Relationship between Lipoprotein(a) and Thyroid Hormones in Hypothyroid Patients

Lipoprotein(a) and other lipoproteins in hypothyroid patients before and after thyroid replacement therapy

Women who undergo assisted reproductive technology (ART) are exposed to a supra-physiological hormonal environment, which can affect the hypothalamus-pituitary-thyroid axis. Understanding these changes can help us improve the outcomes of ART. In this study we discuss the changes of thyroid hormone levels during ovarian stimulation as part of intrauterine insemination (IUI) and compare hypothyroid and euthyroid patients. Fifty-two infertile women aged 22 to 40 who underwent induction ovulation (I/O) as part of IUI were enrolled in this study. Out of 52 patients, 13 had underlying thyroid disease receiving levothyroxine treatment, and their thyroid test results were normal (<2.5) for more than 6 weeks and had taken fixed levels of levothyroxine for more than 6 weeks. The TSH levels were measured by electrochemiluminescence at 3 times: baseline TSH (before starting of I/O), the day of HCG administration, and 4 weeks after. The change of TSH levels during this period and its relationship with baseline hypothyroidism, oestradiol levels, and I/O and pregnancy outcome were studied. Mean central index, frequency percentage, the median, and dispersion of standard deviation and interquartile range (IQR) were used to describe the data. Statistical tests, including t-test and chi-square, were used to analyse the data. Mean difference and relative risk indices were used to measure the differences. There was a significant increase in TSH level at the time of hCG injection compared with basal TSH in hypothyroid patients under treatment, TSH increased from 1.61 ± 0.81 to 2.75 ± 1.86 (P = 0.045), and this increase was seen in TSH 4 weeks later from 1.61 ± 0.81 to 2.12 ± 0.87 (P = 0.026). However, there were not significant changes in thyroid hormone level during treatment in euthyroid patients. In hypothyroid patients who got pregnant, there was no significant increase in 3 TSH measurements. But for the patients with an unsuccessful cycle this increase was seen at the time of HCG injection and 4 weeks later in comparison with basal TSH, which was statistically significant: 1.55 ± 0.83 v. 2.97 ± 2.09 (P = 0.05) and 1.55 ± 0.83 v. 2.14 ± 0/99 (P = 0.039). But this change was not seen in euthyroid patients with successful and unsuccessful cycle results. The relationship between TSH level with oestradiol in both euthyroid and hypothyroid patients was not significant. There was not a significant correlation between the number of follicles bigger than 16 mm, the mean size of follicles, and endometrial thickness with TSH at the time of HCG injection in both hypothyroid and euthyroid patients. There was a negative and reverse correlation between endometrial thickness and TSH at the time of HCG injection, but it was not significantly different. (P = 0.05). In euthyroid patients who undergo I/O as part of IUI, we did not observe significant TSH level changes during I/O, but in controlled hypothyroid patients a rise in serum TSH levels was observed. The pregnancy rate between 2 euthyroid and controlled hypothyroid groups was not different.

Altered fibrinolytic parameters and serum lipid profile are strongly related to thyroid dysfunction. To investigate the patterns of the fibrinolytic abnormalities and serum lipid profile in the hypo- and hyperthyroid patients. We also took an aim at studying the relationships between free T4 levels (FT4) and these parameters. Hyperthyroid (n = 30), hypothyroid (n = 20) patients and euthyroid control subjects (n = 30) were evaluated for several fibrinolytic parameters including plasma plasminogen activator inhibitor-1 (PAI-1) and D-dimer (D-D). Serum lipid profile and lipoprotein(a) (Lp(a)) were also measured. We found different patterns of fibrinolytic abnormalities and lipid profile in hypo- and hyperthyroid patients. The hypothyroid patients had low plasma PAI-1 levels and high D-D values as compared to hyperthyroid patients (p < 0.001) and euthyroid control subjects (p < 0.05 and 0.001, respectively). In sharp contrast, the hyperthyroid patients had high plasma PAI-1 levels (p < 0.001) but without concomitant change in plasma D-D values, as compared to the euthyroid control subjects. Hypothyroidism was associated with high total cholesterol, triglycerides, LDL-C and Lp(a) levels and low HDL-C levels as compared to both hyperthyroid and euthyroid states (p < 0.001). FT4 levels were correlated positively with HDL-C but negatively with total cholesterol, triglycerides, LDL-C and Lp(a) levels in both hypo- and hyperthyroid patients. Also FT4 levels were correlated positively with PAI-1 but negatively with D-D in both hypo- and hyperthyroid patients (p < 0.02, 0.01, 0.001 and 0.03 respectively). We found hyperfibrinolytic, and hypofibrinolytic patterns in hypothyroid, hyperthyroid patients, respectively. The hypothyroid patients had atherogenic lipid profile. These variations indicate possible pathophysiologic roles for thyroid hormones in the regulation of the fibrinolytic system and lipid profile. Mechanisms of these variations are open for future investigations.

Heart failure (HF) is a major public health and economic problem in Western countries and is one of the most common causes of hospitalization and death. Coronary artery disease is the underlying cause in more than two thirds of chronic HF patients. By 2020, the World Health Organization projects that ischemic heart disease alone will be the most important global cause of morbidity and mortality. The estimated increases in HF-related morbidity and mortality suggest that our understanding of the pathophysiological mechanisms of this syndrome is inadequate. Interest in the role of thyroid hormones (THs) in HF has increased in recent years. The driving considerations can be summarized as follows: (1) the known effects of THs on contractile and relaxation properties of the heart; (2) experimental findings offering strong support for the hypothesis that TH signaling is critical in preserving cardiac structure and performance under normal conditions and after cardiac injury; and (3) evidence that mildly altered TH function is strongly associated with a worsening prognosis in cardiac patients in general and in HF patients in particular. Diastolic function and systolic function are clearly influenced by THs.1 Ventricular contractile function is also influenced by changes in hemodynamic conditions secondary to TH effects on peripheral vascular tone.1 TH homeostasis preserves positive ventricular-arterial coupling, leading to a favorable balance for cardiac work. A study in rats demonstrated that chronic hypothyroidism alone can eventually lead to HF.2 Other studies suggest reduced cardiac tissue triiodothyronine (T3) levels after myocardial infarction (MI) or with development of hypertension by upregulating type 3 deiodinase (D3), which leads to deactivation of T3 and T4 (thyroxine).3–6 This review highlights a growing body of evidence from animal studies and small-scale clinical trials suggesting that low cellular thyroid activity at the cardiac tissue level may adversely affect HF …

Lipoprotein(a) [Lp(a)] is a unique lipoprotein complex in the blood. At high levels (> 30 mg/dl), Lp(a) is considered an independent risk factor for cardiovascular diseases. Serum Lp(a) levels are largely genetically determined, remain relatively constant within a given individual, and do not appear to be altered by factors known to influence other lipoproteins (e.g. lipid-lowering drugs, dietary modification and change in body mass). Since regular exercise is associated with favourable changes in lipoproteins in the blood, recent attention has focused on whether serum Lp(a) levels are also influenced by physical activity. Population and cross-sectional studies consistently show a lack of association between serum Lp(a) levels and regular moderate physical activity. Moreover, exercise intervention studies extending from 12 weeks to 4 years indicate that serum Lp(a) levels do not change in response to moderate exercise training, despite improvements in fitness level and other lipoprotein levels in the blood. However, recent studies suggest the possibility that serum Lp(a) levels may increase in response to intense load-bearing exercise training, such as distance running or weight lifting, over several months to years. Cross-sectional studies have reported abnormally high serum Lp(a) levels in experienced distance runners and body builders who train for 2 to 3 hours each day. However, the possible confounding influence of racial or ethnic factors in these studies cannot be discounted. Recent intervention studies also suggest that 9 to 12 months of intense exercise training may elevate serum Lp(a) levels. However, these changes are generally modest (10 to 15%) and, in most individuals, serum Lp(a) levels remain within the recommended range. It is unclear whether increased serum Lp(a) levels after intense exercise training are of clinical relevance, and whether certain Lp(a) isoforms are more sensitive to the effects of exercise training. Since elevation of both low density lipoprotein cholesterol (LDL-C) and Lp(a) levels in the blood exerts a synergistic effect on cardiovascular disease risk, attention should focus on changing lifestyle factors to decrease LDL-C (e.g. dietary intervention) and increase high density lipoprotein cholesterol (e.g. exercise) levels in the blood.

Background: Hypothyroidism is a common hormonal disorder affecting various organs including lungs and pulmonary dysfunction in hypothyroid patients has been noted.&#x0D; Objective: To observe maximum voluntary ventilation (MVV) in hypothyroid female patients.&#x0D; Materials and method: This cross-sectional study was carried out in the Department of Physiology, BSMMU, Dhaka, Bangladesh, from 1st July 2008 to 30th June 2009 on 60 hypothyroid female patients of 30-50 years old. Based on treatment, hypothyroid patients were divided into B1 (untreated patients on their 1st day of diagnosis) and B2 (patients treated for at least 12-18 months). For comparison, 30 age and BMI matched apparently healthy subjects (Group A) were also studied. The study group was selected from the Out Patient Department of Endocrinology, BSMMU, Dhaka, Bangladesh, and the control group was selected by personal contact. Serum TSH and serum FT4 levels were measured by Microparticle Enzyme Immunoassay (MEIA) principle in AxSYM system. Maximum voluntary ventilation (MVV), which is a lung function parameter, was measured by a digital MicroDL spirometer. Data were analyzed by one way ANOVA test, independent sample t-test and Pearson’s correlation coefficient test.&#x0D; Results: The mean percentage of predicted values of lung function parameter of MVV in control subjects and treated hypothyroids were within normal ranges. However, this value was significantly lower in untreated hypothyroid subjects in comparison to those of control and treated hypothyroid subjects. In addition, MVV showed negative correlation with serum TSH level and positive correlation with serum FT4 level and these relationships were statistically significant in control group and treated hypothyroid subjects.&#x0D; Conclusion: This study reveals that MVV may be lower in untreated hypothyroid female patients compared to control and treated hypothyroids and the deterioration may be positively correlated with serum FT4 level and negatively correlated with serum TSH level. Treatment of hypothyroids may reverse these changes.&#x0D; Delta Med Col J. Jul 2020;8(2): 55-60

There are so many studies that suggest the changes in lipid profiles and lipoprotein (a) [Lp(a)] are associated with early atherosclerosis in rheumatoid arthritis (RA). But there are some opposite studies also. Because of marked ethnicity differences in the distribution of Lp(a), we aimed to investigate the associations of Lp(a) levels and lipid changes in Turkish RA patients. There were 30 women and 20 men, a total of 50 patients with RA (mean age 47.6 +/- 13.2 years), included and 21 healthy women and 14 healthy men (mean age 45.7 +/- 14.5 years) were recruited as a control (C) group. Serum Lp(a), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were analysed for each group. Analysis of six different studies was performed. In the RA and C groups, mean serum Lp(a) levels were 39.7 +/- 64.4 and 10.5 +/- 13.4 mg/dl, respectively (P=0.001). Mean TC levels were 189.2 +/- 142.5 and 174.0 +/- 29.3 mg/dl (P=0.294), mean TG levels were 121.4 +/- 65.4 and 106.5 +/- 80.0 mg/dl (P=0.030), mean HDL-C levels were 44.5 +/- 10.0 and 47.7 +/- 4.8 mg/dl (P=0.014) and mean LDL-C levels were 94.3 +/- 35.3 and 102.0 +/- 24.6 mg/dl (P=0.98), respectively. Analysis of the six studies showed Lp(a) level was higher and HDL level was lower in RA patients than in healthy controls. Patients with RA may have altered lipid profiles from one country to another one. Especially in Turkey, higher serum Lp(a), lower HDL-C and higher TG levels may be found in RA patients instead of some findings of other countries showing different results. Ethnicity may be a reason for these findings.

Serum lipoprotein(a) {Lp(a)} is accepted as a potent risk factor for atherosclerotic disease. C4b binding protein (C4bp), a regulatory protein in complement system, plays important roles in blood coagulation and fibrinolysis, and is identical with proline-rich protein. Our previous study showed a positive correlation between serum Lp(a) and C4bp levels (Nagata et al., J. Jpn. Atheroscler. Soc., 20: 651-655, 1992). Both the serum amyloid A (SAA) and serum amyloid P (SAP) components are precursors of the amyloid A and P proteins, which are the main amyloid components deposited in the tissue of secondary amyloidosis. In human blood, SAP binds with C4bp, and SAA binds with HDL lipoprotein.We examined effects of oral administration of niceritrol (750mg/day, for 16 weeks) on serum lipids, apolipoproteins, Lp(a), C4bp, SAP, and SAA in 26 patients (12 males and 14 females) who had high serum Lp(a) levels (>30mg/dl) and the following cerebrovascular diseases: cerebral infarction (16 patients), cerebral bleeding (8 patients), and subarachinoidal hemorrhage (2 patients).Niceritrol therapy decreased total cholesterol and triglyceride levels, confirming previous reports. HDL-cholesterol levels had increased 4 weeks after administration, but the increases after 16 weeks were not significant. Apolipoproteins B and C-III levels had decreased after 16 weeks, but other apolipoproteins showed no significant change.Niceritrol obviously lowered serum Lp(a) levels; the percentage decrease from the pre-treatment level was 22±8% (12±4mg/dl) after administration for 16 weeks. Lp(a) levels rebounded to pre-treatment levels 4 weeks after niceritrol therapy was discontinued. C4bp levels had also decreased after 4 weeks, but the decreases after 16 weeks were not significant. However, the percentage decreased in Lp(a) and C4bp levels showed a positive correlation. In addition, both SAA and SAP levels decreased after 16 weeks, and the decreases, in percentage terms, percentage were positively correlated. Niceritorol therapy lowered the serum levels of C4bp, SAA, and SAP as well as Lp(a). We speculate that niceritrol suppressed the production of these proteins in the liver.

To further understand lipoprotein (a) [Lp(a)] and atherosclerosis, we measured serum Lp(a), lipoprotein, and apolipoprotein levels in 55 patients (males, 24-73 years old) on maintenance hemodialysis, and compared them with those of 82 controls (males, 21-81 years old). The serum Lp(a) levels in patients on maintenance hemodialysis were significantly higher than those of the normal controls, while serum total cholesterol (TC), high-density lipoprotein-cholesterol, (HDL-C), HDL2-C, HDL3-C, apolipoprotein (apo) Al, apo All levels, and lecithin-cholesterol acyltransferase (LCAT) activities were significantly (p < 0.05) reduced in the patient group. The frequency distribution of serum Lp(a) levels in the patients was different from that in the control group, and no prognostic tendency of serum Lp(a) levels was noted by the etiology of renal failure as histologically determined by the renal biopsies. In the patient group, we also found that serum Lp(a) levels negatively correlated with serum triglycerides (TG) and total protein (TP) concentrations (p < 0.05), but no correlation was found between the duration of hemodialysis therapy or patient age and the serum levels of TC, TG, apo B and Lp(a) levels when tested for simple regression. Significant (p < 0.05) positive correlations were also found between TP and serum TG, apo B, and LCAT activities. These opposing tendencies of Lp(a) and serum TG, apo B, when measured against TP concentrations, indicate that serum TP levels may not affect serum lipoprotein and Lp(a) levels in the same direction. These data suggest that hemodialysis or end-stage renal disease itself, rather than hypoproteinemia, may hold the key to high serum Lp(a) levels in hemodialysis patients.

Antidepressant-Resistant Depression in Patients With Comorbid Subclinical Hypothyroidism or High-Normal TSH Levels.

Basal TSH levels are known to rise during the evening, but the mechanism by which this rise occurs is poorly understood. The rise in TSH in response to dopamine (DA) receptor blockade with metoclopramide in the morning in normal subjects and hypothyroid patients has provided evidence for a tonic inhibitory role for DA in the control of TSH secretion. We have tested the hypothesis in normal, euthyroid volunteers (14 females, aged 20--40 yr; 12 males, aged 22--45 yr) that the nocturnal elevation of serum TSH levels might result from a reduction in DA action on the thyrotroph, in which case a reduced TSH response to metoclopramide would be expected. We found, however, that the TSH response to DA receptor blockade with metoclopramide (10 mg, iv) was significantly greater at 2300 h than at 1100 h [net incremental response over 120 min, 14.9 +/- 2.5 vs. 6.7 +/- 1.6 mU/liter (mean +/- SE); P < 0.001], indicating greater DA inhibition of TSH release at night. Thus, the nocturnal elevation of TSH is not due to decreased DA action on the thyrotroph; rather, increased DA tone is present and may limit the TSH response to other as yet unknown factors. Thyroid hormone levels also rose significantly after metoclopramide at both 1100 and 2300 h compared with control values after placebo [incremental difference (in nanomoles per liter) between 0 and 120 min values (mean +/- SE): 1100 h, T3, 0.24 +/- 0.09 vs. -0.05 +/- 0.08 (P < 0.02); T4, 19.4 +/- 6.1 vs. -1.8 +/- 2.5 (P < 0.01); 2300 h, T3 +/- 0.53 +/-0.07 vs. 0.04 +/- 0.07 (P < 0.01); T4 20.9 +/- 5.6 vs. 2.8 +/- 3.2 (P < 0.01)]. Incremental thyroid hormone and TSH responses to metoclopramide were directly related (T3 vs. TSH, r = 0.59 and P < 0.001; T4 vs. TSH, r = 0.41 and P < 0.01), suggesting that the thyroid hormone responses were mediated by TSH and illustrating the sensitivity of the thyroid gland to even small increases in endogenous TSH levels.

This study is taken up to estimate and compare the level of serum Lp(a) in hypothyroid patients and in healthy controls. A total of 50 hypothyroid patients within aged group 20-60 years and total of 50 healthy controls within 20-60 years were enrolled in the study after taking written consent. Thyroid profile and Lp(a) were measured by CLIA and immune turbidemetric method respectively. Data collected was analysed using Stata version 14.1 software. Result shows an increased level of Lp(a) among hypothyroid patients when compared to healthy controls.

The catabolism of lipoprotein(a), Lp(a), remains unclear. Very recently we observed that estrogen, a hormone known to increase low-density lipoprotein (LDL) receptor activity, reduced serum Lp(a) levels in a man with familial hypercholesterolemia (FH) (JAMA 267: 2328, 1992). In the present study, we attempted to further evaluate this Lp(a)-lowering action of estrogen in men without FH. Seven men, aged 61-84 yr, treated with estrogen for prostatic cancer were the subjects and seven men who underwent surgical treatment without estrogen therapy served as controls. Fasting blood was collected before and 1-3 months after estrogen therapy, and serum Lp(a) levels and lipoprotein profiles were determined. Estrogen treatment caused significant changes in serum lipoproteins, i.e., decreases in LDL-cholesterol, and increases in high-density lipoprotein (HDL)-cholesterol. Serum triglyceride levels tended to increase. Serum apo A-1 underwent a two-fold increase, while apo B did not change. Serum Lp(a) levels ranged from 8 to 62 mg/dl. After estrogen treatment serum Lp(a) was reduced markedly, with a mean reduction of 81% (71-95%). Serum lipids, lipoproteins and Lp(a) did not change significantly in the controls. The results demonstrated a regulating effect of estrogen on serum Lp(a) levels, and the findings further suggested that Lp(a) is removed via LDL receptors. However, previous studies have shown that maneuvers causing a decrease in LDL-cholesterol do not always cause a reduction in serum Lp(a). Thus, our findings suggested the possible presence of a receptor which is estrogen-inducible and different from the LDL receptor.

Introduction: Dysfunction of thyroid gland are among the most common disease of endocrine glands which affect a considerable portion of the population. Thyroid abnormalities are accompanied by changes in various intermediary metabolism which results in body weight alteration, insulin resistance, lipid profile and various biochemical parameters. Changes in dehydroepiandrosterone (DHEA) and its sulfated metabolite (Dehydroepiandrosterone sulfate) have been reported in patients with thyroid hypofunction but the evidence is controversial and not yet established. The present study planned to explore the association between thyroid function with DHEA and DHEAS levels in hypothyroid patients. Materials and Methods: An observational case control study was conducted in OPD patients of Rajshree Medical College of Rohilkhand region. RMRI, Bareilly.70 newly diagnosed hypothyroid patients were selected and all the biochemical parameters (plasma glucose, thyroid profile, DHEA and DHEAS) were compared with 70 age and sex matched healthy euthyroid controls. Statistical analysis was done using SPSS 22.0. version. Results: We found that serum DHEA and DHEAS levels were significantly reduced in hypothyroid patients as compared to control (p Conclusion: The present study demonstrated that hypothyroidism is associated with significantly low levels of DHEA and DHEAS concentration. Alteration of these sterols in hypothyroidism clearly indicates that thyroid hormone may stimulate the synthesis of these androgen precursors, though more elaborate study with increased sample size may provide more insights. Keywords: Hypothyroidism, Dehydroepiandrosterone, Dehydroepiandrosterone sulfate.

Background: Polycystic ovarian syndrome (PCOS) is associated with dyslipidaemia and may render the affected women “at risk” of developing cardiovascular disease. Lipoprotein(a) [Lp(a)] is an independent risk factor for development of atherosclerosis and along with dyslipidaemia may add to cardiovascular risk. In this background the levels of Lp(a) and lipid profile are assessed in PCOS patients. Material and Methods: The study was carried out on 30 newly diagnosed PCOS subjects aged 18-35 years and 30 age-matched healthy women. Blood samples were collected in a fasting state and serum Lp(a), lipid parameters were estimated. Results: The lipid profile parameters were comparable between patients and control subjects. There was no statistically signi-ficant difference in the median [interquartile range (IQR)] Lp(a) levels between patients with PCOS and normal controls. However, the proportion of subjects with elevated (> 30 mg/dL) Lp(a) levels were significantly higher in patients with PCOS compared to control subjects. Conclusion: Elevated Lp(a) levels may contribute for development of atherosclerosis and increased cardiovascular risk in PCOS patients.