Primary hyperaldosteronism

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Classification according to ICD-10
E26.0 Primary hyperaldosteronism
  • Conn syndrome
ICD-10 online (WHO version 2019)

The primary hyperaldosteronism (also Conn syndrome and Connsche disease called) is in its classic, with potassium deficiency associated form with a frequency of about 1% of the rarer causes of hypertension . According to recent epidemiological findings, up to 10% of high blood pressure patients have primary hyperaldosteronism , which, in contrast to the classic form, is associated with normal potassium levels.


In 1955, the American endocrinologist Jerome W. Conn described the case of a 34-year-old female patient who presented with pronounced hypertension. The patient suffered from muscle cramps and paralysis, among other things . At that time, Conn determined by laboratory tests to be hypokalemia , hypernatremia and metabolic alkalosis . He was able to detect the steroid hormone aldosterone in the urine . The case described by Conn became known as "Conn syndrome" and was due to an adenoma of the adrenal cortex with autonomous aldosterone production. The clinical picture is therefore referred to as "primary hyperaldosteronism".


Primary hyperaldosteronism (PHA) is a partially or completely autonomous production of the steroid hormone ( mineralocorticoids ) aldosterone, which is formed in the zona glomerulosa of the adrenal cortex.


Hypertension and hypokalaemia follow an autonomous, increased secretion of aldosterone . The plasma renin activity (PRA) in the context of the renin-angiotensin-aldosterone system (RAAS) is typically reduced. In contrast, in secondary hyperaldosteronism ( e.g. as a result of cirrhosis of the liver ), both aldosterone and PRA are increased.

Three causes of primary aldosteronism are described. These include bilateral (bilateral) adrenal cortical hyperplasia , aldosterone-producing adrenal adenoma and familial hyperaldosteronism types I – III (see below). Due to the increased aldosterone secretion, there is an increased excretion of potassium and an increase in sodium absorption, which is associated with water retention, in accordance with the effect of the hormone. The increased water retention leads to greatly increased blood pressure.

Genetic causes

If there is a positive family history of primary aldosteronism and young adulthood, familial aldosteronism must be suspected. In spite of the clear genotype, the phenotype often varies . There are three types of familial hyperaldosteronism (FH):

  • Type I : This is glucocorticoid- suppressible hyperaldosteronism (GSH), which was first described in 1966 . The disease is autosomal - dominant inherited and is based on a chimeric gene from the ACTH -dependent 11-β-hydroxylase (CYP11B1) and the angiotensin-II-dependent aldosterone synthase CYP11B2. The result is a hybrid gene that expresses an enzyme that now falsely produces ACTH-dependent aldosterone. As a therapy option, lowering the ACTH secretion by means of a low dose of dexamethasone is available (for more see therapy).
  • Type II : The clinical picture of type II does not differ from that of type I, but cannot be suppressed by dexamethasone. A specific genotype of this disease has not yet been localized. Diagnosis is based on family history. There is an association with the gene locus of chromosome 7 gene locus p22. The therapy corresponds to that of the incident PHA.
  • Type III : There is currently no identified genotype for this type either. It differs from type II in that it manifests very early within the first decade of life, pronounced bilateral hyperplasia of the adrenal glands and very high serum levels of 18-oxocortisol and 18-hydroxycortisol (in addition to hyperaldosteronism). In contrast to type I, it cannot be suppressed; dexamethasone therapy even leads to an exacerbation . The drug-based antihypertensive therapy failed in the case described, so that bilateral removal of the adrenal glands was the only curative therapy option. In 2012, type III mutations in the selectivity filter of the potassium channel KCNJ5 were identified as the genetic cause of FH. The same genetic change is found in about 30% of the sporadic aldosterone-producing adenomas.


Except for familial type I of primary hyperaldosteronism, all other forms lead to hyperplasia or an adenoma of the adrenal cortex, which is responsible for the increased aldosterone production.

If it was previously assumed that an aldosterone-producing adenoma was the cause in most patients, this is not supported by the current study situation. Instead, it is believed that less than 30% of all cases are caused by adrenal adenoma. In more than 70% it is mostly an idiopathic bilateral adrenal cortex hyperplasia. The genetic forms only have a share of approx. 1%.


Primary aldosteronism is one of the so-called secondary forms of hypertension. In contrast to primary essential hypertension, it therefore offers a causal therapy option. The proportion of hypertensive patients with secondary hypertension is around 20%. With the severity of the hypertension, the proportion of patients suffering from PHA also increases. The prevalence is currently estimated to be between 3 and 14%, making PHA one of the most important forms of secondary hypertension alongside sleep-related hypertension (up to 5%) and renal artery stenosis (1–4%). Up to 20% of patients with refractory hypertension, in whom drug therapy fails or only works inadequately, suffer from a PHA.

If a distinction is made between patients with normal and reduced serum potassium, the prevalence of an adenoma is about 65% in the group of hypokalemic patients than in the group of normokalemic patients (<30%), with the prevalence of hypertensive patients with hypokalemic PHA at is less than 1%. The prevalence of hypertensive patients with normocalemic PHA is between 3–14%.

The peak of the disease is between the ages of 30 and 50.


The symptoms can be classified according to the physiological effects of aldosterone that lead to hypertension and electrolyte changes:

The symptom complex of hypertension includes headache, head flush, chest tightness and angina pectoris , shortness of breath, ringing ears, nosebleeds , visual disturbances and others.

The symptoms of hypokalaemia are diverse and essentially include cardiac arrhythmias and EKG changes (flattening of the T wave, lengthening of the QT interval), muscle weakness through to paresis , weakening of reflexes and tetany . Possibly. ADH-refractory tubulopathy develops with polydipsia and polyuria (renal diabetes insipidus).

In the context of blood pressure derailments, sudden neurological and cardiovascular symptoms such as syncope , severe headaches , nosebleeds, but also angina pectoris and cardiac decompensation with previously damaged hearts can occur. If such a hypertensive crisis is accompanied by the symptoms mentioned, it is a hypertensive emergency which must be clarified in any case and treated medically.


The diagnosis of the PHA is based on two pillars: On the one hand, the general diagnosis of hypertension, on the other hand, the dedicated diagnosis of the presence of a PHA. The general diagnosis of hypertension includes the exact diagnosis of the severity of the hypertension and, accordingly, clarification of the secondary causes, which are only discussed here within the scope of the PHA. A PHA should be suspected if the following points occur:

  • 2nd to 3rd degree hypertension
  • Refractory hypertension
  • Hypokalemic hypertension
  • Hypertension with adrenal incidentaloma (randomly diagnosed mass of the adrenal glands)
  • Hypertension with a positive family history
  • First-degree hypertensive relatives with PHA

Screening for the presence is possible by measuring renin and aldosterone in the serum in the morning. In the presence of a PHA, the aldosterone-renin quotient (ARQ) is greatly increased due to the strong suppression of the renin with increased aldosterone. It is important that with this diagnosis, drugs that influence the renin-angiotensin-aldosterone system are avoided at an early stage, as these can strongly falsify the diagnosis. To confirm this, a so-called salt exposure test is recommended, which should significantly reduce the aldosterone secretion in healthy individuals. If this is not the case, the suspicion of a PHA is confirmed.

For further diagnostics, computed tomographic imaging (or magnetic resonance imaging ) is recommended , which can possibly depict hyperplasia or an adenoma. For confirmation or further diagnostics in the case of borderline or unclear findings, it is advisable to take blood from the adrenal vein separately. The determined aldosterone secretion from the respective adrenal gland compared to the opposite side enables the exact diagnosis of the presence of an adenoma or bilateral hyperplasia.


In the presence of an aldosterone-producing adenoma, adrenalectomy (surgical removal of the adrenal gland) is the treatment of choice. If there is bilateral adrenal hyperplasia, therapy with a mineralocorticoid receptor blocker ( aldosterone antagonists ; e.g. spironolactone , eplerenone ) should be started. Depending on the success of the therapy, persistent high blood pressure must also be treated with medication.

Dexamethasone-suppressible primary aldosteronism (familial type I) is treated with glucocorticoids (dexamethasone). The suppression of ACTH, which is the stimulus for the mutated aldosterone synthase, reduces aldosterone production and thus blood pressure.

Conn register

The National Conn Register was founded in Munich in 2006. It is used for multicenter data collection on diagnostics, therapy and the course of the disease of Conn syndrome (primary hyperaldosteronism). The participating institutions include centers that specialize in treating patients with Conn's syndrome.

Web links

Individual evidence

  1. Martin Reincke, Lysann Seiler, Lars C Rump: Normokalaämischer primary hyperaldosteronism . In: Deutsches Ärzteblatt , 100, issue 4, January 24, 2003, pages A-184 / B-169 / C-165
  2. ^ JW Conn: Primary aldosteronism . In: J Lab Clin Med , 1955, 45 (4), pp. 661-664
  3. I. Quack, O. Vonend, LC Rump: Familial hyperaldosteronism I-III. In: Hormone and metabolic research. Volume 42, Number 6, June 2010, pp. 424-428, ISSN  1439-4286 . doi : 10.1055 / s-0029-1246187 . PMID 20131203 . (Review).
  4. a b C Schirpenbach, F Segmiller, S Diederich et al .: The diagnosis and treatment of primary hyperaldosteronism in Germany - results on 555 patients from the German Conn Registry . In: Dtsch Arztebl Int , 2009, 106 (18), pp. 305-311
  5. Gerd Herold: Internal Medicine . 2010, pp. 744, 562
  6. Michael Stowasser, Paul J Taylor, Eduardo Pimenta, Ashraf H Al-Asaly Ahmed, Richard D Gordon: Laboratory investigation of primary aldosteronism . In: The Clinical Biochemist. Reviews / Australian Association of Clinical Biochemists . 31, No. 2, May 2010, ISSN  0159-8090 , pp. 39-56. PMID 20498828 .