Hello and welcome to this episode. Today we will be discussing an approach to a low TSH.

We will be going over 2 review studies from The Journal of Clinical Endocrinology and Metabolism and then Cleveland Clinic Journal of Medicine. But first today’s question:

A 50-year-old postmenopausal woman with no other notable history presenting with palpitations, frequent bowel movements, and tremors. She has no family history of thyroid dysfunction. She has mild tachycardia. Her thyroid gland is 20 g and nontender to palpation. Her TSH is < 0.1.

What is the best next step in evaluating this patient?

A Thyrotropin receptor antibodies

B Check Total T4

C Check Free T4 and T3

D Thyroid US

And the answer is T4 and Total T3. These questions, while seemingly simple, are actually guaranteed on board exams.

Initial thyroid function evaluation should start with TSH. In this case the TSH is low and there is clinical suspicion for hyperthyroidism. If TSH is suppressed, the immediate next step is to check T4 and T3 to confirm and further characterize the thyroid dysfunction (overt vs subclinical). This is worth repeating: investigating the cause of the suppressed TSH by checking thyroid hormones is important in determining how to proceed with evaluation and treatment.

In this question, checking the Free T4 is favored over total T4 because Total T4 levels can be affected by alterations in binding proteins. Checking T4 only is not sufficient because there are cases of isolated T3 thyrotoxicosis. Ordering receptor antibodies or starting treatment are premature at this point. Thyroid US is not a routine part of the diagnostic algorithm to hyperthyroidism. For this case, an iodine uptake scan could be performed to differentiate thyroiditis from true hyperthyroidism, but this would not be the best next step in this question.

An Approach to Low TSH

If the T4 and T3 level are normal, repeat TSH, T4, and T3 in 6-8 weeks before giving a diagnosis. When TSH suppression is transient, most times thyroid dysfunction will be resolved in this time. A suppressed TSH that is not normalized in this period requires more investigation.

Low TSH can be differentiated by level of TSH suppression such as mild (TSH 0.1 – 0.4 mIU/L) milli-international units per liter and complete TSH suppression TSH < 0.1 mIU/L. It is unclear the incidence of low TSH within the population but in a representative sample of the US without known thyroid condition that 0.7% of patients had suppressed TSH (< 0.1 mU/L) and 1.8% of patients had a TSH level below the reference range (< 0.4 mU/L)

It can be helpful to think of the etiologies of low TSH 1) in their relation to the pituitary/hypothalamus or 2) in terms of accuracy of the assay measurement / drug effect

Relationship to Pituitary/Hypothalamus

· Category #1: low TSH due to an appropriate pituitary response to high thyroid hormone, the pituitary is actively attempting to reduce thyroid hormone production because of advanced or early elevated thyroid hormone levels

In this category differentiating the source of the excess thyroid hormone can be helpful

· #1 Excess endogenous thyroid hormone production from multinodular goiter, autonomous thyroid nodule, Graves’ disease,

· #2 Exogenous thyroid hormone commonly from excess levothyroxine supplementation (iatrogenic or intentional in context of high risk thyroid cancer) or ingestion of natural thyroid preparations (athletic performance and integrative health) – in these cases exogenous T4 is suppressing TSH so will be characterized by low TBG

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