Abstract
Introduction
Migraine is a prevalent condition of unknown origin, defined as a periodic, commonly unilateral, throbbing headache, with or without cerebral disturbance, with intervening periods of relative freedom from headache and without evidence of primary structural abnormality (1).
Headache is a frequent condition in patients with pituitary adenoma, being more prevalent in prolactin-secreting adenomas (2). Prolactin (PRL)-secreting pituitary adenomas are the most common cause of hyperprolactinaemia (3). The increased production of PRL often leads to reproductive dysfunction and galactorrhea.
Bromocriptine and cabergoline are agonist drugs of the D2 dopaminergic receptors, both safe and effective in the treatment of prolactinoma; in particular, they are able to lower serum PRL, restore gonadal function, decrease tumour size and improve visual fields (3).
We report a case of complete resolution of migraine with aura after successful bromocriptine treatment of a microprolactinoma.
Case history
A 19-year-old woman was referred to our headache centre for disabling chronic headache of 6 years' duration, in November 1993. According to the criteria established by the International Headache Society (IHS) (1), a diagnosis of migraine with aura was made, with a reported severe intensity, a frequency of about eight attacks per month, and a median duration of 48–72 h. Collecting her clinical history, she also reported suffering, since puberal age (first menstruation at 12 years), from oligomenorrhea. She had not been taking any drugs in the immediate period before admission, excluding common analgesics for migraine episodes. No history of migraine was present in her family. Physical examination on admission revealed a body mass index of 25 (normal range: 19–25). No disturbances of visual fields were detected.
The common laboratory examinations were normal. Endocrinological assessment, however, revealed an elevated serum level of PRL (54.1 ng/mL; normal value: 3–20 ng/mL); follicle-stimulating hormone, luteinizing hormone, growth hormone, adrenocortical hormone, thyroid stimulating hormone, cortisol, oestrogen hormones, total and free thyroxine, total and free tetraiodothyronine and progesterone were within normal ranges.
Magnetic resonance imaging revealed a mass of the pituitary gland of about 0.4 millimetres in size, consistent with a microadenoma. In January 1994 oral bromocriptine therapy was initiated at 7.5 mg daily. After 2 months the patient was re-evaluated to assess efficacy of the pharmacological treatment. She reported the complete disappearance of migraine attacks, with regression of oligomenorrhea. In particular, after beginning bromocriptine therapy, she reported only two mild episodes in the first month, the former lasting about 20 h, the latter 12 h, whereas no episode of migraine occurred in the following 2 months. The serum PRL level was strongly affected by the treatment (0.11 ng/mL in March 1994). The patient was re-evaluated in September 1994 and in February 1995. At both times the patient did not report migraine attacks. Moreover, the menstrual cycles remained regular. The serum PRL level remained in the normal range (0.36 ng/mL in September 1994 and 0.24 ng/mL in February 1995). In September 1994 and February 1995 the patient also underwent magnetic resonance imaging, in both cases not showing significant change in the size of the lesion.
Comments
Headache is a frequent condition in patients with pituitary adenoma, being migraine-prevalent in the female patients. Headache is more prevalent in PRL-secreting adenomas and significantly improves after surgery (2).
We report a case of resolution of chronic migraine with aura after treatment of a microprolactinoma with bromocriptine.
It is not unreasonable to hypothesize that the disappearance of migraine may be due to the normalization of high PRL levels. As bromocriptine treatment did not affect the size of the pituitary adenoma, a decrease in a mass effect or traction on adjacent structures appears unlikely. A direct analgesic effect of bromocriptine cannot be excluded.
Hartman and colleagues (4) reported a case with similar features, but concerning migraine without aura. A patient suffering from a chronic migraine for 27 years had a PRL-secreting pituitary microadenoma, diagnosed as an incidental finding following an automobile accident. Treatment of the microprolactinoma with bromocriptine, together with a normalization of plasmatic PRL level, led to a complete resolution of the migraine. Moreover, Lee and colleagues (5) reported resolution of classical migraine following surgical removal of a pituitary microadenoma, supporting hyperprolactinaemia as the associated factor.
Studies on series of patients are also available, concerning hyperprolactinaemia in association with headache and the possible efficacy of dopaminergic agonists in this condition. Kemman and colleagues (6) showed tension-type headaches to be highly prevalent in hyperprolactinaemic women without evidence of sellar abnormalities, often preceding the finding of elevated PRL levels for several years. Moreover, in the same study, treatment with bromocriptine in women with associated ovulation problems led to a decrease of headache frequency.
The possible mechanisms behind the association between hyperprolactinaemia and migraine could be various. In particular, it has been recently hypothesized that hyperprolactinaemia may induce a decrease of beta-endorphinergic activity in the hypothalamus (7).
However, arguments exist against hyperprolactinaemia as the factor associated with migraine. No data suggest that PRL is increased above the normal range in patients with migraine. Moreover, flunarizine, an effective migraine prophylactic, is associated with raised basal PRL concentrations (8).
It is possible that bromocriptine plays a beneficial role in migraine patients per se, independently of PRL levels. Some evidence seems to support this hypothesis. A possible direct analgesic effect has been invoked for this drug, involving dopaminergic transmission (9). Herzog (10) showed a continuous bromocriptine therapy to be able to significantly reduce the frequency of attacks in patients with disabling menstrual migraine. Moreover, a reduced tuberoinfundibolar dopaminergic tone (11) and an altered dopaminergic control of PRL secretion (12) have been shown in patients with migraine. Both these phenomena could be affected by bromocriptine, independently of the action on the serum PRL level.
In conclusion, with the limited evidence available, it is only possible to conclude that in this patient with hyperprolactinaemia resulting from a pituitary microadenoma, treatment with bromocriptine was associated with resolution of migraine. This association warrants further study.