Cardiovascular mortality and morbidity in hypopituitary patients and metabolic effects of growth hormone treatment

Abstract: Premature atherosclerosis, cardiovascular risk factors and increased cardiovascular mortality have been shown in patients with hypopituitarism on conventional hormone treatment, but without growth hormone (GH) replacement. The aims of paper I-III were to investigate separately the risks for cerebrovascular and cardiac mortality as well as the incidence of cardiovascular disease in patients with hypopituitarism and to assess the long-term prognosis for patients with craniopharyngioma. GH replacement has been associated with an impairment of glucose tolerance and the objectives of paper IV-V were to investigate whether individualized GH replacement therapy could avoid such a deterioration. There was a 1.75-fold increased cardiovascular mortality in 344 hypopituitary patients operated for a pituitary tumour compared to the general population. The risk for death in cerebrovascular disease was higher than for cardiac disease and females had a higher risk increase than males. A survival analysis of 60 patients operated for craniopharyngioma showed a more than 3-fold increase in cardiovascular mortality compared to the general population. There were no protective effects of radicality at surgery or radiotherapy on survival in patients with craniopharyngioma. Increased incidence of cardiovascular disease and increased prevalence of cardiovascular risk factors, such as lower degree of physical exercise, higher WHR, lower HDL-cholesterol and higher LDL:HDL ratio were observed in 33 hypopituitary females compared to a control group matched for sex, age, smoking habits, educational level and residence location. The increased cardiovascular mortality and morbidity could not be explained by inadequate treatment with corticosteroids, thyroid hormones or sex hormones alone. Unsubstituted GH deficiency (GHD) is likely to be a more important contributing factor. Individualized GH treatment to ten patients with childhood onset GHD caused a significant decrease in fat mass, but no impairment was observed in glucose tolerance during euglycemic conditions. The GH dose was adjusted after serum insulin-like growth facor-I (IGF-I) levels, which could be a useful method for monitoring GH treatment in adults with childhood onset GHD. During hypoglycemia, GH therapy caused an increase in insulin resistance, which could not be explained by changes in the counterregulatory hormones or serum IGF-binding protein-1.