Discordance Between Prolactinoma Size and Prolactin Level: An Unusual Laboratory Finding

Background: Prolactinomas are a common cause of hyperprolactinemia. Prolactin (PRL) level higher than 250 mcg/L is associated with a prolactinoma and serum prolactin levels generally correlate with tumor size. It is unusual to find a PRL level that is markedly elevated out of proportion to prolactinoma size. We present the case of a 32-year-old man who was referred to Endocrinology Clinic with fatigue and low testosterone, found to have a PRL level of 1302 mcg/L with a 9 x 8 x 9 mm microprolactinoma. Clinical Case: A 32-year-old man with past medical history of migraines reported fatigue, weight gain, low libido and erectile dysfunction and was referred to Endocrinology Clinic due to PRL elevation. His medications included a multivitamin and chasteberry herbal supplement. Physical exam was unremarkable and no visual field abnormalities were detected. Baseline lab results showed PRL: >1000 mcg/L and 1302 mcg/L after serial dilutions, FSH: 1.8 mIU/mL [0.7- 10.8 mIU/ml], LH:0.9 L [1.2- 10.6 mIU/ml], total testosterone 136 ng/dL [250-1100 ng/dl], free testosterone: 32 [35- 155 pg/ml], with normal cortisol, ACTH, IGF-1, TSH and Free T4 levels. MRI pituitary revealed a 9 mm x 8 mm x 9 mm microadenoma on the right side of the pituitary gland without optic chiasm compression. He was diagnosed with microprolactinoma, with very high PRL level causing secondary hypogonadism. Cabergoline 0.25 mg twice weekly resulted in significant improvement in PRL level. With dose increment to 0.5 mg twice weekly, PRL level improved further along with improvement in symptoms related to hypogonadism. Five months after initiation of treatment, total PRL was 58 ng/mL with monomeric PRL of 41 mcg/L, indicating only trace contribution of macroprolactin to the total PRL level. Review of the Literature: In a retrospective study by Colao et al. (2003), men with hyperprolactinemia due to micro-prolactinoma had average pre-treatment PRL levels of 187.7 mcg/L (SD 51.8 mcg/L) and average pre-treatment diameter of 8.0 mm (SD 1.4 mm). A retrospective study of 1234 patients by Vilar et al. (2008) reported similar findings: microprolactinomas had average baseline PRL of 165.6 mcg/L (SD 255.1 mcg/L) and the highest reported level of PRL due to microprolactinoma was 525 mcg/L. Conclusion: Our case illustrates that assumptions about prolactinoma size should not be made based on laboratory findings alone. References: Melmed S. et al, Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 96: 273-288, 2011.Colao A. et al. Gender differences in the prevalence, clinical features and response to cabergoline in hyperprolactinemia. European Journal of Endocrinology 148: 325-331.Vilar L. et al. Diagnosis and Management of Hyperprolactinemia: Results of a Brazilian Multicenter Study with 1234 Patients. J Endocrinol Invest 31:436-444.