The Cholesterol and Thyroid Connection

Also see:
High Cholesterol and Metabolism
High cholesterol ‘does not cause heart disease’ new research finds, so treating with statins a ‘waste of time’
The Truth about Low Cholesterol
Thyroid Status and Oxidized LDL
Inflammatory TSH
“Normal” TSH: Marker for Increased Risk of Fatal Coronary Heart Disease
Thyroid Status and Cardiovascular Disease
High Blood Pressure and Hypothyroidism
A Cure for Heart Disease
Hypothyroidism and A Shift in Death Patterns
Low Blood Cholesterol Compromises Immune Function
Ray Peat, PhD on Thyroid, Temperature, Pulse, and TSH

“Circumstantial evidenced convicted cholesterol as the villain in heart attacks for many years. Finally the truth emerged when it was shown that indeed high cholesterol is frequently found in heart attacks. However, evidence has been accumulating for 100 years indicating that the real culprit is a thyroid deficiency, and cholesterol, which is usually increased in hypothyroidism, is only an innocent bystander.” -Dr. Broda Barnes, MD, PhD

“In other words, the thyroid has a profound effect on the liver. We have other evidence that a lack of thyroid is accompanied by a sluggish liver. In the first place, it has been apparents for a century that patients with myxedema (very low thyroid activity) have a yellowish tint to their skins. This has been found to be due to the presence of too much carotene in the blood. The liver converts carotene into vitamin A which is colorless. Under the administration of thyroid, the liver becomes more active and the carotene soon disappears. In the second place, the cholesterol level in the blood sis usually elevated in hypothyroidism. Thyroid administration will lower cholesterol, and if too much is given, the cholesterol will fall below normal. The liver converts cholesterol into bile salts which are eliminated in the bile; this process is the usual means of eliminating excess cholesterol. The liver is sluggish in this function among thyroid-deficient individuals…Since a sluggish liver is the most common cause of hypoglycemia, it should follow that the hypothyroid patient is highly susceptible to low blood sugar.” -Broda Barnes, MD, PhD and Charlotte Barnes

“Actually, twelve years before, Dr. L.M. Hurxthal at the Lahey Clinic in Boston had clearly shown that thyroid secretion controls cholesterol level in most patients. In patients with hyperthyroidism, or excessive thyroid activity, he had found, the cholesterol level in the blood was below the average normal level. After surgery on the excessively active thyroid gland, the cholesterol level climbed above normal if too much thyroid tissue has been removed, making the patient hypothyroid. But then if the hypothyroid patient were given the proper dosage of thyroid, the cholesterol level fell into the normal range and stayed there.” -Broda Barnes, MD, PhD

“By the mid-1930s, it was generally known that hypothyroidism causes the cholesterol level in the blood to increase; hypercholesterolemia was a diagnostic sign of hypothyroidism. Administering a thyroid supplement, blood cholesterol came down to normal exactly as the basal metabolic rate came up to the normal rate.” -Ray Peat, PhD

“In the healthy organism, cholesterol is constantly being synthesized, and constantly converted into steroid hormones, and, in the liver, into the bile salts that are secreted to emulsify fats in the intestine. Thyroid hormone and vitamin A are used in the process of converting cholesterol into pregnenolone, the immediate precursor of progesterone and DHEA. Anything that interfered with these processes would be disastrous for the organism. The supply of cholesterol, thyroid and vitamin A must always be adequate for the production of steroid hormones and bile salts. When stress suppresses thyroid activity, increased cholesterol probably compensates to some extent by permitting more progesterone to be synthesized.

In very young people, the metabolic rate is very high, and the rapid conversion of cholesterol into pregnenolone, DHEA, and progesterone usually keeps the level of cholesterol in the blood low. In the 1930s, a rise in the concentration of cholesterol was considered to be one of the most reliable ways to diagnose hypothyroidism (1936 Yearbook of Neurology, Psychiatry, and Endocrinology, E.L. Sevringhaus, editor, Chicago, p. 533). With aging, the metabolic rate declines, and the increase of cholesterol with aging is probably a spontaneous regulatory process, supporting the synthesis of the protective steroids, especially the neurosteroids in the brain and retina.” -Ray Peat, PhD

“High cholesterol compensates for low thyroid, keeping your pregnenolone, progesterone, and DHEA up. Sugar allows you to dispose of free fatty acids by turning them into triglycerides for storage. Free fatty acids activate stress hormones, which in turn cause the synthesis of fatty acids, even from the breakdown of amino acids, derived from protein by the action of cortisol. When cholesterol is that high, it’s almost always because of low thyroid activity, and stored PUFA are probably the commonest cause of that. I think free fatty acids, and their degree of unsaturation, would be the most meaningful blood lipids to test, but it’s easier to test for cholesterol and triglycerides.” -Ray Peat, PhD

“The accumulation of cholesterol clearly indicates the failure to convert it to steroids, so elevated cholesterol is a fairly reliable diagnostic indicator of hypothyroidism.” -Ray Peat, PhD

“Cholesterol is used rapidly under the influence of T3, and ever since the 1930s it has been clear that serum cholesterol rises in hypothyroidism, and is very useful diagnostically.” -Ray Peat, PhD

“In the adrenals, cholesterol passes quickly from pregnenolone to DHEA, in the ovaries it goes right from pregnenolone to progesterone. T3 is responsible for the oxidative activity that governs the conversion of cholesterol.” -Ray Peat, PhD

Prev Cardiol. 2001 Autumn;4(4):179-182.
An Association Between Varying Degrees of Hypothyroidism and Hypercholesterolemia in Women: The Thyroid-Cholesterol Connection.
Feld S, Dickey RA.
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.

Arch Intern Med. 2000 Feb 28;160(4):526-34.
The Colorado thyroid disease prevalence study.
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC.
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.
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.
Cross-sectional study.
Participants in a statewide health fair in Colorado, 1995 (N = 25 862).
Serum thyrotropin (thyroid-stimulating hormone [TSH]) and total thyroxine (T4) concentrations, serum lipid levels, and responses to a hypothyroid symptoms questionnaire.
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.
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.

J Clin Invest. 1939; 18(1):45–49 doi:10.1172/JCI101024
Kenneth B. Turner, Alfred Steiner
4. Thyroid administration produced a sharp drop in serum cholesterol in every case. This accompanied by a rise in the basal metabolic rate.

Clin Endocrinol (Oxf). 1997 Jan;46(1):17-20.
The effect of the treatment of hypothyroidism and hyperthyroidism on plasma lipids and apolipoproteins AI, AII and E.
O’Brien T, Katz K, Hodge D, Nguyen TT, Kottke BA, Hay ID.
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.
A prospective study of lipids and apolipoproteins before and after treatment of hypothyroidism and hyperthyroidism.
Eighteen patients with hypothyroidism and 5 patients with hyperthyroidism were included.
Plasma cholesterol, triglycerides, HDL cholesterol, apo AI, apo AII, and apo E were measured before and after treatment of the thyroid abnormality.
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.
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.

Nihon Naibunpi Gakkai Zasshi. 1989 Aug 20;65(8):781-93.
[Clinical studies on lipid metabolism in hyperthyroidism and hypothyroidism–evaluation of serum apolipoprotein levels before and after treatment].
[Article in Japanese]
Oribe H.
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.

J Clin Endocrinol Metab. 1982 Sep;55(3):459-64.
Serum lipids and apolipoproteins A-I, A-II, and B in hyperthyroidism before and after treatment.
Muls E, Blaton V, Rosseneu M, Lesaffre E, Lamberigts G, De Moor P.
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.

Clin Chem. 1995 Feb;41(2):226-31.
Changes in serum lipoprotein(a) and lipids during treatment of hyperthyroidism.
Kung AW, Pang RW, Lauder I, Lam KS, Janus ED.
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.

J Clin Endocrinol Metab. 2000 May;85(5):1857-62.
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.
Diekman MJ, Anghelescu N, Endert E, Bakker O, Wiersinga WM.
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.

J Clin Endocrinol Metab. 2001 Oct;86(10):4860-6.
TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study).
Meier C, Staub JJ, Roth CB, Guglielmetti M, Kunz M, Miserez AR, Drewe J, Huber P, Herzog R, Müller B.
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 Intern Med. 2006 Jul;260(1):53-61.
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.
Iqbal A, Jorde R, Figenschau Y.
To evaluate the relation between serum thyroid-stimulating hormone (TSH) and lipids.
Cross-sectional epidemiological study, nested case-control study, and a placebo-controlled double-blind intervention study.
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.
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.
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.

Clin Endocrinol (Oxf). 1995 Oct;43(4):445-9.
Elevated serum lipoprotein(a) in subclinical hypothyroidism.
Kung AW, Pang RW, Janus ED.
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.
Thirty-two Chinese subjects with asymptomatic subclinical hypothyroidism were compared to 96 age and sex-matched healthy controls.
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).
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.

Endocr Pract. 2008 Jul-Aug;14(5):570-5.
Increased atherogenic low-density lipoprotein cholesterol in untreated subclinical hypothyroidism.
Mikhail GS, Alshammari SM, Alenezi MY, Mansour M, Khalil NA.
To evaluate the effects of physiologic doses of levothyroxine replacement on the lipoprotein profile in patients with subclinical hypothyroidism (SCH).
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.
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.
In premenopausal women, SCH has a negative effect on the lipoprotein profile and may translate into a sizable cardiovascular risk if left untreated.

J Clin Endocrinol Metab. 2000 Sep;85(9):2993-3001.
Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature.
Danese MD, Ladenson PW, Meinert CL, Powe NR.
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.

J Biol Chem. 2003 Sep 5;278(36):34114-8. Epub 2003 Jun 26.
Thyroid hormone regulation and cholesterol metabolism are connected through Sterol Regulatory Element-Binding Protein-2 (SREBP-2).
Shin DJ, Osborne TF.
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.

Proc 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.

Biochem J. 1935 March; 29(3): 513–516.
The effect of thyrotropic hormone upon serum cholesterol
Leonard Irving Pugsley
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.

Korean J Intern Med. 2003 Sep;18(3):146-53.
Thyroid dysfunction and their relation to cardiovascular risk factors such as lipid profile, hsCRP, and waist hip ratio in Korea.
Jung CH, Sung KC, Shin HS, Rhee EJ, Lee WY, Kim BS, Kang JH, Kim H, Kim SW, Lee MH, Park JR, Kim SW.
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.
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.
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.

Thyroid. 2002 May;12(5):421-5.
Risk factors for cardiovascular disease in women with subclinical hypothyroidism.
Luboshitzky R, Aviv A, Herer P, Lavie L.
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.

Vojnosanit Pregl. 2007 Nov;64(11):749-52.
[Cardiovascular risk factors in patients with subclinical hypothyroidism].
[Article in Serbian]
Pesić M, Antić S, Kocić R, Radojković D, Radenković S.
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.
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.
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.
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.

Clin Endocrinol (Oxf). 2005 Dec;63(6):670-5.
Thyroid dysfunction and serum lipids: a community-based study.
Walsh JP, Bremner AP, Bulsara MK, O’leary P, Leedman PJ, Feddema P, Michelangeli V.
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.

J Endocrinol Invest. 2004 Nov;27(10):897-903.
The effect of L-thyroxine replacement therapy on lipid based cardiovascular risk in subclinical hypothyroidism.
Serter R, Demirbas B, Korukluoglu B, Culha C, Cakal E, Aral Y.
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.

Thyroid. 2005 May;15(5):455-60.
Thyroid substitution therapy induces high-density lipoprotein-associated platelet-activating factor-acetylhydrolase in patients with subclinical hypothyroidism: a potential antiatherogenic effect.
Milionis HJ, Tambaki AP, Kanioglou CN, Elisaf MS, Tselepis AD, Tsatsoulis A.
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.
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.
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.
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).
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.

Arch Gerontol Geriatr. 2007 Jan-Feb;44(1):13-9. Epub 2006 Apr 18.
Evaluation response and effectiveness of thyroid hormone replacement treatment on lipid profile and function in elderly patients with subclinical hypothyroidism.
Arinzon Z, Zuta A, Peisakh A, Feldman J, Berner Y.
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.

Intern Med. 1994 Jul;33(7):413-7.
Disturbed lipid metabolism in patients with subclinical hypothyroidism: effect of L-thyroxine therapy.
Miura S, Iitaka M, Yoshimura H, Kitahama S, Fukasawa N, Kawakami Y, Sakurai S, Urabe M, Sakatsume Y, Ito K, et al.
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.

Med Hypotheses. 2002 Dec;59(6):751-6.
Hypercholesterolemia treatment: a new hypothesis or just an accident?
Dzugan SA, Arnold Smith R.
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.

Clin Endocrinol (Oxf). 1988 Feb;28(2):157-63.
LDL/HDL-changes in subclinical hypothyroidism: possible risk factors for coronary heart disease.
Althaus BU, Staub JJ, Ryff-De Lèche A, Oberhänsli A, Stähelin HB.
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.

Scand J Prim Health Care. 1993 Jun;11(2):141-6.
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”.
Thorell B, Svärdsudd K.
To examine whether early menopause has a negative influence on the traditional ischaemic heart disease (IHD) risk factor pattern and on well-being.
Cross-sectional population study.
Kungsör, a semirural community in mid-Sweden.
All 155 women in Kungsör who became 50 years old in 1984-7.
Traditional IHD risk factors and self assessed well-being measures.
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.
These findings may be interpreted as evidence indicating that the menopause affects the IHD risk factor profile and well-being negatively.

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