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stressful situations affect all endocrine axes and differ in the response during acute and chronic phases of stress .
the physiological rationale behind these alterations is to change the internal milieu of the organism helping to fight the external threat to the homeostasis .
previous attempts to correct these hormonal imbalances did not yield beneficial results in clinical trials .
low circulating thyroid hormones with hypogonadism and hypercortisolism are the predominant changes in acute stress .
few studies have reported that the low thyroid hormones are independent predictors of mortality in patients admitted to intensive care units ( icu ) , suggesting the inclusion of the thyroid profile in these scoring systems .
there appears a continuum of changes in critically ill patients , starting with low triiodothyronine ( t3 ) followed by low thyroxine ( t4 ) and lastly low thyroid stimulating hormone ( tsh ) .
the pendulum of intensive glycemic control in icu is swinging with different trials giving conflicting opinions .
the varying cutoff of glycemic control coupled with rapidity of change in glycosylated hemoglobin ( hba1c ) lead to increase in mortality in recent studies .
prolactin is a hormone with a variety of roles , and the secretion is increased in a variety of conditions including stressful situations .
there are no data available to assess the level of prolactin as a marker of the severity of the stress or indirectly leading to increase in mortality .
surprisingly , no data exist from india regarding the endocrinological parameters in critically ill patients and hence we conducted this prospective observational study to assess the thyroid hormone profile , prolactin levels , and hba1c in relation to survival in patients admitted to medical icu .
a total of 100 consecutive patients admitted to medical icu irrespective of the underlying diagnosis and diabetes state were included in this prospective , observational study .
admission into icu was based on the presentation of the patient and underlying clinical conditions unrelated to the study objectives .
patients with a known history of thyroid disease , intake of drugs altering thyroid function , were excluded from the study .
all the patients had a detailed clinical examination and were managed appropriate to their primary condition .
the patients were divided into two groups for comparison : group 1  survivors ( discharged from the hospital ) and group 2  nonsurvivors ( patients succumbed to their illness inside the hospital ) .
an informed consent , to participate in the study , was obtained from the patients or relatives where appropriate , and the study protocol was approved by the local hospital ethics committee .
fasting venous blood samples were collected immediately on admission to icu from all patients and were subjected for hormone analyses .
samples were tested for total t3 , total t4 , tsh , prolactin , and glycosylated hemoglobin in addition to the standard icu protocol tests . the normal reference range for thyroid hormones in our laboratory
miu / l ) , t3 ( 67156 ng/ dl ) , t4 ( 4.511.6 g / dl ) , prolactin ( 015 ng / ml males , 025 females ) .
any deviation of the hormone results from the normal ranges is considered to be abnormal ( low or elevated ) .
thyroid and prolactin hormones were estimated by solid phase competitive chemiluminescence and hba1c using the high performance liquid chromatography method .
we did not repeat the hormonal assays a second time in the icu or prior to discharge in survivors .
free thyroid hormones were not measured in the study group to prevent the variability associated with these hormones .
summary data are presented as mean values  sd and comparison between groups was done by mann 
fisher 's exact test and chi - square test were used to compare frequency of variables among two groups .
p values were reported for all statistical tests and a value of < 0.05 was considered to be significant .
a total of 100 consecutive patients admitted to medical icu irrespective of the underlying diagnosis and diabetes state were included in this prospective , observational study .
admission into icu was based on the presentation of the patient and underlying clinical conditions unrelated to the study objectives .
patients with a known history of thyroid disease , intake of drugs altering thyroid function , were excluded from the study .
all the patients had a detailed clinical examination and were managed appropriate to their primary condition .
the patients were divided into two groups for comparison : group 1  survivors ( discharged from the hospital ) and group 2  nonsurvivors ( patients succumbed to their illness inside the hospital ) .
an informed consent , to participate in the study , was obtained from the patients or relatives where appropriate , and the study protocol was approved by the local hospital ethics committee .
fasting venous blood samples were collected immediately on admission to icu from all patients and were subjected for hormone analyses .
samples were tested for total t3 , total t4 , tsh , prolactin , and glycosylated hemoglobin in addition to the standard icu protocol tests . the normal reference range for thyroid hormones in our laboratory
is given below : tsh ( 0.34.6 miu / l ) , t3 ( 67156 ng/ dl ) , t4 ( 4.511.6 g / dl ) , prolactin ( 015 ng / ml males , 025 females ) .
any deviation of the hormone results from the normal ranges is considered to be abnormal ( low or elevated ) .
thyroid and prolactin hormones were estimated by solid phase competitive chemiluminescence and hba1c using the high performance liquid chromatography method .
we did not repeat the hormonal assays a second time in the icu or prior to discharge in survivors .
free thyroid hormones were not measured in the study group to prevent the variability associated with these hormones .
summary data are presented as mean values  sd and comparison between groups was done by mann 
fisher 's exact test and chi - square test were used to compare frequency of variables among two groups .
p values were reported for all statistical tests and a value of < 0.05 was considered to be significant .
the baseline profile of study population ( 48 females and 52 males ) is given in table 1 .
the mean age of the study population was 58.7  16.9 years ( range , 1694 ) with average duration of icu stay 3.3  3.1 days ( range , 118 ) .
there was a significant linear correlation of tsh with age in the entire study population [ figure 1 ] .
hba1c did not show such correlation with age in the entire study subjects ( r = 0.00012 , p = 0.9124 ) .
baseline profile of study participants correlation between tsh and age in entire study population . out of the 100 patients studied , 64 survived and discharged from the hospital whereas remaining 36 succumbed to their illness .
low t3 is the only significant difference in nonsurvivors when compared with all other studied parameters [ figure 2 ] .
the distribution of thyroid hormone abnormalities in our study group are as follows : low t3 alone ( 45 ) , low t3 and t4 ( 13 ) , low t3 , t4 and tsh ( 3 ) , mixed patterns ( 16 ) , and normal thyroid profile ( 23 ) .
a total of 61 patients had low t3 ( defined as less than 65 ng / dl ) and out of them 16 also had low t4 ( defined as less than 4.5 g / dl ) .
the mortality rate was not different between patients with low t3 alone ( 19 nonsurvivors out of 45 ) and low t3 and t4 [ 9 nonsurvivors out of 16 ( which includes 13 patients of low t3 and t4 and 3 patients of low t3 , t4 and tsh ) ] at presentation ( p = 0.5697 ) .
however out of 39 patients with normal t3 , only 8 patients succumbed to their illness ( p = 0.0111 ) when compared with 28 nonsurvivors in patients with low t3 .
there was no significant difference observed in the profile between survivors and nonsurvivors with respect to t4 , tsh and prolactin .
our study demonstrated that low t3 is an important marker of the severity of the illness and predicts mortality in icu .
our study showed low t3 ( 61% ) is the commonest abnormality followed by lowt4 ( 14% ) and low tsh ( 7% ) .
previous data from pediatric icu patients from mumbai showed low t3 in 80% , low t4 in 50% , and low tsh in 6.7% patients , and it was conducted in 30 critically ill children and controls of less than 12 years age admitted in pediatric icu .
two samples were collected from all patients , first at admission and second sample at the time of discharge from icu or death .
this study showed that mean t3 and t4 levels were significantly lower in critically ill children than controls .
the combination of low t3 and t4 together increased the mortality risk by 30 times .
our study differs in the age of the study population ( adults ) , number of study samples ( single sample at admission only ) , and lack of the control group from the previous study explaining the discrepancy in observed data .
euthyroid sick syndrome is the term used to describe thyroid hormonal changes in critically ill patients due to nonthyroidal illness .
low t3 is the earliest manifestation followed by low t4 and finally low tsh , indicating a continuum of changes in the spectrum .
a similar study involving pediatric icu patients showed that low t3 is a good predictor of mortality , and the risk is increased by 30 times when it is associated with low t4 .
however , that trend was not observed in our study , and this could be due to difference in age and number of study population and performing a single sample estimation instead of serial monitoring in our study . the demographic profile of the study patients did not differ significantly between the survivors and nonsurvivors .
cardiovascular diseases constitute the common reason as we have a combined medical icu and cardiac icu in our hospital .
this is followed by infectious diseases ( complicated malaria , sepsis with multiorgan dysfunction syndrome ) and neurological disorders ( cerebrovascular accident , subarachnoid hemorrhage and intra cerebral hemorrhage ) .
tsh showed a linear correlation with age in our study population [ figure 1 ] .
this was explained earlier by many investigators that the age - related elevation in tsh could be due to increasing autoimmunity , environmental , and genetic factors .
although insulin resistance and diabetes are also related to the age , our data did not show any correlation between hba1c and age .
this could be explained because of the selection bias of critically ill patients in the study which does not represent the general population .
elevated prolactin is seen in 31 patients of the study group . out of them , 14 survived and 17 succumbed to their illness .
prolactin is an immunomodulatory hormone involved in the endocrine response to the stress , and hyperprolactinemia is a common finding in initial phases .
blunted prolactin response during chronic stress is speculated to lead to increased susceptibility to infection .
previous reports demonstrate that admission and fasting glucose is an important marker of short - term outcomes in hospitalized patients .
our data did not show any difference in outcomes based on hba1c and glucose values .
hba1c does not vary with acute stress and admission hyperglycemia in icu patients may be an indirect marker of severe stress
. the limitations of our study include small sample size , single blood sample for hormonal assay , lack of control group , and serial monitoring for the hormonal changes .
to conclude , our study suggests that low t3 is an important marker of mortality in critically ill patients .
further studies involving a large number of patients with serial evaluation for changes in the hormone profile are required to unravel the mystery of critical care endocrinology .
objective : alteration in thyroid hormones are seen in critically ill patients admitted to intensive care units . 
 our objective was to study the thyroid hormone profile , prolactin and , glycosylated hemoglobin ( hba1c ) at admission and analyze their correlation with mortality.materials and methods : in this single centre , prospective , observational study , 100 consecutive patients ( 52 m ; 48f ) admitted to medical icu irrespective of diagnosis were included . 
 patients with previous thyroid disorders and drugs affecting thyroid function were excluded . 
 all participants underwent complete physical examination and a single fasting blood sample obtained at admission was analyzed for total triiodothyronine ( t3 ) , total thyroxine ( t4 ) , thyroid stimulating hormone ( tsh ) , hba1c , and prolactin . 
 the patients were divided into two groups : group 1  survivors ( discharged from the hospital ) and group 2  nonsurvivors ( patients succumbed to their illness inside the hospital ) . 
 the data were analyzed by appropriate statistical methods and a p - value of < 0.05 was considered significant.results:the mean age of the participants was 58.7  16.9 years and the mean duration of icu stay was 3.3  3.1 days . 
 a total of 64 patients survived , whereas remaining 36 succumbed to their illness . 
 the baseline demographic profile was comparable between survivors and nonsurvivors . 
 nonsurvivors had low t3 when compared with survivors ( 49.1  32.7 vs. 66.2  30.1 , p = 0.0044 ) . 
 there was no significant difference observed between survivors and nonsurvivors with respect to t4 , tsh , hba1c , and prolactin.conclusion:our study showed that low t3 is an important marker of mortality in critically ill patients . 
 admission hba1c , prolactin , t4 , and tsh did not vary between survivors and nonsurvivors .