THYROTOXIC PERIODIC PARALYSIS

(TPP)
Neurologic Complication of
Endocrine Disease

JUMRAINI TAMMASSE

Department of Neurology
Faculty of Medicine – Hasanuddin University

Introduction
Definition
• Periodic paralysis comprises a
group of neuromuscular diseases
in which the patients present
with paroxysmal muscle weakness
of the limbs.
• The most common causes are
thyrotoxic hypokalemic periodic
paralysis (TPP) and familial
hypokalemic periodic paralysis
(FPP).
Thyrotoxic periodic paralysis (TPP):
- a medical emergency
- acute and reversible attack of muscle
weakness associated with the hypokalemia.
- acquired flaccid paralysis in adults with
hyperthyroidism
- occur in patients of any ethnicity,
- more frequent in Asian populations
-newest form of endocrine channelopathy
-group of periodic paralysis
- acute muscle weakness -seeking
emergency care.
 Epidemiology

first published by Rosenfeld in the

German literature at the beginning of the TPP symptoms : occur in young adults,
last century.
in contrast to FPP, in which the paralysis
crises begin at an earlier age, usually
In English, the first report : by
Dunlap and Kepler in 1931, before puberty.
describing four patients.

TPP : is more common between the 2-3

In 1968, the first case of TPP
diagnosed in Brazil : by Pereira decades of life, with the peak incidence
et al of thyrotoxicosis

TPP is more frequently : in Asian

descendants, but it can occur in
patients of other ancestries.
TPP appears as a sporadic disease.
thyro‐toxicosis has a higher incidence in women,
the paralysis affects predominantly men,
male:female ratio of approximately 30:1.
Etiology and Genetic
Susceptibility

The paralysis crises occur only in

the presence of the thyrotoxic
state, regardless of its etiology.

Several causes of thyrotoxicosis with paralysis

have been reported, including Graves’
disease(GD), toxic adenoma, toxic
multinodular goiter, amiodarone-induced
thyrotoxicosis, TSH producingpituitary tumor,
lymphocytic thyroiditis, and factitious
thyrotoxicosis.

TPP is associated with the

hyperthyroidism in GD, and the
paralysis crisis may be an atypical form
of initial presentation of the disease.
 Theoretical model of multifactorial
interaction in TPP
The genetic factors :
one of these genes would
defect in one of the ion
be responsible
channels involved in for the generation of non-
excitationcontraction functional ion channels,
coupling (Ca2+, Na+, and K+) endocrine channelopathy

The environmental
the activity of the Na+/K+- factors : excessive
ATPase pump is increased in consumption of
thyrotoxicosis carbohydrate-rich foods,
hypokalemia  K+influx alcohol, or resting after
into a cell and by the intense exercise
hyperinsulinemic response
to carbohydrate intake in
patients susceptible to TPP.
Androgens  increase the activity of the
Na+/K+-ATPase pump, which explains the
higher incidence of the disease in young males
 Physiopathology

According to the mechanism illustrated in the Figure 2, during the TPP crisis,
the mutated Kir2.6 potassium channel retains potassium in the sarcolemma,
causing hypokalemia and flaccid paralysis.
 Mechanisms For Acute Muscle
Weakness In Thyrotoxic Periodic
Paralysis.
 Clinical Presentation
Adult young men

Sporadic

Recurrent acute paralysis with complete recovery

Limb trunk involvement

Precipitated by heavy carbohydrate load, high-salt diet, alcohol,

exertion

Family history of hyperthyroidism

 Distinguishing features between TPP and FHPP
TPP HPP
 Age (yr) 20–40 20

 Sex distribution Predominantly male Equal

 Heredity Sporadic Autosomal

dominant
 Ethnicity Asian, American
Indian/Hispanic, Caucasian, Asian
 Family history History of History with
thyrotoxicosis hypokalemic
 Clinical features of paralysis
hyperthyroidism Yes
 Genetic No
predisposition Genetic
predisposition Mutations of Cav1.1
Associated with SNPs (R5258H, R1239H,
of Cav1.1 (476A3G, R1239G), Nav1.4
intron 2 nt 57G3A, (R669H, R672G,
intron 26 nt 67A3G) R672H),
 Electrodiagnostic studies
EMG
Electromyogram performed during
spontaneous reduced amplitude of
compound muscle action potentials
Nerve conduction studies are normal

ECG
(ECG) abnormalities : ventricular arrhythmias ,
rapid heart rate, high QRS voltage, and first-
degree atrioventricular block
EMG

ECG
Electrodiagnostic studies

ECG
(ECG) abnormalities : ventricular
arrhythmias , rapid heart rate, high QRS
voltage, and first-degree atrioventricular
block
 Treatment of TPP
Emergency therapy
• Potassium replacement
• KCl 10 mEq/h iv and/or KCl 2 g every 2 h, orally
• Monitor serum K level, avoid rebound hyperkalemia
• Propranolol 3–4 mg/kg, orally

Prevention of recurrent attacks

• Avoid precipitating factors (heavy carbohydrate meals, high salt,
• alcohol, undue exertion) until euthyroidism is achieved
• Propranolol 20–80 mg every 8 h, orally

Determine the cause of TPP

Definitive therapy of hyperthyroidism with

antithyroiddrugs/thyroidectomy/radioiodin
 Conclusion
TPP is a rare condition in non-Asians,

The diagnosis at initial presentation is often delayed because of the

subtleness of the clinical features of thyrotoxicosis and the
similarities of the paralysis with other more common conditions.
With population mobility and admixture, TPP is becoming more
common in Western countries.

Early diagnosis prevents serious cardiopulmonary complications.

TPP is a curable disorder that resolves when a euthyroid status is

achieved.