REVIEW Considering GH replacement for GH-deficient adults with a previous history of cancer: a conundrum for the clinician Kevin C. J. Yuen 1 • Anthony P. Heaney 2 • Vera Popovic 3 Received: 5 October 2015 / Accepted: 18 December 2015 / Published online: 5 January 2016 Ó Springer Science+Business Media New York 2015 Abstract Previous studies have shown that GH and IGF-I may enhance tumorigenesis, metastasis, and cell prolifer- ation in humans and animals. Evidence supporting this notion is derived from animal model studies, epidemio- logical studies, experience from patients with acromegaly, molecular therapeutic manipulation of GH and IGF-I actions, and individuals with GH receptor and congenital IGF-I deficiencies. Prior exposure to radiation therapy, aging, family history of cancer, and individual suscepti- bility may also contribute to increase this risk. Therefore, the use of GH replacement in patients with a history of cancer raises hypothetical safety concerns for patients, caregivers, and providers. Studies of GH therapy in GH- deficient adults with hypopituitarism and childhood cancer survivors have not convincingly demonstrated an increased cancer risk. Conversely, the risk of occurrence of a second neoplasm (SN) in childhood cancer survivors may be increased, with meningiomas being the most common tumor; however, this risk appears to decline over time. In light of these findings, if GH replacement is to be consid- ered in patients with a previous history of cancer, we propose this consideration to be based on each individual circumstance and that such therapy should only be initiated at least 2 years after cancer remission is achieved with the understanding that in some patients (particularly those with childhood cancers), GH may potentially increase the risk of SNs. In addition, close surveillance should be undertaken working closely with the patient’s oncologist. More long- term data are thus needed to determine if GH replacement in GH-deficient adults with a history of cancer is associated with the development of de novo tumors and tumor recurrence. Keywords Growth hormone Á Growth hormone deficiency Á Adults Á Cancer Á Malignancy Introduction Growth hormone deficiency (GHD) in adults can be caused by any destructive process in the hypothalamic-pituitary region. This may be due to sellar tumors, infiltrative pro- cesses, or as a result of surgery [1] and/or cranial radio- therapy [2]. Current recommended regimens of GH replacement therapy are effective in restoring linear growth and improving adult height outcomes of children with GHD [3, 4], whereas in adults, many of the metabolic and psychological abnormalities associated with GHD may be reversed [2, 5]. Given that GH and IGF-I may enhance tumorigenesis, metastasis, and cell proliferation, there are hypothetical safety concerns for patients, caregivers, and providers of long-term GH replacement in patients with a history of cancer [6–8]. Circumstantial evidence supporting this notion is derived from animal model studies, epidemio- logical associations between high-normal serum IGF-I levels and increased cancer risk, experience from patients & Kevin C. J. Yuen kevin.yuen@swedish.org 1 Department of Neurosurgery and Neurology, Swedish Pituitary Center, Swedish Neuroscience Institute, Seattle, WA 98122, USA 2 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90073, USA 3 Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Center Belgrade, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia 123 Endocrine (2016) 52:194–205 DOI 10.1007/s12020-015-0840-2