Question

How do patients with Cushing disease pair with osteoporosis? Explain in detail the connection between the two diseases. Do they need special considerations in the diagnosis and management of either condition? Are they at a disadvantage compared to an otherwise healthy individual?

Answer 1

Cushing's disease actually refers to the disease that occurs only due to ACTH producing tumor of pituitary. Decreased bone mineralization and decreased bone mass develops osteoporosis.They may cause collapse of vertebral bodies and pathologic fractures of bones.

As cortisol inhibits bone formation by decreasing synthesis of type-I collagen of bone matrix, by inhibiting conversion of osteoprogenitor cells to osteoblasts, by decreasing absorption of Ca+2 from GIT, also decreases synthesis of vitamin D thus decreasing calcium supply to bone and it also facilitates bone resorption.

All of these conditions leads to osteoporosis in cortisol excess. They are diagnosed by means of bone X-rays for osteoporotic changes or MRI of brain, for any pituitary tumors in case of ACTH dependent cortisol excess of cushing's disease.

Diagnosis of cushing's disease is mainly made by the measurement of plasma ACTH levels, which is measured in the morning around 9 am. ACTH levels >3.3pmol/L suggests pituitary cause/ectopic ACTH. In these cases pituitary cause is confirmed by supression of ACTH secretion by high-dose dexamethasone and ACTH stimulation by corticotrophin-releasing hormone. MRI detects pituitary tumors secreting ACTH. Bilateral inferior petrosal sinus sampling (BI PSS) along with the measurement of ACTH is the best method to confirm cushing's disease when tumor size is morethan 6mm.

Treatment of choice is mainly surgical. Trans-sphenoidal surgery with selective removal of adenoma. Laparoscopic bilateral adrenalectomy is performed in some cases of cushing's disease. Medical treatment include pasireotide, an analogue of somatostatin which works by suppressing ACTH secretion by tumor. It may also cause tumor shrinkage. This type of treatment may result in adrenal insufficiency in some patients which is a main disadvantage.