Review of Specific Guidelines for Use of Growth Hormone Therapy
Adults With Growth Hormone Deficiency (GHD)
Growth hormone (GH) treatment of adults with GHD should be considered and has been
associated with improved body composition, reduced body fat,
and increased lean body mass. Patients with documented
idiopathic GHD in childhood should be restudied
in adulthood. For the average 70-kg man, the recommended
dosage at the start of therapy is not more than 0.3
mg, given as a daily subcutaneous injection. Maximal doses are
variable, with younger patients (<25 years) sometimes requiring up
to 2 mg/day and older patients much less (sometimes
only 0.1 or 0.2 mg/day). The clinician must exercise
good clinical judgment by assessing side effects, serum
insulin-like growth factor I (IGF-I) levels, and changes in
body composition to determine the appropriate maintenance
dose. In older or overweight patients, lower doses
may be needed to minimize the occurrence of adverse
events. During therapy, the dosage should be decreased if
side effects occur or IGF-I levels are excessive. The maintenance
dose depends on the clinical and biochemical
response. These doses should be altered to maintain circulating
levels of IGF-I in the normal range for the patient’s
age and sex. Serum free thyroxine and lipid levels should
be assessed initially and at 6 to 12 months thereafter.
Plasma glucose concentration is analyzed initially and
every 3 months. Long-term treatment is being evaluated at
this time.
Children With GHD
GH treatment is indicated in children with documented GHD for correction of
hypoglycemia and for induction of normal statural growth. If such patients are
known to have had malignant tumors, remission should be substantiated for 6 to
12 months before initiation of GH treatment. A weekly dosage of up to 0.3 mg/kg
of body weight divided into daily or 6-times-per-week subcutaneous injections is
recommended. Periodic monitoring of thyroid function is indicated at
approximately 6-month intervals. The appropriate time to discontinue GH
treatment is controversial. Treatment for growth promotion should be continued
at least until the handicap of short stature is ameliorated or until the patient
is no longer responding to such treatment.
Turner Syndrome
GH treatment is indicated for girls with Turner syndrome. Patients may
be treated with GH in starting dosages of 0.05 mg/kg per
day. Anabolic steroids, such as oxandrolone, may be used
concomitantly in dosages of less than 0.05 mg/kg per day,
with careful monitoring of bone maturation and of serum
glucose levels. Estrogen replacement therapy should
be discussed with each patient. If adolescent patients strongly believe that estrogen replacement is
desirable, very low doses should be given (such as ethinyl
estradiol, 50 ng/kg per day) until adequate growth has
been achieved.
Chronic Renal Insufficiency
In patients with end-stage renal disease and growth
retardation, GH treatment may be considered after growth-inhibiting metabolic derangements (such as acidosis, secondary hyperparathyroidism,
and undernutrition) are minimized. Treatment may be initiated
with GH in a dosage of 0.35 mg/kg per week.
Small for Gestational Age (SGA) or Intrauterine Growth Retardation
The recommended dosage of GH is 0.48 mg/kg per week, with continuous
treatment until final height is achieved. The GH dose in SGA is higher because
data suggest that these children may have partial GH resistance.
Prader-Willi Syndrome
GH treatment is indicated for patients with Prader-Willi syndrome. Their
short stature should be treated with GH at a dosage of 0.24 mg/kg per
week.
Clinical Practice of GH Therapy
GH therapy is best accomplished under the direct supervision of a clinical
endocrinologist. Short-term GH treatment is safe in both children and adults.
Continued monitoring of side effects and long-term treatment results is needed.
Optimal replacement dosages in adults
have not been well defined; studies have suggested
0.1 to 1.0 mg/day. Considerable variability exists, however, in
the appropriate GH dose for different patients and
the various conditions being treated. A single subcutaneous
self-injection of GH into the abdomen, preferably in
the evening, is best. The injection site should be
rotated to minimize lipoatrophy. Daily administration
is more effective in stimulating growth than
injections 3 times per week. Although twice-daily GH
schedules produce higher GH levels and may be superior
to once-daily injections, the inconvenience may compromise compliance.
Physiologic GH replacement must be distinguished from pharmacologic therapy.
Replacement therapy of daily GH injections does not simulate the normal,
physiologic pulsatile pattern of GH secretion. Starting replacement therapy
dosages for GH range from 0.02 to 0.05 mg/kg per day in children and from 0.001
to 0.008 mg/kg per day in adults. For a 70-kg man, the usual starting dosage is
0.1 to 0.3 mg/day, with a maintenance dosage of 0.3 to 0.6 mg/day, or
approximately 2 to 4 mg of GH weekly. The dosage should be increased slowly
(probably best at monthly intervals), on the basis of clinical and biochemical
responses.
GH replacement may be given throughout most of the lifetime of some affected
patients. Physicians caring for these patients should be aware that dose
requirements may decrease with time. Replacement therapy should be monitored
carefully as the patient ages, and special emphasis should be placed on
perceived and objectively measured benefits and side effects. If the patient
receives no benefit, a withdrawal period should be considered. Because the
diagnosis of GHD in adult patients, initiation of therapy, maintenance
treatment, and monitoring of side effects are complex, these patients should
remain under long-term surveillance by an endocrinologist experienced in
treating pituitary-related disorders. Such a program of surveillance, which is
the cornerstone of successful therapy, can be undertaken in partnership with an
internist or family practitioner. Initial follow-up should be at monthly
intervals. Thereafter, visits may be less frequent but should never be less than
twice yearly. Because reimbursement for testing and treatment is often complex
and time-consuming, patient advocacy involves a considerable commitment. The
practicing endocrinologist can help the patient achieve appropriate and lasting
reimbursement for optimal medical care.
The GH products approved for use in the United States in 2002 are summarized in Table 6 in the
original guideline document.
