- Email: [email protected]
GROWTH-HORMONE AND PROLACTIN RESPONSE TO LEVODOPA IN AFFECTIVE ILLNESS
1308 even a
be
glance at a revealing.
naked
baby by
an
experienced observer can
most
11 Park Road
West,
Wolverhampton
H. EVERLEY
JONES
GROWTH-HORMONE AND PROLACTIN RESPONSE TO LEVODOPA IN AFFECTIVE ILLNESS
SIR,-We have found significant differences in plasmagrowth-hormone (G.H.) and prolactin responses to levodopa between subgroups of depressed and manic patients. Since monoamine neurotransmitters are important regulators of the hypothalamic/pituitary axis,’ these differential neuroendocrine responses may constitute markers of specific monoamine dysfunctions in subgroups of patients with affective illness. 20 patients with primary affective disorder diagnosed according to the criteria of Spitzer et al.2 and 10 healthy volunteers were studied in hospital. All subjects had a controlled monoamine diet and received no medication for 3 wk before the study. Since high oestrogen levels potentiate neuroendocrine responses to levodopa, premenopausal women were tested only during the first 5 days of the menstrual cycle, when oestrogen levels were low. After an overnight fast, all subjects received 500 mg of oral levodopa, and plasma was drawn sequentially over a 3 h period and analysed for growth hormone and prolactin. G.H. and prolactin were assayed by the double-antibody
technique. No relationship was sponses to levodopa and
found between neuroendocrine reage. There was no significant differ-
Fig. 1--Growth-hormone response to levodopa tients and controls (mean±S.B.M.).
in
depressed pa-
in G.H. or prolactin response to levodopa between the whole group of depressed patients and controls. However, the bipolar group had a significantly larger peak G.H. increment than did unipolar patients (P<0-01) or controls (p<0-01) (fig. 1). Bipolar patients showed a significantly greater suppression of levodopa-induced prolactin response (fig. 2) than unipolar patients (p<0’001) or controls (p<0.05); the baseline prolactin level was 35% higher in the bipolar compared to the unipolar patients, but this difference was not significant. Among the bipolar patients, those in the depressive phase showed a larger peak G.H. response (fig. 3) than those in the manic phase ence
Fig. 2-Prolactin suppression after levodopa (meamiS.E.M.).
administration
Fig. 3-Growth-hormone response to levodopa in depressed and manic phases in bipolar patients (meaniS.E.M.). In normal subjects, response to stimuli which release c,H. is related to circulating oestrogen levels,3 so that this response is highest in premenopausal women, intermediate in men, and somewhat lower in postmenopausal women.’To our knowledge prolactin response to levodopa is not influenced by oestrogen levels. Because sex and ovarian status are unequally distributed in our patient subgroups (unipolar depressed 5 premenopausal and 3 postmenopausal women; bipolar depressed 4 men, 3 premenopausal women; bipolar manic 5 premenopausal women; controls 4 men, 6 premenopausal women) we must consider the possibility that these factors contribute to the G,H.n
(p<0.05). 1. Frohman, L. A., Strachura, M. E. Metabolism, 1975, 24(2), 211. 2. Spitzer, R. L., Endicott, J., Robbins, E. Psychopharmac. Bull. 1975,
3. 4. 5.
11,
22.
Frantz, A. G., Rabkin, M. T. J. clin. Endocr. Metab. 1965, 25, 1470. Merimee, T. J., Fineberg, S. E. ibid. 1971, 33, 890. Sachar, D. J., Altman, N., Gruen, P. H., et al. Archs gen. Psychiat 1975, 32, 502.
1309 differences reported. Since all groups included premenopausal women, we used them to evaluate subgroup differences inde-
pendent of sex and ovarian status; the premenopausal bipolar depressed women still showed a significantly greater response and manics (P<005). Furtherthan the unipolars (P<0-02) more, among the men the bipolar depressed patients showed a significantly greater growth-hormone response than controls
lP(O.02). Spinal-fluid
and
urinary
the neurotransmitter regulation of G.H. is complex, the increased prolactin suppression in bipolar depressed patients, coupled with increased G.H. response in this group, implies that the dopaminergic system is hyperresponsive to exogenous stimulation. This interpretation is consistent with the sensitivity of bipolar depressed patients to pharmacologically induced dopaminergic stimulation,8 which often provokes a switch into mania. One previous study failed to show differences in the G.H. response to levodopa between male unipolar and bipolar depressed patients, although there was a trend towards a greater response in the bipolar patients.5 Although the absence of male unipolars in our study precludes a direct comparison, it should also be noted that our patients were on a controlled monoamine diet at the time of levodopa stimulation. Fluctuations in dietary monoamines can apparently alter brain-amines in affective illness.9 Unipolar/bipolar differences in plateletmonoamine-oxidase activity’" might also affect the degree to which brain-dopamine levels are increased by a levodopa load. We have recently reported a unipolar/bipolar difference in the response of thyroid-stimulating-hormone to thyrotrophin releasing hormone."These two groups of neuroendocrine findings taken together are consistent with the hypothesis of a primary neurotransmitter difference between the subgroups.
Although
Section on Psychiatry, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20014, U.S.A.
PHILIP W. GOLD FREDERICK K. GOODWIN THOMAS WEHR
National Institute of Child Health and Human Development, Bethesda
ROBERT REBAR
of Psychiatry,
Palo Alto, California
Department of Radiology, Royal Southern Hospital, Liverpool L8 5SH
G. C. MARKHAM
metabolite studies also suggest
brain-amine alterations in subgroups of depressed patients.67
Department Stanford University,
instrument of choice for hysterosalpingography, particularly for assessment of tubal patency when patient should be comfortable and relaxed so that cornual spasm is avoided.
ROBERT SACK
CHOICE OF CANNULA IN HYSTEROSALPINGOGRAPHY
SIR,-In our experience with hysterosalpingographyl2 the procedure is painless twice as frequently with a cannula having a smooth tip and olive (Everard Williams) than with a screwtip cannula (Leech Wilkinson). Questionnaires were sent to 58 patients who had had hysterosalpingograms without anaesthetic or sedation. Screw-tip cannula? had been used in 31patients and smooth-tipped cannula: in 27. The instrumentation had been done by members of the gynaecological department, each using the cannula of his choice. All examinations were techni-
cally satisfactory. Instrumentation was painless in 14 patients (52%) with the smooth-tip cannula but in only 8 patients (26%) when the screw-tip cannula was used. This experience suggests that the Everard Williams smooth-tip cannula is the 6 Goodwin, F. K., Post, R. M. Psychopharmac. Comm. 1975, 1, 641. 7.Goodwin, F. K in Neuroregulators and Hypotheses of Psychiatric Disorders (edited by J. D. Barchas and E. Usdin).London (in the press). 8. Murphy, D. L., Brodie, H. K. H., Goodwin, F. K., et al. Nature, 1971, 229, 135 9. Muscettola, G., Wehr, T., Goodwin, F. K. Presented at American Psychiatric Association, May, 1976. 10. Murphy, D. L., Weiss, R. Am. J Psychiat. 1972, 128, 1351. 11. Gold, P., Rebar, R., Wehr, T., Goodwin, F. K. Presented at American Psychiatric Association, May, 1976. 12. Markham, G. C., the Br (in G. press). Ansell, J. Radiol. Bottomley, J. P.,
SCREENING FOR GONOCOCCAL SALPINGITIS risen sharply in years. In Bradford the number of cases of gonorrhoea in females increased from 28 in 1955 to 386 in 1975. If associated salpingitis occurs in about 10% of cases,! there should be 30-40 cases of gonococcal salpingitis in Bradford each year. However, in the twelve months before this study, the condition had not been diagnosed. It was decided to initiate a policy of
SIR, The incidence of gonorrhcea has
recent
uniform management of all patients admitted with suspected acute pelvic inflammatory disease and to make a specific medical officer responsible for implementation of the policy. In the year that followed, 48 patients were admitted to St Luke’s Hospital with a provisional diagnosis of acute pelvic inflammatory disease. Full bacteriological studies were undertaken before any treatment. If the patient was admitted at night, the swabs were taken at 9.00 A.M. the following morning. If the patient was admitted during working hours, swabs were taken immediately. Swabs were taken from urethra, cervix, and vagina, plated on chocolate agar, and incubated at 37°C in an atmosphere enriched by 10% carbon dioxide. Specimens were also taken with a loop from the urethra and cervix and were examined directly after staining for gram-negative intracellular diplococci. The diagnosis of gonorrhoea was considered proven only where gonococci were isolated from the swabs and culture was confirmed by fermentation tests. If the patient was on antibiotic therapy before admission, only a high vaginal swab was taken because further bacteriological tests were considered pointless. All patients had blood-samples taken for Wasserman reaction, Reiter protein complement-fixation test, gonococcal complement-fixation test, and Venereal Disease Research Laboratory test. All patients had a haemoglobin estimation, erythrocyte-sedimentation rate, white-blood-cell count, and culture of a midstream urine sample. The patients were monitored by four-hourly pulse and temperature charts. The provisional diagnosis of acute pelvic inflammatory disease was correct in only 21 of 48 cases. In 7 cases the diagnosis was incorrect (2 ectopic pregnancies, 2 urinary-tract infections, 1 twisted ovarian cyst, 1 bleeding corpus luteum, and 1 intrauterine pregnancy), and in the remaining 20 cases it was not possible to prove any diagnosis. 7 of the 21 patients with proven acute pelvic inflammatory disease had gonococcal salpingitis. Neisseria gonorrhaeae was not isolated in the other 14 proven cases, but the admission diagnosis of acute pelvic inflammatory disease was confirmed by laparoscopy on 10 occasions. In acute pelvic inflammatory disease, the rate of detection of gonorrhoea depends heavily on how thoroughly the disease is sought. By adhering to a simple routine, it was possible to make the diagnosis 7 times in a year. Despite our high index of suspicion, we diagnosed less than half the number of cases of gonococcal salpingitis that could have been expected on a statistical basis. It seems likely that many of these cases were treated by their general practitioners without a definite diagnosis being established. We thank Dr T. D. St Luke’s
Spencer for the bacteriological studies. J. G. FEENEY A. EL BADRI
Hospital,
Bradford, Yorkshire BD5 0NA
1. Rees, E., Annels, E. H. Br. J. ven. Dis 2. Sparks, R. A. Br. med J. 1975, iii, 346
1969, 45, 205
be
glance at a revealing.
naked
baby by
an
experienced observer can
most
11 Park Road
West,
Wolverhampton
H. EVERLEY
JONES
GROWTH-HORMONE AND PROLACTIN RESPONSE TO LEVODOPA IN AFFECTIVE ILLNESS
SIR,-We have found significant differences in plasmagrowth-hormone (G.H.) and prolactin responses to levodopa between subgroups of depressed and manic patients. Since monoamine neurotransmitters are important regulators of the hypothalamic/pituitary axis,’ these differential neuroendocrine responses may constitute markers of specific monoamine dysfunctions in subgroups of patients with affective illness. 20 patients with primary affective disorder diagnosed according to the criteria of Spitzer et al.2 and 10 healthy volunteers were studied in hospital. All subjects had a controlled monoamine diet and received no medication for 3 wk before the study. Since high oestrogen levels potentiate neuroendocrine responses to levodopa, premenopausal women were tested only during the first 5 days of the menstrual cycle, when oestrogen levels were low. After an overnight fast, all subjects received 500 mg of oral levodopa, and plasma was drawn sequentially over a 3 h period and analysed for growth hormone and prolactin. G.H. and prolactin were assayed by the double-antibody
technique. No relationship was sponses to levodopa and
found between neuroendocrine reage. There was no significant differ-
Fig. 1--Growth-hormone response to levodopa tients and controls (mean±S.B.M.).
in
depressed pa-
in G.H. or prolactin response to levodopa between the whole group of depressed patients and controls. However, the bipolar group had a significantly larger peak G.H. increment than did unipolar patients (P<0-01) or controls (p<0-01) (fig. 1). Bipolar patients showed a significantly greater suppression of levodopa-induced prolactin response (fig. 2) than unipolar patients (p<0’001) or controls (p<0.05); the baseline prolactin level was 35% higher in the bipolar compared to the unipolar patients, but this difference was not significant. Among the bipolar patients, those in the depressive phase showed a larger peak G.H. response (fig. 3) than those in the manic phase ence
Fig. 2-Prolactin suppression after levodopa (meamiS.E.M.).
administration
Fig. 3-Growth-hormone response to levodopa in depressed and manic phases in bipolar patients (meaniS.E.M.). In normal subjects, response to stimuli which release c,H. is related to circulating oestrogen levels,3 so that this response is highest in premenopausal women, intermediate in men, and somewhat lower in postmenopausal women.’To our knowledge prolactin response to levodopa is not influenced by oestrogen levels. Because sex and ovarian status are unequally distributed in our patient subgroups (unipolar depressed 5 premenopausal and 3 postmenopausal women; bipolar depressed 4 men, 3 premenopausal women; bipolar manic 5 premenopausal women; controls 4 men, 6 premenopausal women) we must consider the possibility that these factors contribute to the G,H.n
(p<0.05). 1. Frohman, L. A., Strachura, M. E. Metabolism, 1975, 24(2), 211. 2. Spitzer, R. L., Endicott, J., Robbins, E. Psychopharmac. Bull. 1975,
3. 4. 5.
11,
22.
Frantz, A. G., Rabkin, M. T. J. clin. Endocr. Metab. 1965, 25, 1470. Merimee, T. J., Fineberg, S. E. ibid. 1971, 33, 890. Sachar, D. J., Altman, N., Gruen, P. H., et al. Archs gen. Psychiat 1975, 32, 502.
1309 differences reported. Since all groups included premenopausal women, we used them to evaluate subgroup differences inde-
pendent of sex and ovarian status; the premenopausal bipolar depressed women still showed a significantly greater response and manics (P<005). Furtherthan the unipolars (P<0-02) more, among the men the bipolar depressed patients showed a significantly greater growth-hormone response than controls
lP(O.02). Spinal-fluid
and
urinary
the neurotransmitter regulation of G.H. is complex, the increased prolactin suppression in bipolar depressed patients, coupled with increased G.H. response in this group, implies that the dopaminergic system is hyperresponsive to exogenous stimulation. This interpretation is consistent with the sensitivity of bipolar depressed patients to pharmacologically induced dopaminergic stimulation,8 which often provokes a switch into mania. One previous study failed to show differences in the G.H. response to levodopa between male unipolar and bipolar depressed patients, although there was a trend towards a greater response in the bipolar patients.5 Although the absence of male unipolars in our study precludes a direct comparison, it should also be noted that our patients were on a controlled monoamine diet at the time of levodopa stimulation. Fluctuations in dietary monoamines can apparently alter brain-amines in affective illness.9 Unipolar/bipolar differences in plateletmonoamine-oxidase activity’" might also affect the degree to which brain-dopamine levels are increased by a levodopa load. We have recently reported a unipolar/bipolar difference in the response of thyroid-stimulating-hormone to thyrotrophin releasing hormone."These two groups of neuroendocrine findings taken together are consistent with the hypothesis of a primary neurotransmitter difference between the subgroups.
Although
Section on Psychiatry, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20014, U.S.A.
PHILIP W. GOLD FREDERICK K. GOODWIN THOMAS WEHR
National Institute of Child Health and Human Development, Bethesda
ROBERT REBAR
of Psychiatry,
Palo Alto, California
Department of Radiology, Royal Southern Hospital, Liverpool L8 5SH
G. C. MARKHAM
metabolite studies also suggest
brain-amine alterations in subgroups of depressed patients.67
Department Stanford University,
instrument of choice for hysterosalpingography, particularly for assessment of tubal patency when patient should be comfortable and relaxed so that cornual spasm is avoided.
ROBERT SACK
CHOICE OF CANNULA IN HYSTEROSALPINGOGRAPHY
SIR,-In our experience with hysterosalpingographyl2 the procedure is painless twice as frequently with a cannula having a smooth tip and olive (Everard Williams) than with a screwtip cannula (Leech Wilkinson). Questionnaires were sent to 58 patients who had had hysterosalpingograms without anaesthetic or sedation. Screw-tip cannula? had been used in 31patients and smooth-tipped cannula: in 27. The instrumentation had been done by members of the gynaecological department, each using the cannula of his choice. All examinations were techni-
cally satisfactory. Instrumentation was painless in 14 patients (52%) with the smooth-tip cannula but in only 8 patients (26%) when the screw-tip cannula was used. This experience suggests that the Everard Williams smooth-tip cannula is the 6 Goodwin, F. K., Post, R. M. Psychopharmac. Comm. 1975, 1, 641. 7.Goodwin, F. K in Neuroregulators and Hypotheses of Psychiatric Disorders (edited by J. D. Barchas and E. Usdin).London (in the press). 8. Murphy, D. L., Brodie, H. K. H., Goodwin, F. K., et al. Nature, 1971, 229, 135 9. Muscettola, G., Wehr, T., Goodwin, F. K. Presented at American Psychiatric Association, May, 1976. 10. Murphy, D. L., Weiss, R. Am. J Psychiat. 1972, 128, 1351. 11. Gold, P., Rebar, R., Wehr, T., Goodwin, F. K. Presented at American Psychiatric Association, May, 1976. 12. Markham, G. C., the Br (in G. press). Ansell, J. Radiol. Bottomley, J. P.,
SCREENING FOR GONOCOCCAL SALPINGITIS risen sharply in years. In Bradford the number of cases of gonorrhoea in females increased from 28 in 1955 to 386 in 1975. If associated salpingitis occurs in about 10% of cases,! there should be 30-40 cases of gonococcal salpingitis in Bradford each year. However, in the twelve months before this study, the condition had not been diagnosed. It was decided to initiate a policy of
SIR, The incidence of gonorrhcea has
recent
uniform management of all patients admitted with suspected acute pelvic inflammatory disease and to make a specific medical officer responsible for implementation of the policy. In the year that followed, 48 patients were admitted to St Luke’s Hospital with a provisional diagnosis of acute pelvic inflammatory disease. Full bacteriological studies were undertaken before any treatment. If the patient was admitted at night, the swabs were taken at 9.00 A.M. the following morning. If the patient was admitted during working hours, swabs were taken immediately. Swabs were taken from urethra, cervix, and vagina, plated on chocolate agar, and incubated at 37°C in an atmosphere enriched by 10% carbon dioxide. Specimens were also taken with a loop from the urethra and cervix and were examined directly after staining for gram-negative intracellular diplococci. The diagnosis of gonorrhoea was considered proven only where gonococci were isolated from the swabs and culture was confirmed by fermentation tests. If the patient was on antibiotic therapy before admission, only a high vaginal swab was taken because further bacteriological tests were considered pointless. All patients had blood-samples taken for Wasserman reaction, Reiter protein complement-fixation test, gonococcal complement-fixation test, and Venereal Disease Research Laboratory test. All patients had a haemoglobin estimation, erythrocyte-sedimentation rate, white-blood-cell count, and culture of a midstream urine sample. The patients were monitored by four-hourly pulse and temperature charts. The provisional diagnosis of acute pelvic inflammatory disease was correct in only 21 of 48 cases. In 7 cases the diagnosis was incorrect (2 ectopic pregnancies, 2 urinary-tract infections, 1 twisted ovarian cyst, 1 bleeding corpus luteum, and 1 intrauterine pregnancy), and in the remaining 20 cases it was not possible to prove any diagnosis. 7 of the 21 patients with proven acute pelvic inflammatory disease had gonococcal salpingitis. Neisseria gonorrhaeae was not isolated in the other 14 proven cases, but the admission diagnosis of acute pelvic inflammatory disease was confirmed by laparoscopy on 10 occasions. In acute pelvic inflammatory disease, the rate of detection of gonorrhoea depends heavily on how thoroughly the disease is sought. By adhering to a simple routine, it was possible to make the diagnosis 7 times in a year. Despite our high index of suspicion, we diagnosed less than half the number of cases of gonococcal salpingitis that could have been expected on a statistical basis. It seems likely that many of these cases were treated by their general practitioners without a definite diagnosis being established. We thank Dr T. D. St Luke’s
Spencer for the bacteriological studies. J. G. FEENEY A. EL BADRI
Hospital,
Bradford, Yorkshire BD5 0NA
1. Rees, E., Annels, E. H. Br. J. ven. Dis 2. Sparks, R. A. Br. med J. 1975, iii, 346
1969, 45, 205