Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Pediatric Growth Hormone Deficiency. 
Treatment: Humatrope (Pre-Service). 

The insurer denied the Humatrope. 
The denial is upheld. 

This is a male diagnosed with growth hormone deficiency (GHD). This request is for Humatrope. The patient started showing early signs and growth decelerated over the past two years. He started a trial of growth hormone (GH) and it has had an overall positive affect not only for growth but he is having less headaches and asthma than ever before. Two years ago, the patient was diagnosed with familial juvenile polyposis. He has been on GH therapy for approximately eight months. 

The patient's growth hormone stimulation test with L-dopa and clonidine peaked at 1.6 and 2.7 respectively.  His magnetic resonance image (MRI) was normal. Two years ago, the patient's insulin-like growth factor one (IGF1) was 239 (97-407); insulin-like growth factor binding protein three (IGFBP3) was 4212. Approximately a year and a half later, his insulin-like growth factor one (IGF1) was 324 (82-423); insulin-like growth factor binding protein three (IGFBP3) was 3503 (2385-5956). Toward the beginning of this year, his testes were 15 cubic centimeters (cc) bilaterally and pubic hair was at tanner III-IV. His pretreatment height velocity is reported to be 7.6 centimeters per year. 

No, the proposed Humatrope is not medically necessary. 

The peer reviewed literature including consensus clinical guidelines, randomized controlled trials are summarized below: 

Classic Growth Hormone Deficiency (GHD): 
Classic growth hormone deficiency criteria are outlined in the consensus guidelines for the diagnosis and treatment of growth hormone deficiency published by the Growth Hormone (GH) Research Society [1], the Lawson Wilkins Pediatric Endocrinology Society [2], [3], and the medical guidelines for growth hormone use provided by the American Association of Clinical Endocrinologists [4]. The above referenced guidelines are the latest available guidelines from these respective societies. The diagnosis is based on height, height velocity, biochemical and sometimes radiological findings. The height and height velocity criteria based on consensus guidelines upon which a biochemical evaluation is to be initiated are 1) severe short stature, defined as a height more than 3.0 standard deviations below the mean; 2) height more than 1.5 standard deviations below the mid parental height standard deviation; 3) height more than 2.0 standard deviations below the mean and a height velocity over one year more than 1.0 standard deviations below the mean for chronological age, or a decrease in height standard deviation of more than 0.5 over one year in children over two years of age; 4) in the absence of short stature, a height velocity more than 2.0 standard deviations below the mean over one year or more than 1.5 standard deviations sustained over two years. The biochemical criteria include low insulin-like growth factor one (IGF1) or insulin-like growth factor binding protein three (IGFBP3) or growth hormone (GH) stimulation testing with a peak growth hormone less than ten nanograms per milliliter (ng/mL). 

The patient's pretreatment height was 132.08 centimeters (-1.03 standard deviations [SDS]) and on approximately two years later was 151.49 centimeters (+0.07 SDS) with height velocity over 2.26 years of 8.6 centimeters per year.  His height on therapy was 154 centimeters (+0.25 standard deviations [SDS]). His mother's height is 157.48 centimeters and father's height is 172.72 centimeters and mid parental height is 171.6 centimeters (-0.73 standard deviations [SDS]). 

The patient did not meet height and height velocity criteria as pretreatment height and height velocity are normal.  Growth hormone stimulation testing peaked at less than ten nanograms per milliliter (ng/mL). Insulin-like growth factor one (IGF-I) was normal. Insulin-like growth factor binding protein three (IGFBP-3) was normal. 

The Pediatric Endocrine Society recommends against making a diagnosis of growth hormone deficiency based solely on failed growth hormone stimulation testing. 

Idiopathic Short Stature (ISS): 
Growth hormone in the treatment of idiopathic short stature (ISS) is supported by randomized controlled trials and consensus guidelines  [4, [5, [6, [7, [8, [9]. Food and Drug Administration (FDA) approval for this indication is for "non-growth hormone-deficient short stature, defined by height SDS less than or equal to -2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range, in pediatric patients whose epiphyses are not closed and for whom diagnostic evaluation excludes other causes associated with short stature that should be observed or treated by other means." 

The patient does not have a pretreatment height less than or equal to -2.25 standard deviations. The patient therefore does not meet idiopathic short stature criteria. 

The request does not meet any nationally accepted criteria for use of growth hormone. The request is therefore not medically necessary.