Pathogenesis (disease development)
Conn syndrome involves primary hyperaldosteronism (overproduction of aldosterone).
The group of forms of primary hyperaldosteronism* includes:
- Idiopathic hyperaldosteronism (IHA) with bilateral adrenocortical hyperplasia (65%).
- Aldosterone-producing adenoma (APA) (Conn syndrome; 30%).
- Primary unilateral adrenal hyperplasia (3%).
- Aldosterone-producing adrenocortical carcinoma (malignant tumor; 1%).
- Aldosterone-producing tumor of the ovary/ovary (<1%).
- Glucocorticoid-suppressible primary hyperaldosteronism (GSH; synonym: dexamethasone-suppressible hyperaldosteronism, glucocorticoid-remediable aldosteronism, GRA).
- Familial form (familial hyperaldosteronism type I; <1%).
- Familial hyperaldosteronism type II, type III (frequency unknown).
- Ectopic aldosterone-producing adenomas/carcinomas (<0.1%).
* In primary hyperaldosteronism (Conn syndrome), the adrenal cortex produces increased aldosterone without activation by the renin-angiotensin-aldosterone system (RAAS). In secondary hyperaldosteronism, the adrenal cortex produces increased aldosterone through chronic activation of the renin-angiotensin-aldosterone system (RAAS).
Aldosterone is a mineralocorticoid produced in the adrenal cortex. It is an important link in the renin-angiotensin-aldosterone system (RAAS), which helps regulate blood pressure and salt balance. Increased renin is produced when a lack of sodium in the blood or hypovolemia (decreased blood volume) is determined by the receptors. Renin in turn stimulates the activation of angiotensinogen to angiotensin I, which is then converted to angiotensin II by other hormones. Angiotensin II leads to vasoconstriction (narrowing of blood vessels) and thus to an increase in blood pressure. In addition, it leads to a release of aldosterone, which results in sodium and water reabsorption.
In the case of excess aldosterone, sodium and body water are retinated (retained) and potassium is lost. This subsequently causes increased secretion of atrial natriuretic peptide (ANP) and thus normalization of sodium excretion. Potassium loss and fluid retention remain and lead to the leading symptoms of hypokalemia (potassium deficiency) and hypertension (high blood pressure).
In addition to the production of aldosterone, there is also a marked glucocorticoid excess (11,306 μg/24 h; control group 8,262 μg/24 h). This prompted the authors, who were able to prove this fact for the first time, to give the observation the name Connshing syndrome, which is a combination of Conn syndrome and Cushing syndrome. Patients with glucocorticoid excess benefited esp. from adrenalectomy (adrenalectomy).
Etiology (Causes)
Biographic Causes
- Genetic burden
- Genetic risk is dependent on genetic variants: Mutation in the ClC-2 chloride channel causing depolarization due to efflux of Cl- through the permanently open channel; consequence of this mutation is angiotensin II-independent overproduction of aldosterone (→ hypertension (high blood pressure)).
- Genetic diseases
- Glucocorticoid-suppressible primary hyperaldosteronism (GSH; synonym: dexamethasone-suppressible hyperaldosteronism, glucocorticoid-remediable aldosteronism, GRA).
- Familial form (familial hyperaldosteronism type I; <1%).
- Familial hyperaldosteronism type II, type III (frequency unknown).
- Glucocorticoid-suppressible primary hyperaldosteronism (GSH; synonym: dexamethasone-suppressible hyperaldosteronism, glucocorticoid-remediable aldosteronism, GRA).
Causes related to disease
Neoplasms – tumor diseases (C00-D48).
- Aldosterone-producing adenoma of the adrenal gland – benign neoplasm.
