Association between premature mortality and hypopituitarism

• Published in: The Lancet (British edition) Vol. 357; no. 9254; pp. 425 - 431
• Main Authors: Tomlinson, JW, Holden, N, Hills, RK, Wheatley, K, Clayton, RN, Bates, AS, Sheppard, MC, Stewart, PM
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 10.02.2001; Lancet; Elsevier Limited
• Subjects: Age; Analysis. Health state; Biological and medical sciences; Cardiovascular diseases; Cerebrovascular system; Diagnosis; Disease; Endocrinopathies; Epidemiology; Fatalities; General aspects; Gonadotropins; Growth hormones; Health risks; Hypertension; Hypopituitarism; Hypothalamus. Hypophysis. Epiphysis (diseases); Insulin; Medical disorders; Medical prognosis; Medical research; Medical sciences; Mortality; Neoplasia; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Patients; Pituitary; Pituitary (anterior); Pituitary gland; Population; Premature mortality; Public health. Hygiene; Public health. Hygiene-occupational medicine; Radiation therapy; Regression analysis; Respiratory diseases; Risk analysis; Risk factors; Sex; Surgery; Tumors; United Kingdom; Europe; United Kingdom > UK; Midlands (England); England; Endocrinopathy; Human; Hypophyseal insufficiency; Follow up study; Mortality; Pituitary diseases; Cause; Risk factor; Adult; Child; Epidemiology; Public health
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(00)04006-X

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 endocrine deficiencies, and the mechanisms underpinning any excess mortality are unknown. Furthermore, the suggestion has emerged that endogenous growth-hormone deficiency might account for any excess mortality. We aimed to clarify these issues by doing a large prospective study of total and specific-cause mortality in patients with hypopituitarism. We followed up 1014 UK patients (514 men, 500 women) with hypopituitarism from January, 1992, to January, 2000. 573 (57%) patients had non-functioning adenomas, 118 (12%) craniopharyngiomas, and 93 (9%) prolactinomas. SMRs were calculated as the ratio of observed deaths to the number of deaths in an age-matched and sex-matched UK population. The number of observed deaths was 181 compared with the 96·7 expected (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 diagnosis 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 1·66 [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 of hormonal deficiency on mortality, except for gonadotropin deficiency, which, 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 untreated gonadotropin deficiency as independent significant factors affecting mortality. Patients with hypopituitarism have excess mortality, predominantly 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 gonadotropin deficiency, does not seem to have a role.