Renal tubular defect causing severe heritable
hypertension with hypokalemia and metabolic alkalosis.
Autosomal dominant trait with variable
penetrance. The variability is particularly evident with regard to serum
potassium concentration. Complete linkage of the disorder localized to gene
Liddle syndrome is the result of specific
mutations that prevent the binding of a regulatory protein to a specific
proline-rich region in the carboxyl terminal of the three subunits that
compose the epithelial sodium channel SCNN1. This prevents normal
degradation of the sodium channel so that the total number of channels is
increased, giving rise to constitutive activation of the channel, which
increases renal sodium absorption and excretes potassium despite the virtual
absence of mineralocorticoids, accounting for the clinical and biochemical
Liddle syndrome is characterized by hypertension,
hypokalemia, severe metabolic acidosis, decreased renin, and angiotensin.
The hallmark is the finding of markedly suppressed serum aldosterone levels
and the lack of response to administration of the mineralocorticoid receptor
Clinically, patients resemble those with primary
hyperaldosteronism. They may present with severe hypertension in their
teenage years, and this is usually the presenting symptom. Amiloride and
triamterene, but not spironolactone, are effective treatments for
hypertension and hypokalemia in patients with this syndrome as long as
dietary sodium intake is restricted. Hypokalemic metabolic alkalosis is
present. Renal function is normal apart from the inability to conserve
potassium. However, renal failure may occur secondary to hypertension. The
metabolic defects are completely corrected with renal transplantation.
Evaluate the extent and severity of
end-organ damage secondary to long-standing hypertension, in particular the
cardiorespiratory and neurologic systems. Optimize antihypertensive therapy;
addition of triamterene may help reverse the biochemical abnormalities.
Treatment of any volume deficit helps in the correction of a persistent
metabolic alkalosis and hypokalemia. Investigations: urea, creatinine,
electrolytes, ECG, chest radiography, echocardiography. A sedative
premedicant to reduce anxiety and its hypertensive response should be
The anesthetic technique should avoid
hypotensive and hypertensive events. Invasive arterial and central venous
pressure monitoring should be determined by the severity of cardiovascular,
neurologic, and renal impairment secondary to hypertension. Esmolol and
labetalol are useful antihypertensive agents. Regional techniques, by itself
or in conjunction with general anesthesia, offer excellent intraoperative
and postoperative analgesia and reduce considerably the stress response to
surgery. Capnography monitoring is essential as hyperventilation exacerbates
a preexisting metabolic alkalosis.
Hypokalemia and metabolic acidosis
may not only increase sensitivity to but may also prolong the duration of
action with nondepolarizing muscle relaxants. These problems should be
corrected before anesthesia.
Conn Syndrome: Potentially curable endocrine disorder resulting
from hyperaldosteronism; presents with symptoms associated with hypertension
Botero-Velez M, Curtis JJ, Warnock DG: Liddle's syndrome revisited—A
disorder of sodium reabsorption in the distal tubule. N Engl J Med
Palmer BF, Alpern RJ: Liddle's syndrome. ...