RAJIV GANGHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA.
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERATION
1. NAME OF THE CANDIDATE : DR.SHINE J PAKALOMATTOM
& ADDRESS
DEPT.OF MEDICINE
5th FLOOR
ST.JOHN’S MEDICAL COLLEGE HOSPITAL
SARJAPUR ROAD
BANGALORE - 560 034.
2. NAME OF THE INSTITUTION : ST.JOHN’S MEDICAL COLLEGE,
BANGALORE
3. COURSE OF STUDY & : P.G. (M.D.GENERAL MEDICINE)
SUBJECT
4. DATE OF ADMISSION TO : 16-04-2012
COURSE
5. TITLE OF THE TOPIC :
6. INTRODUCTION:
Systemic lupus erythematosus (SLE ), is an autoimmune disorder in which the body's immune system incorrectly attacks the body's own tissues and organs, leading to inflammation and damage. Lupus most commonly affects women of childbearing age 85% of patients developing the disease before the age of 552, of which 20% are children below 16 years of age2. Estimates of the prevalence of SLE vary greatly, ranging from 20 to 150 per 100 000 2,3, higher among Afro-Americans and Asian. A sex hormone influence on pathogenesis is assumed based on the 7:1 to 15:1 female-to-male ratio of SLE. The cause of lupus is unknown, but it has been associated with genetic, environmental, and infectious causes. The disorder may affect almost all organs in the body. It may be mild in some cases (for example, involving only the skin) and very severe in other cases (affecting multiple organs, including the brain). The disease course is characterized by flares (intervals of active disease) and remissions (intervals of inactive disease)
Hypothyroidism:
The earliest biochemical abnormality in hypothyroidism is an increase in serum TSH concentration associated with normal T3 and T4 concentration (subclinical hypothyroidism). This is followed by a decrease in the serum T4 concentration, at which stage most patients have symptoms and benefit from treatment (overt hypothyroidism). In persons living in iodine replete areas,, the cause is either autoimmune thyroiditis (Hashimotos thyroiditis)or destructive treatment for thyrotoxicosis .
Thyroid dysfunction may be broadly classified as hypothyroidism and hyperthyroidism.The most common cause of thyroid disorders worldwide is iodine deficiency leading to goitre formation and hypothyroidism. In iodine replete areas most persons with thyroid disorders have autoimmune disease, ranging from thyrotoxicosis to hypothyroidism.
Prevalence of hypothyroidism in iodine replete communities is between 1%-2%, and it is more common in older females and about 10 times more common in females than in males.6
In the Wickham survey, the prevalence of newly diagnosed overt hypothyroidism was 3 per 1000 females.7 The overall prevalence in men was <1 case per 1000.
Thyrotoxicosis:
A decrease in serum TSH concentration is the earliest measure of thyroid overactivity.(subclinical thyrotoxicosis ) followed by an increase in the serum thyroxine (T4) and triiodothyronine(T3) concentration( overt thyrotoxicosis). The most common cause of thyrotoxicosis is Graves disease followed by multi nodular goitre. Prevalence of thyrotoxicosis in females is 0.5%-2% and is 10 times more common in females than in males in iodine replete communities.5
6.1 NEED FOR THE STUDY:
Many patients with thyroid dysfunction (especially hypothyroidism) have symptoms (fatigue, arthralgias, myalgias, arthritis) similar to those found in SLE, and thyroid dysfunction may be over looked.
SLE is associated with many different type of auto antibodies which can also be directed against thyroid cells.Its clinical relevance and appropriate treatment of thyroid disease in SLE need to be studied.
There are very few reports of studies of prevalence of thyroid dysfunction and clinical implications of thyroid disorders in SLE in India. Studies in India shows a prevalence of about 13% of thyroid disease in SLE.
6.2 REVIEW OF LITERATURE:
Although several studies around the world have described an increased prevalence of thyroid disease in SLE, it remains controversial whether SLE is in fact a risk factor for the development of thyroid disease. In an attempt to determine the genetic and environmental factors contributing to autoimmunity, clinical investigators have looked for relations between various autoimmune disorders such as systemic lupus erythematosus and autoimmune thyroid disease.
Simon Appenzeller et al studied hundred twenty-four consecutive patients with 4 or more criteria for SLE diagnosis that were regularly evaluated from January 1999 to July 2003.12,13 Symptomatic autoimmune thyroid disease was observed in 6.1% SLE patients , predominantly hypothyroidism. Subclinical thyroid disease was identified in 11.5% and positive thyroid autoantibodies in the absence of thyroid disease in 17% SLE patients.11
Adriana Maria Kakehasi et al.studied a total of one hundred patients with SLE in which 17% had abnormal thyroid function by laboratory testing, which included ten patients 10% with subclinical hypothyroidism, 2% with subclinical hyperthyroidi,4 with primary hypothyroidism.Regarding antithyroid antibodies, 4% for antiperoxidase,1% for antithyroglobulin and 1% for both antibodies.11
D Pyne et.al studied the prevalence of autoimmune thyroid disease and thyroid antibodies in 300 patients with SLE, followed up between 1978 and 2000, by a retrospective analysis of case notes.The prevalence (5.7%) of hypothyroidism was higher than in the normal population (1%), while that of hyperthyroidism (1.7%) was not significantly different. 14% of the patients had thyroid antibodies.15
K L Wong and F Wang et.al studied 319 patients with SLE 9 had thyrotoxicosis,2 had hypothyroidism and 3 had thyroiditis.Prevalance seems greater than that of thyroid disorders in general population.12
Miry Blich et al review also shows high prevalance of thyroid disorder in SLE.The prevalance of anti TPO Antibodies was higher in SLE in than in general population.13
W Hijmans et al studied serological overlap of SLE ,rheumatoid arthritis and auto immune thyoiditis ,which showed a 3 times higher titres of anti thyroid antibodies in SLE than in general population.8
Y Kohno et al studied anti TPO activity in sera of SLE patients shows anti TPO antibodies with different specificities from those of patients with thyroid disorders thus shows an association between SLE and thyroid disorders.14
R Porkodi S Ramesh et al (Indian study) shows 20 of 153 SLE patients (13.1%) had thyroid dysfunction. All were females. Hyperthyroidism, a less common abnormality (10%) occurred in younger individuals (mean age 27 years). Subclinical hypothyroid(TSH alone raised) was the next dysfunction seen in 20% of patients (mean age 28 years). Clinical hypothyroid was the commonest dysfunction in 60% of patients, who belonged to an older age group (meanage 30.4 years). Euthyroid state with elevation of antibodies alone was seen in 10% (mean age 30 years).Antimicrosomal antibody was positive in 100% and antithyroglobulin antibody was present in 82.4% and both were positive in 82.4%. Of the 798 RA patients 41 (5.1%) had thyroid dysfunction. There were 40females and one male. Hyperthyroidism was seen in 7.3% (mean age was 30.7 years). Subclinical hypothyroid occurred in 17.1% (mean age was 35.7 years). Clinical hypothyroid was present in 73.2% (mean age of 48.3 years). 2.4% of patients, (mean age 30.7 years) had euthyroid state with raised antibodies alone. Antimicrosomal antibody was positive in 88%, antithyroglobulin antibody in 56% and both in 52% of patients.9
In 1982,American college of Rheumatology proposed a criteria based on the clinical symptoms and signs of SLE,which was revised in 1997.
6.3 OBJECTIVES OF THE STUDY:
Primary objective :
1) To study the prevalence of thyroid dysfunction in patients with SLE.
Secondary objective:
1) To assess the prevalence of anti TPO in patients with SLE.
2) To assess the clinical features of hypo /hyperthyroid patients with SLE.
7. MATERIALS AND METHODS:
. STUDY DESIGN: Descriptive, cross sectional study
7.1 SAMPLE SIZE AND SOURCE OF DATA:
100 patients who are diagnosed as SLE seen in St.John’s Medical College Hospital will be the source of data.
The sample size would be=100
Inclusion criteria:
1) All patients diagnosed as SLE, either newly or previously diagnosed.
2) Age greater than 18 yrs.
Exclusion criteria:
1) Patients on medication that are known to cause thyroid dysfunction. (Amiodarone, lithium, PAS, interferon alpha).
2) Patients who have undergone thyroidectomy- surgical/radiation
3) Any major organ damage that can significantly alter TFT
7.2 METHODS OF COLLECTION:
All patients with SLE will undergo complete physical examination with specific focus on features of hypo or hyperthyroidism as detailed in the annexure. For women menstrual history will be taken in detail. Past treatment details will be recorded for SLE, thyroid disorders and all co morbidities .All subjects will undergo lab evaluation (FT4 TSH and TPO).
Demographic data, type of thyroid dysfunction, duration of SLE and thyroid disease, and whether thyroid dysfunction preceded SLE will be recorded. Thyroid dysfunction will be classified as hyperthyroid (clinical and subclinical) clinical hypothyroid, subclinical hypothyroid (TSH alone elevated), sick euthyroid status (TSH alone elevated) and euthyroid (antibodies alone elevated).
STATISTICAL ANALYSIS
Descriptive statistics will be reported using mean, standard deviation and number and percentage as appropriate. The prevalence of thyroid dysfunction and antiTPO in SLE will be reported using proportion or percentages. One way ANOVA will be used to compare the characteristics of the patients between hypothyroid, hyperthyroid and euthyroid subjects. Chi-square test will be used to compare the proportions between the groups. Probability value of <5% will be considered as statistically significant. Analysis will be performed using SPSS Version 18.0 software.
7.3 Does the study require any investigations or interventions to be conducted on patients or
other humans or animals? If so, please describe briefly.
No
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
Ethical clearance obtained
PROFORMA
NAME______MRD No:______
AGE:______SEX:M/F
ADDRESS AND TELEPHONE No:
DURATION OF SLE:______DURATION OF THYROID DISEASE_____
SYMPTOMS:
Hyperthyroidism / Hypothyroidism / SLEHyperactivity,irritability,dysphoria
Heat intolerance and sweating
Palpitations,
Fatigue and weakness
Weight loss with increased appetite
Diarrhoea,
polyuria
oligomenorrhea
loss of libido
tachycardia
tremor
goitre
warm moist skin
muscle weakness, proximal myopathy
lid retraction or lag
gynecomastia
thyromegaly / Fatigue, weakness,
Dry skin
Feeling cold
Hair loss
Poor concentration/memory
Constipation
Weight gain with poor appetite
Dyspnoea
Hoarse voice
Menorrhagia( later oligomenorrhea)
Paresthesia
Impaired hearing
Dry coarse skin, cool extremities
Puffy face hands and feet
Diffuse aloepecia
Bradycardia
Peripheral edema
Delayed tendon reflexes
Carpal tunnel syndrome
Serous cavity effusions
Thyromegaly / Fever,
Fatigue
Anorexia
Joint pains,
Loss of wt
Chest pain
Photsosensitivity
Malar Rash
Discoid rash
Alopecia
Oral ulcers
Dry eyes
Pallor
Pleural effusion
Others (specify)
PAST HISTORY: Hypertension Diabetes Others
MENSTRUAL HISTORY:
OBSTETRIC HISTORY:
Year / Outcome (abortion, still birth, normal) / CauseFAMILY HISTORY:
Autoimmune diseases
Thyroid diseases-
DRUG HISTORY:
DRUG DOSE DURATION ADVERSE EFFECTS
NSAIDSCORTICOSTEROIDS
CONTRACEPTIVES
THYROID/ANTI THYROID DRUGS
AZATHIOPRINE
METHOTREXATE
CYCLOPHOSPHAMIDE
MYCOPHENOLATE
MOFETIL
OTHERS
EXAMINATION:
Height: ------Weight: ------BSA: ------m square pulse: ------/min
BP: ------mm/Hg Temp.:------F Thyromegaly------Tender joint count------
INVESTIGATIONS:
Hb: ------TC------DC------ESR: ------Platelet: ------
Creatinine: ------Urine R/E------
Thyroid function tests:
FT4 :------TSH: ------anti-TPO: ------
Others:
Immunologic Investigations:
ANA______APLA______CRP______C3______C4______
dsDNA______Immunoline______OTHERS______
CONCLUSIONS:
SLE / THYROID STATUS / ANTI TPO AB / COMORBIDITIES8) REFERENCES
1. Schaller J, Lupus in childhood. Clin Rheum Dis,1982;8:219-28.
2. Pons-Estel GJ, Alarcon GS, Scofield L, Reinlib L, Cooper GS . Understanding the
epidemiology and progression of systemic lupus erythematosus. Semin Arthritis
Rheum,2010; 39: 257-68.
3. Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT et al. (1998). Estimates of
the prevalence of arthritis and selected musculoskeletal disorders in the United
States. Arthritis Rheum.1998; 41: 778-99.
4. Lahita RG . The role of sex hormones in systemic lupus erythematosus. Curr
Opin Rheumatol.1999; 11: 352-56.
5.Tunbridge WMG, Vanderpump MPJ. Population screening for autoimmune thyroid disease. Endocrinology clinic North America 2000; 29:239-53.
6.Vanderpump MPJ, Tunbridge WMG, Epidemiology and prevention of clinical and subclinical hypothyroidism. Thyroid 2002;12: 837-47
7.Tunbridge WMG, Evered DC, Hal R, et al. The spectrum of thyroid diseases in the community: The Whickham survey. Clin endocrinology(oxf) 1977; 7:481-91
8.Hijmans W, Doniach D, Roitt M et al. Serological overlap between lupus erythematosus, rheumatoid arthritis and thyroid autoimmune disease Br. Med J 1961; 5257: 90914.
9.R. Porkodi, S. Ramesh , A. Mahesh, P. Kanakarani, S. Rukmangathrajan, Panchapakesa C.Rajendran.: Thyroid dysfunction in Sysytemic Lupus Erythematosus and Rheumatoid Arthritis. J Indian Rheumatol Assoc 2004 : 12 :88 - 90
10.Simone Appenzeller, MD, PhD, Ana T. Pallone, MD,Ricardo A. Natalin, MD,and Lilian T. L. Costallat, MD, PhD, Prevalence of Thyroid Dysfunction in Systemic Lupus Erythematosus, J Clin Rheumatol 2009;15: 117–119
11.Adriana Maria Kakehasi,Vinícius Naves Dias, Juliana Elias Duarte, Cristina Costa Duarte LannaMarco Antônio Parreiras de Carvalho,Thyroid Abnormalities in Systemic Lupus Erythematosus: a Study in 100 Brazilian Patients,Rev Bras Reumatol, 2006;46(6):375-79
12.K L Goh and F Wang, Thyroid disorders in systemic lupus erythematosus,
Annals of the Rheumatic Diseases, 1986; 45, 579-83
13.Miry Blich MD,Alexander Rozin MD,Yeouda Edoute MD,PHD,Systemic Lupus Erythematosus and Thyroid disease, IMAJ 2004:6:218-20
14. Kohno, N. Naito, K. Saito, A. Hoshioka, H. Niimi, H. Nakajima & T. Hosoya,
Anti-thyroid peroxidase antibody activity in sera of patients with systemic lupus erythematosus.Clin. exp. Immunol. (1989) 75, 217-221
15.D Pyne, D A Isenberg .Autoimmune thyroid disease in systemic lupus Erythematosus,Annals of Rheumatic Diseases. 2002;61:70–72
9. SIGNATURE OF THE CANDIDATE:
10. REMARKS OF THE GUIDE:
11.1 NAME AND DESIGNATION OF
GUIDE : DR. SARA CHANDY
DEPARTMENT OF GENERAL MEDICINE
11.2 SIGNATURE :
11.3 Co-GUIDE (if any) : DR.VINEETA SHOBHA
DEPARTMENT OF GENERAL MEDICINE
11.4 SIGNATURE :
11.5 HEAD OF
THE DEPARTMENT : DR.G.D RAVINDRAN
PROFESSOR HEAD
DEPARTMENT OF GENERAL MEDICINE
11.6 SIGNATURE
12.1REMARKS OF THE PRINCIPAL:
12.2 SIGNATURE :