what-when-how
In Depth Tutorials and Information
GROWTH HORMONE TREATMENT:
CURRENT FDA-APPROVED
INDICATIONS
the possibility of GH deficiency at the same frequency
as occurs in the general population (approximately
1:3480
97
). FDA approval has also been obtained for an
increased dosing level in adolescents in puberty. Finally,
there are three FDA-approved indications for rGH use in
adults which include adult GH deficiency, AIDS wasting
and small bowel syndrome. All FDA-approved indica-
tions with the corresponding doses of GH are shown in
Table 29.1
(for review see
78,92,93
).
Growth hormone therapy has been available for over
50 years and is administered by subcutaneous injection
6 to 7 days per week (for review see
78,92
). Prior to recom-
binant growth hormone (rGH) being produced, human
growth hormone was extracted from pituitaries from
human cadavers. The development of Jakob-Creutzfeldt
disease in some of these patients led to the withdrawal of
this supply. rGH had become available at that time (1985)
in order to replace the cadaveric form. The initial FDA-
approved indication was for GH deficiency. There are
now eight FDA-approved indications for GH use in con-
ditions involving poor linear growth in children which
include GH deficiency, chronic renal disease, Turner syn-
drome, Prader-Willi syndrome, Small for Gestational
Age, Idiopathic Short Stature, SHOX deletion (including
Leri-Weill dyschondrosteosis) and Noonan syndrome
(
Table 29.1
).
78,92
Prader-Willi children are thought most
likely to be GH deficient based on hypothalamic dys-
function.
94-96
In the other conditions (other than GH
deficiency), the indications are for children who are GH
sufficient; however, within each disorder there is always
GROWTH HORMONE TRIALS IN
SKELETAL CONDITIONS
Patients with Leri-Weill dwarfism, a subgroup within
SHOX deficiency, respond to rGH and treatment is FDA
approved. This condition is characterized by mesomelic
dwarfism and Madelung deformity.
98
Overall, how-
ever, patients with skeletal dysplasias respond poorly
to rGH,
99
including a minimal response in achondro-
plasia.
100
However, an exception is hypochondroplasia
in which a recent 6-year trial revealed an improvement
in height and body proportions.
101
Preliminary trials in
hypophosphatemic rickets have shown an increase in lin-
ear growth velocity without progression of body dispro-
portion as well as improvements in phosphate wasting
although there are no final height data.
102-104
TABLE 29.1
fdA-approved Indications and doses for rGH
Treatment
Indications
FDA-Approved Doses (mcg/kg/day)
BENEFITS OF rGH TREATMENT IN
GH-DEFICIENT PATIENTS
GH Deficiency
Childhood growth hormone
deiciency
a
22-50
In addition to linear growth and improved self-
esteem, rGH has other benefits in several of the FDA-
approved indications previously mentioned. In the
setting of GH deficiency, rGH treatment results in
decreased fat mass, increased muscle mass, increased
bone mineral density, normalization of serum lipid pro-
files, improvement in renal and cardiac function and an
improved sense of well-being.
105-112
In Prader-Willi syn-
drome (PWS), in which GH deficiency is thought to be
likely based on hypothalamic dysfunction, patients have
improvement in tone and muscular strength, as well as
improvements in weight and decreases in body mass
index,
113-116
although the impact on obesity is controver-
sial
117
in PWS. One study revealed an improvement in
neurodevelopmental status in young children.
116
Adolescent pubertal dosing
a
up to 100
Adult growth hormone
deiciency
a
4-16
Other Indications
Chronic kidney disease
a
50
Turner syndrome
a
47-67
Prader-Willi syndrome
a,b
34-50
Small for gestational age
a
50-68
Idiopathic short stature
a
≤67
SHOX haploinsuficiency
a
50
Noonan syndrome
a
≤66
AIDS wasting
c
0.1
mg
/kg, 3 times per week (up to
6
mg
/d) for 12 weeks
GROWTH HORMONE USE IN
G
H-SUFFICIENT CHILDREN
Small bowel syndrome
c
0.1
mg
/kg/d (up to 8
mg
/d) for 4 weeks
a
Cook DM, Rose SR. A review of guidelines for use of growth hormone in pediatric and
transition patients. Pituitary 2012; 15(3): 301-10.
93
b
Hypothalamic dysfunction with GH-deficiency can be associated.
c
Franklin SL, Geffner ME. Growth hormone: the expansion of available products and
indications. Pediatr Clin North Am. 2011;
58
(5): 1141-65.
78
In 2003, rGH treatment was FDA approved for idio-
pathic short stature (ISS), defined as a height less than
the 3rd percentile (or <2.25 standard deviations below
