Rare ‘double Cushing’s’ case highlights need to check cortisol
Report shows persistent symptoms during tapering led to finding adrenal tumor
Persistent symptoms during corticosteroid tapering should prompt evaluation for an internal source of excess cortisol — usually from the adrenal glands above the kidneys — because exogenous steroid use can mask signs of Cushing’s syndrome that the body is producing on its own.
That’s what happened in the case of a man described in “Co-Occurrence of Endogenous and Exogenous Cushing’s Syndromes: Does ‘Double Cushing Syndrome’ Really Exist? A Case Report,” published in Clinical Case Reports by researchers in Iran.
Cushing’s syndrome occurs when the body is exposed to too much of the hormone cortisol. Most cases are caused by prescribed corticosteroids (exogenous Cushing’s). When the body produces the excess cortisol itself, as in Cushing’s disease, the source is considered endogenous.
Having both exogenous and endogenous Cushing’s syndrome simultaneously — called “double Cushing’s syndrome” — is extremely rare and can make diagnosis difficult. But when symptoms persist or cortisol levels remain high after tapering or stopping corticosteroids, an internal source becomes likely.
“The simultaneous occurrence of endogenous and exogenous [Cushing’s syndrome] is an exceptionally uncommon phenomenon. This dual manifestation has been reported in a few case reports, highlighting its rarity and the complex diagnostic and therapeutic challenges it poses,” the researchers wrote.
Case report details symptoms that raised suspicion beyond steroid use
In their report, the team describes the case of a 46-year-old man with newly diagnosed hypertension (high blood pressure) and two episodes of deep vein thrombosis, blood clots that form in deep blood vessels. He had severe hip pain, and his legs felt weak.
He had been taking 50 mg of the corticosteroid prednisolone daily for three years, along with inhaled medications for breathing problems that began after COVID-19 vaccination. Despite starting blood thinners after his first clot, he developed a second one soon afterward.
This raised suspicion that a hormonal problem might be increasing his tendency to form clots. Over the previous two years, he had gained weight, grown weaker, bruised easily, lost libido, and experienced mood swings ranging from euphoria to irritability. He had also broken bones from minimal trauma.
Bone density testing showed osteopenia (loss of bone density) in the hip and severe osteoporosis (a more advanced stage of osteopenia) in the spine. He began treatment with calcium and vitamin D supplements, along with teriparatide, a medication that stimulates bone formation.
Two months earlier, his prednisolone dose had been reduced to 12.5 mg, but “pain and muscle weakness worsened to such an extent that the patient was unable to walk,” the researchers wrote. He also had new-onset hypertension and swollen legs, which were treated with diuretics to control blood pressure and reduce fluid buildup.
Classic Cushing’s features emerged as doctors paused steroids to test cortisol
On examination, he showed classic signs of Cushing’s syndrome: moon face, buffalo hump, thin skin, acne, and purple stretch marks. “He was sitting in a wheelchair due to weakness and severe pain in the hip,” the researchers wrote. As a first step, doctors stopped prednisolone for three days to check his cortisol levels.
His morning cortisol remained high, and ACTH — the hormone that normally stimulates the adrenal glands — was almost undetectable. This pattern suggested his body was still producing too much cortisol despite stopping prednisolone. The lack of adrenal-insufficiency symptoms supported this conclusion.
He then underwent a 1-mg overnight dexamethasone suppression test, which checks whether cortisol levels fall after a dose of dexamethasone, a potent synthetic form of cortisol. Because his cortisol levels stayed high, the test confirmed excess cortisol coming from inside the body.
This dual manifestation has been reported in a few case reports, highlighting its rarity and the complex diagnostic and therapeutic challenges it poses.
A CT scan of the adrenal glands showed a solid, relatively large tumor on the left side. Since some adrenal tumors can mimic Cushing’s syndrome or make other hormones, doctors also tested for pheochromocytoma, a rare type of tumor; those results were normal.
After surgeons removed the left adrenal gland, the man received temporary replacement therapy because his remaining adrenal gland had been suppressed by long-term excess cortisol. Examination under a microscope showed a lipid-poor adrenal cortical adenoma — a benign, cortisol-producing tumor.
Over the next months, his replacement corticosteroids were tapered off safely. His muscle strength returned, his pain eased, and his Cushing’s features gradually resolved. He lost weight, his blood pressure normalized without medication, and all lab tests remained normal six months after surgery.
“The co-occurrence of an endogenous [Cushing’s syndrome] in the setting of an exogenous [Cushing’s syndrome] is curious,” the researchers wrote. “The diagnosis is based on a high clinical suspicion,” so doctors should watch “for symptom resolution after tapering and discontinuing corticosteroids.”
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