Hyperaldosteronism (HA) is a particular pathological condition characterized by an overproduction of aldosterone from the adrenal glands which causes the plasma potassium levels to decrease.
Primary HA is frequently asymptomatic, especially the mild cases. On the contrary, if signs manifest themselves, they are usually connected with hypertension and hypokalemia. The hypertension-related signs include headache, facial flushing and weakness, as well as visual impairment, impaired consciousness and seizure in the worst cases. The hypokalemia-related signs, instead, include conspitation, polyuria, polydipsia, as well as paralysis and problems with cardiac rhythm  when the plasma levels are very low. Since insulin secretion is dependent to potassium concentration and might be impaired by hypokalemia, hyperglycemia can occur as additional sign.
The signs which characterize secondary HA include the ones seen above  , plus a series of other symptoms related to the primary etiological factors such as flushing, diaphoresis, anxiety attacks, hematuria and abdominal fullness. Other signs include myalgia, tremor, muscle cramps, flaccid paralysis and hyporeflexia, which tend to appear in the most severe states of hypokalemia.
Entire Body System
Hypertension, polyuria, polydipsia, fatigue, tinnitus, paresthesia, and paralysis of variable duration (from 1 hour to weeks), failure to thrive, and muscle loss. [accessanesthesiology.mhmedical.com]
We describe a 62-year-old man who presented with fatigue and dizziness 2 weeks after unilateral adrenalectomy for aldosterone-producing adenomas. Physical examination showed decreased skin turgor and postural hypotension. [ncbi.nlm.nih.gov]
Their symptoms are often vague and may include headaches, fatigue, muscle weakness, thirst and frequent urination. [oregonclinic.com]
Too much aldosterone leads to the retention of sodium and loss of potassium, resulting in chronic high blood pressure in patients along with a host of other symptoms including fatigue, sleep apnea, heart arrhythmia and diabetes. [cedars-sinai.org]
<http://www.loripuente.com/myeloma-fatigue/ >. Bazos, M. J.. "Hyperaldosteronism.". N.p., n.d. Web. <http://www.healthcoachmd.com/handouts/hyperaldosteronism.html >. "Male and Female Signs." PSDGraphics. N.p., 16 Jun 2009. Web. [slideshare.net]
RESULTS: Of 3428 hypertensive patients, 575 (17%) had hyperaldosteronism. [ncbi.nlm.nih.gov]
However, patients may continue to be hypertensive and require lifelong antihypertensive therapy. Risk factors for long-term hypertension include older age at diagnosis. [patient.info]
A tale of two patients with Mendelian hypertension. Hypertension. 2008; 51 609-614 10 Sutherland DJ, Ruse JL, Laidlaw JC. Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. [doi.org]
- Muscle Cramp
Other signs include muscle pain, tremor, muscle cramps, flaccid paralysis and hyporeflexia, which tend to appear with the lowest level of potassium. Treatment includes drugs called aldosterone antagonists. [symptoma.com]
Very low levels of potassium can lead to: Weakness Irregular heart rhythm Muscle cramps Excess thirst or urination Oct. 09, 2019 AskMayoExpert. Primary aldosteronism. Mayo Clinic; 2018. Kellerman RD, et al. Hyperaldosteronism. [mayoclinic.org]
The hypokalemia (low potassium level) can cause symptoms like fatigue, numbness, increased urination, increased thirst, muscle cramps, and muscle weakness. [columbiasurgery.org]
While it doesn’t always cause symptoms, more moderate cases of hypokalemia may cause: fatigue muscle cramps increased thirst increased urination muscle weakness palpitations There are two types of hyperaldosteronism, known as primary and secondary hyperaldosteronism [healthline.com]
The diagnosis of HA is mainly based on laboratory studies, in particular tests for renal function, renin activity and aldosterone levels, which should be performed when the patient has been off diuretics, beta-blockers and dihydropyridine calcium-channel blockers for several weeks. The aldosterone/renin levels might be difficult to interpret, and doctors could need appropriate clinical guidelines which take into consideration the clinical history of the patient as well as the data coming from the imaging studies .
Electrocardiography should also be performed, to detect any sign of arrhythmias due to the marked hypokalemia. Imaging studies can be very useful in the diagnosis of HA since they can help localize adrenal adenomas and hyperplasias. The most important imaging techniques used include CT and MRI scans, but single-photon emission computed tomography (SPECT) or positron emission tomography (PET)/CT are also frequently employed.
Adrenal venous sampling is another important test for the diagnosis of HA, which can help distinguish between unilateral and bilateral adrenal diseases and localize the cause of primary HA, even though it is technically very challenging and not generally preferred among clinicians. Inherited forms of HA, instead, can be easily diagnosed through genetic testing, appropriately and carefully planned in advance.
The medical treatment of HA is mainly based on the use of aldosterone antagonists, like spironolactone , amiloride  and eplerenone. These should be integrated by potassium chloride supplements, both of natural and pharmaceutical nature.
Surgery is used especially with the presence of adenomas, and mainly consists in adrenalectomy. One of the main complications of the surgical procedure is the persistence of hypertension due to the deep effect of the previous hypertensive states on the vasculature.
The prognosis of HA is generally very good, especially in younger patients due to the shorter duration of the disease and the lower prevalence. However, complications are frequent, especially in primary HA which can often cause vascular, renal, and cardiac problems. Hypokalemia can be frequently observed in patients with adenomas and in those previously receiving treatment with diuretics for hypertension. Very frequent are also neuromuscolar complications, like weakness, constipation, polyuria, polydipsia, and cardiac fibrosis.
There are several etiological factors responsible for the occurrence of HA. The causes of primary HA include bilateral idiopathic adrenal hyperplasia , adrenal adenoma, primary adrenal hyperplasia, and familial hyperaldosteronism. Some cases of primary HA can also have genetic origin, like the mutations of the gene KCNJ5 , a particular G protein-gated ion channel . The causes of the secondary HA include edema disorders (especially cardiac failure and nephritic syndrome), renovascular hypertension, renin-producing tumors and pregnancy .
It is important to notice that sometime HA might be mimicked by other pathological conditions with similar clinical manifestations, such as primary glucocorticoid resistance, Liddle syndrome, or gain of function mutations of the mineralocorticoid receptor .
Primary HA is very rare in children, and the patients affected by it represent more than 10% of all hypertensive cases and 17 to 23% of the hypertensive population with resistance to treatment     . The inherited forms of HA are also quite rare, accounting for just 1% of the cases, and they are most likely to occur during childhood and adolescence. Secondary HA, instead, tends to be more frequent in adults, accounting for 15% of the subjected affected by hypertension with elevated levels of plasma renin activity.
As previously mentioned, inherited forms of HA tend to appear much more frequently among children, while the not-inherited ones, especially the forms of secondary HA, tend to appear more frequently in adulthood. Statistical data suggest that HA has a female predominance in adulthood, but there is no equivalent information available regarding children. Furthermore, people with African origins are at higher risk for hypertension-related morbidity and mortality than people with Caucasian ancestry.
Potassium is an essential component for the correct functioning of many organic systems, especially the muscular and the nervous ones. In these potassium serves to depolarize cell membrane after the passing of an action potential. Therefore, maintaining an appropriate potassium concentration is paramount for the body, and any deviation from the proper physiological range might have severe consequences. In particular, when the potassium concentration is low, repolarization is impaired resulting into a state of permanent hyperpolarization around the muscle or nerve cell. As consequences, higher electrical stimuli are needed to depolarize the membrane and start a new action potential. This is the reason why a great part of the HA clinical manifestation consists in neurological and muscular signs such as weakness and myalgia. When hyperpolarization develops in heart muscle cells, episodes of arrhythmias occur.
Around 99% of the cases of primary HA are due to aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). APAs are benign adenomas less than 2 cm in diameter, while IHA is a thickening of the adrenal cortex. Both these pathological conditions are responsible for the increased aldosterone production. The other 1% of the cases is due to inherited forms of primary HA and include familial hyperaldosteronism type I, II, and III. All these forms are due to mutations in the keys genes controlling aldosterone synthesis and regulation, such as CYP11B1, CYP11B2, G151R, and G151E   .
The pathophysiology of secondary HA is more complex, since this conditions is due to a diverse groups of disorders which are characterized by the physiologic activation of the renin-angiotensin-alsosterone (R-A-A) axis. In this case HA is the result of another problem elsewhere in the body, such as elevated plasma renin activity, renal artery stenosis, renal failure or tumors. In other words, any condition which can influence renin-angiotensin-alsosterone axis might cause secondary HA.
There is no suggested measure to prevent HA, apart from following a healthy lifestyle and diet, practicing daily physical exercises and sleeping well with the appropriate number of hours. Experts also highly recommend to avoid drinking, smoke and harmful substances which predispose the human body to develop tumor masses and abnormal hormone production. Regular endocrine checkup is also highly advised.
Aldosterone is one of the major steroid hormones produced by the outer section of the adrenal cortex, the zona glomerulosa . This compound plays a pivotal role in blood pressure regulation, by acting on the distal tubules and collecting ducts of the renal nephron. In particular, aldosterone causes an increase in the reabsorption of ions and water, indirectly fostering the increase of blood pressure and volume. Its action in the resin-angiotensin system is counterbalanced by the atrial natriuretic peptide, a powerful vasodilator secreted by the heart muscle cells    to reduce blood pressure in the homeostatic control.
During HA the secretion of aldosterone increases, causing an elevated sodium reabsorption and the loss of potassium and hydrogen ions. These elevated levels of aldosterone can be independent from the renin-angiotensin system or due to high levels of renin connected to problems occurred elsewhere in the body. In the first case HA in also known as primary HA while in the second it is also known as secondary HA.
Hyperaldosteronism (HA) is a disorder characterized by an overproduction of the hormone aldosterone from the adrenal glands which causes the plasma potassium levels to decrease. Aldosterone is one of the major steroid hormones produced by the outer section of the adrenal cortex and it plays a pivotal role in blood pressure regulation. There are two forms of HA known as “primary HA” and “secondary HA”.
The main clinical manifestations of primary HA include headache, facial flushing and weakness, as well as visual impairment, impaired consciousness and seizure in the worst cases. The signs which characterize secondary HA include the ones seen above, plus a series of other symptoms such as flushing, sweating, anxiety attacks, hematuria and abdominal fullness. Other signs include muscle pain, tremor, muscle cramps, flaccid paralysis and hyporeflexia, which tend to appear with the lowest level of potassium.
Treatment includes drugs called aldosterone antagonists. There is no suggested measure to prevent HA, apart from following a healthy lifestyle and diet, practicing daily physical exercises and sleeping well with the appropriate number of hours. Experts also highly recommend to avoid drinking, smoke and harmful substances which predispose the human body to develop tumor masses and abnormal hormone production. Regular endocrine checkup is also highly advised.
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