The authors explore four (4) major areas:
- Cerebrovascular disease following pituitary radiotherapy
- Cerebrovascular mortality following pituitary radiotherapy for non-functioning adenomas
- Impact of pituitary radiotherapy on mortality in acromegaly
- Hypopituitarism and excess mortality following pituitary radiotherapy
I am mainly interested in the first and the last in the list above. These impact those with Cushing's who are considering or have undergone radiotherapy.
Cerebrovascular disease is already a risk with Cushing's patients. In Mortality in Patients Treated for Cushing’s Disease Is Increased, Compared with Patients Treated for Nonfunctioning Pituitary Macroadenoma (Dekkers, et al), the authors conclude:
[M]ortality is increased in patients with Cushing’s disease, compared with both NFMA and acromegaly. This implicates that transient exposure to cortisol excess is a major contributor of the increased mortality, even after cure of Cushing’s disease. This observation may also be of relevance for patients treated with exogenous glucocorticoids for nonendocrine diseases.
Cited in the same study, "Causes of death were cardiovascular disease in 23.4%, cerebrovascular disease in 12.8%, malignancy in 19.1%, and infectious diseases in 17% of all patients. " Thus, there is already a link to mortality due to cerebrovascular disease and Cushing's.
The Ayuk/Stewart analysis cited a "study of 331 patients with pituitary adenomas treated with surgery and radiotherapy [where] increasing doses of radiotherapy were associated with increasing risk of cerebral infarction." They go on to admit there is a lot of debate about what caused the cerebrovascular events, with radiation thought to be a cause due to "changes to the cerebral vasculature".
The Dekkers study counters that: "By regression analysis, in a model adjusted for age and gender, radiotherapy and hypopituitarism were not associated with increased mortality risk."
Ayuk and Stewart, when analyzing the data from multiple sources, disagree. Hypopituitarism is common after treatement for pituitary adenomas. They cite several studies which show "over 50% of patients treated with pituitary radiotherapy will develop deficiencies in one or more anterior pituitary hormones over the following decade." They then analyzed numerous studies which "examined mortality in patients with hypopituitarism and which found increased mortality compared with age-matched controls, predominantly due to cerebrovascular and cardiovascular disease."
In two of the studies analyzed, radiotherapy did not seem to attribute to increased mortality. But in another, larger study of over 1000 patients, "treatment with radiotherapy was associated with a significantly increased mortality rate" when comparing patients who had hypopituitarism from radiotherapy with patients who had hypopituitarism from other treatments or due to tumor.
Age may play a part, also:
The authors also reported higher mortality in patients who had been diagnosed at a younger age, with a standardized mortality ratio of 4.87 in the group younger than 20 years, decreasing to 1.0 in those older than 60 years. This is of particular relevance as over half of the radiotherapy-treated patients were younger than 50 years at the time of treatment.
Overall, the data is unclear about the link between radiotherapy and mortality. The authors were also unclear about whether the hypopituitarism was treated with hormone replacements and what significance this may have. I suspect this was partially due to the information available to them from the studies they analyzed.
John Ayuk, Paul M. Stewart (2008). Mortality following pituitary radiotherapy Pituitary, 12 (1), 35-39 DOI: 10.1007/s11102-007-0083-1