The Curbsiders podcast

#39 Secondary hypertension, hyperaldosteronism, Cushing’s, and pheochromocytoma

May 15, 2017 | By

Expert tips on the diagnosis and management of secondary hypertension in this conversation with Dr. Richard Auchus MD, PhD, Professor of Pharmacology and Internal Medicine & Director of the Diabetes, Endocrinology, & Metabolism Fellowship Program at the University of Michigan. Topics include: primary hyperaldosteronism, use of spironolactone, Cushing’s syndrome, pheochromocytoma, and which tests to utilize.

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Clinical Pearls:

  1. 5 causes of resistant hypertension (HTN): Medication nonadherence, alcohol use (>3 drinks per day), sleep apnea, renal insufficiency, mineralocorticoid excess
  2. Resistant HTN: On 3 drugs at maximum dose including a diuretic and BP is still not controlled.
  3. Pseudo-resistant HTN: BP uncontrolled due to medication noncompliance, inadequate dosing, poor choice of agents, etc.
  4. Renin-Angiotensin-Aldosterone-System (RAAS) pathway: If kidney senses volume expansion: response = decreased renin and aldosterone production. If kidney senses volume depletion: response = increased renin, converts angiotensinogen to angiotensin 1, converted to angiotensin 2 by the converting enzyme. Angiotensin 2 is a direct vasoconstrictor and also stimulates aldosterone production by the adrenal gland.
  5. Aldosterone: Mineralocorticoid/steroid hormone from the adrenal cortex. Stimulates reabsorption of water and sodium, and excretion of potassium in distal convoluted tubules. Hyperkalemia directly increases aldosterone production. Hypokalemia lowers aldosterone production.
  6. Primary aldosteronism: Common disease affecting 8% of all people with HTN and 20% of people with resistant HTN. About 60% of these patients will maintain a normal K+ so normal K+ does NOT rule out hyperaldosteronism.
  7. Diagnosis of primary hyperaldosteronism: No need to stop BP medications. Okay to test even if on spironolactone. In general, BP meds cause kidneys to sense low volume due to vasodilation and volume depletion. Use of spironolactone and other BP meds should cause increases in both renin and aldosterone. Testing abnormal if renin suppressed, but aldosterone is elevated. Note: Imaging is not part of initial testing!
  8. Diagnosis (continued): Check aldosterone, renin, potassium preferably in the morning. *Suppressed plasma renin activity (older assay) is <1 ng/ml. Suppressed direct renin (newer assay) is <10 ng/ml. Diagnosis confirmed if aldosterone >15, and renin is suppressed. If aldosterone level between 10-15, then refer to Endocrinology for further testing.
  9. Treatment of resistant hypertension: Add spironolactone 12.5 mg daily and titrate up by 12.5 mg monthly up to about 50 mg. Check RFP in 1 week (if CKD present), or 1 month (if no CKD).
  10. Cushing’s syndrome: Clinical diagnosis supported by lab findings! Weight gain, glucose intolerance, striae, skin thinning, increase in cervical, supraclavicular fat pad, facial plethora, muscle weakness, or osteoporosis in an obese patient. Consider testing if clinical findings (above), or recent unexplained change in patient’s glucose control.
  11. Dexamethasone suppression test: Test for adrenal Cushing’s. Give 1 mg dexamethasone between 11pm-midnight then check morning serum cortisol by 8:30am. Cortisol should be <1.8mcg/dL. Urinary free cortisol (not recommended) is difficult to interpret with modern testing since normal range is much lower.
  12. Pheochromocytoma: Do not routinely check. Plasma metanephrines and normetanephrines positive only if 3-10 times upper limit of normal. Clinical clues: incidentaloma; heart failure in young person without risk factors.
  13. Incidentalomas: If lipid rich, then no further testing needed. If not lipid rich, then need functional tests for secretion.

Goal: Listeners will learn to identify the common causes of resistant hypertension, including the diagnosis and management of primary hyperaldosteronism.

Learning objectives:
By the end of this podcast listeners will:

  1. Define resistant and pseudo-resistant HTN
  2. Recall the top five causes of resistant HTN
  3. Describe the normal physiology of the renin-angiotensin-aldosterone-system
  4. Utilize the appropriate tests to identify hyperaldosteronism
  5. Safely utilize spironolactone for resistant HTN
  6. Interpret plasma metanephrine and normetanephrine testing
  7. Recognize the clinical features of Cushing’s syndrome
  8. Utilize the overnight dexamethasone suppression test


Time Stamps
00:00 Intro
05:16 Rapid fire questions
08:40 Defining secondary, resistant, and pseudo-resistant HTN
11:50 Diagnosing hyperaldosteronism
18:21 Review of the renin-angiotensin system
23:00 Pheochromocytoma
25:00 The role or lack thereof for imaging
27:55 Cushing’s syndrome
32:52 Take home points
33:36 Closing remarks by Stuart and Paul
39:20 Outro

Links from the show:

  1. General overview of the RAAS system video from Khan Academy
  2. Renin-Angiotensin-Aldosterone-System diagram. Best diagram I found is from Wikipedia!
  3. Williams B, MacDonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet (London, England). 2015;386(10008):2059-2068. doi:10.1016/S0140-6736(15)00257-3.
  4. Judd EK, Calhoun DA, Warnock DG. Pathophysiology and Treatment of Resistant Hypertension: The Role of Aldosterone and Amiloride-Sensitive Sodium Channels. Seminars in nephrology. 2014;34(5):532-539. doi:10.1016/j.semnephrol.2014.08.007.
  5. Chapman N, Dobson J, Wilson S, Dahlöf B, Sever PS, Wedel H, Poulter NR. Effect of Spironolactone on Blood Pressure in Subjects with Resistant Hypertension. Hypertension 2007;49(4):839-845.

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