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Cited by 184Pituitary Gland Disorders and TreatmentsAdrenal Hormones and DisordersStress Responses and Cortisol

Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality

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Burman, P., Mattsson, A. F., Johannsson, G., Höybye, C., Holmer, H., Dahlqvist, P., Berinder, K., Engström, B. E. +5 more·2013·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2012-4059
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Abstract

CONTEXT: Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified. OBJECTIVE: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up. DESIGN AND METHODS: All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed. MAIN OUTCOME MEASURES: Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up. RESULTS: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy. CONCLUSION: Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

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  • Excess cardiovascular mortality might be specifically related to adrenal crisis.

    “Excess cardiovascular mortality might be specifically related to AC (30).”

    From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [30]

    The Discussion (pp. 8–9) says this cohort’s excess mortality was not accounted for by cardiovascular or cerebrovascular deaths; cardiovascular mortality did not significantly exceed that of the reference population. It instead identifies adrenal crisis as a contributor to deaths associated with infection, so the paper does not link an excess of cardiovascular deaths to adrenal crisis. (LLM, conf=0.87)

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Research works printed but not linked: 4

  1. [4]4. Tomlinson JW, Holden N, Hills RK, et al, and the West Midlands Prospective Hypopituitary Study Group. Association between prematuremortality and hypopituitarism. Lancet. 2001;357:425-431.
  2. [7]7. vanBunderenCC,vanNieuwpoortC,ArwertLI,etal. Doesgrowth hormone replacement therapy reduce mortality in adults with growthhormonedeficiency?DatafromtheDutchNationalRegistry of Growth Hormone Treatment in Adults. J Clin Endocrinol Metab. 2011;96:3151-3159.
  3. [22]22. RonE,ModanB,BoiceJDJr,etal. Tumorsofthebrainandnervous system after radiotherapy in childhood. N Engl J Med . 1988;19: 1033-1039.
  4. [20]20. Tsang RW, Laperriere NJ, Simpson WJ, Brierley J, Panzarella T, Smyth HS. Glioma arising after radiation therapy for pituitary adenoma. A report of four patients and estimation of risk. Cancer 1993;72:2227-2233.

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Authors
Burman, P., Mattsson, A. F., Johannsson, G., Höybye, C., Holmer, H., Dahlqvist, P., Berinder, K., Engström, B. E., Ekman, B., Erfurth, E. M., Svensson, J., Wahlberg, J., & Karlsson, F. A.
Affiliations
  • Skåne University Hospital (SE)
  • Pfizer (Sweden) (SE)
  • Department of Endocrinology (G.J.), SE-413 45 Gothenburg, Sweden
  • Karolinska University Hospital (SE)
  • Centralsjukhuset Kristianstad (SE)
  • Umeå University (SE)
  • Uppsala University (SE)
  • Linköping University (SE)
  • University of Gothenburg (SE)
Corresponding author
Burman, P.
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2013-04-01
Volume
98
Issue
4
Pages
1466-1475
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2012-4059
OpenAlex
W2032579876
Semantic Scholar
d11009fa0be3f643281d362bc59272dcf27737b8
Cited by
184
References
34
Citations by year
2026: 3 · 2025: 2 · 2024: 13 · 2023: 13 · 2022: 9 · 2021: 20 · 2020: 16 · 2019: 15 · 2018: 14 · 2017: 23 · 2016: 16 · 2015: 12 · 2014: 20 · 2013: 7
FWCI
14.42
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
hypopituitarism, mortality, adrenal crisis, adrenal insufficiency, acute stress, pituitary radiotherapy, ACTH deficiency, infection, sudden death, standardized mortality ratio
MeSH terms
Acute Disease, Adult, Aged, Astrocytoma, Brain Neoplasms, Cause of Death, Female, Glioma, Humans, Hydrocortisone, Hypopituitarism, Male, Middle Aged, Stress, Psychological, Age of Onset, Young Adult

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