Thyrotoxicosis and Thyrotoxic Storm

Transcription

Thyrotoxicosis and
Thyrotoxic Storm
Jeerunda Santiprabhob, M.D.
Division of Endocrinology
Department of Pediatrics
Siriraj Hospital Mahidol University
Tips and Tricks in Pediatric Emergency
Outline
Definition
Causes of thyrotoxicosis
Management of severe thyrotoxicosis or
thyroid crisis
Case
Management of thyrotoxicosis
Definition
Thyrotoxicosis
A clinical syndrome of hypermetabolism that
results when the serum free thyroxine (T4),
free triiodothyronine (T3)or both are increased
Hyperthyroidism
A sustained increase in thyroid hormone
biosynthesis and secretion by the thyroid
gland
Thyrotoxicosis ≠ Hyperthyroidism
Causes of Thyrotoxicosis
Common Causes
THYROTOXICOSIS ASSOCIATED WITH
HYPERTHYROIDISM
Graves’ disease
Intrinsic thyroid autonomy
Toxic adenoma/Toxic multinodular goiter
THYROTOXICOSIS NOT ASSOCIATED WITH
HYPERTHYROIDISM
Inflammatory disease
Subacute thyroiditis
Lymphocytic thyroiditis with hyperthyroidism
(Hashitoxicosis)
Exogenous thyroid hormone
Uncommon Causes
THYROTOXICOSIS ASSOCIATED WITH
HYPERTHYROIDISM
Production of thyroid stimulators
TSH-producing pituitary tumor
Intrinsic thyroid autonomy
Thyroid carcinoma
Drug-induced hyperthyroidism
Iodine and iodine-containing drugs and
radiographic contrast agents
Uncommon Causes
THYROTOXICOSIS NOT ASSOCIATED WITH
HYPERTHYROIDISM
Inflammatory disease
Drug-induced thyroiditis (amiodarone, interferon-α)
Infarction of thyroid adenoma
Radiation thyroiditis
Manifestations of Hyperthyroidism

Symptoms
Hyperactivity, irritability, insomnia, nervousness
Heat intolerance, increased sweating
Palpitations
Fatigue, weakness
Dyspnea
Weight loss with increased appetite
Oligomenorrhea or amenorhea
Pruritus
Increased stool frequency
Thirst and polyuria
Manifestations of Hyperthyroidism

Signs
Sinus tachycardia, atrial fibrillation,
increased pulse pressure,
hypertension
Fine tremor, hyperreflexia
Warm, moist skin
Palmar erythema, onycholysis
Hair loss
Congestive (high-output) heart failure,
Muscle weakness and wasting
onycholysis
Graves’ disease
The vast majority of cases of
thyrotoxicosis are caused by Graves’
disease
Prevalence in children ∼0.02 %
Peak incidence 11-15 years of age
Girls are more commonly affected than
boys (3.5-6:1)
Thyrotropin-receptor antibodies
are found in 80% of patients
Manifestation of Graves’ disease

Diffuse goiter
Localized dermopathy
Thyroid acropachy
Ophthalmopathy
Thyrotoxic Storm (Crisis)
Rare but life-threatening
Incidence 1-2% of hospital admission for
thyrotoxicosis
Exaggerated manifestations of thyrotoxicosis
The diagnosis is largely a clinical one,
based on determination of the presence of
decompensation of a number of organ
systems in a thyrotoxic patient
Cardinal manifestations
Fever (T>38.5°C)
Tachycardia (out of proportion to the fever)
Gastrointestinal dysfunction (nausea,
vomiting, diarrhea, jaundice
CNS signs (confusion, apathy, coma)
Mortality rates 10-75%
Precipitation of thyrotoxic crisis
Infection
Surgery
Parturition
Vigorous palpation of thyroid
Emotional stress
Withdrawal of antithyroid drug therapy
Iodine-131 therapy
Management of Thyroid Crisis or
Severe Thyrotoxicosis
Therapy directed against the thyroid gland
Inhibition of new hormone synthesis
Antithyroid drugs of thionamide: PTU, MMI
Lithium carbonate
Inhibition of hormone secretion
Iodine
Oral: potassium iodide (SSKI), Lugol’s
solution, ipodate
Intravenous: sodium iodide
Lithium carbonate
Therapy directed against thyroid hormone action
in the periphery
Inhibition of T4 to T3 conversion
Ipodate, iopanoate, amiodarone
Corticosteroids
Propranolol
PTU
β-Adrenergic blockade
Propranolol, selective β1-blocking agents
Removal of excess circulating hormone
Plasmapheresis,dialysis
Treatment directed against a precipitating factors
Therapy to avoid decompensation of normal
homeostatic mechanisms
Treatment of hyperthermia
Acetaminophen
Cooling
Correction of dehydration and poor nutrition
Fluids and electrolytes, glucose
Vitamins
Supportive therapy
Oxygen
Vasopressors
Treatment of congestive heart failure (digoxin,diuretics)
Inhibition of new hormone synthesis
Adult dosage: PTU 200-250 mg PO q 4 hr
MMI 20 mg PO q 4 hr
Children: PTU 6-8 mg/kg/d (not exceed 1200 mg/d)
MMI 0.6-0.8 mg/kg/d
Inhibition of hormone secretion
Iodine: Lugol’s solution 3-10 drops PO q 6-8 hr
Saturated solution (SSKI) 1 drop PO q 8 hr
Given 1 hr after antithyroid drugs
Inhibition of T4 to T3 conversion
Corticosteroids
Adult: dexamethasone 2 mg q 6 hr or
hydrocortisone 300 mg stat then 100 mg q 8 hr
Children: dexamethasone 1-2 mg q 6 hr
Propranolol
β-Adrenergic blockade
Propranolol: 0.5-2.0 mg/kg/d or greater
Case
Case
เด็กหญิงอายุ 11 ป จาก จ.ราชบุรี
อาการสําคัญ: คอโตมาก 1 ป
ประวัติปจจุบัน:
1 ปกอน มีอาการเหนื่อยงาย ใจสั่น หงุดหงิดงาย คอโต
ไดรับการวินิจฉัย Graves disease และรักษาที่โรงพยาบาล
ตางจังหวัด ดวย PTU 1 tab tid, propranolol 1/2 tab bid
มารดาพาผูปวยมารักษาตัวตอที่ร.พ. ศิริราช เนื่องจากคอยัง
โตมาก
ประวัติอดีต: แข็งแรงดี ไมมีโรคประจําตัว
ประวัติครอบครัว: ปฏิเสธโรคของธัยรอยดในครอบครัว
ผูปวยไดรบั การรักษาที่ศิริราชดังนี้
Date
T4
TSH
T3
FT4
(ng/dl) (ug/dl) (ng/dl) (uU/ml)
80-185 4.9-13 0.8-2.3 0.5-4.8
18/10/47
575
16.4
1.96
0.008
15/11/47
399
5.5
0.77
0.005
26/1/48
312
4.7
0.71
0.008
10/2/48
Treatment
↑PTU 2 tab tid
Propranolol 1 tab tid
Recommend radioactive
iodine (I-131)
I-131
10/3/48
620
23
6.9
0.005
Restart PTU 2 tab tid
Propranolol 1 tab tid
1/4/48
234
9.81
1.2
0.005
Develop rash
suspecting druginduced rash, D/C med
Case
2 สัปดาหหลังหยุด PTU ผูปวยมีอาการใจสั่น เหนื่อยมากขึ้น
อยูไมสุข น้ําหนักลดลง 2 กิโลกรัม และตอมธัยรอยดโตขึ้น
มาก จนรูสึกอึดอัด ผื่นที่ขึ้นกอนหนานี้ยุบหายหมดแลว
Case
Physical Exam
Weight 42.7 kg (P75), height 160 cm (P97),
T 37.8°C, BP 137/66 mmHg, pulse 140 /min,
R 20 min
GA: jittering,exopthalmos
CVS: systolic murmur gr II at apex
RS: normal breath sounds
Abdomen: no hepatosplenomegaly
Case
6.5
9
10.5
9 cm
Case
TFT: T3>651 ng/dl, T4>24 ug/dl, FT4>7.77 ng/dl,
TSH 0.009 uU/ml
CBC: Hb 10.8, Hct 33.9%, WBC 6890, N 40%,
L46%, Mo 9%, E 5%
E’lyte: BUN 16, Cr 0.4, Na 138, K 4, Cl 102,
HCO3 27
LFT: TB 0.7, DB 0.1, AP 275, SGOT 28, SGPT
27, GGT 27, GLOB 2.9, ALB 3.4
CXR: CT ratio 0.56
EKG: left ventricular hypertrophy
Severe exacerbation of thyrotoxicosis after
antithyroid drug withdrawal
Treatment
Methimazole (5mg) (0.8 mg/kg/d)
4 tab am, 3 tab pm
Propranolol (10 mg)
1.5 tab PO q 6 hr (1.4 mg/kg/d)
2.5 tab PO q 6 hr (2.5 mg/kg/d)
Dexamethasone (0.5 mg)
2 mg PO q 6 hr (8 mg/d)
Lugol’s solution
1 ml PO q 8 hr
Case
Date
Vital sign
T3
(ng/dl)
80-185
T4
(ug/dl)
4.9-13
FT4
(ng/dl)
0.8-2.3
TSH
(uU/ml)
0.5-4.8
Treatment
15/4/48
P 140
BP137/66
>651
>24
>7.77
0.009
MMI 0.8 MKD
Lugol 1 ml q
8hr,
Propranolol
Dexa 8 mg/d
16/4/48
P 120
17/4/48
P 100
252
>24
>7.77
0.011
19/4/48
P 84
BP118/70
115
15
3.98
0.008
↓Lugol 0.5 ml
q 8 hr
↓ Dexa 4 mg/d
21/4/48
68
9.51
2.4
0.006
↓Lugol 0.3 ml
q 8 hr
↓ Dexa 1 mg/d
24/4/48
61
4.7
1.09
0.008
Off Dexa/Lugol
/Propranolol
Case
Consider other alternative treatment
Total thyroidectomy
Post operative course
10 hr after surgery: Ca 8.2 mg/dl, iCa 4.4 mg/dl
Treatment: IV calcium gluconate/ oral Ca carbonate
Day 7: Ca 8.5 mg/dl, iCa 4.8 mg/dl
T3 39, T4 2.2, FT4 0.3, TSH 0.02
Treatment: off Ca, start Eltroxin (0.1 mg) 1 tab QD
Case
Treatment of Thyrotoxicosis
Medical treatment
Surgical treatment
Radioactive iodine
Medical treatment
Propylthiouracil (PTU) blocks organification
and coupling of iodine, inhibition of T4 to T3
conversion; given 2-3 times a day
Methimazole (MMI) blocks organification of
iodine; can be given once a day
Renders the patient euthyroid within 6 weeks
There will be little improvement for the initial
1-3 weeks
Thus patients may require β-Adrenergic
blocker for few weeks to control symptoms
Medical treatment
Patients are often treated with antithyroid drugs
for 2-3 years
Younger, male patients, and large goiter are more
resistant to drug therapy
Remission rate in adults 30- 40%
N Engl J 2000;343(17);1236-48
25% of children remit after each 2 year period of
medical therapy
J Clin Endocrinol Metab 1987;64(6):1241-5
Medical treatment
Dosage of thionamide
Drugs
PTU
Methimazole
Initial dose
6-8 mg/kg/d
0.6-0.8 mg/kg/d
Maintenance
1-3 mg/kg/d
0.1-0.3 mg/kg/d
Side effects of antithyroid drugs
Minor
Major
Common (1%-5%)
Rash
Urticaria
Arthralgia
Fever
Transient leukopenia
Rare (0.2%-0.5%)
Agranulocytosis
Very rare
Aplastic anemia
Thrombocytopenia
Hepatitis
Cholestatic hepatitis
Vasculitis, LE-like syndrome
N Engl J 2005;352(9);905-917
Thyroidectomy
Near-total or total thyroidectomy
Advantage: rapid control of hyperthyroidism
Indications
Severe drug reactions
Relapse or failure to be cured after 2-3 years on
antithyroid drugs
Enlarging gland
Radioiodine Therapy
Indications
If patients developed serious
side effects from antithyroid
drugs
Recurrent hyperthyroidism
after thyroidectomy
Non-compliance
Advantages: simple and cheap
Contraindications: pregnancy,
gross enlargement
Radioiodine Therapy
Several medical centers are now using this
modality for children with hyperthyroidism
Use I-131 large dose: ablate the thyroid gland
and render patient hypothyroid
Antithyroid drugs should be stopped 3-7 days
prior to RI therapy and be recommended, if
necessary, one week afterwards
No increase in thyroid (or extra-thyroid)
malignancy risk
JAMA 1998; 280:347-55
Treatment of Thyrotoxicosis in Children
Advantages
Disadvantages
Medical
•Relatively simple
•Relatively cheap
•Non-invasive
•Potentially life threatening
side effects
•Compliance issues
•Low remission rates
Surgical
•Definitive
(total
thyroidectomy)
•Removes an
unsightly goiter
•Surgical expertise required
•Anesthetic risk
•Surgical complications
•Specific complications:
hypoparathyroidism,
laryngeal nerve palsy,
visible scar
Treatment of Thyrotoxicosis in Children
Radioiodine
Advantages
Disadvantages
•Usually
definitive
•Cheap
•Non-invasive
•Short term side effects:
neck discomfort, transient
hypoparathyroidism
•May precipitate thyroid
crisis
•Opthalmopathy may
deteriorate
•Relative lack of long term
safety data in the young
Long term
remission rate
Medical
Surgery
Radioactive
iodine
15-25%
90-100%
90-100%
Highlights Thyroid 2005;132:10-12
Side Effects of Antithyroid Drugs
Case
I
II
III
IV
V
VI
Diag
age
10 5/12
6 9/12
11 11/12
12 9/12
8 yr 7 mo
3 yr
Med
PTU
PTU
PTU
MMI, PTU
PTU, MMI
PTU
Age
11 5/12
6 11/12
12 1/12
12 11/12
12 2/12
5 8/12
Side
effects
hepatitis
cholestatic cholestatic myositis
vasculitis
jaundice
jaundice
(MMI)
bicytopenia
(PTU)
Tx
I-131
I-131
Subtotal
I-131 x 2
thyroidectomy
Total
Total
thyroidect- thyroidectomy
omy
I-131
I-131
PTUinduced
vasculitis
Total
thyroidectomy
Meijinee Densriwiwat, MD
Patient 2
PTU induced
cholestatic jaundice
Patient 6
PTU-induced vasculitis
Tip and Tricks
Side effects of antithyroid drugs are more
common than we think
Always educate patients about medication’s side
effect
MMI might be drug of choice; better compliance
and ± less side effects
Awareness of alternative treatment of
thyrotoxicosis; consider I-131 in older children or
patient with poor compliance
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Thyrotoxicosis and Thyrotoxic Storm

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