eMedicine Specialties > Endocrinology > Adrenal Gland

Conn Syndrome: Treatment & Medication

Author: Serge A Jabbour, MD, Associate Professor, Department of Medicine, Division of Endocrinology, Thomas Jefferson University
Contributor Information and Disclosures

Updated: May 21, 2009

Treatment

Medical Care

In patients with primary hyperaldosteronism, the goal of treatment is to prevent the morbidity and mortality associated with hypertension and hypokalemia. The appropriate treatment depends on the cause (Conn syndrome vs IHA). Although hypertension is frequently cured after unilateral adrenalectomy in patients with Conn syndrome, the mean cure rate is only 19% after unilateral or bilateral adrenalectomy in patients with IHA, in whom treatment mainly is medical.

In the case of APA, medical therapy is used preoperatively to control blood pressure and correct hypokalemia, thus decreasing surgical risk. Medical therapy is administered to patients with persistent hypertension postoperatively, poor surgical candidates, and those who refuse surgery.

  • A sodium-restricted diet (<80 mEq or <2 g of sodium per d), maintenance of ideal body weight, and regular aerobic exercise contribute substantially to the success of pharmacologic treatment.
  • Frequently, hypertension and hypokalemia can be controlled with a potassium-sparing agent (first-step agent), such as spironolactone.6 Hypokalemia is promptly corrected, but hypertension may take as long as 4-8 weeks to correct. Potassium supplementation should not be routinely administered with spironolactone because of the potential for the development of hyperkalemia. If hypertension persists despite titration, a second-step agent is added to the treatment.
  • Second-step agents include thiazides diuretics, ACE inhibitors, calcium channel antagonists, and angiotensin II blockers.7
  • GRA is treated with physiologic doses of glucocorticoid, which correct the hypertension and hypokalemia.

Surgical Care

Surgery is the main therapy for Conn syndrome. A laparoscopic adrenalectomy is favored, when possible.6,4

  • In patients with Conn syndrome, the blood pressure response to spironolactone preoperatively is a predictor of the blood pressure response to unilateral adrenalectomy.
  • Surgical risk can be decreased by correcting the hypokalemia and controlling the blood pressure by administering spironolactone for at least 1-2 weeks, preferably 6 weeks, before surgery.
  • Hypertension typically does not resolve immediately postoperatively but, rather, over 3-6 months; however, almost all patients have improved control of blood pressure after surgery. Long-term cure rates with unilateral adrenalectomy for Conn syndrome average 69%. A retrospective study of 168 patients with primary hyperaldosteronism who underwent an adrenalectomy found that hypertension was cured or controlled in 77% of patients with a unilateral adenoma and in 68% of patients with hyperaldosteronism but no adenoma.8 Persistent hypertension may be related to resetting of baroreceptors, established hemodynamic changes, structural changes in the blood vessels, or coincidental essential hypertension.

Medication

As mentioned previously, potassium-sparing agents, especially spironolactone, are useful for patients with primary hyperaldosteronism. They act as specific antagonists of aldosterone.

Antihypertensives/diuretics

Treat hypertension, edematous conditions, and hypokalemia.


Spironolactone (Aldactone)

Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions. May block effects of aldosterone on arteriolar smooth muscles.

Adult

100 mg PO qd initially, increase to 400 mg/d prn for control of blood pressure

Pediatric

Not established

Blocks testosterone biosynthesis and peripheral androgen action, causing impotence, decreased libido, and gynecomastia
May cause menstrual irregularities in women
High doses increase half-life of digoxin (adjust digoxin dose)
Avoid concomitant therapy with salicylates because they decrease effectiveness
Concomitant therapy with ACE inhibitors or indomethacin has been associated with severe hyperkalemia

Documented hypersensitivity; anuria; renal failure; hyperkalemia

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Not recommended during pregnancy because may cross placenta; in male fetus, may cause pseudohermaphrodism
Not recommended in nursing mothers because of excretion in breast milk
Caution in renal and hepatic impairment


Eplerenone (Inspra)

Indicated for hypertension. Selectively blocks aldosterone at mineralocorticoid receptors in epithelial (eg, kidney) and nonepithelial (eg, heart, blood vessels, brain) tissues; thus, decreases blood pressure and sodium reabsorption.

Adult

50 mg PO qd; may increase dose after 4 wk, not to exceed 100 mg/d

Pediatric

Not established

CYP450 3A4 substrate; potent CYP3A4 inhibitors (eg, ketoconazole) increase serum levels approximately 5-fold; less potent CYP3A4 inhibitors (eg, erythromycin, saquinavir, verapamil, fluconazole) increase serum levels approximately 2-fold; grapefruit juice increases serum levels approximately 25%; coadministration with potassium supplements, salt substitutes, or drugs known to increase serum potassium (eg, amiloride, spironolactone, triamterene, ACE inhibitors, angiotensin II inhibitors) increases risk of hyperkalemia

Documented hypersensitivity; hyperkalemia or coadministration with drugs causing increase in potassium; type 2 diabetes with microalbuminuria; moderate-to-severe renal insufficiency (eg, CrCl <50 mL/min or serum creatinine >2 mg/dL in males, or >1.8 mg/dL in females)

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause hyperkalemia, headache, and dizziness; caution with hepatic insufficiency

More on Conn Syndrome

Overview: Conn Syndrome
Differential Diagnoses & Workup: Conn Syndrome
Treatment & Medication: Conn Syndrome
Follow-up: Conn Syndrome
Multimedia: Conn Syndrome
References
Further Reading
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References

  1. Born-Frontsberg E, Reincke M, Rump LC, et al. Cardiovascular and cerebrovascular comorbidities of hypokalemic and normokalemic primary aldosteronism: results of the German Conn's Registry. J Clin Endocrinol Metab. Apr 2009;94(4):1125-30. [Medline].

  2. Bernini G, Galetta F, Franzoni F, et al. Arterial stiffness, intima-media thickness and carotid artery fibrosis in patients with primary aldosteronism. J Hypertens. Dec 2008;26(12):2399-405. [Medline].

  3. Bravo EL. Primary aldosteronism: new approaches to diagnosis and management. Cleve Clin J Med. Sep-Oct 1993;60(5):379-86. [Medline].

  4. Funder JW, Carey RM, Fardella C, et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. Sep 2008;93(9):3266-81. [Medline].

  5. Doppman JL, Gill JR Jr. Hyperaldosteronism: sampling the adrenal veins. Radiology. Feb 1996;198(2):309-12. [Medline].

  6. Carey RM. Primary aldosteronism. Horm Res. Jan 2009;71 Suppl 1:8-12. [Medline].

  7. Wu VC, Chang HW, Liu KL, et al. Primary aldosteronism: diagnostic accuracy of the losartan and captopril tests. Am J Hypertens. May 14 2009;[Medline].

  8. Letavernier E, Peyrard S, Amar L, et al. Blood pressure outcome of adrenalectomy in patients with primary hyperaldosteronism with or without unilateral adenoma. J Hypertens. Sep 2008;26(9):1816-23. [Medline].

  9. Al Fehaily M, Duh QY. Clinical manifestation of aldosteronoma. Surg Clin North Am. Jun 2004;84(3):887-905. [Medline].

  10. Capricchione A, Winer N, Sowers JR. Adrenocortical hypertension. Curr Hypertens Rep. Jun 2004;6(3):224-9. [Medline].

  11. Gill JR. Primary aldosteronism: Strategies for diagnosis and treatment. The Endocrinologist. 1991;1:365-9.

  12. Hirohara D, Nomura K, Okamoto T, et al. Performance of the basal aldosterone to renin ratio and of the renin stimulation test by furosemide and upright posture in screening for aldosterone-producing adenoma in low renin hypertensives. J Clin Endocrinol Metab. Sep 2001;86(9):4292-8. [Medline].

  13. Jabbour SA, De Papp AE. Pitfalls in the diagnosis and management of primary hyperaldosteronism. The Endocrinologist. 1999;9:395-8.

  14. Montori VM, Schwartz GL, Chapman AB, et al. Validity of the aldosterone-renin ratio used to screen for primary aldosteronism. Mayo Clin Proc. Sep 2001;76(9):877-82. [Medline].

  15. Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. Mar 2004;89(3):1045-50. [Medline].

  16. Rose BD, Kaplan NM. Approach to the patient with hypertension and hypokalemia. UpToDate [CD-ROM and online]. 1997;1-8.

  17. Seiler L, Rump LC, Schulte-Monting J, et al. Diagnosis of primary aldosteronism: value of different screening parameters and influence of antihypertensive medication. Eur J Endocrinol. Mar 2004;150(3):329-37. [Medline].

  18. Vallotton MB. Primary aldosteronism. Endocrine Investigation. 1996;45:47-60.

  19. Weinberger MH, Fineberg NS. The diagnosis of primary aldosteronism and separation of two major subtypes. Arch Intern Med. Sep 27 1993;153(18):2125-9. [Medline].

  20. Young WF Jr. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med. Feb 8 2007;356(6):601-10.

  21. Young WF Jr. Pheochromocytoma and primary aldosteronism: diagnostic approaches. Endocrinol Metab Clin North Am. Dec 1997;26(4):801-27. [Medline].

  22. Young WF Jr, Hogan MJ, Klee GG, van Heerden JA. Primary aldosteronism: diagnosis and treatment. Mayo Clin Proc. Jan 1990;65(1):96-110. [Medline].

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Keywords

Conn syndrome, Conn's syndrome, adrenal, adrenal gland, adrenal glands, hyperaldosteronism, aldosteronism, adenoma, spironolactone, renin, primary hyperaldosteronism, adrenalectomy, hypertension, hypokalemia, adrenal hyperplasia, unilateral aldosterone-producing adenoma, bilateral adrenal hyperplasia, idiopathic hyperaldosteronism, increased aldosterone secretion, primary hypersecretion of aldosterone, secondary hypertension, renin-responsive adenoma, primary adrenal hyperplasia, glucocorticoid-remediable aldosteronism

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Contributor Information and Disclosures

Author

Serge A Jabbour, MD, Associate Professor, Department of Medicine, Division of Endocrinology, Thomas Jefferson University
Serge A Jabbour, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, American Thyroid Association, Endocrine Society, and Pennsylvania Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Barry J Goldstein, MD, PhD, Director, Division of Endocrinology, Diabetes and Metabolic Diseases, Professor, Department of Internal Medicine, Thomas Jefferson University
Barry J Goldstein, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, and Endocrine Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS, Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC
Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, American Society of Law Medicine and Ethics, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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