ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P736 | DOI: 10.1530/endoabs.63.P736

Prevalence of silent acromegaly in prolactinomas (PASP): an Italian experience

Chiara Bona1, Nunzia Prencipe1, Giovanna Mantonavi2, Roberto Lanzi3, Marie-Lise Jaffrain-Rea4, Maria Rosaria Ambrosio5, Daniela Pasquali6, Roberto Vettor7, Salvatore Cannavò8, Ezio Ghigo1 & Silvia Grottoli1

1Endocrinology, Diabetology and Metabolism Unit, University of Turin, Turin, Italy; 2Endocrinology Unit, IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; 3General Medicine Unit with Diabetologic and Endocrino-Metabolic Address, San Raffaele Foundation Milan, Milan, Italy; 4DISCAB, University of L’Aquila (AQ) and Neuroendocrinology, Neuromed, IRCCS Pozzilli (IS), L’Aquila, Italy; 5Endocrinology and Internal Medicine Unit, Department of Medical Sciences Ferrara, Ferrara, Italy; 6Endocrinology and Metabolic Diseases, University of Campania L. Vanvitelli Naples, Naples, Italy; 7Clinical Endocrinology Unit, Department of Internal Medicine 3, University of Padua, Padua, Italy; 8Endocrinology Unit, Polyclinic G. Martino, Messina, Messina, Italy.

Patients with prolactinomas may develop acromegaly during D2-agonists (DA), suggesting the existence of somatomammotroph adenomas with asynchronous secretion of GH and PRL. This may be due to the acquisition of somatotroph characteristics by lactotroph cells or to GH co-secretion by somatommammotroph cells unmasked after PRL inhibition by DA. The prevalence of silent acromegaly in prolactinomas during DA is 4.1%. The purpose of this study was to evaluate the somatotroph axis in a large series of patients with prolactinomas on DA. N 144 patients were enrolled in an Italian multicenter study (8 centers) [43±12.5 year, 93F/64.6%, macroadenomas 50/34.7%]. Ninety patients [43.6±13.0 year; 58 F/64.4%, macroadenomas 33/36.7%] were on DA and enrolled in a Cross-Sectional arm (CS), with a single PRL, GH and IGF1 determination after at least 3 months of treatment, whereas 54 untreated patients [42.3±11.8 year; 35 F/64.8%, macroadenomas 17/31.5%] were enrolled at diagnosis in a Prospective arm (PR), PRL, GH and IGF1 being measured before and after 6 and 12 months of treatment. In the presence of high IGF1, DA was withdrawan for 3 months and basal GH, IGF1, PRL as well as GH during oGTT were measured. As expected, PRL was lower in CS (P <0.007). High IGF1 (ULN 1.01-1.56) was found in 9 patients (6.25%, 5F; 4 CS and 5 PR). In CS, high IGF1 was observed after 5–144 months of therapy. In PR, IGF1 increased after 6 months of therapy. After DA withdrawal, IGF1 returned to normality in 6/9 patients, abnormal GH secretion was excluded through oGTT in 7/9 cases (GH nadir 0.1–0.3 ng/ml). In one patient oGTT was unavailable, but basal GH was < 0.4 ng/ml. One patient had slightly elevated IGF1(1.01 ULN) and no GH inhibition during oGTT on DA. Re-evaluation on DA treatment was performed in 7/9 cases. In one patient, IGF1 was mildly elevated (1.2 ULN) but GH hypersecretion was excluded at oGTT. In 5 patients IGF1 normalized. The patient showing no GH inhibition during oGTT on DA was re-tested with similar results: she underwent neurosurgery with pathological diagnosis of GH/PRL adenoma.

Conclusions: High IGF1 may be encountered in prolactinomas during DA. Drug withdrawal determines IGF1 normalization in most cases. Such alteration may be due to the stimulatory effect of DA on normal somatotroph cells, or may reflect assay variability. Rarely, persisting high IGF1 may reveal silent acromegaly. oGTT appears to reliably distinguish between both conditions.