Dopamine Agonists and Pituitary Tumor Shrinkage

Abstract

The primary aim of this review has been to clarify the tumor shrinking effects of dopamine agonists on pituitary macroadenomas of different cell types. Shrinkage is most dramatic for macroprolactinomas and is due to cell size reduction. Seventy-nine percent of 271 definite macroprolactinomas were reduced in size by at least 25%, and 89% shrank to some degree. Most shrinkage occurs during the first 3 months of treatment, although in a minority shrinkage is delayed. Dopamine agonist resistance during long-term therapy is exceptional. Drug withdrawal nearly always leads to a return of hyperprolactinemia, even after several years treatment, although early tumor reexpansion is unusual. About 10% of true macroprolactinomas do not shrink with dopamine agonists; the molecular mechanisms of such resistance have yet to be determined. Alternative formulations of BC and new dopamine agonists (CV 205-502 and cabergoline) are useful for the minority of patients unable to tolerate oral BC, but do not seem to further improve overall shrinkage rates. The risks of pregnancy have probably been overstated, and BC is suitable primary treatment for women with prolactinomas of all sizes; the drug can be used safely during pregnancy in the event of clinically relevant tumor expansion. The interpretation of different degrees of hyperprolactinemia is discussed and management strategies suggested. Most patients with macroprolactinomas now avoid surgery, but drug-induced, time-dependent tumor fibrosis should be remembered if surgery is contemplated. Nonfunctioning pituitary tumors are mostly of gonadotroph cell origin and may be associated with significant disconnection hyperprolactinaemia. Seventy-six of 84 well-characterized tumors showed no tumor shrinkage during dopamine agonist therapy. Possible explanations include abnormalities of dopamine receptor number and function. Preliminary evidence suggests that dopamine agonists may restrain the growth of some functionless tumors; most of these tumors, however, can be satisfactorily debulked using transsphenoidal surgery. In contrast to macroprolactinomas, other functioning pituitary tumors (GH-, TSH-, and ACTH-secreting) rarely shrink during dopamine agonist therapy, although the number of tumors studied is small.

THERAPY OF ENDOCRINE DISEASE: The challenges in managing giant prolactinomas

“…No reliable pretreatment predictor of tumour response has so far been identified in patients with macroprolactinomas (75,77). The same is true for giant prolactinomas: tumour response is not correlated with age, gender, baseline PRL level or tumour size.…”

Physiological effects of electroconvulsive therapy and transcranial magnetic stimulation in major depression

“…Prolactin, largely regulated by inhibitory effects of dopamine [Bevan et al, 1992], is released from the anterior pituitary and can be stimulated by TRH [Kjellman et al, 1985]. Depression studies of prolactin levels and responses to hormonal challenges have produced conflicting results.…”

Cabergoline monotherapy in the long-term treatment of Cushing's disease

“…Studies using dopamine agonists like bromocriptine or cabergoline were initiated based on the demonstration of D 2 receptor expression in corticotroph tumors (11) and their ability to reduce ACTH and cortisol secretion in in vitro and in vivo studies (11)(12)(13). The effectiveness of bromocriptine was first reported in Nelson's syndrome and in the short-term treatment of CD with a shrinkage effect on pituitary tumors (14)(15)(16)(17). However, long-term studies with bromocriptine demonstrated limited efficacy, with !30% of response during chronic treatment (9,10,18).…”