Annexure – I NEED FOR STUDY

Thyroid disease is common in the general population, and the prevalence increases with age. The assessment of thyroid function by modern assays is both reliable and inexpensive. Screening for thyroid dysfunction is indicated in certain high-risk groups, such as the elderly.

Diabetic patients have a higher prevalence of thyroid disorders compared with the normal population . A number of reports have also indicated a higher than normal prevalence of thyroid disorders in type 2 diabetic patients, with hypothyroidism being the most common disorder.

Hypothyroidism is by far the most common thvroid disorder in the adult Populationalso and is more common in older women. It is usually autoimmune in origin, presenting as either primary atrophic hypothyroidism or Hashimoto's thyroiditis. Thyroid failure secondary to radioactive iodine therapy or thyroid surgery is also common. Rarely, pituitary or hypothalamic disorders can result in secondary hypothyroidism1.

Millions of people in India are hypothyroid and receive thyroxine replacement therapy. By contrast, hyperthyroidism is much less common, with a female-to-male ratio of 9:1. Graves disease is the most common cause and affects primarily young adults. Toxic multi-nodular goiters tend to affect the older age-groups. Moreover nodular thyroid structure and parenchymatous goiter occurs more frequently in Type 2 diabetics2.

According to the WHO age classification (1963) people aged 45 – 59 are considered ‘middle aged’ and those above the age of 60 years are considered to be Geriatrics.

How Thyroid Dysfunction May Affect Diabetic Patients

The presence of thyroid dysfunction may affect diabetes control. Hyperthyroidism is typically associated with worsening glycemic control and increased insulin requirements. There is underlying increased hepatic gluconeogenesis, rapid gastrointestinal glucose absorption, and probably increased insulin resistance. Indeed, thyrotoxicosis may unmask latent diabetes.

In practice, there are several implications for patients with both diabetes and hyperthyroidism. First, in hyperthyroid patients, the diagnosis of glucose intolerance needs to be considered cautiously, since the hyperglycemia may improve with treatment of thyrotoxicosis. Second, underlying hyperthyroidism should be considered in diabetic patients with unexplained worsening hyperglycemia. Third, in diabetic patients with hyperthyroidism, physicians need to anticipate possible deterioration in glycemic control and adjust treatment accordingly. Restoration of euthyroidism will lower blood glucose level.

Although wide-ranging changes in carbohydrate metabolism are seen in hypothyroidism, clinical manifestation of these abnormalities is seldom conspicuous. However, the reduced rate of insulin degradation may lower the exogenous insulin requirement. The presence of hypoglycemia is uncommon in isolated thyroid hormone deficiency and should raise the possibility of hypopituitarism in a hypothyroid patient. More importantly, hypothyroidism is accompanied by a variety of abnormalities in plasma lipid metabolism, including elevated triglyceride and low-density lipoprotein (LDL) cholesterol concentrations. Even subclinical hypothyroidism can exacerbate the coexisting dyslipidemia commonly found in type 2 diabetes and further increase the risk of cardiovascular diseases. Adequate thyroxine replacement will reverse the lipid abnormalities.

However, the underlying thyroid dysfunction can produce clinically important physiological effects. Subclinical hypothyroidism can elevate serum LDL cholesterol and worsen pre-existing dyslipidemia, further increasing the risk of atherosclerosis. Subclinical hyperthyroidism may increase the risk of cardiac arrhythmias and exacerbate angina. Since diabetic patients are at high risk for cardiovascular diseases, the diagnosis and treatment of subclinical thyroid diseases is important.

Thyroid dysfunction is common in diabetic patients and can produce significant metabolic disturbances. Therefore, regular screening for thyroid abnormalities in all diabetic patients will allow early treatment of thyroid dysfunction. A sensitive serum TSH assay is the screening test of choice. In type 2 diabetic patients, a TSH assay should be done at diagnosis and then repeated at least every 5 years1.

Annexure – IIREVIEW OF LITERATURE

Wang Hei anatomically described the thyroid gland in 1475.Paracelcus some fifty years later attributed goiter to mineral impurities in the water. Kocher demonstrated that total thyroidectomy caused hypothyroidism and was awarded the noble prize. Thyroid hormone was only identified in the 19th century.

Zondek H detected an increased association of coronary artery disease in hypothyroidism3.In a study done by Sawin et al on elderly women 3% were found to be hypothyroid, in a report of Bahemuka and Hodgkinson 2.3% of elderly women had hypothyroidism4.Kutty.K.M,Bryant and Farrid.N.R detected that clinically hypothyroid patients are associated with hyperlipidaemia 5 .

The Colorado Thyroid Disease Prevalence Study showed that the consequences of untreated subclinical hypothyroidism include cardiac dysfunction or adverse cardiac end points {atherosclerotic disease and cardiovascular mortality},elevation in total and LDL cholesterol, systemic hypothyroid symptoms or neuropsychiatric symptoms ,progression to overt symptomatic hypothyroidism.

Thyroid function done in 298 type 2 diabetics showed 38 (12.7%) suffered from thyroid dysfunction- 10.7% had hypothyroidism(>2/3rdsub clinical) and 2% had hyperthyroidism. In 31 cases (10.4%) the diagnosis was performed 'de nova'. Thyroid disease was more prevalent among females and elderly6

In a study done on 908 T2DM and 304 non-diabetics at Amman, Jordan78, the overall prevalence of thyroid disease in diabetics was found to be 12.5% of which 5.9% were known to have thyroid disease and rest (6.6%) were newly diagnosed cases as a direct result of screening. The most common was subclinical hypothyroidism (4.1%). The prevalence ofthyroid disease was 6.6% in the control group7

The Indian study done at GND hospital, Amritsar,8 of 184 cases of T2DM showed thyroid disease (TD) present in 78 (40.4%) cases (50 males, 28 females), but autoimmune thyroiditis (AT) was present in 32 (17.4%) cases (8 males, 24 females). There was positive correlation with age of patient in TD group but no correlation was found with complication of diabetes. There was no correlation of age, severity or complications in AT group but this finding was significantly more in female cases8

In the study sample of 100 patients with T2DM at Chennai9, the prevalence of TD was 15% - subclinical hypothyroidism 11%, hypothyroidism 1%, subclinical hyperthyroidism 2% and hyperthyroidism 1%. The prevalence is higher than in the general population and in females.

In the study of 120 T2DM patients at Hyderabad10, hypothyroidism was seen in 32 (27%, 10% being subclinical), of which 80% were females. 70% of patients with hypothyroidism were between 40-60 years age. Only in 1% hypothyroidism preceded T2DM. Only 2% of hypothyroid patients had significant AMA titres. Goiter was noted in 2% of patients10

Annexure – III OBJECTIVE OF THE STUDY

  1. To assess the co-relation and association of the two endocrinal disorders in randomly selected geriatric and non – geriatric patients and to make a comparison of the probable outcomes between both groups.
  2. To determine the prevalence of co – morbid conditions especially CAD in both age groups and to aim at a better understanding of a definitive association inorder to specify treatment at reducing morbidity.

Annexure – IV (4.1)SOURCE OF DATA

Patients attending the Medicine Out Patient Department and In-patients of Dr. B.R Ambedkar Medical College and Hospital.

Annexure – IV (4.2)METHOD OF COLLECTION OF DATA

50 Patients each (Total 100 patients) in the Geriatric & non – Geriatric age groups of people with Type 2 Diabetes Mellitus will be randomly selected and will be subjected to detailed Medical History, General and Systemic physical examination with prior consent of the patient and they will then be subjected to Thyroid function tests and other appropriately related tests, the results of which will be statistically analysed.

Annexure – IV (4.3)EXCLUSION CRITERIA

  1. Type 1 Diabetics
  2. Patients on Steroids
  3. Pregnant Women
  4. Patients on Drugs known to cause Hypothyroidism

Annexure – IV (4.4)EVALUATION AND INVESTIGATIONS

  1. Thyroid Profile
  2. FBS, PPBS.
  3. HbA-1C% (If necessary)
  4. TPO Antibodies, FreeT3 and T4, USG and FNAC of Thyroid Gland (If necessary)
  5. ECG
  6. 2D – Echo (if necessary)
  7. Blood Urea
  8. Serum Creatinine
  9. Lipid Profile
  10. CBC with ESR
  11. Urine Routine

DOES THE STUDY REQUIRE ANY INVESTIGATIONS OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS AND ANIMALS? IF SO , PLEASE DESCRIBE BRIEFLY.

NO

7.5HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF THE ABOVE

Annexure– VREFERENCES

1 Patricia Wu, MD Feb 2000, Thyroid Disease and Diabetes, original article.

2 Junik R, Kozinski M, Debska – Kozinska. K – Department of Endocrinology and Diabetology, and Department of Cardiology and internal diseases, Nicolaus Copernicus University of Poland, Acta Radiologica 2006 (Vol 47, No7, Pages 687 – 691).

3 Zondek,H. (1959). Association of Myxoedema, heart and atherosclerotic heart disease.

JAMA, 170, 1920-1.

4Sawin, CT, Chopra, D., Azziz, F.et al(1979). The aging thyroid. Increased prevalence of elevated serum thyrotrophin in elderly. JAMA, 242, 247-50.

5Kutty, K.M Bryant, D.G. and Farried, N.R (1978). Serum liids in hypothyroidism; a reevaluation J. Clinical Endocrinology – Metab., 46,55-60.

6Nobre E L, Jorge Z, Prastas S, Silva C, Castro J J. Profile of the thyroid function in a population with type 2 diabetes. Endocrine abstract. 3;298.

7Radaieh A R, Nusier M K, Amari F L, Bateiha A E, El-Khateeb M S, Naser A S. Thyroid dysfunction in patients with type 2 diabetes mellitus in Jordan. Saudi Medical Journal. 2004 Aug; 25(8): 1046-50.

8Bal BS, Kaur P P, Singh B M, Singh Gurpal, Singh S P. Prospective analysis of thyroid abnormalities in cases of type 2 diabetes mellitus. JAPI. 2003 Dec; 51:1165-6.

9Rajan S K, Ezhilarasi A, Sasidharan Madhu. Thyroid dysfunction in patients with type 2 diabetes mellitus. JAPI. 2003 Dec; 51:1229.

10RamaSwamy M, Balaraju B, Prahlad B, Vijay Mohan M, Rao Mohan B, RaoRama Chander, et al.Profile of hypothyroidism in type 2 DM in Hyderabad. JAPI. 2003 Dec; 51:1168.

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