Horizon BCBSNJ

Medical Necessity Guideline Section Drugs

Policy Number
Effective Date 6/27/04
Review Date 5/27/05, 8/23/07, 12/22/08

DRUG CLASS Growth Hormones

BRAND NAME Growth Hormone (GH)

Genotropin (all injectable)

(Generic) (somatropin)

Humatrope (all injectable)

(somatropin)

Norditropin (all injectable)

(somatropin)

Nutropin AQ (all injectable)

(somatropin)

Nutropin (all injectable)

(somatropin)

Nutropin Depot (all injectable)

(somatropin)

Protropin (all injectable)

(somatrem)

Saizen (all injectable)

(somatropin)

IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of outpatient prescription drug
benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively
“Horizon BCBSNJ”) insures or administers. Outpatient prescription drugs are not covered under all Horizon benefit
plans. If the member’s contract benefits differ from the pharmacy guideline, the contract prevails. Although a service, supply
drug or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan.
If a service, supply drug or procedure is not covered and the member proceeds to obtain the service, supply drug or procedure,
the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the
physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not
replace a physician’s or pharmacist’s independent professional clinical judgment or duty to exercise special knowledge and skill
in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold
itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services
provided to a Horizon BCBSNJ member.

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Horizon BCBSNJ pharmacy guidelines do not constitute medical advice, authorization, certification, approval,
explanation of benefits, offer of coverage, contract or guarantee of payment.

FDA-APPROVED INDICATIONS

Genotropin:
Genotropin is indicated for:
• Long-term treatment of pediatric patients who have growth failure due to an inadequate secretion of
endogenous growth hormone
• Long-term treatment of pediatric patients with Prader-Willi Syndrome. The diagnosis of Prader-Willi Syndrome
should be confirmed by appropriate genetic testing
• Long-term treatment of growth failure in children born small for gestational age (SGA) who fail to manifest
catch-up growth by age two years.
• Long-term replacement therapy in adults with growth hormone deficiency (GHD) of either childhood- or adult-
onset etiology.
GHD should be confirmed by an appropriate growth hormone stimulation test. Other causes of short stature in
pediatric patients should be excluded.

Humatrope:
Pediatric patients
Humatrope is indicated for the long-term treatment of pediatric patients who have growth failure due to an inadequate
secretion of normal endogenous growth hormone.

Humatrope is indicated for the treatment of short stature associated with Turner’s syndrome in patients whose epiphyses
are not closed.

Adult patients
Humatrope is indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency who
meet both of the following two criteria:
• Adult Onset: Patients who have growth hormone deficiency either alone or with multiple hormone deficiencies
(hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma;

• Childhood onset: Patients who were growth hormone deficient during childhood who have growth hormone
deficiency confirmed as an adult before replacement therapy with Humatrope is started.

Norditropin:
Norditropin is indicated for the long-term treatment of children with growth failure due to inadequate secretion of
endogenous growth hormone, short stature associated with Noonan syndrome, short stature due to Turner syndrome, and
short stature in children born small for gestational age (SGA) with no catch-up growth by age 2-4 years.

Adult Patients
Norditropin is indicated for replacement of endogenous GH in adults with GHD who meet either of the following two
criteria:
• Adult Onset: Patients who have GHD either alone, or associated with multiple hormone deficiencies
(hypopituitarism) as a result of pituitary disease, hypothalamic disease, surgery radiation therapy or trauma; or
• Childhood Onset: Patients who were GHD during childhood should have GHD confirmed as an adult before
replacement therapy with Norditropin is started.

In both of these patient populations, GHD should be confirmed by an appropriate GH stimulation test.

Nutropin/Nutropin AQ:
Pediatric Patients:
Nutropin and Nutropin AQ are indicated for the long-term treatment of growth failure due to a lack of adequate
endogenous GH secretion.

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Nutropin and Nutropin AQ are also indicated for the treatment of growth failure associated with chronic renal insufficiency
up to the time of renal transplantation. Nutropin or Nutropin AQ therapy should be used in conjunction with optimal
management of chronic renal insufficiency.

Nutropin and Nutropin AQ are also indicated for the long-term treatment of short stature associated with Turner syndrome.

Adult Patients
Nutropin and Nutropin AQ are indicated for the replacement of endogenous GH in patients with adult GH deficiency who
meet both of the following two criteria:
• Biochemical diagnosis of adult GH deficiency by means of a subnormal response to a standard
growth hormone stimulation test (peak GH less than or equal to 5 mcg/L), and
• Adult-onset: Patients who have adult GH deficiency either alone or with multiple hormone
deficiencies (hypopituitarism) as a result of pituitary disease, hypothalamic disease, surgery,
radiation therapy, or trauma; or childhood-onset: Patients who were GH deficient during childhood,
confirmed as an adult before replacement therapy with Nutropin and Nutropin AQ is started.

Nutropin Depot:
Nutropin Depot for is indicated for the long-term treatment of growth failure due to lack of adequate endogenous GH
secretion.

Considerations for Use:

As with any GH treatment, patients should be monitored closely throughout therapy for growth response to Nutropin
Depot. Failure to respond adequately requires careful assessment. Patients for whom no discernible cause is found
should be considered for a course of treatment with a daily form of rhGH. Experience in patients who were treated with
daily GH and switched to Nutropin Depot is limited.

Protropin:
Protropin (somatrem) is indicated only for the long-term treatment of children who have growth failure due to a lack of
adequate endogenous growth hormone secretion. Other etiologies of short stature should be excluded.

Saizen:
Saizen [somatropin (rDNA origin)] is indicated for the long-term treatment of children with growth failure due to inadequate
secretion of endogenous growth hormone.

Serostim is not approved for the treatment of growth hormone deficiency.

Horizon does not cover growth hormone for the following indications:
• Treatment for children with idiopathic or non-growth hormone deficient short stature, defined as > 2.25
standard deviation below the mean height for age and sex;
• Treatment for children born small for gestational age (SGA) who failed to catch up growth by age 2; OR
• Treatment for adults with adult-onset isolated growth hormone deficiency

CRITERIA FOR APPROVAL

1. Does the patient have any of the following:

● acute critical illness due to complications following open heart surgery,
abdominal surgery, multiple accidental trauma, or acute respiratory failure.
● an active neoplasia or tumor activity.
● proliferative or preproliferative diabetic retinopathy Yes No
[If the answer to this question is yes, then no further questions required.]

2. Is the growth hormone being prescribed for the promotion of wound healing due to Yes No
life-threatening third (3rd) degree burns?
[If the answer to this question is yes, then no further questions required.]

3. Is the patient >18 years of age or has closed or fused epiphyses? Yes No
[If the answer to this question is yes, then may skip to question 21.]

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4. Does the patient have the diagnosis of Prader-Willi Syndrome confirmed by appropriate
genetic testing? Yes No
[If the answer to this question is no, then may skip to question 6.]

5. Is the patient severely obese or has a history of severe respiratory impairment? Yes No
[If the answer to this question is yes, no further questions required.]
[If the answer to this question is no, may skip to question 11]

6. Is the patient female and has the diagnosis of Turner syndrome confirmed by appropriate genetic
testing? Yes No
[If the answer to this question is no, then skip to question 8.]

7. At the initiation of therapy, did the patient have a height that is less than the 5th percentile for normal
children the same chronological age and gender, or the mid-parental target height? Yes No
[If the answer to this question is yes, may skip to question 11.]
[If the answer to this question is no, no further questions required]

8. Does the patient have the diagnosis of chronic renal insufficiency or chronic renal failure? Yes No
[If the answer to this question is no, then may skip to question 10.]

9. At the initiation of therapy, did the patient have a height that is less than the 3rd percentile for normal
children the same chronological age and gender? Yes No
(Equivalent to more than 2.5 standard deviations below the mean for normal children of the same age)
[If the answer to this question is yes, may skip to question 11]
[If the answer to this question is no, no further questions required]

10. Does the patient have either:

● a diagnosis of short stature homeobox-containing gene (SHOX) deficiency confirmed by
appropriate genetic testing?
● a diagnosis of Noonan’s Syndrome confirmed by appropriate genetic testing? Yes No
[If the answer to this question is no, may skip to question 12 ]

11. Has the patient received at least 6 months of therapy as a Caremark administered benefit? Yes No
[If the answer to this question is yes, skip to question 20.]
[If the answer to this question is no, no further question required]

12. Does the patient have a diagnosis of growth hormone deficiency? Yes No
[If the answer to this question is no, then may skip to question 19.]

13. Has the patient received at least 6 months of therapy as a Caremark administered benefit? Yes No
[If the answer to this question is yes, then skip to question 20.]

14. Does the patient have evidence of another pituitary hormone deficiency or has received a treatment
known to cause GH deficiency? Yes No
[If the answer to this question is yes, may skip to question 17.]

15. Does the patient have a height that is ≥ 2 standard deviations below the mean for Yes No
normal children of the same chronological age and gender?

16. Does the patient have a delayed bone age that is ≥ 2 standard deviations below the
mean for normal children of the same chronological age and gender? Yes No

17. Has the patient experienced a poor growth velocity defined as less than 7 cm per year for
children before the age of 3 years or less than 5 cm per year for children 3 years of age or older? Yes No
(Equivalent to more than 1 standard deviation below the mean for normal children of the same age)

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18. Has the patient had either of the following evaluation results:
● failed at least two growth hormone (GH) stimulation tests (A failure is generally defined as a
peak serum growth hormone value of less than 10 mcg/L after GH stimulation.)
● the patient had at least one growth hormone stimulation test level < 15mcg/L and IGF-1 and
IGFBP3 levels below normal for normal children of the same chronological age and gender Yes No
[No further questions required.]

19. Does the patient have a diagnosis of small for gestational age (SGA) and have: Yes No
● a birth weight and/or length 2 standard deviations (SD) or more below mean for
gestational age
● the patient is 2 years of age or older and has failed to catch up (height 2SD or more below
mean for age and sex or mid-parental target height) Yes No
[If the answer to this question is no, no further questions required]

20. Does the patient have any of the following:

• growth velocity of the patient less than 2 cm per year
• the height of the patient reached the 5th percentile of the mid-parental target height for
children of same chronological age and gender
[No further questions required]

21. Is the patient an adult that has a diagnosis of documented growth hormone deficiency secondary
to any of the following:
● pituitary surgery related panhypopituitarism
● trauma related panhypopituitarism
● cranial irradiation related panhypopituitarism Yes No
[If the answer to this question is yes, then no further questions required.]

22. Does the patient have a documented childhood-onset growth hormone deficiency? Yes No

23. Has the patient received at least 6 months of therapy as AN ADULT (> 18 years old) as a Yes No
Caremark administered benefit?
[If the answer to this question is yes, then no further questions required.]

24. Has the patient achieved both:

• documented growth hormone replacement therapy with achievement of adult height
• the patient has completed linear growth Yes No

25. Was the patient off therapy for at least 1 month since receiving growth hormone as a child? Yes No

26. After being off growth hormone for at least 1 month, has the patient failed at least one Yes No
growth hormone (GH) stimulation tests?
[A failure is generally defined as a maximum peak of less than 5 mcg/L when
measured by RIA (polyclonal antibody), less than 3.5 mcg/L when measured
by IRMA (monoclonal antibody) or less than 3 mcg/L during hypoglycemia.]

Guidelines for Approval

Duration of Approval 12 months
Set 1 – Prader Willi - Initial Set 2 – Prader Willi - Renewal Set 3 – Turner’s - Initial
Yes to question(s) No to question(s) Yes to question(s) No to question(s) Yes to question(s) No to question(s)
4 1 4 1 6 1
2 11 2 7 2
3 3 3
5 5 4
11 20 11

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Set 4 – Turner’s – Renewal Set 5 – CRF – Initial Set 6 – CRF– Renewal
Yes to question(s) No to question(s) Yes to question(s) No to question(s) Yes to question(s) No to question(s)
6 1 8 1 8 1
7 2 9 2 9 2
11 3 3 11 3
4 4 4
20 6 6
11 20

Set 7 – Child GHD – Initial Set 8 – Child GHD – Initial Set 9 – Child GHD – Renewal
Yes to question(s) No to question(s) Yes to question(s) No to question(s) Yes to question(s) No to question(s)
12 1 12 1 12 1
14 2 15 2 13 2
17 3 16 3 3
18 4 17 4 4
6 18 6 6
8 8 8
10 10 10
13 13 20
14

Set 10 – Adult Trauma/Surgery Set 11 – Adult GHD – childonset initial Set 12 Adult GHD-childonset renewal
Yes to question(s) No to question(s) Yes to question(s) No to question(s) Yes to question(s) No to question(s)
3 1 3 1 3 1
21 2 22 2 22 2
24 21 23 21
25 23
26

Set 13 – SGA Set 14 – 3rd degree burns

Yes to question(s) No to question(s) Yes to question(s) No to question(s)
19 1 2 1
2
3
4
6
8
10
12
20
Set 15 – SHOX/Noon Initial Set 16 –SHOX/Noon Renewal
Yes to No to Yes to No to
question(s) question(s) question(s) question(s)
10 1 10 1
2 11 2
3 3
4 4
6 6
8 8
11 20

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Horizon BCBSNJ Pharmacy Guideline Development Process: This Horizon BCBSNJ Pharmacy Guideline (the
“Pharmacy Guideline”) has been developed by Horizon BCBSNJ’s Pharmacy Drug Policy Subcommittee, Clinical Issues
Subcommittee, and Quality Improvement Committee which include practicing physicians and pharmacists. This guideline
is consistent with generally accepted standards of medical and pharmacy practice, and reflects Horizon BCBSNJ’s view of
the subject health care services, supplies drugs or procedures, and in what circumstances they are deemed to be
medically necessary or experimental/ investigational in nature. This Pharmacy Guideline also considers whether and to
what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type,
frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed.
Where relevant, this Pharmacy Guideline considers whether the subject prescription drugs are being requested primarily
for the convenience of the covered person or the health care provider. It may also consider whether the prescription
drugs are more costly than alternative prescription drugs that are at least as likely to produce equivalent therapeutic or
diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion
regarding what it considers to be the generally accepted standards of medical and pharmacy practice, Horizon BCBSNJ reviews
and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by
the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians
and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the
appropriate specialty), the findings and directives of the Food and Drug Administration and any other relevant factor as
determined by applicable State and Federal laws and regulations.

BLACK BOX WARNINGS

None

RATIONALE

The intent of the criteria is to ensure that patients follow selection elements established by Horizon BCBS New Jersey’s
medical policies.

ADDITIONAL INFORMATION

Actions that have been demonstrated for growth hormone (hGH) include:

1. Tissue Growth
A. Skeletal Growth: Growth hormone stimulates skeletal growth in pediatric patients with GHD. The measurable
increase in body length after administration of GH results from an effect on the epiphyseal plates of long
bones. Concentrations of IGF-1, which may play a role in skeletal growth, are generally low in the serum of
pediatric GHD patients but tend to increase during treatment with GH. Elevations in mean serum alkaline
phosphatase concentration are also seen.
B. Cell Growth: It has been shown that there are fewer skeletal muscle cells in short-statured pediatric patients
who lack endogenous growth hormone as compared with the normal pediatric population. Treatment with GH
results in an increase in both the number and size of muscle cells.
C. Organ Growth: Growth hormone influences the size of internal organs, including kidneys, and increases in red
cell mass. Treatment of hypophysectomized or genetic dwarf rats with GH results in organ growth that is
proportional to the overall body growth. In normal rats subject to nephrectomy-induced uremia, GH promoted
skeletal and body growth.

2. Protein Metabolism
Linear growth is facilitated in part by increased cellular protein synthesis. Nitrogen retention, as demonstrated by
decreased urinary nitrogen excretion and serum urea nitrogen, follows the initiation of therapy with GH.

3. Carbohydrate Metabolism
Pediatric patients with hypopituitarism sometimes experience fasting hypoglycemia that is improved by treatment with GH.
Large doses of growth hormone may impair glucose tolerance. Untreated patients with Turner syndrome have an
increased incidence of glucose intolerance. Administration of human growth hormone to normal adults or patients with
Turner syndrome resulted in increases in mean serum fasting and postprandial insulin levels although mean values
remained in the normal range. In addition, mean fasting and postprandial glucose and hemoglobin A1c levels remained in
the normal range. Although the precise mechanism of the diabetogenic effect of GH is not known, it is attributed to

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blocking the action of insulin in rather than blocking insulin secretion. Insulin levels in serum actually increase as GH
levels increase.

4. Lipid Metabolism
In GHD patients, administration of GH has resulted in lipid mobilization, reduction in body fat stores, and increased
plasma fatty acids.

5. Mineral Metabolism
Growth hormone induces retention of sodium, potassium, and phosphorus. Serum concentrations of inorganic phosphate
are increased in patients with GHD after therapy with GH. GH does not significantly alter serum calcium. Growth hormone
could increase calciuria. Sodium retention also occurs. Adults with childhood-onset GH deficiency show low bone
mineral density.

6. Body Composition
Adult GHD patients treated with GH at the recommended adult dose demonstrate a decrease in fat mass and an increase
in lean body mass. When these alterations are coupled with the increase in total body water, the overall effect of GH is to
modify body composition, an effect that is maintained with continued treatment.

7. Connective Tissue Metabolism

Growth hormone stimulates the synthesis of chondroitin sulfate and collagen as well as the urinary excretion of
hydroxyproline.

Serostim is not approved for the treatment of growth hormone deficiency.

CONTRAINDICATIONS/WARNINGS/PRECAUTIONS

Contraindications:
Growth hormone therapy should not be initiated to treat patients with acute critical illness due to complications following
open heart or abdominal surgery, multiple accidental traumas or to patients having acute respiratory failure. Two placebo-
controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions revealed a significant
increase in mortality (41.9% versus 19.3%) among somatropin treated patients (doses 5.3-8 mg/day) compared to those
receiving placebo.

Growth hormone should not be used for growth promotion in children with closed epiphyses.

Growth hormone should not be used in patients with active neoplasia. Growth hormone therapy should be discontinued if
evidence of neoplasia develops. Intracranial lesions must be inactive and anti-tumor therapy complete prior to the
initiation of growth hormone.

Growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe
respiratory impairment.

Warnings:
The safety of continuing growth hormone treatment in patients receiving replacement doses for approved indications who
concurrently develop acute critical illnesses has not been established. Therefore, the potential benefit of treatment
continuation with growth hormone in patients having acute critical illnesses should be weighed against the potential risks.

Precautions:
Because growth hormone may reduce insulin sensitivity, patients should be monitored for evidence of glucose
intolerance.

For patients with diabetes mellitus, the insulin dose may require adjustment when growth hormone therapy is instituted.
Because growth hormone may reduce insulin sensitivity, particularly in obese individuals, patients should be observed for
evidence of glucose intolerance. Patients with diabetes or glucose intolerance should be monitored closely during growth
hormone therapy.

Patients with symptomatic hypoglycemia associated with growth hormone deficiency should be closely monitored.

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Patients with a history of an intracranial lesion should be examined frequently for progression or recurrence of the lesion.

Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders or in patients undergoing
rapid growth.

Progression of scoliosis can occur in patients who experience rapid growth. Because growth hormone increases growth
rate, patients with a history of scoliosis who are treated with growth hormone should be monitored for progression of
scoliosis. Growth hormone has not been shown to increase the incidence of scoliosis.

In patients with hypopituitarism (multiple hormonal deficiencies) standard hormonal replacement therapy should be
monitored closely when treatment with somatropin is instituted. Hypothyroidism may develop during treatment with
somatropin, and inadequate treatment of hypothyroidism may prevent optimal response. Therefore, patients should have
periodic thyroid function tests and be treated with thyroid hormone when indicated.

Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting has been reported in a
small number of patients treated with growth hormone products. Symptoms usually occurred within the first eight weeks of
the initiation of growth hormone therapy. In all reported cases, IH-associated signs and symptoms resolved after
termination of therapy or a reduction of the growth hormone dose. Funduscopic examination of patients is recommended
at the initiation, and periodically during the course of, growth hormone therapy.

Before continuing treatment as an adult, a post-pubertal GHD patient who received growth hormone replacement therapy
in childhood should be re-evaluated with proper testing as described in indications and usage. If continued treatment is
appropriate, growth hormone should be administered at the reduced dose level recommended for adult GHD patients.

Geref Diagnostic
The Geref Diagnostic test should not be conducted in the presence of drugs that directly affect the pituitary secretion of
somatotropin. These include preparations that contain or release somatostatin, insulin, glucocorticoids, or
cyclooxygenase inhibitors such as aspirin or indomethacin. Somatotropin levels may be transiently elevated by clonidine,
levodopa, and insulin-induced hypoglycemia. Response to Geref Diagnostic may be blunted in patients who are receiving
muscarinic antagonists (atropine) or who are hypothyroid or being treated with antithyroid medication such as
propylthiouracil. Obesity, hyperglycemia, and elevated plasma fatty acids generally are associated with subnormal GH
responses to Geref Diagnostic. Exogenous growth hormones therapy should be discontinued at least one week before
administering the Geref Diagnostic test.

HISTORY
6/25/04 Reviewed with revision
5/27/05 Reviewed with revisions: aligned medical and pharmacy policies.
8/23/07 Reviewed with revisions: aligned with the revised medical policy; added contraindication
questions
12/22/08 Reviewed with revisions: simplified criteria

REFERENCES
1. Genotropin product information. Pharmacia/Upjohn. April 2003.
2. Nutropin Depot product information. Genentech, Inc. December 1999.
3. Geref Diagnostic product information. Serono Laboratories, Inc. March 1998.
4. Humatrope product information. Eli Lilly and Company. July 2002.
5. Nutropin product information. Genentech. April 2002.
6. Nutropin AQ product information. Genentech. April 2002.
7. Norditropin product information. Novo Nordisk. November 2008.
8. Protropin product information. Genentech. February 2001.
9. Saizen product information. Serono Laboratories, Inc. December 2002.
10. AACE Clinical Practice Guidelines for Growth Hormone Use in Adults and Children. Endocrine Practice
January/February 2003; 9(1): 65-76.
11. USPDI Drug Information for Healthcare Professionals. MICROMEDEX Thomson Healthcare. Greenwood, CO. 2003.
12. Kamp, G.A., Mul, D. et al. A Randomized Controlled Trial of Three Years Growth Hormone and Gonadotropin-
Releasing Hormone Agonist Treatment in Children with Idiopathic Short Stature and Intrauterine Growth Retardation.
The Journal of Clinical Endocrinology and Metabolism. 86 (7). 2001.

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13. Consensus. Critical Evaluation of the Safety of Recombinant Human Growth Hormone Administration: Statement from
the Growth Hormone Society. The Journal of Clinical Endocrinology and Metabolism. 2001; 86 (5).
14. Consensus. Consensus Guideline for the Diagnosis and Treatment of Growth Hormone (GH) Deficiency in Childhood
and Adolescence: Summary Statement of the GH Research Society. The Journal of Clinical Endocrinology and
Metabolism. 2000; 85 (11): 3990-3993.
15. Spaenger, P., Albertsson, K., Wikland, G.S., et al. Recommendations for the Diagnosis and Management of Turner
Syndrome. The Journal of Clinical Endocrinology and Metabolism. 2001; 86 (7).
16. DeZegher, Francis, Algertsson-Wickland, Kerstin, Wollman, Hartmut, et al. Growth Hormone Treatment of Short
Children Born Small for Gestational Age: Growth Responses with Continuous and Discontinuous Regimens over 6
years. The Journal of Clinical Endocrinology and Metabolism. 2000; 85 (8): 2816-2821.
17. Lee Vance M, Mauras N. Growth hormone therapy in adults and children. N Eng J Med 1999; 341(16): 1206-1216.
18. Cummings, David E., Merriam, George R. Age-Related Changes in Growth Hormone Secretion: Should the
Somatopause be Treated? Sem Reproductive Endocrinology.1999; 17(4): 311-396.
19. Bengtsson, Bengt-Ake, Johannsson, Gudmundur, Shalet, Stephen M., et al. Therapeutic Controversy, Treatment of
Growth Hormone Deficiency in Adults. The Journal of Clinical Endocrinology and Metabolism. Volume 85, No. 3.
2000.
20. Kilbanski, Anne, Clemmons, David R., Christiansen, Jens, and Underwood, Louis. Growth Hormone Replacement
Therapy for Growth Hormone Deficiency in Adults: The Changing Role of Growth Hormone Therapy (Review Article).
Endocrine Practice. March/April 1999; 5 (2).
21. Myers, Susan E., Carrel, Aaron L., Whitman, Barbara Y., and Allen, David B. Sustained Benefit after 2 years of
Growth Hormone on Body Composition, Fat Utilization, Physical Strength and Agility, and Growth in Prader-Willi
Syndrome. The Journal of Pediatrics. July 2000; 137 (1).
22. Prakash-Cheng, Ainu and McGovern, Margaret. Russell-Silver Syndrome. eMedicine Journal. October 26,2001; 2
(10).
23. DeZegher, F. Ong, K. VanHelvoirt, M, et al. High-dose growth hormone (GH) treatment in non-GH-deficient children
born small for gestational age induces growth responses related to pre-treatment GH secretion and associated with a
reversible decrease in insulin sensitivity. The Journal of Clinical Endocrinology and Metabolism. 2002; 87 (1): 148-151
24. Buckway, CK, Selva, KA, Pratt, E, et al. Insulin-like growth factor binding protein-3 generation as a measure of GH
sensitivity. The Journal of Clinical Endocrinology and Metabolism. 2002; 87 (10): 4754-4765.
25. Cutfield, WS. Jackson, WE, Jefferies, C, et al. Reduced insulin sensitivity during growth hormone therapy for short
children born small for gestational age. The Journal of Pediatrics. February 2003; 113-116.

Pharmacy Guidelines can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making
coverage determinations. Members referring to this policy should discuss it with their treating physician or pharmacist, and
should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

This Horizon BCBSNJ Pharmacy Guideline is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its
affiliates. The contents of this Pharmacy Guideline are not to be copied, reproduced or circulated to other parties without the
express written consent of Horizon BCBSNJ. The contents of this Pharmacy Guideline may be updated or changed without
notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of
Pharmacy Guidelines existing at the time of the decision and are not subject to later revision as the result of a change in
Pharmacy Guideline.

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