Diabetes & Metabolic Syndrome: Clinical Research & Reviews 11S (2017) S57–S59

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Diabetes & Metabolic Syndrome: Clinical Research &

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Original Article

Impact of diabetic ketoacidosis on thyroid function tests in type 1

diabetes mellitus patients
Homeira Rashidi* , Seyed Bahman Ghaderian, Seyed Mahmoud Latifi, Forogh Hoseini
Health Research Institute, Diabetes Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, 61357-15794, Iran

A B S T R A C T

The aim of current study was to evaluate the function of thyroid during diabetic acidosis, just after the treatment and two weeks after the treatment.
This was the analytic study. The study subjects included 20 patients, aged 18–36 years old, with type1 diabetes and diabetic ketoacidosis. All subjects
were evaluated for thyroid function tests such as triiodothyronine (T3), thyroxine (T4), T3 resin uptake (T3RU), free T3 (FT3), free T4 (FT4) and thyroid
stimulating hormone (TSH), before treatment. After completing DKA treatment and two weeks after discharge, the thyroid function tests were repeated
on the subjects and the results were analyzed using paired T-test, ANOVA or repeated measure and Pearson correlation tests. the current study showed
that the mean levels of T3 and T4 were at hyperthyroid range and lower than normal before the treatment and significantly increased after the
treatment (P < 0.001). The serum levels of T3RU, FT4 and T4 were at the normal range, but their mean level increased significantly following the
treatment progression (P < 0.001).A significant relationship was observed among blood pH and the serum levels of FT3 and T3, before the treatment;
the lower pH, the lower levels of FT3 and T3. The results of the current study showed that DKA causes euthyroid sick syndrome. The disease
complications were resolved two weeks after treatment and the severity of acidosis was the main factor to decrease the level of active form of thyroid
hormones such as FT3 and T3.
© 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

1. Introduction hyperglycemia which lead to more severe findings (1). Since

Altered thyroid function in systemic diseases and stress
conditions is still a complicated problem. It seems that these
changes occur at all levels of hypothalamic-pituitary-thyroid
axis and the situation is called non-thyroidal illness syndrome
(NTI) or euthyroid sick syndrome. The changes consist of lower
levels of free T3 (FT3) and total T3 (TF3), lower level of T4,
increase of reverse T3 and changes in thyroid stimulating
hormone (TSH) (1).
Changes in thyroid function followed by stress occur in 75% of
the hospitalized patients (2). These changes can occur within
hours after onset of a disease. Some studies revealed that T4
levels lower than 4 and 2 mg/dL are associated with 50% and 80%
mortality, respectively. Other evidence also suggested that
decrease in T3 level, increase in RT3 level and decrease in T3/
RT3 ratio are an independent factors affecting patients’ lifetime
(3). Ketoacidosis is one of the most severe body stresses, which is
an acute outcome of diabetes. Metabolic disorders can happen in
line with a slight acidosis spectrum along with mild
* Corresponding author.
E-mail addresses: hrashidi2002@gmail.com (H. Rashidi),
bahmanint@yahoo.com (S.B. Ghaderian), sml1381@yahoo.com (S.M. Latifi),
hoseini.forogh@yahoo.com (F. Hoseini).
diabetic ketoacidosis (DKA) is a major stress to the body, it is
assumed
that the healthy thyroid involves in euthyroid sick syndrome.
There are a few studies in this regard; a study (1992) in India
evaluated the direct effect of DKA on thyroid function and
reported that only the level of total T3 was within hypothyroid
range before the treatment and returned back to normal just after
the treatment (4), but the study did not show the relationship
between the ketoacidosis and thyroid function changes, the
affecting factors and suitable time to evaluate the thyroid
function in patients with DKA. Hence, the current study aimed
to evaluate thyroid function in DKA and two weeks after the DKA,
more comprehensively.
In the current analytic epidemiology conducted in Imam
Khomeini Hospital of Ahvaz, Iran, in the spring and summer of
2010, 20 subjects (12 females and 8 males), aged 18–38 years, with
diabetic type 1 (insulin-dependent diabetes) and ketoacidosis,
without any history of thyroid problems, systemic diseases and
using drugs which interfere with thyroid function were enrolled
into the study.
Subjects were admitted in the emergency ward of the hospital
and treated after performing thyroid function tests as triiodothy-
ronine (T3), thyroxine (T4), T3 resin uptake (T3RU), free T3 (FT3),
free T4 (FT4) and thyroid stimulating hormone (TSH).

http://dx.doi.org/10.1016/j.dsx.2016.12.001
1871-4021/© 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.
S58 H. Rashidi et al. / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 11S (2017) S57–S59

The thyroid function was retested just after the treatment and (Continued)
two weeks after the treatment; the results were analyzed using FT3 T3 T4 FT4 TSH T3RU
paired T-test, ANOVA and repeated measure.
Just after the treatment
PH r 0.149 0.44 0.171 0.325 0.279 0.044
P-Value 0.541 0.52 0.47 0.162 0.233 0.586
2. Results HCO3 r 0.150 0.207 0.174 0.269 0.351 0.156
P-Value 0.54 0.381 0.46 0.251 0.129 0.511

The mean (SD) age of the subjects was 24  6.8 years old; two
subjects only showed the primary demonstrations of DKA and the
rest of the subjects with the mean age of 25  1 years were treated
by insulin upon diagnosis. The percent of hemoglobin A1C in the
subjects was 13.4  /0.41. Weakness and lethargy were the main
causes of referring to the hospital.
The subjects were admitted to the emergency ward upon arrival
with PH = 7.16  0.08, HCO3 = 8.7  3.7 mEq/L[h1] and blood sugar
(BS) = 430  20.3 mg/dL, based on the performed thyroid function
tests. By treatment onset, the subjects came out of DKA and the
following measures were recorded: PH = 7.36  0.01, HCO3 = 18.4
 20.1 mEq/L and BS = 185 mg/dL.
Two weeks after hospital discharge, the thyroid function and
blood gases were retested and the arterial blood gas (ABG) value
was reported accordingly: pH = 7.40  0.17, HCO3 = 23.9  0.64
mEq/L and BS = 149 mg/dL.
The level of free T3 was in the hypothyroid range (147  0.4 ng/
dL) at the time of admission and after the treatment dropped to
2.61  0.8 ng/dL and decreased to 3.8  0.86 ng/dL, both in the
normal range. Results of the repeated measure test showed that
the level of free T3 before the treatment significantly rose to the
normal range just after treatment and two weeks after the
treatment (P = 0.001); the highest rate of increase was observed
just after the treatment.
The level of total T3 was lower than normal range (86  25.7 ng/
dL) before the treatment which rose to the normal range
(109.5  24.6 and 161.25  38 ng/dL) just after treatment and
two weeks after the treatment, respectively.
Comparing the means of total T3 before and after treatment was
shown significant differences between them (P = 0.001). Results of
paired T-test showed significant increase between the mean levels
of both groups.
The mean levels of FT4 were in the normal range, before the
treatment (1.07  0.43 ng/dL), just after the treatment
(1.26  0.45 ng/dL) and two weeks after the treatment
(1.58  0.62 ng/dL); results of repeated measure test showed a
significant difference between the three rates, indicating the
increase of FT4 level (P = 0.001).
The mean levels of total T4 before, just after treatment and two
weeks after the treatment were in the normal range 7.6  2.53,
7.98  2.59 and 8.41  2.51, respectively (P = 0.014). There was a
significant difference between the mean levels of total T4, but not
so high as the previous parameters.
The mean level of T3RU was 1.7  0.46 before the treatment,
which rose to 6.7  0.84 and 4.05  0.77 just after the treatment
and two weeks after the treatment, respectively. There was a
significant different between the three levels (P = 0.001).
To evaluate the relationship of different parameters (T3RU,
FT4, T4, FT3 and T3) with pH and HCO3 in different situations of
before the treatment, just after the treatment and two weeks
after the treatment, the Pearson correlation coefficient was used
and the results are shown in the following table:
FT3 T3 T4 FT4 TSH T3RU
Before the treatment
PH r 0.546 0.5 0.161 0.78 0.002 0.130
PH P-Value 0.015 0.009 0.498 0.44 0.993 0.585
HCO3 r 0.411 0.467 0.062 0.032 0.012 0.132
P-Value 0.072 0.049 0.79 0.895 0.959 0.580
Two weeks after the treatment
PH r 0.201 0.202 0.161 0.253 0.434 2.246
P-Value 0.396 0.406 0.499 0.282 0.056 0.297
HCO3 r 0.042 0.096 0.089 0.036 0.279 0.267-
P-Value 0.859 0.702 0.709 0.88 0.233 0.256
According to the above tables, there was a significant
relationship between pH, FT3 and T3 levels before the treatment
(P > 0.015); in other words, by growing the pH level, FT3 and T3
increase.
There was a significant relationship between the levels of HCO3
and FT3 before the treatment (P = 0.049); in other words, by
growing HCO3, FT3 increases and vice versa.
But there was no relationship between the levels of other
parameters just after the treatment and two weeks after the
treatment.
3. Conclusion
The current study showed that DKA is a major stress to the body
and the thyroid is in the stress condition up to the elimination of
stress. These changes were under the influence of the severity of
disease; complications resolved after two weeks following the
proper treatment and controlling blood sugar.
During the DKA, total T3 and FT3 were the affected parameters
and decreased more than the others. For better explanation, FT3
was in the hypothyroid range and T3 lower than the normal range,
and both rose to the normal range just after the treatment and two
weeks after the treatment.
Similar changes were also observed in FT4, T4 and T3RU due to
DKA, but the changes were less than those of FT3 and T3. These
parameters were in the normal range but showed significant
increase following the resolve of DKA. The level of TSH was in the
normal range in all steps with no significant changes following the
resolve of acidosis.
The results of the current study also showed that more severe
acidosis (lower pH) and higher HbA1C lead to decrease in the levels
of FT3 and T3; also, lower level of blood HCO3 before the treatment
leads to lower level of FT3.
Other thyroid parameters were not affected by acidosis and
blood sugar.
A study conducted in India (1992) showed changes in thyroid
function at RT3, T4 and T3 levels due to the DKA, which were
resolved following the treatment (4).
Another study conducted in Hong Kong (1991) on three groups
of patients with diabetes reported that lower control over blood
sugar results in lower levels of total T3 and higher levels of RT3
(5).
The current study also evaluated the other aspects of thyroid
function such as TSH, T3, T4, FT4, FT3 and T3RU parameters and
assessed the relationships of these parameters with pH, HCO3 and
blood sugar, which determine the severity of DKA.
The current study also evaluated the suitable time to assess
thyroid function in patients with insulin-dependent diabetes
considering the high prevalence of autoimmune thyroid diseases
among them.
 H. Rashidi et al. / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 11S (2017) S57–S59 S59

The current study shows that DKA causes euthyroid sick resolved; severity of acidosis was the main factor that decreased
syndrome. Two weeks after the treatment the changes were the active form of thyroid hormones (FT3 and T3).