Endocrine · Year 2 · from Endocrine

Case 3: Understanding Adrenal Zones - Zona Glomerulosa Physiology

Patient Demographics

  • Age: 45 years
  • Sex: Male
  • Occupation: Long-haul truck driver

Chief Complaint

"I've had high blood pressure that won't come down despite taking 4 medications."

History of Present Illness

A 45-year-old man is referred for evaluation of resistant hypertension. Despite taking lisinopril 40 mg, amlodipine 10 mg, hydrochlorothiazide 25 mg, and metoprolol 100 mg daily with good adherence, his blood pressure remains consistently elevated at 165-175/100-105 mmHg. He reports muscle cramps, weakness, frequent urination (nocturia), and excessive thirst. He has no family history of early hypertension. His potassium has been consistently low (2.8-3.2 mEq/L) despite potassium supplementation.

Physical Examination

  • Vital Signs: BP 172/104 mmHg, HR 68 bpm
  • General: Well-appearing man
  • Cardiovascular: Regular rate, no murmurs, PMI slightly displaced
  • Neurologic: Mild proximal muscle weakness (4+/5), reflexes normal
  • Fundoscopic: Grade II hypertensive changes

Workup

  • Laboratory Studies (off interfering medications x 4 weeks):
  • Potassium: 2.9 mEq/L (low)
  • Sodium: 144 mEq/L (high-normal)
  • Bicarbonate: 31 mEq/L (elevated - metabolic alkalosis)
  • Aldosterone: 28 ng/dL (elevated)
  • Plasma renin activity (PRA): 0.3 ng/mL/hr (suppressed)
  • Aldosterone-to-renin ratio (ARR): 93 (elevated, >30 suggestive)
  • Confirmatory Testing:
  • Oral sodium loading test: Aldosterone remains >10 ng/dL (confirms autonomous secretion)
  • CT Adrenal: 1.8 cm left adrenal nodule, low density
  • Adrenal Vein Sampling: Left adrenal aldosterone:cortisol ratio markedly higher than right (lateralization confirmed)

Diagnosis

Primary aldosteronism (Conn syndrome) due to unilateral aldosterone-producing adenoma (APA) arising from the zona glomerulosa

Treatment

  1. Pre-operative:
  • Mineralocorticoid receptor antagonist (spironolactone 25-50 mg daily or eplerenone)
  • Normalize potassium
  • Blood pressure control
  1. Definitive treatment:
  • Laparoscopic left adrenalectomy (unilateral disease confirmed by AVS)
  1. Post-operative:
  • Monitor for hyperkalemia (suppressed contralateral zona glomerulosa)
  • Temporary mineralocorticoid supplementation rarely needed
  • Blood pressure often normalizes or significantly improves
  1. If bilateral disease or surgery declined:
  • Long-term mineralocorticoid receptor antagonist therapy

Clinical Pearl

The adrenal cortex has three functional zones: zona glomerulosa (mineralocorticoids - aldosterone), zona fasciculata (glucocorticoids - cortisol), and zona reticularis (androgens - DHEA). Each zone has distinct enzymatic machinery: the zona glomerulosa uniquely expresses aldosterone synthase (CYP11B2). Primary aldosteronism is now recognized as the most common cause of secondary hypertension (5-10% of hypertensives), and screening with the aldosterone-to-renin ratio is recommended for resistant hypertension, hypokalemia with hypertension, adrenal incidentaloma with hypertension, and family history of early stroke or primary aldosteronism.

Clinical Image

Diagram of adrenal cortex showing the three zones (glomerulosa, fasciculata, reticularis) with their respective hormones and key synthetic enzymes.

Image Source: Wikimedia Commons - "Adrenal cortex zones" License: CC BY-SA 3.0 URL: https://commons.wikimedia.org/wiki/File:Adrenal_gland_(cortex).jpg

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