Human Growth Hormone Replacement Therapy
DESCRIPTION
Human growth hormone (GH, hGH, somatropin or somatotropin) is synthesized in and secreted by the anterior pituitary. GH binds to cell surfaces, eliciting intracellular signals and initiating a phosphorylation cascade. Additionally, GH stimulates the production of insulin-like growth factors, primarily insulin-like growth factor 1(IGF-1). In these ways, GH regulates cell division and protein synthesis for normal growth and metabolic functions. While most active in childhood, GH continues to be secreted in adulthood, influencing important metabolic functions.
Growth hormone deficiency (GHD) occurs in multiple conditions with negative effects on body composition, cardiovascular risk factors and quality of life. Clinical treatment with GH uses recombinant human growth hormone (rhGH).
Examples of preparations of rhGH are: Accretropin™, Genotropin®, Humatrope®, Norditropin®, Nutropin®, Saizen®, Serostim®, Tev-Tropin® and Zorbtive®.
REFER TO DECISION SUPPORT TREE
POLICY
Recombinant human growth hormone therapy for the promotion of wound healing for burns is considered medically necessary.
Recombinant human growth hormone therapy for the treatment of the following conditions is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Conditions related to growth hormone deficiency (GHD)
Growth failure
Short stature
Acquired immune deficiency (AIDS)
Short bowel syndrome
Recombinant human growth hormone therapy for other conditions, including, but not limited to, the following: any condition unrelated to GHD, growth failure, the promotion of wound healing for burns, AIDS or short bowel syndrome is considered investigational.
MEDICAL APPROPRIATENESS
Recombinant human growth hormone therapy for the treatment of conditions related to GHD is considered medically appropriate if ALL of the following criteria are met:
GHD is proven by ANY ONE of the following:
A child, pre-or post-pubescent, with failure of two GH stimulation tests, defined as a peak serum growth hormone value of less than 10 mcg/L after GH stimulation
An adult with ANY ONE of the following:
Failure of the insulin tolerance test (ITT) with an insulin-induced hypoglycemia value less than 5 µg/L (micrograms/liter)
Failure of a stimulation test using arginine and hypothalamic-releasing hormone for GH (GHRH) with a value less than 5 µg/L in individuals for whom an ITT is contraindicated
Individual with ANY ONE of the following:
Growth failure evidenced by ANY ONE of the following:
Epiphyseal opening with x-ray evidence in a child
Genetically confirmed Prader-Willi syndrome
An adult with ANY ONE of the following:
Proven GHD alone
Multiple hormone deficiencies (hypopituitarism) resulting from ANY ONE of the following:
Hypothalamic or pituitary disease
Radiation therapy
Surgery
Trauma
Childhood onset not confirmed until adulthood by a negative response to standard growth hormone stimulation tests
Cranial irradiation
GHD that is iatrogenic (e.g., caused by medical treatment or diagnostic procedures)
Recombinant human growth hormone therapy for the treatment of growth failure is considered medically appropriate if ANY ONE of the following criteria is met:
Individual with chronic renal insufficiency defined as a glomerular filtration rate (GFR) less than 60ml/minute/1.73 meter squared prior to renal transplantation
Individual is a child born small for gestational age (SGA) with failure to manifest catch up by age two
Recombinant human growth hormone therapy for the treatment of short stature is considered medically appropriate if the individual is diagnosed with ANY ONE of the following conditions:
Turner syndrome (i.e., 45, XO genotype)
Noonan syndrome
Short-stature homeobox-containing gene (SHOX) deficiency when epiphyses are not closed
Idiopathic short stature, (i.e., non-growth hormone deficient short stature) with ALL of the following:
Height standard deviation less than -2.25
Growth rates that are unlikely to permit attainment of adult height in normal range
Epiphyses remain open
Exclusion by diagnostic evaluation of other causes associated with short stature that should be observed or treated by other means
Recombinant human growth hormone therapy for the treatment of acquired immune deficiency (AIDS) is considered medically appropriate if ALL of the following criteria are met:
Individual is an adult
Individual has AIDS wasting or cachexia with greater than 10% of baseline weight loss not explained by a concurrent illness other than HIV infection
Individual has simultaneous treatment with antiviral agents
Recombinant human growth hormone therapy for the treatment of short bowel syndrome is considered medically appropriate if ALL of the following criteria are met:
Individual is receiving specialized nutritional support
Therapy is used in conjunction with optimal management of short bowel syndrome
Recombinant human growth hormone therapy is considered not medically appropriate for, but not limited to, the following conditions:
AIDS in children
Anabolic therapy to enhance body mass or strength
Athletic performance enhancement
Constitutional delay of growth and development defined as the following:
Lower than expected height percentiles compared with the target height percentiles
Delayed skeletal maturation when growth velocities and rates of bone age advancement are normal
Crohn's Disease
Cystic fibrosis
Diabetic foot ulcer
Down syndrome and other syndromes associated with short stature
Syndromes associated with malignant diathesis
Dwarfism other than SHOX deficiency
Gastrointestinal hemorrhage
Glucocorticoid-induced growth failure
Growth retardation with juvenile idiopathic arthritis
Hand-Schuller Christian Disease
Hyperinsulinism
Idiopathic dilated cardiomyopathy
Infertility
Inflammatory bowel disease, short gut syndrome
Kwashiorkor
Obesity
Osteogenesis imperfecta
Osteoporosis
Sepsis
Short stature post-renal transplantation
Skeletal dysplasias
Somatopause (older adults)
Testing or any other treatment of the geriatric and/or adult of normal stature as denoted by fused growth (epiphyseal) plates
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
Tennessee State law requires coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is relative to life-threatening illnesses, such as cancer, AIDS, and coronary heart disease and recognized in one of the standard reference compendia (As defined in the statute: The United States Pharmacopoeia Drug Information, The American Medical Association Drug Evaluations, & The American Hospital Formulary Service Drug Information) or in the medical literature. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts, but coverage for off-label uses may be provided based on the contractual agreement.
ADDITIONAL INFORMATION
For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).
Growth hormone stimulation tests involve the use of various agents and combinations of agents including insulin [insulin tolerance test (ITT)], growth hormone–releasing hormone (GHRH), growth hormone-releasing peptide (GHRP), hexarelin, L-dopa and arginine.
In children, GH therapy is typically discontinued when the growth velocity is less that 2 cm per year, when epiphyseal fusion has occurred, or when the height reaches the 5th percentile of adult height.
No controlled studies were found in the published literature that validate the use of human growth hormone therapy for other conditions / diseases.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (6:2008). Human Growth Hormone (5.01.06). Retrieved December 8, 2008 from BlueWeb.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2008). Somatropin. Retrieved December 8, 2008 from MICROMEDEX Healthcare Series.
U. S. Food and Drug Administration. (2003). Center for Drug Evaluation and Research. Zorbtive® [somatropin (rDNA origin) for injection] label. Retrieved December 8, 2008 from http://www.fda.gov/cder/foi/label/2003/20604s026_zorbtive_lbl.pdf.
U. S. Food and Drug Administration. (2003). Center for Drug Evaluation and Research. Zorbtive® [somatropin (rDNA origin) for injection] approval letter. Retrieved December 8, 2008 from http://www.fda.gov/cder/foi/appletter/2003/21597,20604slr026ltr.pdf.
U. S. Food and Drug Administration. (2006). Center for Drug Evaluation and Research. Humatrope® somatropin (rDNA origin) for injection label. Retrieved January 9, 2007 from http://www.fda.gov/cder/foi/label/2006/019640s058lbl.pdf.
U. S. Food and Drug Administration. (2006). Center for Drug Evaluation and Research. Humatrope® somatropin (rDNA origin) for injection approval letter. Retrieved December 8, 2008 from http://www.fda.gov/cder/foi/appletter/2006/019640s058ltr.pdf.
U. S. Food and Drug Administration. (2007). Center for Drug Evaluation and Research. Saizen® [somatropin (rDNA origin) for injection] label. Retrieved December17, 2008 from http://www.fda.gov/cder/foi/label/2007/019764s035lbl.pdf.
U. S. Food and Drug Administration. (2007). Center for Drug Evaluation and Research. Saizen® [somatropin (rDNA origin) for injection] approval letter. Retrieved December17, 2008 from http://www.fda.gov/cder/foi/appletter/2007/019764s035ltr.pdf.
U. S. Food and Drug Administration. (2007). Center for Drug Evaluation and Research. Serostim® [somatropin (rDNA origin) for injection] label. Retrieved December 8, 2008 from http://www.fda.gov/cder/foi/label/2007/020604s044_2lbl.pdf.
U. S. Food and Drug Administration. (2007). Center for Drug Evaluation and Research. Serostim® [somatropin (rDNA origin) for injection] approval letter. Retrieved December 8, 2008 from http://www.fda.gov/cder/foi/appletter/2007/020604s044_v2ltr.pdf.
U. S. Food and Drug Administration. (2007). Center for Drug Evaluation and Research. Tev-Tropin® [somatropin (rDNA origin) for injection] label. Retrieved December 17, 2008 from http://www.fda.gov/cder/foi/label/2007/019774s014lbl.pdf.
U. S. Food and Drug Administration. (2007). Center for Drug Evaluation and Research. Tev-Tropin® [somatropin (rDNA origin) for injection] approval letter. Retrieved December 17, 2008 from http://www.fda.gov/cder/foi/appletter/2007/019774s014ltr.pdf.
U. S. Food and Drug Administration. (2008). Center for Drug Evaluation and Research. Accretropin™ (somatropin) injection label. Retrieved December 17, 2008 from http://www.fda.gov/cder/foi/label/2008/021538lbl.pdf.
U. S. Food and Drug Administration. (2008). Center for Drug Evaluation and Research. Accretropin™ (somatropin) approval letter. Retrieved December 17, 2008 from http://www.fda.gov/cder/foi/appletter/2008/021538s000ltr.pdf.
U. S. Food and Drug Administration. (2008). Center for Drug Evaluation and Research. Genotropin® [somatropin (rDNA origin) for injection] label. Retrieved December 8, 2008 from http://www.fda.gov/cder/foi/label/2008/020280s060lbl.pdf.
U. S. Food and Drug Administration. (2008). Center for Drug Evaluation and Research. Genotropin® [somatropin (rDNA origin) for injection] approval letter. Retrieved December 8, 2008 from http://www.fda.gov/cder/foi/appletter/2008/020280s060ltr.pdf.
U. S. Food and Drug Administration. (2008). Center for Drug Evaluation and Research. Norditropin® Cartridges [somatropin (rDNA origin) for injection], for subcutaneous use label. Retrieved December 8, 2008 from http://www.fda.gov/cder/foi/label/2008/021148s023lbl.pdf.
U. S. Food and Drug Administration. (2008). Center for Drug Evaluation and Research. Norditropin® Cartridges [somatropin (rDNA origin) for injection], for subcutaneous use approval letter. Retrieved December 8, 2008 from http://www.fda.gov/cder/foi/appletter/2008/021148s023ltr.pdf.
U. S. Food and Drug Administration. (2008). Center for Drug Evaluation and Research. Nutropin® AQ [somatropin (rDNA origin) injection] label. Retrieved December 17, 2008 from http://www.fda.gov/cder/foi/label/2007/019676s030,020522s033lbl.pdf.
U. S. Food and Drug Administration. (2008). Center for Drug Evaluation and Research. Nutropin® AQ [somatropin (rDNA origin) injection] approval letter. Retrieved December 17, 2008 from http://www.fda.gov/cder/foi/appletter/2007/019676s030,%20020522s033ltr.pdf.
ORIGINAL EFFECTIVE DATE: 5/1/2000
MOST RECENT REVIEW DATE: 3/10/2009
ID_BT
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
Pharmaceutical Decision Support Tree
Human Growth Hormone Therapy (Accretropin™, Genotropin®, Humatrope®, Norditropin®, Nutropin®, Saizen®, Serostim®, Tev-Tropin® and Zorbtive®)
Most contracts/benefit plans contain limitations regarding human growth hormones. Please refer to any applicable benefit plan exclusions/limitations prior to beginning the questions below.
Is the requested medication being used to treat ANY ONE of the following?
Any condition unrelated to ANY ONE of the following:
Growth hormone deficiency (GHD)
Growth failure
Short stature
Acquired immune deficiency (AIDS)
Short bowel syndrome
AIDS in children
Anabolic therapy to enhance body mass or strength
Athletic performance enhancement
Constitutional delay of growth and development defined as the following:
Lower than expected height percentiles compared with the target height percentiles
Delayed skeletal maturation when growth velocities and rates of bone age advancement are normal
Crohn's Disease
Cystic fibrosis
Diabetic foot ulcer
Down syndrome and other syndromes associated with short stature
Syndromes associated with malignant diathesis
Dwarfism other than SHOX deficiency
Gastrointestinal hemorrhage
Glucocorticoid-induced growth failure
Growth retardation with juvenile idiopathic arthritis
Hand-Schuller Christian Disease
Hyperinsulinism
Idiopathic dilated cardiomyopathy
Infertility
Inflammatory bowel disease, short gut syndrome
Kwashiorkor
Obesity
Osteogenesis imperfecta
Osteoporosis
Sepsis
Short stature post-renal transplantation
Skeletal dysplasias
Somatopause (older adults)
Testing or any other treatment of the geriatric and/or adult of normal stature as denoted by fused growth (epiphyseal) plates
If yes, this does not meet medical necessity and/or medical appropriateness criteria
If no, go to question #2
Is the requested medication being used for the promotion of wound healing for burns?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #3
Does the individual have a diagnosis of growth hormone deficiency (GHD)?
If yes, go to question #4
If no, go to question #8
Is the GHD proven by ANY ONE of the following?
Individual is a child, pre-or post-pubescent, with failure of two GH stimulation tests, defined as a peak serum growth hormone value of less than 10 micrograms/liter (µg/L) after GH stimulation
An adult with ANY ONE of the following:
Failure of the insulin tolerance test (ITT) with an insulin-induced hypoglycemia value less than 5 µg/L
Failure of a stimulation test using arginine and hypothalamic-releasing hormone for GH (GHRH) with a value less than 5 µg/L in individuals for whom an ITT is contraindicated
If yes, go to question #5
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual have growth failure evidenced by ANY ONE of the following?
Epiphyseal opening with x-ray evidence in a child
Genetically confirmed Prader-Willi syndrome
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #6
Is the individual an adult with ANY ONE of the following?
Proven GHD alone
Multiple hormone deficiencies (hypopituitarism) resulting from ANY ONE of the following:
Hypothalamic or pituitary disease
Radiation therapy
Surgery
Trauma
Childhood onset not confirmed until adulthood by a negative response to standard growth hormone stimulation tests
Cranial irradiation
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #7
Does the individual have GHD that is iatrogenic (e.g., caused by medical treatment or diagnostic procedures)?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual have a diagnosis of growth failure with ANY ONE of the following?
Individual with chronic renal insufficiency defined as a glomerular filtration rate (GFR) less than 60ml/minute/1.73 meter squared prior to renal transplantation
Individual is a child born small for gestational age (SGA) with failure to manifest catch up by age two
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #9
Does the individual have short stature from a diagnosis of ANY ONE of the following conditions?
Turner syndrome (i.e., 45, XO genotype)
Noonan syndrome
Short-stature homeobox-containing gene (SHOX) deficiency when epiphyses are not closed
Idiopathic short stature, (i.e., non-growth hormone deficient short stature) with ALL of the following?
Height standard deviation less than -2.25
Growth rates that are unlikely to permit attainment of adult height in normal range
Epiphyses remain open
Exclusion by diagnostic evaluation of other causes associated with short stature that should be observed or treated by other means
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #10
Does the individual have a diagnosis of acquired immune deficiency (AIDS) with ALL of the following?
Individual is an adult
Individual has AIDS wasting or cachexia with greater than 10% of baseline weight loss not explained by a concurrent illness other than HIV infection
Individual has simultaneous treatment with antiviral agents
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #11
Does the individual have a diagnosis of short bowel syndrome with ALL of the following?
Individual is receiving specialized nutritional support
Therapy is used in conjunction with optimal management of short bowel syndrome
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
This document has been classified as public information.