Effect of 2 years of cortisol normalization on the impaired bone mass and turnover in adolescent and adult patients with Cushing's disease: a prospective study.
BACKGROUND
Osteoporosis is a frequent, severe and often underestimated consequence of long-term hypercortisolism, often presenting as bone fracture.


OBJECTIVE
This prospective study was designed to evaluate whether the abnormalities of bone mass and turnover can be similarly reversed in adolescent and adult patients with Cushing's disease, after correction of hypercortisolism.


METHODS
Bone mineral density (BMD) at lumbar spine, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were measured at diagnosis and 2 years after cure of Cushing's disease (CD) in six patients with childhood-onset and nine with adulthood-onset disease. Fifteen age-, sex- and body mass index (BMI)-matched healthy subjects served as controls.


RESULTS
At diagnosis, BMD Z scores at lumbar spine and OC levels were lower (2.3 +/- 0.1 vs.-0.2 +/- 0.01; P < 0.01 and 1.6 +/- 0.1 vs. 9.6 +/- 1.2; P < 0.01 respectively) while urinary Ntx levels were significantly higher (139.9 +/- 6.1 vs. 82.0 +/- 1.6; P < 0.01) in CD patients than in controls. Among CD patients, similar values of Z scores (-2.4 +/- 0.3 vs.-2.2 +/- 0.1, P = 0.4) and OC levels (1.7 +/- 0.2 vs. 1.6 +/- 0.2, P = 0.6) were observed in adolescent and adults patients, whereas urinary Ntx levels were significantly higher (159.7 +/- 7.9 vs. 125.9 +/- 3.3, P < 0.001) in the former than in the latter group. Two years after remission from hypercortisolism, OC levels (P < 0.001) and lumbar BMD Z scores (-2.2 +/- 0.3, P < 0.05; and -1.9 +/- 0.2; P < 0.01, respectively) increased significantly, while urinary Ntx levels reduced significantly (P < 0.001) in both adolescent and adult patients. However, biochemical markers and Z scores of BMD remained significantly suppressed compared to controls.


CONCLUSIONS
Bone impairment in childhood- and adulthood-onset Cushing's disease patients can be partly, but not completely, reversed 2 years after normalization of cortisol levels. Longer recovery times or additive therapeutic approaches are necessary to maximize peak bone mass in children and restore bone mass in adults with Cushing's disease.
Di Somma
Carolina
C
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University Naples, Italy.
Pivonello
Rosario
R
Loche
Sandro
S
Faggiano
Antongiulio
A
Klain
Michele
M
Salvatore
Marco
M
Lombardi
Gaetano
G
Colao
Annamaria
A
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density; D016723:Bone Remodeling; D016022:Case-Control Studies; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D003480:Cushing Syndrome / Q000097:blood* / Q000503:physiopathology* / Q000628:therapy; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000652:urine; D011446:Prospective Studies
D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D003094:Collagen; D006854:Hydrocortisone