ANGELES UNIVERSITY FOUNDATION

Angeles City
COLLEGE OF ALLIED MEDICAL PROFESSIONS

CLINICAL CHEMISTRY 3 LABORATORY

(ENDOCRINOLOGY, TOXICOLOGY AND DRUG TESTING)

HYPERALDOSTERONISM

Submitted by:
Group 7
BSMT 3-E
Group Leader: Collado, Marc Jeffrey S.
Members: Concepcion, Vixy
Roque, Theresa
.
Submitted to:
Mr. Raphael Tiongco
Mr. Franz Cabrera
CC03 Laboratory Professors

November 24, 2016

I.

II.

INTRODUCTION
Aldosterone controls the retention of Na+, CP, and H2O, the excretion of K+ and H+ and,
therefore, the amount of fluid in the body. Aldosterone production is controlled by the
renin-angiotensin system of the kidney.
Angiotensin II stimulates the secretion of aldosterone and is a potent vasoconstrictor.
Steroid Hormone
18-hydroxysteroid dehydrogenase enzyme needed fpr the synthesis of aldosterone
Function of aldosterone is to increase salt and water conservation through renal tubular
retention of Na+ and Cl~ and H2O secondarily and to promote excretion of K+ and H+.
1) Overall effect is vasoconstriction, which increases blood pressure (BP) and Na+
retention, which promotes increase in blood volume (BV).
2) Increase in BP and BV suppresses secretion of renin and, thus, the synthesis of
aldosterone.

SUMMARY OF THE CASE

HYPERALDOSTERONISM
A 57 year old lady has complaints of uncontrolled blood pressure for a year despite using
multiple combinations of anti-hypertensive drugs. Transabdominal ultrasonography revealed
bilateral simple renal cortical cysts and a solid mass of 3.1x2.8 cm in the right adrenal gland.
Lab tests are as follows:
FBS: 107 (85-120 mg/dL)
Creatinine: 1.6 (0.8 1.9 mg/dL)
Sodium: 140 (135-145 mmol/L)
Potassium: 3.9 (3.5-5.4 mmol/L)
Serum Aldosterone: 48.3 (4-31 ng/dL)
Plasma Renin Activity: 0.006 (0.15 2.33 ng/mL/hr)

III.

ANSWER TO GUIDE QUESTIONS

1. Explain briefly the pathophysiology of hyperaldosteronism.

Hyperaldosteronism, commonly referred to as Conn syndrome, is a

syndrome associated with hypersecretion of the major mineralocorticoid,
aldosterone. Primary and secondary are the two types of
hyperaldosteronism. Levels of circulating aldosterone are inappropriately
high, causing excessive reabsorption of Na and excretion of K+ and H+
ions. The patient will be hypernatremic and hypokalemic and will exhibit a
mild metabolic alkalosis.

2. What are the abnormal results? Give the indication of these results.

Serum Aldosterone : 48.3 ng/dL (4-31 ng/dL)

Plasma Renin Activity: 0.006 ng/mL/hr (0.15-2.33 ng/mL/hr)
Sodium and Potassium exhibit a normal results in the given case but it
should exhibit high sodium levels and low potassium levels.
Solid mass of 3.1x2.8cm in the right adrenal gland indicates that there is
a possible adenoma which causes increase aldosterone levels.

3. Give the characteristic signs and symptoms of the disease.

Hypertension
Hypokalemia
Mild Hypernatremia
Metabolic alkalosis

4. Give the difference between primary, secondary, and

pseudoaldosteronism based on the following: Serum aldosterone, serum
renin, signs & symptoms
PRIMARY

SECONDARY

PSEUDOALDOSTERONISM
(Liddle Syndrome)

PLASMA
ADOSTERONE

Elevated aldosterone

Elevated aldosterone

Low aldosterone

PLASMA
RENIN

Low renin

Elevated renin

Variable renin & aldosterone

levels

SIGNS &
SYMPTOMS

Hypertension ,
hypokalemia, mild
hypernatremia and
metabolic alkalosis

Malignant
hypertension,
hypokalemia, and renal
artery stenosis

Hypertension, metabolic alkalosis,

and hypokalemia

5. Different tests/methods for the diagnosis of primary aldosteronism. What

is the expected result?
SCREENING TESTS

Plasma Aldosterone (PA): Plasma Renin Activity (PRA) ratio

o Helps distinguish primary from other forms of
aldosteronism
o

Expected result: > 30 ratio suggestive of primary

hyperaldosteronism > 50 ratio- diagnostic of primary
hyperaldosteronism

CONFIRMATORY TESTS
Saline Suppression Test - It involves infusing 2 L of 0.9% saline over 4
hours, or by administering 10-12 mg NaCl tablets daily for 3 days.
o Expected result: (+) >10 ng/dL PAC

Oral Sodium Loading Test - a 24-hour urine is collected for

aldosterone, creatinine (to assess for adequacy of the collection), and
sodium (>200 mmol/day confirms adequate sodium intake).
o An aldosterone greater than 10 mg/24 hours (28 nmol/24
hours) following 3 days of sodium loading confirms the
diagnosis

Fludrocortisone Suppression Test - 0.1 mg fludrocortisone is given

orally every 6 hours for 4 days, together with slow-release potassium
chloride supplements and slow-release sodium chloride.
o

Captopril Challenge Test - Baseline blood is collected for PRA, PAC,

and cortisol; then 2550 mg of captopril is administered orally. PRA,
PAC, and cortisol are again collected at 1 and 2 hours post captopril.
o

IV.

Reference

A PAC greater than 6 ng/dL with a PRA less than 1 ng/mL/hour

confirms the diagnosis, provided that the 10 am cortisol is less
than the 7 am value.

The patient is kept seated throughout the entire test. PAC is

normally suppressed to greater than 30%; however in primary
hyperaldosteronism, the PAC remains elevated and the PRA
suppressed.

Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics, 7e (Fundamentals of

Clinical Chemistry by Carl A. Burtis
Henry's Clinical Diagnosis and Management by Laboratory Methods by Richard A. McPherson
Clinical Chemistry: Principles, Techniques, and Correlations by Michael L. Bishop
http://emedicine.medscape.com/article/920713-clinical#b2
http://onlinelibrary.wiley.com/doi/10.1111/j.1751-7176.2008.07470.x/full

c. Reference ranges: Adult supine, 3-16 ng/dL; adult upright, 7-30 ng/dL;
blood levels of aldosterone are higher in the morning
d. Clinical significance
1) Hyperaldosteronism

a) Primary hyperaldosteronism: Adrenal disease such as an

aldosterone-secreting adrenal adenoma (Conn syndrome), aldosterone-secreting adrenal
carcinoma, or hyperplasia of adrenal cortex
b) Secondary hyperaldosteronism: Renin-angiotensin system
disorder due to excess production of renin, malignant hypertension, or a renin-secreting renal
tumor
When the juxtaglomerular apparatus of the kidney detects low serum sodium or pressure
changes in the blood perfusing the kidneys, due to decreased blood pressure or blood volume,
renin is produced. Renin is a protein that acts on angiotensinogen to produce angiotensin I,
which is acted on by angiotensin-converting enzyme to catalyze the formation of angiotensin II.
High PRA and high aldosterone suggest secondary hyperaldosteronism, which includes diuretic
therapy, renal artery stenosis, malignant hypertension, renin producing tumors, and hereditary
defects in renal salt transport (Bartters syndrome and Gitelmans syndrome). Blood pressure
would be normal in subjects with Bartters syndrome or Gitelmans syndrome, and in a
normotensive person on diuretic therapy. Blood pressure would be high in all other conditions
and in a hypertensive subject on diuretic therapy. Low PRA and high plasma aldosterone
suggest primary hyperaldosteronism, which is caused by adrenal adenoma or bilateral
hyperplasia. If PRA and plasma aldosterone are low, likely conditions include Liddles syndrome,
apparent mineralocorticoid excess states (both hereditary and drug- or licorice-induced), 11hydroxylase deficiency, and 17-hydroxylase deficiency. Reduction in renal K+ excretion will be
achieved with spironolactone in all these conditions except for Liddles syndrome, which will
respond to ENaC blockers such as triamterene and amiloride
Primary HyperaldosteronismScreening and Confirmation Tests
The algorithm proposed by Blumenfeld for evaluating hypertensive patients suspected of having
primary hyperaldosteronism is to initially measure the serum potassium (Blumenfeld, 1994). If it
is less than 3.6 mmol/L, then plasma renin activity is measured. Plasma renin activity of <1.0
ng/mL/hour leads to 24-hour urine collection for aldosterone and potassium excretion. Findings
of 24-hour urinary potassium greater than 30 mmol/24 hours in the face of hypokalemia and of
aldosterone greater than 15 mg/24 hours lead to the localization of the underlying pathology to
the adrenal. A more recent set of guidelines for the detection and diagnosis of primary
hyperaldosteronism, as proferred by the Endocrine Society, include the following (Funder,
2008). Although patients with primary hyperaldosteronism classically present with spontaneous
or easily provokable hypokalemia, many in fact will have serum potassium levels that are within
the normal range. Thus, the preferred screening test is a plasma aldosterone
concentration/plasma renin activity (PAC/PRA) ratio, PAC expressed in ng/dL, and PRA in
ng/mL/hour. This is performed after the patient has remained upright for at least 2 hours. The
patient should have stopped spironolactone and eplerenone for 46 weeks and other diuretics
for at least 2 weeks before testing. Hypokalemia should be corrected (as it may suppress
aldosterone secretion), and the patient should not be on a sodium-restricted diet. A PAC/PRA

ratio greater than 30 is suggestive of primary hyperaldosteronism; a value greater than 50 is

virtually diagnostic (Weinberger, 1993; Blumenfeld, 1994). It is of note that the lower limit of
normal for the PRA assay varies by laboratory; therefore, the diagnosis is supported only when
both the PAC/PRA ratio and the PAC are elevated. The preferred technique for measuring PRA
is a validated immunometric assay. HPLC tandem mass spectrometry is preferred for measuring
plasma and urine aldosterone (Funder, 2008). The PAC/PRA ratio is highly dependent on the
renin concentration; as such, it is important to use an assay with sufficient sensitivity in the
lower ranges (e.g., <0.20.3 ng/mL/hour). The diagnosis of primary hyperaldosteronism is
confirmed by performing one of the four following confirmatory tests: oral sodium loading test,
saline infusion test, fludrocortisone suppression test, or the captopril challenge test (Funder,
2008). Saline suppression can be accomplished by infusing 2 L of 0.9% saline over 4 hours, or
by administering sodium chloride tablets 1012 g daily for 3 days. PAC at the end of the 4-hour
infusion of less than 5 ng/dL (140 pmol/L) makes the diagnosis of hyperaldosteronism unlikely. A
PAC greater than 10 ng/dL (280 pmol/L) strongly supports the diagnosis of primary
hyperaldosteronism, whereas values greater than 5 ng/dL (140 pmol/L) but less than10 ng/dL
(280 pmol/L) are considered indeterminate and may be seen with IHA. On the last day of oral
sodium administration, a 24-hour urine is collected for aldosterone, creatinine (to assess for
adequacy of the collection), and sodium (>200 mmol/day confirms adequate sodium intake). An
aldosterone greater than 10 mg/24 hours (28 nmol/24 hours) following 3 days of sodium loading
confirms the diagnosis (Bravo, 1983, 1994; Holland, 1984). For the fludrocortisone suppression
test, 0.1 mg fludrocortisone is given orally every 6 hours for 4 days, together with slow-release
potassium chloride supplements (in doses sufficient to maintain the plasma potassium close to
4.0 nmol/L) and slow-release sodium chloride (30 mmol three times a day) and liberalization of
dietary sodium intake (enough to maintain a urinary sodium excretion of at least 3 mmol/kg). On
day 4, an upright plasma cortisol is measured at 7 am and 10 am, and PAC and PRA are
measured at 10 am. A PAC greater than 6 ng/dL with a PRA less than 1 ng/mL/hour confirms
the diagnosis, provided that the 10 am cortisol is less than the 7 am value. For the captopril
challenge, baseline blood is collected for PRA, PAC, and cortisol; then 2550 mg of captopril is
administered orally. PRA, PAC, and cortisol are again collected at 1 and 2 hours post captopril.
The patient is kept seated throughout the entire test. PAC is normally suppressed to greater
than 30%; however in primary hyperaldosteronism, the PAC remains elevated and the PRA
suppressed. The choice of test depends on several factors, including patient compliance,
presence of uncontrolled hypertension, renal insufficiency, congestive heart failure, and local
expertise.