an d in f lu e n c e o f s e ru m T S H on t h e s e ru m t o t al c h o le s t e r ol le v e l

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1 : T SH, =A b s t r a c t = P re v ale n c e o f s u b c lin ic al h y p ot h y r oi di s m in h y p e rc h o le s t e r ole m ic a du lt s an d in f lu e n c e o f s e ru m T S H on t h e s e ru m t o t al c h o le s t e r ol le v e l Won - Jea Jeong, M.D., Young - Seol Kim, M.D., Byeong - Heon Park, M.D., Cheol- Young Park, M.D., Mee- Sook Ryu, M.D., Seung - Joon Oh, M.D., Jeong - T ack Woo, M.D., Sung - Woon Kim, MD., In - Myoung Yang, M.D., Jin - Woo Kim, M.D., Young - Kil Choi, M.D. and Jeong - Ryung Paeng, M.D. M etabolism, Department of Internal M edicine, K yung -H ee University College of M edicine, Endocrine R esearch Institute, Seoul, K orea B ackg round : Subclinical hypothyroidism is frequently discovered from hypercholesterolemic adults. It is defined as an asymptomatic state which characterized by normal free thyroxine (FT 4) and elevated thyroid stimulating hormone (T SH) level. Hypercholesterolemia is a major risk factor for coronary heart disease, however hypercholesterolemia caused by hypothyroidism can be easily managed by thyroid hormone replacement. The screening of thyroid disease in hypercholesterolemia patient must be emphasized in order to find out correctable hypothyroidism. So we screened the prevalence of overt and subclinical hypothyroidism at different hypercholesterol levels in middle- aged men and women and also analyzed the correlation between T SH and total cholesterol level. Meth ods : We measured serum T SH levels and FT4 by radioimmunoassay from 491 patients with hypercholesterolemia. The subjects were divided into two groups according to serum cholesterol level. Group I was serum cholesterol mg/ dl and group II was mg/ dl. Subclinical hypothyroidism was defined as T SH levels higher than 4 mu/ L, in the presence of normal FT 4 concentration. Re s ult s : T he overall prevalence of subclinical and overt hypothyroidism was 3.4% and 2.5% in men and 4.7% and 3.5% in women of middle age. In men the prevalence of overt and subclinical hypothyroidism increased from 2.3% of group I to 16.1% in the group II (p <0.05). In women that increased from 5.2 % to 12.9 % (p <0.05). After age correction, an increase of 1 mu/ L T SH in men was associated with an increase of 3.2 mg/ dl total cholesterol (p <0.01). A similar trend was also found in women (2.1 mg/ dl p =0.052). : : :, 1, E -mail :

2 Korean Journal of Medicine : Vol. 62, No. 2, 2002 Conclus ion : In this population, the prevalence of hypothyroidism is up to 16.1% in middle- aged men, 12.9% in middle- aged women with high total cholesterol and it may justify screening of thyroid disease in hypercholesterolemic patients especially in clinical practice.(korean J Med 62: , 2002) Key W ords : Hypothyroidism; Hypercholesterolemia; T hyrotropin %, 1, 2 ). (subclinical hypothyroidism) (thyroid stimulating hormone, T SH). 10% 3, 4 ). (low density lipoprotein, LDL), 5, 6 ). T SH, 20 mg/ dl 4 ). LDL-, (high density lipoprotein- cholesterol, HDL- C) 7-9 ). 1 0 ). 3 7, 8, 1 1 ). T SH ( 2.0- <4.0 U/ ml) 1 2 )..,. T SH mg/ dl <300 mg/ dl, 2 >300 mg/ dl , 2 62, 1 154, Hitach- 747 T SH IRMA- mat (Byk- Sangtec, Diagnostica, Dietzenbach, Germany) T 4 (free thyroxine, FT 4) AMERLEX- MAB (Ortho- Clinical Diagnostics, USA). T SH>4 mu/ L FT 4 ( ng/ dl), T SH>4 mu/ L FT 4<0.8 ng/ dl.,, chisquare, p T SH

3 Won- Jea Jeong, et al : Prevalence of subclinical hypothyroidism in hypercholesterolemic adults and influence of serum T SH on the serum total cholesterol level Fig ure 1. T SH- Cholesterol Correlation in Men Fig ure 2. T SH- Cholesterol Correlation in Women T able 1. Numbers of the study sample and mean ag e Men Women Cholesterol (mg/ dl) Number AGE p Values are expressed as mean S.D T able 2. Prev alence (%) of ov ert & subclinical hy pothy roidism according to strata of total plasma cholesterol in men Cholesterol (mg/ dl) T otal p Overt Hypothyroidism Subclinical Hypothyroidism T otal 1/ 174 (0.6%) 3/ 174 (1.7%) 4/ 174 (2.35%) 5/ 62 (8.1%) 5/ 62 (8.1%) 10/ 62 (16.1%) 6/ 236 (2.5%) 8/ 236 (3.4%) 14/ 236 (5.9%) (linear regression model). 491 T SH FT , , , % 8.15% (p <0.01), 1.7% 8.1% (p <0.05). 2.3% 16.1% (p <0.05) % 5.9%, 3.2% 6.9%

4 : T able 3. Prev alence (%) of ov ert & subclinical hypothy roidism according to strata of total plasma cholesterol in w omen Cholesterol (mg/ dl) T otal p Overt Hypothyroidism Subclinical Hypothyroidism T otal 3/ 154 (1.9%) 5/ 154 (3.2%) 8/ 154 (5.2%) 6/ 101 (5.9%) 7/ 101 (6.9%) 13/ 101 (12.9%) 9/ 255 (3.5%) 12/ 255 (4.7%) 21/ 255 (8.2%) T able 4. Me an chole s terol lev els acc ording to T S H lev el in w omen and men Men W omen T SH (mu/ L) 4 > 4 4 > 4 n=222 n=14 n=234 n=21 Cholesterol (mg/ dl) p Values are expressed as mean S.D. T able 5. Mean T S H lev els acc ording t o ch ole s terol lev el in w omen and men Men W omen Cholesterol (mg/ dl) T SH (mu/ L) p Values are expressed as mean S.D % 12.9% (p <0.05). T SH 4 mu/ L mg/ dl mg/ dl (p <0.01), mg/ dl mg/ dl (p <0.05) mg/ dl. T SH, mu/ L, mu/ L (p <0.01) mu/ L, mu/ L. T SH,. T SH 1 mu/ L 3.2 mg/ dl (p <0.01), 2.1 mg/ dl (p =0.052).. LDL, LDL LDL. LDL- 5 ). (chylomicron remnants) 1 3 )., 50 3 ) , T SH

5 11 : T SH. mg/ dl 16.1%.., 7-9, 1 4 ). HDL 3, 7-9, ). LDL,, 7-9, 1 4 ). Alexander 4 ) 20 mg/ dl, 37 mg/ dl. r 2 =0.039 (p =0.002), r 2 =0.015 (p =0.052). LDL- C HDL- C. LDL- C HDL- C, Wiseman 1 9 ) LDL 13 A vaii (polymorphism). HDL- C (cholesterol ester transfer protein) TaqIB (intron 1), M spi (intron 8) R sai (exon 14) 2 1 ) , 8, 1 1 ). T SH ( mu/ L) 1 2 ).. homocystein, 2 2, 2 3 ). 2 4, 2 5 ).. T SH. mg/ dl.. :. : <300 mg/ dl mg/ dl T SH. :,, 3.4, 2.5,

6 Korean Journal of Medicine : Vol. 62, No. 2, %, 4.7, 3.5, 8.3% %, %, % 12.9%. T SH 1 mu/ L 3.2 mg/ dl (p =0.002) 2.1 mg/ dl (p =0.052). : T SH,. R E F E R E N C E S 1) Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, Evans JG, Young E, Bird T, Smith PA. The sp ectrum of thyroid disease in a community: the whickham survey. Clin Endocrinol 7: , ) Sawin CT, Castelli WP, Hershman JM, McNamara P, Bacharach P. The aging thyroid: thyroid def iciency in the F ramingham study. A rch Intern M ed 145: , ),,,,,,,,,.. 13: , ) Bindels AJ, Westendorp RG, Frolich M, Seidell JC, Blokstra A, Smelt AH. The p revalence of subclinical hypothyroidism at different total plasma cholesterol levels in middle aged men and women: a need f or case-f inding? Clin Endocrinol 50: , ) Thompson GR, Soutar AK, Spengel FA, Jadhav A, Gavigan SJ, Myant NB. Def ects of recep tormediated low density lip op rotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. P roc N atl A cad Sci U SA 78: , ) Scarabottolo L, Trezzi E, Roma P, Catapano AL. Exp erim ental hyp othyroidism m odulates the expression of the low density lipoprotein receptor by the liver. A therosclerosis 59: , ),,,,.. 7:31-38, ),,,,,,,,,. Thyroxine. 11:41-51, ),,,,,,,,,. LP (a). 12:11-17, ) Becker C. Hyp othyroidism and atherosclerotic heart disease: pathogenesis, medical management, and the role of coronary artery bypass surgery. Endocr R ev 6: , ) T anis BC, Westendorp GJ, Smelt HM. Eff ect of thyroid substitution on hyp ercholesterolemia in patients with subclinical hypothyroidism : a reanalysis of intervention studies. Clin Endocrinol 44: , ) Michalopoulou G, Alevizaki M, Piperingos G, Mitsibounas D, Mantzos E, Adamopoulos P, Koutras DA. H igh serum cholesterol levels in p ersons with 'high- normal' TSH levels: should one extend the def inition of subclinical hyp othyroidism? Eur J Endocrinol 138: , ) Weintraub M, Grosskopf I, Trostanesky Y, Charach G, Rubinstein A, Stern N. Thyroxine rep lacement therapy enhances clearance of chylomicron remnants in patients with hyp othyroidism. J Clin Endocrinol M etab 84: , ) Arem R, Patsch W. L ip op rotein and ap olip op rotein levels in subclinical hypothyroidism. A rch Intern M ed 150: , ) Oettgen P, Ginsburg GS, Horowitz GL, Pasternak RC. F requency of hyp othyroidism in adults with serum total cholesterol levels>200 mg/ dl. A m J Cardiol 73: , ) Althaus BU, Staub JJ, Ryff- De Leche A, Oberhansli A, Stahelin HB. LDL/ HDL change in subclinical hyp othyroidism: p ossible risk factors f or coronary heart disease. Clin Endocrinol 28: , ) Aviram M, Luboshitzky R, Brook JG. L ip id and lip op rotein pattern in thyroid dysf unction and the eff ect of therapy. Clin B iochem 15:62-66, ) Feely J, Iqbal SJ, Isles T E, Bakry M. T otal cholesterol/ HDL cholesterol ratio in hyp erthyroidism, hyp othyroidism and subclinical hyp othyroidism. H orm M etab R es 12: , ) Wiseman SA, Powell JT, Humphries SE, Press M. The magnititude of the hyp ercholesterolemia of hyp othyroidism is associated with variation in the low density lip op rotein recep tor gene. J Clin Endocrinol M etab 77: , ) Kuusi T, T askinen MR, Nikkila EA. L ip op roteins, lip olytic enzymes, and hormonal status in hyp othy

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