RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA, BANGALORE

PERFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

(to be submitted in duplicate)

NAME OF THE CANDIDATE: DR. HARIT KOTHARI

AND ADDRESS S/O DR. GOVARDHAN KOTHARI

192, MOHAN COLONY,

BANSWARA [RAJASTHAN]

PIN-327001

NAME OF INSTITUTION : M.S.RAMAIAH MEDICAL COLLEGE

BANGALORE, KARNATAKA.

COURSE OF STUDY SUBJECT : M.D GENERAL MEDICINE

DATE OF ADMISSION TO

COURSE : 01-06-2011

TITLE OF THE TOPIC : TO STUDY THE FREQUENCY AND

PATTERN OF NON THYROIDAL

ILLNESS SYNDROME IN PATIENTS

WITH SEPSIS ADMITTED TO MEDICAL

INTENSIVE CARE UNITS IN TERTIARY

CARE HOSPITALS.

6. BRIEF RESUME OF INTENDED WORK:

6.1  INTRODUCTION –

Critical illness can affect physiological functions of various organs, though not affected by primary disease. This can also have an impact on the outcome of critically ill patients. The Non Thyroidal Illness Syndrome is one of these syndromes seen in ICU patients. Sepsis is a significant problem in critically ill patients. It is the leading cause of death in noncoronary ICUs. In patients, with no previously diagnosed intrinsic thyroid disease, critical illness can cause profound changes in thyroid hormone metabolism along with changes within the hypothalamus-pituitary-thyroid axis.1 Such changes have been named “Euthyroid Sick Syndrome” or more recently “Non thyroidal Illness Syndrome(NTIS)”. The abnormalities observed in cases of NTIS include low levels of Triiodothyronine T3, normal or low levels of Thyroxine T4 and normal or low levels of Thyroid Stimulating Hormone(TSH). Sometimes transient elevation of TSH is also seen.1 (Pattern seen in Non Thyroidal Illness Syndrome)

NTIS affects about 70% of patients hospitalized with diseases of various etiologies.4

6.2 NEED FOR WORK –

Most of the studies of Non Thyroidal Illness Syndrome (NTIS) are Western and there are few Indian studies which have examined this issue in our Intensive Care Units1.The pattern of abnormalities that is seen in Non Thyroidal Illness Syndrome is little different in our country where iodine deficiency is higher in some areas2.The influence of Non Thyroidal Illness Syndrome on underlying disease also needs to be studied. In studies done on Non Thyroidal Illness syndrome, it was observed that it is sensitive independent predictor of short term survival and mortality.

Hence, an attempt has been made to study the frequency and pattern of Non Thyroidal Illness Syndrome in Intensive Care Units in the subgroup of patients with Sepsis.

6.3 REVIEW OF LITERATURE:

The evaluation of altered thyroid function parameters in systemic illness and stress remains complex because changes occur at all levels of the Hypothalamo-Pituitary-Thyroid axis. The so called “Non Thyroidal Illness Syndrome” also known as the low T3 syndrome or Euthyroid Sick Syndrome is not a true syndrome but rather reflects alterations in Thyroid Function Tests in a variety of clinical situations. That commonly include a low serum Triiodothyronine(T3),normal to low Thyroxine(T4) and a high reverse T3(rT3).

These typical changes may be observed in up to 75% of hospitalized patients1. Changes in metabolism of Thyrotropin Releasing Hormone in Non Thyroidal Illness Syndrome, responsible for TRH degradation in states of acute Non Thyroidal Illness Syndrome3.

Unique changes in Thyroid Function parameters are observed in various relevant clinical states including starvation and fasting, cardiac disease, renal disease, hepatic disease and infection4. Many pharmacological agents also cause changes in thyroid economy that can complicate the interpretation of thyroid function parameters in systemic illness. Decrease in thyroid function at baseline might be associated with a worse outcome of patients with sepsis or septic shock5. In patients with moderate to severe heart failure, Sick Euthyroid Syndrome shows a prevalence of 18%6. Also in human and animal models of sepsis and trauma indicate that expression of THRs and their coactivators are decreased in acute illness.7 It was also observed that increased concentrations of cytokines, especially IL-6, are often found in Non Thyroidal Illness patients.8

Clinical significance of Non Thyroidal Illness Syndrome, it was observed that a low serum T3 level predicts increased mortality from liver cirrhosis, advanced congestive heart failure and possibly several other systemic illnesses. Similarly, low total T4 is associated with increased mortality from systemic illnesses, and those patients with low T4 who have very low serum T3 levels have the worst prognosis.9 Also, low T3 syndrome is very common in the hospitalized older population , emerging as the most sensitive independent predictor of short term survival.10

6.4 OBJECTIVES OF THE STUDY

  1. To study the frequency of Non Thyroidal Illness Syndrome in patients with sepsis admitted to Medical Intensive Care Units.
  2. To study the pattern of Non Thyroidal Illness Syndrome in patients with sepsis.
  3. To study the association between severity of Non Thyroidal Illness Syndrome and outcomes of patients with sepsis.


MATERIALS AND METHODS

7.1 SOURCE OF DATA:

Patients admitted to Medical Intensive Care Unit (MICU) in M.S. Ramaiah Hospitals >18 years of age of both Sexes.

7.2 METHODS OF COLLECTION OF DATA:

•  Study Design: Hospital based Cross Sectional study

•  Duration of study: September 2011 to September 2013

All patients admitted to MICU with diagnosis of Sepsis based on Clinical profile, features of Systemic Inflammatory Response Syndrome (SIRS), Serum Procalcitonin (PCT) levels and isolation of microbiological flora will be included in the study. The American College of Chest Physician/Society of Critical Care Medicine Consensus Conference definitions were used to delineate patients with SIRS, Sepsis, Severe Sepsis and Septic Shock. All patients-in addition to clinical assessment will be subjected to Baseline investigations. Outcome is assessed on the basis of survivability: survivors and non-survivors at the time of discharge from MICU.

7.3 INCLUSION CRITERIA

All patients admitted to MICU >18 years of age with diagnosis of Sepsis.

7.4 EXCLUSION CRITERIA

·  All patients aged <18 years.

·  Known case of pre-existing Thyroid illnesses.

7.5 Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, describe briefly.

Investigations Required

All patients-in addition to clinical assessment will be subjected to Baseline investigations.

·  Haemogram

·  Blood Urea Nitrogen and creatinine

·  Random Blood Sugars

·  Liver Function Test and Serum Electrolytes

·  Arterial Blood Gas Analysis

·  Urine Examination

·  ECG and Chest X Ray

·  Blood Culture and Urine Culture

·  Serum Procalcitonin Level

Special investigations: Thyroid Function Test [T3, T4 , TSH Levels]


STUDY DESIGN:

Hospital based Cross Sectional study

SAMPLE SIZE : 100

Two Means - Estimating the difference between two means
Standard deviation in the Ist group / 13.4
Standard deviation in the IInd group / 19.6
Precision (%) / 5
Desired confidence level (1- alpha) % / 95
Number needed (n) / 87
20% extra to account for data loss ,rounded off / 100

The Sample size was estimated based on evidence from study “Anna G Angelousi, Drosos E Karageorgopoulos et al: Association between thyroid function tests at baseline and the outcome of patients with sepsis or septic shock: a systematic review; European Journal of Endocrinology (2011)164 147-155”.

It was based on levels of T3 hormones between sepsis patients having favorable and unfavorable outcomes. The mean T3 and S.D. of T3 levels to diagnose Non Thyroidal Illness Syndrome among patients with and without sepsis were taken into consideration for calculating sample size.

From the study it was observed that mean (SD) of T3 levels among unfavorable outcome is 30.40+-13.40 and among favorable outcome is 52.5+-19.60.

Substituting this the sample size was calculated based on difference between means between the two groups , using precision of 5%, desired confidence level 95% and accounting 20% for attrition, it was estimated to be 87 rounded off to 100 patients.

STATISTICAL ANALYSIS:

·  Statistical Analysis is going to be done using the SPSS(Statistical Package for the Social Sciences)

·  Descriptive Statistics:- It will be applied to describe the baseline Quantitative variables like Age, Sex, Laboratory parameters and Thyroid Hormone Levels etc.

·  Using Mean and Standard Deviation all continous variables like Age, Sex, Sepsis T3, T4 etc will be expressed in frequency and Percentage.

·  Analytical Statistics:- The frequency and pattern of Non Thyroidal Illness Syndrome in Sepsis patients will be expressed in Percentage and Frequency.

·  The association between severity of Non Thyroidal Illness Syndrome and Outcomes of Sepsis will be assessed using Chi Square test of significance.

·  Independent t test will be used to compare the mean (SD) of thyroid hormone levels between the two groups.

7.6 Has ethical clearance been obtained from your institution?

YES

8. LIST OF REFERENCES

  1. Suzanne Myers Adler, Leonard Wartofsky: The Nonthyroidal Illness Syndrome; Endocrinol Metab Clin N Am, 2007, 36, 657-672
  2. AH Zargar, MA Ganie, SR Masoodi et al: Prevalence and pattern of Sick Euthyroid Syndrome in Acute and Chronic Non Thyroidal Illness-its relationship with Severity and outcome of the Disorder; JAPI Jan 2004, Vol.52, 27-31
  3. L H Duntas, T T Nguyen, F S Keck et al: Changes in metabolism of TRH in euthyroid sick syndrome; European Journal of Endocrinology, 1999, 141, 337-341
  4. G.Bello, S. Silva et al: The role of thyroid dysfunction in the critically ill: a review of the literature; Minerva Anestesiologica, Nov 2008, Vol.76-No.11, 919-928
  5. Anna G Angelousi, Drosos E Karageorgopoulos et al: Association between thyroid function tests at baseline and the outcome of patients with sepsis or septic shock: a systematic review; European Journal of Endocrinology, 2011, 164, 147-155
  6. C. Opasich, F. Pacini, N. Ambrosino et al: Sick Euthyroid Syndrome in patients with moderate to severe chronic heart failure; European Heart Journal, 1996, 17,1860-1866

7.  Maria H Warner and Geoffrey J Beckett: Mechanisms behind the non-thyroidal illness syndrome: an update; Journal of Endocrinology, 2010, 205, 1-13

8.  Luigi Bartalena, Fausto Bogazzi, Sandra Brogioni et al: Role of cytokines in the pathogenesis of the euthroid sick syndrome; European Journal of Endocrinology, 1998, 138, 603-614

9.  Inder J. Chopra: Euthyroid Sick Syndrome: Is it a Misnomer? Clinical Review 86; Journal of Clinical Endocrinology and Metabolism, 1997, Vol 82, No. 2

9. SIGNATURE OF THE CANDIDATE :

10. REMARKS OF THE GUIDE :

11. NAME AND DESIGNATION OF GUIDE : DR SHIVA KUMAR N.S.

Professor of Medicine

12. SIGNATURE :

13. HEAD OF THE DEPARTMENT : DR ARUN NARAYAN

Professor of Medicine

14. SIGNATURE :

15. REMARKS OF CHAIRMAN

AND PRINCIPAL :

16. SIGNATURE :

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