Pituitary Microadenoma vs. Macroadenomas in Cushing`s Disease: Does Size Matter?

Background:
Reports on the differences of clinical and biochemical behavior of adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent.

Objective:
Describe the clinical and biochemical characteristics of patients with corticotroph macroadenomas and microadenomas.

Methods:
Retrospective charts review of patients with Cushing`s disease, treated at Rabin Medical Center between 2000 and 2017, or at Maccabi Healthcare Services between 2005 and 2017. Epidemiologic, clinical and biochemical factors were compared between patients with corticotroph macroadenomas and microadenomas.

Results:
The cohort included 105 patients (82 women, 78%; mean age, 41.5±14.5 years), including 80 patients with microadenomas (mean size, 5.2±2.2 mm) and 25 patients with macroadenomas (mean size, 18.0±7.7 mm) . Baseline characteristics were similar between groups. Most common reasons for completing an investigation for Cushing`s syndrome among patients with microadenomas and macroadenomas were weight gain (46.3% vs. 52.0%, P=NS) and Cushingoid features (27.5% vs. 20.0%, P=NS). While mean urinary free cortisol levels (5.2±5.4xULN vs. 7.8±8.7xULN) and serum cortisol levels following low-dose dexamethasone (487.6±329.8 vs. 372.0±324.5 nmol/L) were higher with macroadenomas, the differences were not significant with considerable overlap between groups. Concentrations of ACTH were greater with macroadenoma (1.9±1.2xULN vs. 1.3±0.8xULN, respectively, P =0.01). Rates of recurrent/persistent disease were similar with microadenomas and macroadenomas (35.2% vs. 28.6%, respectively; P = NS), as was the rate and duration of post-operative glucocorticoid treatment.

Conclusions:
While ACTH-secreting macroadenomas exhibit higher plasma ACTH levels than microadenomas, there was no correlation between tumor size with cortisol secretion values or clinical characteristics in patients with Cushing`s disease.