1.) NAME OF THE CANDIDATE: DR. ANOOP JOSEPH
2.) ADDRESS: : DEPARTMENT OF MEDICINE
ST.JOHNS MEDICAL COLLEGE HOSPITAL
JOHNNAGAR, SARJAPUR ROAD,
KORAMANGALA, BANGALORE-560034
PH. NO. 8892307255
3.) NAME OF THE HOSPITAL : ST.JOHN’S MEDICAL COLLEGE, BANGALORE
4.) COURSE OF STUDY AND SUBJECT: MD GENERAL MEDICINE
5.) DATE OF ADMISSION TO THE COURSE: 21st MARCH 2011
6.) TITLE
:PREVALENCE OF THYROID DYSFUNCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS
7. INTRODUCTION:
Rheumatoid arthritis(RA) is a chronic multisystem disease of unknown cause that may affect many tissues and organs, but principally attacks synovial joints. The pathology of the disease process often leads to the destruction of articular cartilage andankylosisof the joints. Rheumatoid arthritis can also produce diffuse inflammation in thelungs,pericardium,pleura, andsclera, and also nodular lesions, most common insubcutaneous tissue. Although the cause of rheumatoid arthritis is unknown, autoimmunityplays a pivotal role in both its chronicity and progression, and RA is considered asystemic autoimmune disease. Prevalence of RA is 0.8%of the population. Range(0.3-2%).
Thyroid dysfunction may be broadly classified as hypothyroidism and hyperthyroidism.The mostcommon causeof thyroid disordersworldwide isiodine deficiency leadingtogoitre formation andhypothyroidism. In iodinereplete areas mostpersonswith thyroid disorders have autoimmune disease, ranging fromthyrotoxicosis to hypothyroidism.
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 iodinereplete areas,, the cause is either autoimmune thyroiditis( Hashimotosthyroiditis )or destructive treatment for thyrotoxicosis . 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 (2).
In the Wickham survey, the prevalence of newly diagnosed overt hypothyroidism was 3 per 1000 females (3). 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 thyrotoxicosisisGraves 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 (1)
7) REVIEW OF LITERATURE:
The relationship between thyroid disease and rheumatic disorders has been the subject ofconsiderable debate,.Studies show that abnormal or changing thyroid status may precipitate or exacerbate musculoskeletal disease. This has been demonstrated for rheumatoid arthritis(7). In an attempt to determine the genetic andenvironmental factors contributing to autoimmunity, clinical investigators have looked forrelations between various autoimmune disorders such as rheumatoid arthritis (RA) andautoimmune thyroid disease. In several surveys conducted since the early 1960s a relation was suggested to exist between Hashimoto's thyroiditis and RA.(1-4). In a controlled prospective survey done by Shiroky et al in 1993, thyroid dysfunction was seenat least three times more often inwomen with RA than in women withsimilar demographic features with noninflammatory rheumatic diseases such asosteoarthritis and fibromyalgia.In a retrospective study of 26patients with both thyroid disease and rheumatoid arthritis, by Delamere Scott and Felix Davies in 1982, 4 patients had a simultaneousonset of both myxoedema and rheumatoid arthritis, the activity of which was greatlyImproved by correction of the hypothyroid state.
A higher prevalence of ATD in female RA patients compared with controls indicates the need for screening not only of thyroid function, but also of the presence of anti-TPO antibodies as the ATD marker in RA patients. Monitoring of thyroid function in patients with RA is of particular importance, since as already shown, the course of thyroid disease in RA patients is often asymptomatic.(13)
The ARA proposed diagnostic criteria for RA in 1987. It consisted of 7 criteria;
1)morning stiffness for at least 1 hour
2)arthritis of atleast 3 or more joint areas, simultaneously
3)hand arthritis ( wrist, metacarpophalangeal or proximal interphalangeal joint)
4)symmetric joint involvement
5)subcutaneous rheumatoid nodules
6)presence of rheumatoid factor
7)radiographic erosion or bony decalcification of involved joints
Diagnosis was based on the presence of at least 4 of the 7 criteria; the first 4 must have been present for at least 6 weeks.
In 2010 the 2010 ACR/EULAR rheumatoid arthritis classification criteria were introduced. These criteria are adapted for early diagnosis. This classification criteria jointly published by the American college of rheumatology and the European league against rheumatism (EULAR), establish a point value between 0-10. Patients with a score of > 6 are classified as having RA, provided he has synovitis in at least one joint and given that there is no other diagnosis explaining the synovitis better. Four areas are covered in the diagnosis
EULAR CRITERIA:(14)
Target population (Who should be tested?): Patients who
1) Have at least 1 joint with definite clinical synovitis (swelling)
2) With the synovitis not better explained by another disease†
Classification criteria for RA (score-based algorithm: add score of categories A–D;
a score of 6/10 is needed for classification of a patient as having definite RA)
A. Joint involvement
1 large joint 0
2-10 large joints 1
1-3 small joints (with or without involvement of large joints) 2
4-10 small joints (with or without involvement of large joints) 3
10 joints (at least 1 small joint)** 5
B) Serology (at least 1 test result is needed for classification)
Negative RF and negative ACPA 0
Low-positive RF or low-positive ACPA 2
High-positive RF or high-positive ACPA 3
C). Acute-phase reactants (at least 1 test result is needed for classification)
Normal CRP and normal ESR 0
Abnormal CRP or abnormal ESR 1
D. Duration of symptoms
6 weeks 0
>=6 weeks 1
The progression of Rheumatoid arthritis can be followed using scores such as the Disease Activity Score of 28 joints(DAS 28), it is widely used as an indicator of disease activity and response to treatment, but is not always a reliable indicator of treatment effect. The joints included in the DAS 28 are (bilaterally): proximal interphalangeal joints (10), metacarpophalangealjoints (10), wrists (2), elbows(2), shoulders(2) and knees(2). When looking at these joints, both the no. of jointswith tenderness upon touching (TEN 28) andswelling (SW28) are counted. In addition the ESR is measured. Also the patientmakes a subjective assessment (SA) of disease activity in the last 7 dayson a scale between 0 and 100, where 0 is “no activity” and 100 is “highest activity possible”. With these parameters, DAS 28 is calculated as(15)
From this the disease activity of the patient can be classified as follows(16)
CURRENT DAS28 DAS28 FROM INITIAL VALUE
1.2 / > 0.6 but <= 1.2 / <= 0.6Good improvement / Moderate improvement / No improvement
<_ 3.2 / Inactive
>3.2 but <_5.1 / Moderate
>5.1 / Very active
8. NEED FOR THE STUDY:
Many patients with thyroid dysfunction (especially hypothyroidism) have symptoms (fatigue, arthralgias, myalgias, arthritis) similar to those found in RA,as such thyroid dysfunction maybe missed in patient with RA.
Some workers have suggested that thyroid dysfunction may exacerbate RA.
It has been assumed that RA and thyroid dysfunction may share a genetic predisposition.
9. OBJECTIVES OF THE STUDY:
1)To study the prevalence of thyroid dysfunction in patients who are newly diagnosed or have already been diagnosed with RA.
2) To assess the clinical features of hypo/hyperthyroid patients with RA.
3) To determine if anyassociation exists between Rheumatoid factor positivity and anti thyroid peroxidaseantibodies.
10. MATERIAL AND METHODS:
A) STUDY DESIGN: Descriptive, prospective,cross sectional study.
B) SAMPLE SIZE AND SOURCE OF DATA:
This is a prospective study from July 2011 to July 2013. 100 consecutive patients with rheumatoid arthritis visiting medicine or the rheumatology OPD or hospitalizedin St.John’s Medical College Hospital will be the source of data.
The sample size would be= 100
C) Inclusion criteria:
1) All patients diagnosed as rheumatoid arthritis, either newly diagnosed or those on regular follow up.
2) Age greater than 18 yrs.
3) Those consenting to participatein the study.
D)Exclusion criteria:
1) Patients on medication that are known to cause thyroid dysfunction. (Amiodarone, lithium, PAS, interferon alpha).
2)Patients who have undergone thyroidectomy.
E) Methods of data collection:
All patients with rheumatoidarthritis 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 RA, thyroid disorders and all comorbidities .All subjectswill undergo lab evaluation (FT4 TSH and TPO). If thyroid dysfunction is confirmed further investigations and treatment, will be initiated
Demographic data, type of thyroid dysfunction, duration of rheumatic disease and thyroid disease, and whether thyroid dysfunction preceded RA will be recorded. Thyroid dysfunction will be classified as hyperthyroid(clinical and subclinical) clinical hypothyroid, subclinical hypothyroid (TSH alone elevated), sickeuthyroid status ( TSH alone elevated)and euthyroid (antibodies alone elevated).
EVALUATION OF HYPOTHYROIDISM:
Elevatednormal
Measure unbound FT4no intervention
Normal low
(Mild hypothyroidism) (Primary hypothyroidism)
TPO Ab+ or TPO Ab-, TPO Ab+ TPO Ab-
Symptomatic no symptoms(autoimmune rule out other causes
Hypothyroidism) of hypothyroidism)
T4 treatment annual follow up T4 treatment
EVALUATION OF THYROTOXICOSIS:
TSH low, uncombined TSH low, uncombined TSH normal or TSH &T4
T4 highT4 normal increased, high T4 normal
Primary thyrotoxicosis measure uncombined T3 TSH secreting pituitary
Adenoma or thyroid
High normal hormone resistance synd.
T3 toxicosis subclinical hyperthyroidism
Features of Graves disease? follow up in 6-12 weeks no more tests
Yesno
Graves dsmultinodulargotre or
Toxic adenoma
Features of Graves ds: diffuse goitre, positive TPO antibodies, ophthalmopathy, dermopathy
PROFORMA NO:
NAME______MRD NO______
AGE:______SEX:M/F
ADDRESS AND TELEPHONE NO:
DURATION OF RHEUMATOID ARTHRITIS:____ DURATION OF THYROID DISEASE_____
SYMPTOMS:
Hyperthyroidism / Hypothyroidism / RAHyperactivity,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
Joint pains,
Loss of wt
Chest pain
Skin nodules
Rash
Dry eyes and mouth
Paresthesias of the hands and feet,
Joint deformity,
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
OTHERS
EXAMINATION:
Height: ------Weight: ------BSA: ------m square pulse: ------/min
BP: ------mm/Hg Temp.:------F Thyromegaly------Tender joint count------
INVESTIGATIONS:
Hb: ------ESR: ------Platelet: ------
Creatinine: ------Urea: ------bilirubin: ------SGOT/SGPT: ------
Thyroid function tests:
FT4:------TSH: ------anti-TPO: ------
Others:
Immunologic Investigations:
RF:_____ ANA_____ CRP_____OTHERS_____
CONCLUSIONS:
SEROPOSITIVE /SERONEGATIVE RA / DAS SCORE / THYROID STATUS / ANTI TPO AB / COMORBIDITIES11) STATISTICAL ANALYSIS:
SPSS 16 will be used for entry and analysis of all data. T – Test will be used to analyse all variables. The Chi square test will be used for nominal variables.
13) REFERENCES:
1)Tunbridge WMG, Vanderpump MPJ. Population screening for autoimmune thyroid disease. Endocrinology clinic North America 2000; 29:239-253.
2) Vanderpump MPJ, Tunbridge WMG, Epidemiology and prevention of clinical and subclinical hypothyroidism. Thyroid 2002;12: 837-847
3)Tunbridge WMG, Evered DC, Hal R, et al. T he spectrum of thyroid diseases in the community: The Whickham survey. Clinendocrinology(oxf) 1977; 7:481-491
4) Hijmans W, Doniach D, Roitt M et al. Serological overlap between lupus erythematosus, rheumatoid arthritis and thyroid autoimmune disease Br. Med J 1961; 5257: 909-914.
5)Shiroky JB, Cohen M, Ballachey ML, Neville C. Thyroid dysfunction in rheumatoid arthritis; a controlled prospective survey. Ann RheumDis 1993, 52: 454-6.
6)Roitt IM, Doniach D, Campbell PN et al: Auto antibodies in Hashimoto’s disease (lymphadenoidgoiter); preliminary communications. Lancet 1956, ii : 820-821.
7) 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 : 0 - 0
8)J P Delamere, D L Scott, D D Felix-Davies Thyroid dysfunction and rheumatic diseases. Journal of the Royal Society of Medicine Volume 75 February 1982
9) Buchanan W W, Crooks J, Alexander W D, Koutras D A, Wayne E J, Gray K G. Association of Hashimoto's thyroiditis and rheumatoid arthritis. Lancet 1961; i: 245-8.
10)BuchananWW. The relationship of Hashimoto's thyroiditis to rheumatoid arthritis.Geriatrics 1965; 20: 941-8.
11) Gibberd F B. A survey of four hundred and six cases of rheumatoid arthritis. ActaRheumatol Scand 1965; 11: 62-70.
12) Raymond J P, Kahn M F, Bourgeois P, et al. Etude prospective controllee des parametresthyroidienscliniques et biologiquesdans la polyarthriterhumatoide. Rev Rhum Mal Osteoartic 1985;
52: 317-21.
13)Prevalence of thyroid diseases and antithyroid antibodies in women with rheumatoid arthritis. Przygodzka M,Filipowicz-Sosnowska A.
14))2010 Rheumatoid Arthritis Classification CriteriaAn American College of Rheumatology/European League Against Rheumatism Collaborative Initiative Daniel Aletaha,1 Tuhina Neogi,2 Alan J. Silman,3 Julia Funovits,1 David T. Felson,2 Clifton O. Bingham, III,4 Neal S. Birnbaum,5 Gerd R. Burmester,6 Vivian P. Bykerk,7Marc D. Cohen,8 Bernard Combe,9 Karen H. Costenbader,10 Maxime Dougados,11Paul Emery,12 Gianfranco Ferraccioli,13 Johanna M. W. Hazes,14 Kathryn Hobbs,15Tom W. J. Huizinga,16 Arthur Kavanaugh,17 Jonathan Kay,18 Tore K. Kvien,19 Timothy Laing,20Philip Mease,21 Henri A. Ménard,22 Larry W. Moreland,23 Raymond L. Naden,24Theodore Pincus,25 Josef S. Smolen,1 Ewa Stanislawska-Biernat,26 Deborah Symmons,27
Paul P. Tak,28 Katherine S. Upchurch,18 Jirˇí Vencovsky´,29Frederick Wolfe,30 and Gillian Hawker31
15)DAS28 not always a reliable indicator of treatment effect in RA by Janis Kelly, Medscape Medical News
16)Prevoo, ML; Vont Hof, MA; Kuper HH; Van Leeuwen,MA; Van de Putte, LB; Van Riel, PL(1995). “modified disease activity scores that include twenty eight joint counts. Development and validation in a prospective longitudinal study of patients with Rheumatoid arthritis”. Arthritis and rheumatism 38(1): 44-8.