Transcript Lithium用於Graves disease

Lithium用於Graves Disease
主講人:郭人瑚
指導藥師：張美琪
99/7/29
Question
Patient History

Objective
Family history of thyroid disease
 Thyroid Gr1-2 diffuse firm goiter, combine
Graves disease
 Palpitation, proximal muscle weakness ,
menstral cycle : irregular, stool passage
increased, soft loose stool

Drug profile
使用Propanolol耐受性
不佳→Bisprolol
980728
980803
0.5＃
QD
methimazole
2#TID
0.5＃
BID
1#HS
PTU
2#BID
lithium
981012
981109
981109
981223
990208
990406
990505
HR一直很快
1#BID
使用Methimazole會癢→
PTU
2#TID
cetirizine
diphenidol
980914
1＃
TID
bisoprolol
alprazolamXR
980817
1＃TID
peptidine
propanolol
980810
1#HS
2#TI
D
3#QID
1#HS
1#QID
1#QD
3#TID
Lab Data
Thyroglbulin: 519.2ng/ml [<50ng/ml]
 TRab: (+) 61.79% [(-) <15%]

檢驗值
正常值0.73-2.01ug/dL
TSH 正常值0.35-4.94ulU/ml
Free-T4
9
7
6.97
5.35
5
3.68
3
3.19
3.48
2.81
3.56
FT4
1
4月
99
年
3月
99
年
2月
99
年
1月
99
年
12
月
98
年
11
月
98
年
10
月
98
年
9月
98
年
8月
-1
98
年
TSH
Outline
 何謂Graves
Disease
 臨床表徵及診斷
 治療
What is Graves’ Disease?

Disease in which the immune system attacks
the thyroid gland, causing the thyroid gland to
react by making too much thyroid hormone.

The over-activity of a thyroid gland is
referred to as hyperthyroidism.
Graves Disease
Causes of Graves’ Disease
Genetic tendencies of the immune
system to attack itself
 Stress

Symptoms
Diagnose


TSH ↓＆ FT4↑＆
RAIU瀰慢性

TRAb (+)
Diagnosed
Treatment

Anti-thyroid drugs
Make it harder for the thyroid gland to create
hormones by decreasing the thyroid gland’s
ability to use iodine
 Radio active iodine: iodine 131
Impairs thyroid cells, thereby reducing the
amount of thyroid hormone produced
 Surgery
Removal of the majority of the thyroid gland
Treatment

主要藥物治療

Antithyroid drugs
methimazole
 propylthiouracil

Treatment

輔助治療β-blocker
 Lithium
 Glucocorticoids


inhibit peripheral T4 to T3 conversion and,
reduce thyroid secretion. They have been used
in patients with severe hyperthyroidism and
thyroid storm, although their efficacy is not well
demonstrated
Lithium用於Graves Disease的治療

機轉:



作用機轉相似於碘
Lithium acts by inhibiting T4 and T3 release from
the thyroid and possibly also by inhibiting their
synthesis.
優點
不影響甲狀腺碘的攝取
停藥後不會加重甲狀腺機能亢進
放射碘治療或手術前後的準備和輔助治療。
Evidence
 Micromedex
FDA Approval: Adult, no; Pediatric, no
 Efficacy: Adult, Evidence is inconclusive
 Recommendation: Adult, Class III
 Strength of Evidence: Adult, Category B

Impact of lithium on efficacy of radioactive iodine
therapy for Graves' disease: a cohort study on cure rate,
time to cure, and frequency of increased serum thyroxine
after antithyroid drug withdrawal.

Patients:
651 patients with newly diagnosed Graves' disease

Intervention:
298 patients RAI plus lithium (900 mg/day for 12 day)
353 patients RAI alone

Results:
(1)cure rate : RAI plus lithium (91.0%) vs RAI alone 85.0% (P =
0.030)
(2) RAI plus lithium were cured more rapidly (median 60 day) than those
treated with RAI alone (median 90 day, P = 0.000).
(3) Treatment with lithium prevented the serum free T(4) increase
after methimazole withdrawal and RAI therapy.
J Clin Endocrinol Metab. 2010 Jan;95(1):201-8.
Use of lithium in the treatment of thyrotoxicosis

Patients:




Dosage : 500-1500 mg/day
血清中濃度0.63 mmol/L
Results:




13名等候以放射性碘或施手術的病人
(對Antithyroid drugs 治療有不良反應或對此藥療效不佳)
有八名病患對lithium治療反應滿意,且均在1-2星期內FT4減少了40%
或以上。
4名在治療3-5星期內獲得效果,
一名對lithium治療反應緩慢
Conclusions:

如果病人不能接受thionamides類的治療或對 thionamides類的治療
沒有療效反應,低劑量的鋰治療是控制甲狀腺機能亢進的另一個安全有
效的治療方式
Hong Kong Med J 2006;12:254-9
Comparison of Radioiodine with Radioiodine plus
Lithium in the Treatment of Graves’ Hyperthyroidism*

Patients:


Dosage :


110 patients with newly diagnosed, untreated Graves’ disease,
age more than 20 yr, recent onset of hyperthyroidism (≦6
months), and nonsevere or absent Graves’ ophthalmopathy
900 mg/day for 6 days starting on the day of radioiodine
administration
Results:

Goiters shrank in both groups (P<0.0001), more effectively
and promptly (P < 0.0005) in the radioiodine-plus-lithium
group.
Journal of Clinical Endocrinology and Metabolism JCE & M² 1999 Vol. 84, No. 2
Successful outcome with methimazole and lithium
combination therapy for propylthiouracil-induced
hepatotoxicity.

49-year-old man with severe thyrotoxicosis and
propylthiouracil-induced hepatotoxicity , indices of liver
function continued to increase despite discontinuation of
propylthiouracil treatment.
 Adjunctive therapy with methimazole and lithium

Conclusion：Adjunctive therapy with methimazole and
lithium is synergistic in promptly achieving a euthyroid
state.
Endocr Pract. 1998 Jul-Aug;4(4):197-200.
The Use of Lithium Carbonate in the Preoparation for
Definitive Therapy in Hyperthyroid Patients

Patients:

6 patients
Methods :


in 5 patients with Graves’ diseaseand in 1 patient with
toxic multinodular goiter because of side effects of thionamide in 5
patients and ineffectiveness of antithyroid medication in the
remaining patient.

Results:


All 6 patients had a benign course following treatment without
thyroid storm. No adverse effects or complications of lithium
carbonate were observed.
Conclusions:

This report shows that lithium carbonate can be safely used
preoperatively or prior to radioiodide therapy in circumstances
where antithyroid medications are contraindicated and are ineffective
in obtaining an euthyroid status.
Med Princ Pract 2008;17:167-170
注意事項

Lithium血中濃度


Trough :服用藥物8-12小時後 ,早上給藥前
治療範圍：




0.60~1.20 meq/L
警示範圍：1.20-1.50 meq/L
Toxic：Over 1.50 meq/L
血清濃度超過1.5 meq/L—
產生運動失調、震顫、下 瀉、衰 弱、鎮定、嘔吐

超過2.5 meq/L—


舞蹈狀、迷惑、痙攣、意識下降、增加肌腱反射、嗜睡、肌
肉高張液體、不醒人事，腎臟毒性
超過2.5 meq/L—

昏迷，也有可死亡。
注意事項

其它影響甲狀腺功能

Amiodarone - due to amiodarone’s high
iodine content
Conclusion

In patients who develop serious sideeffects due to thionamides or who do
not respond to these drugs, lithium
therapy can be used as an effective
interim measure before undertaking
definitive therapy.
Hong Kong Med J 2006;12:254-9
Reference

Endocrinol Metab Clin North Am - 01-JUN-2009; 38(2):
355-71
 J Clin Endocrinol Metab. 2010 Jan;95(1):201-8.
Micromedex ,Up toDate , MD consult, CMAJ
 Hong Kong Med J 2006;12:254-9
 Adapted from Weetman AP: Graves disease. N Engl J Med
2000;343:1236–1248.
 AACE Thyroid Guidelines, Endocr Pract. 2002;8(No. 6)
461
• Endocr Pract. 1998 Jul-Aug;4(4):197-200.
Propranolol
(1)10mg/tab, (2)40mg/tab,
Bisoprolol
25mg/tab
非心臟選擇性(β1+β2- Receptor )
具心臟選擇性(β1 Receptor)
短效型20-80 mg PO tid; 1-2 mg IV q4-8h
長效型2.5-20mg qd; max: 40mg/day
Cardiovascular: Bradyarrhythmia,
Hypotension
Dermatologic: Dermatitis, Pruritus,
Urticaria
Gastrointestinal: Nausea, Vomiting
Neurologic: Fatigue, Insomnia,
Paresthesia
Psychiatric: Depression, Psychotic
disorder
Respiratory: Dyspnea
Cardiovascular: Bradyarrhythmia (9%),
Cold extremities, Hypotension
Gastrointestinal: Diarrhea (4%),
Indigestion, Nausea (2%), Vomiting (2%)
Musculoskeletal: Arthralgia (3%)
Neurologic: Dizziness (10%), Headache
(11%)
Psychiatric: Dyssomnia (8%-10%)
Respiratory: Cough (3%), Dyspnea (2%),
Pharyngitis (2%), Rhinitis (4%), Sinusitis
(2%), Upper respiratory infection (5%)
Other: Fatigue (8%)
Propylthiouracil
(PTU)
Methimazole
Protein Binding
75 ~ 80 %
0
T 1/2 (h)
1~2
6 ~ 13
Initial Dose
300 ~ 400mg /day, 分3~4 15 mg (mild); 30 to 40 mg
次服用
(moderately severe); 60 mg
(severe) ORALLY per day
Maintenance Dose
100~150 mg/ day
5~ 15 mg /day
Neonates
5~ 10 mg/ kg/day
0.5 ~ 1 mg/ kg/day
Transplacental
passage
Low
Higher
Levels in breast
milk
Low
Higher