JIACM 2006; 7(4): 302-7

P O S T G R A D U AT E C L I N I C

Hypokalaemic Thyrotoxic Periodic Paralysis

SN Chugh*, Surekha Dabla**, Kiran Chugh***, HK Aggarwal****

A 22-year-old male person was admitted with symptoms
and signs suggestive of thyrotoxicosis (Fig. 1). He
described sudden weakness of all the four limbs 5 days
before admission. He also complained of shooting pain in
the legs while walking and painful cramps in his arms and
neck associated with difficulty in breathing. There was no
history of any gastrointestinal or any cardio-vascular
problems though he complained of palpitations and
sweating off and on.
Past history
discomfort, and weakness in all the four limbs. He had
been experiencing repeated episodes of weakness during
this period, following either a heavy meal or rest after
exercise.
Personal history
The patient was a non-smoker and a teetotaler.
Family history
There was no history of similar illness in the family.

1½ years ago the patient had similar episodes of pain,

Examination
The patient was afebrile and had obvious exophthalmos.
The pulse rate was 92/minute, regular, and of good volume.
The blood pressure was 150/60 mm Hg on right arm in
supine posture; the respiratory rate was 24/minute.
Examination of neck revealed diffuse goitre with systolic
bruit over it. Neurological examination revealed fine tremors
of both hands, proximal muscle weakness in both arms and
legs associated with hyporeflexia in all the four limbs.
Cardiovascular system was within normal limits. The patient’s
look was anxious, whereas the higher mental functions and
the cranial nerves were normal. There was no sensory
abnormality. Systemic examination was normal.

The results of the laboratory investigations done during

hospitalisation of the patient are shown in (Table I).

Table I: The results of the laboratory investigations

done during hospitalisation of the patient.
Investigations Values/results
Haemoglobin(Hb) 9.5gm%
Totalleucocytecount(TLC) 7,900/cumm
Differentialleucocytecount(DLC) Polymorphs-85;Lymphocytes-15;
Monocytes - 0; Eosinophils - 0;
Fig. 1: Basophils-0

* Professor of Medicine and Head Unit-V and Endocrinology and Metabolism, ** Lecturer, Department of Medicine,
*** Lecturer, Department of Biochemistry, **** Associate Professor, Department of Medicine,
Pandit BD Sharma Post-Graduate Institute of Medical Sciences, Rohtak, Haryana.
Bloodurea 25 mg% and legs lasting from a few hours to a few days.
Bloodsugar 88 mg% Occasionally, there may be involvement of
Serumsodium 126mEq/l muscles of the eyes, respiration, and swallowing3.
The mental functions remain normal, and the
Serumpotassium 2.1mEq/l
sensory modalities are preserved with
Serumcalcium 10.8mg%
diminished tendon reflexes. These patients may
Serumphosphate 3.4mg% have sinus tachycardia, diffuse ST-T changes,
Serummagnesium 2.9mmol/l flattening of ‘T’ waves, prolonged QT intervals
T-3;T-4;TSH 454.05ng/dl;17.9ng/dl;<0.01µIU/ml and ‘U’ waves and cardiac arrhythmias on ECG
Arterialbloodgasanalysis pH - 7.32; pCO2 - 44.7%; Oxygen because of a drop in potassium levels (< 3.0 mEq/
saturation-75.6%;Bicarbonates(HCO3) l). Sometimes dangerous arrhythmias such as
-20.4 torsade de pointes and ventricular fibrillation may
Electrocardiogram(ECG)showed S.tachycardiawithQTprolongationand develop4.
TUPsegmentwithoccasionalventricular
ectopicbeats(Fig.2) Q. 3. What is the aetiopathogenesis of this
Skiagramofchestshowed Mildcardiomegaly condition?
Ultrasonographyofthyroid Bothlobesofthyroidshowedaltered Ans: The pathogenesis of hypokalaemic thyrotoxic
echotexturewithincreasedbloodflow. periodic paralysis (HTPP) has not been clearly
Eachlobemeasured4.3cmsinlength
elucidated. However, it is known to occur most
and2.0cmsinantero-posteriorplane.
commonly in patients with Graves’ disease or in
Urineexamination Noabnormalitywasdetected
nodular toxic goitre5. Attacks of periodic paralysis
can also, though not always, be experimentally
Q. 1. What is the probable clinical diagnosis induced by a provocation test with glucose (3 g/
in this patient? kg) and insulin (0.1 IU/kg IV)6 indicating that
Ans: In view of unequivocal evidence of thyrotoxicosis paralysis is due to hypokalaemia and not because
with frequent periodic paralysis and documented of thyrotoxicosis itself. Patients with this type of
hypokalaemia (2.1 mEq/l) during the episodes of paralysis have an inherent defect in Na+-K+-
paralysis, the diagnosis of hypokalaemic thyrotoxic ATPase activity which is sensitive to thyroid
periodic paralysis (HTPP) was kept in this case. hormone7. The thyroid hormone alters the cell
membrane permeability to potassium through
Q. 2. What is the clinical presentation of Na+-K+- ATPase pump leading to intracellular shift
hypokalaemic thyrotoxic periodic of potassium resulting in hypokalaemic periodic
paralysis (HTPP)? paralysis without depleting the total body K+
(potassium) stores.
Ans: Hypokalaemic thyrotoxic periodic paralysis
(HTPP) is a rare disorder affecting mainly men of
Q. 4. What are the causative/aggravating
Asian descent. It begins at 20 - 40 years of age.
factors for repeated episodes of
The sex ratio (M:F) is 20:1. It is characterised by
weakness? How can they be
sudden recurrent episodes of painless weakness
or paralysis without alteration in consciousness,
prevented?
usually occurring after a high-carbohydrate meal Ans: Hypokalaemia is the underlying biochemical
or heavy exertion followed by a prolonged rest disturbance which provokes periodic paralysis in
in patients with thyrotoxicosis1, 2. Patients usually these patients2.
present with clinical features of thyrotoxicosis
Factors leading to hypokalemia are:
followed by episodic muscular weakness.
Weakness commonly affects the muscles of arms
Gastrointestinal loss of potassium

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Vol. 7, No. 4
October-December, 2006 303

Renal loss of potassium condition lasting from hours to

Diet lacking in potassium days. The cerebrospinal fluid (CSF)
is characteristic in Guillain-Barré

High-carbohydrate or high-salt meals
syndrome, showing increased

After intake of alcohol protein content with few or no

Rest after heavy and unaccustomed exercise cells (albumino-cytological

Certain drugs such as diuretics, laxatives, insulin dissociation) while it is normal in
therapy, Amphotericin B, α-adrenergic hypokalaemic thyrotoxic periodic
antagonists, β-2 agonists, steroids paralysis.
(glucocorticoids as well as mineralocorticoids), 2. Polymyositis Polymyositis is frequently
penicillin and its derivatives, etc. associated with malignancies and
is characterised by elevated
The episodes, hence, can be prevented by taking
creatinine kinase (CK) levels and
low carbohydrate, low salt, and potassium rich diet
abnormal electromyography
including fruit juices. The diuretics, if the patient is
(EMG). Polymyositis is usually a
taking for some other disorder, must be stopped
diagnosis by exclusion.
and replaced with other potassium-sparing
diuretics, if needed. Abstinence of alcohol should 3. Myasthenia gravis An acquired autoimmune disorder
always be recommended. in which autoantibodies (IgG) are
produced against acetylcholine
Q. 5. Do the paralytic attacks have any receptors at neuromuscular
relation to season or time? junctions; Ocular muscles
weakness is characteristic. The
Ans: Yes, the attacks appear to have seasonal variation, diagnosis is confirmed by
usually occurring during the warmer months (May electromyography (EMG) and
through September in our country) and less often serological tests for the presence
during the colder months (December through of acetylcholine receptor
March). The paralysis also follows a diurnal pattern, antibodies.
often occurring at night when the person is resting
4. Spinal cord These cases present with definite
in bed 8. It does not occur when the person is
compression focal neurological deficit involving
performing any physical activity.
motor, sensory, and bladder
functions which is progressive.
Q. 6. What are the common conditions
There is a definite level reflecting
simulating periodic paralysis?
the site of compression.
Ans: The following are the common conditions which Radiological imaging (CT
simulate periodic paralysis. Their clinical myelogram) confirms the
differentiation is tabulated (Table II). diagnosis.

Table II: Common conditions simulating periodic 5. Andersen An autosomal disorder with
paralysis. syndrome mutation in potassium channel
and it is characterised by periodic
1. Guillain-Barré The weakness in Guillain-Barré
paralysis and distinct facial
syndrome syndrome follows some infection
features with short stature, low-
(post-infectious) in 60% of the
set ears, hypertelorism, and long
cases and it lasts for several weeks;
QT interval predisposing to
whereas hypokalaemic thyrotoxic
ventricular tachyarrhythmia.
periodic paralysis is a transient

304 Journal, Indian Academy of Clinical Medicine
Vol. 7, No. 4
October-December, 2006
6. Brodie disease An autosomal recessive exercise-
induced myopathy that causes
muscular stiffness due to impaired
muscle relaxation.
7. Thomsen An autosomal dominant disorder
disease with the defect lying in the
channel gene. It usually occurs in
infancy and childhood. Myotonia
is worsened by exposure to cold
and decreased by activity. Muscle
strength is normal.
8. Becker muscular An autosomal recessive disorder
dystrophy characterised by severe muscle
weakness associated with muscle
hypertrophy. EMG is diagnostic.
9. Schwartz- An autosomal recessive disorder
Jampel characterised by myopathy,
Syndrome muscle stiffness, short stature,
chondrodystrophy, bone and joint
deformities, hypertrichosis, and
blepharophimosis.
10. Idiopathic familial The clinical and biochemical
periodic paralysis features of hypokalaemic
thyrotoxic periodic paralysis are
similar to those of idiopathic
familial periodic paralysis except
that in the latter, thyroid functions
are normal and there is positive
family history. Idiopathic familial
periodic paralysis is transmitted by
an autosomal dominant manner
caused by a defect in the gene
CACLNAIA3.
Q. 7. What are the various causes of
hypokalaemic periodic paralysis and
what are their differentiating features?
Ans: The various conditions associated with
hypokalaemia and periodic paralysis are:-
1. Primary idiopathic familial periodic
paralysis: It is caused by mutations in
CACLNAIA3 gene. It is an autosomal dominant
disease in which defect lies in the Ca++
Journal, Indian Academy of Clinical Medicine
Vol. 7, No. 4
channels. The patients present with complete
paralysis with sparing of bulbar musculature
usually in childhood or adolescence. Diagnosis
is confirmed by positive family history, absence
of other secondary causes of hypokalaemia,
EMG, and muscle biopsy. Avoidance of high
carbohydrate diet, physical exercise, and
acetazolamide are helpful in treating this
condition.
2. Thyrotoxic periodic paralysis: It is common
in males of Asian descent. Mutations in
potassium channel are identified. Features of
thyrotoxicosis may or may not be observed.
Presentation is usually at adult life with
abnormal thyroid functions. The treatment
consists of restoration of serum potassium
levels and antithyroid drugs.
3. Primary hyperaldosteronism (Conn
syndrome): This condition is characterised by
hypertension (specially diastolic), polyuria,
polydipsia, and muscular weakness. There is
hypersecretion of aldosterone by adrenal glands.
Hypokalaemia, hypernatraemia, and alkalosis are
the underlying metabolic disturbances. The
diagnosis is made by elevated plasma and urine
aldosterone levels and low plasma renin level.
Treatment is of the positive basic cause.
4. Barium poisoning: Barium is used in various
alloys, in paints, soap, paper, and rubber, and in
the manufacture of ceramics and glass; and the
workers in these industries are predisposed to
it. It lowers the serum potassium levels by
blocking calcium-activated potassium channels
that control cellular potassium efflux. Thus,
barium intoxication results in a rise of
intracellular potassium and a corresponding
drop of extracellular potassium leading to
hypokalaemia9.
5. Liquorice ingestion: Liquorice is a medicinal
plant having therapeutic uses as expectorant,
demulcent, anti-inflammatory and laxative; and
is also used to normalise immune functions. It
contains glycyrrhizin which inhibits the activity

October-December, 2006 305
 of 11β-HSDH (hydroxy steroid dehydrogenase)
which ultimately leads to mineralocorticoid
excess and hypokalaemia. Liquorice root toxicity
following prolonged ingestion leads to periodic
paralysis.
6. Thyroid hormone abusers: Thyroid hormone
drives potassium into cells via sodium-
potassium ATPase pump and leads to
hypokalaemia. Iatrogenic use by obese patients
with intention to lower their weight may
predispose them to it.
Q. 8. How will you confirm the diagnosis?
Ans: The diagnosis of hypokalaemic thyrotoxic
periodic paralysis is confirmed by clinical and
biochemical evidence of thyrotoxicosis and
hypokalaemia with or without an abnormal
electrocardiogram (ECG) during the attacks.
Electromyography (EMG) is confirmatory and
shows electrical silence during attacks10. Muscle
biopsy occasionally may show abnormality.
Molecular genetic testing identifies the mutation
in the disease causing gene (KCNE 3)11.
Q. 9. How will you treat such a patient?
Ans: The aims of treatment are:-
1. To treat the acute episode and to prevent its
further episodes;
2. To normalise the serum potassium levels.
The treatment of hypokalaemia is determined by
severity of symptoms, serum potassium levels, and
the ECG changes, if any. Accordingly, the cases can
be managed as:
Mild hypokalaemia (3 - 3.5 mmol/l): Oral
potassium supplements in the form of potassium
chloride 30 to 100 mmol/day are adequate and
given with juice and at meals.
Moderate hypokalaemia (2.5 - 3.0 mmol/l):
Initially these cases are managed with oral
potassium supplements, and if the patient still
remains symptomatic then 10 mmol of potassium/
306 Journal, Indian Academy of Clinical Medicine
hour is started intravenously in 5% mannitol (avoid
glucose and saline as diluent) with cardiac
monitoring and serum potassium levels
monitoring.
Moderately severe hypokalaemia (2 - 2.5
mmol/l): Oral potassium supplements if tolerated
by the patient are given, and if there is no
improvement in 1 to 2 hours then 15 mmol of
potassium per hour is given intravenously in 5%
mannitol with continuous monitoring of cardiac
system and serum potassium concentrations.
Severe hypokalaemia (< 2 mmol/l): Oral
potassium replacement if tolerated by the patient.
In addition, administer upto 20 mmol of potassium
per hour intravenously in 5% mannitol with
continuous cardiac and serum potassium
concentration monitoring.
In the present case, the patient having serum
potassium concentration 2.1 mEq/l was treated as
a case of moderately severe hypokalaemia with
intravenous potassium infusion.
Q. 10. How will you prevent such attacks?
Ans: Prevention of attacks: Preventive treatment is
aimed at decreasing the frequency of symptoms
and paralytic attacks; therefore, the patient is
advised to take oral potassium supplements 20 -
40 mEq/day in 2 to 4 divided doses which are
available as potassium acetate, potassium chloride,
potassium bicarbonate, potassium citrate, and
potassium gluconate, etc. In patients with
hypokalaemia and metabolic alkalosis, the
supplement is given in the form of potassium
chloride, whereas in patients with hypokalaemia
and metabolic acidosis as in d-RTA/type-I RTA (renal
tubular acidosis), potassium gluconate, potassium
citrate, and potassium bicarbonate are the
preferred choice. In addition, the underlying
aetiological or precipitating factor must be
identified and treated/avoided. Acetazolamide is
highly effective in individuals with familial/primary
periodic paralysis; whereas in individuals with
thyrotoxic periodic paralysis; it is not found to be

Vol. 7, No. 4
October-December, 2006
 beneficial. Beta-blockers may reduce the number
and severity of attacks by controlling hyperthyroid
status and restoration of euthyroid status. The
achievement of euthyroid status is definitive
treatment.
Q. 11. What are the complications of
hypokalaemic thyrotoxic periodic
paralysis?
Ans: The complications of hypokalaemic thyrotoxic
periodic paralysis are:-

Cardiac arrhythmias during attacks

Respiratory muscles paralysis or bulbar paralysis

Malignant hyperthermia

Delayed recovery during anaesthesia
Q. 12. What is the relevance of genetic
counselling in hypokalaemic thyrotoxic
periodic paralysis?
Ans: Genetic counselling and prenatal testing are
indicated in hypokalaemic periodic paralysis
because it is inherited in autosomal dominant
manner. In hypokalaemic thyrotoxic periodic
paralysis, the mode of inheritance is not known
and there is no positive family history and de novo
genetic mutation is also not known12; hence
genetic counselling is usually not necessary.
Journal, Indian Academy of Clinical Medicine
Vol. 7, No. 4
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