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  1. Explain the basic pathophysiology of congenital adrenal hyperplasia (CAH).

  2. Name at least one pre-analytical and one analytical factor that can lead to a false positive diagnosis of 21-hydroxylase deficiency (21OHD) based on measurement of 17-hydroxyprogesterone (17OHP).

  3. Discuss the methodologic advantages of steroid assays (immunoassay or mass spectrometry) that involve upfront sample purification by extraction and chromatography.

  4. Define the term “gene conversion” and describe its importance in the etiology of 21OHD.

  5. State the rationale for newborn screening for classical 21-hydroxylase deficiency (21OHD).

  6. Outline the essential steps to the evaluation of a short or poorly-growing child.

  7. Understand why random measurement of growth hormone is rarely useful.

  8. Explain how biological and analytical variability contribute to both low diagnostic sensitivity and specificity of laboratory testing for growth hormone deficiency.

  9. Name at least two reasons why different growth hormone assays can yield widely different results from the same patient sample.

  10. Identify the difficulties in establishing reference intervals for insulin-like growth factor I (IGF-I).


Many endocrine disorders are known to affect the pediatric population, beginning from birth and extending throughout childhood, adolescence, and into adulthood. This chapter will focus on the pathophysiology and diagnostic testing for two specific endocrine disorders, congenital adrenal hyperplasia (CAH) and disorders of growth, specifically those related to growth hormone deficiency.



Understanding the diagnostic approach to congenital adrenal hyperplasia (CAH) is useful for anyone caring for children from birth through adolescence. Although classical forms of CAH are relatively uncommon (world-wide incidence around 1:15,000 live births), the nearly universal screening of infants born in North America and Europe mandates familiarity with the methods used for screening, their limitations, and the proper diagnostic follow-up of the child with an abnormal newborn screen. CAH is also the most common cause of ambiguous genitalia of the newborn, and the one cause that can lead to sudden decompensation and death if not diagnosed in a timely manner. Less severe forms of CAH (so-called non-classical disease, NCCAH) are common (incidence around 1:1000) in the general population and may have a prevalence as high as 5% or more among children presenting for evaluation of early pubic and/or axillary hair appearance (premature pubarche/premature adrenarche) or among adolescent females complaining about excess facial/abdominal hair (hirsutism) or irregular menstrual periods.

Basic Pathophysiology

At its simplest, CAH refers to a group of heritable (autosomal recessive) deficiencies in enzyme activity required for the proper conversion of cholesterol to cortisol (adrenal steroidogenesis, Figure 12-1). The cortisol deficiency can lead to fatigue, hypoglycemia, hyponatremia (due to decreased free water clearance), and hypotension/shock. If the enzyme deficiency also hinders aldosterone production, severe hyperkalemia may also be present. Due to the lack of feedback from cortisol, pituitary ACTH secretion increases, leading to hyperplasia of the adrenal cortex, accumulation of precursor steroids ...

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