A 5-year-old male child is admitted post valvular surgery to cardiac ICU.
A consultation is sent saying that there is a suspicion of secondary hypo-thyroidism. The results are as below
• T3–80 ng/dL (94–269 ng/dL)
• T4–3 μg/dL (7–15 μg/dL)
• TSH–0.02 μ IU/mL (0.5–5.0 μ IU/L)
What is the clinical diagnosis in this case?
What is the next step in evaluation of this patient?
What other parameters can help in the diagnosis?
The child was evaluated for other evidences of hypopituitarism as below The child is in the 5th centile which is expected as the child had untreated cyanotic congenital heart disease because of which the growth is stunted so probably growth hormone deficiency does not exist. The child has no evidence of micropenis so hypopituitarism was less of a possibility as it can be a marker of hypopituitarism. The child is maintaining blood pressure and is not requiring any ionotropic support which is an indirect evidence of normal cortisol levels. Thus, the clinical diagnosis in this child is kept as sick euthyroid syndrome as the other pituitary hormones are normal and there is no clinical evidence of hypopituitarism in this child. The levels of FT4 and FT3 are also done and FT4 is found to be in the normal range for age while FT3 is low. The other anterior pituitary hormones including random serum cortisol, FSH, LH and prolactin are measured in this child and the levels are found to be normal as per the clinical state of the patient. An IGF-1 level is done to screen for growth hormone deficiency and it is found to be in the normal range for age and sex matched controls. Different critical illness states leading to NTIS
• Sepsis and trauma
• Starvation
• Cardiac dysfunction
• Renal disease
• Hepatic disease
• Nonseptic shock
• Burns
• Respiratory failure
• Other disease states like systemic sclerosis
How to diagnose a case of NTIS?
Medicine
The diagnosis of sick euthyroid syndrome is very challenging. History may not provide any clue to the diagnosis of nonthyroidal illness syndrome (NTIS), only there may not be any past history of any thyroid illness and the recent illness may be severe enough to cause NTIS. The physical examination is mostly unremarkable. There may be masking of hypothyroidism or hyperthyroidism in such cases. The thyroid gland examination is mostly normal. The patient will mostly have signs of the illness he is having. The two general principles which should be kept in mind while evaluating thyroid function in a sick patient are that the thyroid functions should be done only if there is a strong suspicion of thyroid disease and the full thyroid profile is mostly necessary for proper interpretation of results. Within hours after the illness the level of T3 decrease while the level of T4 and TSH may increases slightly. If any patient has a low TSH value then if the T3 is low it may go in favor of sick euthyroid syndrome and if the T3 is high it is suggestive of hyperthyroidism.
Some patients who are very sick may have low T3 value even with hyper-thyroidism. The measurement of FT4 as it may mostly be in the normal range in normal patients even in the sick state except in cases where the patient is very sick where even FT4 may decrease. In most cases of hyperthyroidism TSH is suppressed to less than 0.01mIU/mL but in cases of NTIS it is mostly more than 0.01 mIU/mL. In the recovery phase the level of TSH mostly reaches up to 20 mIU/mL but in about 3% cases it may even reach up to 30 mIU/mL. The levels of TSH more than 30 mIU/mL mostly favors a diagnosis of primary hypothyroidism.
The cases of secondary hypothyroidism may be difficult to differentiate from nonthyroidal illness as both will show low TSH, T4 and T3 values but measurement of rT3 may provide some guidance though it has also not been shown to be a very accurate tool for differentiation. The measurement of prolactin, serum gonadotropin, stimulated cortisol may be of help in such cases where differentiation from secondary hypothyroidism is difficult. The low levels of other pituitary hormones may be an indicator of pituitary deficiency and may thus suggest secondary hypothyroidism. In some cases differentiation from hyperthyroidism is difficult as these patients may present with suppressed TSH with a normal value of T3 and T4 because of the coexistent catabolic state or infection. The levels of thyroxine-blinding globulin (TBG) may be decrease in such cases which may give a lower value of total T4 and T3, thus measurement of FT4 may be more useful in such cases as elevated FT4 with undetectable or suppressed TSH may confirm the diagnosis of hyperthyroidism. Any previous history of thyroid disorder, presence of goiter, history of irradiation to the neck or a surgical scar suggesting previous thyroidectomy may point towards a primary thyroid disorder. Thyroid imaging may provide some clue to the correct diagnosis.
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