REVIEW: Low T3 in a thyroid patient caused myxedema coma

Myxedema ComaHere’s an example of the problem with judging thyroid hormone sufficiency for an individual on T4 replacement therapy by reference ranges for a larger healthy population.

In this article, a woman maintained on T4 monotherapy almost died from her low T3.

Only T3 therapy saved her from death by hypothyroidism, since she entered the extremely hypothyroid state of myxoedema coma.

This Laboratory’s reference range for free T3 was incredibly wide, much wider than most. Her Free T3 level was low but the reference range made it seem that she had “normal” thyroid hormone levels when they were actually in the basement, considering her body’s need for a higher level of thyroid hormone.

The researchers acknowledged that some individuals can have a higher “set point” for thyroid hormone before their thyroid gland fails, and that means that thyroid hormone levels in the lower part of the reference range may be extremely insufficient for a specific individual.

Source

Mallipedhi, A., Vali, H., & Okosieme, O. (2011). Myxedema coma in a patient with subclinical hypothyroidism. Thyroid: Official Journal of the American Thyroid Association, 21(1), 87–89.

Abstract

BACKGROUND: Myxedema coma is the extreme manifestation of hypothyroidism, typically seen in patients with severe biochemical hypothyroidism. Its occurrence in association with subclinical hypothyroidism is extremely unusual. We describe a patient with subclinical hypothyroidism who developed clinical manifestations of myxedema coma.

SUMMARY: A 47-year-old woman presented to our endocrine clinic with complaints of fatigue and biochemical findings of subclinical hypothyroidism.

She was started on treatment with thyroxine (T4) but remained unwell and was later admitted to hospital with hormone profile showing persisting subclinical hypothyroidism (elevated thyrotropin and normal free T4 [FT4] and free triiodothyronine [FT3]):

  • FT4 10.7 pmol/L (reference range 10.3-24.5),
  • FT3 2.7 pmol/L (reference range 2.67-7.03),
  • and thyrotropin (TSH) 6.09 mU/L (reference range 0.4-4.0).

She subsequently developed hypothermia (temperature 33.2°C), circulatory collapse, and coma. Biochemical profile showed hyponatremia, elevated creatinine phosphokinase, metabolic acidosis, and renal failure. An echocardiogram revealed a moderate-sized pericardial effusion.

We diagnosed myxedema coma and started treatment with intravenous T3.

She responded dramatically with improvement in level of consciousness and normalization of metabolic parameters.

We found no explanation other than hypothyroidism to account for the presentation.

Adrenocorticotrophic hormone (ACTH) stimulation tests excluded adrenal insufficiency, and serum gonadotrophins were within the normal reference range. FT4 estimation by equilibrium dialysis excluded analytical interference, and molecular analysis for the thyroid hormone receptor β (THRB) gene associated with thyroid hormone resistance was negative.

CONCLUSIONS: To the best of our knowledge this is the first report of myxedema coma in a patient with subclinical hypothyroidism. The reason for normal thyroid hormone levels is unclear but may reflect deviation from a higher pre-morbid set-point. The case highlights the importance of careful clinical evaluation in patients with disparate clinical and laboratory findings.”

Our commentary

Not only does this show the potential dangers at the low end of the Free T3 reference range, but it also shows the poor logic of applying the category “subclinical hypothyroidism” to a patient who is maintained on T4 hormone therapy.

The category of “subclinical hypothyroidism” is meant to be applied pre-diagnosis, when there is a possibility that hyperstimulation of a thyroid gland by TSH is effective in maintaining endogenous T4 and T3 levels.

“Subclinical hypothyroidism” is derived from population statistics of people who are NOT taking exogenous thyroid hormones.

Here is the problem with applying this category to a patient who has already been diagnosed and treated for primary hypothyroidism and is taking thyroid hormone.

  • T4-monotherapy not only supplements bloodstream T4 levels but it “locks in place” the TSH and T3 to the degree that a patient lacks healthy thyroid gland tissue.

Only the interplay between TSH and thyroid gland tissue enables a patient’s body to internally adjust thyroidal secretion of T3 and T4 to meet the changing needs of their body during illness and recovery from illness. A patient with a fully healthy thyroid gland has the ability to raise TSH temporarily above the normal reference range in order to quickly raise both T4 and T3 levels in bloodstream, and this happens during recovery from severe illness. Gradually the TSH will return to normal levels once their healthy set-point has been reestablished.

Such TSH-T4-T3 adjustments are simply not possible in a patient whose thyroid gland has been artificially “replaced” by a static dose of thyroid hormone.

When patients on thyroid therapy are maintained in a state of “subclinical hypothyroidism,” their T3 and T4 levels are being maintained by drugs for much longer than they would be if they had a healthy thyroid gland.

Living thyroid gland tissue plays a key role in patients’ recovery from Low T3 Syndrome in critical illness. If a patient has no thyroid gland tissue, they are not likely to recover from this Low T3 state in severe illness — UNLESS their thyroid hormone metabolism increases the rate of conversion of their T4 medication into a larger amount of T3 than usual (and this is extremely unlikely to happen in illness, when hormone inactivation is increased).

Therefore, recovery will most likely require supplementation with external T3 as in the case of this patient, for whom therapy with T4 alone was insufficient.