J. Endocrinol. Invest. 13: 247 -249, 1990
CASE REPORT
Hyperprolactinemia and temporal lobe epilepsy in a woman: concomitant and persistent prolactin suppression and temporal lobe epi lepsy relief A. Gattereau, J. Vezina,
s. Rousseau, and P. Bielmann
Sections of Endocrinology, Neuro-Radiology and Gynaecology, Höpital Hötel-Dieu and Universite de Montreal, Montreal, Ouebec, Canada ABSTRACT. It has been reported that' hyperprolactinemia may be associated with increased temporal lobe activity. Coexisting hyperprolactinemia (97.5 ± 3.2 ng/ml) related to a pituitary tumefaction (8 mm) and Temporal Lobe Epilepsy (TLE), were observed in a 37-year-old woman. Carbamazepin (CBZ) therapy induced a marked improvement in TLE symptoms and EEG recordings, but did not influence hyperprolactinemia and related symp~ toms. Long-Iasting (27 months) normoprolactinemia (19.4 ± 0.6 ng/ml) and TLE relief were
achieved on a dopamine (DA) agonist medication, e.g. pergolide mesylate, 25-50 }.Lg/day given over 8 months, and persisted as long as 27 months after drug withdrawal. Posttreatment CT scans showed progressive shrinkage of the pituitary tumor (2 mm) associated with an empty-sella. It is proposed that, whenever TLE and hyperprolactinemia coexist, therapy with a DA agonist such as pergolide mesylate, resulting in normoprolactinemia, may be beneficial in TLE control.
INTRODUCTION There is some evidence in humäns (1-3) to implicate hyperprolactinemia in the pathogenesis of sexual and reproductive dysfonction in relation to Temporal Lobe Epilepsy (TLE). This report describes the findings in a woman presenting with hyperprolactinemia and TLE, in whom long-Iasting normoprolactinemia and TLE relief persisted as long as 27 months after treatment with pergolide mesylate, a dopamine agonist (DA), has been stopped.
tour years duration. In early 1983, she received a 3-month course of bromocriptin which she did not . tolerate. When seen by us, clinical examination was not remarkable except for moderate and generalized obesity. She was not hirsute. Galactorrhea was abse nt. Surgical reduction of the breasts was performed four months previously. Anormal size uterus, with severe atrophia of the endometrium, was noted. The gonads were not palpable, nor visualized by ultrasound. Visual fields were normal. Pretreatment serum prolactin (PRL) levels were increased (97.5 ± 3.2 ng/ml) and PRL responses to TRH (Fig. 1), to chlorpromazine (CPZ) and to Ldopa, were impaired. The patterns were consistent with autonomy of the PRL-cells as usually reported with prolactinomas (4, 5). Serum GH was normal (1.46 ± 0.09 ng/ml) and responses to CPZ and to L-dopa was appropriate. Basal serum concentrations of the other pituitary hormones were normal (TSH, 2.25 ± 0.05 }.LU/mi; FSH, 16.1 ± 1.4 mIU/ml; LH, 11.6 ± 0.9 mIU/ml) with optimal responses to their standard stimuli. Serum estrogens (E1 + E2, 51.1 ± 4.9 pg/ml) were low. Other peripheral hormone levels were within the normal ranges (TT 4,
CASE HISTORY A 37-year-old woman, gravida 2, para 2, was admitted to our hospital in 1984 for hyperprolactinemia and TLE. She had a history of amenorrhea, decreased libido, galactorrhea, headaches and transient episodes of disorientation and absences, of
Key-words. Prolactinoma. hyperprolactinoma, TLE. pergolide mesylate. Correspondenee: Dr. A. Gattereau, Höpital Hötel-Dleu, 3840 St-Urbain. Montreal (quebee). CANADA H2W 1T8 Reeeived March 15, 1989; aeeepted Oetober 2. 1989.
247
A. Gattereau, J. Vezina,
s. Rousseau, et al.
130 120 110 100
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-'
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60
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PRE-TREATMENT PER 100 I FES. 1984 I
. . . - PRE-TREATMENT PERIOD I MAV 1984 I
0
0-
50
0
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TREATMENT PER IOD I MAV 1985 I
. . . - POST-TREATMENT PERIOD I APR. 1986 I
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-15
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- ---0- - - - - - ---0
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TIME ( minutes )
120
Fig . 1 - Serum prolactin responses to TRH, 200 /1g iv belore, during and after pergolide treatment.
8.5 ± 0.2 J,Lg/ dl, TT3, 104.5 ± 1.4' ng/ dl; cortisol [00:00], 19.5, [20:00], 8.2 J,Lg/ml). A CT scan made in coronal plane (1984) demonstrated fullness and isodense tumefaction of the pituitary gland measuring 8 mm in size on the right side, indicative of a pituitary adenoma. TLE was documented by EEG, using sphenoidal leads. Paroxysmal epileptic activity was recorded from bilateral mesiobasal and anterior temporal regions. Magnetic resonance imaging (MRI) revealed an area of gliosis and demyelination in the right temporal lobe (Fig. 2). A 3 1/2 month carbamazepin (CBZ, 400 mg per day) therapy resulted in marked improvement of TLE symptoms and EEG recordings while serum PRL levels (95.6 ± 7.8 ng/ml) were not influenced . In order to test the therapeutic effect of a DA agonist on both hyperprolactinemia and TLE, CBZ was stopped and replaced six weeks later by pergolide mesylate at a dose of 50 J,Lg alternating with 25 J,Lg every other day for 8 months. This medication resulted in resumption of menstruation and libido, complete remission of TLE symptoms and sustained improvement of EEG recordings. No further anticonvulsant therapy was required. Serum PRL levels decreased trom 97.5 ± 3.2 ng/ml to normal values (10.0 ± 0.7 ng/ml) after 12 days of medication while PRL response to TRH was still suppressed
Fig. 2 - Axial MR image of the brain showing an areaof highsignal (arrow) in the central right temporal lobe indicative of gliosis or demyelination (SE 0.5 Tesla, TR = 220 msec, TE = 30 msec).
248
Hyperprolactinemia, TLE and pergolide mesylate
(Fig. 1). Clinical recovery and normoprolactinemia persisted up to the last visit in September 1987, 27 months after cessation of pergolide. The mean of four PRL serum concentrations measured at 4 to 6 months interval over the post-treatment period was 19.4 ± 0.66 ng/ml. PRL response to TRH tested in April 1986 (Fig. 1) was sluggish. Posttreatment EEG recordings were unchanged. Follow-up CT scans made in 1986 and 1987 showed progressive decrease in size of the pituitary gland now measuring 2 mm in height and associated with an invagination of the arachnoid to fill the partially emptied sella.
tinemia coexist, treatment with a DA such as pergo lide mesylate may be beneficial in TLE control.
DISCUSSION
REFERENCES
ACKNOWLEDGMENTS We gratelully acknowledge the technical help 01 Mr. Yves Courchesne, pharmacist; Drs. D. Boghen, Perez-de-Leon and Louise Berube, Sections 01 Neurology and Neuro-Ophtalmology, HotelDieu Hospital; and the secretarial assistance 01 Mrs Sylvie Sauve. We wish to thank the medical department 01 Lilly Research Laboratories (Indianapolis) lor the generous gift 01 pergolide mesylate.
1. Herzog A.G., Sei bel M.M., Schomer O.L., Vaitukaitis J.L., Geschwind N. Reproductive endocrine disorders in women with partial seizures of temporal lobe origin. Arch Neurol. 43: 341, 1986.
The distlnctive aspect of our report is the concomitant and persistant normoprolactinemia ·and TLE relief, following a DA withdrawal, in a female presenting with hyperprolactinemia (97.5 ± 3.2 ng/ml) associated with an enlarged pituitary gland, and concomitant Temporal Lobe Epilepsy. Whether our patient had an adenoma or hyperplasia of the PRLcells is uncertain. There is some evidence, in humans, to implicate hyperprolactinemia as·a cause of sexual and reproductive dysfunction in relation to TLE (1-3). Recently, Spark et al. (3) reported on two men with TLE, whose PRL levels became normal and sexual function was restored on anticonvulsant therapy alone. In our case, carbamazepin had no effect on prolactin secretion. TLE symptoms did not recur after normoprolactinemia was achieved on pergolide medication and during the post-treatment period. Thus, our observation is in accordance with the view that hyperprolactinemia may be associated with increased TLE activity (1). It is proposed that whenever TLE and hyperprolac-
2. Herzog A.G., Sei bel M.M., Schomer O.L., Vaitukaitis J.L., Geschwind N. Reproductive endocrine disorders in men with partial seizures of temporal lobe origin. Arch Neurol. 43: 347, 1986.
3. Spark R.F., Wills CA, Royal H. Hypogonadism, hyperprolactinaemia, and temporal lobe epilepsy in hyposexual men. Lancet 1: 413, 1984. 4. Müller E.E., Cavagnini F., Martinez-Campos A., Maraschini C., Giovannini P., Novelli A., Oe Leo V. Oynamic testing of prolactin and growth hormone secretion in patients with neuroendocrine disorders. Acta Endocrinol. (Copenh) 107: 155, 1984. 5. Grossman A., Besser G.M. Prolactinomas. Br. Med. J. 290: 182, 1985.
249
CASE REPORT
Hyperprolactinemia and temporal lobe epilepsy in a woman: concomitant and persistent prolactin suppression and temporal lobe epi lepsy relief A. Gattereau, J. Vezina,
s. Rousseau, and P. Bielmann
Sections of Endocrinology, Neuro-Radiology and Gynaecology, Höpital Hötel-Dieu and Universite de Montreal, Montreal, Ouebec, Canada ABSTRACT. It has been reported that' hyperprolactinemia may be associated with increased temporal lobe activity. Coexisting hyperprolactinemia (97.5 ± 3.2 ng/ml) related to a pituitary tumefaction (8 mm) and Temporal Lobe Epilepsy (TLE), were observed in a 37-year-old woman. Carbamazepin (CBZ) therapy induced a marked improvement in TLE symptoms and EEG recordings, but did not influence hyperprolactinemia and related symp~ toms. Long-Iasting (27 months) normoprolactinemia (19.4 ± 0.6 ng/ml) and TLE relief were
achieved on a dopamine (DA) agonist medication, e.g. pergolide mesylate, 25-50 }.Lg/day given over 8 months, and persisted as long as 27 months after drug withdrawal. Posttreatment CT scans showed progressive shrinkage of the pituitary tumor (2 mm) associated with an empty-sella. It is proposed that, whenever TLE and hyperprolactinemia coexist, therapy with a DA agonist such as pergolide mesylate, resulting in normoprolactinemia, may be beneficial in TLE control.
INTRODUCTION There is some evidence in humäns (1-3) to implicate hyperprolactinemia in the pathogenesis of sexual and reproductive dysfonction in relation to Temporal Lobe Epilepsy (TLE). This report describes the findings in a woman presenting with hyperprolactinemia and TLE, in whom long-Iasting normoprolactinemia and TLE relief persisted as long as 27 months after treatment with pergolide mesylate, a dopamine agonist (DA), has been stopped.
tour years duration. In early 1983, she received a 3-month course of bromocriptin which she did not . tolerate. When seen by us, clinical examination was not remarkable except for moderate and generalized obesity. She was not hirsute. Galactorrhea was abse nt. Surgical reduction of the breasts was performed four months previously. Anormal size uterus, with severe atrophia of the endometrium, was noted. The gonads were not palpable, nor visualized by ultrasound. Visual fields were normal. Pretreatment serum prolactin (PRL) levels were increased (97.5 ± 3.2 ng/ml) and PRL responses to TRH (Fig. 1), to chlorpromazine (CPZ) and to Ldopa, were impaired. The patterns were consistent with autonomy of the PRL-cells as usually reported with prolactinomas (4, 5). Serum GH was normal (1.46 ± 0.09 ng/ml) and responses to CPZ and to L-dopa was appropriate. Basal serum concentrations of the other pituitary hormones were normal (TSH, 2.25 ± 0.05 }.LU/mi; FSH, 16.1 ± 1.4 mIU/ml; LH, 11.6 ± 0.9 mIU/ml) with optimal responses to their standard stimuli. Serum estrogens (E1 + E2, 51.1 ± 4.9 pg/ml) were low. Other peripheral hormone levels were within the normal ranges (TT 4,
CASE HISTORY A 37-year-old woman, gravida 2, para 2, was admitted to our hospital in 1984 for hyperprolactinemia and TLE. She had a history of amenorrhea, decreased libido, galactorrhea, headaches and transient episodes of disorientation and absences, of
Key-words. Prolactinoma. hyperprolactinoma, TLE. pergolide mesylate. Correspondenee: Dr. A. Gattereau, Höpital Hötel-Dleu, 3840 St-Urbain. Montreal (quebee). CANADA H2W 1T8 Reeeived March 15, 1989; aeeepted Oetober 2. 1989.
247
A. Gattereau, J. Vezina,
s. Rousseau, et al.
130 120 110 100
-
. -
E
90
10
Oll
z
~
u
c(
-'
70
,.-«
60
a:
"-
PRE-TREATMENT PER 100 I FES. 1984 I
. . . - PRE-TREATMENT PERIOD I MAV 1984 I
0
0-
50
0
0{]
TREATMENT PER IOD I MAV 1985 I
. . . - POST-TREATMENT PERIOD I APR. 1986 I
30 20 10 0
-15
_ _ o{}-". -
o
_0-- - - ' 0 - - - . -0-. - - ; : ) - . - - -
IS
3
4S
60
- ---0- - - - - - ---0
90
TIME ( minutes )
120
Fig . 1 - Serum prolactin responses to TRH, 200 /1g iv belore, during and after pergolide treatment.
8.5 ± 0.2 J,Lg/ dl, TT3, 104.5 ± 1.4' ng/ dl; cortisol [00:00], 19.5, [20:00], 8.2 J,Lg/ml). A CT scan made in coronal plane (1984) demonstrated fullness and isodense tumefaction of the pituitary gland measuring 8 mm in size on the right side, indicative of a pituitary adenoma. TLE was documented by EEG, using sphenoidal leads. Paroxysmal epileptic activity was recorded from bilateral mesiobasal and anterior temporal regions. Magnetic resonance imaging (MRI) revealed an area of gliosis and demyelination in the right temporal lobe (Fig. 2). A 3 1/2 month carbamazepin (CBZ, 400 mg per day) therapy resulted in marked improvement of TLE symptoms and EEG recordings while serum PRL levels (95.6 ± 7.8 ng/ml) were not influenced . In order to test the therapeutic effect of a DA agonist on both hyperprolactinemia and TLE, CBZ was stopped and replaced six weeks later by pergolide mesylate at a dose of 50 J,Lg alternating with 25 J,Lg every other day for 8 months. This medication resulted in resumption of menstruation and libido, complete remission of TLE symptoms and sustained improvement of EEG recordings. No further anticonvulsant therapy was required. Serum PRL levels decreased trom 97.5 ± 3.2 ng/ml to normal values (10.0 ± 0.7 ng/ml) after 12 days of medication while PRL response to TRH was still suppressed
Fig. 2 - Axial MR image of the brain showing an areaof highsignal (arrow) in the central right temporal lobe indicative of gliosis or demyelination (SE 0.5 Tesla, TR = 220 msec, TE = 30 msec).
248
Hyperprolactinemia, TLE and pergolide mesylate
(Fig. 1). Clinical recovery and normoprolactinemia persisted up to the last visit in September 1987, 27 months after cessation of pergolide. The mean of four PRL serum concentrations measured at 4 to 6 months interval over the post-treatment period was 19.4 ± 0.66 ng/ml. PRL response to TRH tested in April 1986 (Fig. 1) was sluggish. Posttreatment EEG recordings were unchanged. Follow-up CT scans made in 1986 and 1987 showed progressive decrease in size of the pituitary gland now measuring 2 mm in height and associated with an invagination of the arachnoid to fill the partially emptied sella.
tinemia coexist, treatment with a DA such as pergo lide mesylate may be beneficial in TLE control.
DISCUSSION
REFERENCES
ACKNOWLEDGMENTS We gratelully acknowledge the technical help 01 Mr. Yves Courchesne, pharmacist; Drs. D. Boghen, Perez-de-Leon and Louise Berube, Sections 01 Neurology and Neuro-Ophtalmology, HotelDieu Hospital; and the secretarial assistance 01 Mrs Sylvie Sauve. We wish to thank the medical department 01 Lilly Research Laboratories (Indianapolis) lor the generous gift 01 pergolide mesylate.
1. Herzog A.G., Sei bel M.M., Schomer O.L., Vaitukaitis J.L., Geschwind N. Reproductive endocrine disorders in women with partial seizures of temporal lobe origin. Arch Neurol. 43: 341, 1986.
The distlnctive aspect of our report is the concomitant and persistant normoprolactinemia ·and TLE relief, following a DA withdrawal, in a female presenting with hyperprolactinemia (97.5 ± 3.2 ng/ml) associated with an enlarged pituitary gland, and concomitant Temporal Lobe Epilepsy. Whether our patient had an adenoma or hyperplasia of the PRLcells is uncertain. There is some evidence, in humans, to implicate hyperprolactinemia as·a cause of sexual and reproductive dysfunction in relation to TLE (1-3). Recently, Spark et al. (3) reported on two men with TLE, whose PRL levels became normal and sexual function was restored on anticonvulsant therapy alone. In our case, carbamazepin had no effect on prolactin secretion. TLE symptoms did not recur after normoprolactinemia was achieved on pergolide medication and during the post-treatment period. Thus, our observation is in accordance with the view that hyperprolactinemia may be associated with increased TLE activity (1). It is proposed that whenever TLE and hyperprolac-
2. Herzog A.G., Sei bel M.M., Schomer O.L., Vaitukaitis J.L., Geschwind N. Reproductive endocrine disorders in men with partial seizures of temporal lobe origin. Arch Neurol. 43: 347, 1986.
3. Spark R.F., Wills CA, Royal H. Hypogonadism, hyperprolactinaemia, and temporal lobe epilepsy in hyposexual men. Lancet 1: 413, 1984. 4. Müller E.E., Cavagnini F., Martinez-Campos A., Maraschini C., Giovannini P., Novelli A., Oe Leo V. Oynamic testing of prolactin and growth hormone secretion in patients with neuroendocrine disorders. Acta Endocrinol. (Copenh) 107: 155, 1984. 5. Grossman A., Besser G.M. Prolactinomas. Br. Med. J. 290: 182, 1985.
249
