Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Idiopathic Short Stature
Treatment: Norditropin FlexPro 10 MG (milligrams)
The insurer denied the Norditropin FlexPro 10 MG.
The denial is overturned.

The patient is a female diagnosed with ISS (idiopathic short stature). This request is for Norditropin. Her GH (growth hormone) stimulation test with arginine and clonidine peaked at 8.23 and 10.6 respectively. Her height velocity is reported to be 8.39 cm/yr (centimeters per year).

The patient's IGF1 (insulin-like growth factor 1) was 105 (152-593), Z-score was -2.4 SD (standard deviations), IGFBP3 (insulin like growth factor binding protein 3) was 4.3 (2.4-8.4). Her more recent IGF1 was 102 (152-593), Z-score was -2.5 SD, IGFBP3 was 4.0 (2.4-8.4). 

The patient's height was 127 cm (centimeters), and a couple of months later 
129.54 cm (-2.52 SDS [standard deviation score]) with height velocity over 0.524 years of 4.8 cm/yr.

The patient's mother's height is 165.1 cm, and father's height is 170.18 cm, giving a mid-parental height of 161.14 cm (-2.18 SDS).

Yes, the requested Norditropin is medically necessary.

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

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 10 ng/ml (nanograms per milliliter).

The patient did not meet biochemical criteria. Growth hormone stimulation testing peaked at greater than 10.

In addition, GH is indicated for the treatment of GH deficiency (GHD) 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 GH 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 IGF-I and/or IGFBP3 and/or
5) Other clinical features suggestive of GHD."

This patient met criterion 1 as pretreatment height was -2.54 SD. IGF1 was low. Bone age was delayed. Height velocity is less than the 25th percentile. The patient therefore met 4 of the above criteria. The patient meets accepted criteria for the diagnosis of GHD. GH in the treatment of GHD is medically necessary.

Growth hormone in the treatment of ISS is supported by randomized controlled trials and consensus guidelines (4-9). FDA (Food and Drug Administration) 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 had a pretreatment height less than or equal to -2.25 SD. The patient's height velocity and bone age would not allow the patient to reach a normal adult height. The patient does not meet ISS criteria only because the patient has GHD.

No, the health plan did not act reasonably, with sound medical judgment, or in the best interest of the patient, as the request is medically necessary, as described above.