Endocrine Abstracts

Background: The presence of functional ACTH receptors (MC2R) on osteoblasts and fact, that their activation lead to the proliferation of osteoblasts is consistent with the presence of receptors for another anterior pituitary hormones (FSH and TSH) on bone cells. Does ACTH directly regulate bone? Is it possible, that this is another hormone of a novel regulatory axis, pituitary-bone axis, in which hormones bypass traditional endocrine targets to regulate bone mass directly? Supraphysiological doses of glucocorticoids lead to different metabolic complications as well as to osteoporosis and osteonecrosis. However, osteonecrosis is not a cardinal feature of ACTH-producing adenomas.

Aim: To compare bone mineral density (BMD) in patients with ACTH-dependent and ACTH-independent Cushing syndrome (CS).

Patients and methods: Retrospective analysis of BMD by X-ray absorptiometry (Hologic Discovery) in patients with ACTH-dependent (n=15) and ACTH-independent (n=7) form of CS.

Results: Patients with ACTH-dependent (ACTH 92.7 pg/ml) and ACTH-independent (ACTH 3.0 pg/ml) form of CS did not differ by their body height (165.1 vs 164.4 cm), body weight (80.6 vs 74.4 kg), BMI (29.6 vs 27.6 kg/m²), UFC_rel (3.78 vs 3.54 xURR), nor BMD at femoral neck (neck 0.69 vs 0.73 g/cm², trochanter 0.61 vs 0.61 g/cm², inter 1.01 vs 0.99 g/cm², total 0.85 vs 0.85 g/cm²), neither at the lumbar spine (L₁ 0.82 vs 0.83 g/cm², L₂ 0.89 vs 0.93 g/cm², L₃ 0.91 vs 0.95 g/cm², L₄ 0.92 vs 0.97 g/cm², total 0.88 vs 0.91 g/cm²).

Conclusions: We did find differences in BMD in patients with ACTH-dependent and ACTH-independent CS. However, the fact that low ACTH is associated with osteonecrosis and that ACTH administration reduces such necrosis in animal model, even despite methylprednisolone acetate, provides a firm rationale for the use of ACTH in humans to decrease the risk of osteonecrosis.