Growth Hormone Deficiency in Adults Treatment & Management

Updated: Jun 17, 2022
  • Author: Mohsen S Eledrisi, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
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Treatment

Approach Considerations

Measurement of bone mineral density using dual-energy X-ray absorptiometry (DXA) is suggested in adult patients with growth hormone (GH) deficiency before starting GH therapy. If the initial bone mineral density findings, are abnormal, repeat testing at intervals of 2-3 years is recommended. [18]

Malignancy

Published data do not confirm an association between GH therapy and recurrence or regrowth of pituitary tumors or craniopharyngiomas. [27, 28, 29] However, because of the possible association between increased insulin-like growth factor-1 (IGF-1) levels and the risk of malignancy, there has been a theoretical concern that GH therapy could lead to regrowth of malignancies. [30] Therefore, GH therapy is contraindicated in patients with active malignancy (other than basal-cell or squamous-cell skin cancers) or proliferative or severe nonproliferative diabetic retinopathy. [9, 15, 18]

For adults with a previous history of cancer, GH therapy should be individualized and may be considered at least 5 years after cancer remission and in consultation with the oncologist. [18]

A 2018 population-based study of 6,874 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. [31]

Consultations

Consult with an endocrinologist.

Consult with a neurosurgeon for evaluation of pituitary tumors.

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Medical Care

Growth hormone (GH) replacement therapy is provided in the form of human recombinant GH, 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. [32] The following treatment regimen is suggested [15, 18] :

  • Age < 30 years or women on oral estrogen therapy: 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, obesity, or previous gestational diabetes: 0.1-0.2 mg/day
  • For patients transitioning from childhood to adulthood GH deficiency: resume GH doses at 50% of the dose last used in childhood

For patients with adherence issues, a less frequent dose regimen such as alternate days or three times per week using the same total weekly dosage can be used. [15]

Serum insulin-like growth factor-1 (IGF-1) levels are the main determinant for adjusting the dose of GH. [33] 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. [15]

Similarly, 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. [15]

GH therapy can also be continued indefinitely if benefits such as significant improvement in quality of life and objective improvements in biochemistry, body composition, and bone mineral density are observed. [18] If no objective or subjective benefits are seen after 1 year of treatment, discontinuation of GH therapy should be considered. [15, 18] If patients decide to discontinue GH therapy, a 6-month follow-up appointment is recommended, as some patients may choose to resume therapy if they felt unwell while off treatment.

Somapacitan, a once-weekly form of GH, has been approved by the FDA for use in adults with GH deficiency. It has been shown to improve body composition parameters (including reduced truncal and visceral fat) and lean body mass. [34]

Long-acting GH formulations can improve patients’ adherence to therapy compared to daily injections. However, further studies are required to assess their methods of dose adjustment, timing of monitoring of IGF-I, efficacy, cost-effectiveness and long-term safety. [35]

Patients on hormone replacement therapy

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. [36]

Women who are taking oral estrogen replacement therapy usually need higher doses of GH, but those on transdermal estrogen preparations may not. [37]

Adverse effects

The most common side effects of GH therapy are related to fluid retention and include paresthesia, 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. [38]

GH therapy is associated with a mild increase in both fasting serum glucose and fasting plasma insulin levels. [39] Patients with diabetes mellitus who receive GH therapy may require adjustment in their glucose-lowering medications.

Monitoring

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.

GH therapy can decrease levels of serum free T4 and cortisol, therefore, 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. [40, 41]

Follow-up

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 IGF-1 levels, and side effects. Longer time intervals and smaller dose increments are suggested for older patients.

Once maintenance doses of GH are achieved, follow-up is provided at intervals of 6 months. Monitoring includes clinical parameters (blood pressure, pulse, body mass index, and waist circumference), assessment of side effects, and measurement of serum IGF-1, fasting glucose, hemoglobin A1C, and lipid profile. Quality of life (QOL) is also assessed using standardized questionnaires that reflect a variety of health-related, economic, and social factors. [42, 43] This is assessed before starting GH treatment and at 12-month intervals. [18]

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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, insulin resistance, impaired glucose metabolism, and decreased quality of life.​

Cardiovascular disease

Early epidemiologic data showed that patients with hypopituitarism who were on hormone replacement therapy, not including GH, had increased cardiac and cerebrovascular events, suggesting an association of GH deficiency with cardiovascular disease. [12, 44, 45, 46, 47, 48] 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 and left ventricular function, decreased ejection fraction, high levels of serum low-density lipoprotein cholesterol (LDL-C) and triglycerides, low levels of high-density lipoprotein cholesterol (HDL-C), elevated inflammatory markers (eg, C-reactive protein, proinflammatory cytokines, adipokines), and high coronary calcium scores. [12, 45, 48, 49, 50, 51, 52, 53]

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, inflammatory markers, left ventricular mass, and cardiac output. [46, 48, 50, 53, 54, 55, 56, 57, 58, 59] However, evidence is limited regarding the effect of GH replacement therapy on cardiovascular morbidity and mortality. [46, 47, 48, 60]

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. There was a reduction in abnormal waist circumference as well as a decrease in HDL-C levels and worsening in glucose metabolism. [61]

Osteopenia/osteoporosis

Patients with GH deficiency have reduced bone mineral density and increased rates of fractures. [62, 63, 64, 65, 66] About 20% of adult-onset and 35% of childhood-onset adult patients with GH deficiency have osteoporosis. [15] GH therapy improves bone mineral density, but there are no adequately powered controlled studies on its effect on fracture rate. [62, 67, 68]

A gender difference in the response to GH treatment has been hypothesized, as bone mineral density has been shown to improve with this therapy more in men than in women. [69, 70] The effect of GH therapy on fracture rate was less pronounced, with stabilization of the incidence of clinical fracture after GH treatment. [51]

Effect on body composition and physical performance

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. [71, 72] GH therapy decreases total body fat and increases muscle mass. [72, 73] Some, but not all, studies have shown increased muscle strength along with improved exercise capacity and physical performance after GH therapy. [74, 75, 76, 77, 78, 79]

In an observational, single-center 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. [80] The investigators noted the following [80] :

  • A 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, but no significant positive correlation between the main parameters that evaluated response to GH treatment in children and adults

  • No correlation between growth-promoting effects of GH as children and metabolic changes induced by GH as adults

  • A negative correlation between weight at the end of childhood GH treatment and the IGF-I response during the first year of treatment in adults

  • Final growth velocity was identified as a parameter that could predict future response to GH treatment in adulthood

Insulin resistance

Impaired glucose metabolism characterized by insulin resistance, fasting hyperinsulinemia, and impaired glucose tolerance has been reported in patients with GH deficiency. [20, 81, 82]

Decreased life expectancy

Patients with hypopituitarism have decreased life expectancy compared with age- and sex-matched healthy people despite replacement with adrenal, thyroid, and gonadal hormones, primarily owing to cardiovascular and cerebrovascular disease. [15, 83, 84, 85, 86, 87, 88, 89] Therefore, it has been speculated that GH deficiency in patients with hypopituitarism is associated with premature mortality. [15] However, other factors potentially contribute to the increased mortality in these patients, including the following [15] :

  • 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 study 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. [60, 89]

Psychological disturbances/quality of life

Relative to matched healthy persons, patients with GH deficiency have lower quality-of-life scores, with reduced energy, social isolation, and disturbed sexual life. [45, 90, 42, 91]

Studies of quality of life of patients with GH deficiency have shown significant variability, ranging from severe impairment of quality of life to normal quality of life. [7] Reported complaints have included reduced energy levels, mental fatigue, social isolation, anxiety, reduced self-confidence, disturbed sex life, decreased physical mobility, dissatisfaction with body image, poor memory, and reduced cognitive function. [92]

Some, but not all, studies showed improvement in quality of life after patients received GH replacement therapy. [45, 90, 42, 91, 92] Improvement in quality of life was similar regardless of the etiology of GH deficiency, and much of the improvement occurred within the first year of treatment.

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