Transcript Born in 1942, in Tehran, the capital city of Iran, Fereidoun Azizi obtained his MD from Tehran University, School of Medicine in.

Born in 1942, in Tehran, the capital city of Iran, Fereidoun
Azizi
obtained his MD from Tehran University, School of Medicine in 1966, Dr. Azizi
then completed his internal medicine speciality, endocrinology and
methabolism subspeciality and nuclear medicine speciality from Tufts University,
School of Medicine, Boston, USA and obtained three American Boards of Internal
Medicine, Endocrinology and Metabolism, and Nuclear Medicine in 1972, 1973 and
1974, respectively. He was appointed assistant professor of medicine at Tufts
University, and Chief of Endocrinology and acting-chief of Nuclear Medicine at St.
Elizabeth’s Hospital of Boston, Tufts Medical School from 1974 until 1979, when he
returned to Iran. He began his affilation with Beheshti University, and has since served as associate
professor in 1979 and as professor of medicine and endocrinology since 1985. His appointements have
been Dean of the medical school, Chancellor of Shahid Beheshti University of Medical Sciences, Head of
the medical group of Supreme Council for Educational Programming and Director of Medical Commission
of Council for Scientific Research in the Islamic Republic of Iran. He has served as President of Iranian
College of Internal Medicine and is currently the president of the Iran Endocrine Society.
Professor Azizi has been the Leading Professor and Director of Endocrine Division at Taleghani
Medical center, Shahid Beheshti University of Medical Sciences since 1989 and Director of Endocrine
Research Center since 1994. He has had a large endocrine practice since 1979.
Professor Azizi’s many research contributions have been in various fields of endocrinology and
metabolism, in particular the hypothalamic-pituitary-thyroid axis. He began his work with Professor L.E.
Braverman in Boston and continued his interest in thyroid pathophysiology in Iran. He focused many of his
research projects in 80’s in iodine deficiency in Iran, presented the results to the Minister of Health of Iran
in 1988 and initiated the first national IDD survey, which led to the formation of National Council for
Control of Iodine Deficiency Disorders in Iran in 1989;
in order to ensure sustained elimination of iodine deficiency in the last 20
years in Iran. He also directed the national research project of Tehran
Lipid and Glucose Study in the last 14 years.
Professot Azizi was the Regional Coordinator for the Middle East and
North Africa of Internaltional Council for Control of Iodine Deficiency
Disorders (ICCIDD) and has served as consultant and advisor to WHO and
UNICEF on multiple occasions. He is the Editor-in-Chief of the
International Journal of Endocrinology and Metabolism. Professor Azizi
has 1040 publications including 486 peer reviewed international paper
and 524 scientific papers in Iranian medical Journals and 30 full text or
chapters in scientific books. He is an invited reviewer for more than 26
scientific medical journals. He has received many awards including five
awards from presidents of I.R. Iran for “Distinguished Professor”,
“Research Excellence”, “Kharazmi Feitival”, “Distinguished Research
Center”and “Health Promition” in 1992, 1994, 1997, 2002 and 2008; State
of Kwait Prize for excellence in diabetes in Eastern Mediterranean Region
in 2007 and Nagataki Prize from Asia-Oceania Congress of Endocrinology
in 2009. He was selected, as Distinguished Scienctist of the Year by Iranian
Academy of Medical Sciences in 2011.
3
Continuous Methimazole or Radioiodine
Treatment for Hyperthyroidism
F.Azizi, V.Yousefi, A.Bahreynian ,
F.Sheikholeslam, M.Tohidi, Y.Mehrabi
Research Institute for Endocrine Sciences
Shahid Beheshti University of Med Sci
Tehran, I.R.Iran
10th Asia and Oceania Thyroid Assocition Congress
21-24 Oct. 2012, Bali, Indonesia
INTRODUCTION
Reasons for increased reliance in radioiodine treatment:
• ↑ Atrial fibrillation due to hyperthyroidism
• ↑ Cardiovascular and cerebrovascular morbidity
• High relapse after discontinuation of antithyroids
• Ease, effectiveness and low cost of RAI
5
Long Term Consequences of RAI Therapy:
• Thyroid failures 50-70% to 90-100%
• ↑ Morbidity from vascular causes
(? Due to hyperthyroidism itself)
• ↑ Cancer incidence and mortality
• Dependency on thyroxine therapy
6
Patients on levothyroxine replacement:
* 30-40% abnormal TSH concentration
(subclinical hypo-and hyperthyroidism) due to:
→ Variable potency, uniformity & reproducibility
of thyroxine preparations
→ Lack of patiens’ compliance
7
“In patients with recurrent hyperthyroidism after
disontinution of antithyroid drugs, long term
(mean 10 years) continuous treatment with
methimazole (MMI) was safe, and had comparable
expense
and
complications
with
treatment”
Azizi F, et al. Europ J Endocrinol 2005; 152: 695
8
radioiodine
PATIENTS AND METHODS
• Clinical trial
• Between march 1989 and July 2009
• Mean follow up 14 ±3 (range 5-20) years
• Patients with diffuse toxic goiter
• Tehran; area of iodine sufficiency
• 59 patients on continuous MMI and 73 on levothyroxine
treated radioiodine induced hypothyroidism
• Followed every 3-6 months with TFT’s for mean of 14 years
9
Patients with recurrent hyperthyroidism
(104)
Randomization
Radiiodine therapy
(51)
LFU (10)
Hypothyroid
(25)
MMI treatment
(34)
Excluded
(29)
LFU (6 )
Hyper (1)
Euthyroid
(16)
Hypo (1)
Euthyroid(26)
Thyroxine treated
Euthyroid
(25)
RAI
(73)
RAI R%
Hypothroid on
T4 R%
(48)
Euthyroid
(32)
10
Non
Randomized
(135)
MMI R%
Euthyroid (33)
MMI
(59)
LFU
(22)
Measurements at final visit
• Weight, height, BMI
• LRC questionnaire for physical activity
• Grades of goiter
• Thyroid function tests
• TPOAb and TRAb
• Serum lipids and lipoproteins
• Bone mineral density
• Echochardiography
11
Health Status and Neuro-psychology Tests
12
Name of test
Assessment
1. SF 36 Health Survey Questionnaire
General health
2. General Health Questionnaire (GHQ)
Mental disorders
3. Rey Complex Figure Test
Cognitive processes
4. Bender-Gestalt test (BGT)
Cognitive ability
5. Wechsler Memory Scale-Revised (WMSR)
Memory
6. Wechsler Adult Intelligence Scales (WAIS)
Intelligence quotient
7. Symptom Checklist-90 (SCL-90)
Psychological distress
8. Hospital Anxiety and Depression Scale (HADS)
Anxiety & Depression
Age, BMI and physical activity in methimazole and
radioiodine treated patients at final visit
Variable
MMI
(n=59)
RAI
(n=73)
P
Gender (F/M)
41/18
62/11
0.02
Age (yr)
51±16
53±11
0.53
0.65
26.2±3.5
27.8±4.5
0.04
0.143
53
77
0.009
BMI (kg/m2)
Adjusted
P (sex)
Physical activity (%)
Mild
0.012
Moderate
47
23
0.006
Goiter rate (%)
62
3
0.001
0.001
TPOAb (IU/ml)
23
(7-82)
8
(5-15)
0.001
0.001
2.1
(1.6-3.6)
1.8
(1.4-2.2)
0.02
0.86
TRAb (U/ml)
13
Serum lipids and lipoproteines concentrations in
methimazole and radioiodine treated patients
219±34
100
100
50
0
0
MMI
MMI
RAI
47±11
SERUM HDL-C
(mg/dl)
*
115
(90-152)
100
RAI
52±10
167
(120-212)
TRIGLYCERIDES
(mg/dl)
112±22
†
*
200
102±23
SERUM LDL-C
(mg/dl)
CHOLESTERL
(mg/dl)
192±36
50
†
25
0
MMI
0
MMI
14
* p<0.001,
RAI
† p<0.02
RAI
Findings of echocardiography in methimazole and
radioiodine treated patients
240
78
Ejection fraction (%)
75
50
left ventricular mass (gm)
100
RAI
0
RAI
8
14.9 ±4.3
5.7 ±1.8
7
15
11.5 ±45
10
5
Earlydistolic ( E/é) ratio
Early diastolic annular velocity (é)
(cm)
MMI
80
20
6
4.8 ± 4.3
5
4
3
2
1
0
0
MMI
RAI
P<0.001
15
149 ±45
160
0
MMI
153 ±43
MMI
RAI
P<0.02
Occurrence of abnormal serum TSH in methimazole and radioiodine treated
patients during mean 15 years follow up
80
71.2
Frequency (%)
60
41.7
40
33.8
27.1
MMI
RAI
20
13.8
9.7
1.7
0
0
0
1-3
4-6
Occurance of TSH>5 mU/L (TIMES)
>6
P<0.001
100
84.3
Frequency (%)
80
60
44.4
42.7
MMI
40
20
RAI
11.9
11.1
6.8
2.8
0
0
0
16
1-3
4-6
Occurance of TSH <0.3 mU/L (TIMES)
P<0.04
>6
Summary statistics and p values for neuro-psychologic tests
Measure
MMI
(n=59)
RAI
(n=73)
48 (81)*
61 (84)
P
SCL - 90
Compulsion
Normal & marginal
0.281
Abnormal
11 (19)
12 (16)
Normal & marginal
53 (90)
61 (84)
Abnormal
6 (10)
12 (16)
Direction
5 (5-6)†
5 (4-5)
0.033
Logical memory
6 (4-7)
4 (3-6)
0.049
Repeating numbers
9 (8-11)
9 (8-11)
0.010
96.6±13.9
93.6±13.9
NS
107±20
99±15
0.02
Psychotic
0.046
WMSR
Memory score
WAIS
Intelligence quotient
*:Number in parenthesis denote percentage; †: numbers are median (interquartile interval); ‡ mean± SD
SCL- 90: . Symptom Checklist-90
WMSR: Wechsler Memory Scale-Revised; WAIS: Wechsler Adult Intelligence score
17
The relative risk and confidence interval of the drangements in TSH secretion and the rates
of occurrence of goiter elevated, TPOAb and TRAs and dislipidemia in the continues MMI –
treated, compared to radioiodine- treat patients
Variable
During follow up
At final visit
Relative risk
(95% CI)
P Value
The relative risk and confidence interval of the rate of
occurrence of bone mineral density <-1 SD Zscore
and é velocity <12 and 16.8 cm and early diastolic E/é
ratio <6.7 in continuous MMI- treated, compared to
radioiodine-treated patients
Variable
At final visit
Relative risk
(95% CI)
P Value
CONCLUSIONS (1)
Long-term continuous MMI tratement:
• Effective
• Safe, rare side effects
• High treatment compliance
• Comparable expense with RAI therapy
20
CONCLUSIONS (2)
Long-term continuous MMI tratement compared to thyroxine-
treated RAI-induced hypothyroidism:
• More physical activity
• More goiter
• Better lipid profile
• Higher TPOAb titers
• Better memory, mood and IQ
• Less psychotic
• Less subclinical hypo-and hyperthyroidism
21
CONCLUSIONS (3)
Continuous methimazole treatment should
be considered as an optional approach to
long – term treatment of patients with
diffuse toxic goiter, in particular those
with recurrent hyperthyroidism.
22
Algorithm for the Use of Antithyroid Drugs
among Patients with thyrotoxicosis
Small or moderately enlarged
thyroid; children or pregnant
or lactating women; patients
with severe eye disease
Very large diffuse goiter,
multinodular goiter, toxic
adenoma
Radioiodine therapy
Antithyroid drug therapy
? surgery
Discontinue drug therapy after 18 mo
Normalization of thyroid function
With antithyroid drugs before
therapy in elderly patients and those
with heart disease
Monitor thyroid function
Relapse
Definitive radioiodine
therapy
Continuous MMI therapy
Remission
Second course of antithyroid drug
therapy in children and adolescents
Monitor thyroid
function every 12
mo indefinitely
24
The relative risk and confidence interval of the drangements in TSH
secretion and the rates of occurrence of goiter elevated, TPOAb and
TRAs and dislipidemia in the continues MMI – treated, compared to
radioiodine- treat patients
Variable
During follow up
At final visit
é
é
é
Relative risk
(95% CI)
P Value