Association between premature mortality and hypopituitarism

Background Four retrospective studies have reported premature mortality in patients with hypopituitarism with standard mortality ratios (SMRs) varying between 1.20 and 2.17. Patients with hypopituitarism have complex endocrin e deficiencies, and the mechanisms underpinning any excess mortality are un known. Furthermore, the suggestion has emerged that endogenous growth-hormo ne deficiency might account for any excess mortality. We aimed to clarify t hese issues by doing a large prospective study of total, and specific-cause mortality in patients with hypopituitarism. Methods We followed up 1014 UK patients (514 men, 500 women) with hypopitui tarism from January, 1992, to January, 2000, 573 (57%) patients had non-fun ctioning adenomas, 118 (12%) craniopharyngiomas, and 93 (9%) prolactinomas. SMRs were calculated as the ratio of observed deaths to the number of deat hs in an age-matched and sex-matched UK population. Findings The number of observed deaths was 181 compared with the 96.7 expec ted (SMR 1.87 [99% CI 1.62-2.16], p<0.0001). Univariate analysis indicated that mortality was higher in women (2.29 [1.86-2.82]) than men (1.57 [1.28- 1.93], p=0.002), in younger patients, in patients with an underlying diagno sis of craniopharyngioma (9.28 [5.84-14.75] vs 1.61 [1.30-1.99], p<0.0001), and in the 353 patients treated with radiotherapy (2.32 [1.71-3.14] vs 1.6 6 [1.30-2.13], p=0.004). Excess mortality was attributed to cardiovascular (1.82 [1.30-2.54], p<0.0001), respiratory (2.66 [1.72-4.11], p<0.0001), and cerebrovascular (2.44 [1.58-4.18], p<0.0001) causes. There was no effect o f hormonal deficiency on mortality, except for gonadotropin deficiency, whi ch, if untreated was associated with excess mortality (untreated 2.97 [2.13 -4.13] vs treated 1.42 [0.97-2.07], p<0.0001). Multiple regression analyses identified age at diagnosis, sex, a diagnosis of craniopharyngioma, and un treated gonadotropin deficiency as independent significant factors affectin g mortality. Interpretation Patients with hypopituitarism have excess mortality, predomi nantly from vascular and respiratory disease. Age at diagnosis, female sex, and above all, craniopharyngioma were significant independent risk factors . Specific endocrine-axis deficiency, with the exception of untreated gonad otropin deficiency, does not seem to have a role.