ACTH and gonadotropin deficiencies predict mortality in patients treated for nonfunctioning pituitary adenoma: long-term follow-up of 519 patients in two large European centres.
OBJECTIVE
Nonfunctioning pituitary adenomas (NFPAs) are the most common subtype of pituitary tumour. Hypopituitarism is observed in NFPAs due to tumour- or treatment-related factors and may increase mortality risk. Here, we analysed the associations of hypopituitarism, hormone replacement and mortality in a large NFPA cohort derived from two large European centres.


METHODS
Case note review of all patients treated for NFPA in University Hospitals Birmingham and Beaumont Hospital Dublin between 1999 and 2014 was performed.


METHODS
Clinical presentation, treatment strategies, pituitary function and vitality status were recorded in each patient. A multivariate Cox regression model was used to examine the association between hypopituitarism, hormone replacement and premature mortality.


RESULTS
A total of 519 patients were included in the analysis. Median duration of follow-up was 7·0 years (0·5-43). A total of 81 deaths were recorded (15·6%). On multivariate analysis, adrenocorticotropic hormone (ACTH) and gonadotropin (Gn) deficiencies were associated with an increased relative risk of death (OR 2·26, 95% CI 1·15-4·47, P = 0·01 and OR 2·56, 95% CI 1·10-5·96, P = 0·01, respectively). Increased hydrocortisone (HC) (P-trend = 0·02) and lower levothyroxine (LT4) doses (P-trend = 0·03) were associated with increased risk of death. Mortality increased with the degree of pituitary failure observed (P-trend = 0·04).


CONCLUSIONS
ACTH and gonadotropin-deficient patients have higher mortality rates compared to those with intact hormonal axes. Excessive HC and suboptimal LT4 replacement may also increase risk of death. Complex associations between hormone deficiency and replacement underpin the increased mortality risk in NFPA patients.
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. m.oreilly@bham.ac.uk.|Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK. m.oreilly@bham.ac.uk.|Department of Endocrinology, University Hospitals Birmingham, Birmingham, UK. m.oreilly@bham.ac.uk.
Michael W
MW
O'Reilly
School of Health and Population Sciences, University of Birmingham, Birmingham, UK.
Raoul C
RC
Reulen
Division of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland.
Saket
S
Gupta
Division of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland.
Claire A
CA
Thompson
Division of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland.
Rosemary
R
Dineen
Division of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland.
Eirena L
EL
Goulden
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
Gabriella
G
Bugg
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
Harriet
H
Pearce
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.|Department of Endocrinology, University Hospitals Birmingham, Birmingham, UK.
Andy A
AA
Toogood
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.|Department of Endocrinology, University Hospitals Birmingham, Birmingham, UK.
Neil J
NJ
Gittoes
Department of Neurosurgery, University Hospitals Birmingham, Birmingham, UK.
Rosalind
R
Mitchell
Division of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland.
Christopher J
CJ
Thompson
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.|Department of Endocrinology, University Hospitals Birmingham, Birmingham, UK.
John
J
Ayuk
D000236:Adenoma; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000172:deficiency*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006062:Gonadotropins / Q000172:deficiency*; D020249:Hormone Replacement Therapy; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D007018:Hypopituitarism; D008297:Male; D008875:Middle Aged; D009026:Mortality; D010911:Pituitary Neoplasms / Q000401:mortality*; D011379:Prognosis; D013974:Thyroxine / Q000008:administration & dosage; D055815:Young Adult
D006062:Gonadotropins; D000324:Adrenocorticotropic Hormone; D013974:Thyroxine; D006854:Hydrocortisone