A RARE CASE OF THYROTOXIC PERIODIC PARALYSIS

IN 17 YEAR-OLD BOY WITH GRAVES’ DISEASE

Putu Dianisa Rosari Dewi

Supervisors:
I Made Arimbawa, Dr. MD, PAED, Consultant

DEPARTEMENT OF CHILD HEALTH

MEDICAL FACULTY UDAYANA UNIVERSITY/SANGLAH GENERAL HOSPITAL
 INTRODUCTION Thyrotoxic Periodic Paralysis

Hyperthyroidism‐related condition  abrupt onset muscle

weakness and hypokalemia resulting from rapid intracellular
shift of potassium

In adult males in Asian populations, very rarely seen in the

pediatric population

Clinical picture: onset of generalized paralysis, more severe in the lower

extremities and in the early morning, often occurring after strenuous
exercise and/or a high-carbohydrate meal.

Most attacks resolve spontaneously and leave no residual weakness, cardiac

arrhythmias can be life-threatening
 CASE
REPORT
 HISTORY
17 year-old male
Symmetric paralysis of his lower extremities and weakness of his upper
extremities

Weakness on both feet 15 hours prior to hospital admission

Weakness on his upper extremities 10 hours before admitted, difficulty in urinating 6

hours before admitted

No history of fever, swallowing difficulty, shortness of breath nor cervical or pelvic

pain. History of trauma was denied. Pain nor numbness in four extremities were
denied.
One month prior, he began having episodes of palpitation but have not yet evaluated by
cardiologist.
Sweated heavily at the same time when palpitation appeared, which worsen at night

Increased appetite since the last two months, weight decrease 2 kilograms for the last
two months

Neck lump since one year ago and getting bigger since two months. The lump was
located at front of the neck. There was no pain when patient swallowed or at any activity.
Lump at any other site (-).

Voice changes, fever, and shortness of breath since lump enlarged were denied. There
was no complaint of tremor and goggled eyes. No respiratory difficulties.
PHYSICAL EXAMINATION

Soft diffuse symmetric mass on front neck, 4x5 cm in size, fixated, fine border,
follow down when swallowing, no pain in palpation, and no redness on the skin. No
bruits were detected
PHYSICAL EXAMINATION

Motor grade
222

Decreased
muscle tone
Deep tendon
reflexes ↓↓

Motor grade
111
 LABORATORY
• Hypokalemia 1.53 [3.5-5.5] mmol/L
• Decreased TSH <0.01 [0.27-4.20] µU/mL,
• Increased T3 11.82 [0.8-2.0] ng/mL, and fT4 7.66 [0.93-1.70] pmol/L
• Sinus tachycardia, right bundle branch block, and old inferior ischemic on
ECGs.
• Normal potassium urine was 46.49 mmol/24 hours [25.00-100.00], sodium
276.00 mmol/24 hours [30.00-300.00], chlorine 293.10 mmol/24 hours [85-
170], high calcium 8.25 mmol/24 hours [2.5-9.00] in 24-hours urine collector.
• High hyroid peroxidase antibody level of 2,230 [-34] IU/mL
 ULTRASONOGRAPHY

Enlargement thyroid glands and Multiple lymphadenopathy on cervical

increased vascularization and parotid area

FNAB on cervical anterior lymphadenopathy: resulted folicle cell proliferation with

toxic sign in accordance to Graves’ disease
BONE AGE

Appropriate with boys aged 18-

year-old
THERAPY
• 0.75 mEq/kg of intravenous potassium chloride
• oral propranolol 10 mg BID
• methimazole 10 mg BID

• resolution of paralysis
• potassium level was to 5.85 [3.5-5.5] mmol/L.

• Potassium correction was stopped

• Potassium level was 4.13 mmol/L
 THERAPY
  May June Sept Oct 2019 Dec 2019 Jan 2020 March
2019 2019 2019 2020

TSH <0.01 <0.01 <0.01 <0.01 11.34 0.01 0.77

fT4 7.66 2.25 5.42 1.04 0.54 2.17 1.54
TrAb 2.230            
IU/mL
Drug dose 10 mg 10 mg 10 mg 10 mg 5 mg OD 2.5 mg 2.5 mg
BID BID BID OD OD OD

History of experiencing another paralysis episode

was denied during 1 year follow-up
DISCUSSI
ON
Thyrotoxic Periodic Paralysis

a sporadic muscle disorder characterized by episodes of muscle

paralysis associated with hypokalemia in thyrotoxic individuals, lasts
from a few hours to several days

A male predominance has been widely described, with an overall male

to female ratio ranging from 17:1 to 70:1.

Some of 80% of TPP cases arise in the acute phase of hyperthyroidism.

It can be preceded by endocrine symptoms lasting 3 months to 12
months.
Insulin also induces Na/K-ATPase
activity

Hyperthyroidism-induced
hyperinsulinemia can also trigger
TPP.
 Thyrotoxic Periodic Paralysis

Attacks only occur during hyperthyroidism

Prodromes: muscle aches, stiffness, weakness or cramps 1 hour to 3 days

InInthis
thiscase,
case,
Patient
Patient
Start: suffered
suffered
weakness frommuscle
from
of proximal muscleaches
muscles aches
of lower and
and weakness
weakness
extremities beforeparalysis
 before paralysis
tetraplegia; correlates
whichbegan
which beganwith
withweakness
weakness
with of ofthe
degreethemuscles
ofmuscles fromlower
hypokalemia
from lowerextremities
extremitiesand and
progresstototetraparesis.
progress tetraparesis.ThisThispatient
patientalsoalsohad
hadinvolvement
involvementofofbladder
bladder
No correlations
function.
function.
with serum T3 or T4 levels

Bowel and bladder function, facial expression, swallowing, and respiration are usually
unaffected
 LABORATORY FINDINGS
Typical:

hypokalemia hypophosphatemia hypomagnesemia

InInthis
thiscase,
case,
thispatient
this patienthad
had
low elevated
urine potassiumfT4
elevated andT3T3levels
excretion
fT4 and levels along
along
suppressed
with
with
TSH,
lowTSH
low
elevated
TSHlevel.
level.
with a normal
Electrocardiography acid-base
examination revealed T4 sinus tachycardia,right
and/or T3 right
Electrocardiographybalance
examination revealed sinus tachycardia,
bundlebranch
bundle branchblockblockand
andinferior
inferiorischemic.
ischemic.

ECGs: tachycardia, increased QRS voltage, and first-degree atrioventricular block

 Precipitating factors for TPP
identified in 34% of patients

high carbohydrate ingestion, alcohol, infection, excessive exercise, and use of β2-
adrenergic bronchodilators

glucose loading
InInthis
thiscase,
case,
Patient denied consumption warm
of seasons
high carbohydrate,alcohol,
alcohol,nor
norhad
hadany
any
Patient denied consumption of high carbohydrate,
infections.Paralysis
infections. Paralysisattack
attackhappened
happenedatatearly
earlymorning.
morning.
 Clinical Manifestations

InInthis
thiscase,
case,
• Presence of diffuse goiter
patientcomplained
patient
• Tachycardia complainedofofnecknecklump
lumpsince
since1 1year
yearago
agowithout
withoutany any
• Anxietysymptoms.AtAt2 2months
symptoms. monthsago,
ago,the
theneck
necklump
lumpgetting
gettingbigger
biggerwithwith
• Increased blood pressure
complainedofofpalpitation,
• complained
Proptosis palpitation,easliy
easliysweating,
sweating,and and increased
• increased
Premature ofofappetite
appetite
craniosynostosis
• Increased
followed
appetite by weight loss. Patient’s height was • Growth
consistent with
acceleration and his
followed by weight loss. Patient’s height was consistent
• Tremor advancement inwith his
epiphyseal
genetic
• genetic potentialand
Easily sweating
potential andbone
boneage
ageexamination
examinationwas wasmaturation
accordingtotohis
according hisage.
age.
• Weight loss • Pubertal onset and progression
may be delayed
 THERAPY
correction of hypokalemia
treatment of the underlying
immediate supplement potassium
chloride hyperthyroid state
↓ antithyroid drugs
rebound hyperkalemia radiation
occurred in 40-70% of patients surgery
In this case,
In this case,
Patient received total of 35 mEq of potassium. Rebound hyperkalemia occured
Patient received total of 35 mEq of potassium. Rebound hyperkalemia occured
with insignificant sign and symptoms. Normal potassium level was achieved after 3
with insignificant sign and symptoms. Normal potassium level was achieved after 3
days. patient received 10 mg thyrozol BID then gradually decreased to 2.5 mg OD
days. patient received 10 mg thyrozol BID then gradually decreased to 2.5 mg OD
according to his TSH and fT4 level. He also treated with propranolol.
according to his TSHprevention of attacks
and fT4 level. He alsountil
treated with propranolol.
euthyroid condition achieved
selective beta-blocker
The doses of ATD are progressively reduced and maintained at minimum doses required to maintain a
clinical and biochemical euthyroid (Normal T3 and T4) for a period of 12–24 months  vulnerable to
adverse effects.

“Relationship between dose of hyperthyroid drugs and adverse events in

pediatric patients with Graves’ disease”

by Yasuda et al, in Clinical InIn this case,

Pediatric Endocrinology Journal 2017
this case,
Patient treated withofantithyroid
(level evidence drugs,
2b, which
grade of is twice daily thyrosol
recommendation B) 10 milligram.
Patient treated with antithyroid drugs, which is twice daily thyrosol 10 milligram.
Along monitoring of the disease, the patient shows significant positive changes
Along monitoring of the disease, the patient shows significant positive changes
along the treatment. His palpitation, easily sweating, and tachycardia were
along the treatment. His palpitation, easily sweating, and tachycardia were
improved.
improved.
The journal concluded that with treatment transition to low-dose
methimazole according to the Japanese Society for Pediatric Endocrinology
guidelines, we expect a decrease in the incidence of adverse events in
future. However, we should be careful as neutropenia and rash can occur
independently of the methimazole dose.
Predictive factors for the successful treatment in pediatric patients with
Grave’s disease.

“Predictive factors for early response to methimazole in children and

adolescents with Graves’ disease: a single-institute study between 1993 and
2013”

by Hwang et al, in Annals of Pediatric Endocrinology & Metabolism Journal 2016

(level of evidence 2b, grade of recommendation B).

The journal concluded that higher serological titers of antimicrosomal antibody at diagnosis may have
prognostic value in the response to initial methimazole treatment in pediatric hyperthyroid Graves’ disease
patients.
Time of normalization of T3/fT4/TSH had no significant correlations with other variables such as age, sex, a
family history of thyroid diseases, thyroglobulin, thyroid-stimulating immunoglobulin, or antithyroglobulin
antibody (ATA).
 DISEASE COMPLICATIONS
Multi organ complication:

Cardiac
Heart failure Cardiomyopathy
arrhythmia

In this case,
In this case,
ECG monitoring was sinus tachycardia, from echocardiography results were mild
ECG monitoring was sinus tachycardia, from echocardiography results were mild
tricuspid regurgitation and mild
Blindness mitral regurgitation.
tricuspid regurgitation Weight
and mildloss Osteoporosis
mitral regurgitation.
 REMISSION

Disease remission: T3, T4, and TSH remain normal 1 year after discontinuation of
antithyroid therapy
US: 20–30% remission after 12–18 months.
European: 50–60% remission rate after 5–6 years. Remission in children are around
20–30%, worse for patients with large glands, high antibody levels or very high
free T4 levels at diagnosis. Younger children have lower remission rates and
higher relapse rates than older adolescents and adult patients.

In this case, the patient performs clinical improvement. This results must be
maintained by a good compliance from the patient to have continuous monitoring to
doctor, or else thyrotoxicosis would appear again or worst, thyroid storm.
Patient with Graves’ disease whom treated with antithyroid drugs should be monitored in long period
of time, since thyrotixicosis of thyroid storm would present in non compliance patient.

“Graves’ disease in children: long-term outcomes of medical

therapy”

by Rabon et al, in Clinical Endocrinology Journal 2016

(level of evidence 4, grade of recommendation B).

Most children with Graves’ disease treated with antithyroid drugs do not experience
remission, but most remissions do not end in relapse. Adverse reactions to methimazole
are common but generally mild.
 METHODS TO ACHIEVE REMISSION

1 no specific standard for treatment discontinuation.

2 a longer duration of minimum dose treatment is associated with a higher remission rate

Endocrinology: Adult and Pediatric  If remission is not achieved after 3–4 yr of antithyroid drug
3 treatment, another treatment method should be selected once the patient reaches 18–20 yr of age

4 ATA: the suggested duration of antithyroid drug treatment is 12–18 mo. The medication dose should be
decreased or discontinued if the TSH level is normal. In such cases, the results of TRAb measurements can be
used to make such judgments. If remission cannot be achieved after 12–18 mo, either 131I therapy or surgical
treatment should be considered
CONCLUS
SION
 ...CONCLUSIONS
17 year-old, male, Indonesian
Symmetric paralysis of his lower extremities and weakness of his upper
extremities, followed by urinary difficulty
Physical examination: soft diffuse symmetric mass on anterior part of neck, 4x5 cm in size,
fine border, fixed, moved when swallowing, no pain on palpation. Motor
grade was II on upper limbs and I on lower limbs.
Laboratory: severe hypokalemia, low TSH, low FT3, high FT4, and high TRab.
Thyroid USG: enlargement of right and left thyroid and isthmus with hypervascularity ~ Graves’ disease.
Echocardiography revealed mild TR and mild MR.

After the management with antithyroid drug, beta-adrenergic blocker and potassium supplementation
for TPP  symptoms was relieved
Antithyroid therapy was continued and he remained euthyroid state and symptom free on the follow-up.
THANK
YOU