ArticlesAssociation between premature mortality and hypopituitarism
Introduction
Four retrospective studies have examined mortality in patients with hypopituitarism and all have confirmed increased mortality compared with age-matched controls.1, 2, 3, 4 The exact cause of this increased mortality remains unclear and has been the subject of much debate. Respiratory, cardiovascular, and cerebrovascular diseases have all been cited as being responsible for the increase in mortality. 1, 2 However, there are major limiting factors with all the studies published to date. They include differences in treatments, inclusion criteria, and duration of follow-up, and above all, none has had sufficient power in terms of numbers of patients to disentangle the complexities of this disorder and to determine exactly which factors are most important in influencing mortality. Patients with hypopituitarism have compound endocrine deficiencies, any of which may have an important role. They also undergo various treatments, surgery, drug therapy, and radiotherapy, all of which might contribute to outcome. Finally, to label all patients as simply having a diagnosis of hypopituitarism is probably unjustified, since this definition encompasses many underlying diagnoses. Acromegaly and Cushing's disease are known to confer excess mortality because of their association with high concentrations of growth hormone and cortisol, respectively.5, 6, 7, 8 Having excluded such cases, whether differing causes of hypopituitarism convey a good or bad prognosis is uncertain.
In this prospective study, we examined total and specific-cause mortality in more than 1000 patients with a diagnosis of hypopituitarism, and attempted to identify factors contributing to the excess mortality. We did subgroup analyses to explore many of the questions that still exist about mortality in hypopituitarism—eg, the role of growth-hormone deficiency, sex-steroid status, and corticosteroid replacement therapy, all of which have been implicated in mortality.2, 4, 9, 10 We also examined the use of radiotherapy amid increasing concern over its long term safety and complications.11, 12
Section snippets
Patients
The West Midlands Hypopituitary database was established in 1990 and has the approval of local hospital ethics committees. The database comprises patients with underlying pituitary disease from 16 referral centres across the West Midlands region in the UK (population about 5·5 million, representing about 10% of the UK population). All patients with a diagnosis of hypopituitarism who were alive on Jan 1, 1992, were entered onto the database the analysis for this study was done 8 years later in
Patients
1014 patients had a diagnosis of hypopituitarism, of whom 514 were men. Median age at diagnosis in men was 46·2 years (range 4–81) and in women 45·3 years (range 4–86). Median duration of disease (from diagnosis) was 12·1 years (range 0·5–49) in men and 12·7 years (range 0·5–49) in women. 573 (57%) patients were diagnosed as having non-functioning adenomas, 118 (12%) craniopharyngiomas, 93 (9%) prolactinomas, and 92 (9%) were labelled as having idiopathic hypopituitarism (table 1). Median
Discussion
Since the seminal publication of Rósen and Bengtsson,1 four retrospective studies have examined mortality in patients with hypopituitarism. All have shown higher mortality than the general population, with an excess mortality among women. However, they all have limitations and have produced conflicting data. First, the cohorts of patients are not identical, have had varying periods of follow-up, and comprise relatively small numbers of patients (172–344). Second, there have been wide variations
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