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OBJECTIVE: Hyperprolactinemia (HPRL) has been identified in more than half of patients with systemic sclerosis (SSc). However, the association with pituitary adenoma and the status of hypothalamic dopaminergic tone using metoclopramide (MTC) test has not been studied. We investigated the prevalence of prolactin (PRL)-secreting pituitary adenoma and evaluated production of PRL by dynamic testing with MTC in SSc. METHODS: We studied 30 patients with SSc (mean age 38 +/- 10 yrs) and 20 healthy controls (mean age 37 +/- 11 yrs). Serum PRL concentrations were determined by radioimmunoassay in all subjects, and PRL response was measured 30, 60, 90, and 120 min after injection of 10 mg of MTC. Computed tomography (CT) of the sella turcica was performed. RESULTS: The mean basal serum PRL levels before and after stimulation with MTC in SSc patients versus controls were: basal 18.2 +/- 5.4 versus 8.7 +/- 1.6 ng/ml, p = NS; 30 min: 175.0 +/- 5.4 versus 61.0 +/- 42 ng/ml, p < 0.001; 60 min: 160 +/- 64 versus 52 +/- 30 ng/ml, p < 0.001; 90 min: 125 +/- 57 versus 42 +/- 21.0 ng/ml, p < 0.05; 120 min: 108.0 +/- 57 versus 30.0 +/- 10 ng/ml, p < 0.005. CT scan showed microadenomas in 24/30 SSc patients and 1/20 controls (p = 0.001). CONCLUSION: Our study suggests that a group of patients with SSc have a high prevalence of HPRL with increased central dopaminergic tone, and microadenomas. PRL may have a role in the pathogenesis of SSc. Further studies are necessary to confirm our results.