Lung cancer revealed as Cushing’s syndrome cause: Case report
Researchers say case shows complex symptoms warrant 'coordinated approach'
A 52‑year‑old woman who came to the hospital complaining of chest pain and difficulty breathing was found to have both lung cancer and Cushing’s syndrome. Researchers said the cancer caused the Cushing’s, a rare occurrence that shows the need for “a coordinated, multidisciplinary approach” to managing complex sets of symptoms.
Doctors’ prompt identification of Cushing’s syndrome allowed them to treat the woman’s hormone-related issues quickly before referring her to the oncology department for chemotherapy to treat her small cell lung cancer (SCLC).
They detailed their efforts in a case report, “Paraneoplastic Cushing Syndrome Unmasking Small Cell Lung Cancer: A Rare Presentation,” published in Cureus.
Cushing’s syndrome is caused by prolonged exposure to high levels of cortisol, a hormone that regulates metabolism, blood pressure, and the body’s stress response, among other functions. The most common cause is Cushing’s disease, which occurs when a tumor in the brain’s pituitary gland produces too much adrenocorticotropic hormone (ACTH), overstimulating the adrenal glands above the kidneys and driving them to produce excess cortisol.
In rarer cases, tumors outside the pituitary gland can also secrete high levels of ACTH, leading to what’s known as ectopic Cushing’s syndrome. When this abnormal hormone production is caused by a malignant tumor, it is known as paraneoplastic Cushing’s syndrome.
Early identification ‘critical’
Paraneoplastic Cushing’s often appears suddenly, with severe metabolic problems such as low potassium levels, high blood sugar, and muscle weakness, sometimes without the classic physical features of Cushing’s syndrome.
“These atypical and rapidly progressing symptoms can delay diagnosis, especially in patients with aggressive malignancies,” the researchers wrote. “Early identification is critical, as the metabolic derangements associated with this syndrome can lead to significant [health issues] if left untreated.”
The woman in the case report arrived at the hospital after a week of worsening chest discomfort and shortness of breath. She had no history of similar symptoms or other significant medical conditions, and physical examination did not reveal any notable abnormalities.
Blood tests, however, showed very low potassium levels, significantly high blood sugar despite no history of diabetes, and metabolic alkalosis — a condition where the body’s pH is higher than normal.
The woman’s potassium levels remained persistently low despite intravenous (into-the-vein) and oral potassium supplementation, and her blood sugar was difficult to control, requiring insulin treatment.
A chest X-ray suggested a lung tumor, and a CT scan confirmed a suspicious mass in the right lung. Because of the persistent metabolic abnormalities, doctors suspected a cancer-related hormone complication.
They found the woman had elevated cortisol and ACTH levels, and her cortisol levels failed to decline with dexamethasone suppression tests, indicating ectopic Cushing’s syndrome. Further imaging and biopsy results confirmed the diagnosis of paraneoplastic Cushing’s syndrome, caused by ectopic ACTH production by the lung cancer cells.
“Although rare, ectopic ACTH syndrome is a well-recognised paraneoplastic manifestation of SCLC, reported in approximately 1-5% of cases,” the researchers wrote. “This rare clinical entity results from autonomous ACTH secretion by the tumour, leading to [enlargement and overactivity of the adrenal glands] and excessive cortisol production.”
Additional scans, including CT of the abdomen and MRI of the brain, found no signs of distant tumor metastasis, and the cancer was classified as limited-stage small cell lung cancer.
Following discussions with the endocrinology team, the woman was started on metyrapone, a medication that lowers cortisol production, and spironolactone, which helps correct low potassium levels. Treatment stabilized her potassium levels.
She was then reviewed by a multidisciplinary team and referred to the oncology department to begin chemotherapy.
“For clinicians, this case reinforces the need to maintain a high index of suspicion for paraneoplastic endocrine disorders in patients with unexplained electrolyte and metabolic abnormalities, particularly when accompanied by respiratory symptoms or imaging suggestive of a pulmonary lesion,” the researchers wrote.
It “also highlights the complexities of managing ectopic Cushing’s syndrome, where severe metabolic disturbances can delay definitive cancer treatment,” they wrote. “A coordinated, multidisciplinary approach involving endocrinology, oncology, and respiratory teams was crucial in optimising patient care and improving the likelihood of a favourable outcome.”
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