Subclinical Cushing’s Triggered Shingles, Cardiac Arrest

The case of an elderly woman who developed shingles triggered by subclinical Cushing’s disease, and later died from sudden cardiac arrest, underscores the importance of closely monitoring immune responses in patients showing signs of that disorder.

Her case was described in the study, “Severe infection including disseminated herpes zoster triggered by subclinical Cushing’s disease: a case report,” published in the journal BMC Endocrine Disorders.

Cushing’s disease is caused by tumors in the brain’s pituitary gland that release excessive amounts of adrenocorticotropic hormone (ACTH), which leads to the overproduction of cortisol. Patients with Cushing’s are at an increased risk of contracting infections and developing metabolic issues, which all are associated with an increased risk of mortality.

Patients with subclinical Cushing’s disease have mildly elevated cortisol levels, but lack the physical features associated with the disease, such as a round face or excessive weight gain around their midsection (central obesity).

The condition has been associated previously with an increased risk of death due to metabolic issues, such as high blood pressure (hypertension) and cardiovascular (heart) disease. Yet, the association between subclinical Cushing’s and infections is less clear.

Here, researchers described the case of an 83-year-old Japanese woman who was diagnosed with subclinical Cushing’s after a brain MRI scan revealed she had a tumor in her pituitary gland. Although her blood ACTH and urinary cortisol levels were elevated, she showed no obvious physical signs of Cushing’s. 

Surgery was ruled out due to the patient’s advanced age and other health complications, such as diabetes. Instead, she was treated with 0.25 mg of cabergoline per week, which was increased gradually to a weekly dose of 1.5 mg when her ACTH levels remained elevated.

Although her pituitary tumor remained roughly the same size for several years, her blood sugar levels became increasingly more difficult to control, prompting physicians to begin treatment with insulin glargine, liraglutide, and mitiglinide calcium. 

Eighteen years later, the patient was admitted to the hospital with impaired consciousness and a slight fever of 99.9 F (37.7 C). Lab tests revealed she had elevated white blood cell counts, as well as high levels of the inflammation marker C-reactive protein (CRP) and ACTH.

A computed tomography scan and bacterial cultures revealed abnormalities suggestive of a bacterial kidney infection. The patient was treated with antibiotics, which lowered her fever and CRP levels. Her blood sugar control, however, remained poor despite intensive insulin treatment.

A rash was found on the patient’s chest on the seventh day of her hospitalization and rapidly spread over her entire body. She was diagnosed with herpes zoster, also known as shingles, and treated with the antiviral valacyclovir.

Further lab tests showed signs of multiple organ dysfunction. The patient went into sudden cardiac arrest caused by septic shock and died. An autopsy later revealed that her pituitary tumor was ACTH-positive, and several signs of disseminated herpes zoster (DHZ), including a kidney abscess and a varicella-zoster virus infection in the esophagus.

“To the best of our knowledge, this is the first report in which [subclinical Cushing’s disease] might be one of the triggers of severe infection including DHZ,” the investigators wrote. “These severe infections induced septic shock and multiple organ failure, ultimately resulted in mortal outcome.”

“As our case emphasized the risk of severe infections in the patients with [subclinical Cushing’s disease], the patients should be assessed not only for the metabolic but also for the immunodeficient status,” they concluded.