Growth Hormone Deficiency in Adults

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



The somatotroph cells of the anterior pituitary gland produce growth hormone (GH), which is stimulated by GH-releasing hormone (GHRH) and inhibited by somatostatin, both of which are produced by the hypothalamus.

Adult GH deficiency can be a transition from childhood-onset GH deficiency, or it can be acquired during adulthood. The majority of cases are caused by pituitary tumors or by their treatment with surgery, radiation therapy, or both.[1] Traumatic brain injury is another important cause.[1, 2, 3, 4, 5]

GH deficiency in adults is associated with multiple metabolic changes such as abnormal lipid metabolism (increased total cholesterol and low-density lipoprotein cholesterol [LDL-C], increased triglycerides, and reduced high-density lipoprotein cholesterol [HDL-C]), increased subcutaneous and visceral fat, decreased muscle mass, decreased bone density, and features of the metabolic syndrome.[6, 7, 8] Patients usually present with reduced physical performance, impaired psychological well-being, low exercise performance, and reduced quality of life.[1]

The goals of GH therapy in adults are to improve conditioning, strength, body composition, and quality of life, as well as reduce the burden of potential associated medical conditions such as cardiovascular disease and decreased bone mineral density.

Patients should be educated about the technique of subcutaneous injection of GH.

For patient education resources, see Thyroid and Metabolism Center as well as Growth Hormone Deficiency, Growth Hormone Deficiency Medications, and Growth Hormone Deficiency FAQs.


Causes of growth hormone (GH) deficiency can be divided into three categories: acquired, congenital, and idiopathic.[9]

Acquired conditions of GH deficiency include tumors of the pituitary gland or the hypothalamus and metastatic disease; surgery or radiation therapy of the pituitary or hypothalamus; infiltrative diseases such as sarcoidosis, tuberculosis, histiocytosis X, hemochromatosis, and lymphocytic hypophysitis; infarction of the pituitary or hypothalamus (which can be spontaneous, or result from Sheehan syndrome or ischemic stroke); subarachnoid hemorrhage; infections of the central nervous system; and head trauma (during the acute stage of the injury and during the rehabilitation stage).[2, 3, 4, 5, 10, 11] ​[12]

Congenital conditions are caused by genetic abnormalities or structural brain defects. Genetic abnormalities include transcription factor defects (PIT-1, PROP-1, LHX3/4, HESX-1, PITX-2), GH-releasing hormone (GHRH) receptor gene defects, GH gene defects, and GH-receptor or post-receptor defects. Structural defects include agenesis of the corpus callosum, septo-optic dysplasia, empty sella syndrome, encephalocele, hydrocephalus, and arachnoid cyst. GH deficiency can occur in association with midline facial defects such as single central incisor, cleft lip, and cleft palate.

In rare cases, no clear etiology can be determined for GH deficiency.[9]


An estimated 6,000 adults are diagnosed with growth hormone (GH) deficiency every year in the United States.[2] Adult GH deficiency has been estimated to affect 1 in 100,000 people annually, whereas its incidence is approximately 2 cases per 100,000 population when childhood-onset GH deficiency patients are considered.[13, 14] About 15-20% of the cases represent the transition of childhood GH deficiency into adulthood.[13] The incidence rate is higher in males with childhood-onset GH deficiency and in people older than 45 years in the adult GH deficiency group.[13]

The age of presentation of acquired GH deficiency in adults often coincides with the discovery of pituitary tumors, usually between the fourth and fifth decades of life.



History and Physical Examination


Patients with growth hormone (GH) deficiency usually have a history of pituitary tumors that may have been treated with surgery or radiation, or they may have had a history of head trauma. Some patients also have manifestations of deficiency of other pituitary hormones, such as gonadal, adrenal, and thyroid hormones.[15] About 15-20% of cases involve transitioning of childhood GH deficiency into adulthood.[13]

The symptoms of GH deficiency in adults are often nonspecific. Reported symptoms include low physical and mental energy, decreased muscle strength and exercise tolerance, increased weight or difficulty losing weight, poor memory, emotional instability, impaired sleep, and decreased quality of life.[15, 16] Some patients are asymptomatic.

Physical examination

Most patients with GH deficiency have a normal physical examination. Some patients may have decreased muscle strength as well as reduced skeletal muscle and lean body mass but increased fat mass, mainly in the abdominal region.[15, 16, 17, 18]



Differential Diagnoses



Approach Considerations

Evaluation for growth hormone (GH) deficiency is recommended in patients with hypothalamic-pituitary disease, surgery or radiation therapy in these areas, head trauma, or the presence of other pituitary hormone deficiencies.[15] For patients with childhood-onset GH deficiency, retesting for GH deficiency is indicated after achievement of adult height to determine the need to continue therapy—unless they have known mutations, embryopathic lesions causing multiple hormone deficits, or irreversible structural lesions/damage.[15, 18] In these patients, discontinuing GH therapy for at least 1 month is recommended before retesting. Patients with congenital or irreversible hypothalamic-pituitary structural abnormalities do not require retesting for GH deficiency.[15]

Magnetic resonance imaging (MRI) of the hypothalamic-pituitary region may be used to define the anatomy of this region for the presence of tumors or structural abnormalities.

Dual-energy x-ray absorptiometry (DXA) may be used to assess bone mineral density.

Laboratory Studies

Random serum growth hormone (GH) levels are of little value because of the pulsatile nature of GH secretion.

GH deficiency is suspected by a low level of serum insulin-like growth factor-1 (IGF-1), but a normal IGF-1 level does not exclude the possibility of GH deficiency. The use of stimulation tests is generally required to confirm the diagnosis of GH deficiency.[15] The presence of deficiency of three or more pituitary hormones in the context of organic hypothalamic-pituitary disease strongly suggests GH deficiency; in this setting, stimulation testing is not needed[12, 19] or is optional.[15]

The insulin tolerance test (ITT), the combination of GH-releasing hormone (GHRH) and arginine (GHRH-arginine test), glucagon stimulation test, or macimorelin test can be used as stimulation tests for the diagnosis of GH deficiency.[9, 12, 15, 20]

Note: Patients should have adequate replacement of other deficient pituitary hormones before being tested for GH secretion. All stimulation tests are performed after an overnight fast and involve measuring serum GH levels.


In the ITT, regular insulin is administered intravenously at a dose of 0.1 unit/kg (time 0) to produce a lowering in plasma glucose level to less than 40 mg/dL (2.2 mmol/L). Glucose levels are monitored by capillary samples every 15 minutes and until symptoms of hypoglycemia develop. A repeated dose of insulin can be administered if hypoglycemia does not develop by 30 to 60 minutes. Serum glucose and serum GH levels are measured at 0, 15, 30, 60, 90, and 120 minutes after administering insulin. GH deficiency is diagnosed if the peak GH level is ≤5.1 mcg/L.[12]

Patients usually develop symptoms of hypoglycemia, including sweating, palpitations, and, rarely, convulsions and loss of consciousness. Therefore, the test should be undertaken by an experienced staff under the direct supervision of a physician.

The ITT should be avoided in patients with cardiovascular disease, cerebrovascular disease, or seizure disorders. Because of these safety concerns and laboriousness, the ITT is less frequently used.

GHRH-arginine test

In the GHRH-arginine test, GHRH is administered intravenously at a dose of 1 mcg/kg body weight (time 0), followed by an intravenous infusion of 0.5 g/kg body weight (maximum 30 g) of arginine over 30 minutes. Serum GH is measured at -30, 0, 30, 60, 90, and 120 minutes.

In patients with GH deficiency of hypothalamic origin (eg radiation therapy), GHRH can stimulate the pituitary and, therefore, the GHRH-arginine test can yield falsely normal results.[21] In such cases, using alternative stimulation tests is recommended.

Because body mass index (BMI) can influence the GH response, the following criteria have been used to establish the diagnosis of GH deficiency when using the GHRH-arginine test[12, 15, 18] :

  • BMI of < 25 kg/m 2: Peak GH level ≤11.0 mcg/L
  • BMI of 25 to 29.9 kg/m 2: Peak GH level ≤8.0 mcg/L
  • BMI of ≥30 kg/m 2: Peak GH level ≤4.0 mcg/L

Glucagon stimulation test

If GHRH is not available, the GHRH-arginine test is expected to give inaccurate results, or performing the ITT is either contraindicated or not practical, the glucagon stimulation test[9, 12, 15, 18, 20] or the macimorelin test[18, 22, 23, 24] can be used to diagnose GH deficiency. Because GHRH is not widely available (the only US commercial formulation was discontinued in 2008) and because of safety concerns over the use of ITT, the glucagon stimulation test is increasingly used.[9, 15]

The glucagon stimulation test has become the most commonly used diagnostic test for the diagnosis of GH deficiency because of its availability, reproducibility, safety, and lack of influence by sex and hypothalamic cause of GH deficiency. The test is carried out by administering intramuscular glucagon at a dose of 1 mg (1.5 mg for patients who weigh >90 kg); serum GH levels are measured just before the injection and every 30 minutes for 4 hours.

The following criteria are recommended by the American Association of Clinical Endocrinologists to establish a diagnosis of GH deficiency using the glucagon stimulation test[18, 25] :

  • BMI of < 25 kg/m 2: Peak serum GH level ≤3.0 mcg/L
  • BMI of 25 to 29.9 kg/m 2: Peak serum GH level ≤3.0 mcg/L
  • BMI of ≥30 kg/m 2: Peak serum GH level ≤1.0 mcg/L

Macimorelin test

In 2017, the US Food and Drug Administration (FDA) approved macimorelin, an oral ghrelin agonist that stimulates GH, for the diagnosis of adults with GH deficiency.[22] Approval was based on comparative test results between macimorelin and ITT in adult patients with GH deficiency and healthy control subjects.

The macimorelin test has an accuracy comparable to that of the ITT.[26] The test is performed by administering macimorelin as an oral solution at a dose of 0.5 mg/kg body weight. Serum GH levels are measured just before and at 30, 45, 60, and 90 minutes after the administration of macimorelin. GH deficiency is diagnosed if the peak GH level is ≤2.8 mcg/L.[18]



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]


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]


Consult with an endocrinologist.

Consult with a neurosurgeon for evaluation of pituitary tumors.

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.


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 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]


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]


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.



2019 American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines

Guidelines for the management of growth hormone (GH) deficiency in adults and patients transitioning from pediatric to adult care were published in 2019 by the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE).[18] Select recommendations are summarized below.

In the setting of clinical suspicion of adult GH deficiency, it is crucial to establish the diagnosis before considering replacement therapy with recombinant human GH (rhGH).

Consider the possibility of adult GH deficiency in patients with a history of hypothalamic-pituitary disease.

It is important to recognize the differences in the etiology of childhood-onset GH deficiency (CO-GHD) versus adult-onset GH deficiency (AO-GHD). Because CO-GHD occurs during the developmental years, adults with this condition may have been GH-deficient for a longer period than patients with AO-GHD.

GH–stimulation testing should be performed to confirm the diagnosis, as random serum GH and insulin-like growth factor-1 (IGF-1) levels cannot be used alone to diagnosis adult GH deficiency.

Use the insulin tolerance test (ITT) to establish a diagnosis of GH deficiency. If this test is contraindicated, then use the glucagon stimulation test or macimorelin stimulation test instead.

Perform one GH-stimulation test to confirm the diagnosis in patients with two or fewer pituitary hormone deficiencies (PHD), as low-serum IGF-1 levels alone are not sufficient to make a diagnosis of adult GH deficiency.

Use body mass index (BMI)–appropriate GH cut-points to diagnose adult GH deficiency. Use the GH cut-point of 3 μg/L for normal-weight (BMI < 25 kg/m2) and overweight (BMI 25 to 30 kg/m2) patients with a high pretest probability, and a lower GH cut-point of 1 μg/L for obese (BMI >30 kg/m2) and overweight (BMI 25 to 30 kg/m2) patients with a low pretest probability.

Closely monitor adults with CO-GHD caused by structural pituitary or brain tumors during their transition to adult-care services. These patients tend to have lower bone mineral density, impaired bone microarchitecture, and more adverse body composition abnormalities and cardiovascular risk markers than patients with AO-GHD.

Individualize rhGH replacement therapy and initiate at low dosages. Suggested starting doses are as follows:

  • Age < 30 years: 0.4-0.5 mg/day (doses may be higher for those transitioning from pediatric care. For transitioning patients, resume rhGH at half the dose used in childhood.)
  • Age 30-60 years: 0.2-0.3 mg/day
  • Age >60 years: 0.1-0.2 mg/day

Lower starting rhGH doses (eg, 0.1-0.2 mg/day) are recommended for those with concurrent diabetes mellitus or previous gestational diabetes, obesity, and older age.

Reduce rhGH dosing in the elderly, patients with elevated serum IGF-1, persons discontinuing use of oral estrogen or changing from oral to transdermal estrogen, individuals with worsening glucose tolerance, or those who have fluid retention-related side effects.

After starting rhGH therapy, follow patients at 1- to 2-month intervals, increasing the rhGH dose in increments of 0.1 to 0.2 mg/day.

Never use rhGH replacement therapy for age-related conditions or to enhance athletic performance.

2011 Endocrine Society Guidelines

The Endocrine Society clinical practice guideline on the evaluation and treatment of adult growth hormone (GH) deficiency includes the following recommendations[15] :

  • Patients with childhood-onset GH deficiency who are candidates for GH therapy after adult height achievement should be retested for GH deficiency unless they have known mutations, embryopathic lesions causing multiple hormone deficits, or irreversible structural lesions/damage.
  • Adult patients with structural hypothalamic/pituitary disease, surgery or irradiation in these areas, head trauma, or evidence of other pituitary hormone deficiencies should be considered for evaluation for acquired GH deficiency.
  • Because idiopathic GH deficiency in adults is very rare, stringent criteria are necessary to make this diagnosis, and because in the absence of suggestive clinical circumstances there is a significant false-positive error rate in the response to a single GH stimulation test, it is suggested that two tests be used before making this diagnosis. The presence of a low insulin-like growth factor-1 (IGF-1) also increases the likelihood that this diagnosis is correct.
  • The insulin tolerance test (ITT) and the GH releasing hormone (GHRH)-arginine test have sufficient sensitivity and specificity to establish the diagnosis of GH deficiency, but in those with clearly established, recent (within 10 y) hypothalamic causes of suspected GH deficiency (eg, irradiation), testing with GHRH-arginine may be misleading.
  • When GHRH is not available and performance of an ITT is either contraindicated or not practical in a given patient, the glucagon stimulation test can be used to diagnose GH deficiency.
  • Because of the irreversible nature of the cause of GH deficiency in children with structural lesions with multiple hormone deficiencies and those with proven genetic causes, a low IGF-1 level at least 1 month off GH therapy is sufficient documentation of persistent GH deficiency without additional provocative testing.
  • A normal IGF-1 level does not exclude the diagnosis of GHD but makes provocative testing mandatory to make the diagnosis of GH deficiency. However, a low IGF-1 level, in the absence of catabolic conditions such as poorly controlled diabetes, liver disease, and oral estrogen therapy, is strong evidence for significant GH deficiency and may be useful in identifying patients who may benefit from treatment and therefore require GH stimulation testing.
  • The presence of deficiencies in three or more pituitary axes strongly suggests the presence of GH deficiency, and in this context provocative testing is optional.
  • GH dosing regimens should be individualized rather than weight-based and started with low doses and be titrated according to clinical response, side effects, and IGF-1 levels.
  • During GH treatment, patients should be monitored at 1- to 2-month intervals during dose titration and semiannually thereafter with a clinical assessment and an evaluation for adverse effects, IGF-1 levels, and other parameters of GH response.


Growth Hormone Analogs

Class Summary

Recombinant growth hormone analogs are indicated for replacement therapy in patients with growth hormone deficiency.

Somatropin (Genotropin, Humatrope)

Human recombinant growth hormone is produced by recombinant deoxyribonucleic acid (DNA) technology. It stimulates the growth of linear bone, skeletal muscle, and organs and stimulates erythropoietin, increasing red blood cell mass. Actions are either direct or from the hepatic production of IGF-I. It is currently widely available in subcutaneous injection form. 

Somapacitan (Sogroya, somapacitan-beco)

Long-acting growth hormone indicated for replacement in adults with growth hormone deficiency. Administered by SC injection once-weekly.

Diagnostic Agents

Class Summary

Macimorelin is the first oral test available for diagnosis of GH deficiency.

Macimorelin (Macrilen)

Macimorelin is an oral ghrelin agonist. Ghrelin is a neuropeptide released mainly from cells in the stomach and pancreas in response to hunger and is a growth hormone-releasing peptide. It stimulates GH release by activating GH secretagogue receptors present in the pituitary and hypothalamus. Macimorelin is indicated for diagnosis of adult growth hormone deficiency.


Questions & Answers


What is adult growth hormone (GH) deficiency?

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