May an Altered Hypothalamo–Pituitary–Adrenal Axis Contribute to Cortical Bone Damage in Primary Hyperparathyroidism?

Cortisol secretion has been reported to be increased in primary hyperparathyroidism (PHPT). Our aim was to evaluate circulating and urinary cortisol levels and the relationships with biochemical and bone parameters in patients with PHPT at the time of diagnosis. We studied 180 consecutive patients with PHPT (mean age ± SD 60.0 ± 13.2 years; F/M 140/40, BMI 25.8 ± 4.8 kg/m²) and 56 subjects with incidentally discovered adrenal adenoma who served as controls (age 56.2 ± 12.8 years, F/M 40/16, BMI 25.7 ± 3.9 kg/m²). Serum morning and midnight cortisol and urinary free cortisol were measured in both groups. In PHPT patients bone mineral density was measured at the lumbar spine, femur, and forearm. Serum morning cortisol and urinary cortisol were similar in PHPT patients and controls, whereas midnight cortisol was higher in PHPT patients (5.3 ± 4.7 vs. 2.9 ± 0.9 μg/dL, P = 0.001). In this group, midnight cortisol correlated positively with age (r = 0.27, P = 0.008) and negatively with forearm (r = −0.36, P = 0.003) and total-femur T score (r = −0.30, P = 0.02). Multivariate regression analysis, including age, calcium, parathyroid hormone (PTH), and midnight cortisol as independent variables and forearm T score as dependent variable, indicated that age (β = –0.29, P < 0.0001), PTH (β = –0.33, P < 0.0001), and midnight cortisol (β = –0.14, P < 0.04) were independently associated with forearm T score. Our findings show increased midnight cortisol levels in patients with PHPT, indicating a subtle alteration of the hypothalamo–pituitary–adrenal axis dynamics that is unrelated to the degree of disease activity; further data are needed to demonstrate the supplementary effect of this subtle alteration to bone damage in this condition.