Year : 2014 | Volume
: 25 | Issue : 4 | Page : 869--871
A case of liddle's syndrome; unusual presentation with hypertensive encephalopathy
Sunil Kumar Kota1, Siva Krishna Kota2, Sandip Panda3, Kirtikumar D Modi1,
1 Department of Endocrinology, Medwin Hospital, Hyderabad, India
2 Department of Anesthesia, Central Security Hospital, Riyadh, Saudi Arabia
3 Department of Cardiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
Sunil Kumar Kota
Department of Endocrinology, Medwin Hospitals, Nampally, Hyderabad -500 001, Andhra Pradesh
Liddle«SQ»s syndrome is a rare cause of secondary hypertension. Identification of this disorder is important because treatment differs from other forms of hypertension. We report an interesting case of a 35-year-old lady, a known diabetic and hypertensive patient, who presented with features of hypertensive encephalopathy. The family history was unremarkable. Past treatment with various combinations of antihypertensive medications including spironolactone, all at high doses, failed to control her blood pressure. Upon evaluation, the patient had hypokalemic alkalosis, low 24-h urine potassium and suppressed plasma renin activity. Although these findings were similar to hyperaldosteronism, plasma aldosterone was lower than the normal range. Blood pressure decreased markedly after administration of amiloride. Along with hyporeninemic hypo-aldosteronism, the non-responsiveness to spironolactone and good response to amiloride established the diagnosis of Liddle«SQ»s syndrome.
|How to cite this article:|
Kota SK, Kota SK, Panda S, Modi KD. A case of liddle's syndrome; unusual presentation with hypertensive encephalopathy.Saudi J Kidney Dis Transpl 2014;25:869-871
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Kota SK, Kota SK, Panda S, Modi KD. A case of liddle's syndrome; unusual presentation with hypertensive encephalopathy. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2019 Aug 24 ];25:869-871
Available from: http://www.sjkdt.org/text.asp?2014/25/4/869/135185
A patient presenting with hypertension with associated hypokalemia calls for additional evaluations for secondary causes of hyper-tension.  A few conditions are associated with combined hypertension and hypokalemia. One of those rare conditions is Liddle's syndrome. Cases of Liddle's syndrome presenting with newly detected hypertension, hypokalemic myopathy have been described. 
To our belief, Liddle's syndrome patients presenting with hypertensive encephalopathy are not yet reported so far. We therefore report an interesting case of a patient with Liddle's syndrome presenting with hypertensive ence-phalopathy. Hypertension in our patient was well controlled with amiloride. 
A 35-year-old lady presented with chief complaints of headache, nausea, vomiting and one bout of generalized tonic clonic convulsion lasting for two minutes. There was no history of hemiparesis, facial palsy or transient ische-mic attack. She denied having any paroxysmal headache, palpitations, profuse sweating, weakness of muscles, polyuria or swelling of her body. She has been known as a diabetic for two years with good glycemic control. However, for the last four years, despite receiving various combinations of calcium channel blocker, beta blocker, angiotensin-converting enzymes (ACE) inhibitors, angiotensin receptor blockers (ARB), alfa blockers and spironolactone and centrally acting sympathomimetics, her blood pressure was not controlled. There was no family history of hypertension.
On examination, her blood pressure (BP) was 210/130 mm Hg without significant asymmetry or postural variation, with palpable pulses in all extremities. There was no edema. She was confused without any focal neurologic signs, but had evidence of hypertensive retinopathy (retinal hemorrhages, exudates and papilledema). The rest of the systematic examination including cardiovascular system was normal.
The laboratory investigations revealed hypokalemia (2.2 mmol/L) with normal serum sodium (137 mmol/L), high 24-h urine potassium (40 meq/L) and metabolic alkalosis (pH 7.47, and HCO 3 28 meq/L). Urine examination was normal with normal serum creatinine (1.3 mg%). Doppler ultrasonography of the abdomen was normal. ECG revealed left ventricular hypertrophy with strain pattern. The patient's serum cortisol (12.5 µg/dL) and adrenocorticotropic hormone (ACTH) (15 pg/L) levels were normal. Urinary fractionated catecholamine levels disclosed epinephrine 2.95 μg/day (normal: 0-20 μg/day), norepinephrine 17.02 μg/day (normal: 10-80 μg/day) and dopamine 130.8 μg/day (normal: 65-400 μg/day). Her serum aldosterone level was low (30 pg/mL, normal: 40-480 pg/mL) with low plasma renin activity (0.04 ng/mL/h). Computed tomography (CT) of the abdomen was negative for adrenal enlargement or adenoma. CT scan of the brain was normal.
Hypertensive emergency was treated with sodium nitroprusside infusion, resulting in gradual improvement of BP and the patient's neurological status over two days. With a provisional diagnosis of Liddle's syndrome, the patient was prescribed amiloride, which is available in a combination with frusemide (Amioride 5 mg + Frusemide 40 mg). Oral potassium supplementation was also instituted. Three months later, the patient's BP stabilized at 130/80 mm Hg with serum potassium at 3.6 mmol/L.
In a patient with hypertension and hypokalemic alkalosis, primary aldosteronism, Cushing's syndrome, pheochromocytoma, renovascular hypertension, essential hypertension with diuretic use, some forms of congenital adrenal hyperplasia, Liddle syndrome and syndrome of apparent mineralocorticoid excess have to be considered as differential diagnoses.  Low serum aldosterone with normal CT abdomen ruled out primary aldosteronism. Cushing's syndrome and pheochromocytoma were excluded on the basis of normal serum cortisol, ACTH and normal urinary catecholamines. The patient denied any intake of diuretics or licorice. Age of presentation was against the congenital adrenal hyperplasia. Renovascular hypertension was ruled out by normal USG Doppler and low-plasma rennin activity with low aldosterone.
With a combined picture of hypertension hypokalemia with metabolic alkalosis and hyporeninemic hypoaldosteronism, possibilities of Liddle's syndrome and syndrome of appa-rent mineralocorticoid excess were considered. The syndrome of apparent mineralocorticoid excess is associated with the deficiency of 11β hydroxysteroid dehydrogenase 2, an enzyme that converts cortisol into inactive cortisone.  This leads to elevated cortisol, which binds to the mineralocorticoid receptor to produce a state of apparent mineralocorticoid excess, resulting in hypokalemic hypertension. This form of hypertension responds to spironolac-tone as it occurs via an aldosterone receptor-dependent mechanism. In our patient, normal serum cortisol and absence of response to earlier usage of spironolactone ruled out the option of the syndrome of apparent mineralo-corticoid excess. Response to amiloride without any recurrence of hypertension and hypokalemia confirmed the diagnosis of Liddle's syndrome.
Liddle's syndrome is a rare autosomal dominant condition characterized by a primary increase in sodium reabsorption from the collecting tubule and secretion of potassium in the majority of the cases.  Liddle et al described a familial syndrome of severe hypertension, hypokalemia and metabolic alkalosis mimicking hyperaldosteronism.  However, these patients have low renin and aldosterone levels, and there is conservation of sodium and excretion of potassium in the absence of mineralo-corticoid excess.  Genetic studies have revealed that mutations affecting the cytosolic tail of the ί subunit of the epithelial sodium channel (ENaC) could lead to this disorder.  These mutations apparently cause constitutive activation of the epithelial sodium channel of the luminal membrane of the collecting tubule and result in excessive absorption of sodium, leading to volume expansion. This in turn causes hypertension, leading to inhibition of rennin and aldosterone secretion. Lack of down-regulation of the epithelial sodium channels despite persistent volume expansion is the basis behind the pathogenesis of this syndrome. A similar lack of down-regulation of the activity of the epithelial sodium channels may underlie more common forms of low-renin hypertension. 
Patients with Liddle's syndrome present with hypertension, often hypokalemia (in most cases) and metabolic alkalosis, similar to that seen in mineralocorticoid excess.  Patients mostly present at a young age, although occasionally cases may not be detected until adulthood. However, presentation in the 6 th decade of life or later has been reported very rarely. , Presentation with hypertensive encephalopathy has not been reported in patients with Liddle's syndrome. However, muscle weakness associated with hypokalemia (especially in the lower limbs) has been described, although rarely, in elderly patients with Liddle's syndrome.  It is important to screen for this condition in patients with hypertension, hypokalemia and metabolic alkalosis, as the treatment of Liddle's syndrome differs from other forms of essential or secondary hypertension.  Potassium-sparing diuretics such as amiloride and triamterene, which directly close the sodium channels, are effective in Liddle's syndrome, whereas the mineralocorticoid antagonist spironolactone is ineffective as the increase in sodium channel activity is not mediated by aldosterone in this disorder. 
All the authors would like to heartily thank Mrs. Sruti Jammula, a PhD research scholar in the Department of Pharmaceutics, Roland Institute of Pharmaceutical Sciences, Berhampur, India for her sincere help in preparing the manuscript, formulating the basic intellectual content in its basic format and giving them valuable inputs regarding treatment of the condition mentioned in this case report.
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