1. Thyroid dysfunctionThyroid dysfunction
in critical care settingsin critical care settings
Dr Pranab Kumar Sahana
MD, DM (Endocrinology)
Department of Endocrinology
NRS Medical College Hospital,
Kolkata
2. CaseCase
• A 61 year old man with severe
decompensated CHF admitted in ICU.
• He diureses well and responds
to initial therapy but does not regain
normal mental status as quickly.
• Blood sent to rule out reversible causes of
altered mental status.
• TSH is 13. free T4 is normal, but T3 is
low.
Is this patient hypothyroid?
How will you manage him?
3. Thyroid physiologyThyroid physiology
• > 99% of T4 and T3 is
bound to TBG, TBPA
and albumin
• 80% of T3 comes from
T4
• 0.3% of T3 and 0.02%
of T4 are free
• fT3 : metabolically
active hormone
4. Iodothyronine deiodinaseIodothyronine deiodinase
• D1: Outer and inner ring deiodination
Site: thyroid, liver, kidney, pituitary
Role: activation of T4 to T3
• D2: Outer ring deiodination
Site: brain, thyroid, pituitary, skeletal muscle
Role: activation of T4 to T3
• D3: Inner ring deiodination
Site: brain, skin ,pregnant uterus
Role: inactivation of T4 to rT3 and T3 to T2
5. Non thyroid illness syndromeNon thyroid illness syndrome
(NTIS)/(NTIS)/
Sick euthyroid syndromeSick euthyroid syndrome
• Alterations in thyroid hormone
concentrations during a variety of acute
and chronic illnesses in patients with no
previously diagnosed intrinsic thyroid
disease
• Wartfosky and Bunnan in 1982 coined the
term Sick Euthyroid Syndrome
• Prevalence: 40-70%
• Starvation, sepsis, surgery, myocardial
infarction, CABG surgery, trauma, bone
marrow transplantation
6. What clinical scenarios have beenWhat clinical scenarios have been
described in NTIS?described in NTIS?
• The most common scenario is a low normal TSH
with normal T4 and low T3.
• Low serum total T3: the most commonly
identified abnormality (70% of patients
• Low serum total T3 and T4: most common in
critically ill patients in the MICU.
• High serum total T4:(acute intermittent
porphyria, chronic hepatitis, primary biliary
cirrhosis).
• Low, normal or high TSH
7. Alterations in thyroid parametersAlterations in thyroid parameters
in hypothyroidism and non-in hypothyroidism and non-
thyroid illnessthyroid illness
Primary
hypothyroid
Central
hypothyroid
Non thyroid
illness
T4 Low Low Normal or
low or
elevated
T3 Low or low-
normal
Low or low-
normal
Low
rT3 Low or normal Low Elevated
TSH Elevated Low or normal High or
Normal or Low
8. Pathogenesis of thyroidPathogenesis of thyroid
dysfunction in critical illnessdysfunction in critical illness
• Reduction in D1 activation and induction of
D3 results in decreased T3 and increased
rT3
• Reduction in TBG , TTR, Albumin
• Presence of inhibitors of thyroid hormone
binding to proteins: NEFA, bilirubin,
indoxyl sulfate
• Decresed tissue uptake of thyroid
hormones
• Cytokines: IL1, IL6, TNF alpha
9. Thyroid axis during health andThyroid axis during health and
critical illnesscritical illness
10. Hypothalamic pituitary thyroid axisHypothalamic pituitary thyroid axis
in acute and chronic phase of criticalin acute and chronic phase of critical
illnessillness
• Nocturnal TSH surge
• Pulsatile TSH surge
• T4
• T3
• rT3
• TRH mRNA in
hypothalamus
Acute Chronic
absent absent
present absent
normal low
low very low
elevated normal
normal low
11. Relationship between serum thyroid hormoneRelationship between serum thyroid hormone
concentrations and severity of nonthyroidal illnessconcentrations and severity of nonthyroidal illness
12. Low T4 and mortality in SESLow T4 and mortality in SES
Mortality rate
• Total T4 < 3 µg/dl 84 %
• Total T4 < 5 µg/dl 50 %
• Total T4 > 5 µg/dl 15 %
Maldonado et al.Thyroid 1992
13. Prognostic impact of thyroidPrognostic impact of thyroid
hormones on outcomehormones on outcome
• In 1995, Rothwell and Lawler used thyroid
hormone levels to predict outcome in adult
intensive care patients
• showed that an endocrine prognostic index
based on intensive care unit admission
measurements of thyroid hormone levels is a
superior discriminator of patient outcome than
the APACHE II score.
Rothwell PM, Lawler PG: Prediction of
outcome in intensive care patients using
endocrine parameters. Crit Care Med 1995,
23:78-83.
14. Prevalence and pattern of sick euthyroidPrevalence and pattern of sick euthyroid
syndrome in acute and chronic non thyroidsyndrome in acute and chronic non thyroid
illnessillness
• Low T3 was found in 32.6% of cases and
combined low T3 and T4 was found
in13.1% of cases
• Severity of illness correlated with decrease
in T3 and T4
• Low T3 and T4 were associated with
increased mortality
Zargar et al.J Assoc Physician India 2004
15. A study on Endocrine Changes inA study on Endocrine Changes in
patients in Intensive Care Unitpatients in Intensive Care Unit
• A total of 50 men ( mean: 48.6 ± 16 yrs) and 30
women ( mean: 42.6 ±17.5 yrs) admitted to the
ITU of IPGMER & SSKM (Seth Sukhlal Karnani
Memorial) Hospital were studied.
• Patients with the preexisting endocrinopathies,
known intracranial disease or poisoning, drugs
known to affect endocrine axis were excluded
from the study.
• August 2005 and July 2006, were screened for
inclusion. 80 patients who met the inclusion and
exclusion criteria and had APACHE II scores >10
were enrolled in the study
Sahana et al. J Indian Med Assoc 2008
16. No of patients who had abnormalNo of patients who had abnormal
thyroid functionsthyroid functions (N=80)(N=80)
Parameters Number
(percentage)
Low T3 16 (20)
Low T3+T4 4 (5)
Low T3+FT4 12 (15)
Low T3+T4+FT4 10 (12.5)
High T4 6 (7.5)
High TSH (with normal
T3 + T4 + FT4)
6 (7.5)
Low TSH (with normal
T3 + T4 + FT4
10 (12.5)
Total 64 (78)Sahana et al. J Indian Med Assoc 2008
20. Should we treat low thyroidShould we treat low thyroid
hormones in critical illness ?hormones in critical illness ?
?
adaptive/protective
against hypercatabolism
or
maladaptive
21. Outcome of T4 replacement inOutcome of T4 replacement in
critical carecritical care
• In 12 patients with low T4 :
Normalization of serum T4 but T3 did not
normalize. Mortality was same in both
treated and controlled group.
Brent et al. J Clin Endocrinol Metab 1986
• Acute renal failure patients:
No effect on ARF severity. Mortality was
higher in the thyroxine group.
Acker et al. Kidney Int 2000
22. Outcome of T3 intervention inOutcome of T3 intervention in
critical carecritical care
• T3 administration in Sepsis:
improved pulmonary function, histologic
integrity and surfactant availability
• T3 administration in adults who underwent
myocardial revascularization or valve
replacement : no benefits
23. Outcome of T3 replacementOutcome of T3 replacement
in critical carein critical care
• In patients undergoing CABG, T3 administration:
improved cardiac output and decreased systemic
vascular resistance
Dulchavsky SA et al. J Cardiovasc Sugery 1994
• At release of cross clamp after myocardial
revascularizationT3 administration:
improvement in cardiac indexes, decreased
postoperative ischemia, mortality
Teiger E et al. Eur Heart J 1993
24. Thyroid hormone replacement inThyroid hormone replacement in
children after cardiac surgery – ischildren after cardiac surgery – is
it worth a try?it worth a try?
• Children after cardiac surgery are at specific risk
to develop a clinically important SES peri-
operatively.
• Despite clear evidence from the studies
available, the demonstrated beneficial effects and
the clear lack of negative effects make the
prophylactic supplementation of T3 a desirable
treatment option, especially in high-risk groups.
Nicolus A Haas et al. Critical Care 2006, 10:213
25. What should be theWhat should be the
replacementreplacement
• T3 : 50 µg/ day in divided doses
• T4 :100 µg/ day
• Serum T3 and T4 should be
monitored every 48 hrs
• Target serum T3 : 70-100 ng /dl
• T3 should gradually be tapered
• Serum free cortisol should be
estimated
26. Diagnosis of thyroid diseaseDiagnosis of thyroid disease
in setting of acute illness?in setting of acute illness?
• Do not rely on results of one test alone
• Wait at least a week after resolution of a NTI to
reassess thyroid status.
• Tips for primary hypothyroidism
• Hypothyroidism is a strong possibility if TSH is
>25-30. (will be above 20 only 3% of the time in
NTI)
• Subnormal free T4 in the absence of treatment
with agents that suppress TSH is strongly
suggestive of hypothyroidism
• Presence of goiter and anti-thyroid antibodies
favour primary hypothyroidism
• Elevated rT3 in the setting of TSH >10 renders
diagnosis of hypothyroidism unlikely.
27. Case follow upCase follow up
• While undergoing evaluation for
altered mental status, the patient is
found to have UTI and is treated for
the same. His mental status
improves. The patient recovers from
his CHF exacerbation and follow up
thyroid function tests one month
after his hospitalization showed
normal results.
28. Take home messageTake home message
• Replacement of T4 or T3 can not
cure patients who have NTIS
• Modest increment in overall
physiologic functions and decrease
in mortality
• Not a magic bullet which would
reverse all the metabolic changes
• Ongoing future trial will answer
