Clinical and biochemical characteristics of patients with acromegaly and normal or increased prolactin levels

Background: Prevalence of hyperprolactinemia in patients with acromegaly is 30 to 40%. Since recently, the necessity of screening for acromegaly in hyperprolactinemic patients with pituitary adenoma has been actively debated. The literature on this issue has been controversial, with some authors describing significant differences of clinical and biochemical parameters in acromegaly patients with normal or increased prolactin levels, while others state the absence of such differences. Aim: To identify hallmarks of clinical and biochemical parameters in patients with acromegaly and normal or increased prolactin level. Methods: We performed a single center, single sample retrospective, observational cohort uncontrolled non-interventional study in 306 patients (70 men and 236 women) with acromegaly examined from July 2021 to June 2024, 50 of them with a pituitary microadenomas and 256 with macroadenomas. The patients were divided into two groups: acromegaly without hyperprolactinemia (n = 234) and acromegaly with hyperprolactinemia (n = 72). The groups were compared for age, gender, clinical manifestations, insulin-like growth factor 1 (IGF1) levels, characteristics of pituitary adenomas and efficacy of the treatment. In the patients with acromegaly and hyperprolactinemia we additionally analyzed prolactin levels at disease manifestation, an association between the suprasellar adenoma growth and prolactin, and an association between prolactin levels and adenoma volume at the disease onset, before treatment. Results: Hyperprolactinemia was significantly less common, than acromegaly without hyperprolactinemia, associated with acromegalic enlargement of the face (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.19–0.62, р 0.001), hands and feet enlargement (OR 0.06, 95% CI 0.03–0.12, р 0.001), but more common with visual field derangement (OR 2.8, 95% CI 1.06–7.39, р = 0.043), menstrual cycle abnormalities in women (OR 4.11, 95% CI 2.14–7.88, р 0.001) and breast discharge (OR 18.71, 95% CI 4–87.61, р 0.001). The patients with acromegaly and hyperprolactinemia noticed their first symptoms of the disease at a younger age (median 37 [25; 46] years vs 41.5 [32; 51.5] years, р = 0.004) and were diagnosed with acromegaly also earlier, than the patients with acromegaly without hyperprolactinemia (45 [34.5; 55] years vs 52 [42; 61] years, р 0.001). There were no differences in the disease latency, biochemical activity of acromegaly and gender distribution. The volume of pituitary adenomas in the patients with acromegaly and hyperprolactinemia was larger, compared to that in the patients without hyperprolactinemia (4445 [1649; 7767] mm3 vs 1242 [448; 3740] mm3, р 0.001). No correlation was found between the pituitary adenoma volume and prolactin levels. The rates of acromegaly control in both groups were not significantly different. Conclusion: The results of our study emphasize the importance to exclude acromegaly in patients with prolactinomas and in those with suspected pituitary stalk compression (which is characterized by moderate hyperprolactinemia and suprasellar growth of the pituitary adenoma), even in the absence of pathognomic signs of increased secretion of growth hormone. Hyperprolactinemia does not affect the treatment outcomes in acromegaly, and more frequent administration of dopamine receptor agonists does not result in an increased proportion of patients with biochemical control of the main disease.