The disease is a rare autosomal dominant disorder. 1959 Ross reported the first case of a 13-year-old boy with hypertension and hypokalemia, suspected to be primary aldosteronism, but with very low urinary aldosterone, which did not improve after bilateral adrenalectomy. 1963 was named Liddle (Liddle) syndrome due to its detailed description by Liddle.
It is characterized clinically by hypertension, hypokalemia, hyporenin, hypoaldosteronism, and alkalosis. It is called pseudo-aldosteronism because the clinical presentation resembles primary aldosteronism, but the salt corticosteroid receptor antagonist spironolactone is ineffective against it.
Etiology and pathogenesis
Liddle syndrome is caused by a mutation in the epithelial sodium channel gene, which is a congenital abnormality of K and Na exchange in the distal renal tubules and collecting ducts, resulting in increased Na absorption and excessive K excretion. The erythrocytes also have a similar defect in sodium transport to that of the renal tubular cells, so the disease may be a manifestation of a systemic inherited sodium transport abnormality.
Clinical manifestations
The clinical presentation is similar to that of primary aldosteronism, with hypokalemia due to renal K loss, increased Na absorption and water retention, resulting in increased extracellular fluid volume, inhibition of the renin-angiotensin-aldosterone system, and decreased plasma renin, angiotensin, and aldosterone, even in the presence of a low sodium diet, standing position, and furosemide (tachyphylaxis). The adrenal gland function was normal, and there was no abnormal secretion of salt corticosteroids other than aldosterone, and renal function was normal. The hypertension of this disease is related to water and sodium retention from small arterial wall intracellular Na elevation, but there is no clinical edema, and the blood sodium is not necessarily elevated. Patients often have metabolic alkalosis, the degree of which is positively correlated with hypokalemia.
The clinical phenotype is highly variable depending on the genetic epistasis and the environment. Some patients have elevated blood pressure and normal potassium, others have low potassium and normal blood pressure, and others have normal blood pressure and potassium but low aldosterone levels. Plasma HCO3- levels also vary greatly, with some patients having no metabolic alkalosis and others having high HCO3- levels.
1. Hypertension
It often begins in childhood, but is mostly detected with adolescence or adulthood because of insidious symptoms. Mostly benign development, general antihypertensive treatment is ineffective, and Ativan does not work, but it is effective for aminoglutethimide and amiloride.
2.The manifestation of electrolyte disorder
It is also a common symptom, but about 50% of the patients have high blood pressure and normal blood potassium. Blood potassium is usually 2.4-2.8 mmol/L; sometimes it is only mildly low, 3.0-3.6 mmol/L. Very low blood potassium (1.8-2.2 mmol/L) is rarely seen. Metabolic alkalosis has elevated plasma HCO3- levels and elevated arterial blood pH. Blood sodium is increased and plasma renin and aldosterone levels are low. Urinary sodium is decreased, urinary potassium is increased, and urinary aldosterone levels are low.
3.Low renin, low aldosteronism
4.Paradoxical aciduria
Auxiliary examination
1, electrolyte disorders. Hypokalemia, hypomagnesemia, elevated blood sodium
2.Alkalosis
3, paradoxical acidic urine
4, urinary potassium, urinary magnesium elevation
5, low renin, low aldosterone
Diagnosis and differential diagnosis
For hypertension, hypokalemia, hypoaldosteronism can be proposed to diagnose this disease, if drugs, renal disease is excluded, and normal development of sex characteristics, to adrenocorticotropic hormone and anisodone is not effective, but to aminopterin and amiloride, can confirm the diagnosis.
The disease needs to be differentiated from primary aldosteronism, similar lesions caused by steroid medications, and renal disease.
Treatment
The disease is sensitive to salt restriction and sodium channel blockers (potassium-preserving diuretics). The potassium-preserving diuretics aminopterin and amiloride are effective and directly inhibit ENaC in the luminal membrane of the distal convoluted tubule and collecting duct, inhibiting Na+ reabsorption, resulting in increased urinary sodium and decreased urinary potassium. Strict salt restriction or moderate salt restriction plus potassium-protective diuretics can restore blood pressure to normal and restore the levels of plasma renin and aldosterone. Diuretic dosage: Aminopterin 100-300mg/d or Amiloride 5-20mg/d.
1.Low sodium diet
2. Potassium-preserving diuretics: aminopterin, amiloride
Thiazide diuretics can also be effective in treating Liddell syndrome. The mechanism is to correct hypernatremia by aggravating hypokalemia, but large amounts of potassium chloride supplementation are required; or to restrict sodium intake and take thiazide diuretics or aminopterin or amiloride.
Some patients may require a combination of calcium antagonists, or direct vasodilators.
Blood pressure and potassium should be monitored frequently during treatment, and the treatment plan should be adjusted according to blood pressure and potassium. If blood pressure is elevated, diuretics should be increased or sodium intake should be further restricted. If blood potassium levels are low, potassium chloride should be supplemented and aminopterin or amiloride should be increased. Potassium chloride should be used instead of potassium bicarbonate because the disease itself is alkaline and therefore alkaline potassium salts should not be used.