Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Growth Hormone Deficiency 
Treatment: Humatrope. 
The insurer denied Humatrope.
The denial is Upheld.

The patient is a male diagnosed with GHD (growth hormone deficiency). This request is for Humatrope. He has been on GH (growth hormone). Per the records, he had an IGF-I (insulin-like growth factor one) generation test with clonidine.

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

Classic GH deficiency
Classic GH deficiency criteria are outlined in the consensus guidelines for the diagnosis and treatment of GH deficiency published by the GH research society (1), the Lawson Wilkins Pediatric Endocrinology Society (2, 3), and the medical guidelines for GH 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 auxological, biochemical and sometimes radiological findings. 

The auxological criteria based on consensus guidelines upon which a biochemical evaluation is to be initiated are 
1) Severe short stature, defined as a height of more than 3 SD below the mean; 2) Height of more than 1.5 SD below the midparental height; 3) Height of more than 2 SD below the mean, and a height velocity over one year of more than 1 SD below the mean for chronological age, or a decrease in height SD 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 of more than 2 SD below the mean over one year, or more than 1.5 SD sustained over two years. 

The biochemical criteria include low IGF1 or IGFBP3 or GH stimulation testing, with a peak GH of less than 10ng/ml. 
		
The patient did not meet biochemical criteria. Growth hormone stimulation testing was not performed. The patient had an IGF-I generation test with clonidine but the testing protocol is not reported. The patient's height prior to treatment was normal. The patient's height velocity data does not include data over one and two years.

The patient does not meet auxological or biochemical criteria.

Alternate GH deficiency criteria
In addition, GH is indicated for the treatment of GH deficiency in certain patients who do not fail GH stimulation tests, based on the Lawson Wilkins Pediatric Endocrine Society (LWPES) alternate criteria (2), which state, "No gold standard exists for the diagnosis of GHD. Although children severely affected by GHD fail GH stimulation tests, there is no doubt that some children with GHD achieve stimulated GH concentrations above the arbitrary cutoffs that have been applied. A trial of GH therapy should be approved for children with otherwise unexplained short stature who pass GH stimulation tests, but who meet most of the following criteria: 
1) Height greater than 2.25 SD below the mean for age or greater than 2 SD below the midparental height percentile; 2) Growth velocity less than 25th percentile for bone age; 3) Bone age greater than 2 SD below the mean for age; 4) Low serum insulin-like growth factor 1 (IGF-I) and/or insulin-like growth factor binding protein 3 (IGFBP3); and/or 5) Other clinical features suggestive of GHD."

This patient did not meet criterion #1, as pretreatment height was normal. IGF1 was low. Bone age was delayed. Height velocity over one year is not reported. The patient therefore does not meet three of the above criteria. 

Idiopathic Short stature
Growth hormone in the treatment of idiopathic short stature (ISS) is supported by randomized controlled trials and consensus guidelines (4-9). 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 SD. 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.