Tests
1st tests to order
x-ray wrist
Test
Bone maturation is delayed for the chronologic age. This is assessed by radiography. The appearance of representative epiphyseal centers on the x-ray is compared with age- and sex-appropriate published standards. The most commonly used method is that of Greulich and Pyle, which examines the left wrist and hand. Bone age is of limited use in infants, but, if required, other methods such as the knee exam may be more helpful than wrist exam. Bone age may also be used to predict final height, using the tables of Bayley and Pinneau.[39]
Result
delayed skeletal age
thyroid function tests
Test
Free thyroxine (T4) and thyroid-stimulating hormone (TSH) should be measured in all children with poor growth to rule out hypothyroidism as the primary cause of short stature. It may help reveal TSH deficiency in combination with GHD.
Result
normal in isolated GHD; low free T4 and TSH with TSH deficiency
IGF1 and IGFBP3
Test
Values of insulin-like growth factor 1 (IGF1) and its binding protein (IGFBP3) more than two standard deviations below the mean, corrected for age and sex, are indicative of GHD; however, normal concentrations do not rule out GHD (e.g., in post-irradiation patients).[40][41] The concentrations may be altered in hypothyroidism, malnutrition, and chronic diseases.
Result
low
baseline pituitary function tests
Test
This should include 8 a.m. adrenocorticotrophic hormone, cortisol, luteinizing hormone, follicle-stimulating hormone, testosterone/estradiol, and prolactin tests to look for potentially associated combined pituitary hormone deficiencies (CPHD). The status of the hypothalamo-pituitary-adrenal axis must be known prior to embarking on more detailed GH provocation testing.
Result
low in CPHD
basic hematology and biochemistry screen
Test
All children with short stature should have a full basic hematology and biochemistry screen, including a complete blood count, renal and liver function tests, bone profile, serum/plasma electrolytes, and inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) to exclude other causes.
Result
normal
Tests to consider
GH provocation test
Test
The GH-IGF1 axis can be stimulated with various provocative agents such as insulin, glucagon, arginine, and clonidine. The insulin tolerance test is considered as the definitive test for assessing both the GH-IGF1 axis and the hypothalamo-pituitary-adrenal axis. GH provocation tests are contraindicated in children <1 year of age.[30][56] Two provocation tests improve the sensitivity. Priming may be considered in certain age groups.[12][42]
Result
peak GH <7 nanograms/mL (<7 micrograms/L) (range 5-10 nanograms/mL [5-10 micrograms/L])
MRI brain
Test
Helps identify congenital abnormalities of the forebrain and pituitary, optic chiasm, and optic nerves.[45][46] Anterior and posterior pituitary abnormalities in congenital GHD are highly variable.[2]
MRI will also detect acquired abnormalities such as a solid/cystic suprasellar mass extending into the hypothalamus and third ventricle (craniopharyngioma), optic gliomas, Rathke cleft cysts, and arachnoid cysts. Inflammatory lesions such as Langerhans cell histiocytosis will be revealed as thickening of the pituitary stalk.
Result
variable: small anterior pituitary, midline forebrain defects, posterior pituitary/stalk abnormalities, central nervous system tumors/cysts
CT brain/x-ray skull
Test
CT brain and x-ray skull may help detect bony abnormalities and intracranial calcification (craniopharyngiomas).
Result
calcification
full pituitary hormone evaluation
Test
Confirmation of the diagnosis of GHD requires a full pituitary evaluation to rule out other anterior ± posterior pituitary hormone dysfunction.
Neonates: low serum insulin in the presence of hypoglycemia with low serum GH and cortisol concentrations suggests hypopituitarism, although chronic hypoglycemia can be associated with poor counter-regulatory GH and cortisol responses.[47] The diagnosis of combined pituitary hormone deficiencies (CPHD) should be further confirmed with thyroid function tests (low free thyroxine [T4], low thyroid-stimulating hormone [TSH]) and a low 24-hour plasma cortisol profile.
In older children, a low TSH with low T4 concentrations indicates TSH deficiency. A routine thyrotropin-releasing hormone (TRH) test may not always be necessary.[48][49][50] Basal serum prolactin concentrations of <5 nanograms/mL are usually indicative of prolactin deficiency and may be confirmed by a suboptimal response to TRH. Gonadotropin deficiency is confirmed by a poor response to gonadotropin-releasing hormone depending on age. Adrenocorticotropic hormone (ACTH) deficiency can be diagnosed as a poor cortisol response after an insulin tolerance test or ACTH. A 24-hour plasma cortisol sampling may be necessary in some patients.[51] Stimulation of testes with human chorionic gonadotropin (hCG) in males at puberty may also be used to diagnose gonadotropin deficiency.[52]
Result
normal or variable deficiencies
specialist referral
Test
Patients with eye abnormalities should be referred to an ophthalmologist to rule out optic nerve hypoplasia/septo-optic dysplasia.
Patients with central nervous system tumors should continue to be assessed and monitored by a team of pediatric specialists, including neurologists, neurosurgeons, oncologists, endocrinologists, ophthalmologists, and radiologists.
Other specialist referral may be required as indicated: for example, a psychologist and social services for psychosocial deprivation.
Result
variable
genetic studies
Test
The role of genetics in congenital GHD remains to be established, but is increasingly offered within the clinical rather than research setting. Parental consanguinity, positive family history, craniofacial and brain midline abnormalities, and other syndromic features all make a genetic diagnosis more likely. Appropriate mutational screening is an important adjunct to assessment and management of the patient because it provides a better understanding of the pathophysiologic process, although mutations are rare in patients with sporadic hypopituitarism.[10][53] However, detection of mutations may lead to early diagnosis of additional hormone deficiencies if patients have mutations in genes with a well-established hormonal phenotype (e.g., PROP1, POU1F1 mutations).
Result
identify mutations in congenital GHD
random GH
Test
A single, randomly taken GH level <7 nanograms/mL (<7 micrograms/L), during the first week of life, has been found to be 90% sensitive and 98% specific in diagnosing neonatal GHD.[35]
Result
<7 nanograms/mL (<7 micrograms/L) during the first week of life; <5 nanograms/mL (<5 micrograms/L) in the presence of other pituitary hormone abnormalities
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