Craniopharyngioma in Adults

Erratum to: Acta Neuropathol (2007) 114:97–109 DOI 10.1007/s00401-007-0243-4 References 5, 11 and 17 were incorrect. The correct references are given below. 5. Daumas-Duport C, Scheithauer B, O’Fallon J, Kelly P (1988) Grading of astrocytomas. A simple and reproducible method. Cancer 62:2152–1265 11. Giannini C, Scheithauer BW, Burger PC, Christensen MR, Wollan PC, Sebo TJ, Forsyth PA, Hayostek CJ (1999) Cellular proliferation in pilocytic and diffuse astrocytomas. J Neuropathol Exp Neurol 58:46–53 17. Hsu DW, Louis DN, Efird JT, Hedley-Whyte ET (1997) Use of MIB-1 (Ki-67) immunoreactivity in differentiating grade II and grade III gliomas. J Neuropathol Exp Neurol 56:857–865

Pituitary disease is associated with increased mortality predominantly due to vascular disease. Control of cortisol secretion and GH hypersecretion (and cardiovascular risk factor reduction) is key in the reduction of mortality in patients with Cushing's disease and acromegaly, retrospectively. For patients with acromegaly, the role of IGF-I is less clear-cut. Confounding pituitary hormone deficiencies such as gonadotropins and particularly ACTH deficiency (with higher doses of hydrocortisone replacement) may have a detrimental effect on outcome in patients with pituitary disease. Pituitary radiotherapy is a further factor that has been associated with increased mortality (particularly cerebrovascular). Although standardized mortality ratios in pituitary disease are falling due to improved treatment, mortality for many conditions are still elevated above that of the general population, and therefore further measures are needed. Craniopharyngioma patients have a particularly increased risk of mortality as a result of the tumor itself and treatment to control tumor growth; this is a key area for future research in order to optimize the outcome for these patients.

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.