2

By ultrasound there are many nodules in Thyroid gland but all thyroid tests (TSH,T4,T3, microsomal and thyreoglobulin antibodies) are within normal range but there is clear heperthyroidism signs like hair thinning,anxiety,irritability,cardio neurosis,fatigue etc. Why lab tests don't show any disfunction? What is the cause of these overactive thyroid signs?

1 Answer 1

2

This constellation may result from at least five reasons:

  1. Hypothesis #0: Both conditions (thyroid nodules and symptoms of hyperthyroidism) are independent. Hyperthyroid symptoms including anxiety, hair loss, fatigue and palpitations are unspecific. Although they are typical for thyrotoxicosis, they may also result from other conditions, e.g. masked depression or pheochromocytoma.

  2. Hypothesis #1: The nodules represent fully compensated toxic adenomas, where somatic mutations lead to constitutive activation of TSH signaling. Since autonomic production is fully compensated, concentrations of thyroid hormones remain within their respective reference ranges. Symptoms of thyrotoxicosis result from deviation of free T4 concentrations from the personal set point of thyroid homeostasis. It is well known that the intra-individual variation of TSH and free T4 concentrations is much smaller than inter-individual variance (see http://www.ncbi.nlm.nih.gov/pubmed/11889165 and http://www.ncbi.nlm.nih.gov/pubmed/25567792 ). This is a consequence of an individual set point of the pituitary-thyroid feedback control mechanism, which is encoded as TRH signaling from the hypothalamus. Deviations of thyroid hormones within the reference range may still lead to symptoms if they are far from the personal set point. See http://www.ncbi.nlm.nih.gov/pubmed/26635726 for a review article discussing this topic and http://www.ncbi.nlm.nih.gov/pubmed/24480737 for a method for reconstructing the personal set point.

  3. Hypothesis #2: This is somewhat similar to hypotheses #1. The nodules represent fully compensated toxic adenomas (like in hypothesis #1), but they predominantly produce T3, which results from intracellular hyperdeiodination (ensuing from constitutive activation of TSH signaling and consecutive stimulation of the distal part of the TSH-T3 shunt). T3 concentrations remain within their reference ranges, but are above the range of concentrations that are appropriate for the personal receptor sensitivity. See http://www.ncbi.nlm.nih.gov/pubmed/23339744/ for a discussion of this topic. It may be helpful to calculate the sum activity of peripheral deiodinases (SPINA-GD), see also http://www.ncbi.nlm.nih.gov/pubmed/27375554 for a methodological overview.

  4. Hypothesis #3: The thyroid nodules produce non-classical thyroid hormones (e.g. 3,5-T2, a highly active T4 metabolite), which destabilize the heart rhythm and exert other symptoms of hyperthyroidism. This is an understudied topic. One of the few papers discussing this condition is http://www.ncbi.nlm.nih.gov/pubmed/26279999 .

  5. Hypothesis #4: T3 is secreted episodically from thyroid nodules, so that it is missed from diagnostic work-up. This is also an understudied topic. See http://www.ncbi.nlm.nih.gov/pubmed/2045066 for more details.

It may be beneficial to determine concentrations of free T3 and free T4 (rather than total T3 and total T4) in order to avoid false negative results due to low plasma protein binding.

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service and acknowledge that you have read and understand our privacy policy and code of conduct.

Not the answer you're looking for? Browse other questions tagged or ask your own question.