Unraveling the Gordon Knot

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Unraveling the Gordon Knot

• Vanessa Tremblay
• PGY 5, Internal Medicine
• Université de Sherbrooke

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Clinical Case

• 29 year-old man referred for hyperkalemia
• No known PMH
• Habits alcohol and cocaine stopped one year ago
• Family history mother hypertensive, no
  hyperkalemia
• No medications or natural products

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Clinical Case

• K 6,1 meq/L discovered on a routine blood test
  by his family physician
• Repeated measures between 5,6 and 6,8 meq/L
• Failure to improve with Sodium polystyrene
  sulfonate (Kayexalate?)
• No excess dietary potassium
• No muscle weakness

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Physical Exam

• BP 150-170/90-110 mmHg
• HR 70 bpm
• Grade 1 hypertensive retinopathy
• Otherwise normal

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Laboratory data

• Na 140 meq/L K 6,1 meq/L
• Creatinine 79 ?mol / L
• Venous gas pH 7,4 HCO3- 22 mmol / L
• CK, CBC, glucose ? normal
• No hemolysis of specimens

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Laboratory data

• TTKG 1,2
• UK/Uosm x Posm/PK
• Aldosterone 207 pmol /L normal 138-413
• Renin 0,14 ng/ L /s normal 0,25-0,70

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To sum it all up!!!

• 29 yo man
• Hypertension
• Persistent hyperkalemia
• Normal renal function
• Decreased renal excretion of potassium according
  to TTKG
• Normal aldosterone level
• Low plasma renin activity

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GORDONS SYNDROME
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Gordons Syndrome

• AKA
• Familial hyperkalemic hypertension
• Pseudohypoaldosteronism type 2
• Definition
• Hyperkalemia
• Arterial hypertension
• Normal renal function

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Gordons Syndrome

• First case reported in 1964
• Syndrome named by RD Gordon in 1970
• More then 100 cases reported
• First case in Canada

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Pathophysiology

• Autosomal dominant
• Chromosomes 1,12,17
• Mutation of WNK-1 and WNK-4
• With no lysine K kinase

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Normal WNK-4

• Reduces the expression of thiazide sensitive NaCl
  channels (NCCT)
• Reduces the expression of renal outer medullary
  potassium channels (ROMK)

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Mutant WNK-4

• Increased activity of NaCl channels (NCCT)
• Decreased activity of ROMK

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Mutant WNK-4

• Increased activity of NCCT
• Volume expansion
• Hypertension
• Suppression of the renin-angiotensin-aldosterone
  axis
• Diminished sodium and water delivery to
  collecting duct
• Impaired excretion of potassium and bicarbonate
• ? aldosterone production
• Hyperchloremic acidosis

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WNK-1

• Normal function
• Prevents inhibition of NCCT by WNK-4
• Mutant WNK-1
• Gain-of-function mutation
• Net result
• Increased activity of NCCT

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Gordons Syndrome

• Other findings
• Short stature
• Muscular weakness
• Hypoplasia of incisors
• Hypocalciuria with lithiasis
• Intellectual retardation

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A simple therapeutic intervention was performed
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• Hydrochlorothiazide 25 mg ID
• Resolution of hypertension and hyperkalemia
  within 24h
• After screening, no other family member were
  identified with Gordons syndrome

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Treatment of Gordons Syndrome

• Inhibition of NCCT with a thiazide diuretic
• Effective for hypertension as a monotherapy
• Effective for hyperkalemia and acidosis

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Conclusion

• The Gordons syndrome should be considered when
  hypertension and hyperkalemia are present without
  renal failure
• The clinical findings of Gordons syndrome can be
  explained by an increased function of NCCT
• Thiazide diuretics are effective to treat the
  hypertension and the laboratory anomalies of
  Gordons syndrome

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Conclusion

• This is another reason why thiazide diuretics
  should be a first line treatment for
  hypertension!!!

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Special Thanks

• Dr Donald Echenberg for his help with the
  translation!
• Dr Luc Lanthier for his help with the case and
  article in CJGIM5

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References

• 1. Gordon RD, Geddes RA, Pawsey CG, O'Halloran
  MW. Hypertension and severe hyperkalaemia
  associated with suppression of renin and
  aldosterone and completely reversed by dietary
  sodium restriction. Australas Ann Med 1970 19
  287-94.
• 2. Gordon RD, Hodsman GP. The syndrome of
  hypertension and hyperkalaemia without renal
  failure long term correction by thiazide
  diuretic. Scott Med J 1986 31 43-4.
• 3. Soppi E, Viikari J, Seppala P, Lehtonen A,
  Saarinen R, Miilunpalo S. Unusual association of
  hyperkalemia and hypertension. Hypertension 1986
  8 174-7.
• 4. Bruno CM, Sciacca C, Di Prima P, Castelli Z,
  Neri S. Gordon's syndrome a case report. Clin
  Exp Hypertens 2004 26 461-4.
• 5. Capasso G, Cantone A, Evangelista C, et al.
  Channels, carriers, and pumps in the pathogenesis
  of sodium-sensitive hypertension. Seminars in
  nephrology 2005 25 419-24.
• 6. Hadchouel J, Delaloy C, Jeunemaitre X. WNK1
  and WNK4, new players in salt and water
  homeostasis. Med Sci (Paris) 2005 21 55-60.
• 7. Gamba G. Role of WNK kinases in regulating
  tubular salt and potassium transport and in the
  development of hypertension. Am J Physiol Renal
  Physiol 2005 288 F245-52.

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Learning Objectives

• To review the approach to hyperkalemia
• To recognize Gordons syndrome, which is a rare
  cause of hyperkalemia and hypertension
• To learn about the treatment of Gordons syndrome