Archived Policies - Prescription Drugs

Growth Hormone (GH)


Effective Date:08-01-2007

End Date:09-14-2012


Recombinant/Human Growth Hormone (GH) therapy may be considered medically necessary for:

Medically Necessary condition

Selection Criteria for Coverage

Children with documented growth hormone deficiency (GHD), in order to correct the deficiency.

Children with documented GHD are considered to be appropriate candidates for GH therapy. GHD is defined as an abnormal response of less than 10 ng/ml to TWO provocative stimulation tests, such as:

  • GH – Releasing Hormone (GHRH)
  • Arginine
  • Insulin.
  • L-dopa
  • Clonidine
  • Glucagon.

Also, if the child has a documented history of GHD as a result of destructive lesions of the pituitary or as a result of treatment (e.g., ablative pituitary irradiation, usually provided because of a tumor or surgery) they are candidates for GH therapy. 

In children, GH therapy is typically discontinued when the growth velocity is less than two centimeters per year, when epiphyseal fusion has occurred, or when the height reaches the 5th percentile of adult height. 

Supportive documentation:

  • Documentation of growth velocity under five centimeters per year with documentation of height at least  2.00 standard deviations below mean over one year or more or more than 1.5 SD sustained over two years.
  • Bone age as determined by standard x-ray techniques to be two years or more behind chronological age.

Once Growth Hormone deficiency has been established in childhood no further documentation of need is required through age 18.

Children with height less than 3rd percentile for chronological age with chronic renal insufficiency.

Chronic renal insufficiency is defined as a serum creatinine of greater than 1.5 milligram per deciliter or a creatinine clearance less than or equal to 75 milliliters per minute per 1.73 m2. In patients with chronic renal failure undergoing transplantation, GH therapy is discontinued at the time of transplant.

Promotion of wound healing in burn patients.

Limited to those patients with 3rd degree burns.

Prevention of growth delay in children with 3rd degree burns who meet the criteria .

Treated during acute hospitalization and for up to one year after the burn as scar tissue can interfere with growth.

Zorbtive for patients with short bowel syndrome.

Should be limited to patients receiving specialized nutritional support in conjunction with optimal management of short bowel syndrome.  Optimal management may consist of dietary adjustments, enteral feedings, parenteral nutrition, fluid and micronutrient supplements.  Note: administration of Zorbtive for longer than four weeks has not been adequately studied per the Food and Drug Administration indications.

Patients with AIDS wasting.

AIDS wasting is defined as a loss of greater than 10% of baseline weight loss that cannot be explained by a concurrent illness other than HIV infection.  Patients treated with GH must simultaneously be treated by antiviral agents.  Therapy is continued until this definition is no longer met.

Adults with GH deficiency

Adults with GHD are considered to be appropriate candidates for GH therapy.  GHD is defined as an abnormal response of less than 5 ng/ml to TWO provocative stimulation tests, such as;

  • L-dopa
  • Clonidine
  • Glucagon
  • GH – Releasing Hormone (GHRH)
  • Arginine
  • Insulin*.


Insulin Provocation is the preferred test for confirming GHD in most adults.  It must be one of the TWO test provided for documentation of GHD unless the test is contraindicated because the patient has:

  • History of seizures; or
  • Coronary artery disease; or
  • High risk of coronary artery disease.

A patient with clear clinical documentation of GHD resulting from:

  • A destructive lesion of the pituitary; or
  • Treatment, including but not limited to ablative pituitary radiation or surgery; or
  • Trauma

may be a candidate for GH therapy.  It is not necessary for such a patient to undergo provocation testing.

Up to 75% of children with documented GHD will have sufficient GH when tested as adults.  Therefore, children receiving GH for documented GHD achieve adult height they should be re-tested one time as adults to determine if continuing GH replacement therapy is medically necessary.

When a diagnosis of GHD is established for an adult, and therapy with GH is initiated, documentation may be requested at one- to two-year intervals that the patient is obtaining measurable clinical benefit from GH therapy.  A physician should consider a trial of withdrawal of GH therapy for patients who do not have demonstrated clinical benefit.

Patients with Turner's Syndrome.

Turner's Syndrome is defined as a patient with a 45, XO genotype.

Patients with Prader-Willi syndrome.

Prader-Willi syndrome is a genetic disorder characterized by a micro deletion in the long arm of chromosome 15.  Clinically, the syndrome presents as a complex multisystem disorder characterized by excessive appetite, obesity, short stature, characteristic appearance, developmental disability, and significant behavioral dysfunction.  GHD has been demonstrated in most tested patients with Prader-Willi syndrome.

The following indications are considered not medically necessary:

Not medically necessary indication


Pediatric patients born small for gestational age (SGA) who fail to show catch up growth by age two.

There are no established criteria for SGA or catch-up growth.  However, in the data submitted to the FDA as part of the approval process, the mean height of enrolled patients was at least two standard deviations below mean.  Absence of catch-up growth was defined as a height velocity below 1 standard deviation score, adjusted for age.

Non-GH-deficient pediatric patients with short stature.

Studies have failed to demonstrate a significant impact of height on psychosocial morbidity.  The American Academy of Pediatrics has pointed out that there will always be a population of individuals considered short based on the normal distribution of height, regardless of how the bell-shaped curve may be altered by GH therapy.

NOTE: On July 26, 2003 the FDA approved Humatrope for Short Stature.  However, this indication remains Not Medically Necessary

Partial GH deficiency.



These patients do not meet the criteria required for GH deficiency.  Further lab testing of children without classic GHD to diagnose partial GHD, or other abnormalities of GH secretion or bioactivity, is not considered medically necessary.  This includes overnight hospitalization of children for testing of spontaneous GH secretion.

Neurosecretory GH dysfunction.

Experimental, investigational and unproven applications include but are not limited to the following:

  • Constitutional delay (lower than expected growth percentiles compared with their target height percentiles and delayed skeletal maturation when growth velocities and rates of bone age advancement are normal);
  • In conjunction with GnRH (Gonadotropin releasing hormone) analogues as a treatment of precocious puberty;
  • GH therapy in older adults to counter the effects of aging (without proven GH deficiency);
  • Anabolic therapy (except for AIDS), provided to counteract acute or chronic catabolic illness (e.g., surgery outcomes, trauma, cancer, chronic hemodialysis, chronic infectious disease) producing catabolic (protein wasting) changes in both adult and pediatric patients;
  • Anabolic therapy to enhance body mass or strength for professional, recreational, or social reasons;
  • Glucocorticoid-induced growth failure;
  • Short stature due to Down’s or Noonan’s syndrome;
  • Intrauterine growth retardation;
  • Treatment of altered body habitus (e.g., buffalo hump) associated with antiviral therapy in HIV infected patients;
  • Treatment of obesity;
  • Treatment of cystic fibrosis,
  • Treatment of idiopathic dilated cardiomyopathy; or
  • Treatment of juvenile idiopathic or juvenile chronic arthritis.

The following diagnostic tests for GHD are considered experimental, investigational and unproven:

  • 24 hour continuous monitoring of GH levels,
  • Serum levels of insulin-like growth factors (IGF) or insulin-like growth factor-binding protein (IGFBP).

NOTE:  Refer to Medical Policy RX501.065 for coverage for Recombinant Insulin-Like Human Growth Factor (Increlex®).


Human growth hormone (HGH), also known as somatotropin, is synthesized in somatotropic cells of the anterior lobe of the pituitary gland.  Recombinant GH has been marketed since 1985. 

A major point of controversy is what defines inadequate secretion of normal endogenous growth hormone and what constitutes growth failure.  Prior to the availability of biosynthetic GH, GH was rationed to those children with classic GHD as defined by a subnormal response (< 10 ng/ml) to GH provocation tests.

However, the ready supply of GH has created interest in expanding its use to short-stature children without classic GHD, often referred to as:

  • Partial GHD,
  • Neurosecretory GH dysfunction,
  • Constitutional delay in growth and development (CDGD), or
  • Idiopathic short stature. 

Classic GH deficiency is suggested when there is an abnormal growth velocity (typically below the 10th percentile) in conjunction with a chronological age that is greater than the height age and bone age.  In practical fact, interest in broadening the use of GH to non-GHD children has resulted in GH evaluation in many children who are simply below the 3rd percentile in height with or without an abnormal growth velocity.

However, these broadened patient selection criteria have remained controversial due to uncertainties in almost every step in the diagnosis and treatment process as outlined below:

  • Selection of patients to be tested,
  • Limitations in the laboratory testing for GH,
  • Establishment of diagnostic cutoffs for normal versus abnormal GH levels,
  • Availability of the laboratory tests to predict response to GH therapy,
  • Changes in growth velocity due to GH therapy,
  • Whether resulting final height is significantly improved, and
  • Whether improvement is clinically or emotionally significant for the patient.

There are many ethical considerations regarding GH therapy, most prominently the appropriate informed consent when therapy is primarily requested by the parent due to their particular psychosocial concerns regarding height.

In 2001, Genotropin received a new U.S.  Food and Drug Administration (FDA) labeled indication for treatment of pediatric patients born SGA who fail to show catch-up growth by age two years.  Most children born SGA normalize their stature during infancy, but about 15% maintain an exceptionally short stature at least throughout childhood.  Epidemiologic surveys have suggested that the average adult height of men and women who did not exhibit catch-up growth as children is 5 feet 6 inches in men and 5 feet 1 inch in women.  GH has been investigated in these children, based in part on the hypothesis that a GH resistance is a possible etiology of the growth retardation.

On July 25, 2003 the FDA approved Humatrope® for use in non-GH deficient short stature, defined by the manufacturer as a height standard deviation score (SDS) of -2.25 below mean.  This new indication for GH is the first indication that is based on short stature alone, without underlying etiology.


The following discussion focuses on the most controversial aspects of GH use.

Laboratory Diagnosis of GHD

Diagnosing GHD in children remains an area of confusion and disagreement.  As a result, guidelines remain vague.  For example, both the 2003 American Association of Clinical Endocrinologists (AACE) guidelines and the 2000 consensus guidelines published by the GH Research Society state that diagnosis is a multifaceted process involving clinical, auxological, radiological, and biochemical assessment.  These guidelines provide an informed discussion of various measures, but no proposal of specific criteria.

Regarding biochemical testing alone, there is little agreement on specific criteria within the pediatric endocrinology community.  Some of the reasons include:

  • GHD has different causes: total or relative lack of GH, secretion of abnormal GH, decreased levels of GH dependent growth factors (e.g., IGF-1).
  • There is continuity between absent and normal GH secretion during childhood, making it difficult to specify a cutoff value for GHD.
  • A variety of agents are available for provocative testing; however, there is a lack of well-designed, adequately powered studies comparing the agents most commonly used in pediatric populations.
  • Provocative testing reproducibility is poor.
  • Various provocative test agents may have adverse effects in general and in certain pediatric subpopulations and require experience, careful administration and monitoring and adequate emergency facilities.
  • Test protocols that administer two agents during a single test (e.g., glucagon-propanolol or GHRH-arginine) are thought to result in fewer GH-sufficient children being falsely identified as GHD than single agent tests.
  • Although the use of two separate provocative tests has been proposed in the past, the many possible combinations have not been investigated and compared for accuracy or to determine the best combinations.
  • GH assays used to measure the outcome of provocative tests differ in the anti-GH antibodies used for detection and in the GH standards used for calibrating the assays.  As a result, cutoff values for deficiency should be defined for each assay and laboratory.
  • Age-adjusted, normative data for comparison is limited; collecting more data in normal populations is limited by ethical considerations due to possible adverse events.

These areas of uncertainty have led some investigators and clinicians to abandon the use of provocative testing as the sole diagnostic for GHD, and instead base diagnoses on a combination of clinical and diagnostic test information.  These often include:

  • IGF-1 testing as a screen.  However, approximately 30% of GHD patients have normal IGF-I and approximately 30% of short GH-sufficient children have low IGF-I.
  • IGF-I in combination with a provocative test.
  • Provocative testing.
  • Magnetic Resonance Imaging (MRI) - In general, sensitivity and specificity are moderate.  However, the presence either of an ectopic posterior pituitary lobe or the association of a hypoplastic pituitary stalk and a hypoplastic anterior pituitary lobe is highly predictive of GHD.  MRI is recommended for any pediatric patient with the provisional diagnosis of GHD.
  • Radiologic bone age.
  • Standard auxologic measurements such as height SDS, height velocity, and comparison of predicted final height and mid-parental height.
  • Clinical features suggesting GHD or genetic conditions associated with severe short stature.

However, it should be noted that for the purposes of this policy, relying on auxological measurements alone is inadequate to document GH deficiency. This policy is based on the premise that GH would be considered medically necessary as a replacement therapy for GH deficiency, and not medically necessary when used as treatment of short stature in the absence of GH deficiency.  For example, as discussed further below, treatment of short stature without accompanying GH deficiency is generally considered not medically necessary due to the lack of a functional impairment.

GH Use in Short Stature Children without Documented GHD

While GH therapy in patients with classic GHD is accepted, the use of GH in short-stature patients without GHD (as identified by standard provocation tests) is controversial.

The controversy is related to difficulties in laboratory diagnosis of GHD:

  • The lack of pretreatment factors, either laboratory or other criteria such as various measurements of height, skeletal maturity, etc., which can predict response to GH;
  • The lack of long-term outcome data to show whether initial gains in growth velocity will result in increased adult height; and
  • Lack of data to determine if such an increase in height is associated with any beneficial functional or psychosocial outcome.

Surveys of endocrinologists suggest that laboratory measures of GH secretion are of limited usefulness in the decision of whether to initiate therapy.  The most useful criteria cited by endocrinologists appear to be abnormal height, growth velocity, and delayed bone age.  However, there are inadequate outcome data in terms of final height to validate this approach.  These surveys also suggest that GH treatment is sought primarily to treat the potential psychosocial morbidity of short stature, and yet this outcome has not been studied in GH recipients.  In addition, other studies have suggested that short stature is only variably related to psychosocial morbidity. There has been one controlled trial that examined the behavior of children without documented GHD who were treated with GH due to idiopathic short stature.

Across measures of behavior, including IQ, self-esteem, self-perception, or parental perceptions of competence, there were no significant differences between the control and treatment groups, either at baseline or after five years of GH therapy.  The authors concluded that while there have been no demonstrated psychosocial benefits of GH therapy; likewise, there have been no documented psychosocial ill effects of GH treatment.

In January 1997, the American Academy of Pediatricians (AAP) published a document that recommended the following patient selection criterion for children with short stature (not associated with classic GH deficiency):

“Therapy with GH is medically and ethically acceptable in patients whose extreme short stature keeps them from participating in basic activities of daily living and who have a condition for which the efficacy of GH therapy has been demonstrated."

In addition, the AAP noted:

"Numerous considerations argue against widespread administration of GH therapy to other short children.  First, the therapy's risk benefit ratio in this population is not established.  There could be unknown long-term risks, and the treatment could result in either no increase or only an insignificant increase in final adult height.   Even if the clinical data show a positive risk benefit ratio, however, the benefits of GH therapy will inevitably remain somewhat elusive.  Individual children may escape the stigma of being very short, but a group of very short children will always exist.  On a broader scale, the best therapy for these children would be a campaign against the current prejudice against short people instead of an implicit medical reinforcement of such prejudice."

GH Use in SGA Children

As noted in the Description section, in 2001, one GH preparation received FDA approval for treatment of SGA children. This FDA approval was based on four randomized, open-label controlled clinical trials.  Patients were observed for 12 months before being randomized to receive 0.24 mg/kg/week or 0.48 mg/kg/week GH or no treatment for 24 months.  After 24 months all patients received GH.  In patients receiving the higher GH dosage of 0.48 mg/kg/wk, the patients' height improved from a baseline of -3.4 standard deviations to -1.7 standard deviations below the mean.  In contrast, in the control group the standard deviation score improved to a lesser degree, from -3.1 to -2.9 standard deviations below the mean.  The issues associated with this indication for GH are similar to those for other short-stature children without documented GH deficiency.  There are no documented functional impairments associated with short stature and no data regarding final adult height in the control or treatment group.  It should be noted that the dosage recommended for SGA children, 0.48 mg/kg/week, is a supraphysiologic dose.  For example, in patients with documented GHD, in which the intent is to provide normal physiologic replacement levels of GH, the recommended dosage is only 0.24 mg/kg/week.  There are very minimal data regarding the psychosocial outcomes of short pediatric or adult stature related to intrauterine growth retardation, and how these outcomes may be affected by GH therapy.  As noted above, there are inadequate data to document that short-stature youths have either low self-esteem or a higher than average amount of behavioral or emotional problems.

For both small-for-gestational-age children and short-stature children, an additional strategy to achieve target adult heights is to combine GH therapy with gonadotropin releasing hormone (GnRH) analogs, which prolong the prepubertal growth period.  The combined therapy is intended to increase the critical pubertal height gain by delaying the fusion of the epiphyseal growth plates, thus prolonging the period during which GH is active.  This therapy has been suggested for children who are considered short when they enter puberty.

GH Therapy in Conjunction with GnRH Therapy as a Treatment of Precocious Puberty

Precocious puberty is generally defined as the onset of secondary sexual characteristics before eight years of age in girls and nine years in boys.  Central precocious puberty is related to hypothalamic pituitary gonad activation, leading to increase in sex steroid secretion, which accelerates growth and causes premature fusion of epiphyseal growth plates, thus impacting final height.  Children with precocious puberty are often treated with GnRH (gonadotropin-releasing hormone) analogs to suppress the pituitary gonad activity, to slow the advancement of bone age, and to improve adult height.  Several long-term studies have reported that treatment with GnRH analogs is associated with improved adult height in most cases, particularly in those with the most accelerated bone age progression at treatment onset, the shortest predicted height, and the greatest difference between the target height and the predicted height. 

In contrast, patients with a slowly progressive form in which the predicted height does not change after two years of follow-up may not require any treatment.  In another subset of patients, GnRH analog therapy may be associated with a marked deceleration of bone growth that may ultimately result in an adult stature that is less than the targeted midparental height.  GH may be offered to these patients in order to achieve the targeted adult height.  There have been no randomized controlled trials comparing final adult height in those treated with GnRH analogs alone versus GnRH analogs combined with growth hormone therapy, and the largest case series includes 35 patients.  Case series suggest that GH is most commonly offered as an adjunct to GnRH analogs when the growth velocity drops below the 25th percentile for chronological age.

A series of comparative case series that have included final adult heights have been reported by the same group of investigators from Italy.  This group of investigators is the only one to have reported final adult heights.  The most recent reports focus on a group of 17 girls with precocious puberty and a growth velocity below the 25th percentile who were treated with a combination of GnRH and GH, and 18 girls who refused treatment with adjunctive GH.   Those in the combined group attained a significantly greater adult height (161.2 +/- 4.8 cm) than the “control” group (156.7 +/- 5.7 cm) This small study is inadequate to permit scientific conclusions.  Tuvemo and colleagues reported on the results of a trial that randomized 46 girls with precocious puberty to receive either GnRH analogs or GnRH analogs in addition to GH.   Of interest, all the participants were adopted from developing countries; precocious puberty is thought to be common in such cross-cultural adoptions.  Criteria for participation in this trial did not include predicted adult height or growth velocity.  After two years of treatment, the mean growth and predicted adult height were greater in those receiving combined treatment compared to those receiving GnRH analogs alone.  The absence of final height data limits interpretation of this trial.

As noted above, the “not medically necessary” status of other applications of GH for non-GH deficient short-stature children is based on the absence of a functional impairment associated with a less than predicted final adult height.  While these same considerations may apply to using GH therapy as a component of therapy for precocious puberty, the “investigational” status of this indication is based on lack of final height data from controlled trials.

Turner's syndrome

Short stature is almost universal in Turner's syndrome.  Poor growth is evident in utero and further deceleration occurs during childhood and at adolescence.  The mean adult height for those with Turner's syndrome is 58 inches (4 ft 10 inches). Unlike Prader-Willi syndrome, GHD is not seen.  The FDA approvals for Humatrope® and Nutropin® were based on the results of randomized, controlled clinical trials that included final adult height as the outcome.  A group of patients with Turner's syndrome given Humatrope® at a dosage of 0.3 mg/kg/week for a median of 4.7 years achieved a final height of 146.0 +/- 6.2 cm (57.5 +/-2.25 inches)/compared to an untreated control group who achieved a final height of 142.1 +/- 4.8 cm (56 +/- 2 inches).  The results with Nutropin® were similar.  While the data regarding Turner's syndrome are somewhat unique in that final height is known, the clinical significance of a mean increase in height of 3.9 cm (1.75 inches) is unknown.  It should also be noted that earlier initiation of GH therapy might result in more significant increases in adult height.

GH Therapy in Older Adults without Documented GHD

The GH secretion rate decreases by an estimated 14% per decade after young adulthood; mean levels in older adults are less than half those of a young adult.  However, mean GH levels in older adults are greater than age-matched adults with diagnosed GHD.  Older individuals experience changes in body composition, loss of muscle mass, and decreases in bone mineral density that are similar to changes seen in adults with biochemically verified GHD.  Based on these observations, GH therapy has been investigated in older adult without organic pituitary disease. The policy regarding this off label application is based on a 2001 BCBSA Technology Evaluation Center assessment, which offered the following observations and conclusions:

In 1998 the American Association of Clinical Endocrinologists (AACE) published clinical guidelines regarding GH use.  Regarding the use of GH in adults, the AACE guidelines noted that "the benefits of GH supplementation in aging patients remain to be established."  In 1997, the Growth Hormone Research Society published consensus guidelines for the diagnosis and treatment of adults with GHD.  These guidelines state, "partial GH deficiency exists, but further research is needed to distinguish it from physiological causes of reduced GH secretion, e.g., aging.  Furthermore, the benefits of treatment of partial GH deficiency remain to be established."

Only six small controlled trials with at least 10 patients per treatment arm have examined the effect of GH therapy on older patients who may have partial GH deficiency, as compared to younger populations.  These trials used much higher doses than are currently recommended and suffered from potential bias due to disproportionate numbers of dropouts from adverse events.  Bone mineral density outcomes were most often reported, but results did not show consistent time frame (within the time frame tested) and have not been related to fracture rates.  Trials tended to report increases in lean body mass and decreases in fat mass in treated patients compared to controls.  Not all improvements are statistically significant; different methods of measuring body composition across trials may be affected by GH-induced changes in extra cellular fluid, and may not be comparable.

It is not possible to prove effectiveness of GH treatment or lack thereof unless otherwise similar groups of treated versus non-treated patients are compared over a sufficient length of time to allow detection of any significantly and clinically different results.  Limited results do not suggest marked improvement with GH therapy and, in general, are insufficient to permit conclusions regarding the effectiveness of GH at improving disability and quality of life in older populations.

GH Therapy as a Treatment of Altered Body Habitus Related to Antiretroviral Therapy for HIV Infection

There has been research interest in the use of GH to treat the altered body habitus that may be a complication of antiretroviral therapy for HIV infection.  Body habitus changes, also referred to as the fat redistribution syndrome, include thinning of the face, thinning of the extremities, truncal obesity, breast enlargement or an increased dorsocervical fat pad ("buffalo hump").  However, there is minimal published literature regarding the use of GH for this indication. Letters to the editors and small case series dominate the literature.  The largest case series was reported by Wanke and colleagues who treated ten HIV-infected patients (with fat redistribution syndrome) with GH for three months.  The authors reported improved waist/hip ratio and mid-thigh circumference.

GH Therapy for severe Burns

Mortality was studied in a controlled trial of 54 adult burn patients who survived the first seven post-burn days.  Those patients showing difficulty with wound healing were treated with recombinant growth hormone (rhGH) and compared to those healing at the expected rate with standard therapy.  Mortality of rhGH treated patients was 11% compared to 37% not receiving rhGH (p=0.027).  Infection rates were similar in both groups.  In a randomized, double-blind, placebo-controlled trial of 40 severely burned children, the length of hospital stay was reduced from a mean of 0.8 days per % total body surface area (TBSA) burned for the placebo group to 0.54 days per % TBSA burned for the treatment group (p<0.05) (24).  For the average 60% TBSA-burned patient, this approximates a length of stay reduction from 46 to 32 days.  Singh et al studied two groups of patients (n=22) with comparable third-degree burns; those who received GH had improved wound healing and lower mortality (8% vs. 44%).  Demling et al. found significantly improved weight retention and wound healing time with GH or oxandrolone compared to standard treatment in 36 adults with severe burns.

Two phase III double-blind randomized controlled trials of GH treatment in adults following cardiac or abdominal surgery, multiple traumas, or acute respiratory failure found increased in-hospital mortality rates in patients who received GH.  The potential for increased mortality prompted additional studies in critically burned pediatric patients.  Ramirez et al. retrospectively studied 263 pediatric burn patients.  Those treated with GH had no increase in mortality from matched patients who did not receive GH.

However, a randomized, controlled trial in 56 children with more than 40% total body surface area burns found no benefit of GH alone compared to or in combination with propanolol. Another placebo-controlled trial found no benefit to GH with regard to length of hospitalization in 24 adult patients with severe burns.

GH Therapy to Prevent Growth Delay in Children with Severe Burns

Children with severe burns show significant growth delays for up to three years after injury.  GH treatment in 72 severely burned children for one year after discharge from intensive care resulted in significantly increased height in a placebo-controlled, randomized, double-blinded trial.  Aili Low et al. found that GH treatment in severely burned children during hospitalization resulted in significantly greater height velocity during the first two years after burn compared to a similar group of untreated children.

GH Therapy in Conjunction with Optimal Management of Short Bowel Syndrome.

Short bowel syndrome is experienced by patients who have had half or more of the small intestine removed with resulting malnourishment because the remaining small intestine is unable to absorb enough water, vitamins, and other nutrients from food.  The FDA label for Zorbtive® indicates growth hormone has been shown in human clinical trials to enhance the transmucosal transport of water, electrolytes, and nutrients.  The FDA approval for Zorbtive® was based on the results of a randomized, controlled, phase III clinical trial in which patients dependent on intravenous parenteral nutrition who received Zorbtive® (either with or without glutamine) over a four-week period had significantly greater reductions in the weekly total volume of intravenous parenteral nutrition required for nutritional support.  However, the effects beyond four weeks were not evaluated nor were the treatment location (inpatient vs. outpatient) identified.  Several published studies have also demonstrated improved intestinal absorption in short bowel syndrome patients receiving parenteral nutrition.  However, studies have noted the effects of increased intestinal absorption are limited to the treatment period.  Specialized clinics may offer intestinal rehabilitation for patients with short bowel syndrome; GH may be one component of this therapy.  Inpatient intestinal rehabilitation is considered separately in another policy.

Other Indications

GH therapy has been investigated for use in the treatment of cystic fibrosis, idiopathic dilated cardiomyopathy, and juvenile idiopathic arthritis.  No randomized clinical trials were identified to sufficiently demonstrate the appropriateness of GH therapy in these conditions.

Ding and colleagues randomized 48 patients with chronic severe hepatitis B to evaluate growth hormone with lactulose versus no growth hormone.  The authors noted clinical improvement in 90% of patients; however, this study focused on intermediate short-term outcomes and no conclusions can be drawn from the study.  Therefore, chronic infectious disease is added to the investigational policy statement on anabolic therapy for catabolic illness.


Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.



Medicare Coverage:

The information contained in this section is for informational purposes only.  HCSC makes no representation as to the accuracy of this information.  It is not to be used for claims adjudication for HCSC plans.

Medicare does not have a national position on this service.  It is subject to local carrier discretion.  Refer to the local carrier for information.


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American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for Growth Hormone Use in Adults and Children – 2003 Update.  Endocrine Practice (2003 January/February) 9(1), 65-76.

Adamopoulos, S., Parissis, J.T., et al.  Effects of growth hormone on circulating cytokine network, and left ventricular contractile performance and geometry in patients with idiopathic dilated cardiomyopathy.  European Heart Journal (2003) 24(24):2186-96.

Bechtold, S., Ripperger, P., et al.  Growth hormone improves height in patients with juvenile idiopathic arthritis: 4-year data of a controlled study.  Journal of Pediatrics (2003) 143(4):512-9.

Schibler, A., von der Heiden, R., et al.  Prospective randomized treatment with recombinant human growth hormone in cystic fibrosis.  Archives of Disease in Childhood (2003) 88(12):1078-81.

Darmaun, D., Hayes, V., et al.  Effects of glutamine and recombinant human growth hormone on protein metabolism in prepubertal children with cystic fibrosis.  The Journal of Clinical Endocrinology and Metabolism (2004) 89(3):1146-52.

Alber, S.G., and A.D. Mooradian.  Low-dose recombinant human growth hormone as adjuvant therapy to lifestyle modifications in the management of obesity.  The Journal of Clinical Endocrinology and Metabolism. (2004) 89(2):695-701.

Ding, H.G., Shan, J., et al.   Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B.  World Journal of Gastroenterology (2005) 11(19):2981-3.

Mahan, J.D., Warady, B.A.; Consensus Committee.  Assesment and treatment of short stature in pediatric patients with chronic kidney disease: a consensus statement.  Pediatric Nephrology (July 2006) 21(7):917-30.

Molitch, M.E., Clemmons, D.R., et al.  Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline.  Clinical Endocrinology and Metabolism (May 2006) 91(5):1621-34.

Growth Hormone Prior Authorization Criteria.  Prime Therapeutics (2006 February) 1-10.

Issues in Growth Hormone Therapy.  Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program.  TEC Bulletin. (2007 March 6).

Policy History:

8/1/2007          Document updated with literature review.

3/23/2005        Document updated with coverage change.

6/1/2004          Document updated with coverage change.        

12/1/2003        Document updated with literature review.

11/30/2003      Archived.

2/2002             CPT/HCPCS code(s) updated (with bit changes).

6/2001             CPT/HCPCS code(s) updated (with bit changes).

1/2000             Document updated with literature review.

2/1998             Document updated with literature review.

5/1996             Document number changed.

4/1993             Document updated with literature review.

9/1990             New medical document.

Archived Document(s):

Title:Effective Date:End Date:
Human Growth Hormone (GH)07-15-201806-14-2019
Growth Hormone (GH)04-15-201707-14-2018
Growth Hormone (GH)02-15-201604-14-2017
Growth Hormone (GH)07-15-201502-14-2016
Growth Hormone (GH)09-15-201207-14-2015
Growth Hormone (GH)08-01-200709-14-2012
Growth Hormone (GH)03-23-200507-31-2007
Growth Hormone (GH)12-01-200303-22-2005
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