Estrogen Receptor α, a Sex-Dependent Predictor of Aggressiveness in Nonfunctioning Pituitary Adenomas: SSTR and Sex Hormone Receptor Distribution in NFPA

J Clin Endocrinol Metab. 2017 Sep 1;102(9):3581-3590. doi: 10.1210/jc.2017-00792.


Context: Nonfunctioning pituitary adenomas (NFPAs) are fairly common and require a multidisciplinary approach. Reliable markers of a clinically aggressive course are lacking. Medical treatment is not available, and transsphenoidal surgery is the preferred primary treatment.

Objective: We aimed to characterize the somatostatin, estrogen, and progesterone receptor distribution for NFPAs and compare it with factors of tumor aggressiveness.

Design: Tumor samples for immunohistochemistry (n = 145) and quantitative reverse transcription polymerase chain reaction (n = 106) analyses of somatostatin receptor (SSTR) 1, SSTR2, SSTR3, SSTR5, estrogen receptor α (ERα), and progesterone receptor (PR) were measured by immunoreactive score (IRS) and messenger RNA relative quantity and retrospectively compared with variables of aggressiveness.

Setting: All patients were operated at the same tertiary referral center.

Participants: A total of 164 patients with NFPA and tumor tissue from the primary operation were included.

Results: SSTR3 was expressed abundantly by immunohistochemistry in all NFPAs. The IRS of ERα correlated with that of SSTR2 in male patients only (males, P < 0.001; females, P = 0.8). Low ERα level was linked to a higher reintervention rate (P = 0.001) and earlier reintervention (P = 0.004) in male patients only (females, P = 0.95 and P = 0.65, respectively). Absence of ERα together with age provided a good prediction model for reintervention in male patients with gonadotroph adenomas.

Conclusions: SSTR3 is expressed abundantly in NFPAs and is therefore a possible target for medical treatment. Absence of ERα together with young age may predict tumor recurrence in groups of NFPAs. Further validation in systematic prospective studies is needed.

Publication types

  • Comparative Study

MeSH terms

  • Adenoma / metabolism
  • Adenoma / mortality
  • Adenoma / pathology*
  • Aged
  • Biomarkers, Tumor / blood*
  • Cohort Studies
  • Disease-Free Survival
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Pituitary Neoplasms / metabolism
  • Pituitary Neoplasms / mortality
  • Pituitary Neoplasms / pathology*
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Receptors, Progesterone / metabolism*
  • Receptors, Somatostatin / metabolism*
  • Sex Factors
  • Survival Analysis


  • Biomarkers, Tumor
  • Estrogen Receptor alpha
  • Receptors, Progesterone
  • Receptors, Somatostatin
  • SSTR2 protein, human