Primary aldosteronism

Published on 02/03/2015 by admin

Filed under Endocrinology, Diabetes and Metabolism

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 1982 times

CHAPTER 27

Primary aldosteronism

1. Define primary aldosteronism.

2. How common are these disorders?

3. Aside from hypertension, what are the common clinical manifestations of primary aldosteronism?

Aldosterone normally acts at the renal distal convoluted tubule to stimulate reabsorption of sodium ions (Na), as well as secretion of potassium (K) and hydrogen ions (H) and at the cortical and medullary collecting ducts to cause direct secretion of H. Excess secretion of aldosterone in PA results in hypertension, potassium loss, and metabolic alkalosis; hypomagnesemia may also occur (Fig. 27-1). Spontaneous hypokalemia (K < 3.5 mmol/L), however, is an uncommon presenting manifestation of PA, occurring in only 9% to 37% of cases of PA. Therefore, normokalemic hypertension is the most common presentation. Vague symptoms are manifestations of hypokalemia: weakness, muscle cramping, paresthesias, headaches, hyperglycemia (insulinopenia), palpitations, polyuria, and polydipsia.

4. Who should be screened for primary aldosteronism?

Hypertension affects 29% of the adult U.S. population; screening for PA must be judicious. Case detection should be targeted to four groups of patients:

image Patients with moderate to severe hypertension: Joint National Commission (JNC) stage 2 (BP 160-179 systolic/100-109 diastolic mm Hg) or stage 3 (> 180/> 110 mm Hg); PA prevalence 8% to 13%.

image Patients with resistant hypertension: BP higher than 140/90 mm Hg despite treatment with three antihypertensive medications; PA prevalence 17% to 23%.

image Hypertensive patients with spontaneous or diuretic-induced hypokalemia; PA prevalence 50%.

image Patients with adrenal incidentalomas who have hypertension; PA prevalence 1% to 10%.

Hypertension due to aldosterone excess causes enhanced perivascular inflammation and myocardial fibrosis; end-organ damage is therefore more severe than in essential hypertension. Screening and confirmation of the diagnosis are described in questions 14 and 16.

5. What is the most common form of primary aldosteronism?

6. What is the second most common cause of primary aldosteronism?

7. Why differentiate between IHA and APA?

8. How do symptoms of IHA differ from symptoms of APA?

9. How commonly does adrenal cancer cause primary aldosteronism?

10. What is glucocorticoid-remediable aldosteronism?

11. How is aldosterone synthesis normally regulated in the zona glomerulosa?

12. Explain the genetic basis of glucocorticoid-remediable aldosteronism.

13. How is primary aldosteronism diagnosed?

14. How are patients screened for primary aldosteronism?

15. Will antihypertensive agents alter the ARR results?

Nearly every patient screened for PA has begun therapy with one or more antihypertensives. Medications mentioned in question 14 must be withdrawn. Potentially, beta-adrenergic blockers, central alpha-2-receptor agonists, and renin inhibitors all greatly reduce PRA and slightly reduce PAC. Potentially, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and dihydropyridine calcium channel blockers all greatly increase PRA and slightly reduce PAC. These commonly used medications rarely alter the results of ARR, but if a nondiagnostic result is encountered, alternative antihypertensive drugs may be substituted for the potential offending agents for 2 weeks, and the test repeated. The following medications have little effect on the ARR and may be substituted for temporary control during ARR testing: verapamil–slow release, hydralazine, prazosin, doxazosin, and terazosin.

16. How is the diagnosis of primary aldosteronism confirmed?

Several tests confirm PA. The most commonly used is the oral sodium loading test. Intravascular volume expansion should normally suppress aldosterone secretion. In the oral sodium loading test, the patient consumes more than 200 mmol (6 g) of dietary sodium for 3 days, and then from day 3 through day 4, a 24-hour urine collection for aldosterone and sodium is collected. Urinary excretion of aldosterone (high-performance liquid chromatography–tandem mass spectrometry) that exceeds 12 μg/day confirms a diagnosis of PA. Urinary sodium excretion of at least 200 mmol/day ensures adequacy of the test. An alternative test is acute volume expansion by intravenous administration of 2 L of normal saline over 4 hours with measurement of PAC at baseline and at the end of the saline infusion. Failure of the PAC at 4 hours to fall to less than 50% of the baseline PAC also confirms the diagnosis.

17. After confirmation of primary aldosteronism, why is it important to differentiate APA from IHA?

18. Does CT or magnetic resonance imaging (MRI) aid in differentiation?

To a limited extent, both localizing procedures may aid in identifying the cause of PA. A large APA may be discernible on high-resolution CT, which at some institutions can identify adenomas as small as 5 mm. MRI at present performs as well as CT in identifying APA but involves higher cost and longer scan time. The diagnostic accuracy of MRI or CT in preoperatively localizing an APA has been reported to be 70% to 85%, but accuracy declines in older populations, in whom incidental hormonally inactive adrenal masses are more common. Some experts believe that biochemically silent adrenal masses are so rare in patients younger than 40 years that no further evaluation is necessary. In patients older than 40 years, adrenal venous sampling (AVS) must be performed to verify unilateral aldosterone production (see question 19). Adrenal carcinoma, a rare cause of PA, is easily identified with either CT or MRI. See also Chapter 29 for more on this topic.

19. Which localizing test is required if CT or MRI suggests an APA in a patient older than 40 years?

A more invasive localizing procedure to differentiate a normal adrenal gland from one containing an adenoma is AVS. Many institutions believe AVS should be performed before surgical intervention for an APA is considered. In this procedure, catheters are introduced into the left and right adrenal veins and the inferior vena cava. Levels of PAC are determined from these sites, along with concomitant cortisol levels following infusion of cosyntropin (synthetic ACTH). Cortisol levels are determined to ensure that the adrenal veins are properly catheterized. PAC/cortisol is referred to as “cortisol-corrected” aldosterone. APAs produce large amounts of aldosterone; the normal adrenal vein PAC is 100 to 400 ng/dL, whereas APAs may generate concentrations of 1000 to 10,000 ng/dL. The ratio of PAC/cortisol produced on the affected side versus the unaffected side always exceeds 4:1. When compared with CT scan results, discordant AVS results are found in up 30% of cases.

20. Explain the difficulty with adrenal venous sampling.

21. How accurate is adrenal venous sampling?

22. How is the patient with APA managed?

23. What should be done after the APA is localized?

24. Do all patients with APA require surgery?

25. How is a patient with IHA managed?

The patient undergoes screening and confirmatory tests, as described in questions 15 and 16. CT does not reveal unilateral enlargement of the adrenals, and AVS does not show a unilateral abnormality. After the diagnosis of IHA is made, the patient is scrupulously sequestered from surgical colleagues.

26. What is the agent of choice for pharmacologic treatment of IHA?

27. What other pharmacologic options are available?

In patients intolerant of the agents discussed in question 26, amiloride (5-15 mg b.i.d.) corrects hypokalemia within several days. A concomitant antihypertensive agent is usually necessary to reduce blood pressure. Success also has been reported in IHA treated with calcium channel blockers (calcium is involved in the final common pathway for aldosterone production) and angiotensin-converting enzyme inhibitors (IHA appears to be sensitive to low concentrations of angiotensin II).

28. How is a patient with glucocorticoid-remediable aldosteronism managed?

Bibliography

Dluhy, RG, Lifton, RP. Glucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab. 1999;84:4341–4344.

Fardella, CE, Mosso, L, Gomez-Sanchez, C, et al, Primary hyperaldosteronism in essential hypertensives. prevalence, biochemical profile, and molecular biology. J Clin Endocrinol Metab 2000;85:1863–1867.

Funder, JW, Carey, RM, Fardella, CE, et al, Case detection diagnosis, and treatment of patients with primary aldosteronism. an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008;93:3266–3281.

Jossart, GH, Burpee, SE, Gagner, M. Surgery of the adrenal glands. Endocrinol Metab N Am. 2000;29:57–68.

Liftin, RP, Dluhy, RG, Powers, M, et al. A chimaeric 11-hydroxylase/aldosterone synthetase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature. 1992;355:262–265.

Lim, PO, Young, WF, MacDonald, TM. A review of the medical treatment of primary aldosteronism. J Hypertens. 2001;19:353–361.

Magill, SB, Raff, H, Shaker, JL, et al. Comparison of adrenal vein sampling and computed tomography in the differentiation of primary aldosteronism. J Clin Endocrinol Metab. 2001;86:1066–1071.

Milliez, P, Girerd, X, Plouin, PF, et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005;45:1243–1248.

Mulatero, P, Rabbia, F, Milan, A, et al. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism. Hypertension. 2002;40:897–902.

Mulatero, P, Stowasser, M, Loh, K, et al. Increased diagnoses of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004;89:1045–1050.

Rossi, G, Bernini, G, Desideri, G, et al, Renal damage in primary aldosteronism. results of the PAPY study. Hypertension 2006;48:232–238.

Rossi, P. Diagnosis and treatment of primary aldosteronism. Endocrinol Metab N Am. 2011;40:313–332.

Schwartz, GL, Screening for adrenal-endocrine hypertension. overview of accuracy and cost-effectiveness. Endocrinol Metab Clin N Am 2011;40:279–294.

Schwartz, GL, Turner, ST, Screening for primary aldosteronism in essential hypertension. diagnostic accuracy of the ratio of plasma aldosterone concentration to plasma renin activity. Clin Chem 2005;51:386–394.

Tan, YY, Ogilvie, JB, Triponez, E, et al. Selective use of adrenal venous sampling in the lateralization of aldosterone-producing adenomas. World J Surg. 2006;30:879–885.

Tanabe, A, Naruse, M, Takagi, S, et al. Variability in the renin/aldosterone profile under random and standardized sampling conditions in primary aldosteronism. J Clin Endocrinol Metab. 2003;88:2489–2492.

Tiu, SC, Choi, CH, Shek, CC, et al. The use of aldosterone-renin ratio as a diagnostic test for primary hyperaldosteronism and its test characteristics under different conditions of blood sampling. J Clin Endocrinol Metab. 2005;90:72–78.