Growth Hormone Therapy Guidelines: Clinical and Managed Care Perspectives

AJPB® Translating Evidence-Based Research Into Value-Based Decisions®September/October 2014
Volume 6
Issue 5

Current treatment guidelines utilized by healthcare provider organizations and managed care organization insurance coverage policies for growth hormone therapy are reviewed.

The prevalence of growth hormone deficiency (GHD) combined with a growing number of indications approved by the FDA for use of recombinant growth hormone (GH) will continue to increase the number of patients eligible for GH treatment and thereby challenge the economics of healthcare.1,2 Annual incidence of new GHD diagnoses is approximately 5 to 10 per 10,000 children.1,2 Non-GHD diagnoses such as idiopathic short stature (ISS), which has an incidence of up to 120 per 10,000 children, are more prevalent and will therefore have a greater impact on pharmacy formulary development. These diagnoses will also impact payers’ decisions regarding health plan coverage policies and benefits.1,3

For pediatric patients with persistent subnormal growth, early recognition and treatment of GHD with recombinant human GH is recommended for individuals with growth failure due to inadequate secretion of endogenous GH, or whose unexplained short stature meets 1 or more of a set of criteria that include height more than 2.25 standard deviations (SDs) below the mean for age or more than 2 SDs below the mid parental height percentile.4,5 In addition, GH therapy is the standard of care and has been approved by the FDA for the treatment of adult GHD and for the treatment of children with certain disorders that result in short stature, including ISS, Noonan syndrome (NS), Prader-Willi syndrome (PWS), small for gestational age (SGA), Turner syndrome (TS), chronic kidney disease (CKD), and short stature homeobox (SHOX) mutations.4,6 In 1995 the Lawson Wilkins Pediatric Endocrinology Society’s Drug and Therapeutics Committee published the initial guidelines for the use of GH in pediatric patients with GHD, chronic renal insufficiency (CRI), CKD during the pretransplantation period, and TS.4 A number of consensus recommendations and clinical practice guidance statements on the use of GH in pediatric patients have since been published. These include recent guidelines for GH therapy for GHD in adults and in transition patients (these patients are frequently older than adolescents) and for other approved indications in childhood, including ISS, NS, PWS, SGA, and TS.7-13

FDA-approved indications regarding GH treatment for short stature have been based on data showing efficacy in improving growth toward the normal range, with development of minimal safety signals. In addition, a number of these reports have reviewed the beneficial effects of GH on quality of life,4-13 although comprehensive data are not available in all non-GHD conditions.

Despite the availability of recommendations and guidelines for the use of GH, there is a gap between physician recommendations and patients’ access to GH treatment because of the cost of treatment and the strong influence of physician attitudes and family preferences in decisions regarding treatment initiation and continuation.14,15 Although this gap has diminished over time, differences among guidelines, physician recommendations, and health plans’ benefits and coverage still exist. In 1998, Finkelstein and colleagues14 published the results of surveys sent to national insurance companies, primary care physicians, and pediatric endocrinologists. These surveys showed a marked difference between physician recommendations and managed care organization (MCO) clinical policies and/or benefits regarding coverage of the costs of GH therapy. Among the differences noted, 96% of pediatric endocrinologists recommended GH for patients with TS, whereas only 52% of TS cases were covered by insurance policies. A large percentage (78%) of the physicians (ie, primary care, endocrinologists) surveyed in this study recommended that their pediatric patients with GHD, TS, and CRI/CKD receive GH treatment. Insurers, however, denied coverage for this therapy in 28% of these patients because of a clear mismatch between the coverage policies of insurers and the treatment recommendations of endocrinologists.14 Finally, physicians recommended GH treatment for 9% of patients with ISS, whereas coverage was denied for nearly all of these patients because many insurers considered the treatment not medically necessary.14 These published results, which predated final FDA approval for GH treatment of ISS in 2003, exemplify the delays and lack of synchronization that may occur between clinician treatment recommendations for indications other than GHD and expansion of treatment coverage by insurers. More recently, a national census study of 727 pediatric endocrinologists used structured questionnaires to identify factors involved in physician decisions to initiate GH treatment for children with ISS.15 The desire of physicians to initiate GH treatment and family preferences together exerted significantly more influence over decisions to continue treatment, increase dosage, or terminate treatment than did the actual growth response achieved by the patient.15

Disparities continue to exist among current clinical practice guidelines that recommend GH therapy for FDA-approved diagnostic indications, physician recommendation for GH therapy, and coverage of this therapy by third-party payers. We recognize that GH is used for some indications that are outside of FDA-approved diagnostic indications, including steroid-induced growth failure, wound healing, and aging. It is not in the scope of this publication to evaluate the occurrence or efficacy of GH for non—FDA-approved indications. Many factors may influence an insurer’s coverage decisions for GH treatment, but MCO policies should be aligned with updated clinical recommendations and/or guidelines based on the latest evidence. The objective of this review is to provide an update of current clinical guidelines and to examine current managed care criteria for the use of GH in the treatment of pediatric patients with GHD or other causes of short stature, and of adolescent and adult patients with GHD.


GHD should be suspected in a child with a subnormal growth rate and no other identifiable causes such as hypothyroidism, chronic illness, malnutrition, or genetic disorder.4 In children, failure to respond to at least 2 GH stimulation tests (GHSTs) must be used to establish the diagnosis of GHD. Commonly used GHST agents include clonidine, insulin, arginine, GH-releasing hormone (GHRH), and glucagon.16 Some typical combinations of provocative agents for GHSTs include arginine-clonidine, clonidine-glucagon, arginine-glucagon, arginine-insulin, and arginine-GHRH. Cook and Rose16 recently reviewed and summarized the recommended use of GHST and diagnostic cut points published by major clinical societies for peak serum GH responses in children. However, GHSTs may provide inconsistent peak GH responses, and some test agents such as GHRH and arginine are either unavailable or have limited availability in the United States.7,16,17 A diagnosis of GHD should still be considered if all of the following criteria are met: (1) height is shorter than 2.25 SDs below the normal mean for age or shorter than 2 SDs below the mid parental height percentile; (2) growth velocity (GV) is slower than the 25th percentile for bone age; (3) bone maturation is delayed more than 2 SDs below the mean for age; (4) there are low serum levels of insulin-like growth factor 1 (IGF-1) and/or insulin-like growth factor binding protein 3 (IGFBP3); and/or (5) there are other clinical features that suggest significant GHD.4 Treatment with GH should be initiated at as young an age as possible to optimize increased height before puberty. Early GH treatment not only improves response but may also be more cost-effective for payers and families, because standard weight-based dosing in young children requires less GH. In prepubertal children the recommended dose range for subcutaneous GH injection is 25 to 50 μg/kg per day.4

Children Born Small for Gestational Age

Children who are born SGA have a birth weight and/or length more than 2 SDs below the mean for neonates of similar gestational age.11 After SGA birth, children are shorter during childhood and attain an adult height that is on average approximately 1 SD below the mean adult height for their peers.11 Typically, a period of accelerated linear growth, or catch-up growth, occurs during the first year; however, catch-up growth slows down and nears completion by age 2 years.11 Measurements of length, weight, and head circumference are recommended at 3-month intervals during a child’s first year and every 6 months thereafter. Children without significant catch-up growth within the first 6 months or who remain short at age 2 years require evaluation for other conditions that limit growth. SGA children aged 2 to 4 years who show no evidence of normal GV or catch-up growth and whose height is shorter than 2.5 SDs below the normal mean height for age are recommended for GH treatment.11 For SGA children older than 4 years who show no evidence of catch-up growth, a consensus recommendation among clinicians has not yet been reached on whether a height shorter than −2.0 or −2.5 SDs should be used as the criterion to initiate GH treatment.11 Most clinicians favor −2.0 SDs as the height cutoff for starting GH therapy in SGA children at this older age. The FDA-approved dose for eligible SGA children 2 to 4 years and older without evidence of catch-up growth before GH treatment is up to 67 μg/kg per day with a higher dose recommended for an individual with marked growth retardation.11

Turner Syndrome

TS occurs in phenotypic female children who may have characteristic physical features and have complete or partial absence of the second sex chromosome with or without cell line mosaicism.9 Short stature among females with TS is the most readily identifiable feature of this genetic disorder. The goal of GH treatment is to promote normal height through early therapeutic intervention. The optimal age for beginning GH therapy has not been clearly established, but the Toddler Turner Study indicates that GH is effective as early as age 9 months.9 Girls younger than age 9 years are treated with GH alone, whereas girls aged 9 years and older may be treated concomitantly with higher doses of GH and an anabolic steroid and/or low-dose estrogen.9 Ross and colleagues18 have recently shown that concurrent treatment with GH and ultra-lowdose estrogen in girls as young as age 5 years significantly improved growth and provided other potential benefits associated with early initiation of estrogen replacement. FDA-approved GH doses for TS range from 0.33 mg/kg per week up to 0.067 mg/kg per day.9,19-22

Idiopathic Short Stature

Children with ISS have a height standard deviation score (SDS) that is more than 2 SDs below the mean for normal peers without evidence of other disease processes, and have stimulated serum GH levels within the normal range.12 The smaller the child, the stronger the rationale to treat with GH. Some MCO policies do not consider GH therapy for ISS as medically necessary because it is not caused by disease or injury. There is a lack of medical consensus within the pediatric endocrinology community, and the approved use of GH to increase height in ISS remains controversial.23 However, this is a particularly important issue in children with severe short stature, and the ISS consensus statement concurred with the height criterion (ie, less than −2.25 SDS) for approved use of GH treatment in children with ISS who have growth rates unlikely to permit attainment of normal adult height.12 FDA-approved GH doses up to 67 μg/kg per day may be used for children with less than a −2.25 SDS to permit attainment of adult height in the normal range.12,24 Selection and adjustment of the GH dose are weight based; an increased dose may be given if the response to GH is considered to be inadequate.

GH treatment should be monitored at 3- to 6-month intervals by assessing height velocity SD and change in height SD over 1 year.12 Pubertal stage is determined according to the method of Tanner, and bone maturation should also be evaluated to monitor the rate of pubertal development as in other children with growth disorders treated with GH.6,25-27 Discontinuation of treatment with GH should be considered when growth velocity is slower than 2 cm/year and bone age is more advanced than 16 years in boys and 14 years in girls, or when height is taller than −2 SDs for an adult of the same sex.12

Prader-Willi Syndrome

PWS is caused by the lack of expression of genes located on the paternally derived 15q11-q13 chromosome, with 75% of cases due to gene deletion on the chromosome. 13 Growth impairment occurs in utero with length SDS shorter than −2 SDS in 20% of affected patients.13 In infancy, PWS is characterized by general hypotonia, feeding difficulties, and low body weight resulting from poor suck and swallowing reflexes, with short stature becoming more obvious during the second year of life. The goals of GH treatment are to improve growth to achieve improved adult height and to positively alter body composition, thereby increasing the ratio of lean to fat body mass.13 Mean spontaneous adult height has been reported to be 152 to 162 cm for boys and 145 to 150 cm for girls.28

Recent evidence suggests that treatment started as young as age 6 to 12 months confers additional benefits to patients with PWS, such as improvements in muscular hypotonia leading to earlier attainment of developmental milestones, reduction in sleep apnea and cardiovascular risk factors, and beneficial changes in abnormal body composition (ie, decreased lean body mass and increased fat mass before growth hormone treatment), common features in children with PWS.13,29-32 Recommended GH doses start low, ranging from 0.25 to 0.30 mg/m2 per day (or 0.009 to 0.012 mg/kg per day), with increasing doses given during the first few weeks or months of treatment to reach a replacement GH dose of 1.0 mg/m2 per day (or up to 0.034 mg/kg per day) while adverse effects, especially sleep apnea in the setting of respiratory episode and morbid obesity, are monitored.13

Noonan Syndrome

NS is a congenital genetic disorder characterized by distinctive facial features, short stature, chest deformity, and congenital heart disease.8 With an estimated prevalence of 1 in every 1000 to 2500 live births, diagnosis is based on clinical evidence supported by genetic testing. Gene mutations have been identified in approximately 61% of patients.8 Genetic testing should not serve as the sole basis for diagnosis because mutations in the protein tyrosine phosphatase nonreceptor type 11 gene (PTPN11), which is one of the first molecular markers of NS, are only detected in approximately 50% of affected individuals.33

Although up to 80% of individuals born with NS have short stature with normal birth weight and length, growth decelerates to a height at the third percentile or less.8 Therefore, routine measurements for changes in weight and length should be plotted 3 times per year for the child’s first 3 years and at least yearly thereafter. Improved patient outcomes with GH treatment include an increased change in height SD and mean height gain, with the greatest increases in patients who are started early and then maintained on GH for an extended duration.8


For adolescent patients, the period of transition is generally defined as beginning late in puberty and ending in their early to mid 20s.34 The continuation of GH therapy during the transition period is advocated by healthcare providers for treatment of patients with GHD and PWS.13,35,36 However, GH treatment is currently FDA approved for adult patients with either childhood-onset or adult-onset GHD.4 The American Association of Clinical Endocrinologists published guidelines in 2009 that stressed the need for and use of GH for continued treatment of persistently GH-deficient transition and adult patients.7 Most recently, the Endocrine Society published clinical practice guidelines (

Table 1

) for the treatment and management of adults with ongoing GHD from childhood-onset GHD, adultonset GHD, and panhypopituitarism. If left untreated with GH replacement therapy, these conditions are associated with an increased risk for cardiac disease and presumably—but not proven—elevated cardiovascular disease (CVD) mortality rates.17 Diagnosis of adult-onset GHD requires testing as outlined below and comparison of results to age- and sex-specific normal range data. Of note, peak stimulated GH declines in elderly persons.37 GHD will not be overdiagnosed if GHST results are compared with appropriate reference ranges.

Persistent GHD may result from congenital multiple pituitary hormone deficits, pituitary lesions, cranial irradiation therapy, or childhood-onset GHD that meets the criteria for GHD when retested and reevaluated in young adulthood.7 For transition patients who have ceased linear growth, reevaluation of GH status is recommended after discontinuation of GH therapy for at least 1 month using acceptable GHSTs to elicit and measure peak stimulated serum GH levels. Currently, the 3 most commonly recommended and used GHSTs to establish a diagnosis of GHD in adults are the insulin tolerance test (ITT), arginine test, and glucagon test. In individuals with seizure disorder, the ITT test is contraindicated, making the arginine and glucagon tests the better options.17 However, the arginine test by itself is not widely used, and the cut-point is <0.4 ng/mL.16 If the transition patient has 3 or more pituitary hormone deficiencies including GHD, guidelines stipulate that a low serum IGF-1 level is the only additional proof necessary for the diagnosis of adult GHD. Some adult patients with isolated idiopathic GHD may present with a normal IGF-1, so the use of 2 GHSTs is advised to confirm the diagnosis.7,16

When transition patients with persistent GHD reach adult height, continuation of GH treatment is critically important to ensure the development of optimal peak bone mass (

Figure 1

).17,34,38,39 Peak bone mass, which in adults is defined by a T-score greater than −1 when standardized to average adult bone mass, is attained a few years after achieving adult height, normally by age 25 to 30 years in men and age 20 to 25 years in women. The continuation of GH therapy after completion of linear growth has been shown in several studies to enhance bone mineral density and lean body mass compared with untreated patients with severe GHD.36,40-44 Discontinuation of GH therapy in adolescent patients with GHD has been shown to increase fat mass, which contributes to abnormal body composition,45-47 and to increase several biomarkers of CVD risk such as total and low-density lipoprotein (LDL) cholesterol levels.48-50 Current guidelines (Table 1) recommend that weight, body mass index, waist and hip circumference, and quality of life (QOL) be monitored in transition GHD patients on an annual basis.7,16,17 In addition, bone densitometry (ie, dual-energy x-ray absorptiometry scan) to assess bone mineralization, serum lipid levels, fasting plasma glucose, and glycated hemoglobin should be assessed at baseline before starting growth hormone treatment and then every 2 to 5 years.16,17,25,34,51

The periodic assessment of GH-treated patients for QOL improvement is recommended with the use of patientreported outcomes from standardized generic and diseasespecific questionnaires. QOL in Assessment of Growth Hormone Deficiency in Adults52-54 and Questions on Life Satisfaction—Hypopituitarism53,55 are the most frequently recommended (Table 1).

During puberty, FDA-approved doses of GH may be administered over a range from 25 to 100 μg/kg per day.19-22 Pubertal patients with GHD may be treated with a weekly GH dosage of up to 0.7 mg/kg (100 μg/kg per day) that is divided into daily subcutaneous injections.22 Because of the rapid developmental and physiological changes associated with puberty, the transition phase after adolescence is a more appropriate time to adjust GH dose downward (

Figure 2

). If dose adjustments are based on serum IGF-1 levels using age- and sex-specific normative data, GH treatment in transition patients may be initiated at a total dosage of 0.8 to 1.0 mg per day; the initial transition dose can be determined from the patient’s pediatric dose, beginning with half of the prior pediatric dose.34,56,57 Target levels for IGF-1 response using an IGF-1—based dosing strategy should be within the normal range but not exceed the upper limit of normal (IGF-1 SDS of 0 to +2). Discontinuation of GH therapy among transition patients is common once they (or their caregivers) believe adult height has been achieved. However, many will return in their late teens to mid 20s to restart treatment when the benefits of GH continuation become apparent for their overall health and QOL.58 The reinitiation of GH therapy in transition patients involves lower GH doses, with maintenance doses that are based on an individual’s clinical response, serum IGF—1 levels, and age, as well as the onset of any adverse effects. A theoretical risk of adverse effects may exist in some patients receiving high doses of GH, including increased intracranial pressure, edema, worsening of scoliosis, hyperglycemia, and insulin resistance. The risk of malignancy associated with long-term GH therapy still remains unclear.4 Analysis of data from the National Cooperative Growth Study, a large observational database monitoring the safety and efficacy of GH in 54,996 children, showed that even after more than 20 years, an increased incidence of leukemia could not be linked with long-term GH treatment.59 Despite detection of an increased risk of second malignancies in patients treated with irradiation, the overall safety profile for long-term GH treatment was favorable.59


Adults with untreated GHD may be at increased risk for cardiovascular morbidity, particularly those with hypopituitarism. Earlier studies have reported an increased incidence of cardiovascular and cerebrovascular mortality in patients with untreated hypopituitarism, childhood-onset GHD, and adult-onset GHD.60-62 Cardiovascular morbidity in adults with either childhood-onset or adult-onset GHD was shown to be increased in both women and men compared with age- and sex-matched control subjects without GHD.63 A significantly higher hazard ratio (HR) for mortality in adult-onset GHD was found in 1 study, with hypopituitarism proposed as a potential cause of this observed increase in mortality compared with controls: in females, the HR with 95% CI was 3.4 (2.9-4.0); in males, the HR (95% CI) was 1.9 (1.7-2.2); P <.001.63 GHD is the most common hormone deficiency in hypothalamic-pituitary disease; evidence from clinical studies has implicated it as a contributing factor to increased risk of CVD in patients with hypopituitarism.64,65 In addition, hyperglycemia from untreated GHD and from overtreatment with glucocorticoids may also contribute to mortality risk. Recent practice guidelines published by the Endocrine Society (Table 1) regarding evaluation and treatment of adult-onset GHD reviewed clinical evidence that suggests involvement of multiple factors in the increased mortality risk in adults with hypopituitarism.17 GH therapy for adult GHD increases lipolysis, improves cardiovascular function, and decreases total and LDL cholesterol.48-50,63-65 Currently, there is no published clinical evidence that directly links GH treatment with decreased mortality rate from CVD, so this area requires further study.65 Nevertheless, untreated panhypopituitarism in affected adults remains strongly associated with elevated CVD mortality. GH therapy has been shown to reverse many of the negative trends in biomarkers associated with the risk of CVD.

As described for transition patients, the continuation of GH therapy after completion of linear growth (Figures 1 and 2) has multiple positive effects on bone, body composition, and blood chemistries. In addition, continued GH therapy improves several CVD risk factors such as impaired cardiac performance, increased visceral fat, dyslipidemia, and hypertension that could reduce the risk of CVD morbidity and mortality.66 Data from a recently published study by Claessen and colleagues67 in adult patients with GHD treated with GH for 10 to 15 years has shown that the prevalence of metabolic syndrome (ie, waist circumference [P <.001], body mass index [P = .018], and fasting plasma glucose [P <.001] compared with baseline) was significantly increased, especially in males (P <.001).67 This was despite significant improvements in several CVD risk factors (ie, reduced levels of total and LDL cholesterol) and increased high-density lipoprotein (HDL) cholesterol levels compared with baseline (all P <.001). Discontinuation of long-term GH therapy in adults with GHD for as brief a period as 4 months was associated with a self-perceived decrease in QOL, increased accumulation of abdominal fat, and deterioration of markers of systemic inflammation (ie, C-reactive protein) and lipid status (ie, increased total and LDL cholesterol, and decreased HDL cholesterol), while insulin sensitivity actually improved (all P <.05 compared with GH treatment).68 Thus, it is important that recommendations for regular assessment of key biochemical markers and physical parameters be strictly followed to monitor adult patients for development of metabolic (type 2 diabetes mellitus), skeletal, and cardiac dysfunction (Table 1).

Also, adult GH dosages, formerly based on body weight and age, should be carefully monitored and individualized because of the increased likelihood for adverse effects in older adults, including carpal tunnel syndrome, edema, and arthralgia.19-22 In patients younger than 35 years, standard clinical practice is to start with a low GH dose at 5 μg/kg per day and slowly increase it to a maintenance dose of 25 μg/kg per day. GH doses in overweight adults should be based on ideal body weight rather than actual weight. In patients older than age 35 years, the GH dose should not exceed a maximum 12.5 μg/kg per day to avoid adverse effects in this age group (Figure 2). Periodic measurement of serum IGF-1 levels, assessment of symptom response to therapy, and avoidance of adverse effects remain the mainstays of GH treatment monitoring in adults.

Consistent with current recommendations in children and adolescents, serum IGF-1 levels must also be monitored in adult patients and should not exceed the upper limit of the normal range for IGF-1 SDS. GH treatment guidelines now advocate the use of IGF-1 levels to guide and optimize GH dosing in adults.17 Comparing individualized GH dosing (based on IGF-1 response to GH therapy) with conventional dosing (empirical, weight based) in adult patients showed that dose adjustments based on IGF-1 responses reduced occurrence of adverse events in adults with GHD.56


Managed care payers are challenged with appropriately determining eligibility for coverage of GH treatment while aligning their criteria for coverage of FDA-approved indications with updated practice recommendations or guidelines. Current eligibility requirements for GH treatment of children, transition patients, and adults as well as prescribing criteria for the continuation or discontinuation of treatment (presented in

Tables 2



, and


) were reviewed from 5 different managed care providers. These payers were selected based on their prominence in the health insurance marketplace, the scope of their reimbursement for covered medical services and therapies, and the accessibility of current policy statements regarding GH treatment in defined patient populations.

It is clear that different eligibility criteria are used by the different managed care providers. Many managed care providers do not cover GH treatment for some indications that are approved by the FDA.

As more clinical data become available, MCO policies should be reviewed and adjusted to conform to the latest clinical guidelines to optimize outcomes for those individuals who are covered by a healthcare plan. Physicians diagnose GHD and other disorders of growth failure or short stature based on many sources of clinical data: patient history, physical assessments, auxological measurements, peak level of GH in stimulation tests, IGF-1 levels, genetic testing, and evidence-based physician judgment. In contrast, an insurer may determine patient eligibility based on a single objective measure (Tables 2 and 3), such as the peak serum GH level evoked during a GHST.69 In some instances, GHSTs are unable to differentiate between patients with partial GHD and those with ISS.69 Thus, physicians and payers must share a common goal: identification of patients whose best option is GH treatment. As GH treatment paradigms evolve, payers and physicians should be interested in obtaining evidence that supports expanded coverage for GH therapy in persistent GHD or panhypopituitarism for patients at different life stages.38

Managed care payers also want to contain the costs of GH treatment for disorders of short stature such as ISS (Table 2). Debate continues over the approval of GH therapy for ISS as to whether it constitutes a medical treatment or an enhancement therapy, calling into question the cost of a drug seemingly prescribed for the purpose of improving QOL as opposed to treating an illness. The emergence of GH therapy for such an indication in pediatrics combined with the rising cost of prescription drug therapies remains a concern for the US healthcare system, with GH therapy for ISS a major point of contention regardless of the analysis of incremental cost per child, incremental growth per child, and incremental cost per inch of final height gain.70

The high cost of (potentially) long-term GH therapy in certain patient populations is a significant consideration for payers as they develop and continuously update their clinical policies for determining which indications are covered for GH treatment (Table 4). A study by Bazalo and colleagues71 used a budgetary impact model to show that restriction of GH therapy to the recombinant GH drug product with the least waste during use resulted in 10.2% lower annual pediatric care costs (ie, from $19,026 to $17,089 in 2005 US dollars). This suggests that there may be a rationale for systematic changes that can be made to decrease the cost of GH therapy, while expanding coverage and achieving optimal patient outcomes. Increasingly, health plans including Medicaid, Medicare Advantage Prescription Drug, and commercial health plans serving millions of members have implemented the mandatory use of a specialty pharmacy provider to control delivery, distribution, and reduce reimbursements for office-administered and/or self-administered GH.72 These specialty pharmacy providers may impose additional criteria for managing costs associated with prescribed GH regimens; however, few studies have been published examining the advantages and disadvantages of the use of specialty pharmacy providers to payers, prescribers, and patients.72


GH therapy is a safe and well-established management strategy for a number of disorders of growth failure or short stature among pediatric patients. For transition and adult patients with persistent GHD, guidelines for the continued use of GH have been based primarily on clinical expert consensus but also on emerging data from clinical studies. Although consensus recommendations and guidelines for adolescent/transition and adult patient categories have recognized the importance of continued GH treatment to reduce several CVD risk factors and to achieve optimal peak bone mineralization after adult height is attained, the effect of long-term GH treatment on an increased prevalence of metabolic syndrome in adult GHD patients requires further study. Based on our examination of eligibility criteria and policies from select MCOs, the current coverage for GH treatment of FDA-approved indications in each patient category lags behind the latest clinical guidelines. The alignment of MCO coverage policies with current clinical guidelines is important to maximize outcomes for all patients who can benefit from GH therapy. This can be achieved by eliminating the disparities that currently exist between clinical guidelines for FDA-approved indications and the GH treatment criteria set by insurers. Adherence to guidelines by both physicians and MCOs can also reduce waste and unnecessary treatment, allowing for more cost-effective treatment of the eligible patient population.


Editorial and writing assistance were provided by Jeffrey M. Palmer, PhD, ETHOS Health Communications, Newtown, PA, with financial assistance from Novo Nordisk Inc, Princeton, NJ, in compliance with international guidelines on Good Publication Practice.

Sadly, David M. Cook, MD, passed away after completion of this manuscript and before publication. He was a much loved and revered teacher, with teaching awards from medical students, residents, and fellows too numerous to count. He was the quintessential clinician, well loved by his patients, and an accomplished clinical investigator with numerous research grants to his name. He was the international authority on growth hormone deficiency in transition and adult patients. Dr Cook was a strong advocate for seeing transition pediatric patients with pituitary disorders well managed into adulthood.

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