Growth Hormone Deficiency in Adults Treatment & Management

Updated: Jun 26, 2018
  • Author: Mohsen S Eledrisi, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
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Treatment

Medical Care

Growth hormone (GH) replacement therapy is provided in the form of human recombinant GH. This is available in subcutaneous injection form. The starting dose of GH depends on the age and clinical condition of the patient. A dose regimen that is based on age along with dose titration has been associated with less adverse effects compared with a weight-based regimen. [16]  The following regimen is suggested [7] :

  • Age younger than 30 years: 0.4-0.5 mg/day (may be higher for patients transitioning from pediatric treatment)
  • Age 30-60 years: 0.2-0.3 mg/day
  • Age >60 years or those with diabetes mellitus or prediabetes: 0.1-0.2 mg/day

For patients with adherence issues, a less frequent dose regimen such as alternate days or 3 times per week using the same total weekly dosage can be used. [7]

Follow-up is usually planned at intervals of 1-2 months when the dose of GH can be adjusted by increments of 0.1-0.2 mg/day based on the clinical response, serum insulin-like growth factor-1 (IGF-1) levels, and side effects. Longer time intervals and smaller dose increments are suggested for older patients.

Serum IGF-1 levels are the main determinant for adjusting the dose of GH. No studies are available to guide this decision. A commonly used target is the upper half of the normal range appropriate for age and sex, unless significant side effects develop. [5]

Once maintenance doses of GH are achieved, follow-up is provided at intervals of 6 months. Monitoring includes clinical evaluation, assessment of side effects, and measurement of serum IGF-1, fasting glucose, and lipid profile. Quality of life (QOL) is also assessed using standardized questionnaires. If the initial bone mineral density findings, measured by dual-energy x-ray absorptiometry (DXA) scanning, are abnormal, repeat testing at intervals of 2-3 years is recommended. [5]

No studies are available regarding the optimal length of GH replacement therapy. Patients with childhood GH deficiency who attained adult height and had persistent deficiency on retesting should continue to receive GH therapy. [5]

GH therapy can also be continued indefinitely if benefits such as significant improvement in QOL and objective improvements in biochemistry and body composition are observed. If no objective or subjective benefits are seen after 1 year of treatment, discontinuation of GH therapy should be considered. [7]

Published data do not confirm an association between GH therapy and recurrence or regrowth of pituitary tumors or craniopharyngiomas. [17, 18, 19] However, because of the possible association between increased IGF-1 levels and the risk of malignancy, there has been a theoretical concern that GH therapy could lead to regrowth of malignancies. [20] Therefore, GH therapy is not recommended for use in patients with a previous history of malignancy or in the presence of active malignancy. [5, 7]

A separate, more recent population-based study of 6874 adult French patients treated with recombinant GH in childhood for isolated GH deficiency, short stature associated with low birth weight or length, or idiopathic short stature found an increased risk of bone tumors but not an overall cancer risk in these individuals. [21]

GH therapy may increase the activity of the cytochrome P-450 system and alter the clearance of some medications known to be metabolized by this system, such as corticosteroids, anticonvulsants, sex steroids, and cyclosporine. Therefore, monitoring is advised when such medications are used in patients receiving GH therapy.

The most common side effects of GH therapy are related to fluid retention and include paresthesias, joint stiffness, peripheral edema, arthralgia, myalgia, carpal tunnel syndrome, and increased blood pressure. Most of these adverse effects improve with dose reduction. Older age, higher  body mass index (BMI), and female sex confer higher risk of these complications. [22]

GH therapy is associated with a mild increase in both fasting serum glucose and fasting plasma insulin levels. [23] Patients with diabetes mellitus who receive GH therapy may require adjustment in their glucose-lowering medications.

Because GH therapy can decrease levels of serum free T4 and cortisol, regular monitoring of thyroid and adrenal function is recommended. Patients on concurrent thyroid or adrenal hormone replacement may need dose adjustments after starting GH therapy. Patients who have normal thyroid and adrenal function require monitoring of serum free T4 and assessment of the hypothalamic-pituitary-adrenal axis because GH therapy can unmask central hypothyroidism and hypoadrenalism. [24, 25]

Patients who are on testosterone-replacement therapy may require their GH doses to be lowered, because testosterone can potentiate GH action and exacerbate GH-induced adverse effects. [26]

Women who are taking oral estrogen replacement therapy usually need higher doses of GH, but those on transdermal estrogen preparations may not. [27]

Consultations

Consult with an endocrinologist. Consult with a neurosurgeon for evaluation of pituitary tumors.

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Complications

Growth hormone (GH) deficiency has been associated with cardiovascular disease, osteopenia/osteoporosis, alteration in body composition, decreased life expectancy, psychological disturbances, and insulin resistance.​

Cardiovascular disease

Early epidemiologic data showed that patients with hypopituitarism who were on hormone replacement therapy, not including GH, had increased cardiac events, suggesting an association of GH deficiency with cardiovascular disease. [14, 28, 29, 30, 31]  Patients with GH deficiency have increased rates of the presence of markers of cardiovascular disease, such as greater intima-media thickness of the carotid arteries, reduced left ventricular mass, decreased ejection fraction, high levels of serum low-density lipoprotein (LDL) cholesterol (LDL-C) and triglycerides, low levels of high-density lipoprotein (HDL) cholesterol (HDL-C), and high coronary calcium scores. [14, 29, 30, 32]  GH therapy improves certain markers of cardiovascular disease, such as serum lipids (reduction of LDL-C levels and increase in HDL-C levels), systolic function, intima-media thickness of the carotid arteries, endothelial function, left ventricular mass, and cardiac output. [29, 33, 34, 35]  However, evidence is limited regarding the effect of GH replacement therapy on cardiovascular morbidity and mortality. [28, 29, 36]

A study that evaluated the prevalence of metabolic syndrome and associated cardiovascular complications in adult-onset GH deficiency during GH replacement therapy found an essentially unchanged prevalence of metabolic syndrome in these patients during 1 year of GH therapy. [37]  However, there was a significant reduction in abnormal waist circumference (P<0.001), a significant increase in impaired glucose metabolism (P <0.001), and a decrease in HDL-C (P = 0.011). Moreover, over a 7-year period of GH therapy, those with metabolic syndrome had a 66% higher risk of developing a new coronary disease compared to those without metabolic syndrome (P = 0.0016). [37]

Osteopenia/osteoporosis

Patients with GH deficiency have reduced bone mineral density and increased rates of fractures. [38, 39]  A gender difference in the response to GH treatment has been hypothesized, as bone mineral density has been show to improve with this therapy more in men than in women. [40, 41, 42]  The effect of GH therapy on fracture rate was less pronounced, with stabilization of the incidence of clinical fracture after GH treatment. [40]

Effect on body composition

Patients with GH deficiency tend to have a relative increase in fat mass with a preferential increase in visceral fat and a relative decrease in muscle mass. [43, 44]  GH therapy decreases total body fat and increases muscle mass. [43, 45]  Some, but not all, studies have shown increased muscle strength along with improved exercise capacity and physical performance after GH therapy. [45, 46, 47]

In an observational retrospective monocentric study of 47 patients with GH deficiency who were treated with GH during childhood, investigators evaluated changes in pediatric growth parameters  relative to an increase of insulin-like growth factor-1 (IGF-I) z-score as well as other indexes of GH response, such as body composition and lipid profile, after 1 year of treatment in adulthood. [48]  The investigators noted the following [48] :

  • Positive correlation between final growth velocity in the last year of childhood GH treatment and an increase in IGF-I z-score in GH-treated adults ( P< 0.01), but no significant positive correlation between the main parameters that evaluate response to GH treatment in children and adults
  • No correlation between growth-promoting effects of GH as child and metabolic changes induced by GH as adult
  • Negative correlation between weight at the end of childhood GH treatment and the IGF-I response during first year of treatment in adults ( <0.05)
  • Potential predictive response of the final growth velocity in children to GH treatment in adulthood

Decreased life expectancy

Patients with hypopituitarism have decreased life expectancy compared with age- and gender-matched healthy people despite replacement with adrenal, thyroid, and gonadal hormones, primarily owing to cardiovascular and cerebrovascular disease. [7, 49, 50, 51]  Therefore, it has been speculated that GH deficiency in patients with hypopituitarism is associated with premature mortality. [7] However, other factors potentially contribute to the increased mortality in these patients, including the following [7] :

  • Administration of cranial radiation to treat the pituitary disease
  • Use of different thyroid, gonadal, and glucocorticoid replacement regimens, including what is currently considered high doses of glucocorticoids
  • Unavailability of effective treatments for hyperlipidemia and hypertension during the survey periods

There are no published studies on the effect of GH therapy on mortality. Observational data suggest a lower mortality in those who receive GH therapy compared to those who remain untreated, but these findings may be a result of selection bias. [36]

Psychological disturbances

Compared with matched healthy persons, patients with GH deficiency have lower quality-of-life scores, with reduced energy, social isolation, and disturbed sexual life. [52]

Insulin resistance

Impaired glucose metabolism characterized by insulin resistance and fasting hyperinsulinemia has been reported in patients with GH deficiency. [10]

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