1. LIPID METABOLISM IN THYROID DISEASE
John MF Adam
Diabetes and Lipid Centre,
Dr. Wahidin Sudirohusodo Hospital
Division of Endocrinology and Metabolism,
Department of Internal Medicine, Faculty of Medicine,
Hasanuddin University, Makassar, Indonesia

3. INTRODUCTION
It is well known that alteration in thyroid hormones, results in changes in the composition of lipid profiles
These changes in lipid profiles can occur in subjects with hyperthyroidism as well as hypothyroidism, subclinical as well as overt classical cases
Clinically, lipid changes are more frequently seen in subjects with hypothyroidism

4. LIPOPROTEIN METABOLISM
Endogenous pathway
(from the liver)
Exogenous pathway
(from food intake)

5. LIPOPROTEIN METABOLISM
Endogenous pathway
Fat cells
Liver
VLDL
Macrophage
IDL
LDL
FFA
RCTP = reverse cholesterol
transport pathway
stools
remnants
chylomicron
intestine
Food
cholesterol
HDL
RCTP
Exogenous pathway
Shepherd J. Eur Heart J Supplements 2001;3(suppl E):E2-E5

6. LIPOPROTEIN METABOLISM – endogenous pathway
Liver
LDL receptor
Scavenger receptor-A / CD 36
VLDL
VLDL
ABC-1
VLDL
SRB-1
IDL CE CE
LDL CE
Macrophage
CETP
Ox-
LDL
Cholesterol TG
CETP = cholesterol ester transport protein
LCAT=lecithin:cholesterol acyltransferase
HDL
LCAT
Nascent HDL
Kwiterovich PO, Jr. The metabolic pathways of high-density lipoprotein, low-density lipoprotein, and triglycerides: A current review. Am J Cardiol 2000;86:5L-10L

7. T4
The way thyroid hormones modulate lipid metabolism by variety of ways-hyperthyroidism + 3
LPL
VLDL
IDL 2 +
CETP T4
CETP
HDL2
LPL HL T4 + T4 HL 4 4 +
HDL3
CETP 5
Liver -
Ox-LDL
LDL
LDL
Receptor
LDL
Receptor +
Peripheral tissue
Macrophage 1 T4
Liberopoulos EN. Hormones 2002, 1(14):

8. DYSLIPIDEMIA - HYPERTHYROIDISM
Decrease in
total-cholesterol, LDL-cholesterol, apolipoproteinB, HDL-cholesterol, TG levels remain unchanged

9. T4
The way thyroid hormones modulate lipid metabolism by variety of ways-hypothyroidism - 3
LPL
VLDL
IDL 2 -
CETP T4
CETP
HDL2
LPL HL T4 - 4 T4 HL 4 -
HDL3
CETP 5
Liver +
Ox-LDL
LDL
LDL
Receptor
LDL
Receptor -
Peripheral tissue
Macrophage 1 T4
Liberopoulos EN. Hormones 2002, 1(14):

10. DYSLIPIDEMIA – HYPOTHYROIDISM
Raised of
total-cholesterol, LDL-cholesterol,
Ox-LDL-cholesterol, hyper TG, HDL-cholesterol,
increased Lp (a)
Clinically, lipid changes are more frequently seen
in subjects with hypothyroidism
These abnormal dyslipidemia enhanced the risk
of CAD

11. HYPOTHYROIDISM
In general population (western countries) hypothyroidism is
more frequent than hyperthyroidism (9.5% vs 2.2% )
More frequent in the western countries due to:
- high incidence of autoimmune thyroiditis Hashimoto
- active screening among elderly subjects
- more frequent use of I131 for Graves’ hyperthyroidism
Indonesia very low:
- low prevalence of Hashimoto thyroiditis, our observa-
tional study 2000 – 2010 only 45 patients
- screening in the elderly is not a routine procedure
- less frequent use I131 for Graves’ hyperthyroidism

12. THE MANAGEMENT OF DYSLIPIDEMIA IN THYROID DISEASE
Levels of total-C and LDL-C tend to increase as the thyroid function declines. Hypothyroidism constitutes a significant cause of secondary dyslipidemia Therefore the treatment of thyroid dyslipidemia is always focus on hypothyroidism Substitution with L-thyroxine therapy significantly improves the abnormal dyslipidemia, especially in overt hypothyroidism The reduction of cholesterol was larger in individuals with higher cholesterol levels

13. MANAGEMENT OF DYSLIPIDEMIA IN SUBCLINICAL HYPOTHYROIDISM
Subclinical hypothyroidism (SH) is defined by mildly elevated TSH levels (up to 10 uIU/L) with normal levels of FT4 and FT3 SH been detected with increasing frequency in recent years (more common than overt hypothyroidism) and causing major controversies concerning management and treating with L-thyroxin SH patients, tend to have high levels of total-C and LDL-C, ApoB and LP(a)

14. MANAGEMENT OF DYSLIPIDEMIA IN SUBCLINICAL HYPOTHYROIDISM
This dyslipidemia, make SH has been associated with in-
creased risk of CAD
Even though, the treatment with L-thyroxine is still contro-versies
Monzani F et al: L-T4 replacement therapy improved the atherogenic lipoprotein profiles and CIMT thickening
Carracio N et al: L-T4 treatment has significant decrease of both total-C and LDL-C
Hueston WJ et al: SH does not appear to be associated with abnormal serum lipid
Pearca EN: Clinical trials to date have not shown a beneficial effect of L- thyroxine on serum lid profiles in SH

15. CASE
TE male, 32 years, no DM, not HT, but heavy smoker, was diagnosis with thyroid follicular Ca. A total thyroidecto-my was performed followed by I131. Thyrax suppres-sion was given but sub-optimal (1992) The cholesterol levels was always high ( mg/dL), and still smoking, while TSHs showed subclinical hypothyridism In February 1998, he was admitted to the hospital due to acute myocardial infarction AMI due to dyslipidemia in subclinical hypothyroidism ??

16. MANAGEMENT OF DYSLIPIDEMIA IN THYROID DISEASE SUMMARY
Dyslipidemia is frequent in hypothyroidism Substitution with L-thyroxin will improve the abnormal lipid profiles L-thyroxin for subclinical hypothyroidism remain contro-versial Since both overt and subclinical hypothyroidism may occur in elderly subjects, where either diabetes mellitus, hyper-tension or CVD may coincidence with these conditions, statin therapy should be consider for the prevention of CVD

17. THANK YOU
Thank you
AOTA
Bali, Oktober 2012