GROUP 2

GROUP 1

Mariana Purice, I.H. Ursu, A. Goldstein

National Institute of Endocrinology C.I. Parhon, Bucharest, Romania

HYPERHOMOCYSTEINEMIA, A RISK FACTOR INTERACTING IN MODERATE AND SEVER HYPOTHYROIDISM

1. Thyroid status is an important determinant of plasma tHcy and affects serum folate levels .

2. Significantly lower serum folate in the study group is pleading for the role of folate deficiency in hyperhomocysteinemia induced by hypothyroidism.

3. High prevalence of hyperhomocysteinemia in hypothyroid patients represent an argument to associate folate supplementation to levothyroxine therapy, especially in patients with other risk factors for cardiovascular disease.

4. Dynamic evaluation of plasmatic homocysteine levels in correlation with Folic Acid and standard laboratory parameters is important for the estimation of supplementary risk factor and follow up of the specific therapy in hypothyroid patients.

CONCLUSIONS

DISCUSSION

Moderate hyperhomocysteinemia was frequent in our study groups: 68% in group 1 and 76% in group 2. Borderline (10-12 mol/L) values were found in 24 % in group 1 and 28 % in group 2.

Mean serum folate was significantly lower in group 1 versus control (5.9 ng/ml versus 9.1ng/ml) and NS lower in group 2

Both serum cholesterol and LDL cholesterol were significant higher in the study groups before treatment. Serum creatinine was in the normal range in both groups.

After six months of folate therapy associated with levothyroxine therapy, plasma homocysteine decreased significantly in the moderate hypothyroid patients from 14.27 mol/L to 8.17 and

from 16.9 to 7.9 in the sever iatrogenic hypothyroidism.

Epidemiologic evidences show that mild hyperhomocysteinemia (>12 mol/L) is an independent risk factor for atherosclerotic and

atherothrombotic vascular disease. Between 5-10 % of normal population and more then 40% of patients with cardiovascular

diseases have hyperhomocysteinemia (HHcy).

Additional risk factors and endocrine disorders (diabetes, hypothyroidism) may additively or by interacting with

hyperhomocysteinemia, increase overall risk.

Hypothyroidism is associated with increased cardiovascular morbidity which might be explained by the atherogenic lipid profile

and/or hyperhomocysteinemia. This may exacerbate the risk of cardiovascular disease in hypothyroidism that is traditionally

attributed to lipid changes.

Study groups:

25 patients with primary hypothyroidism before and during levotyroxine treatment. We measured plasma tHcy , serum folate, TSH, T3, T4 and cholesterol, LDL, HDL, , creatinine. We found moderate low level of serum folate (5.84 ng/ml) .Only 20% of subjects had basal tHcy < 10 mol/L while 44% had plasma tHcy between 10-17 mol/L and 36 % had tHcy >17 mol /L, significant elevated cholesterol, HDL cholesterol at medium risk level . Mean TSH concentration was 24.88 UI/ml. After achieving an euthyroid status, tHcy, folate and hormons leveles were evaluated before and after three and six month of daily folate supplementation therapy (5 mg/day). In 76% of the subjects with basal level t Hcy> 10 mol/lL, a significant decrease (p 20mol/L. High values of tHcy was correlated with high levels of thyroglobuline (> 2 ng/ml) for 10 patients with thyroid cancer metastasis. Normal folate serum mean level was found (7.89 ng/ml). Carotidian ultrasound for measuring the intima - media thickness (IMT) was done.
We evaluated the patients after 3 month and 6 month of folic acid administration (5 mg/day) together with levotyroxine substitution, observing significant decrease of tHcy (p10 IU/ml

Levo thyroxine: 75-150 g/day

Folic acid : 5 mg/day

Group 2:

Sever Hypothyroidism

postoperative hypothyroidism after thyroidectomy for thyroid cancer before radiotherapy.

25

F=20

M=5

52-73

>50 IU/ml

Levo thyroxine: 100-150 g/day

Folic acid: 5 mg/day

Control

euthyroid status

32

F=20

M=12

35-50

2.2 IU/ml

Total homocysteine ( tHcy) was assayed with ELISA method(DRG) after a reduction and enzymatic conversion steps .

Reference values

tHcy < 10 mol/L SAFE

tHcy : 10-12 mol/L Tolerated: normal subjects

Therapy recommended (ac folic +/- Vit B) for subjects with high risk factors

tHcy : > 12-30 mol/L moderate Hyperhomocysteinemy

tHcy : > 30-100 mol/L intermediate Hyperhomocysteinemy

tHcy : > 100 mol/L sever Hyperhomocysteinemia

Folic acid: chemiluminiscence, ACS -180 Bayer Serum cholesterol, HDL, LDL, creatinine: colorimetric (Roche, HITACHI 912) Serum hormones : TSH, T3, T4, FT4 ( RIA/ IRMA, ADALTIS)

Results were subjected to non parametric tests (Mann-Whitney U test) and data are expressed as media+/- SD.

Correlations were tested by Spearman correlation test

All statistical procedure were performed using the SPSS ( for Social Sciences Statistical Package).

Statistical analysis

After therapy

RESULTS

GROUP 2

Fig. 4. Homocystein concentration distribution

24%

28%

48%

tHcy 20 mol/l

Fg. 6. Serum colesterol, HDL and LDL before treatment

Fg. 5. Homocystein and Folic acid before treatment

GROUP 1

Fig.3.

Homocystein

and Folic acid levels in group 1 and

control

0

2

4

6

8

10

12

14

16

Hcy

FolicAcid

9.32

11.9

14.27

5.81

Control

Hypothyr

Before therapy

Chart2HcyHcyHcyFolic acidFolic acidFolic acidCholesterolCholesterolCholesterolHDL- ColestHDL- ColestHDL- ColestBasal3 month6 monthGroup 2: Hcy , Cholesterol , HDL Cholest during folate supplimentation therapy16.799.079.77.718.2915.3638022021460.5749.845.5Grup 5 osteoporozaNrIDDateNumePrenumeSexVirstamedicDiagnosticTimpHomocystFolatT3(ng/dl)(80-200)T4(ug/dl)(4.5-13)FT4TSH( uUI/ml) ( 0.5-4.5)TgAnti TgCreatColestHDLLDLECO17019.06.2007BalanicaRodicaf13374MuseteanuOsteoporoza11.622.330.741784710921407.12.2006BiuElenafDumitracheOsteoporozabaza11.238.060.6622340.3136381Jun-07BuneaGhineaf14054MuseteanuOsteop14.684.030.6818960117480Jun-07CiuleiCristinaf13381MuseteanuOsteop12.024.441.0924048.716956308.06.2007CodinElenaf12521MuseteanuOsteoporoza9.1211.230.6426839.91936102.11.2006ConstantinescuStefanafDumitracheOsteoporozabaza10.80.6416332.19774818.04.2007ConstantinescuStefanafDumitracheOsteoporoza6 luni cu ACTONEL10.124.530.4925482155813812,11,2007ConstantinescuStefanafDumitracheOsteoporoza10.124.5391105.12.2006CorfitaElenafDumitracheOsteoporozabaza10.186.040.9918638.611810927.11.2006CrainiceanuMariafPaunOsteoporozabaza13.368.060.918232.794116207.06.2007CristeaMioaraf12507MuseteanuOsteoporoza10.8911.840.4813249.166121028.11.2006HerjeuEugeniafDumitracheOsteoporozabaza8.314.150.6727767.3143131205.12.2006HodorogVioricafPaunOsteoporozabaza10.8511.010.8621534.112614822.11.2006IntzeVictoriafSucaliucOsteoporozaArtrita reumatoidabaza12.193.21.0820541.8126155208.05.2006IordacheConstantafMuseteanuOsteoporoza9.389.70.8819179.910016720.11.2006LazarescuAnafPaunOsteoporozabaza7.613.330.561613664179608,08,2007LisamaruTeodoraf50MuseteanuOsteop26.259.20.8317052.590186714.06.2007MortasipuFloareafMuseteanuOsteoporoza14.666.690.9417662.2108195408.05.2006MustaceaVasilicaf55MuseteanuOsteoporoza11.586.40.7924737.6187207927.06.2007Nedelcumariaf13992DumitracheOsteop9.823.840.6418483.4942124Jan-07NedelcuMariafDumitracheOsteoporozabaza6.29226612.06.2007PaladeGetaf12093MuseteanuOsteoporoza8.886.90.7116348.20.5231306.12.2006PopescuGicafSimescuOsteoporozaB.Basedowbaza7.629.010.8329848.8200242019.12.2006PuscoiFloricafDumitracheOsteoporozabaza11.256.538.62.30.7318855.9115256815.06.2007SiciacGeorgetaf73osteopcontrol 6 luni11.623.440.7825755.2178265906.06.2007SlatineanuElenafMuseteanuOsteoporoza8.853.840.5618444.8126271712.12.2006SpiciacGeorgetafDumitracheOsteoporozabaza16.743.339.21.20.6922760.6145289501,08,2007SprinceanaFloricafMuseteanuOsteop14.44.190.6124381.9147296107.06.2007TataruElisabetaf12131MuseteanuOsteoporoza11.0920.570.7922161.6144309220,07,2007ZamfirCristinaf65MuseteanuOsteop13.078.410.7622667.8137315730.05.2007ZamfirescuMariafMuseteanuOsteoporoza6.352.310.4716356.992HomocystFolatT3(ng/dl)(80-200)T4(ug/dl)(4.5-13)FT4TSH( uUI/ml) ( 0.5-4.5)TgAnti TgCreatColestHDLLDLmedia11.326.590.008.900.001.750.000.000.74207.2853.34123.33SD3.683.870.000.420.000.780.000.000.1640.8215.3742.51Hcy>10Hcy500.021111.2129745.2189112515,10,2007BadeaRadaf56GoldsteinAkTircontrol- Ac Folic-3luni13.73>2650215322,01,2008BalanElenaf53GoldsteinAkTircontrol- Ac Folic-6luni7.68216822,01,2008BalanElenaf53GoldsteinAkTircontrol- Ac Folic-6luni1226.6312108,10,2007BleandaTatianafGoldsteinAkTirbaza16.885.34130.0441.3136314815,01,2008BleandaTatianaf56GoldsteinAkTircontrol- Ac Folic-3luni9.02412008,10,2007BorinaAncafGoldsteinAkTircontrol- Ac Folic-3luni16.0211.241022.35026390.8622071.312667525.06.2007DrumeelenafGoldsteinAkTirBaza7.59.5652>505.51020.8840567.5300611626,09,2007DrumeElenaf54GoldsteinAkTircontrol- Ac Folic-3luni10.44>2626260.511210003,09,2007MoldoveanuGeorgetaf59GoldsteinAkTir15.847.07191.6400.21310403,09,2007NagyDobraf66GoldsteinAkTir20.16200.9>5034.31.0229054.2222148402,07,2006NinulescuElenaf55GoldsteinAkTirbaza8.4812.02562.982.2390.9223157.61581415806,03,2008NinulescuElenafBelgunAk,tir osteoporozatrat cu ac folic6.981417827,05,008NinulescuElenafBelgunAk,tir osteoporozatrat cu ac folic6.987825.06.2007PatrascutaConstantafGoldsteinAkTirbaza11.936.26190.936.92.2381.05407382341511826,09,2007PatrascutaConstantaf57GoldsteinAkTircontrol- Ac Folic-3luni8.7317.270.041512715,10,2007PeleAnaf56GoldsteinAkTircontrol- Ac Folic-3luni22.4713.6130.0227.80.7917.71615122,01,2008PeleAnaf56GoldsteinAkTirtrat ac foliccontrol 6 luni10.021617322,01,2008PeleAnaf56GoldsteinAkTirtrat ac foliccontrol 6 luni168809,07,2008PopescuElenaf55GoldsteinAkTirbaza15.511.8131>500.22040.88364522471712315,10,2007PopescuElenaf55GoldsteinAkTircontrol- Ac Folic-3luni8.71>260.511714921,01,2008PopescuElenaf55GoldsteinAkTircontrol- Ac Folic-6luni7.891716614,04,2008PopescuElenaf55GoldsteinAkTircontrol- Ac Folic-6luni177725.06.2007StoicaAnetafGoldsteinAkTir11.31500.21.12231106.911209323,07,2007UngureanuTudoraf70GoldsteinAkTir14.024.14210.41.929.40.021.0228765.82192110103,09,2007ZincaMariaf61GoldsteinAkTirbaza17.725.52171.1>500.20.9630561.91242214204,12,2007ZicaMariafGoldsteinAkTirtrat ac folic8.732215603,03,2008ZicaMariaf61BelgunAkTirtrat cu ac Folic6.8924.264.82212815,10,2007MarinescuDanielaf54GoldsteinAkTir15.256.861478.70.092316117,03,2008TudoseMargaretaf63GoldsteinAkTirbaza24bazaHomocystFolatT3(ng/dl)(80-200)T4(ug/dl)(4.5-13)FT4TSH( uUI/ml) ( 0.5-4.5)TgAnti TgCreatColestHDLLDLmedia12.2015.4130.430.401.7922.977.8668.711.00314.0958.38195.67SD5.2536.5415.530.000.9819.3014.1332.640.0768.8614.8060.68HomocystFolatT3(ng/dl)(80-200)T4(ug/dl)(4.5-13)FT4TSH( uUI/ml) ( 0.5-4.5)TgAnti TgCreatColestHDLLDLmedia8.7325.9822.980.001.3821.1410.9950.680.53191.4836.59128.17SD4.9114.9410.530.000.572.604.4325.510.66173.4030.8195.45Hcy>103&LAnti TGGroup Ak Tyr&LECLECTICA ENDO&C&P&R&Dgrup 2 AkThyr00000000000Lot Cancer tiroidian -fara substitutie(hipotiroidism sever indus), n=1700000000000all groups00Corelare valorilor pozitive de Tgl cu hiperhomocisteinemia( Hcy>10umol/l)00AK2-timpi00000000000Lotul 2- Fara interuperea substitutiei cu T4 ( n=8)grup 2 graficeIDDateNumePrenumeSexVirstamedicDiagnosticTimpHomocystFolatT3(ng/dl)(80-200)T4(ug/dl)(4.5-13)FT4TSH( uUI/ml) ( 0.5-4.5)TgAnti TgCreatColestHDLLDLECO102.11.2006ConstantinescuStefanafDumitracheOsteoporozabaza10.80.6416332.197315.11.2006LimbaseanuValeriaf80UrsuHypotiroidiebaza17.323.2621.8415.111.2006IliescuMihaim68UrsuHypotiroidiebaza14.38.8450.3520.11.2006RaduDanutmIoanDownbaza8.617.52.230.5213548.766620.11.2006BeldimanIlincafIoanDownbaza5.955.47.960.5814444.486720.11.2006LazarescuAnafPaunOsteoporozabaza7.610.561613664822.11.2006IntzeVictoriafSucaliucOsteoporozaArtrita reumatoidabaza12.193.21.0820541.8126927.11.2006CrainiceanuMariafPaunOsteoporozabaza13.368.060.918232.7941028.11.2006HerjeuEugeniafDumitracheOsteoporozabaza8.314.150.6727767.31431105.12.2006CorfitaElenafDumitracheOsteoporozabaza10.186.040.9918638.61181205.12.2006HodorogVioricafPaunOsteoporozabaza10.8511.010.8621534.11261306.12.2006PopescuGicafSimescuOsteoporozaB.Basedowbaza7.629.010.8329848.82001407.12.2006BiuElenafDumitracheOsteoporozabaza11.238.060.6622340.31361507.12.2006VoicuIulianaf30UrsuMixedemSdr Downbaza10.143.85>500.8717931.41031611.12.2006IonitaMariaf60UrsuMixedem in trat cu 131Ibaza15.433.278.315.10.8816648.61001712.12.2006SpiciacGeorgetafDumitracheOsteoporozabaza16.743.339.21.20.6922760.61451813.12.2006DenutaIoanaf54UrsuHypotiroidiebaza11.234.47559.20.9222875.31411915.12.2006NicolaeElenaf53UrsuHypotiroidiebaza9.758.19410.99210551162019.12.2006PuscoiFloricafDumitracheOsteoporozabaza11.256.538.62.30.7318855.91152108.01.2007VilcuIustinm17IoanDownbaza7.596.75.920.9317055.410422Jan-07PetrescuAlisiaf5 luniIoanDownbaza7.57950.2210136.93923Jan-07Ionutpaulm7IoanDownbaza9.910.567.619.70.9117646.410424Jan-07NedelcuMariafDumitracheOsteoporozabaza6.2925Feb-07PetrescuMagdaf68UrsuMixedembaza19.568.28>501.1330043.221826Feb-07OpreaIoanaf4.5 aniIoanDownbaza6.056.158.60.4915535.1942728.02.2007StanciuMateim2.4 aniIoanDownbaza5.1793.20.2218040.31252805.03.2007ConstantinGhitam71BelgunAktir26.887.35>500.8622071.31262905.03.2007MarinescuElisabetafUrsuHypotiroidiepost tyroidectbaza10.0110.10.726174.11633006.03.2007IugulescuElenafUrsuHypotiroidiebaza10.96.60.5815754.5903106.03.2007IonescuRodicaf56UrsuHypotiroidiebaza13.676.294.70.6621147.81453207.03.2007HumaAndreeaf5.3IoanDownbaza6.4210.94.890.4113146.3743307.03.2007NeculaeAndreim1.4IoanDownbaza5.2111.66.360.2916547.7873413.03.2007DobrescuStefanaf61UrsuHypotiroidiebaza12.063.2711.617.60.8418885.91003514.03.2007DorobatAlexandraf6IoanDownbaza6.939.54.140.4614559.8733614.03.2007MarinAureliaf54UrsuGusa polinod97.312.9>500.8349612393715.03.2007BirleanuAnafUrsuHypotiroidiebaza10.437.0510.313.30.823244.81693820.03.2007SimidreanuNelum5.4IoanDownbaza9.517.510.115.220.419853.21283920.03.2007VoicuIulianafUrsuHypotiroidiebaza10.080.8521258.5133ECO4021.03.2007EnciuStefanaf72UrsuHypotiroidiebaza12.786.15.50.6321659.21354126.03.2007VoicuTudoritaf55UrsuHypotiroidiebaza9.214.8112.113.80.3515446.8954227.03.2007AngelescuMariaf79PIAterosclebaza7.5611061.451.0218139.81134330.03.2007ChiforMarioarafUrsuHypotiroidiebaza8.869.4246.70.916034974411.04.2007CosteaPetraf59UrsuHypotiroidiebaza23.16.5938.31.1323043.91324516.04.2007MuscaluAna-MariafIoanDownbaza7.080.813641.6834617.04.2007MihalceaCatincaf57MuseteanuSndr Metab18.058.162.21.3317031.61054717.04.2007EremiaCarmenfMuseteanuDiab II19.337.8430.70.8516020.1904818.04.2007ConstantinescuStefanafDumitracheOsteoporoza6 luni cu ACTONEL10.124.530.49254821554924.04.2007BalanAncafMuseteanuSDR metabolic8.3216.42.50.8520538.11395025.04.2007TamasGabrielafUrsuHypotir+Alzheimer12.87.3515.531.20.030.6115056805103.05.2007MiteaEcaterinafUrsuHypotir8.443.30.821270.611.35208.05.2006IordacheConstantafMuseteanuOsteoporoza9.380.8819179.91005308.05.2006PopoviciAureliafFO 9742MuseteanuSDR metabolic12.15.5849.71.2121359.91345408.05.2006MustaceaVasilicaf55MuseteanuOsteoporoza11.580.7924737.61875516.05.2007GeorgescuMihaelafUrsuBB in trat cu radioiodSdr Turner11.956.110.912.70.618476.49856May-06CostandacheLilifFO10886UrsuHypo13.013.92.5>501.0636347.92775730.05.2007ZamfirescuMariafMuseteanuOsteoporoza6.350.4716356.9925804.06.2007ApetreiGherghinafUrsuHypo11.974.430.8116451.4965906.06.2007SlatineanuElenafMuseteanuOsteoporoza8.850.5618444.81266007.06.2007IonitaMariafUrsuHypo11.094.1699.70.8816342.4946107.06.2007TataruElisabetaf12131MuseteanuOsteoporoza11.0920.570.7922161.61446207.06.2007CristeaMioaraf12507MuseteanuOsteoporoza10.890.4813249.1666308.06.2007CodinElenaf12521MuseteanuOsteoporoza9.120.6426839.91936411.06.2007MarinEleonorafUrsuHypo8.596.6380.330.5617357.2966512.06.2007IonescuMadalinaf12647MuseteanuSDR metabolic9.259.42.40.7222232.51466612.06.2007PaladeGetaf12093MuseteanuOsteoporoza8.880.7116348.20.56714.06.2007MortasipuFloareafMuseteanuOsteoporoza14.666.690.9417662.21086815.06.2007SiciacGeorgetaf73osteopcontrol 6 luni11.623.440.7825755.21786918.06.2007IugulescuElenaf57UrsuHypotiroidieterap cu Ac Foliccontrol 6 luni8.886.82.40.6615941.6997019.06.2007BalanicaRodicaf13374MuseteanuOsteoporoza11.622.330.74178471097121.06.2007PuscoiFloricaf6117?Sindr metabolic14.574.380.8322155.41397221.06.2007MarinaAureliafUrsuGusa polinodcontrol 6 luni7.463.428.95.80.6728766.51987321.06.2007NituStefanaUrsuHypo6.39.411.320.6520846.41457425.06.2007FianuElenafGoldsteinAkTir10.728.652519.4470.9635853.72697525.06.2007DrumeelenafGoldsteinAkTir7.59.56>505.50.8840567.53007625.06.2007MatusaLaurafGoldsteinAkTir9.3212.61>505.51.1239950.53167725.06.2007StoicaAnetafGoldsteinAkTir11.3150505026262618012.50.6412008,10,2007BorinaAncafGoldsteinAkTircontrol- Ac Folic-3luni16.0211.241022.32610013030,10,2007CosteaPetrafUrsuHyporeevaluare 6 luni11.6>261177.23.3113131,10,2007MarinEleonaorafUrsuHyporeevaluare 6 luni13.5>261.5713205,11,2007BalanElenaf53GoldsteinAkTircontrol- Ac Folic-3luni16.5412.8>5013306,11,2007PetrescuMagdaf66UrsuBasedow16.927.2613407,11,2007MarinescuElenaf57voluntarNormal7.6312.2413507,11,2007DumitriuEcaterinaf56voluntarNormal8.147.9913607,11,2007GheorghiuDanielaf51voluntarNormal8.1710.2613712,11,2007BurlacuMariafUrsuHypo17.342.6913812,11,2007ConstantinescuStefanafDumitracheOsteoporoza16.186.9413926,11,2007ToaderElisabetaf58GoldsteinAkTir14.554.3114030,11,2007RaduLilianafUrsuHypo9.546.0514130,11,2007IugulescuElenafUrsuHypo9.424.0514204,12,2007ZicaMariafGoldsteinAkTirtrat ac folic8.7315.914304,12,2007IvanoviciFilipfGoldsteinAkTirtrat ac folic10.210.5614417,12,2007MicuLucretiaf57GoldsteinAkTirtrat ac folic11.372614510,01,2008CojocariuMariafUrsuHypo13.414615,01,2008BadeaRadaf56GoldsteinAkTirtrat ac folic10.552614715,01,2008MatusaLauraf53GoldsteinAkTirtrat cu ac folic7.498.4414815,01,2008BleandaTatianaf56GoldsteinAkTir9.0218.814921,01,2008PopescuElenafGoldsteinAkTirtrat ac folic7.892615021,01,2008PraschivescuElenaf55UrsuHypo10.419.1115122,01,2008PeleAnaf56GoldsteinAkTirtrat ac foliccontrol 6 luni10.022615222,01,2008IonitaMariafUrsuHypotiroidietrat ac folic4a evaluare14.016.9215322,01,2008BalanElenaf53GoldsteinAkTirtrat cu ac folic7.682615425,02,2008ToaderElisabetafGoldsteinAkTirtrat ac folic6.732615529,02,2008RadulescuPetrefUrsuHypocaz nou15.675.9715603,03,2008ZicaMariaf61BelgunAkTirtrat cu ac Folic6.82615703,03,2008OlteanuNiculinaf64UrsuHypocaz nou15.754.7115806,03,2008NinulescuElenafBelgunAk,tir osteoporozatrat cu ac folic6.9821.8815906,03,2008EnciuStefanfUrsuHypocontrol 3 luni7.752616007,03,2008MicuLucretiaf57BelgunAkTirtrat ac folic13.732616117,03,2008TudoseMargaretaf63GoldsteinAkTirbaza7.318.8916224,,03,2008OlteanuNiculinaf64UrsuHypo11.577.651124.947.0916325,03,2008PetrescuMagdaf64UrsuHypo14.39.8814165.8316431,03,2008IvanoviciFilipmGoldsteinAkTirtrat ac folic12.4911.4712912.10.11659,04,2008MatusaLaurafGoldsteinAkTirtrat ac folic6.338.011116.80.116614,04,2008PopescuElenafGoldsteinAkTirtrat ac folic10.48261299.40.0416714,04,2008BadeaRadafGoldsteinAkTirtrat ac folic10261027.50.416808,05,2008BalanElenaf54GoldsteinAkTirtrat ac folic10.94261226.60.0116908,05,2008ParaschivescuElenafUrsu5mg/zi7.787.319010.1500.021111.2129745.21892Balan Elenaf5316.5412.87.8267.6810.89.2253Bleanda Tatianaf5616.885.347.02130.0441.31364Borina Ancaf16.211.241022.35026390.8622071.31266Drume Elenaf7.509.5610.44>2652>505.51020.8840567.53007Fianuf5210.728.659.39>26120.92519.4470.9635853.72698Ivanovici Filipm6122.702.9210.210.5612.4911.47505.51111.1239950.531611Micu Lucretiaf5723.606.6611.372613.7321110.65028.8321.0430178.418912Milea Elenaf5222.0005/01/008.71>2611.86260.5113Moldoveanu Georgetaf5915.847.07191.6400.214Nagy Dobraf6620.16200.9>5034.31.0229054.222215Ninulescu Elenaf558.4812.026.989.5811.39562.982.2390.9223157.615816Patrascuta Constantaf5711.936.268.7317.27190.936.92.2381.054073823417Pelef5622.4713.6010.02130.0227.80.7917.718Popescu Elenaf5515.5011.808.71>267.8913>2610.4>261>500.22040.883645224719Toader Elisabetaf14.554.316.73268.382620Trandafir Paraschivaf7318.524.7650.06>500.21.12231106.91121Ungureanu Tudoraf7014.02210.41.929.40.021.0228765.821922Zinca Mariaf6117.725.528.736.78171.164.20.20.9630561.912423Nenciu Mariamedia59.0616.797.709.0718.299.70815.56min52.007.502.926.739.586.338.10max7326.8813.613.732613.7326SDV6.66397004295.26665605653.21411950781.88623207187.60882977052.60876215868.1709006032CV11.284239018931.3641.7320.8041.6126.870.000.000.0052.51Basal3 month6 month12 monthHcy16.799.079.70Folic acid7.7018.2915.36Cholesterol380.00220.00214.00HDL- Colest60.5749.8Feb-00Sheet1BasalBasal3 month3 month6 month6 monthHcyFolic acidDecrease of plasma Hcy during therapy16.797.79.0718.299.715.36HcyHcyHcyFolic acidFolic acidFolic acidCholesterolCholesterolCholesterolHDL- ColestHDL- ColestHDL- ColestBasal3 month6 monthHcy , Cholesterol , HDL Cholest during folate supplimentation therapy16.799.079.77.718.2915.3638022021460.5749.845.5HcyHcyHcyFolic acidFolic acidFolic acidCholesterolCholesterolCholesterolHDL- ColestHDL- ColestHDL- ColestBasal3 month6 monthHcy , Cholesterol , HDL Cholest during folate supplimentation therapy16.799.079.77.718.2915.3638022021460.5749.845.5BasalBasal3 month3 month6 month6 monthHcyFolic acidDecrease of plasma Hcy during therapy16.797.79.0718.299.715.36HcyHcyHcyFolic acidFolic acidFolic acidCholesterolCholesterolCholesterolHDL- ColestHDL- ColestHDL- ColestBasal3 month6 monthGroup 2: Hcy , Cholesterol , HDL Cholest during folate supplimentation therapy16.799.079.77.718.2915.3638022021460.5749.845.5

24%28%48%

Group 2: Homocystein concentration distribution tHcy20

MBD001284FA.xlsChart7tHcy20Group 2: Homocystein concentration distribution6712BazeNrIDDateNumePrenumeSexVirstamedicDiagnosticTimpHomocystFolatT3(ng/dl)(80-200)T4(ug/dl)(4.5-13)FT4TSH( uUI/ml) ( 0.5-4.5)TgAnti TgCreatColestHDLLDLECO8909,07,2007BadeaRadafGoldsteinAkTirbaza22.73.021>50505.50.8840567.53007425.06.2007FianuElenafGoldsteinAkTirbaza10.728.652519.4470.9635853.72697625.06.2007MatusaLaurafGoldsteinAkTirbaza9.3212.61>505.51.1239950.53168709,07,2007MicuLucretiafGoldsteinAkTirbaza23.66.665028.8321.0430178.418912209,10,2007MileaElenaf52UNAkybaza8.71>2610003,09,2007MoldoveanuGeorgetaf59GoldsteinAkTirbaza15.847.07405034.31.0229054.22228402,07,2006NiculescuElenaf55GoldsteinAkTirbaza8.4812.0280.9223157.61587825.06.2007PatrascutaConstantafGoldsteinAkTirbaza11.936.261.05407382348202,07,2007PopescuElenafGoldsteinAkTirbaza29.169.5>50