over 5 min and 1 p.g/kg/min given over 85 min) to nine uraemic patients not yet on dialysis and metoprolol (blocking only 31 receptors) was given intravenously (priming dose 1.2mg given over 5 min and 1.2 ug/ kg/min given over 85 min) 15 days later to six of these patients. Venous blood was taken before and 15, 30, 60, and 90 min after starting the injection. P.T.H. and plasma concentrations of total and ionised calcium, phosphate, and calcitonin were measured. The antibody used for P.T.H. was specific for the fragment 1-34 and the native human molecule. There was no significant change at any time in phosphate or total ionised calcium. The significant decrease in heart-rate was of the same magnitude with both drugs, suggesting equally effective 31 receptor blockade. P.T.H. decreased significantly (by 36%) at 30 min with propranolol but did not decrease with metoprolol. Calcitonin also decreased significantly at 60 min after propranolol (by 40%) but did not change after metoprolol. It appears, therefore, that propranolol acutely suppresses
