Emma Sy Moeis Division of Nephrology & Hypertension Department of Internal Medicine, Medical Faculty of Sam Ratulangi University, Manado

Blood pressure classification on people age > 18 y.o Adults on no antihypertensive medications and who are not acutely ill.
Category
Systolic (mm Hg) and or or or Diastolic (mm Hg) <80 80-89 90-99 100

Normal < 120 Prehypertension 120-139 Hypertension 140-159 Stage 1 Stage 2 > 160

Primer (essential) No specific causes that can be identified

Hypertension

95% of all hypertension cases

Secondary

Essential

Causes can be identified 5% of all hypertension cases Kidney disease is the main cause (90%) of all secondary hypertension cases

Secondary Causes

NonEndocrine Hypertension

Endocrine Hypertension

 Renal parenchymal disease: acute nephritis, chronic glomerulonephritis, etc.

Renovascular disease: renal artery stenosis, atherosclerosis, fibroplasia, etc.

Endocrine causes

Pheochromocytoma Mineralocorticoid excess (e.g., primary hyperaldosteronism) Glucocorticoid excess (e.g., Cushings syndrome) Acromegaly

Diabetes mellitus Obesity Congenital adrenal hyperplasia Estrogen-induced hypertension Pregnancy-induced hypertension Renin-secreting tumors Hypothyroidism Hyperthyroidism Liddle syndrome

a 47 year old woman referred because of poorly controlled hypertension. She has leg cramps and polyuria, but no episodes of headache, sweating or palpitations. There is no family history of hypertension. She is not obese. HR: 78/min and BP 160/98 mmHg, the exam is otherwise normal. Plasma potassium: 2.5 mM

1. 2.

3.

What symptoms are caused by hypertension? By severe hypokalemia? What are the three major endocrine causes of hypertension (ie, disorder in which the majority of patient has high blood pressure)? How common are they in patient with hypertension? Which endocrine cause of hypertension is most likely in this patient? What test should be done now?

Symptoms caused by hypertension: None Symptoms caused by severe hypokalemia: Leg cramps polyuria

1. What symptoms are caused by hypertension? By severe hypokalemia? 2. What are the three major endocrine causes of hypertension (ie, disorder in which the majority of patient has high blood pressure)? How common are they in patient with hypertension? 3. Which endocrine cause of hypertension is most likely in this patient? What test should be done now?

Three major endocrine causes of hypertension: Primary hyperaldosteronism Pheochromocytoma Cushing syndrome In patient with hypertension, approximately <5% of patient has identifiable underlying cause referred as Secondary hypertension each of the above causes are rare, accounting for <1% of hypertension.

1. 2.

3.

What symptoms are caused by hypertension? By severe hypokalemia? What are the three major endocrine causes of hypertension (ie, disorder in which the majority of patient has high blood pressure)? How common are they in patient with hypertension? Which endocrine cause of hypertension is most likely in this patient? What test should be done now?

The most likely endocrine causes of hypertension in this case is Primary Hyperaldosteronism
Indication for screening for Primary Hyperaldosteronism 1. Hypertension with hypokalemia 2. Refractory hypertension (BP >140/90 despite 3 antihypertensives) 3. Hypertension with adrenal incidentaloma (incidental adrenal tumor) 4. Juvenile patient with hypertension and positive family historyI

Test should be done now: Plasma Renin Activity (PRA) Ratio of Plasma Aldosterone to PRA

A blood sample is drawn with the patient seated Plasma Aldosterone: 25 ng/dl Plasma Renin Activity: <0.5 ng/ml/hr After these results are available, another test is performed. With the patient supine, 2 liters of normal salin (0.9% NaCl) is infused IV over 4 hr. Plasma aldosterone at the end of the infusion is 20 ng/dl

4. Do these result establish a diagnosis? Why were aldosterone and renin activity measured simultaneously? Can a diagnosis be made by measuring either hormone level alone? 5. What is the purpose of saline infusion? 6. What are the major causes of this syndrome? Why is it important to distinguish between them, and how can this be done?

Yes, these result establish diagnosis of primary hyperaldosteronism

Plasma Aldosterone: 25 ng/dl Plasma Renin Activity: <0.5 ng/ml/hr ARR = kdr aldosteron plasma (ng/dL) kdr renin plasma (ng/dl/jam)
DIAGNOSTIC TESTS FOR PRIMARY HYPERALDOSTERONISM Screening: plasma potassium (while not treated with diuretics) Definitive: plasma aldosterone (ng/dl) / plasma renin activity (ng/ml/hr) ratio: <30: probably not primary hyperaldosteronism >50: almost certainly primary hyperaldosteronism
aldosterone suppression: 2 liters 0.9% (normal) saline IV over 4 hrs with patient supine. Normal: plasma aldosterone <4 ng/dl Primary hyperaldosteronism : plasma aldosterone > 20 ng/dl

Plasma Aldosterone: 25 ng/dl Plasma Renin Activity: <0.5 ng/ml/hr

Adapted from Young WF Jr, Hogan, MJ. Renin-independent hypermineralocorticoidism. Trends in Endocrinology and Metabolism 1994;5:97106.

The test should be measured simultaneously because the two hormone may has normal variation caused by body position, salt intake and other factor that affected ECF volume, so for the purpose of having the ratio, it should be taken in the same time The diagnosis should be performed by both test of hormone level

4. Do these result establish a diagnosis? Why were aldosterone and renin activity measured simultaneously? Can a diagnosis be made by measuring either hormone level alone? 5. What is the purpose of saline infusion? 6. What are the major causes of this syndrome? Why is it important to distinguish between them, and how can this be done?

The purpose of NaCl 0.9% iv infusion is to demonstrating that plasma aldosterone cannot be suppressed by ECF volume expansion

Confirmatory test
Oral sodium loading test

Procedure
Sodium intake > 200 mmol (~6 g) per day, verified by 24-hour urine sodium. Adequate slow-release potassium chloride supplementation. Urinary aldosterone is measured in the 24hour urine collection from morning of day 3 to morning day 4.
In recumbent position at least 1 hour before and during infusion 2 ltr NaCl 0.9% IV over 4 hrs, start at 8:009.30am Blood sample (renin, aldosterone,cortisol & plasma Kalium) are drawn at time 0 & after 4 hrs with BP & HR monitored throughout the test.

Interpretation
Unlikely PA : Urinary aldosterone : < 10 mcg/24 hour (27.7 nmol/day) in the absence of renal disease Highly likely PA : Urinary aldosterone : Mayo Clinic : > 12 mcg/24 hr (>33.3 nmol/d) Cleveland Clinic : > 14 mcg/24-hr (38.8 noml/d)
Unlikely PA : aldosterone levels < 5 ng/dL Very Probably PA : Aldosterone levels > 10 ng/dL Indeterminate levels 5 - 10 ng/dL

Concerns
Should not be performed in patients with : - Severe uncontrolled Hpt - renal insufficiency - cardiac insufficiency - Cardiac arrhytmia - Severe hypokalemia

Saline infusion test

Should not be performed in patients with : - Severe uncontrolled Hpt - renal insufficiency - cardiac insufficiency - Cardiac arrhytmia - Severe hypokalemia

Confirm atory test

Procedure

Interpretation

Concerns

Fludrocort Fludrocortisone oral : 0.1 mg per isone 6 hrs for 4 days suppressi Slow-release KCl supplements on test (per 6 hrs, measured 4 x/d, close to 4.0 mmol/L) Slow-release NaCl supplements (30 mmol 3 x with meals) & Dietary salt to maintain urinary sodium excretion rate at least 3 mmol/kgBW Day 4: measured - plasma aldosterone & PRA at 10 am, in seated posture - plasma cortisol: measured at 7 am & 10 am Captopril Challenge test Captopril 25-50 mg oral after sitting/standing at least 1 hr. Measured PRA, plasma aldosterone, cortisol at time 0, 1 or 2 hrs after challenge with remaining seated.

Confirms PA : - upright plasma aldosterone > 6 ng/dL (day 4 at 10 am) - PRA < 1 ng/ml/h - plasma cortisol : lower than the value obtained at 7 am (to exclude confounding ACTH effect)

FST is the most sensitive for confirming PA: - less likey to provoke nonrenin-dependent alteration of aldosterone levels - allows for the potentially confounding effects of potassium to be controlled, for ACTH(via cortisol) to be monitored & detected - Safe when performed by experienced hands Reports of substantial number of false negative or equivocal results.

PA : - Plasma aldosterone remain elevated - PRA remains suppressed Difference APA & IHA: - Some decrease of aldosterone levels is occasionally seen in

4. Do these result establish a diagnosis? Why were aldosterone and renin activity measured simultaneously? Can a diagnosis be made by measuring either hormone level alone? 5. What is the purpose of saline infusion? 6. What are the major causes of this syndrome? Why is it important to distinguish between them, and how can this be done?

The major causing of this syndrome are: Aldosterone-secreting adrenal adenomas

(2/3 of cases) Bilateral adrenal hyperplasia

The importance to distinguish between them is due to different management. In aldosterone-secreting adrenal adenomas, surgery is an option while in bilateral adrenal hyperplasia medical management is needed This can be done by CT scan examination

Abdominal CT scan shows a 2 cm mass in the right adrenal

Answer
This finding confirm the diagnosis of Aldosteronesecreting adenomas on right adrenal as the cause of primary hyperaldosteronism

Adapted from Young WF Jr, Hogan, MJ. Renin-independent hypermineralocorticoidism. Trendsin Endocrinology and Metabolism 1994;5:97106.

Diganosis and Treatment Algorithm for Primary Hyperaldo steronism