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Difficulty: Very hardMedical History Evaluation

A 52-year-old woman is evaluated in the outpatient clinic for persistently elevated blood pressure. Over the past six months, her blood pressure has remained uncontrolled despite reported adherence to a regimen of amlodipine, lisinopril, and chlorthalidone. She complains of generalized weakness, intermittent muscle cramps in her calves, and mild fatigue. Her medical history includes osteoarthritis, seasonal allergic rhinitis, and mild, chronic dyspepsia. She has no prior surgeries. She does not smoke or drink alcohol, follows a standard diet, and walks 30 minutes daily. Her current prescription medications include her antihypertensives, and she frequently takes over-the-counter pain relievers and oral decongestants. Her temperature is 37.0°C (98.6°F), blood pressure is 168/98 mm Hg, and pulse is 76/min. Physical examination reveals no peripheral edema, abdominal bruits, or abnormal facies.

Laboratory studies show:

Laboratory StudyResultReference Range
Serum sodium145 mEq/L136-145 mEq/L
Serum potassium2.7 mEq/L3.5-5.0 mEq/L
Serum chloride101 mEq/L98-106 mEq/L
Serum bicarbonate31 mEq/L22-28 mEq/L
Plasma renin activity0.1 ng/mL/hr0.6-4.3 ng/mL/hr
Serum aldosterone1.5 ng/dL4.0-21.0 ng/dL

Further targeted history-gathering regarding which of the following areas is most critical to establishing the diagnosis in this patient?

  1. Consumption of specific botanical supplements or traditional confectionsAnswer
  2. B
    Frequency and cumulative dosage of over-the-counter analgesic agents
  3. C
    Concurrent use of over-the-counter sympathomimetic cold preparations
  4. D
    History of sudden-onset, severe headaches accompanied by palpitations
  5. E
    Adherence to recommended dietary sodium restriction and aerobic exercise guidelines

Answer

Consumption of specific botanical supplements or traditional confections
The correct answer involves inquiring about the consumption of specific botanical supplements or traditional confections, specifically black licorice or licorice root extract. This patient presents with treatment-resistant hypertension accompanied by hypokalemia, metabolic alkalosis, and markedly suppressed levels of both plasma renin activity and serum aldosterone. This laboratory profile indicates a state of apparent mineralocorticoid excess (AME). Primary hyperaldosteronism (Conn syndrome) would present with elevated aldosterone, whereas secondary hyperaldosteronism (such as from renal artery stenosis) would present with elevated renin. In AME, cortisol inappropriately activates the mineralocorticoid receptor. This is typically prevented by the renal enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2), which converts cortisol to inactive cortisone. Glycyrrhetinic acid, the active ingredient in licorice root (often used as a botanical remedy for dyspepsia) and authentic black licorice confections, inhibits 11-beta-HSD2. This leads to cortisol-mediated mineralocorticoid receptor activation, causing sodium retention, potassium wasting, and secondary suppression of both renin and aldosterone. Therefore, specifically eliciting this dietary/supplement history is the critical next step in establishing the diagnosis.

Step-by-Step Solution

1
Analyze the laboratory data in the context of refractory hypertension.
The patient has severe hypokalemia, metabolic alkalosis, markedly suppressed plasma renin activity, and markedly suppressed serum aldosterone.
Identifying this specific triad of electrolyte and hormonal derangements is required to narrow down the pathophysiologic mechanism.
2
Synthesize the findings to formulate a mechanism of disease.
The combination of suppressed renin and suppressed aldosterone in the setting of mineralocorticoid excess symptoms indicates Apparent Mineralocorticoid Excess (AME) or another non-aldosterone mineralocorticoid agonist.
Primary hyperaldosteronism presents with high aldosterone, while secondary hyperaldosteronism presents with high renin.
3
Link the pathophysiologic mechanism to potential etiologies.
Acquired AME is classically caused by the exogenous ingestion of glycyrrhetinic acid, which inhibits the renal enzyme 11-beta-hydroxysteroid dehydrogenase type 2, allowing cortisol to inappropriately activate mineralocorticoid receptors.
Understanding the pharmacology and common sources of glycyrrhetinic acid is necessary to identify the condition.
4
Determine the necessary historical inquiry to establish the diagnosis.
The physician must specifically ask about the consumption of authentic black licorice confections or licorice root extract, which is often used as a botanical supplement for conditions like dyspepsia.
Establishing this dietary/supplement exposure confirms the exogenous etiology of the patient's condition.

Key Concept

Apparent Mineralocorticoid Excess (AME) is characterized by hypertension, hypokalemia, metabolic alkalosis, and suppressed levels of both renin and aldosterone. An important acquired cause is the ingestion of glycyrrhetinic acid (found in licorice root), which requires targeted dietary and supplement history-taking.
Estimated Time:2m 0s
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Medical History Evaluation

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