Glucocorticoid replacement therapy and vertebral fractures in hypopituitary adult males with GH deficiency

Abstract

Objective: GH deficiency (GHD) and glucocorticoid excess are associated with increased risk of fragility fractures. We aimed to evaluate whether the prevalence of vertebral fractures may be influenced by glucocorticoid over-replacement in hypopituitary males with GHD. Design: Cross-sectional study. Methods: Fifty-one adult hypopituitary patients (all males; mean age 55 years, range: 23-81) with severe adult-onset GHD (replaced in 21 patients and untreated in 30 patients) and glucocorticoid deficiency on replacement treatment were studied for vertebral fractures using a radiological and morphometric approach. Results: Vertebral fractures were observed in 31 patients (60.8%) in correlation with untreated GHD, urinary cortisol values, and cortisone doses. Patients were stratified according to treatment of GHD, and current and cumulative cortisone doses. In untreated GHD, vertebral fractures occurred more frequently in patients who had received higher (greater than median) cumulative and current doses of cortisone compared with patients who had received lower (less than median) drug doses (95.2 vs 50.0%, PZ0.009 and 90.5 vs 55.6%, PZ0.04 respectively). In untreated GHD, fractured patients had significantly higher urinary cortisol values compared with patients without vertebral fractures (84 mg/24 h, range: 24-135 vs 49 mg/24 h, range: 30-96; PZ0.04). In treated GHD patients, by contrast, the prevalence of vertebral fractures was not influenced by cumulative and current cortisone doses and urinary cortisol values. Conclusions: Glucocorticoid over-replacement may increase the prevalence of vertebral fractures in patients with untreated GHD. However, treatment of GHD seems to protect the skeleton from the deleterious effects of glucocorticoid overtreatment in hypopituitary patients.

MECHANISMS IN ENDOCRINOLOGY: Endogenous subclinical hypercortisolism and bone: a clinical review

“…However, in patients with hypercortisolism, data regarding the protective role of sex steroids replacement therapy on bone are lacking and sex steroids administration might potentially worsen the cardiovascular risk. Thirdly, a reduced GH reserve has been described in patients with both overt cortisol excess (100) and SH (66), and the GH deficit has been associated with osteoporosis and fragility fractures (101). In patients with SH, the GH reserve seems to recover shortly after the normalization of cortisol levels (66), but if these patients are conservatively managed, the GH deficit may persist for many years.…”

Pituitary Diseases and Bone

“…44 Replacement therapies of central hypoadrenalism and hypothyroidism were shown to influence the fracture rate in patients with hypopituitarism 49,50 in association with untreated or treated GHD, respectively (Box 6; Fig. 3).…”

Bone and Joint Disorders in Acromegaly

“…On the other hand, notwithstanding the concept that normalizing GH hypersecretion improves skeletal health [54], some patients with well-controlled or cured acromegaly may still fracture in relationship with coexistent risk factors. Therefore, besides the treatment of acromegaly, it is important to correct other potential risk factors for fractures, with special attention to hypogonadism, in addition to vitamin D deficiency, overtreatment of hypoadrenalism and hypothyroidism [13,59,60]. In patients with preexisting vertebral fractures, the cure of acromegaly and the correction of adjustable risk factors may not be sufficient to prevent future fractures.…”