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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2014  |  Volume : 25  |  Issue : 4  |  Page : 869-871
A case of liddle's syndrome; unusual presentation with hypertensive encephalopathy

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

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Date of Web Publication24-Jun-2014


Liddle'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'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;25:869-71

How to cite this URL:
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 2021 Dec 3];25:869-71. Available from: https://www.sjkdt.org/text.asp?2014/25/4/869/135185

   Introduction Top

A patient presenting with hypertension with associated hypokalemia calls for additional evaluations for secondary causes of hyper-tension. [1] 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. [2]

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. [3]

   Case Report Top

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.

   Discussion Top

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. [4] 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. [5] 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. [4] Liddle et al described a familial syndrome of severe hypertension, hypokalemia and metabolic alkalosis mimi­cking hyperaldosteronism. [6] 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. [4] 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. [6] 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. [6]

Patients with Liddle's syndrome present with hypertension, often hypokalemia (in most ca­ses) and metabolic alkalosis, similar to that seen in mineralocorticoid excess. [6] 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. [7],[8] 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. [9] 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. [3] 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. [3]

   Acknowledgment Top

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.

   References Top

1.Onusko E. Diagnosing Secondary Hyper-tension. Am Fam Physician 2003;67:67-74.  Back to cited text no. 1
2.Gadallah MF, Abreo K, Work J. Liddle's syn­drome, an under recognized entity: A report of four cases, including the first report in black individuals. Am J Kidney Dis 1995;25:829-35.  Back to cited text no. 2
3.Garovic VD, Hilliard AA, Turner ST, Mono-genic forms of low rennin hypertension. Nat Clin Pract Nephrol 2006;2:624-30.  Back to cited text no. 3
4.Sagnella GA, Swift PA. The renal epithelial sodium channel: Genetic heterogeneity and impli­cations for the treatment of high blood pressure. Curr Pharm Des 2006;12:2221-34.  Back to cited text no. 4
5.Stewart PM, Corrie JE, Shackleton CH, Edwards CR. Syndrome of apparent mineralo-corticoid excess: A defect in the cortisol-cortisol shuttle. J Clin Invest 1988;82:340-9.  Back to cited text no. 5
6.Scheinman SJ, Guay-Woodford LM, Thakker RV, Warnock DG. Genetic disorders of renal electro­lyte transport. N Engl J Med 1999;340: 1177-87.  Back to cited text no. 6
7.Oh J, Kwon KH. Liddle's syndrome: A report in a middle-aged woman. Yonsei Med J 2000;41:276-80.  Back to cited text no. 7
8.Rezkalla L, Borra S. Saline-resistant metabolic alkalosis, severe hypokalemia and hyper-tension in a 74-year-old woman. Clin Nephrol 2000;53: 66-70.  Back to cited text no. 8
9.Matsushita T, Miyahara Y, Matsushita M, et al. Liddle's syndrome in an elderly woman. Intern Med 1998;37:391-5.  Back to cited text no. 9

Correspondence Address:
Sunil Kumar Kota
Department of Endocrinology, Medwin Hospitals, Nampally, Hyderabad -500 001, Andhra Pradesh
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DOI: 10.4103/1319-2442.135185

PMID: 24969204

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