Growth hormone deficiency medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D [2]

Overview

Growth hormone (GH) supplementation is indicated for children with GH deficiency whose epiphyses are yet to close. The dose for children is between 0.16 and 0.24 mg/kg/week, divided into once daily injections. Serum levels of insulin-like growth factor I (IGF-I) ought to be measured continuously for several weeks after starting GH treatment or making a dose adjustment. Side effects of GH supplementation include headaches, idiopathic intracranial hypertension, slipped capital femoral epiphysis, worsening of existing scoliosis, pancreatitis, and gynecomastia. There is a likely role for GH in cancer risk.

Medical Therapy

Childhood GH deficiency treatment

Indications:

Treatment with Growth hormone (GH) is indicated for children with GH deficiency whose epiphyses are yet to close.
Treatment should be continued after linear growth ceases until full skeletal development.

Dosing:

The dose for children is between 0.16 and 0.24 mg/kg/week, divided into once daily injections.
The dose for patients with severe GH deficiency is 20 micrograms/kg/day.

Dosing during puberty:

A temporary increase in GH dose is preferred if the patient failed to respond to normal doses.
Although, effective treatment with GH before puberty is more efficacious than efforts to treat patients during puberty.

Monitoring:

Serum levels of insulin-like growth factor I (IGF-I) should be measured for several weeks after beginning GH treatment or making a dose adjustment.
This helps to avoid very high IGF-I levels, which are thought to be associated with some of the drug's toxicity as recommended in guidelines from the Pediatric Endocrine Society (PES):^[1]

If the IGF-I level is below the target range, increasing the dose of GH is recommended, as GH is unlikely to be efficacious if IGF-I levels are very low.
If the IGF-I level is above this target range, we reduce the GH dose to prevent GH toxicity. For patients with more than one pituitary hormone deficiencies, adrenal and thyroid function need to be reassessed a few months after initiation of GH therapy.^[1]

Duration of therapy :

Treatment is continued at least until linear growth decreases to less than 2.0 to 2.5 cm.
More than two-thirds of patients have normal outcomes when retested for GH deficiency as adults.
It is vital to repeat the GH stimulation test at some point of the transition period to determine if they will require ongoing therapy.
Patients can attain normal height if treatment is administered at an early age.
Patient's height should be reevaluated every 4 to 6 months to determine if the growth response is adequate.
During the preliminary growth period, the 75th percentile curve for height pace is the proper target as an adequate growth response to GH..

Effect of treatment

Growth :

GH therapy started early in childhood have better prognosis.^[2]
Increase in height continues for more than 2 years even after cessation of treatment.^[3]

Bone mass :

Children with GH deficiency have low bone mass compared with normal children.
To maximize bone mass, it is important to consider the continuation of treatment even after linear growth has ceased until full skeletal development.^[4]
GH therapy increases bone mass.^[5]
Without adequate GH replacement, GH deficiency can be associated with low bone mass during adulthood.^[6]

Adverse effects of growth hormone therapy

Treatment of children with recombinant human GH has generally been safe.^[7]^[8]

Acute effects :

Headaches which usually are benign.
Idiopathic intracranial hypertension (known as pseudotumor cerebri), increased intraocular pressure usually resolves with discontinuation of GH therapy. Treatment can often be resumed at a lower dose without the return of symptoms back up to standard doses.^[9]
Slipped capital femoral epiphysis: routine monitoring is recommended for suggestive symptoms such as hip and/or knee pain, and changes in gait. This condition requires surgical pinning of the capital femoral epiphysis.^[10]
Worsening of existing scoliosis.^[11]
Pancreatitis
Gynecomastia
Increase in the growth and pigmentation of nevi.^[12]
Carpal tunnel syndrome, edema, and arthralgia are more common in adults than in children.
Neutralizing antibodies against GH may be formed resulting in loss of efficacy.^[13]
Development of insulin resistance and glucose intolerance may occur in children receiving GH therapy.^[14]

Chronic effects:

There is a possible role for GH in cancer risk especially prostate cancer.^[15]^[16]
GH therapy does not increase the risk of leukemia or other cancers compared with the general population.^[17]
For patients with a primary cancer diagnosis that led to the GH treatment, recombinant GH was associated with an increase in risk for cancer.^[17]
The increased risk was significant for a variety of secondary cancers including bone, melanoma, kidney, brain, thyroid cancer and leukemia.
For children with cancer, guidelines suggest a 12-month period after completion of cancer-directed therapy to confirm that the cancer was eradicated before initiating GH therapy.

Transition of GH treatment from childhood to adults

The transition period between childhood treatment and adults treatment begins in late puberty and ends with full adult maturation.
Children treated with GH should be retested if they have persistence of GHD near the time of reaching adulthood.
Patients with idiopathic GHD usually do not need GH treatment anymore, children with organic causes of GHD usually are found to have GHD on retesting.
Retesting involves measurement of IGF-I and stimulation with insulin-induced hypoglycemia or arginine.
Most studies have shown benefit of GH treatment in young adults with GHD in body composition, especially the achievement of peak bone mass.

Adult-type GH deficiency treatment

Treatment protocol:

GH is administered by subcutaneous injection once a day, usually in the evening.
The goal should be to start with low doses and increase gradually until the serum IGF-1 concentration is normal.
The eventual goal is to find the GH dose that maintains the serum IGF-1 concentration within the middle of the age-adjusted normal range.^[18]
If side effects occur or the serum IGF-1 concentration increases to above normal at any dose, the dose should be decreased.