Transcript clinical features

Thyrotoxic Periodic Paralysis
R4 尤咨云
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Case Sharing
姓名
: 陳X弦
年齡
: 27 歲
性別
: 男性
病歷號碼 : 002318379B
入院日期 : 102/05/27 (2013)
過去病史 : HIVD 2 years ago
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Case Sharing
Chief Complaint
• Generalized weakness for half a day before coming
to ER
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Case Sharing
Present Illness
• The patient noticed no abnormality when going to bed last night.
• This early morning (4:00 am), he woke up and felt generalized
weakness. Weakness progressed. He has to be helped out of
bed. He tried to walk while holding onto walls, but soon fell down
due to weakness.
• He felt that his legs seemed to be weaker than arms. Severity
was about the same over both legs.
• There was no other focal neurological sign such as numbness
or urinary incontinence.
• He denied fever, chills, or diarrhea.
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Case Sharing
Present Illness
• He metioned about palpitations and body weight loss (75
70kg), but denied resting tremor or heat intolerance.
• He denied strenuous exercise (despite being a soldier).
• He denied having large meals, but recalled that he consumed
more than 1400ml of sweetened drink everyday last week and
especially in recent two days because of hot weather
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Case Sharing
Physical Examination
Consciousness: Clear E4M6V5
Vital signs: TPR : 36.8 /120 / 20
BP:132/81mmHg
HEENT : Conjunctiva: Not pale ,Sclera: Not icteric
Neck : thyroid not enlarged. No lymphoadenopathy
Chest : Normal and symmetric respiratory movement.
Bilateral clear breathing sounds
Heart : Regular heart beats , No S3 , No S4 , No murmur
Abdomen: flat, hypoactive bowel sound, tympanic,
No hepatomegaly , No splenomegaly,
No tenderness , No rebounding pain , No palpable mass
Limbs : No deformity. Warm. No pitting edema. Normal pulse.
Neurology: Muscle power: Arms: 3/3. Legs: 2/2.
Sensation: normal. DTR decreased.
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Case Sharing
Lab
DATE
ALB
1020527 3.3
TP
5.6
BIL.T
0.4
BIL.D
ALKP
61
AST
27
AL
23
DATE
WBC
1020526 7900
HGB
14.9
PLT
253
NEU
84.1
LYM
7.3
MON
8.4
EOS
0.2
BAS
0.0
DATE
NA
1020526 142
1020603 141
1020604
K
1.8
2.4
5.8
CL
116
CA
7.3
Mg
2.1
BUN
14
Cr
0.6
CRP
0.10
DATE
GLU
1020526 110
CK
222
DATE
PH
1020527 7.334
PCO2
41.7
PO2
84.3
SO2
95.7
BEB
-4.0
HCO3
21.7
TCO2
23.0
HGB
14.5
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Case Sharing
Lab
TTKG = 4.13
free-T4 = 41.7
[8.9 - 17.6 pg/ml]
TSH
[0.4- 4.0 uIU/ml]
= 0.005
TGAb(Anti-thyroglobulin antibody (ATA))= POSITIVE 353 AU/mL
TPO Ab(AMiA)= NEGATIVE 58 AU/mL
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Echo
Thyroid
Case
Sharing
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Thyrotoxic Periodic Paralysis
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INTRODUCTION
• Periodic paralysis (PP) is a muscle disease in the family of
diseases called channelopathies
• Manifested by episodes of painless muscle weakness
• Most cases of PP are hereditary, usually with an autosomal
dominant inheritance pattern
• Acquired cases of hypokalemic PP have been described in
association with hyperthyroidism
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EPIDEMIOLOGY
• Thyrotoxic PP is a sporadic form of hypokalemic PP that may occur
in association with hyperthyroidism
(Familial hypokalemic PP has an autosomal dominant inheritance)
• In Asian populations, the incidence among patients with
hyperthyroidism is approximately 2%
• In non-Asian populations, the incidence of thyrotoxic PP among
individuals with hyperthyroidism is estimated to be 0.1 to 0.2 %
• Despite a higher incidence of hyperthyroidism in women, over 95 %
of thyrotoxic PP cases occur in men
• Thus, the incidence of thyrotoxic PP is particularly high among Asian
men with thyrotoxicosis (8.7 to 13 %).
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PATHOGENESIS
• The mechanism by which hyperthyroidism can produce
hypokalemic PP is not well understood
• Thyroid hormone increases tissue responsiveness to betaadrenergic stimulation, which, along with thyroid hormone,
increases Na-K ATPase activity on the skeletal muscle
membrane
• This tends to drive potassium into cells, leading to
hyperpolarization of the muscle membrane and relative
inexcitability of the muscle fibers
• Thyrotoxic patients with PP have been found to have higher
sodium pump activity than those without paralytic episodes
• In this way, excess thyroid hormone may predispose to paralytic
episodes by increasing the susceptibility to the hypokalemic
action of epinephrine or insulin
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PATHOGENESIS
• Insulin also activates the Na-K ATPase pump and may act
synergistically with thyroid hormone to drive potassium into cells.
• This is consistent with the observation that a heavy meal can be
a precipitant for attacks of thyrotoxic PP.
• Insulin resistance with compensatory hyperinsulinemia is
suspected to have a role in the pathogenesis of thyrotoxic PP
• Patients with a history of thyrotoxic PP were heavier and
exhibited reduced insulin sensitivity compared with patients with
thyrotoxicosis without thyrotoxic PP.
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PATHOGENESIS
• It has been suggested that individuals who are susceptible to
thyrotoxic PP may have an ion channel defect, which, in the
euthyroid state, is not sufficient to produce symptoms.
– One study revealed that 10 of 30 Caucasian or Brazilian
patients with thyrotoxic PP had a mutation in the gene
encoding Kir2.6. These mutations were also seen in 26
percent of 26 thyrotoxic PP patients from Singapore, but only
in 1 of 114 patients from Hong Kong or Thailand
• A role for testosterone in the pathogenesis for thyrotoxic PP is
suggested by
– predominance of this condition in men
– Testosterone increases sodium-potassium ATPase activity in
animals
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CLINICAL FEATURES
• The age of onset of symptoms
– between 20 and 39 years in approximately 80 % of patients
• Weakness
– attacks occur suddenly
– weakness is generalized
– Consciousness is preserved
– usually affecting proximal more than distal muscles, and the
legs more than the arms
• Clinical features of hyperthyroidism
– Many precede the onset of PP by months or even years
– but they have been noted to occur at the same time (in 43 to
60 % of patients) or following the development of PP (in 11
to 17%)
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CLINICAL FEATURES
• Mild myalgia (less than half of patients)
• Decreased muscle tone with hyporeflexia or areflexia typically,
although normal or hyperactive reflexes may be observed.
• Tachycardia (mean heart rate = 105 bpm) may be noted at
presentation and distinguished these patients from those with
familial hypokalemic PP.
• Severe, even fatal, arrhythmias.
• Exceptional cases of bulbar weakness and respiratory
weakness requiring ventilatory support have been reported in
thyrotoxic PP
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CLINICAL FEATURES
• Attacks vary in frequency and duration. Intervals of weeks to
months are common, but some patients experience several
attacks per week.
• A duration of symptoms of several hours is typical, but can
range from minutes to days.
• Attacks in thyrotoxic PP can be precipitated by events that are
associated with an increased release of epinephrine or insulin
– both of which cause movement of potassium into cells and
low potassium blood levels
• Most common inciting event includes rest after strenuous
physical activity, stress, or a high-carbohydrate load.
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CLINICAL FEATURES
• Other events reported to induce attacks in thyrotoxic PP include
cold exposure, infection, alcohol intake, pulse corticosteroid
therapy, and menses.
• Although attacks of weakness may occur at any time of the day,
a high frequency of attacks at night or early in the morning has
been reported in thyrotoxic PP.
• A seasonal variation has also been suggested, with more
frequent attacks in summer months.
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LABORATORY FEATURES
• Degree of hypokalemia during an attack is variable;
– In one series the mean serum potassium level was 2.1 mmol/L.
– Cases with levels <1.5 meq/L are frequently reported.
– Severity of weakness usually corresponds to the degree of
hypokalemia.
• Patients with thyrotoxic PP have attacks in the hyperthyroid state.
– Supporting laboratory findings include elevation of serum
thyroxine (T4) and low thyrotropin levels (TSH).
– Patients with elevated T3 and normal T4 levels have been
reported.
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LABORATORY FEATURES
• Other common laboratory findings include mild
hypophosphatemia and hypomagnesemia.
• In one study, a urine calcium to phosphate ratio of higher than
1.7 was a sensitive and specific test to distinguishing thyrotoxic
PP from familial hypokalemic PP
• Creatine kinase may be normal but has been reported to be
mildly elevated in two-thirds of patients, and rhabdomyolysis has
been reported.
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EKG FEATURES
• These include findings consistent with hypokalemia: ST
depression, sinus tachycardia, U waves, as well as abnormal
PR interval, higher QRS voltage, and first degree AV block .
• Severe arrhythmias (eg, sinus arrest, second degree AV block,
Vf, and VT) are not common but are described.
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DIAGNOSIS
• In an acute attack, thyrotoxic PP must be distinguished from
other causes of acute quadriparesis, such as myasthenic crisis,
Guillain-Barré syndrome, acute myelopathy (eg, transverse
myelitis), tick paralysis, and botulism.
• The finding of hypokalemia generally alerts the clinician to the
diagnosis of periodic paralysis, in which the possibility of
thyrotoxicosis must always be evaluated, particularly in the
absence of a family history.
• After a thyrotoxic state is established, the patient is further
evaluated to determine the underlying cause of hyperthyroidism.
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ACUTE TREATMENT
• Potassium supplementation usually lead to improvement of weakness.
• There was a shorter recovery time with use of potassium (6.3 versus
13.5 hours) when comparing treatment with intravenous potassium
chloride to normal saline infusion
• Patients who received intravenous potassium recovered more quickly
than those who received oral supplementation.
• There may be a delayed response of a few hours following potassium
administration.
• Required doses of potassium supplementation are variable and range
from 10 to 200 mEq
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ACUTE TREATMENT
• Rebound hyperkalemia appears to be a prominent problem in
thyrotoxic PP, occurring in approximately 40 to 59 % of treated
attacks.
• Patients who received greater than 90 meq of K within 24 hours,
tend to develope rebound hyperkalemia (80%).
– This has led to a suggested protocol of 30 mEq of oral
potassium every two hours until improvement begins, with a
maximum dose of 90 mEq in 24 hours.
• For some patients who had higher free thyroxine levels, a fall in
serum potassium may occur during initial treatment; these
patients ultimately required higher doses of potassium
supplementation, and were more likely to have severe rebound
hyperkalemia.
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ACUTE TREATMENT
• Close monitoring of serum potassium
• Correct hypomagnesemia if present
• Cardiac monitoring is recommended for all patients during
treatment and observation.
• Cardiology consultation should be obtained for severe
arrhythmias/ECG changes.
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ACUTE TREATMENT
• Replacement of potassium may be insufficient to resolve an attack.
• Propranolol, a beta adrenergic blocker, presumably reverses the
excessive stimulation of the Na-K ATPase and excessive drive of
potassium into cells (see 'Pathogenesis' above).
• Intravenous propranolol has been reported to reverse weakness
and hypokalemia in patients with thyrotoxic PP that is
unresponsive to potassium administration.
– doses of 1 mg of IV propranolol every 10 minutes up to a
maximum dose of 3 mg.
• Oral propranolol (3 mg/kg) administered without potassium
supplementation has been reported to have reversed both
weakness and hypokalemia without inducing rebound
hyperkalemia
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PREVENTIVE TREATMENT
• Restoration of euthyroidism eliminates attacks of thyrotoxic PP.
• When patients become euthyroid, the electromyography (EMG)
exercise test normalizes, and attacks are no longer inducible.
• Thyrotoxic PP can reemerge if thyrotoxicosis recurs.
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PREVENTIVE TREATMENT
• The administration of beta-blocking medications such as
propranolol (40 to 120 mg daily) with or without potassium
supplementation has also been shown to decrease the
frequency and severity of attacks, and may be used as a
temporizing measure until a euthyroid state is achieved
• A nonselective beta blocker (eg, propranolol) should be given;
beta-1 selective agents are less likely to inhibit the beta-2
receptor-mediated hypokalemic effect of epinephrine and may
therefore be less likely to prevent paralytic episodes
• Potassium supplementation is not effective as prophylaxis in
thyrotoxic PP.
• Pprecipitating factors, such as heavy exercise, highcarbohydrate diets, and alcohol, should be avoided.
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This is the End
Thank you for your attention!
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