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Gonadotropin, ACTH deficiencies increase mortality risk
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Gonadotropin and adrenocorticotropic hormone deficiencies in adults with nonfunctioning pituitary adenomas are tied to an increased risk for mortality, according to study findings recently published in Clinical Endocrinology.
Michael W. O’Reilly, PhD, of the Institute of Metabolism and Systems Research at the University of Birmingham in the United Kingdom, and colleagues evaluated data from 519 adults (mean age, 57 years) with nonfunctioning pituitary adenomas treated between 1999 and 2014. Follow-up was a median of 7 years. Researchers sought to determine the relationships between hypopituitarism, hormone replacement and mortality.
Overall, 81 deaths occurred during the study; median age at death was 78 years and median time to death from tumor diagnosis was 108 months. The most common cause of death was cardiovascular (excluding cerebrovascular; 31.4%) followed by cerebrovascular (22.9%), malignancy (17.1%), infection (17.1%), respiratory (10%) and trauma (1.4%). Participants who died had higher rates of deficiencies in growth hormone, gonadotropin, adrenocorticotropic hormone (ACTH) and thyroid-stimulating hormone compared with those who survived (P < .001 for all).
The RR for death was higher among participants treated with radiotherapy compared with those who were not (RR = 1.62; 95% CI, 1.01-2.6) after correction for surgery, age at diagnosis, sex and attained age. The RR for death from infection was also higher among participants treated with radiotherapy compared with those who were not (RR = 2.02; 95% CI, 1.03-3.97) in the cause-specific mortality analysis.
Increased mortality was independently associated with ACTH deficiency (RR = 2.56; 95% CI, 1.1-5.96) and gonadotropin deficiency (RR = 2.26; 95% CI, 1.15-4.47). The RR for death was increased in participants with ACTH deficiency taking hydrocortisone doses of 30 mg or higher (RR = 3.79; 95% CI, 1.49-9.67) and in participants with TSH deficiency taking less than 100 µg daily of levothyroxine (RR = 2.41; 95% CI, 1.23-4.73).
“Excessive [hydrocortisone] replacement, coupled with suboptimal treatment of central hypothyroidism, may contribute further to the adverse cardiometabolic milieu in hypopituitary [nonfunctioning pituitary adenoma] patients,” the researchers wrote. “Whilst pituitary [radiotherapy] is also associated with an increased relative risk of death in [nonfunctioning pituitary adenoma], the connection with increased mortality may be attributable simply to the high prevalence of hypopituitarism in irradiated patients. We have also shown that mortality risk in patients treated for [nonfunctioning pituitary adenoma] increases in a linear fashion across a spectrum of pituitary failure. This suggests a cumulative contribution of multiple hormone deficiencies, which is potentially greater than the sum of individual risk.” – by Amber Cox
Disclosure: The study was funded by the Wellcome Trust Research Training Fellowship.
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