Case Report Describes Rare Cushing’s Complication

A recent report describes the case of a woman with adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome who remained undiagnosed for two years after developing femoral avascular necrosis — a condition in which the bone tissue around the head of the thighbone dies due to lack of blood supply.

Although bone avascular necrosis is rarely caused by excessive levels of cortisol, this case highlights the need to identify unusual features of Cushing’s so that treatments can start sooner, thereby preventing further complications.

“Our case demonstrates that avascular necrosis of the hip may be an alarming presenting feature of [Cushing’s syndrome],” the researchers wrote.

The case report study, “Avascular femoral necrosis as part of Cushing syndrome presentation: a case report,” was published in the Journal of Medical Case Reports.

Cushing’s syndrome is characterized by excessive levels of the hormone cortisol in the body. The condition can be ACTH-dependent or ACTH-independent.

Patients with ACTH-dependent Cushing’s typically have tumors that release high amounts of ACTH, which promotes the production of cortisol by the adrenal glands that sit atop the kidneys. Conversely, in patients with ACTH-independent Cushing’s, the adrenal glands produce too much cortisol independently of ACTH, often due to the presence of benign or malignant tumors.

Although the symptoms and complications of Cushing’s are well-known, some are uncommon and may be overlooked. Avascular necrosis of the femoral head is a painful condition that is caused when the blood supply to the head of the thighbone is interrupted, resulting in the death of bone tissue.

From 10% to 30% of all cases of avascular necrosis of the femoral head are associated with glucocorticoid therapy. Glucocorticoids are used to treat many inflammatory conditions. Only a few case reports have described this condition as a complication of Cushing’s syndrome.

Researchers in Portugal now reported the case of a woman with ACTH-independent Cushing’s syndrome who remained undiagnosed for two years after presenting with avascular necrosis of her right hip.

The 38-year-old woman was referred for evaluation since she had been missing menstrual cycles. She started missing her cycles after stopping hormonal birth control due to a deep-vein thrombosis (DVT), a condition in which a blood clot forms in one or more of the deep veins in the body.

She previously had a surgical procedure on her right hip to treat avascular necrosis of the femoral head. This had been diagnosed after three years of gradual right hip pain and restricted movements.

The patient also had a five-year history of high blood pressure and reported that she had gained weight (4 kilograms, or about 9 pounds) in the past two years. She had no history of fertility issues.

When examined, she had several classical features of Cushing’s, including obesity around her midsection, facial redness, easy skin bruising, and loss of muscle mass and muscle weakness.

The overnight dexamethasone suppression test (ODST) failed to lower her blood cortisol levels to less than 1.8 micrograms per deciliter (mcg/dL), suggesting the presence of Cushing’s syndrome. The ODST measures blood cortisol levels in the morning after patients take dexamethasone, a corticosteroid that normally suppresses cortisol production.

Her 24-hour urinary-free cortisol (UFC) levels also were high at 728.9 mcg/day, and far above the normal range (36–137 mcg/day). But her ACTH levels were very low (under 1.0 picograms/mL, with normal range being less than 63.3 pg/mL). These results were consistent with ACTH-independent Cushing’s syndrome.

A computed tomography (CT) scan of her adrenal glands revealed a 25 mm (almost 1-inch) lesion in her left adrenal gland. Her doctors surgically removed the left adrenal gland and she started cortisol-replacement therapy with hydrocortisone.

Three months after surgery, her blood pressure returned to a normal range and her menstrual cycles had resumed. Her UFC values also normalized (37.4 mcg/day).

Further tests showed the patient had osteoporosis and osteopenia, two conditions that cause bones to become weak and brittle. To reduce the risk of fractures, she was started on alendronate (70 mg/day) and cholecalciferol (600 international units daily).

After 10 months, an ACTH stimulation test, which measures how well the adrenal glands respond to ACTH, showed she had adrenal insufficiency. Since her remaining adrenal gland was still not working normally, her doctors postponed taking her off hydrocortisone.

However, during this period, she lost 9 kg (about 20 pounds.), her blood pressure returned to normal, and she entered in remission from Cushing’s.

Researchers noted that an earlier diagnosis of Cushing’s syndrome and identification of femoral avascular necrosis could have prevented the patient from needing hip surgery at such a young age. They also speculated high levels of cortisol might have contributed to her DVT.

“As this presentation is rare, our case reinforces the importance of a high index of suspicion and early recognition of [Cushing’s syndrome] atypical features, in order to avoid complications and delay in treatment of [Cushing’s syndrome],” the researchers wrote.

The team also noted that further research is needed to investigate why avascular necrosis develops in some patients with Cushing’s syndrome.