1243 NOMIFENSINE TEST FOR INVESTIGATION OF HYPERPROLACTINÆMIA
SIR,—Dr Miiller and colleagues (Aug. 4, p. 257) have drawn attention to their paper’ on the differentiation between hyperprolactinaemic individuals with and without pituitary tumours on the basis of prolactin responses to 200 mg oral nomifens;ne. In a controlled study, we have been unable to confirm the usefulness of this diagnostic test. Prolactin responses to 200 mg nomifensine were measured in eleven healthy normoprolactinwmic controls (five males and six premenopausal women); seven women on day 3 or day 4 postpartum; five women with prolactinomas diagnosed preoperatively according to a published protocol2 and subsequently confirmed at operation; and two women with presumed "functional" hyperprolactinæmia.3 We have also
studied serum prolactin levels after 5 mg oral folate (placebo) in the controls. Serum prolactin was measured by radioimmunoassay4 in samples obtained via an indwelling cannula, in situ for at least 30 min before the start of the test (between 9.30 and 10 A.M.). Over the time course of the test we observed no consistent significant differences in prolactin responses to nomifensine compared with placebo in any of the groups studied (figure). In puerperal women there was considerable individual variation in prolactin levels throughout the test, and two of these patients fulfilled Muller’s criteria for a normal response to nomifensine. However, the group is heterogeneous and, unlike Muller et al., we would suggest that an exaggeration of the normal pulsatility of prolactin secretion in the puerperium together with the other well established factors which may affect circulating prolactin levels are the most likely explanations for heterogeneous responses. It may also be significant that in Muller’s subjects, the basal prolactin level in the puerperal group given nomifensine was almost twice (199±10.5 ng/ml) that in the puerperal group studied for spontaneous fluctuation in prolactin level (101±2-4 ng/ml; variability data not
published).
Thus,
cautious about the value of nomifensine as a tool in the investigation of hyperprolactina:mic
we are
diagnostic states.
M. J. DUNNE
University Department of Medicine and Radioimmunoassay Unit, Department of Biochemistry, Royal Infirmary, Glasgow G4 0SF
J. WALKER E. A. COWDEN J. G. RATCLIFFE
-
SIR,—Your Nov. 24 editorial on 2, 4, 5-trichlorophenoxyacetic acid (2, 4, 5-T) states that the contaminant dioxin is a potent enzyme inducer. This may not be the mechanism responsible for dioxin’s known lethal actions, but other adverse clinical and biochemical effects have been associated with dioxin and with other enzyme inducers in man and/or laboratory animals. Examples are: hypocalcaemia (in my unpublished study of dioxin-exposed workers) and symptoms of osteomalacia ;5 altered drug metabolism ;6 hyperlipideemia and ischa:mic vascular disease;’ and increased susceptibility to other hepatotoxic agents.8 Such effects can occur independently of chloracne-i.e., an individual exposed to dioxin can exhibit other signs of exposure without having chloracne, as I (unpublished) and Oliver9 have found. We must evaluate all evidence of toxicity before concluding that "there is no wolf". Department of Occupational Health, University of Manchester, Manchester M13 9PT J. V. MARTIN
Percentage changes in prolactin levels after nomifensine 0). (8 W) or placebo (0 Top panel: in normal males. Prolactin responses to levodopa and bromocriptine4 in normal subjects are also shown for comparison. Lower panel: in normal females. Also shown are responses to nomifensine in female patients with prolactinoma (O—O) and in puerperal females (•—•). ---
---
EE, Genazzani AR, Murru S. Nomifensine: diagnostic test in hyperprolactinæmic states. J Clin Endocrinol Metab 1978; 47: 1352-58. 2. Cowden EA, Ratcliffe JG, Thomson JA, Macpherson P, Doyle D, Teasdale GM. Tests of prolactin secretion in diagnosis of prolactinomas. Lancet 1979; i: 1155-58. 3. Cowden EA, Ratcliffe JG, Thomson JA, Macpherson P, Doyle D, Teasdale GM. Lancet 1979; ii: 256-57. 1. Müller
*** The "wolf’ was the danger of exposure to careful use of herbicidal sprays prepared from 2, 4, 5-T containing less than 0.00001 % dioxin.-ED. L. 4. Cowden
EA, Ratcliffe WA, Beastall GH, Ratcliffe JG. Laboratory assessof prolactin status. Ann Clin Biochem 1979; 16: 113-21. 5. Hirayama C. Clinical aspects of PCB poisoning. In: Higuchi K, ed. PCB poisoning and pollution. Tokyo: K. Kodansho (Academic Press), 1976. 6. Whitfield JB, Moss DW, Neale, G, Orme M, Breckenbndge A. Changes in plasma &agr;-glutamyl transpeptidase activity associated with alterations in drug metabolism in man. Br Med J 1973: 7. Walker AE Martin JV. Lipid profiles in dioxin exposed workers. Lancet ment
1979; i: 446. 8.
9.
Reynolds ES, Moslen MT, Szabo S, Jaeger RJ, Murphy SD. Hepatotoxicity of vinyl chloride and 1,1-dichloroethylene. Am J Pathol 1975; 81: 219. Oliver RM. Toxic effects of 2, 3, 7, 8 tetrachlorodibenzo-1, 4 dioxin in laboratory workers. Br J Ind Med 1975; 32: 49.
SIR,—Dr Miiller and colleagues (Aug. 4, p. 257) have drawn attention to their paper’ on the differentiation between hyperprolactinaemic individuals with and without pituitary tumours on the basis of prolactin responses to 200 mg oral nomifens;ne. In a controlled study, we have been unable to confirm the usefulness of this diagnostic test. Prolactin responses to 200 mg nomifensine were measured in eleven healthy normoprolactinwmic controls (five males and six premenopausal women); seven women on day 3 or day 4 postpartum; five women with prolactinomas diagnosed preoperatively according to a published protocol2 and subsequently confirmed at operation; and two women with presumed "functional" hyperprolactinæmia.3 We have also
studied serum prolactin levels after 5 mg oral folate (placebo) in the controls. Serum prolactin was measured by radioimmunoassay4 in samples obtained via an indwelling cannula, in situ for at least 30 min before the start of the test (between 9.30 and 10 A.M.). Over the time course of the test we observed no consistent significant differences in prolactin responses to nomifensine compared with placebo in any of the groups studied (figure). In puerperal women there was considerable individual variation in prolactin levels throughout the test, and two of these patients fulfilled Muller’s criteria for a normal response to nomifensine. However, the group is heterogeneous and, unlike Muller et al., we would suggest that an exaggeration of the normal pulsatility of prolactin secretion in the puerperium together with the other well established factors which may affect circulating prolactin levels are the most likely explanations for heterogeneous responses. It may also be significant that in Muller’s subjects, the basal prolactin level in the puerperal group given nomifensine was almost twice (199±10.5 ng/ml) that in the puerperal group studied for spontaneous fluctuation in prolactin level (101±2-4 ng/ml; variability data not
published).
Thus,
cautious about the value of nomifensine as a tool in the investigation of hyperprolactina:mic
we are
diagnostic states.
M. J. DUNNE
University Department of Medicine and Radioimmunoassay Unit, Department of Biochemistry, Royal Infirmary, Glasgow G4 0SF
J. WALKER E. A. COWDEN J. G. RATCLIFFE
-
SIR,—Your Nov. 24 editorial on 2, 4, 5-trichlorophenoxyacetic acid (2, 4, 5-T) states that the contaminant dioxin is a potent enzyme inducer. This may not be the mechanism responsible for dioxin’s known lethal actions, but other adverse clinical and biochemical effects have been associated with dioxin and with other enzyme inducers in man and/or laboratory animals. Examples are: hypocalcaemia (in my unpublished study of dioxin-exposed workers) and symptoms of osteomalacia ;5 altered drug metabolism ;6 hyperlipideemia and ischa:mic vascular disease;’ and increased susceptibility to other hepatotoxic agents.8 Such effects can occur independently of chloracne-i.e., an individual exposed to dioxin can exhibit other signs of exposure without having chloracne, as I (unpublished) and Oliver9 have found. We must evaluate all evidence of toxicity before concluding that "there is no wolf". Department of Occupational Health, University of Manchester, Manchester M13 9PT J. V. MARTIN
Percentage changes in prolactin levels after nomifensine 0). (8 W) or placebo (0 Top panel: in normal males. Prolactin responses to levodopa and bromocriptine4 in normal subjects are also shown for comparison. Lower panel: in normal females. Also shown are responses to nomifensine in female patients with prolactinoma (O—O) and in puerperal females (•—•). ---
---
EE, Genazzani AR, Murru S. Nomifensine: diagnostic test in hyperprolactinæmic states. J Clin Endocrinol Metab 1978; 47: 1352-58. 2. Cowden EA, Ratcliffe JG, Thomson JA, Macpherson P, Doyle D, Teasdale GM. Tests of prolactin secretion in diagnosis of prolactinomas. Lancet 1979; i: 1155-58. 3. Cowden EA, Ratcliffe JG, Thomson JA, Macpherson P, Doyle D, Teasdale GM. Lancet 1979; ii: 256-57. 1. Müller
*** The "wolf’ was the danger of exposure to careful use of herbicidal sprays prepared from 2, 4, 5-T containing less than 0.00001 % dioxin.-ED. L. 4. Cowden
EA, Ratcliffe WA, Beastall GH, Ratcliffe JG. Laboratory assessof prolactin status. Ann Clin Biochem 1979; 16: 113-21. 5. Hirayama C. Clinical aspects of PCB poisoning. In: Higuchi K, ed. PCB poisoning and pollution. Tokyo: K. Kodansho (Academic Press), 1976. 6. Whitfield JB, Moss DW, Neale, G, Orme M, Breckenbndge A. Changes in plasma &agr;-glutamyl transpeptidase activity associated with alterations in drug metabolism in man. Br Med J 1973: 7. Walker AE Martin JV. Lipid profiles in dioxin exposed workers. Lancet ment
1979; i: 446. 8.
9.
Reynolds ES, Moslen MT, Szabo S, Jaeger RJ, Murphy SD. Hepatotoxicity of vinyl chloride and 1,1-dichloroethylene. Am J Pathol 1975; 81: 219. Oliver RM. Toxic effects of 2, 3, 7, 8 tetrachlorodibenzo-1, 4 dioxin in laboratory workers. Br J Ind Med 1975; 32: 49.
