Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Growth Hormone Deficiency 
Treatment: Humatrope 

The insurer denied Humatrope. The denial was upheld. 

This is a young male patient with a diagnosis of growth hormone deficiency (GHD). The patient is on growth hormone (GH) therapy. His GH stimulation test in early 2019 with arginine and L-dopa peaked at 2.3 and 3.3 respectively. His pretreatment height velocity is reported to be 2.1 cm/year. His height velocity on therapy is reported to be 8 cm/year. On early 2019, his insulin-like growth factor 1 (IGF1) was 150 and his insulin-like growth factor binding protein 3 (IGFBP3) was 3575. The patient's magnetic resonance imaging (MRI) was normal. His bone age in the beginning of 2019 a chronological age (CA) of 10 years 8 months. Several months later his testes were 2 cc bilaterally with a Tanner 1, as well as pubic hair. His pretreatment height at that time was 130 cm (-1.79 standard deviation score [SDS]) and in mid 2019 it was 130.70 cm (-1.90 SDS) with a height velocity over 3 months of 2.3 cm/year. His height on therapy in early 2019 was 135.3 cm (-1.93 SDS). His mother's height is 152.4 cm and father's height is 165.1 cm; therefore, the mid parental height is 165.25 cm (-1.62 SDS). A request for Humatrope was made.

The peer reviewed literature including consensus clinical guidelines, randomized controlled trials are summarized as follows: 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 Endocriologists [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 more than 3 standard deviation (SD) below the mean; 2) height more than 1.5 SD below the mid parental height; 3) height more than 2 SD below the mean and a height velocity over 1 year more than 1 SD below the mean for chronological age, or a decrease in height SD of more than 0.5 over 1 year in children over 2 year of age; 4) in the absence of short stature, a height velocity more than 2 SD below the mean over 1 year or more than 1.5 SD sustained over 2 years. The biochemical criteria include a low IGF1 or IGFBP3 or GH stimulation testing with a peak GH less than 10ng/ml. 
		
The patient did not meet auxological criteria as his pretreatment height is normal. Height over 1-2 years is not reported. 

The Pediatric Endocrine Society recommends against making a diagnosis of growth hormone deficiency based solely on failed growth hormone stimulation testing.
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 SD. The patient therefore does not meet idiopathic short stature criteria. The insurer acted reasonably, with sound medical judgement, and in the patient's best interest. 

The medical necessity for the medication Humatrope is not substantiated.  The insurer's denial is upheld.