Dr. Keshava Anvesh G

Date: th OCTOBER, 2011

From,

Dr. Keshava Anvesh G,

Junior resident,

Department of G.Medicine,

A.J.Institute of Medical Sciences,

Kuntikana, Mangalore.

To,

The Chairman/ Member Secretary

Institute Ethics Committee,

A.J.Institute of Medical Sciences,

Kuntikana, Mangalore.

Through the Head of the department of G.Medicine

Subject: Submission of synopsis to Ethical committee-reg.

I am herewith submitting my MD dissertation synopsis titled “RENAL PARAMETERS IN HYPOTHYROIDISM” for the consideration of the Institute Ethics committee. I have also enclosed the proforma for the ethics committee, data collection proforma, consent form and curriculum vitae. I request you to kindly do the needful.

Thanking you,

Yours sincerely

Dr. Keshava Anvesh.G

Encl: as above

Institute Ethics Committee

A J Institute of Medical Sciences, Kuntikana, Mangalore.

Proforma to be filled by the Principal Investigator (PI) for submission to Institutional Ethics Committee (IEC)

(for attachment to each copy of the proposal)

Serial No of IEC Management Office:

Proposal Title: “RENAL PARAMETERES IN HYPOTHYROIDSM”

Name, Designation
Qualifications / Address
Tel & Fax Nos.
Email ID / Signature
Principal Investigator
Guide / Dr. Keshava Anvesh G.
Junior Resident,
Dept.of G.Medicine,
A.J.Institute of Medical Sciences.
M.B.B.S.
Dr. E.V.S Maben
Professor
Dept. of G.Medicine A.J.Institute of Medical Sciences.
M.B.B.S, M.D.(G.Medicine) / AJ Boys Resident’s Hostel,
Room no 410
Kuntikana, Mangalore
Ph: 9980881891

304,Sundari Apartments
Shivbagh,Kadri
Mangalore-575002
Curriculum Vitae of principal investigator and the guide (with subject specific publications limited to previous 5 years) – attached

Institute Ethics Committee

A J Institute of Medical Sciences, Kuntikana, Mangalore.

1.Type of Study:clinical study
2: Brief description of the proposal:Thyroid hormones are responsible for the growth and development of kidneys.Hypothyroidism can cause glomeropathy (nephritic and nephritic syndrome) and occur in diverse forms of chronic kidney diseases. It also causes rhabdomyolysis. Most kidney abnormalities (structural, metabolic and morphological) caused by hypothyroidism can be reverted after supplementation with thyroxin.
3. Subject selection:

Number of Subjects : All enumerated cases during the study period will be considered for the study.

Duration of study: 2 years

iii. Will subjects from both sexes be recruited: / Yes

Inclusion / exclusion criteria given:

/ Yes

Type of subjects: All hypothyroid patients with T.S.H>10.

4. Privacy and confidentiality
Confidential handling of data : Yes
5. Consent : Please find it attached written informed consent
i. Consent form : (included elements)

Understandable language
Statement that study involves research
Statement that consent is voluntary
Purpose and procedures
Risks & Discomforts
Benefits
Confidentiality of records
Right to withdraw
Contact information

ii. Who will obtain consent – Principal investigator

Institute Ethics Committee

A J Institute of Medical Sciences, Kuntikana, Mangalore.

6. Will any advertising be done for recruitment of Subjects?
(posters, flyers, brochure, websites – if so kindly attach a copy) / No
7. Risks & Benefits: No risks, but benefits to the research world
8. Is there compensation for participation? / No
Checklistforattacheddocuments:

Project proposal – 2 Copies
Curriculum Vitae of Investigators
Curriculum Vitae of Guide
Informed Consent form
Copy of data collection Proforma

Place: Signature & Designation of

Date: Principal investigator

CURRICULAM VITAE

Dr’s Name: DR. Keshava Anvesh G

Date of Birth & Age: Aug 05, 1986 – 25 Years

Present Designation:PG

Department :General Medicine

College: A.J. Institute of Medical Sciences

City : Mangalore

Residential Address: AJ Boys Resident’s Hostel,

Room no 410, Kuntikana,

Mangalore.

Phone Number : Mobile No : 9980881891

E-mail address:

Qualifications:

Qualifications / College / University / Year / Registration No. of UG & PG with date / Name of the Medical Council
MBBS / Prathima Institute of Medical Sciences,
Karimnagar / NTRUHS / April 2010 / 66929,
dt May 11,
2010 / AP Medical Council

Details of pervious appointments/teaching experience

Designation / Department / Name of Institution / From
DD/MM/YY / To
DD/MM/YY / Total experience in years & months
PG / General Medicine / A.J. Institute of Medical Sciences,
Mangalore / June 7, 2011 / Till Date

CURRICULAM VITAE

Name : DR.E.V.S Maben

Date of birth & Age : Dec 03, 1962- 47 Years

Present Designation : Professor and HOD

Department : General Medicine

College : A.J. Institute of Medical Sciences

City : Mangalore

Residential Address : 304,Sundari Apartments,

Shivbagh,Kadri

Mangalore-575003

Phone & Fax Number with code : Office: 0824-2225533

Residence:0824-2217367

Mobile number:9845080872

1. Date of joining present institution: April 16, 2004as AssosiateProfessor

2. Qualifications:

Qualification / College / University / Year / Registration No.of UG & PG with date / Name of the State Medical Council
MBBS / Kasturba Medical College,
Mangalore / Mangalore University / July 1986 / 26451,
dt.sep09,1987 / Karnataka Medical council
MD
(General Medicine) / Kasturba Medical College,
Mangalore / Mangalore
University / Dec 1990 / 26451,
dt.June 20,2000 / Karnataka Medical council
DM/M.Ch / NA

CURRICULAM VITAE

Details of the previous appointments /teaching experience

Designation / Department / Name of Institution / From
DD/MM/YY / To
DD/MM/YY / Total Experience in years and months
Tutor/
Resident / General Medicine / Kasturba Medical College, Mangalore / Jan 1988 / Dec 1990 / 3 Years
Lecture / General Medicine / Kasturba Medical College, Mangalore / Mar 15, 1991 / Mar 14, 1991 / 3 years
Assistant
Professor / General Medicine / Kasturba Medical
College Mangalore / March 15,
1991 / March 14,
1953 / 7 years,9 months
Associate
Professor / General Medicine / Kasturba Medical
College Mangalore
A.J Insitute Of Medical Sciences,
Mangalore / Dec 19,2000
Apr 16,2004 / April 15,2004
Dec 17,2004 / 3 Years 4 months
8 months
Professor / General Medicine / A.J Institute of Medical Sciences,
Mangalore / Dec 18,2004 / June 21,2008 / 3 Years 6 months
Professor & HOD / General Medicine / A.J Institute of Medical Sciences,
Mangalore / Jun 22, 2008 / Till date / 3 years

SYNOPSIS

Submission for ethical clearance to Ethical Committee of AJIMS

“RENAL PARAMETERS IN HYPOTHYROIDISM”

Name of the candidate: Dr. Keshava Anvesh.G

Guide: Dr.E.V.S Maben

Course and Subject : M.D. General Medicine

Department of General Medicine,

A.J. INSTITUTE OF MEDICAL SCIENCES,

Kuntikana, Mangalore – 575004

2011

1. Name of the candidate

address:

(In block letters)

2. Name of the Institute:

3. Course of study and Subject: M.D. GENERAL MEDICINE

4. Date of admission to course: 7thJUNE 2011

5. Title of the Topic:“RENAL PARAMETERS IN

HYPOTHYROIDISM”

BRIEF RESUME OF THE INTENDED WORK:

6.1 Need for the study:

Studies have suggested that hypothyroidism should be evaluated in patients’s with kidney abnormalities. Thyroid hormones are responsible for the growth and development of kidneys. They have an influence on substance transportation through the membrane and modify the electrolytic metabolism. So hypothyroidism leads to deficits of renal function, associated with reduction in the cardiac output.1

It can also cause glomeropathy (nephritic and nephritic syndrome) and occur in diverse forms of chronic kidney disease including in haemodialysis patient, therby worsening the prognosis. Most kidney abnormalities (structural metabolic and morphological) caused by hypothyroidism can be reverted after supplementation with thyroxin.1

It also causes rhabdomyolysis. Usually an aggrevating factor such as use of lipid lowering drug,alcohol,chronicrenal failure has been identified. It manifests as muscular symptoms like myalgias, weakness with severly elevated enzymes6

Hypothyroidism is an under-appreciated cause of renal

Impairment. Thyroid function should be assessed in patients with deteriorating

renal function, including those with known

renal impairment in which the deterioration is unexpected.2

The most common kidney derangements associated to hypothyroidism are: elevation of serum creatinine levels, reduction in GFR and renal plasma flow (RPF), disruption of the capacity to excrete free water and hyponatremia.Primary hypothyroidism is associated with a reduction of GFR and RPF that are normalized following levothyroxine administration. Similarly, normalization of circulating TH concentrations with replacement therapy in hypothyroid patients with chronic kidney disease (CKD) can significantly improve GFR.5

6.2Review of literature:

To assess the extent of these defects, serum concentration of electrolytes and glomerular filtration rate were estimated before and after thyroid replacement in patients with primary hypothyroidism. All patients had decreased glomerular filtration rates and patients had increased serum creatinine levels. Although a relationship between creatinine clearance and serum thyrotropin-stimulating hormone was not found, a weak correlation between age and serum creatinine concentration was observed. All these defects were corrected by treatment with thyroid hormone. We conclude that creatinine clearance was slightly decreased in all patients with hypothyroidism, this decrease being more noticeable in elderly patients. 1

Hypothyroidism has also been described as the consequence,

rather than the cause, of renal dysfunction; thyroxin

is heavily protein bound and is lost via the urine

innephritic syndrome. Undiagnosed nephritic syndrome

should therefore be considered in cases of refractory

hypothyroidism, whilst thyroid function should be monitored

in cases of severe, prolonged nephrotic syndrome.2

1. Hypothyroidism is an under-appreciated cause of renalimpairment.

2. Thyroid function should be assessed in patients with deterioratingrenal function, including those with knownrenal impairment in whom the deterioration is unexpected.

3. The classical clinical signs and symptoms may be subtleor absent, even in severe hypothyroidism.2

Short-term hypothyroidism has been associated with a reversible rise in serum creatinine levels in patients with normal renal function. A remarkable decline in serum creatinine levels associated with a treatment of severe and prolonged hypothyroidism has rarely been reported so far. We present here 2 patients with chronic renal failure in whom treatment for hypothyroidism resulted in a significant and sustained reduction of their serum creatinine levels. These cases indicate that because hypothyroidism may aggravate the serum creatinine levels, TSH should be considered in screening procedures of patients with chronic renal failure presenting with recent accelerated aggravation of renal function. Hypothyroidism per se, one of its complications or one of its associated autoimmune diseases might play a role in modifying the underlying renal problem.3

Adult cases of acute renal failure associated with hypothyroidism were taken. All patients presented with symptoms suggestive of moderate to severe hypothyroidism, such as cold intolerance, constipation, muscle weakness, and lower extremity oedema. Initial serum creatinine levels ranged between 115 and 203 micromol/L (1.3 and 2.3 mg/dL), with creatinine clearances (CrCl) ranging between 0.58 and 0.97 mL/s (34.5 and 58 mL/min). After 6-12 weeks of treatment with levothyroxin, serum creatinine levels decreased to the range of 80 and 124 micromol/L (0.9 and 1.4 mg/dL) and CrCl increased to 0.74-1.64 mL/s (44-98 mL/min). One patient had proteinuria of 800 mg/day, which decreased to the normal range (<200 mg/day) after levothyroxin treatment. All of our patients had increased creatine kinase (CK), ranging between 1000 and 2360 U/L (normal range, 22-165 U/L), which normalized after 6 weeks of levothyroxin treatment.4

Kidney and thyroid function and dysfunction are interrelated through several mechanisms. From a clinical practical perspective, in patients with kidney disease, it is generally sufficient to use thyroid function tests commonly used in the clinic. However, to avoid mistakes in diagnosis, it is important to know the effects of hypothyroidism and hyperthyroidism on renal function, as well as the changes in thyroid function tests induced by acute and chronic kidney diseases. Drugs used in the treatment of thyroid and kidney diseases may induce changes in renal and thyroid physiology respectively. Treatment of CKD by HD, PD or renal transplantation is also accompanied by specific changes in thyroid.5

Hypothyroidism, though rare, should be considered a definite and authentic cause of rhabdomyolysis. The exact cause of rhabdomyolysis in hypothyroidism remains unclear. Usually an aggravating factor such as use of lipid-lowering drugs, alcohol, exercise or chronic renal failure has been identified. Rhabdomyolysis manifests with muscular symptoms (e.g. myalgia and weakness) and severely elevated serum levels of muscle enzymes. It can become a life-threatening disorder when complicated by acute renal failure Thyroid hormone replacement therapy improves thyroid and renal functions and reverses rhabdomyolysis.As a result, hypothyroidism must be considered in patients presenting with acute renal failure and elevated muscle enzymes. As soon as the diagnosis is made, levothyroxin should be started.6

6.3Objectives of the study:

To find the association between renal failure and hypothyroidism.

7. Material and methods:

7.1 Source of data.

It will be a Prospective based hospital study, comprising of patints diagnosed with hypothyroidism from AJ Institute of Medical Scienceshospital, Mangalore

7.2 Method of collection of data (including sampling procedure, if any)

Sample and sampling technique:

Study design: two year prospective study.
Set-up: The AJ Institute of Medical Sciences.
Study Period: July 2011 up to July 2013.
Age group: 15 to 75 years.
All hypothyroid patients with T.S.H.>10

Study type: two year prospective study.

Inclusion criteria:

Hypothyroid patients with T.S.H>1O

Exclusion criteria:

H/0 Diabetes Mellitus,
Hypertension,
Drugs causing renal failure,
Previously existing renal diseases.

Plan for data analysis:

The various measures of central tendencies and graphical representations will be used to analyze the data.

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.

This study requiresthe following investigations:

1. Thyroid Stimulating Hormone levels (T.S.H)

2. Urine analysis.

3. Serum creatinine

4. Blood urea

5.24 hr urine output

6. Creatinine Phospho Kinase (C.P.K)

7.F.B.S

Periodic assessment is to be done-

▫Prior to initiating treatment

7.4 Has ethical clearance been obtained from your institution in case of 7.

Awaited

8. References

1.Montenegro J,González O,Saracho R,Aguirre R,González O,Martínez I,
et al,editors.ChangesIn renal function in primary hypothyroidism.American Journal kidney Disease.1996 Feb;27 p.95-98
2. Renal impairment resulting from hypothyroidismA CandJoanne E, editors. Renal impairment resulting from hypothyroidism.Oxford Journals of Medicine NDT Plus Volume 1., issue 6 P.4441-441
3.Hajime N, Katsuhiko S, Yoshio H, Osamu S, Satoko N, Takashi I, etal, editors. Treatment of Severe Hypothyroidism Reduced Serum Creatinine Levels in Two Chronic Renal Failure patients. Nephron2001;88:p264-267

4.Mooraki A,Broumand B,Neekdoost F,Amirmokri P,Bastani B,editors.Reversible acute renal renal failure with hypothyroidism. Nephrology (Carlton).2003 Apr;8(2):p.57-60

5. Iglesias P, Diez JJ,editors.Thyroid dysfunction and kidney diseases.European journal Endocrinology,April 1, 2009160p.503-515

6Mustafa A,Murat D,MevlutCeri,editors.. Rhabdomyolysis due to hypothyroidism Oxford Journals of medicine nephrology dialysis transplantation volume 20, issue 4,p 847-848

9.Signature of the candidate:

10. Remarks of the guide

11.Name and Designation of (in block letters):-

11.1 Guide:

11.2 Signature:

11.3 Head of Department:

11.4 Signature:

12. Remarks of the Chairman and Principal:

12.2Signature:

Proforma:

Case no. : O.P. No. / I.P. No.

Name:Dept / Ward

Age:

Sex:Unit:

Address:Date of Admission:

Occupation:

Religion:Date of discharge

Socio-economic status: Upper class / Middle Class / Lower class

HISTORY:

I. PRESENTING COMPLAINTS:DURATION

II. HISTORY OF PRESENTING COMPLAINTS:DURATION

1. Tiredness / General Weakness / Lethargy

1. Tiredness / General Weakness / Lethargy: Duration Progress

2. Intolerance to Cold / Feeling Cold / Sensation of Cold

3. Dryness of Skin / Coarse Skin

4. Hoarseness of Voice / Slow Speech / Aphonia

5. Puffiness of Face / Eyelids:Progress and Diurnal Variation

6. Swelling of Limbs Lower Limbs/ Upper LimbsProgress and Diurnal Variation

7. Weight Gain Duration How much?

8. Described Appetite / Anorexia Duration

9. Aches / Pain / Muscle Stiffness Duration

10 Anuria

11 oligouria

12 polyuria

13 haematuria

14 nocturnal

15 dysuria

16 retention of urine

17 incontinence of urine

18 enuresis

19 passage of milky urine

20 swelling of the abdomen

21 loin pain

22 renal colic

23 fever (U.T.I, renal tuberculosis, pyelonephritis

24. Paresthesia Duration

25. Others Duration

a. Constipation

b. Falling of Hairs:Hair Loss / Alopecia

c. Palpitation

d. Deafness / Impaired hearing

e. Difficulty in concentration / Poor memory/ Slow in Physical and Mental Activities / Nervousness / Depression

f. Decreased sweating

g. Menorrhagia (in females)

SYMPTOMS SUGGESTIVE OF CARDIOVASCULAR PROBLEMS:

DURATION

1. Chest pain

2. Breathlessness

3. Effort in tolerance

4. Palpitation

5. Syncope

III. HISTORY OF PAST ILLNESS:

H/o Hypertension / Diabetes Mellitus / Other Cardiac Diseases

H/o Neck Surgeries Yes/ No

Any other significant illness

H/o of Psychiatric illness

TREATMENT HISTORY:

IV. PERSONAL HISTORY:

Diet - Vegetarian / Mixed

Appetite - Normal / Decreased

Sleep - Normal / Disturbed

Bowel habits -

Bladder habits

Habits Smoking Yes / No Duration

No. of Beedies / Cigarettes / Day

Alcoholism Yes/ No Duration Type

Amount

V. FAMILY HISTORY:

Single / Married

If Married: No. of Children: Male / Female

Any significant medical / surgical illness in the family

VI. SOCIAL AND OCCUPATIONAL HISTORY:

VII. MENSTRUAL AND OBSTETRIC HISTORY (IN FEMALES):

1. Menarche:

2. Regularity of cycles: Regular / Irregular

3. Duration of cycles:

4. No. of days of flow: Normal / Excess / Reduced Quantity

5. LMP

No. of deliveries:

Abortions if any:

GENERAL PHYSICAL EXAMINATION:

1. Appearance:

2. Built: Well built / moderate / poor

3. Nourishment: Well nourished / moderate / poor

4. Height of Cms:

5. Weight in Kgs: BMI

6. Hair:Texture: Normal / Course / Dry

Hair Loss / Alopecia: Present / Absent

Hair Loss over lateral one-third of eye brow: Present /Absent

7. Skin: Normal / Dry / Rough / Scaly

a. Over face / Upper and Lower Limbs / Body

b. Cold Skin: Present / Absent

8. Nail Texture: Normal / Rough Koilonychia

9. Clubbing: Absent / Present:Grade: I / II / III / IV

10. Pallor: Absent / Present: Mild / Moderate / Severe

11. Icterus: Absent / Present:

12. Cyanosis: Absent / Present:

13. Tongue: Normal / Pale / Glossitis / Thick / Coated / Bald / Ulcer

14. Lymphadenopathy: Absent / Present: Group

15. Oedema: Absent / Facial / Lower Limbs / Upper Limbs / Anasarca /

Pitting / None Pitting

16. Examination of Neck: Thyroid swelling Present / Absent

If Present Details Diffuse / Nodular

Tender / Non Tender

Bruit: Present / Absent

17. J.V.P. Normal / Raised

18. Vitals

Radial pulse: Rate Rhythm

Blood pressure: a. Supine b. Standing

Temperature: Axillary

Respiration: a. Rate

SYSTEMIC EXAMINATION:

I. CARDIOVASCULAR SYSTEM:

Examination of arterial system

Pulse:

Radial pulse:Rate:Rhythm:Volume:

Vessel wall condition

Carotid Pulse:Character:

Peripheral pulses – Normal / Reduced / Absent

Radio – Femoral delay:

Examination of venous system:

Jugular venous pulsation: Normal / Raised

Jugular venous pressure: in cms above sternal angle

Examination of precordium

Inspection:

Shape of the chest:

Precordial Prominence, Pectus excavatum / carinatum/ Kyphosis / Scoliosis

Absent / Present

Apex Location:

Precordial Pulsation: Absent / Present Location:

Parasternal Heave: Absent / Present

Neck / Epigastric Pulsations

Other Findings

Palpation: Apex position / Non-position / Normal / Tapping / Hyper dynamic /

Heaving Diffuse / Other types

Parasternal heave: Absent / if present Grade

Any palpable sound Thrill: Absent Present

Other findings

Percussion: Left Border of the Heart

Right Border of the Heart

Base of the Heart

Auscultation:

Heart sounds: Bradycardia Absent / Present

Mitral Area:

Aortic Area:

Pulmonary Area:

Tricuspid Area:

Other Areas:

Any other auscultatory findings:

II. RESPIRATORY SYSTEM:

Inspection:

Palpation:

Percussion:

Auscultation:

III. ABDOMINAL AND GENITO URINARY SYSTEM:

Inspection:

Genitilia-Penile swelling, vulval edema, scrotal swelling, skin for renal biopy mark, nephrectomyscar, renal transplant scar.

Palpation:

1 1Examination of genitilia for phimosis, scrotal edema, hydrocoel, contact ulcer in genitilia, palpation of the testis.

2 Parietal edema

3 Fluid thrills

4 Detailed examination of the kidneys with special reference to bimanual palpation and ballotment to find out renal mass