Tireoide e a conexão colesterol – um assunto crítico

Colesterol alto e a primeira [e errônea] preocupação em baixá-lo farmacologicamente

[Imagem: kikhtieva.com.ua]

A discussão já é antiga, mas parece não chegar aos ouvidos de muitos cardiologistas: colesterol alto não deveria ser baixado à força de drogas [todas elas tóxicas, diga-se de passagem]. O colesterol alto já foi analisado amplamente pela ciência e, há muito tempo, “seguir a ciência” já não tem nada a ver com amaldiçoar o colesterol  e/entupir pacientes com venenos químicos a pretexto de combater o vilão cardiovascular chamado colesterol [total, ou HDL].

Que tal olhar para o lado da pesquisa que já demonstrou uma e outra vez que  se o colesterol está alto [tipo 300] o problema muito provavelmente estará ... na tireoide hipofuncionante.

Que tal revisitar a fisiologia e relembrar que o colesterol é insumo para síntese dos esteroidais tipo progesterona e testosterona e que estes dependem da tireoide [e da vitamina A] para serem fabricados no corpo.

Em outras palavras, se a pessoa apresenta hipotireoidismo a grande chance é de ela não consumir o colesterol plasmático para síntese de hormônios [além de bile]. E se é assim não é mais lógico avaliar a tireoideɁ E se é assim não seria mais lógico ao invés de focar nos “males” do colesterol alto, investigar se o problema é que ele está “sobrando” em consequência do seu não uso como insumo que ele é, para aqueles hormônios vitaisɁ Por que continuar culpando o colesterol por ataques cardíacos, se existe, há décadas e décadas uma outra verdade apontando a  insuficiência tireoidiana como o grande problema de raizɁ Que tal revisitar o Dr Broda Barnes [Ver aqui ]Ɂ

Conforme já argumentou o pioneiro do uso de tireoide [tireoide dessecada] no tratamento de problemas do coração, o Dr Broda Barnes, “por muitos anos, evidências circunstanciais estabeleceram que o colesterol é o vilão dos ataques cardíacos. [...]  No entanto, evidências vieram se acumulando por cem anos indicando que o verdadeiro culpado é uma deficiência tireoidiana, e o colesterol, que é usualmente aumentado no hipotireoidismo, é apenas uma testemunha inocente”.

Algumas pesquisas das várias que focaram no tema, concluíram claramente os seguintes elementos. “Hipotireoidismo subclínico está associado não apenas com LDL-colesterol elevado como também baixos níveis de HDL-colesterol, mas também lipoproteína-A elevada. Isso pode, mais adiante elevar o risco de desenvolvimento de aterosclerose” [K]. “Em mulheres pré-menopausadas, hipotireoidismo sublínico pode ter um efeito negativo no perfil de lipoproteínas [...]” [L].  “Mesmo elevações suaves de TSH estão associadas com mudanças significantes no perfil lipídico” [U]. “Comparados com controles, pacientes com hipotireoidismo subclínico mostraram mais altos níveis de colesterol total, LDL-colesterol, triglicérides e apolipoproteína-B”[V]. “Nossos dados trazem uma possível explicação para a mais alta prevalência de doença cardíaca coronariana que é reportada em hipotireoidismo subclínico”[Z1]

Novamente, o Dr Barnes: se há colesterol alto, a “administração de tireoide tende a baixar o colesterol e se for oferecido suficiente suplemento tireoidiano o colesterol pode baixar abaixo do normal. O fígado converte colesterol em sais biliares que são eliminados com a bile; este processo é a forma usual de eliminar excesso de colesterol. O fígado tem função lenta entre pessoas com hipotireoidismo”.

Era esse médico quem também argumentava que “na verdade, há 12 anos que o Dr L M Hurxthal da Clínica Lahey em Boston, mostrou claramente que a secreção tireoidiana controle os níveis de colesterol na maioria dos pacientes. E, em pacientes com hipertireoidismo, ou excessiva atividade tireoidiana, ele descobriu que o nível de colesterol no sangue estava abaixo do nível normal médio”.

Na segunda metade do século passado, R. Peat foi pioneiro em mostrar a concexão tireoide-colesterol sempre que tocava no tema colesterol. E argumentava que “por volta dos anos 1930, se sabia, de uma maneira geral, que o hipotireoidismo causa aumento dos níveis de colesterol no sangue: hipercolesterolemia era um sinal diagnóstico de hipotireoidismo. Administrando um suplemento tireoidiano, o colesterol plasmático caía até o normal assim como a taxa metabólica basal subia e se normalizava”.

O colesterol pode perfeitamente subir ou cair por razões puramente fisiológicas, de tal forma que a tendência a usar drogas contrafisiológicas, tóxicas é uma mania basicamente fora de foco.

No argumento de R. Peat, “no organismo saudável, o colesterol está sendo constantemente sendo sintetizado e constantemente convertido em hormônios esteroidais e, no fígado, em sais biliares, que são secretados para emulsificar gorduras no intestino. Hormônio tireoidiano e vitamina A são usados no processo de converter colesterol em pregnenolona, o precursor imediado de progesterona e DHEA. Qualquer coisa que interfira com tais processos seria desastrosa para o organismo”.

Esse é um pensamento da órbita da mais pura fisiologia humana.

Colesterol pode subir como parte de um mecanismo regulatório, mas não um processo originalmente patogênico e sim, defensivo, do organismo. E pode estar baixo simplesmente porque a pessoa – mesmo com tireoide normofuncionante – não oferece insumos para sua síntese pelo organismo [suficiente frutose, por exemplo].

Novamente R. Peat: “Em pessoas muito jovens, a taxa metabólica é muito alta e a rápida conversão de colesterol em pregnenolona, DHEA e progesterona usualmente mantêm o nível sanguíneo de colesterol baixo. Nos anos 1930, uma alta na concentração plasmática de colesterol era consideradada como uma das formas mais confiáveis de diagnosticar hipotireoidismo [1936 Yearbook of Neurology, Psychiatry and Endocrinology, E L Sevringhaus, editor, Chicago p 533]. Com a idade, a taxa metabólica tende a declinar e o aumento do colesterol com o envelhecimento é provavelmente um processo regulatório espontâneo, amparando a síntese dos esteroidais protetores, especialmente os neuroesteroides no cérebro e retina”.

O consumo usual de óleos insaturados também impacta o colesterol indiretamente, fazendo-o aumentar ao provocar hipotireoidismo.

“Quando o colesterol está muito alto, quase sempre tem a ver com baixa atividade tireoidiana e óleos insaturados armazenados serão provavelmente a mais comum causa disso” [R. Peat], já que operam como inibidores notórios da atividade tireoidiana.

Em suma, “o colesterol – como mais uma vez argumenta R. Peat – é rapidamente utilizado pelo organismo sob a influência do T3 e ao menos desde os anos 1930, já estava bem claro que o colesterol plasmático sobre no hipotireoidismo, e se mostra muito útil do ponto de vista diagnóstico”.

E, no entanto, a medicina oficial – sua burocracia e congressos de cardiologia, bem amparados pela Big Pharma – continua desconsiderando o acúmulo de trabalhos científicos que examinam a conexão colesterol-tireoide com a necessária lucidez.

Há muito tempo, na verdade, demasiado tempo, já deixou de ser um problema de evidências, ou como chamam, de “medicina baseada em evidências”. Há vários livros sobre isso. E, no entanto, a saga da satanização do colesterol continua, em franco galope. Naturalmente com aval da OMS.

Cuo usque tandem abutere patientia nostraɁ

Como dizia Cícero [no seu caso, desmascarando o corrupto senador Catilina] há quase dois mil anos atrás: até quando continuarás abusando da nossa paciência, até quando sua loucura há de zombar de nósɁ

Ou: até quando ó burocratas bem remunerados, hão de zombar e abusar das evidências na direção contrária da sua loucura estatinólatraɁ

GM Fontes, Brasília, 19-5-24

As informações aqui presentes não pretendem servir para uso diagnóstico, prescrição médica, tratamento, prevenção ou mitigação de qualquer doença humana.  Não pretendem substituir a consulta ao profissional médico ou servir como recomendação para qualquer plano de tratamento. Trata-se de informações com  fins estritamente educativos. Nenhuma das notas aqui presentes, neste blog, conseguirá atingir o contexto específico do paciente singular, nem doses, modo de usar etc. Este trabalho compete ao paciente com seu médico. Isso significa que nenhuma dessas notas - necessariamente parciais - substitui essa relação.

Referências ____________

[A]   FELD S DICKEY R A, 2001. An Association Between Varying Degrees of Hypothyroidism and Hypercholesterolemia in Women: The Thyroid-Cholesterol Connection. Prev Cardiol. 2001 Autumn;4(4):179-182”Evidence of an association between subclinical hypothyroidism and cardiovascular disease is mounting. The impact of thyroid hormone on lipid levels is primarily mediated through triiodothyronine (T(3))-bound thyroid protein binding and activation of the promoter regions of the low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A-reductase genes, leading to a reduction in serum cholesterol levels. Thus, the decreased T(3) seen in hypothyroidism may result in increased serum cholesterol. Although a clear correlation exists between overt hypothyroidism and clinically significant hypercholesterolemia, there is a logarithmic relationship between thyroid-stimulating hormone and cholesterol, and the effects of subclinical hypothyroidism on cardiovascular disease are under debate. However, current data suggest that normalizing even modest thyroid-stimulating hormone elevations may result in improvement in the lipid profile. (c)2001 CHF, Inc”.

[B]    CANARIS G J MANOWITZ N R 2000. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000 Feb 28;160(4):526-34.  “CONTEXT:
The prevalence of abnormal thyroid function in the United States and the significance of thyroid dysfunction remain controversial. Systemic effects of abnormal thyroid function have not been fully delineated, particularly in cases of mild thyroid failure. Also, the relationship between traditional hypothyroid symptoms and biochemical thyroid function is unclear.
OBJECTIVE:   To determine the prevalence of abnormal thyroid function and the relationship between (1) abnormal thyroid function and lipid levels and (2) abnormal thyroid function and symptoms using modern and sensitive thyroid tests.
DESIGN: Cross-sectional study.
PARTICIPANTS: Participants in a statewide health fair in Colorado, 1995 (N = 25 862).
MAIN OUTCOME MEASURES:
Serum thyrotropin (thyroid-stimulating hormone [TSH]) and total thyroxine (T4) concentrations, serum lipid levels, and responses to a hypothyroid symptoms questionnaire.
RESULTS:  The prevalence of elevated TSH levels (normal range, 0.3-5.1 mIU/L) in this population was 9.5%, and the prevalence of decreased TSH levels was 2.2%. Forty percent of patients taking thyroid medications had abnormal TSH levels. Lipid levels increased in a graded fashion as thyroid function declined. Also, the mean total cholesterol and low-density lipoprotein cholesterol levels of subjects with TSH values between 5.1 and 10 mIU/L were significantly greater than the corresponding mean lipid levels in euthyroid subjects. Symptoms were reported more often in hypothyroid vs euthyroid individuals, but individual symptom sensitivities were low.
CONCLUSIONS:  The prevalence of abnormal biochemical thyroid function reported here is substantial and confirms previous reports in smaller populations. Among patients taking thyroid medication, only 60% were within the normal range of TSH. Modest elevations of TSH corresponded to changes in lipid levels that may affect cardiovascular health. Individual symptoms were not very sensitive, but patients who report multiple thyroid symptoms warrant serum thyroid testing. These results confirm that thyroid dysfunction is common, may often go undetected, and may be associated with adverse health outcomes that can be avoided by serum TSH measurement”.

[C]   K B TURNER STEINER A 1939. A LONG TERM STUDY OF THE VARIATION OF SERUM CHOLESTEROL IN MAN. J Clin Invest. 1939; 18(1):45–49 doi:10.1172/JCI101024
4. Thyroid administration produced a sharp drop in serum cholesterol in every case. This accompanied by a rise in the basal metabolic rate”.

[D]   O´BRIEN T KATZ K HODGE D, 1997. The effect of the treatment of hypothyroidism and hyperthyroidism on plasma lipids and apolipoproteins AI, AII and E. Clin Endocrinol (Oxf). 1997 Jan;46(1):17-20.  “OBJECTIVE:
Although lipid abnormalities are well described in hypothyroidism, effects on apolipoproteins are less well understood. The aim of this study was to examine the effects of thyroid dysfunction on plasma lipids and apolipoproteins.
DESIGN: A prospective study of lipids and apolipoproteins before and after treatment of hypothyroidism and hyperthyroidism.
PATIENTS: Eighteen patients with hypothyroidism and 5 patients with hyperthyroidism were included.
MEASUREMENTS: Plasma cholesterol, triglycerides, HDL cholesterol, apo AI, apo AII, and apo E were measured before and after treatment of the thyroid abnormality.
RESULTS: Total and HDL cholesterol, apo AI and apo E decreased with treatment of hypothyroidism, while triglycerides and apo AII levels were unchanged. The total/HDL cholesterol and LDL/HDL cholesterol ratios also decreased with treatment of hypothyroidism. In contrast, treatment of hyperthyroidism was associated with an increase in total and HDL cholesterol, and apo AI. Triglycerides, apo AII and Apo E were unchanged by treatment of hyperthyroidism. The total/HDL cholesterol and the LDL/HDL cholesterol ratios increased with treatment of hyperthyroidism.
CONCLUSIONS: Hypothyroidism and hyperthyroidism have opposite effects on plasma lipids and apolipoproteins. In hypothyroidism, total and HDL cholesterol, total/HDL cholesterol ratio, apo AI and apo E are elevated. The increase in apo AI without a concomitant increase in apo AII suggests selective elevation of HDL2. In contrast, hyperthyroidism is associated with decreased total and HDL cholesterol, total/HDL cholesterol ratio, and apo AI levels. These effects are reversible with treatment of the underlying thyroid disorder”.

[E]   ORIBE H, 1989. [Clinical studies on lipid metabolism in hyperthyroidism and hypothyroidism–evaluation of serum apolipoprotein levels before and after treatment].  Nihon Naibunpi Gakkai Zasshi. 1989 Aug 20;65(8):781-93.
[Article in Japanese]  “The present study was undertaken to assess lipid metabolism in patients with thyroid dysfunction with special reference to serum apolipoprotein levels. Serum lipid, lipoprotein and apolipoprotein levels were determined in 28 hyperthyroid and 16 hypothyroid female patients while untreated and euthyroid. Apolipoproteins were measured by the method of single radial immuno-diffusion (SRID). These results were compared with the values of 28 female controls. In the untreated hyperthyroid group, the serum levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were significantly decreased compared to the controls and increased after treatment. In hypothyroidism, these values before treatment were higher than those in the controls and decreased after treatment. Serum apo A-I, A-II, B and C-III levels were significantly decreased in the untreated hyperthyroid group compared to the control values. Apo C-II and E levels in hyperthyroidism were identical both before and after treatment compared with the control values, respectively. In the untreated hypothyroidism, apo B, C-II, C-III and E levels were significantly elevated compared to the controls, and these changes in apolipoproteins except apo C-II were restored after treatment. Apo A-I and A-II levels in the untreated hypothyroidism were not statistically different from the values after treatment or those in the control group. Serum thyroid hormone (T3, T4) levels inversely correlated apo B and C-III in all subjects. In hypothyroidism, serum TSH positively correlated with apo B, C-II and C-III. The increase in relative body weight (%RBW) in hyperthyroidism during treatment correlated with the changes of TC and LDL-C. In conclusion, these results indicate that thyroid hormones have a substantial influence on the serum apolipoprotein levels, and that measurement of apolipoproteins as well as lipids and lipoproteins in patients with thyroid dysfunction may be useful to evaluate the lipid metabolism and the effect of therapy”.

[F]   MULS E BLATON V ROSSENEU M, 1982. Serum lipids and apolipoproteins A-I, A-II, and B in hyperthyroidism before and after treatment. J Clin Endocrinol Metab. 1982 Sep;55(3):459-64.  “The serum concentrations of total cholesterol (TC), triglycerides (RG), high density lipoprotein-cholesterol (HDLc), low density lipoprotein-cholesterol (LDLc), and the apolipoproteins (apo) A-I, A-II, and B were measured in 33 hyperthyroid patients before and after treatment. The results were compared with those of healthy controls. Apo A-I, A-II, and B were assayed by immunonephelometry. The serum levels of TC (mean +/- SD, 167 +/- 36 mg/dl, HDLc (40.8 +/- 12 mg/dl), and LDLc (108 +/- 35 mg/dl) were decreased in the untreated hyperthyroid patients compared to both the values after treatment (TC: 215 +/- 54 mg/dl; P less than 0.001; HDLc: 52 +/- 14 mg/dl; P less than 0.001; LDLc: 146 +/- 47 mg/dl; P less than 0.001) and the control values (TC: 206 + 39 mg/dl; P less than 0.001; HDLc: 47.4 +/- 10 mg/dl; P les than 0.01; LDLc: 145 +/- 38 mg/dl; P less than 0.001). TG levels were not statistically different before and after treatment. The apo A-I concentrations (116 +/- 24 mg/dl) were lower before than after treatment (131 +/- 28 mg/dl; P less than 0.01), but they were not statistically different from those in the control group (115 +/- 19 mg/dl). The apo A-II levels were identical in all groups (before treatment, 35 +/- 7 mg/dl; after treatment, 37 +/- 9 mg/dl; control group, 36 +/- 9 mg/dl). The apo B levels were lower in the untreated hyperthyroid patients (86 +/- 23 mg/dl) compared to those in controls (103 +/- 19 mg/dl; P less than 0.001) and patients after therapy (103 +/- 25 mg/dl; P less than 0.001). The increase in HDLc relative to the major HDL apo A-I and A-II during treatment for hyperthyroidism was associated with changes in body weight. The apo A-I to apo A-II and LDLc to apo B ratios, however, were significantly lower before compared to those after treatment, when the influence of increasing body weight during therapy was accounted for. This study emphasizes the important regulating role of thyroid hormones on lipid and apolipoprotein metabolism”.

[G]   KUNG A W PANG R W, 1995.  Changes in serum lipoprotein(a) and lipids during treatment of hyperthyroidism. Clin Chem. 1995 Feb;41(2):226-31”Because of suggestions that thyroid hormones modulate serum lipoprotein(a) [Lp(a)] concentration, we evaluated prospectively the serial changes of serum Lp(a), measured as apolipoprotein(a) [apo(a)], and other lipoproteins in 40 subjects with hyperthyroidism treated with radioactive iodine (RAI) therapy. Hyperthyroid patients had lower (P < 0.001) concentrations of apo(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apo B, but higher apo A-I concentrations compared with age-matched controls [geometric mean (range)]; apo(a) 81 (17-614) vs 187 (17-1808 IU/L): TC 4.07 +/- 0.8 vs 5.22 +/- 1.00 mmol/L (mean +/- SD); LDL-C 2.47 +/- 0.89 vs 3.40 +/- 0.88 mmol/L; HDL-C 1.05 +/- 0.33 vs 1.24 +/- 0.34 mmol/L; apo B 0.66 +/- 0.23 vs 1.13 +/- 0.34 g/L, and apo A-I 2.07 +/- 0.42 vs 1.46 +/- 0.28 g/L, respectively. Euthyroidism was associated with normalization of serum TC, LDL-C, and apo B within 1 month of treatment. However, apo(a) required 4 months to normalize, and HDL-C and apo A-I were still abnormal 6 months after RAI. Serum apo(a), TC, LDL-C, and apo B were negatively correlated with serum thyroxine (T4), free thyroxine index, and triiodothyronine (T3) and positively correlated with thyrotropin during the transitional period from hyperthyroidism to euthyroidism. Parallel changes of these lipoproteins and thyroid hormones were also observed after treatment of hyperthyroidism. In conclusion, thyroid hormones do modulate lipoproteins, particularly Lp(a). The delay in normalization of apo(a) but not LDL suggests an effect on apo(a) production rather than on LDL removal”.

[H   DIEKMAN M J ANGHELESCU N 2000. Changes in plasma low-density lipoprotein (LDL)- and high-density lipoprotein cholesterol in hypo- and hyperthyroid patients are related to changes in free thyroxine, not to polymorphisms in LDL receptor or cholesterol ester transfer protein genes. J Clin Endocrinol Metab. 2000 May;85(5):1857-62.  “Thyroid function disorders lead to changes in lipoprotein metabolism. Both plasma low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increase in hypothyroidism and decrease in hyperthyroidism. Changes in LDL-C relate to altered clearance of LDL particles caused by changes in expression of LDL receptors on liver cell surfaces. Changes in cholesterol ester transfer activity partly explain changes in HDL-C. It has been suggested that the magnitude of these changes is related to polymorphisms of involved genes. The aim of the present study is to investigate whether the polymorphic AvaII restriction site in exon 13 of the LDL receptor gene and the polymorphic TaqIB site in intron 1 of the cholesterol ester transfer protein are associated with the magnitude of the changes in plasma LDL-C and HDL-C, respectively, in the transition from the hypo- or hyperthyroid to the euthyroid state. From a consecutive group of 66 untreated hypothyroid and 60 hyperthyroid patients, 47 Caucasians in each group were analyzed. Fasting LDL-C and HDL-C were measured at baseline and 3 months after restoration of the euthyroid state. Genotype was determined by means of PCR techniques. The homozygous presence of a restriction site was designated as +/+, heterozygous as +/-, and absence as -/-. Trend analysis was done with ANOVA. Among hypo- or hyperthyroid patients, subgroups with different genotypes did not differ in thyroid function pre- or post treatment. The mean decrease in LDL-C (mmol/L +/- SD) in hypothyroid patients with different AvaII genotypes did not differ: – 1.07 +/- 1.44 (-/-, N = 15), -1.25 +/- 1.53 (+/-, N = 19), and -1.18 +/- 1.01 (+/+, N = 13) mmol/L [not significant (NS)]; neither did the mean increase in hyperthyroid patients: 1.07 +/- 0.90 (-/-, N = 18), 0.92 +/- 1.00 (+/-, N = 21), and 1.20 +/- 0.45 (+/+, N = 6) (NS). The mean decrease in HDL-C (mmol/L +/- SD) in hypothyroid patients with different TaqIB genotypes did not differ: -0.22 +/- 0.26 (-/-, N = 13), -0.15 +/- 0.23 (+/-, N = 21), and -0.12 +/- 0.22 (+/+, N = 9) (NS); neither did the mean increase in hyperthyroid patients: 0.29 +/- 0.39 (-/-, N = 7), 0.26 +/- 0.23 (+/-, N = 22), and 0.19 +/- 0.31 (+/+, N = 18) (NS). Changes in LDL-C and HDL-C correlated with the logarithm of the change in free T4 (fT4), expressed as the fT4 posttreatment/fT4 pretreatment ratio (r = -0.81, P < 0.001; and r = -0.62, P < 0.001, respectively). In conclusion, in the transition from hypo- or hyperthyroidism to euthyroidism, no association is found between AvaII genotype and changes in plasma LDL-C nor between TaqIB genotype and changes in HDL-C. Changes in LDL-C and HDL-C correlate with changes in fT4”.

[I]   MEIER C STAUB J J , 2001. TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study).  J Clin Endocrinol Metab. 2001 Oct;86(10):4860-6. “This study evaluated the effect of physiological, TSH-guided, L-thyroxine treatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 +/- 0.8 mIU/liter) were randomly assigned to receive L-thyroxine or placebo for 48 wk. Individual L-thyroxine replacement (mean dose, 85.5 +/- 4.3 microg/d) was performed based on blinded TSH monitoring, resulting in euthyroid TSH levels (3.1 +/- 0.3 mIU/liter). Lipid concentrations and clinical scores were measured before and after treatment. Sixty-three of 66 patients completed the study. In the L-thyroxine group (n = 31) total cholesterol and low density lipoprotein cholesterol were significantly reduced [-0.24 mmol/liter, 3.8% (P = 0.015) and -0.33 mmol/liter, 8.2% (P = 0.004), respectively]. Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low density lipoprotein cholesterol levels at baseline. A significant decrease in apolipoprotein B-100 concentrations was observed (P = 0.037), whereas high density lipoprotein cholesterol, triglycerides, apolipoprotein AI, and lipoprotein(a) levels remained unchanged. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (P = 0.02). This is the first double blind study to show that physiological L-thyroxine replacement in patients with subclinical hypothyroidism has a beneficial effect on low density lipoprotein cholesterol levels and clinical symptoms of hypothyroidism. An important risk reduction of cardiovascular mortality of 9-31% can be estimated from the observed improvement in low density lipoprotein cholesterol”.

[J]   IQBAL A JORDE R 2006. 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 Tromsø Study. J Intern Med. 2006 Jul;260(1):53-61.  “OBJECTIVE: To evaluate the relation between serum thyroid-stimulating hormone (TSH) and lipids.
DESIGN: Cross-sectional epidemiological study, nested case-control study, and a placebo-controlled double-blind intervention study.
METHODS: In the 5th Tromsø study serum TSH, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. Subjects with subclinical hypothyroidism (SHT) and a matching control group were re-examined and apolipoprotein A1 (Apo A1) and apolipoprotein B (Apo B) were also measured. Subjects with SHT were included in an intervention study with thyroxine supplementation for 1 year.
RESULTS: A total of 5143 subjects from the 5th Tromsø study were included. A significant and positive correlation between serum TSH levels and serum TC and LDL-C levels were found in both genders. However, in the females this did not reach statistical significance after adjusting for age and BMI. The serum LDL-C were significantly higher and the Apo A1 levels significantly lower in 84 SHT subjects compared with 145 controls, and in the SHT females the TC levels were also significantly elevated. In the intervention study (32 subjects given thyroxine and 32 subjects given placebo), we observed a significant reduction in the Apo B levels after thyroxine medication. In those that at the end of the study had serum TSH levels in the range 0.2-2.0 mIU L(-1), the serum TC and LDL-C levels were also significantly reduced. CONCLUSIONS: There is a positive association between serum TSH levels and TC and LDL-C levels. These lipid levels are reduced with thyroxine treatment in subjects with SHT”.

[K]   KUNG A W PANG R W, 1995.  Elevated serum lipoprotein(a) in subclinical hypothyroidism. Clin Endocrinol (Oxf). 1995 Oct;43(4):445-9.  “OBJECTIVES:
Asymptomatic lymphocytic thyroiditis and subclinical hypothyroidism are associated with increased risk for coronary artery disease. The present study aimed at evaluating serum lipoprotein(a)(Lp(a)), measured as apo(a), and other lipid parameters in 32 subjects with asymptomatic subclinical hypothyroidism.
SUBJECTS:  Thirty-two Chinese subjects with asymptomatic subclinical hypothyroidism were compared to 96 age and sex-matched healthy controls.
RESULTS:
Subclinical hypothyroid patients had higher (P < 0.005) apo(a), total triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) but lower (P < 0.05) high density lipoprotein cholesterol (HDL-C) levels compared with sex and age-matched controls (apo(a) 296 (48-1650) vs 182 (19-1952 U/l), geometric mean (range); TG 1.86 +/- 0.94 vs 1.33 +/- 0.74 mmol/l (mean +/- SD); TC 6.10 +/- 1.17 vs 5.42 +/- 1.13 mmol/l; LDL-C 4.10 +/- 1.00 vs 3.49 +/- 0.96 mmol/l; HDL-C 1.15 +/- 0.40 vs 1.34 +/- 0.40 mmol/l, respectively). APo A-I and apo B were also higher than controls (1.96 +/- 0.48 vs 1.48 +/ 0.29 g/l and 1.44 +/- 0.42 vs 1.05 +/- 0.29 g/l, respectively). Total cholesterol/HDL ratio and LDL/HDL ratio were also elevated in these subjects (5.77 +/- 1.96 vs 4.28 +/- 1.19 and 3.89 +/- 1.41 vs 2.79 +/- 0.97, respectively, both P < 0.0005). Individual analysis revealed that 16 (50%) subjects had hyperlipoproteinaemia (TC > 5.2 mmol/l in 10; TC > 5.2 mmol/l and TG > 2.3 mmol in six) as compared to 21(20.8%) in the control group (P < 0.005). Subjects with TSH > or = 11.0 mIU/l had significantly higher TC/HDL and LDL/HDL ratios. A significant correlation was observed between TSH levels and TC/HDL ratios (r = 0.455, P < 0.01).
CONCLUSIONS: Subclinical hypothyroidism is associated not only with elevated LDL-cholesterol levels and low HDL-cholesterol levels but also with elevated lipoprotein (a). This may further increase the risk development of atherosclerosis”.

[L]    MIKHAIL G S ALSHAMMARI S M, 2008. Increased atherogenic low-density lipoprotein cholesterol in untreated subclinical hypothyroidism.  Endocr Pract. 2008 Jul-Aug;14(5):570-5.  “OBJECTIVE: To evaluate the effects of physiologic doses of levothyroxine replacement on the lipoprotein profile in patients with subclinical hypothyroidism (SCH).   METHODS: In a prospective, double-blind, placebo-controlled study, we enrolled 120 patients–mostly, but not exclusively, premenopausal women–with SCH. Patients were randomly assigned to either a levothyroxine-treated group (n = 60) or a placebo (control) group (n = 60). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured before and 52 weeks after assignment to either group.
RESULTS: In the levothyroxine-treated group, the lipoprotein mean values before and after the 52-week study were as follows: TC, 5.05 +/- 0.98 mmol/L versus 4.74 +/- 0.87 mmol/L (P<.0001); LDL-C, 3.30 +/- 0.90 mmol/L versus 2.89 +/- 0.59 mmol/L (P<.01); TG, 1.18 +/- 0.71 mmol/L versus 0.95 +/- 0.53 mmol/L (P<.002); and HDL-C, 1.20 +/- 0.33 mmol/L versus 1.19 +/- 0.32 mmol/L (P = .29). In the control group, TC, HDL-C, and TG values remained unchanged after 52 weeks in comparison with baseline, but LDL-C mean values increased from 2.79 +/- 0.60 mmol/L to 3.11 +/- 0.77 mmol/L, a change that was statistically significant (P<.001). At the end of the study, the lipid profile changes between levothyroxine-treated and control groups were compared. Total cholesterol and LDL-C were significantly lower in the levothyroxine-receiving group (P<.029 and P<.0001, respectively) in comparison with the control group. The difference did not reach statistical significance for TG and HDL-C values.
CONCLUSION: In premenopausal women, SCH has a negative effect on the lipoprotein profile and may translate into a sizable cardiovascular risk if left untreated”.

[M]   DANESE M D LADENSON P W, 2000. 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. 2000 Sep;85(9):2993-3001.”The objective of our study was to estimate the expected change in serum lipoprotein concentrations after treatment with T4 in patients with mild thyroid failure (i.e. subclinical hypothyroidism). Our data sources included MEDLINE, between January 1966 and May 1999, and review of references from relevant articles. There were 1,786 published studies identified, 461 abstracts reviewed, 74 articles retrieved, 24 articles evaluated against predetermined entry criteria, and 13 studies systematically reviewed and abstracted. All studies reported serum total cholesterol concentration changes during T4 treatment, 12 reported triglyceride changes, 10 reported high-density lipoprotein (HDL) cholesterol changes, and 9 reported low-density lipoprotein (LDL) cholesterol changes. There were 247 patients in 13 studies. The mean decrease in the serum total cholesterol concentration was -0.20 mmol/L (-7.9 mg/ dL), with a 95% confidence interval of -0.09 to -0.34. The decline in serum total cholesterol was directly proportional to its baseline concentration. Studies enrolling hypothyroid participants receiving suboptimal T4 doses reported significantly larger decreases in serum total cholesterol after thyroid-stimulating hormone normalization than studies enrolling previously untreated individuals with mild thyroid failure [-0.44 mmol/L (-17 mg/dL) vs. -0.14 mmol/L (-5.6 mg/dL), P = 0.05]. The change in serum LDL cholesterol concentration was -0.26 mmol/L (-10 mg/dL), with a 95% confidence interval of -0.12 to -0.41. Serum HDL and triglyceride concentrations showed no change. These results, although based on fewer than 250 patients, suggest that T4 therapy in individuals with mild thyroid failure lowers mean serum total and LDL cholesterol concentrations. The reduction in serum total cholesterol may be larger in individuals with higher pretreatment cholesterol levels and in hypothyroid individuals taking suboptimal T4 doses. There do not seem to be significant effects of T4 on serum HDL or triglyceride concentrations”. Houve declínio no colesterol total.

[N]   SHIN D J OSBORNE T F, 2003. Thyroid hormone regulation and cholesterol metabolism are connected through Sterol Regulatory Element-Binding Protein-2 (SREBP-2). J Biol Chem. 2003 Sep 5;278(36):34114-8. Epub 2003 Jun 26. “High affinity uptake of serum-derived low density lipoprotein (LDL) cholesterol is accomplished through the LDL receptor in the liver. In mammals, thyroid hormone depletion leads to decreased LDL receptor expression and elevated serum cholesterol. The clinical association in humans has been known since the 1920s; however, a molecular explanation has been lacking. LDL receptor levels are subject to negative feedback regulation by cellular cholesterol through sterol regulatory element-binding protein-2 (SREBP-2). Here we demonstrate that the SREBP-2 gene is regulated by thyroid hormone and that increased SREBP-2 nuclear protein levels in hypothyroid animals results in thyroid hormone-independent activation of LDL receptor gene expression and reversal of the associated hypercholesterolemia. This occurs without effects on other thyroid hormone-regulated genes. Thus, we propose that the decreased LDL receptor and increased serum cholesterol associated with hypothyroidism are secondary to the thyroid hormone effects on SREBP-2. These results suggest that hypercholesterolemia associated with hypothyroidism can be reversed by agents that directly increase SREBP-2. Additionally, these results indicate that mutations or drugs that lower nuclear SREBP-2 would cause hypercholesterolemia”.

[O]   THOMPSON G R SOUTAR A K, 1981Proc Natl Acad Sci U S A. 1981 Apr;78(4):2591-5.  Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo.
Thompson GR, Soutar AK, Spengel FA, Jadhav A, Gavigan SJ, Myant NB.
“The role of low density lipoprotein (LDL) receptors in the pathogenesis of hereditary and acquired forms of hypercholesterolemia has been investigated in vivo by simultaneously determining total and receptor-independent LDL catabolism with 125I-labeled LDL and 131I-labeled LDL coupled with cyclohexanedione. Receptor-mediated catabolism of LDL, determined as the difference between the turnover of 125I and 131I, was found to be virtually absent in two homozygotes with familial hypercholesterolemia and markedly reduced in a hypothyroid patient. Treatment of the latter with L-thyroxine markedly stimulated receptor-mediated catabolism and reduced LDL levels as did cholestyramine administration in a control subject. Reduction of LDL levels by plasma exchange in a control subject and homozygote had no such effect. These results demonstrate the existence of an intrinsic and almost total defect of receptor-mediated LDL catabolism in homozygous familial hypercholesterolemia and demontrate an analogous but reversible abnormality in hypothyroidism”.

[P]  PUGSLEY L I 1935. The effect of thyrotropic hormone upon serum cholesterol. Biochem J. 1935 March; 29(3): 513–516.
“The intraperitoneal injection of the thyrotropic hormone caused a marked
decrease in the serum cholesterol of rats and dogs. The serum cholesterol curve shows a reciprocal relationship to the basal metabolic rate curve of rats receiving chronic injections of the thyrotropic hormone”.

[Q]   JUNG C H SUNG K C, 2003. Thyroid dysfunction and their relation to cardiovascular risk factors such as lipid profile, hsCRP, and waist hip ratio in Korea. Korean J Intern Med. 2003 Sep;18(3):146-53. “BACKGROUND:
Thyroid abnormalities affect a considerable portion of the population, and overt hypothyroidism is associated with an elevated risk of cardiovascular disease and adverse changes in blood lipids. Subclinical hypothyroidism is also associated with an increase risk of cardiovascular disease. So, we undertook this study to investigate the prevalence of overt and subclinical thyroid disorders and their associations with cardiovascular risk factors.
METHODS: This study involved 66,260 subjects (43,588 men, 22,672 women; between 20-80 years of age, mean age 41.5 +/- 9.6). Serum free thyroxine (FT4), thyroid stimulating hormone (TSH), total cholesterol, low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were measured by RIA using commercial kits. High sensitivity C-reactive protein (hsCRP) levels were determined by nephelometry.
RESULTS: The prevalences of overt thyrotoxicosis, subclinical thyrotoxicosis, overt hypothyroidism and subclinical hypothyroidism were 5/1000 (334 subjects), 6.4/1000 (426 subjects), 1.6/1000 (108 subjects), and 6.4/1000 (375 subjects). Mean plasma total cholesterol and LDL-C were elevated in overt hypothyroidism than in normal controls (202.1 mg/dL and 121.8 mg/dL versus 197.1 mg/dL and 120.1 mg/dL, respectively) (p < 0.05). In subclinical hypothyroidism, mean total cholesterol and LDL-C levels were also elevated (201.9 mg/dL and 123.7 mg/dL) (p = 0.015, p = 0.047). Waist-to-hip ratio (WHR) was lower in overt thyrotoxicosis and higher in hypothyroidism. CONCLUSION: The prevalence of thyroid dysfunction in Korea is not significantly different from that reported by other countries. It was also age dependent and higher in women, but this elevation in women was lower than expected. Patients with hypothyroidism exhibited higher waist-to-hip ratios, an index of obesity. Patients with subclinical hypothyroidism exhibited elevated atherogenic parameters (Total cholesterol, LDL-C). Therefore screening and treatment for subclinical hypothyroidism may be warranted due to its adverse effects on lipid metabolism”.

[R]   LUBOSHITZY R AVIV A, 2002. Risk factors for cardiovascular disease in women with subclinical hypothyroidism. Thyroid. 2002 May;12(5):421-5.
 “Overt hypothyroidism may result in accelerated atherosclerosis and coronary heart disease (CHD) presumably because of the associated hypertension, hypercholesterolemia, and hyperhomocysteinemia. As many as 10%-15% of older women have subclinical hypothyroidism (SH) and thyroid autoimmunity. Whether SH is associated with risk for CHD is controversial. We examined 57 women with SH and 34 healthy controls. SH was defined as an elevated thyrotropin (TSH) (>4.5 mU/L) and normal free thyroxine (FT(4)) level (8.7-22.6 nmol/L). None of the patients had been previously treated with thyroxine. In all participants we determined blood pressure, body mass index (BMI), and fasting TSH, FT(4), antibodies to thyroid peroxidase and thyroglobulin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, folic acid, vitamin B(12), creatinine, and total plasma homocysteine levels. The SH and control groups did not differ in their total homocysteine values. Mean diastolic blood pressure was increased in SH patients versus controls (82 vs. 75 mm Hg; p < 0.01). Mean values of TC, HDL-C, LDL-C, triglycerides, TC/HDL-C, and LDL-C/HDL-C were not different in patients with SH compared with controls. Individual analysis revealed that the percentage of patients with SH having hypertension (20%), hypertriglyceridemia (26.9%), elevated TC/HDL-C (11.5%), and LDL-C/HDL-C (4%) ratios were higher than the percentages in controls. Hyperhomocysteinemia (> or = 10.98 micromol/L) was observed in 29.4% of SH and was not significantly different from the percentage in controls (21.4%). No significant correlation between TSH and biochemical parameters was detected. We conclude that subclinical hypothyroidism in middle-aged women is associated with hypertension, hypertriglyceridemia, and elevated TC/HDL-C ratio. This may increase the risk of accelerated atherosclerosis and premature coronary artery disease in some patients”.

[S]   PESIC M ANTIC S, 2007. [Cardiovascular risk factors in patients with subclinical hypothyroidism]. [Article in Serbian]  Vojnosanit Pregl. 2007 Nov;64(11):749-52.  “BACKGROUND/AIMS: Overt hypothyroidism is disease associated with accelerated arteriosclerosis and coronary heart disease. Whether subclinical hypothyroidism (SH) is associated with increased cardiovascular risk is contraversial. As SH is a high prevalence thyroid dysfunction, specially in older women, it is important to evaluate cardiovascular risk factors in these patients and that was the aim of this study.
METHODS: We examined 30 patients with SH and 20 healthy controls. Subclinical hypothireoidism was defined as an elevated thyrotropin (TSH) (> 4.5 mU/L) and normal free thyroxine (FT4) level. In all the participants we determined body mass index (BMI), blood pressure, TSH, FT4, antibodies to thyroid peroxidase, antibodies to thyroglobulin, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglicerides, total cholesterol/HDL cholesterol ratio and LDL/HDL cholesterol ratio.
RESULTS: Mean BMI in patients with SH was significantly higher (p < 0.05), as well as diastolic blood pressure (p < 0.01) compared with the controls. Average levels of total cholesterol (5.40 +/- 0.62 vs 5.06 +/- 0.19 mmol/l, p < 0.01) and triglycerides (2.16 +/- 0.56 vs 1.89 +/- 0.24 mmol/l, p < 0.05) were also significantly higher in the group with SH. Individual analysis revealed that the percentage of patients with SH having borderline elevated total cholesterol (63.33%), hypertrigliceridemia (43.33%) and elevated total cholesterol/HDL cholesterol ratio (26.67%) were significantly higher than the percentage in the controls. No significant correlation between TSH and lipid parameters was detected.
CONCLUSION:  Subclinical hypothyroidism was associated with higher BMI, diastolic hypertension, higher total cholesterol and triglicerides levels and higher total cholesterol/HDL cholesterols ratio. This might increase the risk of accelerated arteriosclerosis in patients with SH”.

[T]   WALSH J P BREMNER A P 2005.  Thyroid dysfunction and serum lipids: a community-based study. Clin Endocrinol (Oxf). 2005 Dec;63(6):670-5.  “OBJECTIVE:
It is uncertain whether subclinical hypothyroidism (SCH) is associated with hypercholesterolaemia, particularly in subjects with SCH and serum TSH < or = 10 mU/l. Design, PATIENTS AND MEASUREMENTS: Cross-sectional study of 2108 participants in a 1981 community health survey in Busselton, Western Australia. Serum total cholesterol and triglycerides were measured in all subjects and high density lipoprotein cholesterol (HDL-C) measured (and low density lipoprotein cholesterol (LDL-C) calculated) in a subgroup of 631 subjects at the time of the survey. In 2001, TSH and free T4 concentrations were measured on archived sera stored at -70 degrees C. Serum lipid concentrations in subjects with thyroid dysfunction and euthyroid subjects were compared using linear regression models. RESULTS: In the group as a whole, serum total cholesterol was higher in subjects with SCH (N = 119) than in euthyroid subjects (N = 1906) (mean +/- SD 6.3 +/- 1.3 mmol/l vs. 5.8 +/- 1.2 mmol/l, P < 0.001 unadjusted, P = 0.061 adjusted for age, age(2) and sex). Serum total cholesterol was similarly elevated in subjects with SCH and TSH < or = 10 mU/l (N = 89) (6.3 +/- 1.3 mmol/l, P < 0.001 unadjusted, P = 0.055 adjusted for age, age(2) and sex). In the subgroup analysis, LDL-C was higher in subjects with SCH (N = 30) than in euthyroid subjects (N = 580) (4.1 +/- 1.2 mmol/l vs. 3.5 +/- 1.0 mmol/l, P < 0.01 unadjusted, P = 0.024 adjusted for age, age(2) and sex). LDL-C was significantly increased in subjects with SCH and TSH < or = 10 mU/l (N = 23) (4.3 +/- 1.3 mmol/l, P < 0.001 unadjusted, P = 0.002 adjusted for age, age(2) and sex). CONCLUSION: SCH is associated with increased serum LDL-C concentrations, which is significant after adjustment for age, age(2) and sex”.

[U]   SERTER R DEMIRBAS B, 2004. The effect of L-thyroxine replacement therapy on lipid based cardiovascular risk in subclinical hypothyroidism.  J Endocrinol Invest. 2004 Nov;27(10):897-903.  “The aim of our study was to assess the changes in serum lipid profiles after replacement therapy with L-T4 in patients with subclinical hypothyroidism (SCH), and to see whether there is an improvement in dyslipidemia based cardiovascular risk. Thirty non-smoker pre-menopausal women with newly diagnosed SCH (TSH between 4 and 10 microIU/ml) were involved in our study; twenty-six euthyroid healthy subjects were used as control group. TSH, free T3 (FT3), free T4 (FT4), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were measured before and after 6 months of L-T4 (50-100 microg/ day) therapy. TSH levels were targeted as < 2.0 microIU/ml. LDL-C was calculated using the Friedewald formula, while the cardiovascular risk was assessed with the TC/HDL-C ratio. Pre-treatment serum TC and LDL-C concentrations in SCH patients were significantly higher than those of euthyroid subjects (199.8 +/- 22.2 vs 181.5 +/- 24.6 mg/dl, p < 0.01; 146.3 +/- 26.1 vs 124.8 +/- 12 mg/dl, p < 0.001, respectively). TC, LDL-C levels and the TC/HDL-C ratio were reduced significantly after 6-month replacement therapy (-21.1 +/- 34.4 mg/dl or -10.5%, p < 0.01; -21.5 +/- 30.3 mg/dl or -14.7%, p < 0.001, respectively; and TC/HDL-C from 4.8 +/- 0.6 to 4.1 +/- 0.5 mg/dl, p < 0.01), while body mass index (BMI) values did not change. In conclusion, even mild elevations of TSH are associated with changes in lipid profile significant enough to raise the cardiovascular risk ratio, and these changes are corrected once the patients have been rendered euthyroid”.

[V]   MILIONIS H J TAMBAKI A P 2005. Thyroid substitution therapy induces high-density lipoprotein-associated platelet-activating factor-acetylhydrolase in patients with subclinical hypothyroidism: a potential antiatherogenic effect. Thyroid. 2005 May;15(5):455-60.  “BACKGROUND:  Subclinical hypothyroidism (SH) has been associated with an increased risk of ischemic heart disease, which has been partly attributed to lipid abnormalities. Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme associated with lipoproteins (both low-density lipoproteins [LDL], and high-density lipoproteins [HDL]). Plasma paraoxonase 1 (PON1) is an esterase exclusively associated with HDL.
OBJECTIVE: To evaluate qualitative changes in lipoprotein metabolism with respect to PAF-AH and PON1 activities in patients with SH before and after the restoration of euthyroidism.
DESIGN AND METHODS: We determined the PAF-AH activity in plasma and on HDL and PON1 activities as well as the lipid profile patients with SH at baseline and after 6 months of levothyroxine substitution therapy. Thirty normolipidemic healthy individuals comprised the control group.
RESULTS:  Compared to controls, patients with SH showed higher levels of total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B. Triglycerides were significantly reduced after levothyroxine treatment. Patients with SH exhibited higher plasma baseline PAF-AH activity (63.0 +/- 16.5 versus 44.3 +/- 9.5 nmol/mL per minute p < 0.0001) and lower baseline HDL associated PAF-AH (2.9 +/- 1.1 versus 3.6 +/- 0.9 nmol/mL per minute p = 0.02) compared to the control group. PON1 activities were similar in both groups. Levothyroxine treatment had no effect on plasma PAF-AH activity or PON1 activities but resulted in a significant elevation of HDL-associated PAF-AH activity (from 2.9 +/- 1.1 to 3.5 +/- 1.0 nmol/mL per minute, p = 0.003).
CONCLUSIONS: Patients with SH exhibit increased plasma PAF-AH activity and low HDL-associated PAF-AH activity. Levothyroxine induces a significant increase in HDL-PAF-AH activity. This action may represent a potential antiatherogenic effect of thyroid replacement therapy”.

[X]   ARINZON Z ZUTA A 2007. Evaluation response and effectiveness of thyroid hormone replacement treatment on lipid profile and function in elderly patients with subclinical hypothyroidism.  Arch Gerontol Geriatr. 2007 Jan-Feb;44(1):13-9. Epub 2006 Apr 18.  “Positive effect of thyroid hormone replacement (THR) on lipid profile is well defined. Effectiveness of THR on lipid profile and function among elderly patients with subclinical hypothyroidism (SCH) has not yet been concluded. This is a population-based cross-sectional study. Twenty-six elderly patients with SCH were compared with 31 patients with clinical hypothyroidism (CH). Before the study neither group had received THR therapy. Data on lipid profile, demographic, functional, and cognitive status were obtained at baseline. SCH was defined as an elevated thyroid-stimulating hormone (TSH) level (> 4.67 mU/l) and normal serum free thyroxine (FT(4)) level. Total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) were measured after overnight fast. The level of lower density lipoprotein (LDL) cholesterol was calculated. Both studied groups received levothyroxyne replacement and re-evaluated after 3 months of euthyroidism. Functional and cognitive status were evaluated by the activity of daily living (ADL) and mini mental state evaluation (MMSE), respectively. Participants with SCH did not differ from patients with CH regarding age, gender, cognitive, and functional status, and prevalence of cardiovascular disease (CD) was similar in both groups. Most patients (24/26) with SCH had TSH levels lower than 10 mU/l. Response to THR therapy regarding the improvement of blood levels of TC, LDL, and TG had a non-significant trend, which seemed to be better in patients with SCH than in those with CH. Decreases, TC/HDL and LDL/HDL ratios were greater in patients SCH (p < 0.0001 and p = 0.0004, respectively) than in patients with CH. Improvement in cognitive and functional status and decrease in mean blood pressure and body mass index (BMI) were found in both of studied groups. It was shown that THR among patients with SCH is beneficial not only by improvement in lipid profile, as well as by improvement in cognitive and functional status, but also in decreasing blood pressure and BMI”.

[Y]   MIURA S IITAKA M YOSHIMURA H, 1994. Disturbed lipid metabolism in patients with subclinical hypothyroidism: effect of L-thyroxine therapy.  Intern Med. 1994 Jul;33(7):413-7.  “To evaluate whether patients with subclinical hypothyroidism have a disturbance in lipid metabolism, and whether supplemental L-thyroxine (L-T4) therapy would improve their lipid parameters, we measured serum levels of thyroid hormones, TSH and lipid parameters in 34 patients with subclinical hypothyroidism before and 2 months after treatment with L-T4. Before treatment, patients with subclinical hypothyroidism had elevated serum low density lipoprotein cholesterol (LDL-C) concentrations compared with control subjects (P < 0.05). Overall, L-T4 therapy significantly decreased the serum level of TSH (P < 0.01), total cholesterol (TC; P < 0.02), high density lipoprotein cholesterol (P < 0.02), LDL-C (P < 0.05), and the ratio of apolipoprotein B to apolipoprotein A1 (P < 0.05). Lipid values in patients with basal serum TSH levels below 10 mU/l were not affected by L-T4 therapy, whereas serum levels of TC and LDL-C decreases significantly (P < 0.01) in patients with serum TSH levels above 10 mU/l. Thus, the L-T4 treatment appears to have a preventive effect on the disturbance of lipid metabolism in patients with subclinical hypothyroidism, especially in patients with serum TSH levels above 10 mU/l”.

[Z]   DZUGAN S A SMITH A, 2002. Med Hypotheses. 2002 Dec;59(6):751-6.
Hypercholesterolemia treatment: a new hypothesis or just an accident?” A new hypothesis concerning the association of low levels of steroid hormones and hypercholesterolemia is proposed. This study presents data that concurrent restoration to youthful levels of multiple normally found steroid hormones is able to normalize or improve serum total cholesterol (TC). We evaluated 20 patients with hypercholesterolemia who received hormonorestorative therapy (HT) with natural hormones. Hundred percent of patients responded. Mean serum TC was 263.5 mg/dL before and 187.9 mg/dL after treatment. Serum TC dropped below 200 mg/dL in 60.0%. No morbidity or mortality related to HT was observed. In patients characterized by hypercholesterolemia and sub-youthful serum steroidal hormones, our findings support the hypothesis that hypercholesterolemia is a compensatory mechanism for life-cycle related down-regulation of steroid hormones, and that broadband steroid hormone restoration is associated with a substantial drop in serum TC in many patients”.

[Z1]   ALTHAUS B U STAUB J J 1988. LDL/HDL-changes in subclinical hypothyroidism: possible risk factors for coronary heart disease. Clin Endocrinol (Oxf). 1988 Feb;28(2):157-63. “The aim of the present study was to evaluate the lipid profiles (total cholesterol, triglycerides, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and the electrophoretic low-density lipoproteins and high-density lipoproteins) in patients with subclinical (n = 52) and overt hypothyroidism (n = 18) in comparison to normal controls (28 and 18, respectively), matched for age, sex and body mass index. Subclinical hypothyroidism was defined as a syndrome with normal free thyroxine and total thyroxine but elevated basal thyrotrophin levels and/or an exaggerated TSH response to oral thyrotrophin releasing hormone. In subclinical hypothyroidism there was an elevated LDL concentration (P less than 0.01), a diminished HDL fraction (P less than 0.05) and a borderline elevated LDL-C (not reaching the limit of significance, P = 0.07). Total cholesterol and triglyceride concentrations remained unaltered. For the whole group of patients and controls significant negative correlations were found between LDL-C and T4 (P less than 0.04), total cholesterol and free thyroxine-index (P less than 0.01); positive correlations could be demonstrated between LDL-C and basal TSH (P less than 0.03), the ratio total cholesterol/HDL-C and basal TSH (P less than 0.03), and triglycerides and basal TSH (P less than 0.01). Our data provide a possible explanation for the higher prevalence of coronary heart disease reported in subclinical hypothyroidism. There may well be a case for the detection and early treatment of such individuals”.

[Z2]   THORELL B SVARDSUDD K, 1993. Myocardial infarction risk factors and well-being among 50-year-old women before and after the menopause. The population study “50-year-old people in Kungsör”.  Scand J Prim Health Care. 1993 Jun;11(2):141-6.  “OBJECTIVE:  To examine whether early menopause has a negative influence on the traditional ischaemic heart disease (IHD) risk factor pattern and on well-being.
DESIGN: Cross-sectional population study.
SETTING: Kungsör, a semirural community in mid-Sweden.
PARTICIPANTS: All 155 women in Kungsör who became 50 years old in 1984-7.
MAIN OUTCOME MEASURES:  Traditional IHD risk factors and self assessed well-being measures.
RESULTS: Women who smoked had an earlier menopause than others. Postmenopausal women had significantly higher serum cholesterol levels (and haemoglobin levels), and more sleep disturbances than premenopausal women. There were no significant differences in other self-rated well-being, but home and family situation, patience, anxiety, and sleep disturbances tended to become worse with time from menopause.CONCLUSIONS: These findings may be interpreted as evidence indicating that the menopause affects the IHD risk factor profile and well-being negatively”.

[Z3]   FPS - The Cholesterol and Thyroid Connection.  By Team FPS – January 20, 2012. Disponível em:  Scand J Prim Health Care. 1993 Jun;11(2):141-6. As referências acima estão, originalmente, todas, disponíveis no site abaixo: https://www.functionalps.com/blog/2012/01/20/the-cholesterol-and-thyroid-connection/

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