Growth Hormone Therapy Medical Necessity: Indications and Criteria, Schemes and Mind Maps of Pediatrics

Download Growth Hormone Therapy Medical Necessity: Indications and Criteria and more Schemes and Mind Maps Pediatrics in PDF only on Docsity! 09-J0000-27 Original Effective Date: 11/15/00 Reviewed: 03/09/22 Revised: 04/01/22 Subject: Growth Hormone Therapy THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION. Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions Related Guidelines Other References Updates DESCRIPTION: Growth hormone (GH) is an anterior pituitary hormone that directly influences protein, carbohydrate, and lipid metabolism and controls the rate of skeletal and visceral growth by stimulating the release of Insulin like Growth Factor 1 (IGF-1) from the liver. IGF-1 acts directly on many cell types to stimulate growth. Their secretion of GH is in part controlled by the hypothalamus. Pharmaceutical preparations are referred to as somatropins. Somatropin is a pharmaceutical preparation of growth hormone, prepared by recombinant means. A pegylated form of somatropin (lonapegsomatropin-tcgd) and somapacitan-beco are formulations of growth hormone with an extended dosing interval. POSITION STATEMENT: Growth hormone therapy (recombinant or biosynthetic) meets the definition of medical necessity when administered for the following indications AND indication specific criteria are met (SEE TABLE 1 FOR SPECIFIC CRITERIA):  Growth failure due to growth hormone deficiency (GHD) in children under the age of 21 years  Growth hormone therapy in children with chronic renal failure (before renal transplantation)  Growth hormone therapy with Turner's syndrome  Growth hormone therapy with Noonan’s syndrome  Growth hormone therapy in children with Short Stature Homeobox Gene (SHOX) deficiency  Growth hormone therapy with Prader-Willi syndrome  Growth hormone therapy with Small for Gestational Age (SGA)  Growth hormone deficiency in adults 21 years of age and older OR adolescents whose epiphyses have closed  Growth hormone therapy in members with HIV-associated wasting or cachexia  Growth hormone therapy in members with Short Bowel syndrome. Growth hormone is an effective treatment for conditions that may or may not be related to a deficiency of growth hormone. Growth hormone meets the definition of medical necessity when used for the indications listed in Table 1; conversely, the use of growth hormone to manage linear growth in the absence of one of the above conditions is considered cosmetic. NOTE: Norditropin is the preferred growth hormone product. For non-preferred growth hormone products, the member must meet ONE of the following: 1. The member has a hypersensitivity or FDA labeled contraindication to Norditropin that is not expected to occur with the requested agent – documentation must be submitted 2. ALL of the following – documentation must be submitted: a. The request is for a long-acting growth hormone product (e.g., Skytrofa) indicated for the treatment of growth failure due to pediatric growth hormone deficiency in a child 1 year of age and older b. The member must have received a trial of Norditropin for at least 12 months c. The member failed to achieve a 2 cm/year growth velocity d. The rationale for use of the long-acting formulation is provided and the use is not for convenience SPECIFIC CRITERIA FOR GROWTH HORMONE THERAPY INDICATION COVERAGE CRITERIA Growth failure due to growth hormone deficiency (GHD) in children under the age of 21 NOTE: For adolescents whose epiphyses have closed please also refer to criteria in section below “Growth hormone deficiency in adults 21 years of age and older or adolescents whose epiphyses have closed documentation must indicate all of the following:” Meets the definition of medical necessity when ALL of the following are met: 1. Endocrinologist evaluation must be submitted to Florida Blue for review documenting the need or continued need for growth hormone therapy 2. Other causes of growth failure (e.g. cranial tumors, cranial irradiation, hypothyroidism, chronic systemic disease, infections of the central nervous system, genetic syndromes, skeletal disorders, or other organic causes) have been considered and appropriately excluded. 3. Demonstration of growth hormone (GH) deficiency by ONE of the following: a. Members must have two abnormal growth hormone (GH) provocative stimulation tests with results of 10 ng/ml or less – laboratory documentation must be 9. ONE of the following: a. The member has been previously approved for growth hormone therapy by Florida Blue in the past 2 years b. The member has been previously approved for growth hormone therapy by another health plan in the past 2 years AND historical documentation of GH deficiency is provided (e.g., provocative stimulation test results, medical history of ablative pituitary irradiation) c. The member has previously met all initiation criteria for coverage Approval duration: 1 year Growth hormone therapy in children with chronic renal failure (before renal transplantation) Meets the definition of medical necessity when ALL of the following are met: 1. Endocrinologist evaluation must be submitted to Florida Blue for review documenting the need or continued need for growth hormone therapy 2. Chronic renal insufficiency showing reduction in the glomerular filtration rate (GFR) or creatinine clearance (CrCL) to below 25% of normal level (decline of 30 ml/min/1.73 m2) for at least 3 months (See Table 3 for normal CrCl values) 3. Nutritional status has been optimized, metabolic abnormalities such as acidosis, secondary hyperparathyroidism, and under nutrition corrected. 4. Steroid usage has been reduced to a minimum. 5. Bone age x-ray of the left hand and wrist to determine that epiphyses have not yet closed (children over 10 years of age only) – documentation from the medical record must be provided[a] Approval duration: 1 year Continuation of Therapy for CRF: After the initial 12 months of GH treatment ALL of the following criteria must be documented to demonstrate the medical necessity of continued therapy. 1. Endocrinologist evaluation must be submitted to Florida Blue for review documenting the need or continued need for growth hormone therapy 2. Growth response of at least 4 cm/yr in the first year of GH therapy or 2 cm/yr thereafter must occur for continuation of coverage – documentation from the medical record must be provided 3. Bone age x-ray of the left hand and wrist to determine that epiphyses have not yet closed (children over 10 years of age only) – documentation from the medical record must be provided[a] 4. In members with chronic renal failure undergoing transplantation, GH therapy is discontinued at the time of transplant and will not be continued until at least 1 year after the transplant to allow for evaluation of the functionality of the grafted organ and catch-up growth. 5. The member has been previously approved for growth hormone therapy by Florida Blue or another health plan in the past 2 years, or the member has previously met all initiation criteria for coverage Approval duration: 1 year Growth hormone therapy with Turner's syndrome Meets the definition of medical necessity when ALL of the following are met: 1. Endocrinologist evaluation must be submitted to Florida Blue for review documenting the need or continued need for growth hormone therapy 2. Peripheral blood karyotype showing a 45, XO genotype – laboratory documentation must be provided 3. Member meets ONE of the following: a. Pretreatment height less than 3rd percentile or 2 Standard Deviations (SD) below the population mean for age and gender – documentation from the medical record must be provided b. Growth velocity below the 50th percentile for chronological age over 6 months– documentation from the medical record must be provided 4. X-ray report showing that epiphyses have not yet closed (children over 10 years of age only) – documentation from the medical record must be provided[a] Approval duration: 1 year Continuation of Therapy for Turner’s syndrome: After the initial 12 months of GH treatment ALL of the following criteria must be documented to demonstrate the medical necessity of continued therapy. 1. Endocrinologist evaluation must be submitted to Florida Blue for review documenting the need or continued need for growth hormone therapy 2. Bone age x-ray of the left hand and wrist to determine that epiphyses have not yet closed (children over 10 years of age only) – documentation from the medical record must be provided[a] 3. Growth velocity of >4 cm in the first year and >2 cm thereafter – documentation from the medical record must be provided 4. The member has been previously approved for growth hormone therapy by Florida Blue or another health plan in the past 2 years, or the member has previously met all initiation criteria for coverage Approval duration: 1 year Growth hormone therapy with Noonan’s syndrome Meets the definition of medical necessity when ALL of the following are met: 1. Endocrinologist evaluation must be submitted to Florida Blue for review documenting the need or continued need for growth hormone therapy 2. Member has no serious heart failure 3. IGF-1 levels and cardiac function are monitored regularly 4. Pretreatment height less than 3rd percentile or 2 Standard Deviations (SD) below the population mean for age and gender – documentation from the medical record must be provided 5. Growth velocity (GV) measured over one year prior to initiation of therapy of 1 or more standard deviations below the mean for age and gender – documentation from the medical record must be provided 6. X-ray report showing that epiphyses have not yet closed (children over 10 years of age only) – documentation from the medical record must be provided[a] Approval duration: 1 year Continuation of Therapy for Noonan syndrome: 2. A growth response of >2cm/yr must occur for continuation of coverage – documentation from the medical record must be provided 3. Documentation of improvement in body composition: increase in lean body mass and decreases in fat mass – documentation from the medical record must be provided 4. Bone age x-ray of the left hand and wrist to determine that epiphyses have not yet closed (children over 10 years of age only) – documentation from the medical record must be provided[a] 5. The member has been previously approved for growth hormone therapy by Florida Blue or another health plan in the past 2 years, or the member has previously met all initiation criteria for coverage Approval duration: 1 year Growth hormone therapy with Small for Gestational Age (SGA) Meets the definition of medical necessity when ALL of the following are met: 1. Endocrinologist evaluation must be submitted to Florida Blue for review documenting the need or continued need for growth hormone therapy 2. A child with short stature associated with SGA who is at least 2 years of age 3. Documentation of birth weight less than 5th percentile for gestational age and birth height < 10% for gestational age – documentation from the medical record must be provided 4. At 24 months of age has failed to demonstrate catch up growth and is below the 3rd percentile in height and weight for chronological age or height and weight < 2 SD below the mean for chronological age – documentation from the medical record must be provided Approval duration: 1 year Continuation of Therapy for SGA: After the initial 12 months of GH treatment ALL of the following criteria must be documented to demonstrate the medical necessity of continued therapy. 1. Endocrinologist evaluation must be submitted to Florida Blue for review documenting the need or continued need for growth hormone therapy 2. Insulin-like Growth Factor I (IGF-I) is considered medically necessary to determine adequacy of GH therapy and must be within normal levels for age, gender and tanner development stage – laboratory documentation must be provided (Ranges more than 2 SD below the mean for IGF-I strongly suggests abnormality in the GH axis if other causes of low IGF have been excluded.) 3. Doubling of pre-treatment growth rate or increase in growth rate of 3 cm/year or more in first year of therapy – documentation from the medical record must be provided 4. Growth rate remains above 2 cm/year after the first year – documentation from the medical record must be provided 5. Bone age x-ray of the left hand and wrist to determine that epiphyses have not yet closed (children over 10 years of age only) – documentation from the medical record must be provided[a] 6. The member has been previously approved for growth hormone therapy by Florida Blue or another health plan in the past 2 years, or the member has previously met all initiation criteria for coverage Approval duration: 1 year Growth hormone deficiency in adults 21 years of age and older OR adolescents whose epiphyses have closed Meets the definition of medical necessity when ALL of the following are met: 1. Endocrinologist evaluation must be submitted to Florida Blue for review documenting the need or continued need for growth hormone therapy 2. Member meets ONE of the following: a. For those adults with childhood onset deficiency OR adult growth hormone deficiency due to organic disease presenting with 0, 1, or more anterior pituitary hormone deficiency(s) treated with replacement therapy and ONE of the following: i. An abnormal response as indicated by TWO of the following standard growth hormone provocative stimulation tests:  ITT - Peak GH ≤ 5 ng/ml – laboratory documentation must be provided  Glucagon - Peak GH ≤ 3 ng/ml BMI ≤ 30 kg/m2 – laboratory documentation must be provided  Glucagon - Peak GH ≤ 1 ng/ml BMI > 30 kg/m2 – laboratory documentation must be provided  Arginine - Peak GH ≤ 0.4 ng/ml – laboratory documentation must be provided  Macimorelin - Peak GH ≤ 2.8 ng/ml – laboratory documentation must be provided ii. Baseline pretreatment Serum IGF-1 is low for age and gender as established per the laboratory’s reference range (laboratory documentation must be provided) AND the member has an abnormal response to ONE of the following standard growth hormone provocative stimulation tests:  ITT - Peak GH ≤ 5 ng/ml – laboratory documentation must be provided  Glucagon - Peak GH ≤ 3 ng/ml BMI ≤ 30 kg/m2 – laboratory documentation must be provided  Glucagon – Peak GH ≤ 1 ng/ml BMI > 30 kg/m2 – laboratory documentation must be provided  Arginine - Peak GH ≤ 0.4 ng/ml – laboratory documentation must be provided  Macimorelin - Peak GH ≤ 2.8 ng/ml – laboratory documentation must be provided NOTE: Insulin Tolerance Test (ITT) is considered the gold standard, but alternatives such as the glucagon or macimorelin tests are also acceptable b. Adult GH deficiency as a result of pituitary disease or hypothalamic disease (e.g. panhypopituitarism, multiple pituitary hormone deficiency (MPHD), pituitary tumor, surgical damage, cranial irradiation, Sheehan’s syndrome, autoimmune hypophysitis, or sarcoidosis trauma) presenting with ≥ 3 anterior [a] X-ray must be taken within 6 months of request [b] Step therapy requirement does not apply if a prior health plan paid for the medication - documentation of a paid claim within the past 90 days must be submitted [c] Not required for members with multiple (≥3) anterior pituitary hormone deficiencies, congenital GHD, or GHD resulting from destructive lesions of the pituitary or treatment (e.g., irradiation) NOTE: There is no standardization of IGF-1 assays and what is normal is dependent upon the assays method performed at the performing lab. Growth hormone, a self-administered injectable prescription drug used to increase height or bone growth except for conditions of growth hormone deficiency documented with abnormally low stimulation tests of less than 10 mg/ml and abnormally low growth hormone dependent peptide (IGF-1) or for conditions of growth hormone deficiency associated with loss of pituitary function due to trauma, surgery, tumors, radiation or disease, or for state mandated use as in members with AIDS is not considered medically necessary and therefore not a covered benefit. Growth hormone is not considered a medical necessity for all other indications, including: 1. Use as an antiaging agent 2. Infertility 3. Crohn’s Disease 4. Use in obesity 5. Use in somatopause 6. Use as a performance-enhancing drug for athletes 7. Use for chronic fatigue syndrome, fibromyalgia, or obesity 8. Growth hormone insensitivity (Laron Syndrome) 9. Children with constitutional growth delay 10. Children with idiopathic short stature 11. Children with growth failure caused by glucocorticoids 12. Growth retardation due to amphetamines (e.g., Adderall®, Ritalin®) 13. Children who are not growth hormone deficient but have short stature associated with chronic disease (except chronic renal failure) 14. Children with functioning renal transplants 15. Children with chromosomal and genetic disorders (except Turner’s and Prader-Willi Syndrome) 16. Familial short stature 17. Use as an adjunct to ovulation induction in hypogonadotropic hypogonadism, bilateral tubal occlusion, anovulatory or oligo ovulatory infertility or unexplained infertility 18. HIV lipodystrophy or adipose redistribution syndrome DOSAGE/ADMINISTRATION: THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE. Table 2 Clinical Condition Dose in μ/kg/day Dose in mg/kg/day Only for once weekly products GHD in Children 24 – 34 0.024 – 0.034 0.24 mg/kg/week GHD in Adolescents 25 – 100 0.025 – 0.100 GHD in Adults 4 – 16 0.004– 0.016 1.5 – 8 mg/week Chronic Renal Insufficiency 50 0.050 Turner’s Syndrome Up to 67 Up to 0.067 Noonan Syndrome Up to 66 Up to 0.066 Small for Gestational Age Up to 67 Up to 0.067 Prader Willi Syndrome 35 – 50 0.035 – 0.050 HIV-associated wasting or cachexia - 0.1 (max 6 mg/day) Short-bowel syndrome - 0.1 (max 8 mg/day) PRECAUTIONS: Boxed Warning: none Contraindications:  Acute Critical Illness  Children with Prader-Willi syndrome who are severely obese or have severe respiratory impairment - reports of sudden death  Active Malignancy  Hypersensitivity to somatropin or excipients (or somapacitan-beco)  Active Proliferative or Severe Non-Proliferative Diabetic Retinopathy  Children with closed epiphyses Precautions/Warnings:  Acute Critical Illness: Potential benefit of treatment continuation should be weighed against the potential risk  Prader-Willi Syndrome in Children: Evaluate for signs of upper airway obstruction and sleep apnea before initiation of treatment for GHD. Discontinue treatment if these signs occur  Neoplasm: Monitor patients with preexisting tumors for progression or recurrence. Increased risk of a second neoplasm in childhood cancer survivors treated with somatropin - in particular meningiomas in patients treated with radiation to the head for their first neoplasm  Impaired Glucose Tolerance and Diabetes Mellitus: May be unmasked. Periodically monitor glucose levels in all patients. Doses of concurrent antihyperglycemic drugs in diabetics may require adjustment  Intracranial Hypertension: Exclude preexisting papilledema. May develop and is usually reversible after discontinuation or dose reduction  Hypersensitivity: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention.  Fluid Retention (i.e., edema, arthralgia, carpal tunnel syndrome – especially in adults): May occur frequently. Reduce dose as necessary  Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism  Hypothyroidism: May first become evident or worsen  Slipped Capital Femoral Epiphysis: May develop. Evaluate children with the onset of a limp or hip/knee pain  Progression of Preexisting Scoliosis: May develop  Pancreatitis: Consider pancreatitis in patients with persistent severe abdominal pain  Lipoatrophy: Rotate injection sites  Carpal tunnel syndrome: Discontinue if symptoms do not resolve  Concomitant antiretroviral therapy: Antiretroviral agents should be continued for patients treated for HIV-associated wasting or cachexia. BILLING/CODING INFORMATION: The following codes may be used to describe: HCPCS Coding: J2941 Injection, somatropin, 1 mg J3590 Unclassified drugs or biologicals ICD-10 Diagnosis Codes That Support Medical Necessity: B20 Human immunodeficiency virus (HIV) disease E23.0 Hypopituitarism E23.1 Drug-induced hypopituitarism E23.3 Hypothalamic dysfunction, not elsewhere classified E23.6 Other disorders of pituitary gland E23.7 Disorder of pituitary gland, unspecified E89.3 Post-procedural hypopituitarism E34.3 Short stature due to endocrine disorder E34.8 Other specified endocrine disorder E34.9 Endocrine disorder, unspecified REFERENCES: 1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2017 [cited 2017 Jan 18]. 2. American Academy of Pediatrics: Considerations Related to the Use of Recombinant Human Growth Hormone in Children. Pediatrics Vol. 99 No. 1 January 1997, pp. 122-129. 3. American Association of Clinical Endocrinologists medical Guidelines for Clinical Practice for Growth Hormone Use in Growth Hormone Deficient Adults and Transition Patients. 2009 Update. 4. American Medical Association CPT Coding, 2009, professional edition. 5. Approach to the Growth Hormone-Deficient Child during Transition to Adulthood Sally Radovick and Sara DiVall Division of Pediatric Endocrinology, Department of Pediatrics, The Johns Hopkins University School of Medicine,Baltimore, Maryland J Clin Endocrinol Metab92: 1195–1200, 2007. 6. Arch Dis Child, (2003); 88: 283-285. Growth hormone therapy in the Prader-Willi Syndrome. 7. Baxter L, Bryant J, Cave CB, Milne R. Recombinant growth hormone for children and adolescents with Turner syndrome. Cochrane Database of Systematic Reviews 2003, Issue 3. Art. No.: CD003887. DOI: 10.1002/14651858. CD003887.pub2. 8. BENJAMIN U. NWOSU, MD, and MARY M. LEE, MD. Evaluation of Short and Tall Stature in Children. Am Fam Physician. 2008 Sep 1;78(5):597-604. 9. Berrin Ergun-Longmire, MD, Michael P. Wajnrajch, MD. Chapter 1a – Growth and Growth Disorders. Endotext. Updated January 4, 2010. 10. Blue Cross Blue Shield Association Clearinghouse Update, p.3; January 2000. 11. Blue Cross Blue Shield Association TEC Bulletin. FYI Growth Hormone Guidelines 07/03/96. 12. Blum WF, Crowe BJ, Quigley CA, Jung H, Cao D, Ross JL, Braun L, Rappold G. Growth hormone is effective in treatment of short stature associated with short stature homeobox-containing gene deficiency: Two-year results of a randomized, controlled, multicenter trial. J Clin Endocrinol Metab. 2007 Jan; 92(1): 219-28. 13. Blum WF. SHOX deficiency: does GH treatment do any good? European Congress of Endocrinology 2008; Endocrine Abstracts (2008) 16 S15.1. 14. Bondy CA, Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007; 92: 10-25. 15. Bryant J, Baxter L, Cave CB, Milne R. Recombinant growth hormone for idiopathic short stature in children and adolescents. Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD0044. 16. Butler MG, Brunschwig A, Miller LK et al. Standards for selected anthropometric measurements in Prader–Willi syndrome. Pediatrics 1991; 88: 853–60. 17. Carrel, AL, Moerchen, V, Myers, SE, et al. Growth Hormone Improves Mobility and Body Composition In Infants and Toddlers With Prader-Willi Syndrome. J Pediatr 2004;145:744-9. 18. Clayton P. Consensus on GH Treatment in SGA. European Congress of Endocrinology 2008; Endocrine Abstracts (2008) 16 S15.4. 19. Clayton P. Management of the child born small for gestational age through adulthood: a consensus statement of the international societies of pediatric endocrinology and the growth hormone research society. J Clin Endocrinol Metab. 2007: 92; 804-810. 20. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.;2021. URL www.clinicalpharmacilogy-ip.com Accessed 11/25/21. 21. Collett-Solberg PF, Ambler G, Backeljauw PF et al. Diagnosis, genetics, and therapy of short stature in children: a growth hormone research society international perspective. Horm Res Paediatr. 2019; 92: 1-14. 22. Consortium Health Plans Medical Policy 5.01.06, Human Growth Hormone, 01/16/98. 23. Cook DM, Yuen K, Biller B et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients – 2009 update. Endocr Pract. 2009; 15 (Suppl 2) 24. Dahlgren J. GH therapy in Noonan syndrome – facts and myths. European Congress of Endocrinology 2008; Endocrine Abstracts (2008) 16 S15.2. 25. Deal CL, Tony M, Höybye, C, Growth Hormone Research Society Workshop Summary: Consensus Guidelines for Recombinant Human Growth Hormone Therapy in Prader-Willi Syndrome. J Clin Endocrinol Metab, June 2013, 98(6):E1072–E1087. ECRI. Recombinant Hormone Treatments for Idiopathic Short Stature and Severe Primary Insulin-Like Growth Factor Deficiency. Custom Hotline Response. Updated 12/14/05. 26. Endocrine Practice; Vol 9, No. 1 January/February 2003. American association of Clinical Endocrinologists, Medical Guidelines for Clinical Practice for Growth Hormone Use in Adults and Children, 2003 Update. 27. Facts and Comparisons 4.0, accessed. 28. FDA Talk Paper, T03-56, 07/25/03. 29. Ferry RJ. Short Stature. E-Medicine article, last updated 05/23/08. 30. Genotropin® Prescribing Information. Revised May 2008. 31. Gharib H, Cook DM, Saenger PH,et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children--2003 update. 32. Gravholt CH, Andersen NH, Conway GS et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. European Journal of Endocrinology. 2017; 177: G1-G70. 33. Greenbaum LA, Hidalgo G, Chand D, Chiang M, Dell K, Kump T, Peschansky L, Smith HK, Boyle M, Kopf M, Metz LC, Kamel M, Mahan JD. Obstacles to the prescribing of growth hormone in children with chronic kidney disease. Pediatr Nephrol. 2008 Jun 5. 34. Grimberg A, DiVall SA, Polychronakos C et al. The Pediatric Endocrine Society. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr 2016; 86: 361 – 397. Available at: https://www.pedsendo.org/education_training/healthcare_providers/consensus_statements/assets/FI NAL_GH_CGL.pdf. Accessed 01/23/17. 35. Growth Hormone Research Society. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. J Clin Endo & Metab; 2000: 3990 – 3993. 36. Hayes Medical Technology Directory, Growth Hormone Treatment in Adults, 06/17/02. 37. Hayes Medical Technology Directory, Growth Hormone Treatment in Children, 10/15/03. 38. Hokken-Koelega A. GH therapy in children with Prader Willi Syndrome (PWS). European Congress of Endocrinology 2008; Endocrine Abstracts (2008) 16 S15.3. 39. Hormone Res 2003; 60:53-60. Serum Insulin-Like Growth Factor I Reference Values for an Automated Chemiluminescnece Immunoassay System: Results from a Multicenter Study. 40. Humatrope® Prescribing Information (revised November 2006), accessed 06/18/08. 41. Ingenex, HCPCS Level II Coding, 2009 Expert. 42. J. B. Silvers, PhD, Detelina Marinova, PhD, Mary Beth Mercer, MPH, Alfred Connors, MD, Leona Cuttler, MD A National Study of Physician Recommendations to Initiate and Discontinue Growth Hormone for Short Stature PEDIATRICS Vol. 126 No. 3 September 2010, pp. 468-476 (doi:10.1542/peds.2009-3609). 43. Journal of Pediatrics, Volume 127, Number 6, December 1995. 44. Journal of the American Medical Association, (September 23/30, 1998; Vol. 280, No.12; pp.1052-54). 45. Journal of the American Medical Association. Insurance Coverage, Physician Recommendations, and Access to Emerging Treatments, Growth Hormone Therapy for Childhood Short Stature (03/04/98; p.663-704). 46. Kari JA, Rees L. Growth hormone for children with chronic renal failure and on dialysis. Pediat Nephrol. 2005 May; 20(5): 618-21. 47. Keder L, Butler MG. The Genetics of Prader-Willi Syndrome: An Explanation for the Rest of Us. Prader-Willi Syndrome Association’s The Gathered View. March-May 2000. Revised and updated July 2004. 48. Krysiak R, Okopien B. Growth hormone deficiency in adults. Przegl Lek. 2007; 64(9): 583-9. 49. Lagrou k, Froidecoeur C, Thomas M, Massa G, Beckers D, Craen M, de Beaufort C, Rooman R, Francois I, Heinrichs C, Lebrethon MC, Thiry-Counson G, Maes M, DeSchepper J. Concerns, expectations and perception regarding stature, physical appearance and psychosocial functioning before and during high-dose growth hormone treatment of short pre-pubertal children born small for gestational age. Horm Res. 2008; 69(6): 334-42. 50. McCandless, SE, and The Committee On Genetics. Clinical Report—Health Supervision for Children With Prader-Willi Syndrome Pediatrics Vol. 127 No. 1 January 1, 2011 pp. 195 -204 51. Medscape. The Role of Growth Hormone Therapy in Short Children Born Small for Gestational Age. 52. Medscape. Turner Syndrome: Toward Early Recognition and Improved Outcomes. 53. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 11/25/21. 54. Molitch ME, Clemmons DR, Malozowski S. et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011: 96; 1587-1609. 55. MPA, 2000, MMMC, L.L.C. 56. Munns C, Glass I. SHOX-Related Haploinsufficiency Disorders. Gene Reviews, Funded by NIH. 12/12/05, last updated 02/01/08. 57. National Institute of Clinical Excellence. Guidance on the use of human growth hormone (somatropin) in children with growth failure, 05/02. 58. National Institute of Clinical Excellence. Human growth hormone somatropin) in adults with growth hormone deficiency, 08/03. 59. Noordam K. Expanding the genetic spectrum of Noonan syndrome. Horm Res. 2007; 68 Suppl 5:24- 7. 60. Norditropin®Prescribing Information. Revised January 2018. 61. Nutropin® Prescribing Information. Revised October 2007. 62. Omnitrope® Prescribing Information. Revised March 2009. 63. Osio D, Dahlgren J, Wikland KA, Westphal O. Improved final height with long-term growth hormone treatment in Noonan syndrome. Acta Paediatr. 2005 Sep; 94(9): 1232-7. anterior pituitary hormone deficiencies, updated GH definition, removed somatrem (no longer on the market) from the introduction, and updated the administration code. 02/15/11 Revision to guideline; consisting of formatting changes. 11/15/11 Review and revision to guideline consisting of updating the reimbursement section to remove specific brand names, added somatopause to the list of conditions considered not medically necessary, Added definition of somatopause. 11/15/12 Review and revision to guideline; consisting of updating the chart by adding that a correction for other pituitary deficiencies be corrected before initiating GH therapy in children with idiopathic growth hormone deficiency, removed IGFBP-3 as a diagnostic marker in children, added standard deviation below the mean in addition to height percentile and updated this consistently where applicable throughout the document, Updated the adult GH stim response test values according to agent used and BMI. Added obesity, infertility, amphetamine use, and Crohn’s disease to the non- medically necessary list. 02/13/13 Review and revision to guideline; consisted of updating formatting and moved the note for required ruling out of other organic cause for growth failure in children to the bulleted section. Updated the use of IGF-1 testing in lieu of growth hormone stimulation tests to apply in children with ≥ 3 anterior pituitary deficiencies. 03/15/14 Review and revision to guideline; consisting of updating the recommendation in Prader Willi to 5th percentile based on summarized growth chart comparison for Prader Willi and the GHD charts. Minor formatting changes. 05/11/14 Revision: Program Exceptions section updated. 12/15/14 Revision to guideline; consisting of position statement, other 05/15/15 Revision: updated billing/coding 11/01/15 Revision: ICD-9 Codes deleted. 03/15/16 Review and revision to guideline; consisting of updating the position statement for use in children, adults, Turner Syndrome; updated references. 08/15/16 Revision: update to position statement and coding. 10/01/16 Update to ICD-10 coding. 03/15/17 Review and revision to guideline; consisting of updating dosing, precautions and references. 04/15/17 Revision: update to position statement. 03/15/18 Review and revision to guideline; consisting of updating the position statement; updated dosing, precautions and references. 05/15/18 Review and revision to guideline; consisting of updating the position statement and references. 04/15/19 Review and revision to guideline; consisting of updating references. 01/01/20 Revision to guideline consisting of updating the position statement. 04/15/20 Review and revision to guideline; consisting of updating the position statement and references. 10/15/20 Revision to guideline consisting of updating the position statement. 11/15/20 Review and revision to guideline consisting of updating the position statement, dosing, and references. 01/15/22 Review and revision to guideline consisting of updating the position statement, description, dosing, and references. 04/01/22 Review and revision to guideline consisting of updating the position statement.