From the Guidelines
The workup for dwarfism should begin with a thorough history and physical examination, followed by targeted diagnostic testing based on suspected etiology, including genetic assessment for all children and adolescents with pituitary adenomas to inform management and family surveillance, as recommended by the 2024 consensus guideline 1. The initial evaluation should include accurate height measurements plotted on growth charts, assessment of growth velocity, and evaluation of body proportions to distinguish between proportionate and disproportionate dwarfism.
- Laboratory testing should include:
- Complete blood count
- Comprehensive metabolic panel
- Thyroid function tests (TSH, free T4)
- IGF-1
- IGFBP-3
- Karyotype analysis
- Bone age radiographs
- For suspected skeletal dysplasias, skeletal surveys including AP and lateral views of the skull, spine, pelvis, and extremities are essential.
- Genetic testing is increasingly important and may include targeted gene panels for skeletal dysplasias (FGFR3, COL2A1, etc.) or growth hormone pathway defects (GH1, GHR), as well as testing for genetic abnormalities associated with pituitary adenomas, such as AIP mutations and duplications in GPR101 1.
- Endocrine evaluation should assess growth hormone function through stimulation tests using agents like clonidine (0.15 mg/m²) or arginine (0.5 g/kg).
- MRI of the brain with focus on the pituitary and hypothalamus is indicated for patients with multiple pituitary hormone deficiencies or midline defects. Referrals to specialists including pediatric endocrinologists, geneticists, and orthopedic surgeons are often necessary for comprehensive management.
- Early diagnosis is crucial as some forms of dwarfism may benefit from timely interventions such as growth hormone therapy for GH deficiency (starting at 0.16-0.24 mg/kg/week divided into daily subcutaneous injections) or surgical management for skeletal complications, and growth hormone therapy is a consideration if testing indicates deficiency, as noted in the 2023 updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome 1.
From the FDA Drug Label
Idiopathic Short Stature (ISS) - Nutropin AQ is indicated for the treatment of ISS, also called non-GHD short stature, defined by height SDS ≤ –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 Short Stature Associated with Turner Syndrome (TS) - Nutropin AQ is indicated for the treatment of short stature associated with TS. The workup for dwarfism should include a diagnostic evaluation to exclude other causes associated with short stature that should be observed or treated by other means. Key considerations include:
- Height SDS (Standard Deviation Score) to assess the degree of short stature
- Growth rate to evaluate the likelihood of attaining adult height in the normal range
- Epiphyseal closure to determine the potential for further growth
- Evaluation for other causes of short stature, such as hypothyroidism, under-nutrition, or advanced bone age 2 2.
From the Research
Dwarfism Workup
- A comprehensive medical history, growth analysis, and physical examination are essential in evaluating a child with short stature 3, 4.
- Radiological and laboratory screening may be performed to identify potential causes of short stature 3, 4.
- Genetic testing may be considered in certain cases, such as severe isolated growth hormone deficiency or multiple pituitary dysfunction 3, 5.
- Specific genes, including GH1, GHRHR, PROP1, and POU1F1, may be tested in children with suspected genetic causes of short stature 3, 5.
- A whole genome approach may be taken if no obvious candidate gene can be determined 3.
Diagnostic Considerations
- Growth hormone deficiency (GHD) is a clinical syndrome that can manifest as isolated or associated with additional pituitary hormone deficiencies 6, 7.
- Diminished height velocity and short stature are useful clinical markers to consider testing for GHD in children 6, 7.
- Biochemical testing and imaging are required to confirm the diagnosis of GHD 6, 7.
- Random measurements of serum GH levels are not recommended to screen for GHD, except in neonates 6.
Evaluation and Management
- A detailed evaluation of a child with growth impairment should include an accurate history, a standardized physical examination, general and specific laboratory evaluations, radiologic investigations, and genetic testing 4.
- Short stature could represent an important threat for physical and psychological health in a child, so prompt identification of abnormal growth deviations offers the possibility to early treat the possible cause of shortness 4.
- Advances in genetic causes of short stature and improvements in transitional care can help alleviate the consequent physical and psychological problems that can arise from adult GHD 7.