PEDBASE.org - The Pediatric Database - Detailed information of GROWTH HORMONE DEFICIENCY

GROWTH HORMONE DEFICIENCY

DEFINITION:

Disorders of the hypothalamus, pituitary, or of growth hormone (GH) secretion and metabolism which result in short stature.

EPIDEMIOLOGY:

incidence: 1/4,000-10,000
risk factors:
- familial - see below
- M > F (2.5:1)

PATHOGENESIS:

1. Hypothalamic/Pituitary (GHRH) Disorders

1. Trauma

head
perinatal events (i.e., breech)

2. Infections

meningitis
granuloma

3. Neoplasms

craniopharyngiomas
germinomas
histiocytosis

4. Irradiation

head
whole body

5. Syndromes

Septo-Optic Dysplasia
Cleft Lip +/- Palate
Empty Sella Syndrome

6. Central Nervous System Congenital Abnormalities

anencephaly, arrhinencephaly, cebocephaly, holoprosencephaly, hydranencephaly
Pituitary - Aplasia, Hypoplasia, Thin or Absent Pituitary Stalk

2. Growth Hormone Metabolism Disorders (Genetic)

1. GH Deficiency

Type IA - autosomal recessive (GH gene deletion)
Type IB - autosomal recessive (mutation of GH gene)
Type II - autosomal dominant
Type III - x-linked recessive (Xq21.3-q22)

2. GH Receptor Defects

Deletion (Laron dwarfism, Little Women of Loja)
Defective translation or transcription (Pygmy)

3. IGF-1 Defects

impaired generation of IGF-1

CLINICAL FEATURES:

1. GH Deficiency

1. Birth

normal birth weight and length
usually no prematurity or IUGR
midline defects (Septo-Optic Dysplasia)
hypoglycemia, seizures

2. Infancy/Childhood

short stature
micropenis
fine hair
slow hair and nail growth

2. Hypothalamic Hypopituitarism

1. Birth

persistent hypoglycemia
micropenis
prolonged hyperbilirubinemia (50%)
dysmorphic features

INVESTIGATIONS:

1. GH Stimulation Tests

1. Physiologic

basal
exercise
- baseline <5 ug/L
- after 25 minutes: >7 ug/L (normal); <7 ug/L (GH Deficiency)

2. Pharmacological

arginine +/- insulin
clonidine + L-Dopa
glucagon
L-Dopa + Propranolol

MANAGEMENT:

1. GH Replacement Therapy

1. Growth Hormones

1. Humatrope (Lilly)

recombinant (191 aa)
0.18 mg/kg/week (0.03 mg/kg/dose)

2. Protropin (Genentech)

recombinant (191 aa + Met)
0.3 mg/kg/week (0.05 mg/kg/dose)
both types contraindicated if epiphyses are already fused or if a tumor is present

2. Moniter

1. Growth

expect an increased growth rate (about 3" in 1st year)
injection sites
stage of puberty (Tanner Stage)

2. Others

bone age q12m
thyroid function tests, CBC, blood sugar q3m for the first year then q6m (CBC for small leukemia risk)
GH antibodies q12m

INTERNET LINKS:

The MAGIC Foundation

Pediatric Database - GROWTH HORMONE DEFICIENCY

Pediatric Organization - Pedbase [at] Gmail.com