What is the simplest and most useful initial test for a 17-year-old female with primary amenorrhea, short stature, and lack of pubertal development?

Serum FSH and LH (Option B) is the simplest and most useful initial test for this patient with primary amenorrhea and features suggestive of Turner syndrome.

Clinical Reasoning

The clinical presentation of primary amenorrhea, short stature (135 cm), webbing of the neck, cubitus valgus, and absent pubertal development strongly suggests Turner syndrome (gonadal dysgenesis), making FSH and LH measurement the most appropriate initial diagnostic test. 1

Why FSH and LH Are the Correct Choice

• Elevated FSH and LH levels indicate hypergonadotropic hypogonadism, which is the hallmark of primary ovarian failure or gonadal dysgenesis 2
• In Turner syndrome and other forms of gonadal dysgenesis, FSH levels are typically markedly elevated (>35 IU/L) with LH >11 IU/L, confirming the diagnosis of hypergonadotropic hypogonadism 3
• Baseline FSH and LH assessment is specifically recommended at age 13 years for patients with delayed puberty or failure to initiate pubertal development 1, 3
• These tests directly differentiate between the three main categories of primary amenorrhea: constitutional delay, hypogonadotropic hypogonadism (low FSH/LH), and hypergonadotropic hypogonadism (high FSH/LH) 2

Why Other Options Are Less Appropriate

• TSH and FT4 (Option A): While thyroid dysfunction can cause amenorrhea, it would not explain the characteristic physical findings of Turner syndrome (webbing, cubitus valgus, short stature) and typically presents with other systemic symptoms 1
• Serum estrogen alone (Option C): Estradiol levels would be low in this patient, but this doesn't distinguish between central (hypothalamic-pituitary) versus primary ovarian causes. FSH/LH levels are needed to localize the problem 1
• Serum prolactin (Option D): Elevated prolactin causes hypogonadotropic hypogonadism with galactorrhea, which is not consistent with this clinical presentation 1

Diagnostic Algorithm

For a 17-year-old with primary amenorrhea and absent pubertal development:

1. Measure FSH and LH first to determine the level of dysfunction 1, 3

   • High FSH/LH (>35 IU/L and >11 IU/L respectively) = hypergonadotropic hypogonadism (ovarian/gonadal failure)
   • Low FSH/LH = hypogonadotropic hypogonadism (central cause)
   • Normal FSH/LH with delayed development = constitutional delay

2. If FSH/LH are elevated, proceed to karyotype analysis to confirm Turner syndrome (45,X or mosaic patterns) 4, 5

3. Refer to pediatric endocrinology for any patient with no signs of puberty by age 13 years with elevated FSH levels 1, 3

Critical Clinical Pitfalls

• Do not delay gonadotropin testing in patients with obvious physical stigmata of Turner syndrome - the webbing of neck and cubitus valgus are pathognomonic features that should prompt immediate hormonal evaluation 4
• FSH/LH measurement must be obtained before initiating any hormone replacement therapy, as exogenous hormones will interfere with accurate assessment of the hypothalamic-pituitary-gonadal axis 1
• In hypergonadotropic hypogonadism with 46,XY karyotype, urgent gonadectomy is required due to high risk of gonadoblastoma, emphasizing the importance of proper initial workup 5