What labs are needed to test for adrenal insufficiency or Postural Orthostatic Tachycardia Syndrome (POTS) in a 15-year-old female with primary amenorrhea and orthostatic tachycardia?

Laboratory Testing for Adrenal Insufficiency and POTS in a 15-Year-Old Female with Primary Amenorrhea and Orthostatic Tachycardia

For POTS diagnosis in this adolescent, perform an active standing test measuring heart rate increase ≥40 bpm within 10 minutes of standing without orthostatic hypotension (≥20 mmHg systolic or ≥10 mmHg diastolic drop), while adrenal insufficiency screening requires morning cortisol and ACTH levels, with ACTH stimulation testing if initial results are abnormal. 1

POTS Diagnostic Testing

Orthostatic Vital Signs Assessment

• Active standing test: Measure supine blood pressure and heart rate after 5 minutes lying flat, then immediately upon standing and at 2,5, and 10 minutes upright 1
• Diagnostic criteria for adolescents 12-19 years: Heart rate increase ≥40 bpm within 10 minutes of standing (note: adults require only ≥30 bpm) 1
• Exclude orthostatic hypotension: Systolic BP drop <20 mmHg and diastolic BP drop <10 mmHg 1
• Document symptoms during testing: lightheadedness, palpitations, tremulousness, weakness, blurred vision, and fatigue 1

Additional POTS Evaluation

• Complete blood count: Assess for anemia contributing to tachycardia 2
• Basic metabolic panel: Evaluate electrolytes, particularly sodium and potassium, as hypovolemia is a common POTS mechanism 3, 4
• Thyroid function tests (TSH, free T4): Rule out hyperthyroidism as a cause of tachycardia 2
• Plasma renin activity and aldosterone levels: Many POTS patients demonstrate inappropriately low levels contributing to hypovolemia 3, 5
• Plasma catecholamines (supine and standing): Identify hyperadrenergic POTS subtype if norepinephrine increases >600 pg/mL upon standing 3, 4

Adrenal Insufficiency Testing

Initial Screening

• Morning (8 AM) serum cortisol: Levels <3 μg/dL suggest adrenal insufficiency; levels >15 μg/dL effectively rule it out 1
• Simultaneous morning ACTH level: Distinguishes primary (elevated ACTH) from secondary/central (low ACTH) adrenal insufficiency 1
• Basic metabolic panel: Look for hyponatremia and hyperkalemia, which suggest primary adrenal insufficiency 1

Confirmatory Testing (if screening abnormal)

• ACTH stimulation test: Administer 1 μg or 250 μg cosyntropin; measure cortisol at baseline, 30, and 60 minutes 5
  • Normal response: cortisol rises to >18-20 μg/dL
  • Abnormal response suggests adrenal insufficiency 5
• Aldosterone measurement during ACTH stimulation: Assess mineralocorticoid response, particularly relevant given the POTS association 5

Primary Amenorrhea Evaluation

Hormonal Assessment

• FSH and LH levels: Distinguish between hypothalamic/pituitary (low/normal) versus ovarian (elevated) causes of amenorrhea
• Estradiol level: Assess ovarian function
• Prolactin: Rule out hyperprolactinemia from pituitary dysfunction
• TSH and free T4: Already obtained for POTS evaluation, but hypothyroidism can cause amenorrhea

Additional Considerations

• Pregnancy test (β-hCG): Always exclude pregnancy in any female with amenorrhea
• Testosterone and DHEA-S: Evaluate for hyperandrogenism if virilization signs present 1

Clinical Context and Pitfalls

The combination of orthostatic tachycardia, primary amenorrhea, and concern for adrenal insufficiency suggests possible autonomic dysfunction or hypothalamic-pituitary axis involvement. 1 POTS predominantly affects young females (80% female, ages 15-45 years) and often presents after immunological stressors 2. The hypovolemic subtype of POTS demonstrates perturbed renin-angiotensin-aldosterone profiles, but research shows the adrenal gland response to ACTH remains intact in POTS patients 5.

Critical distinction: Morning cortisol and ACTH must be drawn simultaneously to localize the problem—low cortisol with low ACTH indicates central/secondary adrenal insufficiency (pituitary or hypothalamic), while low cortisol with elevated ACTH indicates primary adrenal insufficiency 1. This distinction is essential because central adrenal insufficiency may coexist with other pituitary hormone deficiencies affecting menstruation.

Avoid the pitfall of replacing thyroid hormone before confirming adequate cortisol levels, as this can precipitate adrenal crisis by increasing cortisol metabolism 1. If multiple pituitary hormones are deficient, hydrocortisone replacement must precede thyroid hormone replacement.

The standing test should be performed when the patient is symptomatic and well-hydrated, as dehydration alone can cause orthostatic tachycardia without true POTS 1. If the active standing test is negative but clinical suspicion remains high, consider tilt-table testing with continuous hemodynamic monitoring 1.