What are the contraindications for growth hormone (GH) replacement therapy in patients under 30 years old with growth hormone deficiency?

Contraindications for Growth Hormone Replacement Therapy in Patients Under 30 Years

Growth hormone replacement therapy has several absolute contraindications that must be excluded before initiating treatment in patients under 30 years, including closed epiphyses, active malignancy, acute critical illness, known hypersensitivity to GH or its excipients, and pre-existing papilledema. 1

Absolute Contraindications

GH therapy must not be started in the following situations:

• Closed epiphyses - Treatment is futile once growth plates have fused, as documented by radiography of the left wrist 2, 1

• Active malignancy - GH therapy is contraindicated in patients with any active tumor 2, 1

• Acute critical illness - GH should not be initiated during acute critical illness 2, 1

• Known hypersensitivity - Documented allergy to the active substance or any excipients is an absolute contraindication 2, 1

• Pre-existing papilledema - Patients with existing optic disc swelling from increased intracranial pressure should not receive GH 1

Relative Contraindications and High-Risk Situations

Several conditions require careful consideration and may necessitate delaying or withholding GH therapy:

• Severe secondary hyperparathyroidism - GH should not be started when parathyroid hormone levels exceed 500 pg/ml, though therapy may be initiated once PTH returns to target range 2, 1

• Proliferative or severe non-proliferative diabetic retinopathy - This represents a relative contraindication requiring ophthalmologic evaluation 2, 1

• Uncontrolled diabetes mellitus - GH therapy should be deferred until glycemic control is achieved 2

Special Considerations for Patients Under 30 Years

The risk of secondary malignancies, particularly meningiomas and malignant brain tumors, is significantly elevated when radiotherapy is administered before age 30 years, with risk increasing 2.4-fold for malignant brain tumors and 1.6-fold for meningiomas for every 10 years younger at treatment. 2

Cancer History and Radiotherapy

• Patients under 30 who previously received radiotherapy for pituitary tumors face substantially higher risks of secondary brain tumors 2

• The incidence rate ratio for malignant brain tumors is 3.34 and for meningiomas is 4.06 in patients who underwent radiotherapy versus those who did not 2

• GH replacement at appropriate doses for documented GH deficiency has not been implicated in increased risk of secondary malignancies, though the underlying radiotherapy exposure remains a significant risk factor 2

Monitoring Requirements Before Initiation

Prior to starting GH therapy, the following assessments are mandatory:

• Baseline fundoscopy to exclude papilledema and assess for intracranial hypertension 2, 3

• Bone age radiography of the left wrist to confirm open epiphyses and assess growth potential 2

• Pubertal staging according to Tanner stages in patients older than 10 years 2

• Thyroid function tests (TSH and free T3) 2, 3

• Metabolic parameters including serum glucose, calcium, phosphate, bicarbonate, and parathyroid hormone levels 2, 3

Common Pitfalls to Avoid

• Do not assume GH is safe simply because epiphyses are open - All contraindications must be systematically excluded 1

• Do not overlook the need for baseline fundoscopy - Intracranial hypertension, though rare (3 in 1,376 CKD patients), can cause permanent vision loss if undetected 2

• Do not initiate GH within the first year after renal transplantation - This represents a specific contraindication in transplant recipients 2

• Do not start GH in patients with unwillingness to comply - Patient or family refusal is an absolute contraindication 2