Severe Hypokalaemia due to Mineralocortocoid Excess Syndrome

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Severe Hypokalaemia due to Mineralocortocoid
Excess Syndrome

• Chris Reeves

Dept. of Clinical Biochemistry, University
Hospital Aintree
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Hypokalaemia

• Common potentially fatal condition
• Defined K lt3.5 mmol/L (RR 3.5 5.0)
• Severe K 2.5 mmol/L
• Clinical features include neuromuscular
  weakness, cardiac arrhymias ECG changes, and
  alkalosis

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Hypokalaemia - causes

• Decreased intake e.g. anorexia nervosa
• Transcellular shifts e.g. alkalosis, insulin,
  catecholamines
• Increased losses
• GI e.g. diarrhoea, vomiting, laxatives
• Renal e.g. diuretics, other drugs,
  hypomagnesaemia, impaired renal tubular ion
  transport, mineralocorticoid xs. (Conn's
  Cushing's), Bartter's syndrome

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Case presentation

• Sept 05
• 60 yo lady
• GP Routine assessment as new patient.
• No clinical details

Na 144 K 1.2 Cl 84 HCO3 43 Urea
2.5 Creat 87 A.Gap 16
Go straight to Casualty. Do not pass Go. Do not
collect 200 !!
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Case presentation

• AED

• Hypertensive
• Myopathy muscle pain leg weakness
• Long Hx of diarrhoea, recent vomiting
• ? Diagnosis
• ? HypoK 2 Diarrhoea
• Rx
• IV K replacement in HEC (for close ECG
  monitoring)
• _at_40mM in 100ml over 2h

Na 142 K 1.5 Cl 86 HCO3 46 Urea
2.9 Creat 87 A.Gap 12 Gluc 7.1
ACa 1.62 PO4 1.22 Ca 1.56 Alb 35 Prot
69 ALP 89 Mg 0.61 CK 1357
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Case presentation

• Endocrine Investigations
• Aldosterone lt69 pmol/L (Supine 80- 300)
  (Upright 140 -850)
• Renin 0.8 ng/ml/hr (Supine 0.2 -
  2.8) (Upright 1.5 - 5.7)
• Cortisol 416 nmol/L (9am 140 500)

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Case presentation

• PMH
• Hypertension, ?BP, oedema, hypoparathyroidism,
  asthma
• Drug Hx
• Lisinopril, loperamide, alphacalcidol, diazepam,
  fluoxetine, salbutamol.

Self-administration of excessive amounts Kaolin
and Morphine mixture up to 6 bottles/day
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Kaolin Morphine mixture

• Antimotility medicine used to treat Diarrhoea

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Kaolin Morphine mixture

• Main Constituents
• (light) Kaolin (200g/L) absorbant, binds toxins
  in gut and water
• Morphine (hydrochloride) (40mmol/L) relaxes
  muscles of the intestine reducing their
  activity. Also eases painful contractions and
  prevents spasms
• Sodium Bicarbonate (50g/L)

Ethanol, Peppermint oil, Anaesthetic ether,
Chloroform, Black treacle, Liquorice liquid
extract, Sucrose, Purified water (45g/L)
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Literature Search Hypokalaemia and Kaolin
Morphine

• Barragry Morris. Fatal dependence on kaolin and
  morphine mixture. Postgrad Med J 1980 56
  180-182
• 24yo female described with a long history of
  abuse of KM which ultimately proved fatal.
• Progressive proximal weakness, hypertension, and
  hypokalaemia alkalosis
• Kirkham et al. Severe hypokalaemia from kaolin
  and morphine abuse. Postgrad Med J 1987 63
  589-590
• 34yo man, muscle weakness, profound hypokalaemia,
  increasing amounts of KM daily (up to 7
  bottles!)

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Mechanism of Action of Liquorice

• Hypokalaemic actions of Liquorice (Glycyrrhiza
  glabra) well documented.
• Contains significant quantities of glycyrrhzinic
  acid, the active metabolite of which,
  glycyrrhetinic acid, inhibits the enzyme
  11ß-hydroxysteroid dehydrogenase (11ß-HSD)
  present in mineralocorticoid receptors (MR) of
  the cortical collecting duct.
• Cortisol (glucocorticoid) is normally inactivated
  to cortisone by the action of 11ß-HSD.
• Allows cortisol to behave as in the syndrome of
  Apparent Mineralocorticoid Excess (AME), caused
  by congentital deficiency of 11ß-HSD enzyme.

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Mechanism of action
Aldosterone
Cortisol
Cortisol
Glycyrrhetinic Acid
11B-Hydroxysteroid dehydrogenase (11ß-HSD)
11ß-HSD
Cortisone (inactive)
Mineralocorticoid Receptor (MR)
Aldosterone pmol/L
Cortisol nmol/L
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Case presentation

• Discharged after adequate potassium replacement
  discontinuation of kaolin and morphine mixture.
• The severe hypokalaemia is most likely to have
  been caused by the combination of liquorice
  extract and sodium bicarbonate in kaolin and
  morphine mixture.

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And finally

• Sept 06
• Patient readmitted via AED,
• K1.8, HCO345, ACa1.59, Mg0.61
• Admitted KM abuse
• Urinary opiates 12,000 ng/ml
• GCMS confirmed only morphine present

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