lipidni status kod novootkrivene subkliniČke i ......u obe grupe pacijenata iz našeg rada izmerili...

46 MEDICINSKI GLASNIK / str. 46-51

Snežana Marinković1 LIPIDNI STATUS KOD NOVOOTKRIVENE SUBKLINIČKE I KLINIČKE FORME HIPOTIREOZE

UVOD

Hipotireoza je bolest koja se može javiti u svakom životnom dobu, karakteriše se smanjenom sintezom tireoidnih hormona. Prema težini kliničke slike, može biti subklinička i klinička. Učestalost subkliničke forme hipotireoze iznosi oko 9 %, a učestalost klinički manifestne forme ove bolesti veća je kod ženske populacije i iznosi oko 2 % , dok se kod muške kreće od 0,1 do 0,2 %. (Larsen et all, 2002) Početak ove bolesti je obično neprimetan i pacijent može da postane svestan prethodnih simptoma, tek pošto se lečenjem postigne eutireoidizam. Ispoljena bolest je udružena sa simpto-mima i znacima, kao što su nepodnošenje hladnoće, dobijanje telesne težine, zatvor, suva koža, bradikardija, promuklost, usporeni mentalni procesi.

Telesna težina raste zbog nagomilavanja telesnih masti i zadržavanja vode uprkos smanjenom apetitu.

U ovoj bolesti čest je porast holesterola u plazmi i to na račun LDL frakcija, a posledica je smanjenje ekspresije LDL receptora u jetri, koji su osetljivi na delova-nje trijodtironina. Smanjen odnos ukupnog holesterola ili LDL holesterola sa HDL holesterolom koriguje se u toku terapije hipotireoidizma. Sve ove promene zajedno smatraju se odgovornim za aterogeni lipidni profil u hipotireoidizmu.

Laboratorijskoj potvrdi bolesti pristupamo nakon dovoljne kliničke sumnje. Potrebno je merenje nivoa TSH, ako je TSH povišen potrebno je izmeriti nivo jedne od slobodnih frakcija hormona štitaste žlezde. Kod subkliničke forme hipotireoze nivo TSH je povišen, a nivo FT4 je u granicama normale. Vrednost TSH u subklinič-koj formi bolesti se kreće do 10 mU/L. Podaci o udruženosti subkliničke hipotire-oze sa neuropsihijatrijskim, lipidnim i kardiovaskularnim poremećajima nejasni su. Poremećaj metabolizma lipida je druga moguća posledica subkliničke hipotireoze. Metaanaliza Danesea i saradnika iz 2000. g. pokazala je da u subkliničkoj hipotire-ozi supstitucija tiroksinom smanjuje ukupan i LDL holesterol, a da ne utiče na HDL holesterol i trigliceride (Danese MD et all 2000). Tokom Tromso studije nađena je

1 Specijalna bolnica Čigota, Zlatibor, [email protected]

47LIPIDNI STATUS KOD NOVOOTKRIVENE SUBKLINIČKE I KLINIČKE FORME HIPOTIREOZE

pozitivna asocijacija između serumske koncentracije TSH i koncentracije ukupnog i LDL holesterola. Kod obolelih od subkliničke hipotireoze terapija tiroksinom je smanjila nivoe ovih lipida. (Igbal et all 2006)

Klinički manifestnu formu ove bolesti imaju pacijenti sa povišenim nivoom TSH preko 10 mU/L i smanjenim nivoom jedne od slobodnih frakcija tireoidnih hormona. Rezultati Framinghamske studije pokazuju signifikantan porast nivoa ukupnog hole-sterola, LDL holesterola i triglicerida sa porastom nivoa TSH kod žena i porast nivoa ukupnog holesterola i triglicerida kod muškaraca. (Report of the 75th Annual Meeting of American Thyroid Association Palm Beach, Florida, USA, 2003)

CILJ RADA

Uporediti nivo TSH sa nivoom holesterola i triglicerida kod novootkrivene subkliničke i klinički manifestne ženske i muške hipotireoze.

MATERIJAL I METODE

Svim pacijentima obuhvaćenim ovim radom izmerili smo hormonski status štita-ste žlezde (FT4 i TSH), kao i nivo ukupnog holesterola i triglicerida. Nivo FT4 i TSH smo izmerili na aparatu DPC Immulite 1000, dok smo nivo holesterola i triglicerida u krvi odredili na aparatu ILAB 300 +.

REZULTATI

Subklinička

Redni broj Inicijali

Godine života FT4 TSH Holesterol Trigliceridi

1. M.S. 58 14,4 5,33 7,43 1,17

2. T.R. 65 13,61 6,25 7,97 3,0

3. V.B. 60 18,1 7,17 5,7 1,70

4. O.M. 48 15,9 6,96 9,31 10,06

5. P.G. 53 18,5 6,59 6,38 1,49

6. D.D. 54 16,64 6,78 5,3 1,52

7. V.D. 40 13,7 9,07 5,15 2,14

8. Z.LJ. 54 15,3 6,42 6,93 0,84




9. B.B. 30 19,3 7,81 3,94 0,44

10. P.Z. 62 13,0 5,48 5,18 6,05

11. DJ.D.m 35 19,6 7,84 8,57 2,84

12. C.R. 56 12,9 5,08 7,11 1,42

13. K.S.m 46 13,7 6,59 6,91 1,29

14. S.R. 48 19,0 6,60 10,06 2,92

15. P.D. 26 10,4 5,75 5,22 1,6

16. C.M. 54 16,7 6,59 7,46 2,13

17. T.Z. 60 14,2 8,18 5,79 1,2

18. P.V. 55 15,9 6,60 8,0 3,0

19. T.Z. 35 13,1 7,72 7,56 2,0

20. V.J. 40 12,3 8,95 5,59 1,74

21. M.M. 30 12,6 8,01 5,22 1,22

22. P.LJ. 51 8,99 6,34 5,46 1,22

23. P.A. 56 10,2 5,18 7,14 2,36

24. P.M. 38 18,1 8,87 5,3 1,5

25. N.G. 60 11,5 4,97 8,90 5,8

Klinička



1. G.B. 37 5,15 100,0 6,47 0,84

2. L.M. 68 6,2 150,0 8,3 2,7

3. J.G. 47 9,10 32,9 4,76 1,8

4. O.D. 47 11,3 55,3 8,41 1,16

5. V.M. 55 5,1 58,76 7,1 2,3

6. DJ.B. 53 11,0 13,0 4,9 0,6

7. A.M. 48 11,6 14,75 7,35 2,3


8. I.S. 50 6,2 74,3 6,95 2,57

9. K.Z. 61 7,4 39,2 8,3 3,1

10. D.J. 41 11,6 42,5 6,10 1,16

11. T.LJ. 44 12,4 10,29 6,03 0,99

12. E.S. 48 9,67 75,0 8,72 1,11

13. T.M.m 30 13,5 29.76 7,47 2,98

14. C.K. 38 12,1 13,3 4,38 2,45

15. A.M.m 68 5,03 87,95 5,56 1,69

16. A.S. 58 15,6 14,2 4,64 2,01

17. K.M. 28 8,0 14,53 6,41 0,8

18. P.J. 29 12,3 69,4 8,04 1,13

19. V.Z. 50 15,4 11,65 7,18 2,44

20. S.M. 21 10,4 10,73 3,8 1,07

21. K.M. 65 10,9 10,64 8,52 2,68

22. N.A. 35 2,7 121,0 8,2 1,0

23. S.M. 35 10,0 39,9 5,55 1,02

24. G.S. 42 10,2 14,2 6,7 1,5

25. M.M. 63 10,5 13,6 7,04 1,93

U obe grupe pacijenata, koje smo pratili u našem radu, odnos muškog i ženskog pola bio je identičan.

Od ukupno 25 pacijenata, koje smo pratili, i u jednoj i u drugoj grupi, 23 su bile osobe ženskog pola, što je 92 % uzorka, dok su u svakoj grupi bila zastupljena po 2 muškarca, što je 8 % uzorka.

Prosečna životna dob u grupi subkliničke forme hipotireoze bila je 48,56, a u grupi kliničke forme ove bolesti bila je 46,44 godine.

U okviru dijagnostike i subkliničke i kliničke forme hipotireoze merili smo vrednost slobodnog tiroksina (FT4) i tireostimulirajućeg hormona (TSH).

U grupi subkliničke forme hipotireoze prosečna vrednost slobodnog tiroksina iznosila je 14,71, dok je u grupi kliničke forme ta vrednost bila 9,73 nmol/l.

Najniža vrednost slobodnog tiroksina bila je u grupi kliničke forme hipotireoze i iznosila je 2,7 nmo/l.

Normalna vrednost slobodnog tiroksina u našoj laboratoriji se kreće od 10,2 do 24,5 nmol/l.


Prosečna vrednost tireostimulirajućeg hormona u grupi subkliničke forme hipo-tireoze bila je 6,84 pg/ml, a kod kliničke 44,67 pg/ml.

Najviša vrednost tireostimulirajućeg hormona u grupi kliničke forme hipotireoze iznosila je 150,0 pg/ml, a u subkliničkoj 9,07 pg/ml.

Normalna vrednost TSH u našoj laboratoriji se kreće od 0,4 do 4,2 pg/ml.Prosečna vrednost ukupnog holesterola u subkliničkoj grupi iznosila je 6,72

mmo/l, a u kliničkoj 6,67 mmo/l.Najviša vrednost ukupnog holesterola u subkliničkoj grupi bila je 10,06, a u

kliničkoj 8,52 mmo/l.U našoj laboratoriji nivo ukupnog holesterola se kreće od 3,2 do 5,7 mmo/l.U obe grupe pacijenata iz našeg rada izmerili smo i vrednost triglicerida u krvi.

Njihove prosečne vrednosti bile su 2,43 mmo/l u subkliničkoj grupi, dok je u kliničkoj grupi ta vrednost bila 1,73 mmo/l.

Najviša vrednost triglicerida u krvi u našim posmatranim grupama bila je 10,06 mmo/l i to u okviru subkliničke forme posmatrane bolesti.

Najviša vrednost triglicerida u krvi u okviru kliničke forme hipotireoze u našoj izabranoj grupi bila je 2,98 mmo/l.

Normalna vrednost triglicerida u krvi u našoj laboratoriji kreće se od 1,1 do 2,26 mmo/l.

DISKUSIJA

Naš rad je pokazao da su i sbklinička i klinička forma smanjene funkcije štitaste žlezde u daleko većem procentu zastupljene kod osoba ženskog pola.

Prema podacima ovog rada nije bilo razlike u životnom dobu između posma-tranih grupa.

Od ukupno 25 pacijenata sa subkliničkom formom hipotireoze, kod njih 10, što je 40 % uzorka, izmerene su normalne vrednosti holesterola u krvi, dok su kod svih ostalih pacijenata iz ove grupe vrednosti holesterola bile povišene.

Kod kliničke forme smanjene funkcije štitaste žlezde od 25 pacijenta obuvaćenih ovim radom samo 6, odnosno 24 % grupe, imalo je vrednost holesterola u granicama normale, dok je ostalih 76 % pacijenata ispitivane grupe imalo povišene vrednosti holesterola u krvi.

U grupi subkliničke forme hipotireoze od 25 pacijenata, njih 17, što je 68 % grupe, imalo je potpuno normalne vrednosti triglicerida u krvi, dok kod kliničke forme ove bolesti normalan nivo triglicerida ima 16 pacijenata, što je 64 % grupe.

Ovim radom pokazano je da i kod subkliničke i kod kliničke forme hipotireoze postoji pozitivna korelacija između nivoa TSH i nivoa holesterola, sa povećanjem nivoa TSH kod najvećeg broja pacijenata došlo je do povećanja nivoa holesterola u krvi.


U grupi subkliničke forme hipotireoze izmerene su najviše vrednosti i holesterola i triglicerida u krvi.

Svi pacijenti obuhvaćeni ovim radom nisu bili na terapiji ni statinima ni fibra-tima.

ZAKLJUČAK

Postoji pozitivna korelacija između nivoa TSH i nivoa holesterola, dok je između nivoa TSH i nivoa triglicerida negativna korelacija i kod subkliničke i kod kliničke forme smanjene funkcije štitaste žlezde.

LITERATURA

1. Larsen PR, Davies TF. Hypothyroidism and Thyroiditis. In Larsen PR, Kronenberg HM, Melmed Sh, Polonsky KS. Wiliams Textbook of Endocrinology, 10th Edition, Saunders, Philadelphia 2002.

2. Report of the 75th Annual Meeting of American Thzroid Association Palm Beach, Florida, USA, September 2003.

3. Wiersinga WM. Adult Hypothyroidism. The Thzroid and its Diseases, March 4, 2004.4. Danese MD, Ladenson PW, Meinert CLm Powe NR. Clinical review 115, effect of

thyroxine therapy on serum lipoproteins in patients with mild thyroid failure, a quanti-tative review of the literature. J Clin Endocrinol. Metab 2000; 2993–3001.

5. Igbal A, Jorde R, Figenschau Y. Serum lipid levels in relation to serum thyroid stimu-lating hormone and the effect of thyroxine treatment on serum lipid levels in subjects with subclinical hypothyroidism. The Tromso Study. J Intern Med. 2006; 53–61.


Snezana Marinkovic1 LIPIDS IN NEWLY DISCOVERED SUBCLINICAL AND CLINICAL HYPOTHYROIDISM

INTRODUCTION

Hypothyroidism is a disease that can occur at any age, is characterized by reduced synthesis of thyroid hormones. According to the severity of the clinical picture may be subclinical and clinical. The frequency of the subclinical form of hypothyroidism is about 9%, and the incidence of clinically manifest forms of this disease is higher in the female population at around 2%, while in the male ranges from 0.1–0.2%. (Larsen et al, 2002) Start of the disease is usually imperceptible and the patient can become aware of previous symptoms, only after the treatment achieve eutireoidizam. Obvious disease is associated with symptoms and signs such as cold intolerance, obtaining body weight, constipation, dry skin, bradycardia, hoarseness, slowed mental processes.

Body weight increases due to the accumulation of body fat and water retention, despite the reduced appetite.

This disease is common COPs increase in plasma at the expense of LDL frac-tion, is a consequence of reduced expression of LDL receptors in the liver, which are sensitive to the action of triiodothyronine. Reduced ratio of total cholesterol or LDL cholesterol with HDL cholesterol is adjusted during therapy hipotireoidizma.Sve these changes together are considered to be responsible for the atherogenic lipid profile in hypothyroidism.

Laboratory confirmation of disease approach after sufficient clinical suspicion. It is necessary to measure the level of TSH, TSH is elevated if it is necessary to me-asure the level of one of the free fraction of thyroid hormones. In subliničke forms of hypothyroidism TSH level is elevated and FT4 level is within normal limits. TSH in the subclinical form of the disease is moving to 10 mU / L. Data on association of subclinical hipotieoze with neuropsychiatric, cardiovascular and lipid disorders are unclear. The disorder of lipid metabolism is long possible consequence of subclinical hypothyroidism. Meta-analysis Danese and associates from 2000g showed that in subclinical hypothyroidism replacement therapy reduces total and LDL cholesterol without affecting HDL cholesterol and triglycerides (Danese MD et al, 2000). During

1 Special hospital for thyroid diseases and metabolic diseases, Zlatibor, [email protected]

53LIPIDS IN NEWLY DISCOVERED SUBCLINICAL AND CLINICAL HYPOTHYROIDISM

Tromso studies found a positive association between serum TSH and serum total and LDL cholesterol. In patients with subclinical hypothyroidism with thyroxine therapy decreased the levels of these lipids. (Iqbal et al 2006)

Clinically manifest forms of this disease have patients with elevated TSH over 10MU / L and a reduced level of one of the free fraction of thyroid hormones. Results of the Framingham study showed a significant increase in levels of total cholesterol, LDL cholesterol and triglyceride levels with increasing levels of TSH in women and increase in total cholesterol and triglyceride levels in men. (Report of the 75th Annual Meeting of the American Thyroid Association in Palm Beach, Florida, USA, 2003)

GOAL OF WORK

Compare the level of TSH and cholesterol and triglyceride levels in newly dia-gnosed subclinical and clinical manifestations of male and female hypothyroidism.

MATERIALS AND METHODS

All the patients is covered by this paper, we measured thyroid hormone status (FT4 and TSH) and total cholesterol and triglycerides. The level of FT4 and TSH were measured on the device DPC Immulite 1000 while we were in cholesterol and triglyceride levels in the blood to determine the camera ILAB 300 +.

RESULTS

Subclinical

Ordinal number Initials Age FT4 TSH Cholesterol Triglycerides

1. M.S. 58 14,4 5,33 7,43 1,17

2. T.R. 65 13,61 6,25 7,97 3,0

3. V.B. 60 18,1 7,17 5,7 1,70

4. O.M. 48 15,9 6,96 9,31 10,06

5. P.G. 53 18,5 6,59 6,38 1,49

6. D.D. 54 16,64 6,78 5,3 1,52

7. V.D. 40 13,7 9,07 5,15 2,14

8. Z.LJ. 54 15,3 6,42 6,93 0,84



9. B.B. 30 19,3 7,81 3,94 0,44

10. P.Z. 62 13,0 5,48 5,18 6,05

11. DJ.D.m 35 19,6 7,84 8,57 2,84

12. C.R. 56 12,9 5,08 7,11 1,42

13. K.S.m 46 13,7 6,59 6,91 1,29

14. S.R. 48 19,0 6,60 10,06 2,92

15. P.D. 26 10,4 5,75 5,22 1,6

16. C.M. 54 16,7 6,59 7,46 2,13

17. T.Z. 60 14,2 8,18 5,79 1,2

18. P.V. 55 15,9 6,60 8,0 3,0

19. T.Z. 35 13,1 7,72 7,56 2,0

20. V.J. 40 12,3 8,95 5,59 1,74

21. M.M. 30 12,6 8,01 5,22 1,22

22. P.LJ. 51 8,99 6,34 5,46 1,22

23. P.A. 56 10,2 5,18 7,14 2,36

24. P.M. 38 18,1 8,87 5,3 1,5

25. N.G. 60 11,5 4,97 8,90 5,8

Clinical


1. G.B. 37 5,15 100,0 6,47 0,84

2. L.M. 68 6,2 150,0 8,3 2,7

3. J.G. 47 9,10 32,9 4,76 1,8

4. O.D. 47 11,3 55,3 8,41 1,16

5. V.M. 55 5,1 58,76 7,1 2,3

6. DJ.B. 53 11,0 13,0 4,9 0,6

7. A.M. 48 11,6 14,75 7,35 2,3


8. I.S. 50 6,2 74,3 6,95 2,57

9. K.Z. 61 7,4 39,2 8,3 3,1

10. D.J. 41 11,6 42,5 6,10 1,16

11. T.LJ. 44 12,4 10,29 6,03 0,99

12. E.S. 48 9,67 75,0 8,72 1,11

13. T.M.m 30 13,5 29.76 7,47 2,98

14. C.K. 38 12,1 13,3 4,38 2,45

15. A.M.m 68 5,03 87,95 5,56 1,69

16. A.S. 58 15,6 14,2 4,64 2,01

17. K.M. 28 8,0 14,53 6,41 0,8

18. P.J. 29 12,3 69,4 8,04 1,13

19. V.Z. 50 15,4 11,65 7,18 2,44

20. S.M. 21 10,4 10,73 3,8 1,07

21. K.M. 65 10,9 10,64 8,52 2,68

22. N.A. 35 2,7 121,0 8,2 1,0

23. S.M. 35 10,0 39,9 5,55 1,02

24. G.S. 42 10,2 14,2 6,7 1,5

25. M.M. 63 10,5 13,6 7,04 1,93

In both groups of patients that we followed in our work, the ratio of males and females was identical.

From a total of 25 patients that we followed in both groups, 23 were females which is 92% of the sample, while in each group were represented by 2 men, which is 8% of the sample.

The average age in the group of the subclinical form of hypothyroidism was 48.56 and in the group of clinical forms of the disease was 46.44 years.

Within diagnostics and subclinical and clinical hypothyroidism, we measured the level of free thyroxine (FT4) and thyroid-stimulating hormone (TSH).

In the group of the subclinical form of hypothyroidism average value of free thyroxi-ne was 14.71, while in the group of clinical forms that value was 9.73 nmol / l.

The lowest level of free thyroxine was in a group of clinical forms of hypot-hyroidism and was 2,7nmo / l.

The normal level of free thyroxine in our laboratories ranging from 10.2 to 24.5 nmol / l.


The average value of thyroid-stimulating hormone in the group of the subclinical form of hypothyroidism was 6.84 pg / ml, and for clinical 44,67pg / ml.

The highest value tireostimulrajućeg hormone in a group of clinical forms of hypothyroidism and was 150,0pg / ml and subclinical 9.07 pg / ml.

A normal TSH in our laboratory ranges from 0.4 to 4.2 pg / ml.The average value of total cholesterol in the subclinical group was 6,72mmo /

l and clinical 6,67mmo / l.The highest value of total cholesterol in the subclinical group was 10.06, and

in clinical 8,52 mmo / l.In our laboratory total cholesterol levels ranging from 3.2 to 5.7 mmol / L.In both groups of patients in our study, we measured the levels of triglycerides

in the blood. Their average values were 2,43 mmo / l in the subclinical group, while the clinical group this value was 1,73mmo / l.

The highest value of triglycerides in the blood in our observed groups was 10.06 mmol / l within the framework of the subclinical form of the particular disease.

The highest value of triglycerides in the blood within clinical forms of hypot-hyroidism in our selected group was 2,98mmo / l.

Normal levels of triglycerides in the blood in our laboratories ranging from 1.1 to 2,26mmo / l.

DISCUSSION

Our work has shown that sbklinička I clinical form of reduced thyroid function are far higher percentage represented in females.

According to this study there was no difference in age between the groups.From a total of 25 patients with subclinical form of hypothyroidism, with 10 of

them which is 40% of the sample were measured by a normal cholesterol levels in the blood, while in all other patients from this group cholesterol levels were elevated.

In clinical form of reduced thyroid function of 25 patients obuvaćenih this work only 6 or 24% of the group had a cholesterol level within the normal range, while the other 76% of patients studied groups had elevated levels of cholesterol in the blood.

In the group of the subclinical form of hypothyroidism of 25 patients, 17 of them as 68% of the group had a completely normal value trtiglicerida in the blood, while the clinical forms of the disease a normal level of triglycerides in 16 patients, which is 64% of the group.

This work demonstrated that with subclinical and clinical forms with hypot-hyroidism there is a positive correlation between the levels of TSH and cholesterol levels, increasing the level of TSH in the majority of patients have increased levels of cholesterol in the blood.


In the group of the subclinical form of hypothyroidism measured the highest values of cholesterol and triglycerides in the blood.

All patients included in this work were not on statin therapy did not even fibrates.

CONCLUSION

There is a positive correlation between the levels of TSH and cholesterol levels, while levels between TSH levels triglicrerida negative correlation with the clinical and subclinical form of reduced thyroid function.

REFERENCES

1. Larsen, PR, Davies TF. Hypothyroidism and Thyroiditis in Larsen PR, Kronenberg HM, Melmed Sh, Polonsky KS. Williams Textbook of Endocrinology, 10th Edition, Saunders, Philadelphia 2002.

2. Report of the 75th Annual Meeting of the American Association Thzroid Palm Beach, Florida, USA, September 2003.

3. Wiersinga WM. Adult Hypothyroidism. The Thzroid and its Diseases, March 4, 2004.4. Danese MD, Assist, Meinert CLM Powe NR. Clinical review 115 Effect of thyroxine

therapy on serum lipoproteins in patients with mild thyroid failure, a quantitative review of the literature. J Clin Endocrinol Metab. Metab 2000; 2993–3001.

5. Igbal A Jorde R, Figenschau Y. Serum lipid levels in relation to serum thyroid stimulating hormone and the effect of thyroxine treatment on serum lipid levels in subjects with subclinical hypothyroidism, the Tromso Study. J Intern Med. 2006; 53–61.

lipidni status kod novootkrivene subkliniČke i ......u obe grupe pacijenata iz našeg rada izmerili...

Documents