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Difficulty: MediumPediatric Endocrine Disorders

During a scheduled health maintenance visit, the parents of an 88-year-old girl express concern about her recent rapid growth and the development of severe facial acne. Over the past eight months, she has required frequent shoe size changes, and her height has crossed from the 5050 th to the 9090 th percentile. The parents also report the onset of adult-type body odor and the appearance of dark, coarse pubic hair. She has not developed any breast tissue and has not had vaginal bleeding. On physical examination, her blood pressure is 102/64 mm Hg102/64 \text{ mm Hg} and heart rate is 82/min82/\text{min}. Genitourinary examination reveals Tanner stage 33 pubic hair and mild clitoromegaly. There are no palpable abdominal or pelvic masses. A radiograph of the left hand and wrist demonstrates a skeletal bone age of 1111 years. Which of the following is the most appropriate next step in the evaluation of this patient?

  1. Measurement of serum 1717-hydroxyprogesteroneAnswer
  2. B
    Gonadotropin-releasing hormone (GnRH) stimulation test
  3. C
    Pelvic ultrasound to evaluate for polycystic ovary syndrome
  4. D
    Measurement of serum thyroid-stimulating hormone and free thyroxine
  5. E
    Reassurance and routine clinical observation

Answer

Measurement of serum 1717-hydroxyprogesterone is the correct diagnostic step to evaluate for non-classic congenital adrenal hyperplasia.
The patient's presentation of rapid growth, advanced bone age, premature pubarche, and clitoromegaly without concurrent breast development indicates an excess of peripheral androgens. In a prepubertal female, this constellation of findings points toward an adrenal etiology, most commonly non-classic congenital adrenal hyperplasia (NCCAH) caused by a partial deficiency of the 2121-hydroxylase enzyme. Because 2121-hydroxylase converts 1717-hydroxyprogesterone to 1111-deoxycortisol, a deficiency leads to the accumulation of 1717-hydroxyprogesterone, which is then shunted into the androgen synthesis pathway. The most appropriate initial screening test for this condition is the measurement of the basal early-morning serum 1717-hydroxyprogesterone level.

Step-by-Step Solution

1
Analyze the clinical presentation and physical exam findings.
The patient is an 88-year-old female with rapid linear growth, advanced bone age (1111 years), premature pubarche, acne, and clitoromegaly, but absent thelarche (no breast development).
Identifying the specific secondary sexual characteristics present dictates the diagnostic algorithm.
2
Differentiate between central and peripheral causes of early puberty.
The presence of virilization (clitoromegaly, acne) and advanced bone age without estrogen-dependent breast development indicates an excess of peripheral androgens (isosexual pseudoprecocity) rather than central precocious puberty.
Central precocious puberty in girls is GnRH-dependent and characterized primarily by early breast development due to ovarian estrogen production.
3
Identify the most likely etiology for peripheral androgen excess in a prepubertal child.
The combination of accelerated growth, virilization, and advanced bone age strongly suggests an adrenal source of androgens, most commonly non-classic congenital adrenal hyperplasia (NCCAH).
NCCAH, due to partial 2121-hydroxylase deficiency, classically presents in late childhood with premature adrenarche and virilization without salt-wasting.
4
Select the appropriate initial diagnostic test.
Measure serum 1717-hydroxyprogesterone.
In 2121-hydroxylase deficiency, the enzymatic block causes an accumulation of precursors proximal to the defect, notably 1717-hydroxyprogesterone, which is then shunted toward adrenal androgen synthesis.

Key Concept

Non-classic congenital adrenal hyperplasia (NCCAH) due to 2121-hydroxylase deficiency typically presents in late childhood with signs of peripheral androgen excess (premature pubarche, rapid growth, advanced bone age, clitoromegaly) and is screened for by measuring serum 1717-hydroxyprogesterone.
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Topics

Pediatric Endocrine Disorders

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