Endocrine Abstracts

Increased mortality in patients with acromegaly has been confirmed in a number of retrospective studies, but causative factors and relationship to serum IGF1 remain uncertain. The West Midlands Acromegaly database contains details of 419 patients (178 males). Serum IGF1 data from the Regional Endocrine Laboratory was available for 338 patients (81%). At diagnosis mean age was 47 years (range 12-84) and mean GH was 70plus/minus5.4 milliunits per litre. 61% were treated by surgery and 39% by non-surgical means. Radiotherapy was used alone or as adjuvant therapy in 50%. All patients were registered with the Office of National Statistics to obtain information on deaths.
Of the 419 patients, 95 had died (43 males). The SMR was 1.26 (CI 1.03-1.54). Mortality was increased in subjects with post-treatment GH levels >4 milliunits per litre compared to the general population (SMR 1.35 [1.06-1.71] p=0.02). By contrast, when controlled for age and sex, elevated post-treatment IGF1 levels were not associated with increased mortality (Rate ratio1.01).
Treatment with radiotherapy resulted in increased mortality (SMR 1.7 [1.10-2.56]; p<0.05), not explained by increased tumour size/extension or GH hypersecretion.
Comparison of 153 patients with no evidence of hypopituitarism with 111 patients with 1 deficient hypothalamic-pituitary axis, 57 with 2 and 78 with 3 deficient axes, revealed a trend towards reduced survival in those with the most deficient axes (effect per axis 1.2, p=0.07).
These results confirm the increased mortality in acromegaly and support the generally held view that reduction of GH levels to >4 milliunits per litre is beneficial in terms of improving long-term outcome. The sole use of IGF1 as a marker for effective treatment is not justified by this data. This study also highlights the potential deleterious effect of radiotherapy suggested in previous studies and indicates that medical therapy should be regarded as optimal second line treatment.