ACTH-producing Lung Tumor Cause of Ectopic Cushing’s in Woman, 71

Lung nodules also linked to fungal infection, likely due to immune deficiency

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by Andrea Lobo |

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An illustration of human lungs.

A 71-year-old woman with ectopic Cushing’s syndrome saw her clinical symptoms ease after undergoing surgery to remove several nodules from her left lung.

One nodule removed was a carcinoid tumor producing adrenocorticotropic hormone (ACTH), while another was due to a lung infection caused by the fungus Cryptococcus. Her infection was associated with immunodeficiency due to elevated ACTH production and, subsequently, high cortisol levels.

“This case provides a valuable lesson in that when ACTH-producing tumors are suspected and multiple nodules are present in the lungs, infectious lesions may be present along with carcinoid tumors,” the researchers wrote.

The case report, “Ectopic adrenocorticotropic hormone-secreting carcinoid with solitary cryptococcosis in the lungs,” published in the journal Cancer Reports.

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Cushing’s syndrome is characterized by symptoms associated with hypercortisolism, or high cortisol levels, possibly due to tumors that lead to the excessive ACTH production. Cushing’s disease, a common form of this syndrome, is caused by benign tumors in the brain’s pituitary gland that trigger ACTH production. Rising levels of this hormone signal the adrenal glands, sitting atop the kidneys, to produce cortisol in excessive amounts.

ACTH-producing lung tumors rare cause of ectopic Cushing’s

In rare cases, Cushing’s is caused by an ACTH-producing carcinoid tumor in the lungs. These and other Cushing’s cases that are not due to pituitary tumors are referred ectopic Cushing’s syndrome.

These patients can be susceptible to infections, since excessive ACTH and cortisol production may lower the effectiveness of the immune system. Small cell lung carcinoma accounts for a majority of ectopic cases (40–50 %) and can be difficult to diagnose, particularly when combined with certain infections.

Scientists in Japan detailed the case of an older woman with ectopic Cushing’s syndrome caused by ACTH-producing lung tumors, who also had a fungal lung infection. Infections due to Cryptococcus are commonly seen in immunocompromised individuals, with the fungus often transmitted by bird droppings. This patient did not keep any birds or animals.

The woman had been treated for diabetes for 30 years. However, despite diet and insulin therapy, her blood-sugar levels — measured by the percentage of glycated hemoglobin, meaning hemoglobin holding glucose, or blood sugar — were in the range of 7.9%–8.5% (normal range is under 5.7%). As such, she was considered to have refractory, or difficult to control, diabetes.

She was admitted to the hospital for diabetic dietary and lifestyle guidance in April 2019. While there, she developed recurrent pneumonia and bronchitis, and showed typical Cushing’s symptoms, including a “moon face” (swelling that makes the face round, full, or puffy), obesity, and red skin lines.

Laboratory tests indicated Cushing’s syndrome but were not conclusive, and brain imaging scans did not show any abnormalities in the pituitary gland. The patient declined to undergo sinus blood sampling — a diagnostic test for Cushing’s that measures ACTH levels in blood from veins that drain the pituitary gland — due to its invasiveness.

High-resolution CT scans showed two nodules in her left lung, suggesting the presence of ectopic Cushing’s syndrome. The nodules, one in the lung’s apex (top) region and the other in the lingual region (bottom), were surgically removed eight months after her hospital admission. Immediately after the surgery, she started taking hydrocortisone (50 mg/day) as a precaution for cortisol replacement in case of adrenal insufficiency.

ACTH-producing tumors raise a likelihood of infection

Tissue examination confirmed that the lingual nodule was an ACTH-producing typical carcinoid tumor, whereas the nodule in the apex region was the result of her fungal lung infection.

Four days after the surgery, her blood levels of ACTH and cortisol were normal, and hydrocortisone was gradually reduced. She was discharged 15 days after surgery, with instructions to take a lower dose of hydrocortisone (20 mg/day). Urinary cortisol levels thereafter were within a normal range, and her diabetes and Cushing’s symptoms eased.

The surgery’s effectiveness in treating her Cushing’s was confirmed in tests six months post-surgery, with the woman remaining on hydrocortisone at 15 mg/day. In July, 18 months after undergoing surgery, she showed no evidence of tumor recurrence and no Cushing’s symptoms or elevated ACTH levels.

She maintained insulin therapy to control her diabetes, with her levels of glycated hemoglobin now around 7%. At two years post-surgery, she stopped taking hydrocortisone.

“This [is a] very instructive case in terms of the difficulty of diagnosing ACTH-producing tumors, the possibility of infection complicating the immunodeficiency caused by ACTH-producing tumors, and the surgical strategy,” the scientists wrote, adding that — as in this case — when one lung carcinoid “with ectopic ACTH production” is found, another “nodule of pulmonary infection may be present at the same time” given the possibility of immune system deficiency.

“Fortunately, no serious perioperative infections [those around the time of surgery] occurred in this case, but ACTH-producing tumors can lead to an increased risk of infection … so care must be taken,” they wrote.