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Cortisol excess linked with increased mortality rate
The all-cause mortality was 16% in patients with Cushing’s disease.
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Patients with Cushing’s disease have a higher mortality risk compared with patients treated for nonfunctioning pituitary macroadenomas.
The increased mortality is due to overproduction of cortisol, according to data published in the Journal of Clinical Endocrinology and Metabolism.
“In Cushing’s disease, the increased mortality is probably due to cardiovascular disease. Clinicians should be aware of this mechanism. Moreover, this underscores the importance of adequate treatment of cardiovascular risk management in Cushing’s disease,” Olaf M. Dekkers, MD, PhD, with the department of endocrinology and epidemiology at Leiden University Medical Center in the Netherlands, said in an interview with Endocrine Today.
Dekkers said that overproduction of cortisol, “leads to vascular damage, which predisposes patients for increased cardiovascular risk.”
Dekkers and colleagues at Leiden University Medical Center compared mortality between patients treated for Cushing’s disease and nonfunctioning pituitary macroadenomas.
“We already knew that Cushing’s disease was associated with an increased mortality. When we compared Cushing’s disease to nonfunctioning pituitary macroadenomas we were able to assess the effect of cortisol production per se on mortality because the main distinction between the two diseases is the cortisol overproduction,” Dekkers said.
12-year follow-up study
Dekkers and colleagues analyzed 248 patients treated by primary transsphenoidal surgery; 174 for nonfunctioning pituitary macroadenomas and 74 for Cushing’s disease. There was a higher prevalence of Cushing’s disease (77%) compared with nonfunctioning pituitary macroadenomas (44%) in women (P<.001).
Each patient was operated on by the same team of neurosurgeons.
The researchers collected clinical, endocrinological and visual characteristics of each patient for two months after surgery, and again every six to 12 months during follow-up.
Fifty patients received conventional postoperative radiotherapy to prevent recurrence of nonfunctioning pituitary macroadenomas, or to treat persistent Cushing’s disease. Persistent or recurrent disease was also treated by bilateral adrenalectomy, repeat surgery or a combination of the two.
To assess mortality in the patients, the researchers calculated the standardized mortality ratio for the entire cohort and performed Cox-regression analysis for comparison between the groups.
Standardized mortality ratios
At the time of operation, patients with Cushing’s disease (mean age, 39.1 years) were younger than patients with nonfunctioning pituitary macroadenomas (mean age, 55.3 years; P<.001). “However, one does not expect younger people to die with the same mortality rate as older people,” Dekkers said.
During the 10-year follow-up, 47 patients died (35 with nonfunctioning pituitary macroadenomas, 12 with Cushing’s disease). The researchers said the all-cause mortality was 20% in patients with nonfunctioning pituitary macroadenomas and 16% in patients with Cushing’s disease. Causes of death included cardiovascular disease (23.4%), cerebrovascular disease (12.8%), malignancy (19.1%) and infectious diseases (17%).
The entire cohort had a standardized mortality ratio of 1.41 (95% CI, 1.05-1.86). Patients with nonfunctioning pituitary macroadenomas had a mortality ratio of 1.24 (95% CI, 0.85-1.74), compared with 2.39 (95% CI, 1.22-3.9) for patients with Cushing’s disease.
The standardized mortality ratio in patients with Cushing’s disease with remission after transsphenoidal surgery was 1.80 (95% CI, 0.71-3.37); in patients with persistent disease, it was 4.38 (95% CI 1.38-9.07).
According to the researchers, the age-adjusted mortality was significantly increased in patients with Cushing’s disease (HR 2.35; 95% CI, 1.13-4.09).
Excess cortisol exposure
According to the researchers, these findings imply that overexposure to cortisol is associated with increased mortality, and the mortality seems to be correlated with the duration of overexposure. “The effects of transient cortisol overproduction may not be reversible with respect to certain biological properties that influence mortality,” the researchers wrote.
Dekkers recommended the adequate treatment of hypopituitarism in both patients with nonfunctioning pituitary macroadenomas and patients with Cushing’s disease, because in addition to the cortisol excess, “hypopituitarism plays a role in the increased mortality rates compared with the general population.” –by Katie Kalvaitis
For more information:
- Dekkers OM, Biermasz NR, Pereira AM, et al. Mortality in patients treated for Cushing’s disease is increased compared with patients treated for nonfunctioning pituitary macroadenoma. J Clin Endocrinol Metab. 2007;1210:2006-2112.