Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality.

CONTEXT

Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified.

OBJECTIVE

To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up.

DESIGN AND METHODS

All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed.

MAIN OUTCOME MEASURES

Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up.

RESULTS

An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy.

CONCLUSION

Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.