Radiological Bone Changes in Cushing's Syndrome and Steroid Therapy

Cushing's syndrome of obesity, hypertension, weakness and depression of sexual function, is associated with over-production of the adreno-cortical steroids, particularly cortisone and hydrocortisone. These excess steroids are produced as a result of hyperplasia or neoplasia of the adrenal cortex. The literature of the radiological changes encountered in the skeleton in this condition is reviewed. The main radiological changes include: 1. Osteoporosis of a widespread nature, which is more easily demonstrated in the axial than in the appendicular skeleton. 2. Pathological fractures, which may occur anywhere in the weakened skeletal structures, but are most commonly seen in the spine, ribs and pelvis. 3. Abnormal callus formation, having a “cotton-wool” appearance, develops round these fractures and in particular appears to be responsible for the sign of marginal condensation, described in connection with crush fractures of vertebral bodies. This calcification represents an incomplete attempt at fracture healing, associated with inhibition of osteoblastic function by the excess hormones. By analogy with the term pseudo-fracture employed in connection with osteomalacia, the term pseudo-callus is now suggested for this appearance. 4. Delay in skeletal development is another effect of excess hormone production. Attention is drawn to the clinical facts that (1) pain is often completely suppressed in association with these fractures and (2) a fatal outcome of the disease is commonly due to infection. Iatrogenic disease of the skeleton resulting from adrenocortical steroid therapy. Steroids were introduced for therapeutic use in 1948. The first reports of their causation of iatrogenic disease appeared in 1950 and the radiological literature since that time in connection with bone changes is reviewed. The following iatrogenic complications are considered. 1. Cushing's syndrome, which cannot be differentiated radiologically from that of the natural form of the disease, has been frequently described. It is liable to occur with a cortisone or cortisone-equivalent dosage of 50 to 100 mg a day over periods varying from six months to three years. 2. Osteoporosis, fractures and joint degenerations may be observed in the absence of the fully developed picture of Cushing's syndrome. Such changes may occur after much shorter periods of steroid therapy. These fractures exhibited the same pseudo-callus formation as that seen in connection with Cushing's syndrome. Associated pain tends to be suppressed, or even completely absent, except in the case of vertebral compression fractures, where girdle pains are common and it is suggested that these may be due to secondary nerve-root irritation. Joint degenerations, in some cases approximating in appearance to a Charcot neuropathy, are not uncommon, particularly in the hips and knees, and have been observed as a result of both general therapy and local intra-articular injections. They are attributed to the improved sense of well-being engendered with consequent increase of mobility and subjection to greater trauma in the absence of the warning sense of pain. For some reason, so far unexplained, pain may continue to be suppressed, even after withdrawal of therapy. 3. Bone and joint infections may develop more easily and spread more rapidly and more silently in the absence of the normal sense of pain and with the suppression of the normal reaction of the body to inflammation. Intra-articular therapy carries with it another hazard. The introduction of infection is dangerous, since symptoms are sometimes suppressed. This appears to be less common than with oral therapy, but a florid, though painless, infective arthritis may lead to a fatal termination. 4. Delay in skeletal development may also occur in children. Attention is drawn to the fact that such complications are not frequent and that they are not in themselves an indication for the cessation of steroid therapy, since many of these effects can be overcome by the employment of other protective hormones and antibiotic drugs.