Pediatric Hypopituitarism Workup

Updated: Jun 06, 2018
  • Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: Sasigarn A Bowden, MD  more...
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Approach Considerations

Laboratory tests are essential in the diagnosis and assessment of patients with hypopituitarism. However, any patient with hypopituitarism must also have a magnetic resonance imaging (MRI) examination to exclude a brain tumor. A brain MRI with specific cuts of the pituitary is the preferred imaging study for hypopituitarism. [23] This may be obtained pre–gadolinium contrast and post–gadolinium contrast, which can be helpful in the delineation of the posterior pituitary and some pituitary tumors.


Laboratory Studies

Screening for GHD using insulinlike growth factor-I (IGF-I) and insulinlike growth factor–binding protein 3 (IGFBP-3) may be useful, [24] except in cases of brain tumors. [25] Random measurement of GH levels has no diagnostic value except during early infancy, when GH levels are usually tonically elevated.

If abnormal growth patterns are seen, and GHD is strongly suspected, further provocative testing of GH secretion is typically performed under the supervision of a pediatric endocrinologist. Insulin-induced hypoglycemia is the most reliable provocative test for GHD and has the added advantage of accurately assessing the CRH-ACTH-cortisol axis. However, this test also has the greatest potential for harm, making its use limited in many pediatric endocrine practices. Currently, Glucagon Stimulation test is recommended for estimation of growth hormone secretion.

Alternative GH secretagogues used successfully in combination as 2 serial tests include arginine, levodopa, GHRH, propranolol with glucagon, exercise, clonidine, and epinephrine. In prepubertal children, consideration should be given to "priming" with sex steroids prior to testing.

Measurement of morning serum cortisol levels can help to exclude a CRH-ACTH-cortisol axis deficiency; a level of 20 mcg/dL virtually excludes this diagnosis.

Insulin-induced hypoglycemia probably is the criterion standard test but has limitations secondary to its inherent risks. On the other hand, ACTH stimulation testing is sensitive, reproducible, and extremely safe. Even though it directly examines the state of the adrenal cortices, indirectly it provides information about the hypothalamic-pituitary unit, because the cortisol response to exogenous ACTH is blunted in long-standing (>10 d) hypopituitarism.

Tests for adrenal insufficiency using Metyrapone or CRH are less-used laboratory examinations in pediatric patients. In patients with acute hypoglycemia, a critical sample documenting low serum glucose, while simultaneously measuring GH and cortisol levels, can be diagnostic. To assess central hypothyroidism (ie, TSH or TRH deficiency), low free thyroxine (FT4) levels assayed by dialysis and reference range or low serum TSH levels are diagnostic. [26]

Laboratory approaches to assess the pituitary-gonadal axis vary based on patient age. Young infants spontaneously secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in amounts that can be detected by radioimmunoassay; they also produce substantial amounts of testosterone and estradiol (Mini Puberty). At this age, random measurements of estradiol or testosterone levels and of LH and FSH levels are adequate to assess the gonadal axis.

From later infancy until about age 4 years, spontaneous secretion of LH and FSH is reduced, but stimulated responses to GnRH are retained, making GnRH testing an option. No method reliably assesses the axis in preadolescent children older than age 4 years. Testing is typically deferred until puberty, when diagnostic findings show low random LH and FSH levels in conjunction with low sex steroid levels (eg, testosterone, estradiol).

Elevated serum sodium and serum osmolality levels, when combined with low or low-normal urine osmolality, suggest diabetes insipidus. A low serum ADH level in this context can be diagnostic for central diabetes insipidus (ie, pituitary vasopressin deficiency). A water deprivation test is definitive; this test is performed under the supervision of a pediatric endocrinologist. In patients with diabetes insipidus, serum sodium and serum osmolality levels rise during water deprivation, while urine fails to concentrate properly. A normal response to administered vasopressin differentiates central diabetes insipidus from nephrogenic diabetes insipidus.