Man’s ectopic Cushing’s syndrome goes undiagnosed for years
Delay shows 'lack of awareness;' need to be educated about symptoms
A 40-year-old man who developed ectopic Cushing’s syndrome as a result of a lung tumor remained undiagnosed for years, despite showing Cushing’s symptoms and progressive physical and mental decline, a recent case study shows.
Once he was diagnosed, surgery to remove the tumor resulted in his health improving substantially.
“While many patients with Cushing syndrome have a delayed diagnosis, this case highlights the critical need to increase awareness of the signs and symptoms of hypercortisolism and to improve the understanding of appropriate screening tests among nonendocrine providers,” the researchers wrote in “Delayed Diagnosis of Ectopic Cushing Syndrome,” which was published in JCEM Case Reports.
Cushing’s syndrome refers to disorders that feature high levels of the stress hormone cortisol, called hypercortisolism. A common form of the condition is Cushing’s disease, wherein a tumor in the pituitary gland releases high amounts of adrenocorticotropic hormone (ACTH), a signaling molecule that prompts the adrenal glands to produce cortisol. In rare cases, Cushing’s syndrome is caused by ACTH-producing tumors in other parts of the body, called ectopic Cushing’s syndrome.
The nonspecific nature of Cushing’s symptoms and clinical signs, along with challenges in interpreting diagnostic tests, often lead to delays in diagnosis, which contributes to disease-associated mortality and morbidity.
The path to a diagnosis of ectopic Cushing’s syndrome
A man remained undiagnosed for more than three years while undergoing repeated evaluations by primary care and specialty providers, despite showing classical signs of Cushing’s syndrome and having progressive physical and mental decline, researchers in North Carolina said.
In 2018, the man, then age 40, complained of insomnia, headaches, swelling under the jaw, soreness in his armpits and groin, along with discomfort in the right side of his chest. He’d had these symptoms since the birth of his son about a year earlier.
A chest X-ray revealed a lung nodule. His symptoms persisted through 2019 and were accompanied by cough.
In 2020, he was found to have high blood pressure and had an ankle fracture. He was diagnosed with fibromyalgia, a condition that causes widespread pain and mental distress, and started physical therapy. He was referred for cognitive behavioral therapy due to cognitive and personality changes.
He later developed leg swelling, hypokalemia, or low blood potassium levels, and gained about 35 pounds (about 16 kg) over several months. His blood cortisol levels were evaluated for the first time, but weren’t considered abnormal, despite being above reference ranges at certain times of the day.
In early 2021, he developed atypical skin infections and abdominal stretch marks. A specialist in kidney diseases evaluated him due to swelling and suspected Cushing’s syndrome, considering his symptoms and high cortisol levels. The man was referred to an endocrinology specialist, who noted Cushing’s symptoms, including skin changes, weight gain, fat accumulation, depressed mood, and cognitive changes, at his first evaluation.
Laboratory tests showed his blood cortisol and ACTH levels failed to drop after a low-dose dexamethasone test, while his urine-free cortisol levels were way above reference values, confirming hypercortisolism and Cushing’s syndrome. Blood cortisol and ACTH levels remained elevated after a high-dose dexamethasone test, consistent with an ectopic Cushing’s diagnosis
Imaging tests didn’t show a pituitary tumor, but did detect a lung nodule. He started treatment with ketoconazole to reduce cortisol levels ahead of surgery to remove the ACTH-producing tumor.
After surgery, his cortisol levels dipped under normal levels and he started hydrocortisone, a glucocorticoid replacement therapy.
Within a month after being discharged, he lost about 30 pounds (about 14 kg), and his sleep and mood improved. He was weaned from hydrocortisone eight months after surgery and it was eventually discontinued. At his last follow-up, he was generally well and continued to see improvements in his mood.
The case “highlights the lack of awareness of Cushing syndrome as a potential unifying diagnosis for multi-organ system problems … [and] underscores the necessity of continued education on the signs and symptoms of hypercortisolism, appropriate screening for hypercortisolism, and early referral to endocrinology,” the researchers said, adding it also “provides an opportunity for systemic change in clinical laboratory practice that could help improve recognition of [disease-causing] hypercortisolism.”
About the Author
