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Assessment by computed tomography of the response of pituitary macroadenomas to bromocriptine
ClinicalRadiology (1985)36,223-226 © 1985Royal Collegeof Radiologists
0009-9260/85/376223502.00
Assessment by Computed Tomography of the Response of Pituitary Macroadenomas to Bromocriptine T. M. H. C H A K E R A , M. S. K H A N G U R E and P. P U L L E N *
Department of Diagnostic Radiology, Royal Perth Hospital, Wellington Street, Perth, Western Australia 6000 and *Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Q.E. H Medical Centre, Nedlands, Western Australia 6009
Eleven patients with large pituitary tumours and with extrasellar extension were studied prospectively to assess the response of these tumours to bromocriptine. Five out of the six patients with high serum prolactin due to prolactinomas showed rapid and dramatic reduction in tumour size when treated with bromocriptine. In contrast, none of the five patients with non-functioning tumours showed any change in tumour size on computed tomography.
et al., 1982)_ To assess this critically a prospective study of 11 patients with large pituitary tumours was undertaken at the Royal Perth Hospital. All of these patients had extrasellar extensions with varying degrees of visual field loss and endocrine dysfunction. None of the patients had received radiotherapy or bromocriptine previously. All patients were treated with the maximum tolerated dose of bromocriptine (20-30 mg/day).
PATIENTS AND M E T H O D S
In the early 1970s it was discovered that dopaminergic drugs lowered elevated prolactin levels in patients with pituitary adenomas secreting this hormone. The treatment of small, prolactin-secreting pituitary adenomas with bromocriptine is now widely accepted (Hancock et al., 1980) but this treatment for large tumours with extrasellar extension is more controversial, surgery being the accepted conventional treatment (Teasdale, 1983). There are, however, small but definite risks attached to pituitary surgery and hormonal cure is not always achieved (Nabarro, 1982). Recently, a number of reports have suggested that patients with large, secreting pituitary tumours and with associated compressive signs respond rapidly to bromocriptine therapy (McGregor et al., 1979; Scotti Address for reprints: Dr T. M. H. Chakera, Department of Diagnostic Radiology, Royal Perth Hospital, Box X 2213 G.P.O., Perth, Western Australia.
The patients were examined on a Siemens Somatom 2, third generation computed tomography (CT) scanner. In eight patients, direct coronal scans were obtained and the remaining three patients, who were elderly and unable to hyperextend their necks, had to have conventional axial slices with coronal reconstruction. The coronal scans were performed with the patient lying supine on a wedge mattress and with the head hyperextended. All patients were scanned following a bolus injection of 100 ml of Urografin 76% (sodium diatrizoate and meglumine diatrizoate; Schering A G ) delivering a dose of 37 g of iodine. In every case a 'topogram' (scout view) was carried out for correct positioning. The topogram was photographed to obtain a permanent record of the patient position and gantry angulation. This allows accurate
Table 1 - Prolactinomas
Patient G,H. Age (years) Sex Compressive problem Endocrine problem Serum prolactin Pre-treatment On treatment CT Pre-treatment On treatment Clinical response Pressure signs Endocrine symptoms
I.H.
S.W.
J.C.
31 M Bitemporal field defect Reduced libido, galactorrhoea
34 M Nil
24 F Nil
Reduced libido, galactorrhoea
42 M R temporal hemianopia Reduced libido
1300 13
7800 8
2690 2
180 22
Suprasellar extension
Para-/infrasellar Suprasellar extension extension
Large parasellar Para-/suprasellar tumour extension
Marked reduction
No c h a n g e
Significant reduction
Marked reduction
Marked reduction
Gross supra- & R parasellar extension Marked reduction
Complete resolution Complete resolution
Nil
Complete resolution Complete resolution
Nil
Marked improvement On replacement therapy
Complete resolution Marked improvement
Complete resolution
Galactorrhoea, amenorrhoea
Complete resolution
H.N.
J.O.
66
47 M R 3rd, 4th nerve palsy Panhypopituitarism Impotence
M Nil
6200 32
7830 105
224
CLINICAL RAD|OLOGY
comparison and assessment of regression of tumour with bromocriptine therapy (Chakera, 1982). We feel that with the availability of the topogram facility on most new CT scanners there is no need for invasive techniques such as air encephalography or metrizamide cisternography, as suggested by other authors (Wass et al., 1982) for accurate assessment of tumour regression.
RESULTS Our patients were divided into two groups, depending on the level of the serum prolactin. The six patients in Group A had an elevated serum prolactin and were considered to have prolactinomas (Table 1). The five patients in Group B had normal serum prolactin levels and clearly had non-functioning Table 2 - N o n - f u n c t i o n i n g
tumours (Table 2)_ Patients in both groups were endocrinologically assessed by one of the authors (P.P.).-Visual field charts were obtained in all patients. Bromocriptine was prescribed in maximum tolerated doses aiming for approximately 20-30 mg/day in three equally divided doses. The primary purpose of prescribing bromocriptine in these patients was to reduce tumour size, although the inhibition of lactation and reversal of hypogonadism was also desired in some patients_ All but one patient in Group A showed a significant reduction in tumour size. Patients were scanned 2 weeks, 4 weeks and 3 months after commencing bromocriptine therapy. Subsequently, all patients living in the metropolitan region have had follow-up scans at 4-monthly intervals. Follow-up period varied from 3 months to 20 months with a mean follow-up time of 14 months.
tumours Patient
Age (years) Sex Compressive problems Endocrine problems Serum prolactin Pre-treatment On treatment CT Pre-treatment Post-treatment Clinical response Pressure signs Endocrine symptoms
M.C.
T.McA.
J.C.
D.G.
M.S.
74 F Bitemporal hemianopia Eupituitary
75 M Nil Panhypopituitarism
71 M Bitemporal hemianopia Impotence
42 M L temporal quadrantanopia Hypothyroid
79 F Severe bitemporal hemianopia Eupituitary
70 1
16 1
Large suprasellar extension No change
Large suprasellar extension No change
Large suprasellar extension No change
Large suprasellar extension No change
Large suprasellar extension No change
No change
No change
No change
No change
No change
No change
Minimal reduction in size Still impotent
On replacement therapy
No change
(a)
7 1
7
18
1
1
(b)
Fig. 1 - (a) Coronal scan of patient S.W. taken in April 1983 showing a large, uniformly contrast-enhancing pituitary tumour. Note suprasellar extension with obliteration of the chiasmatic cistern. The optic chiasm is not identifiable. There is also expansion of the sella turcica and downward extension of tumour into the sphenoid sinus. (b) Coronal scan of S.W. in July 1983 showing significant reduction of tumour size. The suprasellar extension is less marked. (Note that the appearance of the sella floor and sphenoid sinus is identical to that in Fig. l(a), confirming that an accurate comparison of tumour size can be made without resorting to invasive neuroradiology.) (L +40, W 256.)
225
RESPONSE OF PITUITARY TUMOURS TO BROMOCRIPTINE
DISCUSSION Reduction in size occurred within 14-30 days of starting bromocriptine therapy in most cases (Fig. 1)_ A single patient in Group A (I.H.) who showed no reduction in tumour size improved endocrinologically. He regained his potency and his galactorrhoea ceased. His tumour had broken through the cavernous sinus into the superior orbital fissure (Fig. 2). Another patient in Group A (J.O.) had tumour extending into the basal ganglia. This patient's psychiatric problems, as well as his visual field abnormality, resolved with tumour regression on bromocriptine therapy (Fig. 3). In Group B one patient (J.C.) demonstrated minimal decrease in tumour size with corresponding slight improvement in the visual field defect. He is being treated with bromocriptine on a long-term basis. One other young patient in Group B has undergone
surgery. Of the remaining three patients, two have refused surgery and one is considered to be unfit for surgery. Recently, there has been a report of a single case of macroprolactinoma in which bromocriptine failed to maintain tumour regression. Initially, the patient responded with an improvement in the visual fields and tumour shrinkage was confirmed by CT scanning. Subsequently, there was regrowth of the tumour despite an increase in the dosage of bromocriptine (Breidahl et al., 1983). Notwithstanding this case .report of the failure of bromocriptine therapy, we suggest that bromocriptine is an effective and safe way to treat macroprolactinomas with extrasellar extension and chiasmatic compression, but recognise that bromocriptine may not provide long-term control of tumour growth in all patients. Finally, we feel that with the new third- and
R
(a)
(b)
Fig. 2 - (a) Coronal CT scan of patient I.H. A large pituitary tumour has expanded the sella turcica and is invading both the cavernous sinuses, Note that there is no suprasellar extension, The optic chiasm is clearly seen, (b) A more anterior slice of thc coronal CT scan of patient I.H, showing tumour invading the left inferior orbital fissure on the left (curved arrow). (L +40, W 256.)
(a)
(b)
Fig. 3 - (a) Axial CT scan of patient J,O. in March 1983 with coronal reconstruction, showing a large pituitary tumour with eccentric superior extension of the tumour into the right basal ganglia (L +50, W 128). (b) Follow-up CT scan of J.O. in May 1983 showing marked tumour regression seen both in axial plane and in the coronal reconstruction (L +51, W 256).
226
CLINICAL RADIOLOGY
fourth-generation CT scanners, follow-up CT scans can be obtained in identical positions to enable an accurate comparison of tumour size and assessment of the response to therapy without resorting to invasive neuroradiological procedures_ REFERENCES
Breidahl, H. D., Topliss, D. J. & Pike, J. W. (1983). Failure of bromocriptme to maintain reduction in size of macroprolactinoma. British Medical Journal, 287, 451-452. Chakera, T. M. H (1982). Bromocriptine in management of large pituitary tumours. British Medical Journal, 285, 444. Hancock, K. W , Scott, J. S., Lamb, J. T., Myles Gibson, R. & Chapman, C. (1980). Conservative management of pituitary
prolactinomas: evidence for bromocriptine induced regression. British Journal of Obstetrics and Gynaecology, 87, 523-529. McGregor, A. M., Seanlon, M. F., Hall, R. & Hall, K. (1979). Effects of bromocriptine on pituitary tumour size. British Medical Journal, ii, 700--703. Nabarro, J. D. N. (1982). Pituitary prolactinomas. Clinical Endocrinology, 17, 129-155. Scotti, G., Scialfa, G., Pieralli, S., Chiondini, P. G., Spelta, B. & Dellabonazana, D. (1982). Macroprolactinomas: CT evaluation of reduction of tumour size after medical treatment. Neuro. radiology, 23, 123-126. Teasdale, G. (1983). Surgical management of pituitary adenomas. Clinics in Endocrinology and Metabolism, 12, 789-823. Wass, J. A. H., Williams, J., Charles, M., Kingsley, D. P. E., Halliday, A. M., Doniach, I., Rees, L. H., McDonald, W. I. & Besser, G. M. (1982). Bromocriptine in management of large pituitary turnouts. British Medical Journal, 284, 1908-1911.
0009-9260/85/376223502.00
Assessment by Computed Tomography of the Response of Pituitary Macroadenomas to Bromocriptine T. M. H. C H A K E R A , M. S. K H A N G U R E and P. P U L L E N *
Department of Diagnostic Radiology, Royal Perth Hospital, Wellington Street, Perth, Western Australia 6000 and *Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Q.E. H Medical Centre, Nedlands, Western Australia 6009
Eleven patients with large pituitary tumours and with extrasellar extension were studied prospectively to assess the response of these tumours to bromocriptine. Five out of the six patients with high serum prolactin due to prolactinomas showed rapid and dramatic reduction in tumour size when treated with bromocriptine. In contrast, none of the five patients with non-functioning tumours showed any change in tumour size on computed tomography.
et al., 1982)_ To assess this critically a prospective study of 11 patients with large pituitary tumours was undertaken at the Royal Perth Hospital. All of these patients had extrasellar extensions with varying degrees of visual field loss and endocrine dysfunction. None of the patients had received radiotherapy or bromocriptine previously. All patients were treated with the maximum tolerated dose of bromocriptine (20-30 mg/day).
PATIENTS AND M E T H O D S
In the early 1970s it was discovered that dopaminergic drugs lowered elevated prolactin levels in patients with pituitary adenomas secreting this hormone. The treatment of small, prolactin-secreting pituitary adenomas with bromocriptine is now widely accepted (Hancock et al., 1980) but this treatment for large tumours with extrasellar extension is more controversial, surgery being the accepted conventional treatment (Teasdale, 1983). There are, however, small but definite risks attached to pituitary surgery and hormonal cure is not always achieved (Nabarro, 1982). Recently, a number of reports have suggested that patients with large, secreting pituitary tumours and with associated compressive signs respond rapidly to bromocriptine therapy (McGregor et al., 1979; Scotti Address for reprints: Dr T. M. H. Chakera, Department of Diagnostic Radiology, Royal Perth Hospital, Box X 2213 G.P.O., Perth, Western Australia.
The patients were examined on a Siemens Somatom 2, third generation computed tomography (CT) scanner. In eight patients, direct coronal scans were obtained and the remaining three patients, who were elderly and unable to hyperextend their necks, had to have conventional axial slices with coronal reconstruction. The coronal scans were performed with the patient lying supine on a wedge mattress and with the head hyperextended. All patients were scanned following a bolus injection of 100 ml of Urografin 76% (sodium diatrizoate and meglumine diatrizoate; Schering A G ) delivering a dose of 37 g of iodine. In every case a 'topogram' (scout view) was carried out for correct positioning. The topogram was photographed to obtain a permanent record of the patient position and gantry angulation. This allows accurate
Table 1 - Prolactinomas
Patient G,H. Age (years) Sex Compressive problem Endocrine problem Serum prolactin Pre-treatment On treatment CT Pre-treatment On treatment Clinical response Pressure signs Endocrine symptoms
I.H.
S.W.
J.C.
31 M Bitemporal field defect Reduced libido, galactorrhoea
34 M Nil
24 F Nil
Reduced libido, galactorrhoea
42 M R temporal hemianopia Reduced libido
1300 13
7800 8
2690 2
180 22
Suprasellar extension
Para-/infrasellar Suprasellar extension extension
Large parasellar Para-/suprasellar tumour extension
Marked reduction
No c h a n g e
Significant reduction
Marked reduction
Marked reduction
Gross supra- & R parasellar extension Marked reduction
Complete resolution Complete resolution
Nil
Complete resolution Complete resolution
Nil
Marked improvement On replacement therapy
Complete resolution Marked improvement
Complete resolution
Galactorrhoea, amenorrhoea
Complete resolution
H.N.
J.O.
66
47 M R 3rd, 4th nerve palsy Panhypopituitarism Impotence
M Nil
6200 32
7830 105
224
CLINICAL RAD|OLOGY
comparison and assessment of regression of tumour with bromocriptine therapy (Chakera, 1982). We feel that with the availability of the topogram facility on most new CT scanners there is no need for invasive techniques such as air encephalography or metrizamide cisternography, as suggested by other authors (Wass et al., 1982) for accurate assessment of tumour regression.
RESULTS Our patients were divided into two groups, depending on the level of the serum prolactin. The six patients in Group A had an elevated serum prolactin and were considered to have prolactinomas (Table 1). The five patients in Group B had normal serum prolactin levels and clearly had non-functioning Table 2 - N o n - f u n c t i o n i n g
tumours (Table 2)_ Patients in both groups were endocrinologically assessed by one of the authors (P.P.).-Visual field charts were obtained in all patients. Bromocriptine was prescribed in maximum tolerated doses aiming for approximately 20-30 mg/day in three equally divided doses. The primary purpose of prescribing bromocriptine in these patients was to reduce tumour size, although the inhibition of lactation and reversal of hypogonadism was also desired in some patients_ All but one patient in Group A showed a significant reduction in tumour size. Patients were scanned 2 weeks, 4 weeks and 3 months after commencing bromocriptine therapy. Subsequently, all patients living in the metropolitan region have had follow-up scans at 4-monthly intervals. Follow-up period varied from 3 months to 20 months with a mean follow-up time of 14 months.
tumours Patient
Age (years) Sex Compressive problems Endocrine problems Serum prolactin Pre-treatment On treatment CT Pre-treatment Post-treatment Clinical response Pressure signs Endocrine symptoms
M.C.
T.McA.
J.C.
D.G.
M.S.
74 F Bitemporal hemianopia Eupituitary
75 M Nil Panhypopituitarism
71 M Bitemporal hemianopia Impotence
42 M L temporal quadrantanopia Hypothyroid
79 F Severe bitemporal hemianopia Eupituitary
70 1
16 1
Large suprasellar extension No change
Large suprasellar extension No change
Large suprasellar extension No change
Large suprasellar extension No change
Large suprasellar extension No change
No change
No change
No change
No change
No change
No change
Minimal reduction in size Still impotent
On replacement therapy
No change
(a)
7 1
7
18
1
1
(b)
Fig. 1 - (a) Coronal scan of patient S.W. taken in April 1983 showing a large, uniformly contrast-enhancing pituitary tumour. Note suprasellar extension with obliteration of the chiasmatic cistern. The optic chiasm is not identifiable. There is also expansion of the sella turcica and downward extension of tumour into the sphenoid sinus. (b) Coronal scan of S.W. in July 1983 showing significant reduction of tumour size. The suprasellar extension is less marked. (Note that the appearance of the sella floor and sphenoid sinus is identical to that in Fig. l(a), confirming that an accurate comparison of tumour size can be made without resorting to invasive neuroradiology.) (L +40, W 256.)
225
RESPONSE OF PITUITARY TUMOURS TO BROMOCRIPTINE
DISCUSSION Reduction in size occurred within 14-30 days of starting bromocriptine therapy in most cases (Fig. 1)_ A single patient in Group A (I.H.) who showed no reduction in tumour size improved endocrinologically. He regained his potency and his galactorrhoea ceased. His tumour had broken through the cavernous sinus into the superior orbital fissure (Fig. 2). Another patient in Group A (J.O.) had tumour extending into the basal ganglia. This patient's psychiatric problems, as well as his visual field abnormality, resolved with tumour regression on bromocriptine therapy (Fig. 3). In Group B one patient (J.C.) demonstrated minimal decrease in tumour size with corresponding slight improvement in the visual field defect. He is being treated with bromocriptine on a long-term basis. One other young patient in Group B has undergone
surgery. Of the remaining three patients, two have refused surgery and one is considered to be unfit for surgery. Recently, there has been a report of a single case of macroprolactinoma in which bromocriptine failed to maintain tumour regression. Initially, the patient responded with an improvement in the visual fields and tumour shrinkage was confirmed by CT scanning. Subsequently, there was regrowth of the tumour despite an increase in the dosage of bromocriptine (Breidahl et al., 1983). Notwithstanding this case .report of the failure of bromocriptine therapy, we suggest that bromocriptine is an effective and safe way to treat macroprolactinomas with extrasellar extension and chiasmatic compression, but recognise that bromocriptine may not provide long-term control of tumour growth in all patients. Finally, we feel that with the new third- and
R
(a)
(b)
Fig. 2 - (a) Coronal CT scan of patient I.H. A large pituitary tumour has expanded the sella turcica and is invading both the cavernous sinuses, Note that there is no suprasellar extension, The optic chiasm is clearly seen, (b) A more anterior slice of thc coronal CT scan of patient I.H, showing tumour invading the left inferior orbital fissure on the left (curved arrow). (L +40, W 256.)
(a)
(b)
Fig. 3 - (a) Axial CT scan of patient J,O. in March 1983 with coronal reconstruction, showing a large pituitary tumour with eccentric superior extension of the tumour into the right basal ganglia (L +50, W 128). (b) Follow-up CT scan of J.O. in May 1983 showing marked tumour regression seen both in axial plane and in the coronal reconstruction (L +51, W 256).
226
CLINICAL RADIOLOGY
fourth-generation CT scanners, follow-up CT scans can be obtained in identical positions to enable an accurate comparison of tumour size and assessment of the response to therapy without resorting to invasive neuroradiological procedures_ REFERENCES
Breidahl, H. D., Topliss, D. J. & Pike, J. W. (1983). Failure of bromocriptme to maintain reduction in size of macroprolactinoma. British Medical Journal, 287, 451-452. Chakera, T. M. H (1982). Bromocriptine in management of large pituitary tumours. British Medical Journal, 285, 444. Hancock, K. W , Scott, J. S., Lamb, J. T., Myles Gibson, R. & Chapman, C. (1980). Conservative management of pituitary
prolactinomas: evidence for bromocriptine induced regression. British Journal of Obstetrics and Gynaecology, 87, 523-529. McGregor, A. M., Seanlon, M. F., Hall, R. & Hall, K. (1979). Effects of bromocriptine on pituitary tumour size. British Medical Journal, ii, 700--703. Nabarro, J. D. N. (1982). Pituitary prolactinomas. Clinical Endocrinology, 17, 129-155. Scotti, G., Scialfa, G., Pieralli, S., Chiondini, P. G., Spelta, B. & Dellabonazana, D. (1982). Macroprolactinomas: CT evaluation of reduction of tumour size after medical treatment. Neuro. radiology, 23, 123-126. Teasdale, G. (1983). Surgical management of pituitary adenomas. Clinics in Endocrinology and Metabolism, 12, 789-823. Wass, J. A. H., Williams, J., Charles, M., Kingsley, D. P. E., Halliday, A. M., Doniach, I., Rees, L. H., McDonald, W. I. & Besser, G. M. (1982). Bromocriptine in management of large pituitary turnouts. British Medical Journal, 284, 1908-1911.