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Clarification of hypertension – Diagnosis of
primary hyperaldosteronism

Marc Beineke
The significance of the aldosterone/renin
ratio (ARR) in the diagnosis of normo-
alaemic and hypokalaemic primary hyper-
aldosteronism, the most common causes
of secondary hypertension
Epidemiology of primary
On the basis of the new data, which were ob- tained by determining the aldosterone/renin ratio (ARR), the frequency of PH in hyper- Primary hyperaldosteronism (PH) is the most tensives – 5-13% – is much higher than previ- common cause of secondary hypertension. ously suspected (0.1-1%) [1, 2, 3, 19]. Apart from hypertension, hypokalaemia was hitherto considered to be the classical cardinal On the cautious assumption that PH is the un- symptom. Its presence was therefore also derlying cause in 5% of al hypertensives, over usual y a prerequisite for further diagnostic 800,000 people in Germany would be affected clarification in respect of PH. However, numer- by this diagnosis. Aldosterone-producing ous new studies in normokalaemic hyper- adenoma as a cause of hypertension can in tension patients now show that serum principle be cured by surgery. potassium levels are within the reference range in approximately 90% of PH patients. ■ Aetiology of primary hyperaldosteronism

 Aldosterone-producing adenoma (APA = Conn's syndrome) (approx. 30-40%), unilateral  Idiopathic hyperaldosteronism (IH) (approx. 60%), bilateral  Macronodular adrenocortical hyperplasia (MNH), (1-5%), unilateral or bilateral  Aldosterone-producing carcinoma (adrenal or ectopic, e.g. ovarian) (1%)  Familial hyperaldosteronism (FH)* (1-5%), type I (= GSH**) and II : Classification of primary hyperaldosteronism (PH) [1, 2] The stated frequencies refer to the total PH group (normokalaemic and hypokalaemic). If – as before – only the hypokalaemic PH patients are included, APA is the most common cause, at around 70% [3]. * For details of diagnosis and treatment, see [3]. ** GSH = glucocorticoid-suppressible hyperaldosteronism ■ Optimized PH screening: the
aldosterone/renin ratio (ARR)
Since the diagnosis of PH opens up effective, inexpensive treatment options [4, 5], ex- tended laboratory screening with additional determination of the aldosterone/renin ratio (ARR), including normokalaemic patients, is now general y accepted [1, 2, 17, 19]. hyperaldosteronism Primary aldosterone deficiency Plasma aldosterone (ng/dl) Fig. 1: Classification of disturbances of the renin-angiotensin-aldosterone system using the aldosterone/renin ratio (ARR) and aldosterone. Marked in are the limits recommended by our laboratory for the identification of patients with PH (ARR: 30; aldosterone 15 ng/dl), according to [2, 9, 10, 17]. If the ARR is > 30 and aldosterone is < 15 ng/dl, further clarification in respect of PH may also be indicated and successful. ■ Optimized PH screening:
tween 8 and 12 o'clock (contraindication: target groups
heart failure, state after myocardial infarct; severe, uncontrol ed hypertension). In the fol owing groups of patients, optimized At 8 o'clock and 12 o'clock blood is col ected PH screening with additional determination of for analysis of plasma aldosterone and plasma the aldosterone/renin ratio (ARR) is recom- mended [1, 17, 19]: In patients without autonomous aldosterone ■ Hypertensives with hypokalaemia secretion, plasma aldosterone is suppressed by at least 50% by the infusion of saline, or ■ Hard-to-stabilize hypertensives with a aldosterone levels normalize. In PH, there is blood pressure > 140/90 despite no, or no clear, suppression of the elevated treatment with three antihypertensive baseline aldosterone values. The salt loading test should be performed under the same medication as the screening test [15]. The ■ Young hypertensives (< 30 years of fludrocortisone suppression test, which has age) with a positive familial history or a likewise been wel evaluated in the literature, cerebrovascular event is very expensive, because of the need to spend 5 days in hospital. Analysis of aldoster- ■ Incidentaloma (compressive process in one-18-glucuronide in 24-h urine under oral the adrenal gland) with hypokalaemia salt loading should only be carried out as an alternative if the salt loading test is contraindi- cated/impracticable. Administration of 3 x 2 g ■ Hypertensives with other signs of NaCl/day in addition to the normal diet (ap- secondary hypertension proximately 9 g NaCl/day) for a period of 3 days is recommended for this, to give a ■ Al hypertensives with first-degree daily sodium intake of roughly 260 nmol/day. relatives who had primary hyper- Since aldosterone-18-glucuronide represents only about 20% of total aldosterone secretion and there are no up-to-date evaluation stud- ■ Young hypertensives (< 40 years of ies, this test is less conclusive than the salt age) with a blood pressure > 160/100 loading test [15]. On the 3rd day of oral salt loading, aldosterone-18-glucuronide must be ■ Hypertensives with a blood pressure > in the normal range and urinary sodium in the check on salt supply must be > 200 mmol/ ■ Procedure if a pathological result
 Clarification of the aetiology in
is obtained in the PH screening
cases of confirmed diagnosis
 Confirmation of diagnosis
When the diagnosis of PH has been con- firmed, the aetiology is further investigated After a positive result in screening, the diag- using biochemical methods (analysis of aldos- nosis of PH must be confirmed with further terone, renin, and cortisol in the orthostasis test; 8 o'clock (recumbent position), 12 o'clock (standing)) and imaging techniques (CT or The principal confirmatory test recommended, MRI) [see 1, 2, 3]. For the orthostasis test, on the basis of its practicability (for out- care must be taken to ensure that the patient patients) and evaluation [15], is the salt load- remains constantly in horizontal position for at ing test: 2 litres of isotonic saline is infused least 8 h before the start of the test, into the patient, in a recumbent position, be- something which is only possible in an inpatient setting. After col ection of the first For patients with bilateral idiopathic hyperpla- sample of blood in the recumbent position, sia, the only thing left is drug treatment with a the patient is to adopt an erect posture for 4 mineralocorticoid receptor antagonist (e.g. h. Another blood sample is then col ected for spironolactone), possibly in combination with the analysis of aldosterone, renin, and cortisol ACE inhibitors and beta blockers [2]. in the standing position. A typical sign of an aldosterone-producing adenoma is an apparently paradoxical drop in ■ Pre-analysis and sampling for
the aldosterone concentration between 8 determination of the ARR
o'clock [recumbent position] and 12 o'clock [standing] in the orthostasis test, which can be explained by ACTH-dependence on ■ The patient should have been in an erect position (sitting, standing, or aldosterone secretion. walking) for at least 2 h before the In bilateral adrenocortical hyperplasia, on the other hand, preserved angiotensin II-depend- ■ Blood (EDTA blood) to be col ected ence on aldosterone secretion with an in- from the patient in an erect sitting po- crease of over 30% in aldosterone under sition between 8 and 10 o'clock in the orthostasis is typical. 30% of adenomas also morning after a 15-min phase at rest in show an increase in aldosterone in orthosta- a sitting position sis, however. If the results of the orthostasis ■ Since hypokalaemia leads to false- test and imaging techniques agree, the aim is positive results, this must be compen- to give the relevant specific therapy (adrena- lectomy or spironolactone therapy). If a clear potassium supplementation [15] differential diagnosis between adenoma and hyperplasia is not possible with these tests, ■ There should be no restriction of selective adrenal venous blood sampling sodium in the period before blood with analysis of aldosterone and cortisol is in- sampling (sufficient salt) dicated. Selective adrenal venous blood ■ Obtain 2 ml EDTA plasma by sampling should always be carried out, how- centrifuging the EDTA blood ever, if surgical treatment is probable [17]. ■ Transfer the EDTA plasma into a new Patients with aldosterone-producing adenoma tube label ed with a bar code with the typical y show an aldosterone/ cortisol ratio name of the material ("EDTA plasma") gradient of more than 5:1 to the adenoma- and patient data on affected side. [2]. Other sources speak of more than 2:1 [15, 16] or more than 3:1 [18]. ■ Some antihypertensives should be dis- continued for a certain period before If an aldosterone-producing adenoma is blood sampling [see Table 2] present, the treatment of choice is (laparo-scopic) adrenalectomy; long-term therapy ■ Request on the request form as: with spironolactone is an alternative ■ Flow diagram: Procedure to be followed if primary hyperaldosteronism is
suspected/to be excluded
Aldosterone/Renin ratio (If the salt loading test is contraindicated or impracticable: analysis of aldosterone-18- glucuronide in 24-h urine under oral salt loading) or fludrocortisone suppression Differential diagnosis CT or MRI of adrenals and renin- aldosterone orthostasis test Tumour, but increase in Unilateral tumour No tumour, but decrease in Adrenal vein catheterization to aldosterone/cortisol ratio hyperaldosteronism 2 Differential diagnosis and clarification of PH [according to 1, 2] Before surgical treatment, selective adrenal venous blood sampling with determination of the aldosterone/cortisol ratio should always be performed to confirm the diagnosis. Beta receptor blockers At least 2 weeks Imidazoline receptor antagonists (e.g. clonidine) At least 2 weeks Thiazide diuretics At least 2 weeks At least 2 weeks Calcium antagonists Alpha receptor blockers (e.g. doxazosin) Angiotensin II antagonists (sartans) At least 2 weeks Spironolactone, eplerenons, drospirenone, amiloride, triamterene At least 4 weeks References
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Institute for medical Diagnostics GmbH Dr. Marc Beineke, M.D., MSc. Konrad-Adenauer-Strasse 17 55218 Ingelheim, Germany Tel. +49-6132-781 – 203/224/165 Fax + 49-6132-781 – 236 Email:


Experimental Study of Cardiac Functionality for the Wellness of Individual by developing an Android Application Damanpreet Kaur Gowrishankar.S, Siddaraju Department of Computer Science and Engineering, Department of Computer Science and Engineering, Dr. Ambedkar Institute of Technology, Dr.Ambedkar Institute of Technology

Annals of Internal Medicine Systematic Review: Bisphosphonates and Osteonecrosis of the JawsSook-Bin Woo, DMD; John W. Hellstein, DDS, MS; and John R. Kalmar, DMD, PhD Osteonecrosis of the jaws is a recently described adverse side nate therapy is initiated in these patients to reduce the necessity effect of bisphosphonate therapy. Patients with multiple myeloma