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Thyroid Issues as Women Age Berris Burgoyne B.HSc., N.D., Dip.Herb.

Thyroid Issues as Women Age Berris Burgoyne B.HSc., N.D., Dip.Herb. Thyroid Disorders. Thyroid disorders are more common in women than men - for Hashimoto’s disease (HD) also known as chronic lymphocytic thyroiditis and Graves’ disease the ratio is approximately 4-5:1 1

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Thyroid Issues as Women Age Berris Burgoyne B.HSc., N.D., Dip.Herb.

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  1. Thyroid Issues as Women Age Berris Burgoyne B.HSc., N.D., Dip.Herb.

  2. Thyroid Disorders • Thyroid disorders are more common in women than men - for Hashimoto’s disease (HD) also known as chronic lymphocytic thyroiditis and Graves’ disease the ratio is approximately 4-5:11 • The highest incidence of HD occurs in middle aged women2 • Samter M. et al: Immunological Diseases, 4th Edition, Little Brown Publishing, Boston USA 1988:1716-1725 • Matthies A, Nikpoor N. http://www.med.harvard.edu; JPNM/TF96_97/April8/Write Up.html (accessed 16 August 2006)

  3. Thyroid Disorders • In Australia the most common cause of thyroid dysfunction is autoimmunity with Hashimoto’s disease being more common than Graves’ Disease1 • Hypothyroidism occurs in approximately 5% of the adult population, usually presenting as subclinical hypothyroidism (SCH)1 • SCH affects around 4% of the general population and 10% to 15% of older persons2 • Topliss DJ, Eastman CJ. MJA 2004; 180(4):186-193 • Walsh JP, Bremner AP et al. Arch Intern Med 2005; 165(21):2467-2472

  4. The Whickham Survey Thyroid disease in the United Kingdom: The Whickham Survey – • Between July 1972 and June 1974 thyroid health was assessed in 2,779 randomly selected subjects residing in Whickham Urban District1 • A 20-year follow-up of the Whickham Survey included 1,877 participants of the original survey • 825 of the original subjects had died, however data obtained from medical records for many of these were included in the follow-up findings • Turnbridge WMG, Evered DC et al. Clinical Endocrinology 1977; 7:481-493 • Vanderpump MPJ, Turnbridge WMG et al. Clinical Endocrinology 1995; 43:55-68

  5. The Whickham Survey Results from the Whickham Survey and follow-up:

  6. The Whickham Survey • Results from the original Whickham Survey demonstrated that TSH levels did not vary with age in males but increased markedly in females after the age of 45 years and was, in most cases, associated with the presence of anti-thyroid antibodies • There was also a strong association between thyroid cytoplasmic (microsomal) antibodies and the presence of gastric parietal cell antibodies in both sexes Turnbridge WMG, Evered DC et al. Clinical Endocrinology 1977; 7:481-493

  7. The Whickham Survey Risk factors for development of hypothyroidism: • The 20-year follow-up survey found that a rise in serum TSH above 2 mU/l is associated with an increased probability of development of hypothyroidism (TSH normal range 0.5-5.2 mU/l) • This probability is further increased if anti-thyroid antibodies are present Vanderpump MPJ, Turnbridge WMG et al. Clinical Endocrinology 1995; 43:55-68

  8. Iodine and Thyroid Disorders • Iodine deficiency is a major cause of hypothyroidism world wide (excessively high doses of iodine can also cause hypothyroidism) • The results of a study published in 2004 demonstrated that approximately 15.8% of 454 women were iodine deficient when urinary iodine excretion was measured • 40% of the women were borderline iodine deficient • The study was carried out at the James Cook University Hospital, Middlesorough, in the north east of England, an area where the population is thought to be iodine replete Kibirige MS, Hutchison S et al. Arch Dis Child Fetal Neonatal Ed 2004; 89:F436-39

  9. Thyroid Disorders Under Diagnosed? • Two Scandinavian studies of over 3,000 unselected patients who had been assessed by primary care physicians, were given blood tests to determine thyroid function • Approximately one third of these patients (1,000) returned abnormal test results • Thyroid dysfunction had not been suspected in 90% of these patients, even when clinical features were apparent in retrospect1,2 1. Eggertsen R et al. BMJ 1988; 297(6663):1586-1592 2. Petersen K et al. J Intern Med 1991; 229(5):407-413

  10. Thyroid Disorders Under Diagnosed? • Study - 250 women between the ages of 38 years and 80 years (median age 63 years), all without known thyroid disease • 38% - autoimmune thyroid disease • 26% - non-autoimmune thyroid disease1 • Study - 210 postmenopausal women without any past or present history of thyroid disease • 33 (15.7%) - subclinical hypothyroidism • 1 - subclinical hyperthyroidism2 • Turken O, Narin Y et al. Breast Cancer Research 2003; 5(5);r110-13 2. Nagata M, Suzuki A et al. Endocrine Journal 2007; 54(4);625-630

  11. Defining Thyroid Disorders

  12. Thyroid Disorders Blood tests to assess thyroid function • TSH • FT4 • FT3 • Thyroid peroxidase antibodies • Thyroglobulin antibodies • TSH receptor antibodies • Reverse T3 For comprehensive information on the clinical features, diagnosis and aetiology of thyroid disorders refer to The Modern Phytotherapist 1998; 4(1):1-10

  13. Thyroid HormoneIndividual Variations • The distinction between subclinical and overt thyroid disease is somewhat arbitrary because it depends on the position of the patient’s normal set point for T3 and T4 • Serum TSH outside the population-based reference range indicates that serum T3 and T4 are NOT normal for the individual Andersen S, Pedersen KM et al. J Clin Endocrinol Metab 2002; 87(3):1068-72

  14. Thyroid HormoneIndividual Variations Andersen S, Pedersen KM et al. J Clin Endocrinol Metab 2002; 87(3):1068-72

  15. Thyroid HormoneIndividual Variations Andersen S, Pedersen KM et al. J Clin Endocrinol Metab 2002; 87(3):1068-72

  16. Thyroid HormoneIndividual Variations Andersen S, Pedersen KM et al. J Clin Endocrinol Metab 2002; 87(3):1068-72

  17. Thyroid Disorders • What are the long-term consequences of thyroid disorders? • Thyroid disorders have been linked to: • Cardiovascular disease • Breast cancer • Osteoporosis

  18. Cardiovascular Health and Overt Hypothyroidism • The association of overt hypothyroidism with cardiovascular disease (CVD) is widely accepted • Possible mechanisms include: • Increased probability of atherosclerosis • Direct adverse effects on myocardial or cardiovascular function Editorial. Arch Intern Med 2005; 165(21):2451-52

  19. Cardiovascular Health and Subclinical Hypothyroidism • The association between subclinical hypothyroidism (SCH) and cardiovascular health is controversial due to inconsistent results from various studies • Just as there are degrees of overt hypothyroidism, there are also degrees of SCH, which can be categorised depending the degree of TSH elevation Editorial. Arch Intern Med 2005; 165(21):2451-52

  20. Cardiovascular Health and Subclinical Hypothyroidism • A study published in 2005 stratified for TSH levels so that the relationship between the degree of SCH and the incidence of CVD could be determined • Results - SCH is associated with an increased risk of congestive heart failure (CHF) among older adults with a TSH level of 7.0 mIU/L or greater Rodondi N, Newman AB et al. Arch Intern Med 2005; 165(21):2460-2466

  21. Cardiovascular Health and Subclinical Hypothyroidism • An Australian study1 used 2108 archived serum samples from the Busselton Health Study, a 1981 community health survey in Busselton WA, to assess SCH as a risk factor for cardiovascular disease • Results - Subjects with SCH had a significantly higher prevalence of coronary heart disease than euthyroid subjects • Walsh JP, Bremner AP et al. Arch Intern Med 2005; 165(21):2467-2472

  22. Cardiovascular Health and Subclinical Hypothyroidism • Another study using data from the Busselton Health Study, demonstrated that SCH is associated with increased serum LDL cholesterol1 • Overt and subclinical hypothyroid patients have impaired coronary microvascular function which improves with thyroxine therapy2 • A systemic review (2006) concluded that SCH is associated with an increased risk of CHD3 • Walsh JP, Bremner AP et al. Clin Endocrinol (Oxf) 2005; 63(6):670-75 • Oflaz H, Kurt R et al. Endocrine 2008 [Epub ahead of print] 3. Rodondi N, Newman AB et al. Arch Intern Med 2005; 165(21):2460-2466

  23. Cardiovascular Health and Hypothyroidism Cardiovascular risk factors associated with overt and subclinical hypothyroidism include: • Elevated total cholesterol1 • Elevated LDL1 • Increased diastolic blood pressure1 • Increased arterial stiffness1 • Endothelial dysfunction1 • Altered coagulation parameters1 • Elevated C-reactive protein (CRP)2 1. Orzechowska-Powilojc A et al. Endokrynol Pol 2005; 56(2):194-202 2. Gursoy A Ozduman Cin M et al. Int J Clin Pract 2006; 60(6):655-59

  24. Cardiovascular Health and Hypothyroidism • Left ventricular diastolic dysfunction at rest; systolic and diastolic dysfunction on effort, which may result in poor physical exercise capacity1 • Elevated homocysteine • Many papers state that homocysteine is elevated in overt hypothyroidism but not in subclinical hypothyroidism2 • Biodi B, Klein I. Endocrine 2004; 24(1):1-13 • Gursoy A Ozduman Cin M et al. Int J Clin Pract 2006; 60(6):655-59

  25. Cardiovascular Health and Hypothyroidism • However, a paper published in June 2006 demonstrates that homocysteine levels increase alongside increasing TSH levels • The authors suggested that a TSH level of less than 2 might be advisable to lower homocysteine and CRP levels, and possibly lipid parameters Gursoy A Ozduman Cin M et al. Int J Clin Pract 2006; 60(6):655-59

  26. Cardiovascular Health and Overt Hyperthyroidism • Atrial fibrillation occurs in 5-15% of patients with thyrotoxicosis1 and the prevalence is higher among patients over 60 years than in younger patients2 • Effective treatment of thyrotoxicosis usually restores sinus rhythm1 • Boelaert K, Franklyn JA. J Endocrinol 2005; 187(1):1-15 • Sawin CT, Gella A et al. N Engl J Med 1994; 331:1239-1252

  27. Cardiovascular Health and Subclinical Hyperthyroidism • Subclinical hyperthyroidism in people 60 years of age and older is associated with a three fold higher risk of atrial fibrillation developing in the subsequent decade1 • A 10 year follow-up study of 1191 individuals (aged 60 years or older) with subclinical hyperthyroidism demonstrated an increased mortality from circulatory diseases2 • Sawin CT, Geller A et al. N Engl J Med 1994; 331:1249-1252 • Parle JV, Maisonneuve P et al. Lancet 2001; 358(9285):861-65

  28. Cardiovascular Health and Subclinical Hyperthyroidism • In 40 patients with subclinical hyperthyroidism 28% had atrial fibrillation compared with 10% in age-matched euthyroid controls. Mean age was 65 years • In most studies patients with subclinical hyperthyroidism have a higher heart rate and increased prevalence of supraventricular arrhythmias • The most consistent cardiac abnormality associated with subclinical hyperthyroidism is increased left ventricular mass Biondi B, Palmieri EA. European Journal of Endocrinology 2005;152:1-9

  29. Breast Cancer and Thyroid Disease • The possible association between thyroid disease and breast cancer has been debated for decades and remains controversial • Epidemiological studies have provided conflicting results and often do not differentiate the different thyroid conditions • Overall the studies have suggested a clinical but yet unrecognised biologic correlation between thyroid disease and invasive breast carcinoma risk Cristofanilli M, Yamamura Y et al. Cancer 2005; 103(6):1122-28

  30. Breast Cancer and Thyroid Disease • Study 150 women with breast cancer and 100 age-matched controls. Age range 38-80 years. All without known thyroid disease Turken O. Breast Cancer Research 2003; 5(5):R110-R113

  31. Breast Cancer and Thyroid Disease Turken O. Breast Cancer Research 2003; 5(5):R110-R113

  32. Breast Cancer and Thyroid Disease Turken O. Breast Cancer Research 2003; 5(5):R110-R113

  33. Breast Cancer and Thyroid Disease • A prospective study found thyroid pathology in 77.9% of breast cancer patients and in only 47.1% of controls. The mean age of women in this study was 50.56 years • In another study 2775 women between the ages of 47 and 54 years were followed for 9 years (1994 to 2003) • The results demonstrated that hypothyroidism and low-normal FT4 are related with an increased risk of breast cancer in postmenopausal women • Cengiz O, Bozkurt B et al. J Surg Oncol 2004; 87(1):19-25 • Johannes LP, Kuijpens IN. Thyroid 2005; 15(11):1253-59

  34. Breast Cancer and Thyroid Disease • A retrospective study was undertaken to investigate the role of thyroxine therapy (for the treatment of primary hypothyroidism) on breast cancer • The study involved a total of 2224 women. The mean age was 51.6 years • The results indicated that women with hypothyroidism taking thyroxine are less likely to be diagnosed with invasive breast carcinoma than women not diagnosed with hypothyroidism • However, the analysis did not allow for determination of the incidence of subclinical hypothyroidism Cristofanilli M, Yamamura Y et al. Cancer 2005; 103(6):1122-28

  35. Breast Cancer and Thyroid Disease • In women taking thyroxine who did develop breast cancer: • Were diagnosed with breast cancer at an older age • Were more likely to be postmenopausal • Were more likely to be diagnosed with early-stage disease without lymph node involvement and to have a smaller tumour size Cristofanilli M, Yamamura Y et al. Cancer 2005; 103(6):1122-28

  36. Breast Cancer and Thyroid Disease • A study involving 94,939 patients at a tertiary referral centre for breast, thyroid and parathyroid disease concluded: “Patients found initially to have thyroid cancer or breast cancer may be predisposed to develop the other malignancy within a short timeframe. Vigilant screening for associated disorders should accompany initial diagnosis of either cancer” Garner CN, Ganetzky R et al. Surgery 2007; 142(6):806-13

  37. Bone Health and Thyroid Disease Definitions of osteoporosis 1. WHO defines osteoporosis as bone mineral density more than or equal to 2.5 standard deviations below the young adult mean1 • Osteoporosis is defined as a skeletal disorder characterised by compromised bone strength predisposing a person to increased risk of fracture2 1. Mohammadi B. Haghpanah V et al. Theor Biol Med Model 2007; 4:23 2. Nagata M, Suzuki A et al. Endocrine Journal 2007; 54(4):625-630

  38. Bone Health and Thyroid Disease • Numerous studies have emphasised the importance of bone quality as a major BMD-independent risk factor for fracture • In order to measure bone quality biochemical markers of bone turnover need to be measured Hough S. SA Fam Pract 2007; 49(9):26-34

  39. Bone Health and Hypothyroidism • Patients with overt hypothyroidism have an increased risk of fracture up to 8 years prior to diagnosis (compared to euthyroid population) • These overt hypothyroid patients may have had subclinical hypothyroidism for many years prior to diagnosis • The authors suggested that the elevation of serum TSH in subclinical hypothyroid patients may be associated with deterioration of bone architecture Nagata M, Suzuki A et al. Endocrine Journal 2007; 54(4):625-630

  40. Bone Health and Hyperthyroidism • Thyroid hormones exert direct effects upon bone formation and resorption. Thyroid hormone excess results in net loss of bone • Even with effective anti-thyroid therapy a complete restoration of bone mineral density (BMD) to pre-morbid levels does not always occur • Post-menopausal oestrogen-deficient women are the ones at most risk of potential adverse effects of hyperthyroidism on bone metabolism Boelaert K, Franklyn JA. J Endocrinol 2005; 187(1):1-15

  41. Bone Health and Hyperthyroidism • A large prospective study followed 9516 women aged over 65 for an average of 4.1 years • The study revealed a 1.8 fold increased relative risk for fractures of the femur amongst women with previous hyperthyroidism Cummings SR, Nevitt MC et al. N Eng J Med 1995; 332:767-773

  42. Bone Health and Subclinical Hyperthyroidism • In two meta-analyses subclinical hyperthyroidism was associated with a significant bone loss in post-menopausal but not in premenopausal women • There was a 3-fold increased risk for hip fracture and a 4-fold increased risk for vertebral fracture in women over the age of 65 years with TSH levels <0.1mU/l Biondi B, Palmieri EA. European Journal of Endocrinology 2005;152:1-9

  43. Bone Health and Subclinical Hyperthyroidism • Bone turnover and urinary calcium excretion is increased in subclinical hyperthyroidism1 • Two studies demonstrated that patients with subclinical hyperthyroidism had lower bone densities at the femoral neck and radius than age-matched controls2 • Kisokol G, Kaya A et al. Endocrine Journal 2003; 50(6):657-66 • Mohammadi B. Haghpanah V et al. Theor Biol Med Model 2007; 4:23

  44. Bone Health and Subclinical Hyperthyroidism • A Korean study found a link between low-normal and below-normal circulating TSH levels and osteoporosis • These results may reflect the existence of clinically significant thyroid hyperfunction in women with serum TSH in the reference range OR that TSH itself may play a role in the preservation of bone after menopause Morris MS. Bone 2007; 40(4):1128-34

  45. Bone Health and Thyroxine Supplementation Skeletal health - thyroxine replacement • Does thyroxine replacement therapy increase the risk of osteoporosis? • Controversial - conflicting results over a large number of studies • Results can be complicated by a past history of hyperthyroidism in some participants Boelaert K, Franklyn JA. J Endocrinol 2005; 187(1):1-15

  46. Bone Health and Thyroxine Supplementation • For example, the Cummings’ study involving 9516 postmenopausal women reported an increased relative risk of fracture of the femur in those taking thyroid hormone • However, when adjusted for a previous history of hyperthyroidism this was no longer the case • 36% of those prescribed T4 had a history of hyperthyroidism Cummings SR, Nevitt MC et al. N Eng J Med 1995; 332:767-773

  47. Bone Health and Thyroxine Supplementation • The use of thyroid hormone does not appear to increase the risk for fracture if TSH levels are maintained within the normal range1 • However, there are reports of bone loss in patients taking thyroxine treatment for thyroid cancer, goiters or nodules. Most likely because TSH is suppressed beyond the normal range • Biondi B, Palmieri EA. European Journal of Endocrinology 2005;152:1-9 2. Mohammadi B. Haghpanah V et Theor Biol Med Model 2007; 4:23

  48. Summary

  49. Treatment for Autoimmune Thyroid Diseases Therapeutic strategies: • Modulate the immune system with Echinacea • Reduce the production of auto-antibodies with immune suppressing herbs such as Hemidesmus • Reduce inflammation with Rehmannia, Glycyrrhiza, Curcuma, Boswellia

  50. Treatment for Autoimmune Thyroid Diseases • Reduce damage caused by reactive oxygen species with antioxidant herbs and nutrients including Curcuma, Rosmarinus, Vitis, Camellia (Green Tea), Ginkgo Core treatment: • Rehmannia Complex: 1 tablet 3 times daily • Echinacea Premium: 1 tablet 2-3 times daily or tincture 5 mL daily • Vitanox: 1 tablet daily

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