Can Increased Growth Hormone in Adults Cause Increased Cancer Growth?
Elevated growth hormone (GH) levels in adults with no prior cancer history do not appear to increase the risk of developing new cancers when GH is used as replacement therapy for GH deficiency, though caution is warranted in cancer survivors and those with active malignancy.
Evidence from GH Replacement Therapy in Adults
The most reassuring evidence comes from long-term surveillance of adults receiving GH replacement for deficiency:
GH replacement therapy at physiological doses does not increase de novo cancer risk in adults with GH deficiency 1, 2. The FDA label for somatropin explicitly contraindicates its use only in patients with active proliferative diabetic retinopathy, acute critical illness, or active progression/recurrence of intracranial tumors, but does not list cancer risk as a contraindication in adults without prior malignancy 1.
In cancer survivors treated with GH replacement, no increased risk of tumor recurrence has been consistently demonstrated 2. A comprehensive review of long-term safety in survivors of cancer and pituitary tumors found predominantly reassuring results, concluding that GHT can be considered after careful individual risk/benefit analysis 2.
The SAGhE European cohort study of 23,984 patients found no clear raised cancer risk in patients with growth failure without other major disease 3. Cancer incidence was unrelated to duration or cumulative dose of recombinant human GH treatment in patients without previous cancer 3.
Critical Distinction: Endocrine vs. Autocrine/Paracrine GH
The key to understanding GH's relationship with cancer lies in distinguishing between different sources and modes of action:
Endocrine GH (pituitary-derived, replacement doses) acts systemically and has not been shown to increase cancer risk in properly selected patients 4. This is the GH used therapeutically for deficiency states.
Autocrine/paracrine GH (produced locally by tumors) acts as a cellular growth factor and is implicated in cancer progression 4. This tumor-derived GH is fundamentally different from therapeutic replacement.
Supraphysiological doses of GH in animal models can induce malignant tumors, but physiological replacement doses do not demonstrate this effect 5, 6.
Specific Cancer Risks and Nuances
In Adults Without Prior Cancer
Slightly elevated IGF-I levels in healthy individuals are associated with modestly increased risk of some cancers (colorectal, prostate, premenopausal breast) 6. However, this association reflects endogenous IGF-I variation, not therapeutic GH replacement.
Acromegaly (chronic GH excess) shows a slight increase in certain cancers, particularly colorectal cancer 6, 4. This represents decades of uncontrolled GH hypersecretion, not replacement therapy.
In Cancer Survivors
The FDA warns that childhood cancer survivors treated with cranial radiation who develop GHD and receive somatropin have an increased risk of second neoplasms, particularly meningiomas 1. This risk appears related to prior radiation exposure rather than GH per se 7.
In the SAGhE study, cancer mortality risk increased significantly with increasing daily GH dose in patients treated after previous cancer (P < 0.001) 3. This dose-response relationship warrants caution in cancer survivors, though causality remains uncertain.
Radiotherapy for pituitary tumors carries a standardized incidence ratio of 658 for meningiomas, but GH replacement doses were not implicated in secondary malignancy risk 7.
Hodgkin lymphoma incidence increased significantly with longer follow-up in GH-treated patients (P = 0.001 overall, P = 0.002 in those without previous cancer) 3. This unexpected finding requires further investigation.
Absolute Contraindications to GH Therapy
The FDA explicitly contraindicates somatropin in 1:
- Active malignancy or evidence of tumor progression/recurrence
- Active proliferative or severe non-proliferative diabetic retinopathy
- Acute critical illness (increased mortality demonstrated in ICU patients)
- Prader-Willi syndrome with severe obesity, upper airway obstruction, or respiratory infection
Monitoring Requirements for Adults on GH Therapy
All patients with history of intracranial neoplasm must be monitored routinely for tumor progression or recurrence 1.
Fundoscopic examination should be performed before initiating treatment to exclude papilledema, and periodically during therapy 1.
Glucose levels should be monitored periodically, as GH may decrease insulin sensitivity and unmask diabetes 1.
Monitor for increased growth or malignant changes in preexisting nevi 1.
Clinical Algorithm for GH Use in Adults
Step 1: Exclude absolute contraindications
- Active malignancy, tumor progression, acute critical illness, active diabetic retinopathy 1
Step 2: Assess cancer history
- No prior cancer: GH replacement is safe with standard monitoring 3, 2
- Prior cancer survivor: Proceed with caution; use lowest effective dose; enhanced surveillance for second neoplasms 3, 2
- Prior cranial radiation: Highest risk group; consider deferring GH or using minimal doses with intensive monitoring 7, 1
Step 3: Baseline assessments
- Fundoscopic exam, glucose tolerance testing, imaging of pituitary region if indicated 1
Step 4: Ongoing surveillance
- Periodic fundoscopy, glucose monitoring, clinical assessment for new masses 1
- In cancer survivors: More frequent imaging and clinical surveillance 2
Common Pitfalls to Avoid
Do not confuse the cancer-promoting effects of tumor-derived autocrine/paracrine GH with the safety profile of replacement-dose endocrine GH 4. These are mechanistically distinct.
Do not withhold GH replacement in adults with documented GHD and no active malignancy based solely on theoretical cancer concerns 2. The morbidity of untreated GHD (cardiovascular disease, osteoporosis, reduced quality of life) must be weighed against unproven cancer risk.
Do not use higher than recommended replacement doses, especially in cancer survivors 3. The dose-response relationship for cancer mortality in survivors suggests using the minimum effective dose.
Do not assume that normal IGF-I levels on GH therapy eliminate cancer risk 6. While reassuring, IGF-I monitoring does not replace clinical surveillance.