PG IN GENERAL MEDICINE,
DR.B.R.AMBEDKAR MEDICAL COLLEGE,
BANGALORE-560045.
2 / NAME OF THE INSTITUTION. / DR.B.R.AMBEDKAR MEDICAL COLLEGE,
BANGALORE.
3 / COURSE OF THE STUDY AND SUBJECT. / MD GENERAL MEDICINE.
4 / DATE OF ADMISSION TO COURSE. / 01-06-2012.
5 / TITLE OF THE TOPIC. / ANTITHYROGLOBULIN AND ANTITHYROPEROXIDASE AUTOANTIBODIES IN NEWLY DETECTED HYPOTHYROID PATIENTS.
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
6 / BRIEF RESUME OF THE INTENDED WORK6.1 NEED FOR THE STUDY
6.2 REVIEW OF LITERATURE
6.3 OBJECTIVE OF THE STUDY
MATERIAL AND METHODS
6.4 SOURCE OF DATA
6.5 MATERIAL AND METHOD OF COLLECTION OF DATA
6.6 INCLUSION CRITERIA
6.7 EXCLUSION CRITERIA
6.8 REFERENCES / REFER ANNEXURE I
REFER ANNEXURE II
REFER ANNEXURE III
REFER ANNEXURE IV(4.1)
REFER ANNEXURE IV(4.2)
REFER ANNEXURE IV(4.3)
REFER ANNEXURE IV(4.4)
REFER ANNEXURE V
7 / HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION
8 / SIGNATURE OF CANDIDATE
9 / REMARKS OF THE GUIDE / ANNEXURE VI
10 / NAME AND DESIGNATION.
1. GUIDE.
2. PROFESSOR AND HEAD OF
DEPARTMENT OF MEDICINE.
3. SIGNATURE.
4. CO-GUIDE.
5. SIGNATURE. / DR. BINDUMATHI.P.L
DR. BINDUMATHI.P.L
11 / REMARKS OF THE CHAIRMAN AND
PRINCIPAL.
SIGNATURE.
ANNEXURE –I
(6.1) NEED FOR THE STUDY:
The thyroid hormones- thyroxine (T4) and triiodothyronine (T3) are tyrosine-based hormones produced by the thyroid gland, primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half life than T3. The ratio of T4:T3 released in the blood is roughly 20:11.
Within the thyroid, iodide participates in a series of reactions that lead to the synthesis of the active thyroid hormones .The first of these involves oxidation of iodide and incorporation of the resulting intermediate into the hormonally inactive monoiodotyrosines (MIT) and diiodotyrosines(DIT) by a process termed ‘organification’. Iodide is normally oxidised rapidly, immediately appearing in organic combination with thyroglobulin (Tg). Oxidation of thyroidal iodide is mediated by the haem-containing protein called Thyroid peroxidase (TPO). The rate of organic iodination is dependent on the degree of thyroid stimulation by TSH. The MIT and DIT formed via the oxidation and organic binding of iodide are precursors of the hormonally active iodothyronines -T4 and T3. Efficient synthesis of T4 and T3 in the thyroid requires TPO and Tg2.
TPO is a key enzyme in the synthesis of thyroid hormone.TPO is involved in the organification and coupling reactions, for the synthesis of thyroid hormone. TPO is a major antigen corresponding to thyroid microsomal autoantibodies. Anti-TPO autoantibodies are very important to diagnose autoimmune thyroid diseases and estimating its clinical course. Autoimmune thyroid disease is detected mostly by measuring circulating antibodies to thyroglobulin, which is uncommon measurement of antibodies to TPO. This gives reliable information about autoimmune thyroid disease. Hashimoto’s and Grave’s are the commonly seen autoimmune thyroid diseases. 80% of Grave’s patients have high levels of TPO antibodies. About 4% of subclinical hypothyroid patients with positive TPO antibodies develop clinical hypothyroidism. TPO antibodies fix the complement resulting in the formation of a complex of membrane and complement, and these complexes are present in autoimmume thyroid disease patients3.
TPO autoantibodies appear to be a secondary response to thyroid injury and are not thought to cause disease themselves, although they may contribute to its development & chronicity. Antibodies to TPO are detectable in 50% to 90% of patients with grave’s disease, indicative of the associated thyroiditis that is evident histologically as a heterogenous lymphocytic infiltration. High antibody titres are found in 90% of patients with chronic Hashimoto’s thyroiditis. In patients with subclinical hypothyroidism, the presence of TPO antibodies is associated with an increased risk of developing overt hypothyroidism .Both thyroglobulin & TPO antibodies are found in almost 100% of such patients, but TPOAb are of higher affinity and in higher concentrations and are the best choice2.
· Thyroid autoimmunity is a major cause for hypothyroidism. The diagnostic hallmark of the AITD are circulating antibodies, mainly TPO antibodies and Tg antibodies which are elevated in hypothyroidism.
· However these autoantibodies are commonly present in the general population as well.
· Hence, this study is to make a comparison in Anti TPO and Anti Tg antibodies in hypothyroid patients in our set up, which may help in the prognosis and early treatment of the disease.
ANNEXURE –II
(6.2) REVIEW OF LITERATURE: 1.Antithyroperoxidase and Antithyroglobulin Antibodies in a five year follow-up survey of populations with different iodine intakes, by Yushu Li et al4.
Subjects who were TPOAb and TgAb positive at baseline developed thyroid dysfunctions more frequently than seronegative subjects. High iodine intake was a risk factor for developing hypothyroidism in antibody positive subjects. A constant exposure to excessive iodine intake increased the incidence of positive TgAb. The TSH values were significantly higher in patients positive for both TPOAb and TgAb than in those with negative antibodies or only one positive antibody (P<0.05).
People who were TPOAb positive at the first survey were more likely to become TgAb positive than those who were TPOAb negative (cumulative incidene-11/88).Similarly, people who were initially TgAb positive were more likely to become TPOAb positive (cumulative incidence-21/100).
2.Autoimmune Thyroid Disease by Frank Crantz, M5.
Autoimmune thyroid disease is caused by the body making antibodies that attack the thyroid and either turn it on (Grave’s disease, hyperthyroidism) or turn it off (Hashimoto’s thyroiditis, hypothyroidism). Some people with positive thyroid antibodies have normal thyroid function and develop either Grave’s disease or Hashimoto’s thyroiditis in future while some never develop clinical thyroid dysfunction. Thyroid antibodies frequently develop years before the clinical diagnosis of Grave’s disease or Hashimoto’s thyroiditis is made and may be an early marker to identify patients at risk of developing the clinical symptoms of thyroid dysfunction.
3.Autoimmune thyroid diseases:genetic susceptibility of thyroid specific genes and thyroid autoantigens contributions by Hadj-Kacem et al6.
Autoimmune thyroid disorders are polygenic disorders resulting from a combination of genetic predisposition in conjunction with environmental factors. Like human leukocyte antigen-DR, other non-human leukocyte antigen loci have been identified as associated to a higher risk of developing AITD, such as cytotoxic T lymphocyte antigen 4, CD40, protein tyrosine phosphatase N22, thyroglobulin, TSH receptor genes.
4.The clinical significance of subclinical thyroid dysfunction
By Biondi B, Cooper DS
References and further reading may be available for this article. To view references and further reading you must purchase this article.7.
Recently reviewed data disclosed that lymphocytic infiltration of the thyroid gland is present in about 40% of healthy women, the prevalence of anti TgAb and anti TPOAb in the general population is 10-12%, whereas a suggestive ultrasound pattern may precede anti TPOAb positivity in AITD and TPOAb may not be detected in more than 20% of individuals with ultrasound evidence of thyroid autoimmunity.
5.Thyrotropin and thyroid antibodies as predictors of hypothyroidism by John P. Walsh et al8.
The use of TSH cutoffs of 2.5 and 4.0mU/litre, combined with thyroid antibodies, provides a clinically useful estimate of the long term risk of hypothyroidism.
6. Thyroid peroxidase and thyroglobulin autoantibodies in newly diagnosed overt hypothyroidism , by Allan Carle et al9.
In spontaneously hypothyroid patients: >90% were antibody positive (TPOAb or TgAb), TPOAb were more often measurable than TgAb (95.5 vs, 80.7%, p,0.001). A statistically significant but modest correlation was observed between the two antibodies (Pearson’s r2 =0.11, p,0.001).
ANNEXURE-III:
(6.3) AIMS AND OBJECTIVES:
1) To quantify and assess the significance of Antithyroglobulin and Antithyroperoxidase autoantibodies in newly detected hypothyroid patients.
2) To assess their role in Autoimmunity.
ANNEXURE-IV:
(6.4) SOURCE OF DATA:
Freshly detected hypothyroid patients (out patients and in patients) at Dr.B.R. Ambedkar Medical College and Hospital.
(6.5) METHOD OF COLLECTION OF DATA:
30 and above newly detected hypothyroidism patients aged between 18 years to 65 years will be randomly selected. They will be subjected to detailed medical history, general physical and systemic examination with prior consent. All the necessary investigations will be done and the results will be statistically analysed. 30 members from the general population will be taken up for the study as controls and subjected to the same exclusion criteria.
(6.6) EXCLUSION CRITERIA:
1) Patients aged less than 18years and more than 65yrs.
2) Pre-diagnosed thyroid dysfunction or autoimmune thyroid disorder.
3) Patients on steroids or other immunomodulator drugs .
4) Patients who have undergone previous thyroid surgery.
5) Patients who have undergone neck irradiation or iodine therapy.
6) Diabetes Mellitus.
7) Pregnancy.
8) Menopause.
9) Patients on previous lithium or amiodarone medication.
ANNEXURE-IV:
(6.7) EVALUATION AND INVESTIGATIONS:
All the patients will be personally subjected to detailed history regarding name, age, sex, occupation, socioeconomic status, general physical and systemic examinations. Thyroid function will be assessed by measuring T3,T4,TSH values.
Investigations:
· CBC with ESR.
· Fasting Blood sugar.
· Lipid profile.
· Urine routine.
· USG abdomen & pelvis.
· Thyroid profile (T3,T4,TSH).
· Anti-Tg Ab assay.
· Anti TPO Ab assay.
· FNAC (if needed).
(7.0) HAS THE ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUITION IN CASE OF THE ABOVE:
YES/ NO
ANNEXURE-V:
(6.8) REFERENCES:
1. a b Page 493 (Table 33-3) in: Eugster, Erica A.; Pescovitz, Ora Hirsch (2004). Pediatric endocrinology: mechanisms, manifestations and management. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN0-7817-4059-2.
2.Henry M Kronenburg, Shlomo Melmed, Kenneth S.Polonsky, P.Reed Larsen-. Page 303, 385, 11th edition, Williams Textbook of Endocrinology
3. Sabitha Kandi, Pragna Rao.(2012) Anti-thyroid peroxidase antibodies:its effect on thyroid gland and breast tissue. vol 5, pg 1-2 Annals of Tropical Medicine and Public Health.
4. Yushu Li, Di Teng , Zhongyan Shan, Xiaochun Teng, Haixia Guan, X. Yu, C. Fan, Wei Chong, Hong Dai, Yanyan Chen, Rong Yang, Weiping Teng. (2008) Antithyroperoxidase and Antithyroglobulin Antibodies in a five year follow up survey of populations with different iodine intakes.
Journal of Clinical Endocrinology and Metabolism. 93(5); 1751-1757.
5. Frank Crantz M. (2011) Autoimmune Thyroid Disease.
American Thyroid Association, Vol 4 Issue 10p.11-12.
6.Hadj-Kacem H, Rebuffat S, Mnif-Feki M, Belguith-Maalej, Ayadi H, Peraldi-Roux S (2009). Autoimmune thyroid diseases: genetic susceptibility of thyroid specific genes and thyroid autoantigens contribution, Int J Immunogenet 36:85-96.
7.Biondi B, Cooper DS (2008) The clinical significance of subclinical thyroid dysfunction. Endocrine Review 29:76-131.
8.John P. Walsh, Alexandra P. Brenner, Peter Feddema, Peter J.Leedman, Suzanne Brown, Peter O’Leary.(2010) Thyrotropin and Thyroid antibodies as predictors of Hypothyroidism . Journal of Clinical Endocrinology and Metabolism 95(3):1095-1104.
9.Allan Carle, Peter Laurberg, Nils Knudsen, Hans Perrild, Lars Ovesen, Lone Banke, Rasmussen, Torben Jorgensen , Inge B.P. (2006) Thyroid peroxidase and thyroglobulin auto antibodies in patients with newly diagnosed overt hypothyroidism. Dept of Endocrinology and Medicine ,Aarhus University Hospital, Aalborg, Denmark. Vol 39 no.6 pages 497-503.
ANNEXURE VI
REMARKS OF THE GUIDE.
Autoimmunity is a major cause for hypothyroidism. Thyroid antibodies assessment is not done routinely. Hence this is a good study to bring to light the autoimmune status of hypothyroid patients in our setup.
I will be the guide for Dr. Pooja Rahul, PG General Medicine and the thesis work will be done under my supervision.
Signature of the guide.