Men with ectopic Cushing’s prone to diabetes, osteoporosis, study finds
High blood pressure more common in women, work into sex differences finds
High blood-sugar levels and osteoporosis — a condition causing bones to weaken and be prone to fracture — are more common in men with ectopic Cushing’s syndrome than women, who are more likely to have high blood pressure, a Turkish study reports.
“Apart from these, the lack of sex differences, especially regarding long-term disease status, suggested that similar follow-up management was sufficient for both sexes,” the researchers wrote, adding that similar studies involving greater numbers of patients are needed.
The study, “Comparison of clinical, hormonal, pathological and treatment outcomes of ectopic Cushing’s syndrome by sex: results of a multicenter study,” was published in the journal Endocrine.
Studies into sex differences are known in Cushing’s disease
Cushing’s syndrome is an umbrella term that encompasses several conditions marked by unusually high levels of the hormone cortisol. The disease is considered endogenous when the hormone’s excess is caused by a problem within the body, most commonly a pituitary tumor that produces and releases adrenocorticotropic hormone (ACTH).
High levels of ACTH, in turn, cause the adrenal glands atop the kidneys to overproduce cortisol, leading to Cushing’s. This specific form of the syndrome is known as Cushing’s disease.
In a smaller proportion of cases, ACTH-producing tumors found outside the brain’s pituitary gland also trigger cortisol overproduction. This is known as ectopic Cushing’s syndrome.
While previous studies reported that a patient’s sex can influence the clinical outcomes of Cushing’s disease, no such analysis has been conducted in the case of ectopic Cushing’s.
Researchers analyzed data covering 54 patients with ectopic Cushing’s who had been followed at 11 centers in Turkey. They assessed and compared clinical and hormonal data, as well as treatment strategies and survival outcomes.
No significant changes in disease symptoms, hormone levels seen by sex
Among the patients, 28 (52%) were female and 26 (48%) were male. Women had a mean age of 43 years at the time of diagnosis, while men were slightly younger, at a mean age of 41.
Clinical features, including symptoms, and the levels of various hormones were similar between the two groups. General swelling (edema) occurred more frequently in women than in men (36% vs. 12%), as did facial fat accumulation, a characteristic known as moon face (82% vs. 58%).
Diabetes requiring treatment with insulin and osteoporosis accompanied by bone fractures both were significantly more frequent in men than in women (42% vs. 18% for diabetes; 35% vs. 11% for osteoporosis). But high blood pressure, or hypertension, was seen more often in female than male patients (82% vs. 50%).
At diagnosis, 36 tumors were detected in a majority of patients in both groups: 68% of women and 69% of men. The only sex difference seen among these tumors concerned small cell lung carcinoma, which was more frequent in men. Neuroendocrine tumors (NETs) — rare tumors that affect the cells releasing hormones into the bloodstream — were the most common among other tumors noted, which were found in the thymus gland, thyroid gland, pancreas, and adrenal glands.
Ectopic Cushing’s course largely is similar among men and women
Curative surgery was performed on 61% of female patients and 46% of male patients. After surgery, 34 of the 47 tumors (14 from men and 20 from women) were processed for ACTH detection. Results confirmed that all tumors taken from female patients and 93% of those taken from males were ACTH-positive.
At the last follow-up, 65% of the women and 62% of the men were in remission. Deaths due to NETs occurred in 14% of women and 30% of men, a difference that was not considered to be statistically significant.
“While [ectopic Cushing’s syndrome] has a similar disease course in many aspects in males and females, hyperglycemia [high blood sugar] and osteoporosis are more severe in males,” the researchers wrote, with their severity in men possibly due to the difficulty of controlling blood-sugar levels with “central hypothyroidism and the destructive effect of malignancies on bone.”
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