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GH secretion is impaired in adults with idiopathic or acquired childhood-onset or adult-onset GH deficiency and reduced in the elderly. Its action is altered in adults with obesity or those experiencing protein catabolism associated with surgery, severe injury, sepsis, malnutrition/malabsorption, cirrhosis, chronic corticosteroid use and wasting related to cancer treatment or AIDS.

There are many reasons for short stature, some of which are normal, and some due to disease. Height is measured in percentiles of average height; for example, people in the 25th percentile are shorter than 75% of the general population.

DNA-developed recombinant human GH (rhGH) has been administered in an attempt to mimic normal GH secretion or action. Growth hormone is an artificially produced version of the natural hormone, and is injected intramuscularly or subcutaneously either daily or several times a week. Tradenames for GH include Genotropin®, Humatrope®, Norditropin®, Nutropin®, Saizen®, Serostim®, Tev-Tropin®, Omnitrope®, and Zorbtive®.

Growth hormone is also responsible for stimulating the synthesis of insulin-like growth hormone-1 (IGF-1). In some instances children do not make enough IGF-1 which also contributes to bone growth problems. Recombinant DNA technology has produced two insulin-like growth factor-1 (rhGF-1) products which can be given by subcutaneous administration. Tradenames for IGF-1 include Increlex® and Iplex®.

Insulin-like growth factor-1 (IGF-1) is medically necessary according to the following policy guidelines. 

Guidelines for Initiation of  IGF-1 Therapy

IGF-1 therapy is indicated for the treatment of growth failure in children with severe primary IGF-1 deficiency (Primary IGFD) or with growth hormone (GH) gene deletion who have developed neutralizing antibiodies to GH. Severe primary IGFD is defined by: height standard deviation score, < -3 and basal IGF-1 standard deviation score < -3 and normal or elevated growth hormone. Severe primary IGFD includes patients with mutations in the GH receptor (GHR), post (GHR) signaling pathway, and IGF-1 gene defects; they are not GH deficient, and therefore, they cannot be expected to respond adequately to exogenous GH treatment (added 09-21-2006).

In accordance with the individual subscriber contract, the contract may only provide coverage for the growth hormones Omintrope, Serostim, and Zorbtive. Initial Growth Hormone (GH) therapy is medically necessary according to the following policy guidelines. Once initiated, GH therapy is covered only according to the specific Continuation Guidelines.

Guidelines for Initiation of  Human Growth Hormone Therapy

Patients <18 years of age:

GH therapy is medically necessary and covered for growth failure in GH deficient children. [This criteria does not apply to children with subnormal GH levels due to pituitary surgery or radiation therapy] Documentation of growth hormone deficiency must include all of the following:

• Delayed bone age: 2 standard deviations or more below the mean for age and sex
• Subnormal bone-age-specific growth rate less than the 25th percentile
• Evidence that the patient does not have other reasons for short stature, including hypothyroidism. Supporting evidence must include a subnormal response to a least two provocative stimuli of GH release (subnormal response is generally accepted to be a GH level of 10 ng/ml or less)
• No active tumor growth. If GH deficiency results from an intracranial tumor, absence of tumor growth or tumor recurrence should be documented for 6 to 12 months before initiation of GH treatment

Panhypopituitarismor Radiation Therapy

GH therapy is medically necessary  for those patients with panhypopituitarism from pituitary surgery or radiation therapy.

Chronic Renal Insufficiency

GH therapy is medically necessary for short stature in children with chronic renal insufficiency up to the time of renal transplant who do not have a functioning renal transplant and who have both the following:

• Delayed bone age and
• Subnormal bone-age-specific growth rate less than the 25th percentile

Turner's Syndrome

GH therapy is medically necessary for patients with documented Turner's syndrome who have:

• Demonstrated growth failure: height greater than 2 standard deviations (S.D.) below the mean
• Bone age less than 14 years
• Provocative testing is not required, as stimulated levels are often normal
• Estrogen therapy should be delayed until the patient is 15 years of age or when the height deficit is no longer substantial
• Glucose metabolism should be monitored carefully during long-term GH treatment in these patients

HIV Wasting

Serostim® is the only growth hormone FDA approved for HIV wasting

Serostim® is medically necessary for patients with HIV wasting syndrome for 12 weeks only, in patients who meet all of the following:

1. Documented AIDS. Weight loss of at least 10% from baseline weight or BMI < 20. Patients treated with GH must simultaneously be treated with appropriate antiviral agents. Calculate the exact Body Mass Index (BMI) as follows:

• For the final BMI, divide the patient's weight in kilograms, by the number (height x height). In this example, 100 divided by (1.8 x 1.8). This equals 100 divided by 3.24, or a final BMI of 30.86.
• Wasting syndrome rather than malnutrition, mental illness, endocrine disease or other causes for weight loss
• Failed response to Marinol

(For patients who have responded well to 12 weeks of Serostim® therapy, extensions are in some instances medically appropriate. For consideration of an individual patient, physicians may send relevant clinical information.)

Prader-Willi Syndrome

GH therapy is medically necessary  in patients with demonstrated Prader-Willi Syndrome

GH now is contraindicated in patients with Prader-Willi Syndrome who are severely obese or have severe respiratory impairment

Genotropin (somatropin [rDNAorigin]) – new labeling changes to the contraindications and warnings sections regarding a potential increased risk of death associated with use in pediatric patients with Prader-Willi Syndrome

Short Bowel Syndrome

Zorbtive® is the only growth hormone FDA approved for Short Bowel Syndrome. Zorbtive® is medically necessary for patients with Short Bowel Syndrome who are receiving specialized nutritional support

Adult Growth Hormone Deficiency

In adults (age >18) with the appropriate clinical history, only one provocative test of GH secretion is needed. Tests that use glucagon, propranolol, levodopa or clonidine are not accepted. Biochemical markers (serum IGF-I) should not be used, as in the case of childhood onset growth hormone deficiency (untreated) this may not be a reliable marker. Also, other disease states may interfere with serum IGF-I levels. It should be noted that GH therapy is not recommended during pregnancy

GH therapy is medically necessary for adult patients with documented:

• Congenital or acquired GH deficiency. This is defined as a response less than 5µg/L (5ng/mL) to Insulin Tolerance Testing (ITT). ITT is the gold standard for provocative stimulation testing. If this test is contraindicated due to angina, coronary artery disease, history of a seizure disorder or history of cortisol deficiency, then an arginine plus GH - releasing hormone test is acceptable. In general, the ITT is not recommended for patients older than 65 years of age.  The cut off for arginine andGHRH testingis <10µg/L(10ng/ml)
• Symptomatic somatropin deficiency syndrome

GH therapy is contraindicated in patients with active malignant disease, benign intracranial hypertension, and proliferative or preproliferative diabetic retinopathy.

Guidelines for Continuation of  Human Growth Hormone Therapy

GH treatment in children is continued until final height or epiphyseal closure (or both) has been recorded. Treatment into adulthood would be continued at a lower level on the basis of clinical and biochemical responses. Documented GH failure as a child does not have to be re-demonstrated as an adult.

GH therapy in girls with Turner's Syndrome is medically necessary until:

• Bone age is over 14 years, or
• Growth velocity is less than 2.5 cm/year, or
• Attainment of height satisfactory to patient and family, or consistent with genetic potential

GH therapy is considered investigational and NOT medically necessary for other indications not listed above, including the following:

• Short children who are not GH deficient (this includes Small for Gestational Age (SGA), except for Turner's syndrome;
• Patients with the diagnosis of partial growth hormone deficiency, neurosecretory GH dysfunction;
• GH bioresistance and GH insensitivity (Laron Syndrome);
• Constitutional growth delay (lower than expected height percentile compared with their target height percentiles and delayed skeletal maturation when growth velocities and rates of bone age advancement are normal);
• Anabolic therapy, except for AIDS, provided to counteract acute or chronic catabolic illness (e.g., surgery outcomes, trauma, burns, cancer, chronic hemodialysis) producing catabolic (protean wasting) changes in both adult and pediatric patients;
• Anabolic therapy to enhance body mass or strength for professional, recreational, or social reasons;
• Children with growth failure caused by glucocorticoids;
• Short children with intrauterine growth retardation;
• Children with functioning renal transplants;
• Children with chromosomal and genetic disorders, (except Turner's syndrome);
• Short stature due to Down, Fanconi, Bloom or Noonan syndromes; (moved Prader-Willi syndrome 10-4-2000 to medically necessary)
• Children who are not GH deficient but have short stature associated with chronic disease;
• Familial short stature;
• Congestive heart failure (CHF);
• Wound healing in burn patients;
• Infertility;
• Treatment in pregnant or nursing women.

The following diagnostic tests for growth hormone deficiency are considered not medically necessary:

• 24-hour continuous monitoring of GH levels
• Serum levels for insulin-like growth factors (IGF) (see adult guidelines) or insulin-like growth factor binding protein (IGFBP)

None

Investigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

2/1998: Comprehensive revision approved by MPAC

2/2000: Comprehensive revision approved by Pharmacy & Therapeutics (P & T) Committee

10/4/2000: Prader-Willi syndrome moved from investigational to medically necessary. Estrogen therapy should be delayed until the patient is 15 years of age or when the height deficit is no longer substantial added to Turner's Syndrome. Sources updated

5/8/2001: Serostim ® for HIV wasting added.

5/14/2001: BMI calculation formula added.

7/27/2001: Panhypopituitarism from pituitary surgery or radiation surgery added to medically necessary

8/2001: Policy revisions

1/30/2002: Flow of the paragraph revised under "Patients <18 years of age"; "up to the time of renal transplant" added to Chronic Renal Insufficiency; ITT is the gold standard added to "GH therapy is covered for adult patients with documented"; prior authorization added.

2/13/2002: Investigational definition added

3/12/2002: New 2002 codes added

5/1/2002: Type of Service and Place of Service deleted

9/27/2002: Contraindications added to Adult Growth Hormone Deficiency

11/6/2002: Nova Factor new telephone and fax numbers added. Telephone # 1-800-235-8498 and fax # 1-888-355-6652 deleted.

11/27/2002: Indication for Turner's Syndrome added, Sources updated

1/17/2003: Policy section updated

7/2003: Reviewed by MPAC, no changes, Sources updated

9/17/2003: Contraindications added to Prader-Willi syndrome

9/29/2003: Code Reference section updated, ICD-9 diagnosis codes 941.30-941.39, 942.30-942.39, 943.30-943.39, 944.30-944.38, 945.30-945.9 (should have been 945.59), 946.3, 949.3 moved to non-covered, ICD-9 diagnosis 270.0, 402.01, 402.11, 402.91, 404.01, 404.11, 404.91, 428.0, 606.0, 606.1, 606.8, 606.9, 628.0, 628.1, 628.2, 628.3, 628.4, 628.8, 628.9, 656.50, 656.51, 656.53, 757.39, 758.0, 759.89, 764.90, 764.91, 764.92, 764.93, 764.94, 764.95, 764.96, 764.97, 764.98, 764.99, 783.43, 940.0, 940.1, 940.2, 940.3, 940.4, 940.5, 940.9, 941.00, 941.01, 941.02, 941.03, 941.04, 941.05, 941.06, 941.07, 941.08, 941.09, 941.10, 941.11, 941.12, 941.13, 941.14, 941.15, 941.16, 941.17, 941.18, 941.19, 941.20, 941.21, 941.22, 941.23, 941.24, 941.25, 941.26, 941.27, 941.28, 941.29, 941.40, 941.41, 941.42, 941.43, 941.44, 941.45, 941.46, 941.47, 941.48, 941.49, 941.50, 941.51, 941.52, 941.53, 941.54, 941.55, 941.56, 941.57, 941.58, 941.59, 942.00, 942.01, 942.02, 942.03, 942.04, 942.05, 942.09, 942.10, 942.11, 942.12, 942.13, 942.14, 942.15, 942.19, 942.21, 942.22, 942.23, 942.24, 942.25, 942.29, 942.40, 942.41, 942.42, 942.43, 942.44, 942.45, 942.49, 942.50, 942.51, 942.52, 942.53, 942.54, 942.55, 942.59, 943.00, 943.01, 943.02, 943.03, 943.04, 943.05, 943.06, 943.09, 943.10, 943.11, 943.12, 943.13, 943.14, 943.15, 943.16, 943.19, 943.20, 943.21, 943.22, 943.23, 943.24, 943.25, 943.26, 943.29, 943.40, 943.41, 943.42, 943.43, 943.44, 943.45, 943.46, 943.49, 943.50, 943.51, 943.52, 943.53, 943.54, 943.55, 943.56, 943.59, 944.00, 944.01, 944.02, 944.03, 944.04, 944.05, 944.06, 944.07, 944.08, 944.10, 944.11, 944.12, 944.13, 944.14, 944.15, 944.16, 944.17, 944.18, 944.20, 944.21, 944.22, 944.23, 944.24, 944.25, 944.26, 944.27, 944.28, 944.40, 944.41, 944.42, 944.43, 944.44, 944.45, 944.46, 944.47, 944.48, 944.50, 944.51, 944.52, 944.53, 944.54, 944.55, 944.56, 944.57, 944.58, 945.00, 945.01, 945.02, 945.03, 945.04, 945.05, 945.06, 945.09, 945.10, 945.11, 945.12, 945.13, 945.14, 945.15, 945.16, 945.19, 945.20, 945.21, 945.22, 945.23, 945.24, 945.25, 945.26, 945.29, 946.0, 946.1, 946.2, 946.4, 946.5, 947.0, 947.1, 947.2, 947.3, 947.4, 947.8, 947.9, 948.00, 948.10, 948.11, 948.20, 948.21, 948.22, 948.30, 948.31, 948.32, 948.33, 948.40, 948.41, 948.42, 948.43, 948.44, 948.50, 948.51, 948.52, 948.53, 948.54, 948.55, 948.60, 948.61, 948.62, 948.63, 948.64, 948.65, 948.66, 948.70, 948.71, 948.72, 948.73, 948.74, 948.75, 948.76, 948.77, 948.80, 948.81, 948.82, 948.83, 948.84, 948.85, 948.86, 948.87, 948.88, 948.90, 948.91, 948.92, 948.93, 948.94, 948.95, 948.96, 948.97, 948.98, 948.99, 949.0, 949.1, 949.2, 949.4, 949.5 added to non-covered, HCPCS J3490 description revised “Somatotropin®, Somatrem® deleted”

12/2/2003: New labeling changes added for Prader-Willi syndrome

9/24/2004: Code Reference section updated, ICD-9 procedure code 99.24 description revised, HCPCS J2940, J2941, Q2014 description revised, HCPCS S9558 note added “BCBSMS considers the services included in code S9558 an integral component of the nursing visit or the HCPCS code for the injection. A separate allowance will not be made for this code.” non-covered table deleted, non-covered ICD-9 diagnosis code 270.0, 402.01, 402.11, 402.91, 404.01, 404.11, 404.91, 428.0, 606.0, 606.1, 606.8, 606.9, 628.0, 628.1, 628.2, 628.3, 628.4, 628.8, 628.9, 656.50, 656.51, 656.53, 757.39, 758.0, 759.89, 764.90, 764.91, 764.92, 764.93, 764.94, 764.95, 764.96, 764.97, 764.98, 764.99, 783.43, 940.0, 940.1, 940.2, 940.3, 940.4, 940.5, 940.9, 941.00, 941.01, 941.02, 941.03, 941.04, 941.05, 941.06, 941.07, 941.08, 941.09, 941.10, 941.11, 941.12, 941.13, 941.14, 941.15, 941.16, 941.17, 941.18, 941.19, 941.20, 941.21, 941.22, 941.23, 941.24, 941.25, 941.26, 941.27, 941.28, 941.29, 941.30, 941.31, 941.32, 941.33, 941.34, 941.35, 941.36, 941.37, 941.38, 941.39, 941.40, 941.41, 941.42, 941.43, 941.44, 941.45, 941.46, 941.47, 941.48, 941.49, 941.50, 941.51, 941.52, 941.53, 941.54, 941.55, 941.56, 941.57, 941.58, 941.59, 942.00, 942.01, 942.02, 942.03, 942.04, 942.05, 942.09, 942.10, 942.11, 942.12, 942.13, 942.14, 942.15, 942.19, 942.21, 942.22, 942.23, 942.24, 942.25, 942.29, 942.30, 942.31, 942.32, 942.33, 942.34, 942.35, 942.39, 942.40, 942.41, 942.42, 942.43, 942.44, 942.45, 942.49, 942.50, 942.51, 942.52, 942.53, 942.54, 942.55, 942.59, 943.00, 943.01, 943.02, 943.03, 943.04, 943.05, 943.06, 943.09, 943.10, 943.11, 943.12, 943.13, 943.14, 943.15, 943.16, 943.19, 943.20, 943.21, 943.22, 943.23, 943.24, 943.25, 943.26, 943.29, 943.30, 943.31, 943.32, 943.33, 943.34, 943.35, 943.36, 943.39, 943.40, 943.41, 943.42, 943.43, 943.44, 943.45, 943.46, 943.49, 943.50, 943.51, 943.52, 943.53, 943.54, 943.55, 943.56, 943.59, 944.00, 944.01, 944.02, 944.03, 944.04, 944.05, 944.06, 944.07, 944.08, 944.10, 944.11, 944.12, 944.13, 944.14, 944.15, 944.16, 944.17, 944.18, 944.20, 944.21, 944.22, 944.23, 944.24, 944.25, 944.26, 944.27, 944.28, 944.30, 944.31, 944.32, 944.33, 944.34, 944.35, 944.36, 944.37, 944.38, 944.40, 944.41, 944.42, 944.43, 944.44, 944.45, 944.46, 944.47, 944.48, 944.50, 944.51, 944.52, 944.53, 944.54, 944.55, 944.56, 944.57, 944.58, 945.00, 945.01, 945.02, 945.03, 945.04, 945.05, 945.06, 945.09, 945.10, 945.11, 945.12, 945.13, 945.14, 945.15, 945.16, 945.19, 945.20, 945.21, 945.22, 945.23, 945.24, 945.25, 945.26, 945.29, 945.30, 945.31, 945.32, 945.33, 945.34, 945.35, 945.36, 945.39, 945.40, 945.41, 945.42, 945.43, 945.44, 945.45, 945.46, 945.49, 945.50, 945.51, 945.52, 945.53, 945.54, 945.55, 945.56, 945.59, 946.0, 946.1, 946.2, 946.3, 946.4, 946.5, 947.0, 947.1, 947.2, 947.3, 947.4, 947.8, 947.9, 948.00, 948.10, 948.11, 948.20, 948.21, 948.22, 948.30, 948.31, 948.32, 948.33, 948.40, 948.41, 948.42, 948.43, 948.44, 948.50, 948.51, 948.52, 948.53, 948.54, 948.55, 948.60, 948.61, 948.62, 948.63, 948.64, 948.65, 948.66, 948.70, 948.71, 948.72, 948.73, 948.74, 948.75, 948.76, 948.77, 948.80, 948.81, 948.82, 948.83, 948.84, 948.85, 948.86, 948.87, 948.88, 948.90, 948.91, 948.92, 948.93, 948.94, 948.95, 948.96, 948.97, 948.98, 948.99, 949.0, 949.1, 949.2, 949.3, 949.4, 949.5 deleted

11/02/2005:  Description section updated.  Somatram® and Somatropin® deleted.   Policy section updated: changed preferred provider to Accredo, changed telephone # from 1-866-591-9075 to 1-866-240-3373, changed fax # from 1-866-591-9094 to 1-888-355-6682.

11/4/2005:  Code Reference section update, ICD9 diagnosis code 253.5 deleted, 585.1, 585.2, 585.3, 585.4, 585.5, 585.6, 585.9 added, 253.2, 253.3 description revised, the drugs Tev-tropin and Zorbtive added to the description of code  J2941

11/2005: Approved by Pharmacy & Therapeutics (P & T) Committee

2/6/2006: Code Reference table updated: ICD9 diagnosis code 250.40 deleted, codes 250.41, 586, V15.3 added, description updated on code 250.43; HCPCS code Q0515 added, deletion date added to code Q2014, Biotropin added to the description of code J2941, description revised on code S9558

03/09/2006:  Coding updated.  HCPCS 2006 revisions added to policy.

09/12/2006:  Coding updated.  ICD9 2006 revisions added to policy.

09/21/2006: IGF-1 description and policy information added

12/28/2006: Code Reference section updated per the 2007 CPT/HCPCS revisions

1/29/2007: Trade name Omnitrope® added to policy

2/16/2007: Short Bowel Syndrome indication for Zorbtive® added

01/01/2009: Accredo preferred provider information removed. BCBSMS information added.

A national study of physician recommendation patterns. JAMA 1996; 276:531-37.

Sundberg DE, Brook AE, Campos SP. Short stature: A psychosocial burden requiring growth hormone therapy? Ped 1994; 94:832-40.

Wyatt DT, Mark D. Slyper A. Survey of growth hormone treatment practices by 251 pediatric endocrinologists. J Clin Endo Metab 1995; 80:3292-97.

American Academy of Pediatrics. Considerations related to the use of recombinant human growth hormone in children. Ped 1997; 99:122-129.

American Association of Clinical Endocrinologists. Clinical practice guidelines for growth hormone use in adults and children. May-June 1998.

American Journal of Managed Care Volume 6, #15 Supplement Sept 2000

TEC Assessments 1996: Tab 9

TEC Assessments 1996: Tab 10

TEC Bulletin, July 3, 1996

Hayes Medical Technology Directory

Claus Hojbjerg Gravholt, MD, PhD et al. Short-Term Growth Hormone Treatment in Girls With Turner Syndrome Decreases Fat Mass and Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study. PEDIATRICS Vol. 110 No. 5 November 2002; 889-896

Blue Cross Blue Shield Association policy # 5.01.06

Increlex® Prescribing Information

Iplex® Prescribing Information

Covered Codes

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