Too Much of a Good Thing

This week in Morning Report, we discussed the case of a young woman who presented with clinical and biochemical signs of thyrotoxicosis after a viral URTI. This is a great topic to review for primary care providers and internists alike. We discussed physical exam findings, a diagnostic approach, investigations, and management — let’s recap these below.

Thyroid acropachy (top image) and pretibial myxedema (bottom) – two signs seen in significant hyperthyroidism. Image from Wikimedia Commons, used with attribution.

1. Hyperthyroidism affects all systems

Like most endocrinopathies, thyroid disease affects all systems of the body. We went through a head-to-toe review that is nicely captured in this table from an excellent 2016 Lancet review on hyperthyroidism.

Review of the multi-system manifestations of thyrotoxicosis, adapted from a great 2016 Lancet review article that I suggest you read. De Leo S, Lee SY and Braverman LE, ‘Hyperthyroidism’, The Lancet 2016 Aug. 388(10047);P906-918.

We looked at photos of a few advanced physical exam findings including thyroid acropachy, thyroid dermopathy/pretibial myxedema, and thyroid orbitopathy.

2. It is useful to differentiate between ‘thyrotoxicosis’ and ‘hyperthyroidism’

This might seem like a pedantic difference (“you say acidemia, I say acidosis”?), but differentiating between ‘thyrotoxicosis’ and ‘hyperthyroidism’ actually helps frame a useful approach to diagnosis/investigation, and obviates the need to memorize long lists.

  • Thyrotoxicosis: refers to any state of excess thyroid hormone, regardless of source
  • Hyperthyroidism: specifically refers to excess thyroid hormone due to increased synthesis and secretion by the thyroid gland

Remember that a healthy thyroid is composed of follicles that contain colloid — a goopy substance that contains thyroglobulin, or the precursor to thyroid hormones (T3/T4). When normal thyroid structure is disrupted (e.g., in thyroiditis), this causes colloid to leak out freely, leading to a thyrotoxic state.

Normal thyroid gland, showing colloid contained within follicles. Adapted from Dartmouth Histology.

3. Approach to Thyrotoxicosis With and Without Hyperthyroidism

With the above approach in mind, we discussed a list of high-yield diagnoses to consider when confronted with thyrotoxicosis:

4. Investigations

Initial investigations for thyrotoxicosis would typically consist of:

  • Thyroid function testing: TSH, T3, T4
    • TSH low, but T3/T4 normal: nonthyroidal illness, subclinical hyperthyroidism
    • TSH low, but T3/T4 high: thyrotoxicosis
    • TSH normal/high, and T3/T4 high: central hyperthyroidism (rare, think of TSH-secreting adenoma)
  • Thyroid Receptor Antibody (TRAB): to assess for Graves’ disease
  • Thyroid Ultrasound: to look at thyroid gland and assess for suspicious nodules
  • Radioactive Iodine Uptake/Scan: Based on pattern of iodine uptake into the thyroid gland, helps differentiate between Graves’ Disease (very high uptake of iodine, because the thyroid gland itself is hyperfunctioning) vs. Thyroiditis (very low uptake of iodine, because the thyroid gland is not hyperfunctioning, but rather leaking out thyroid hormone). The figure below depicts various levels of uptake with the corresponding diagnoses.
Patterns of radioactive iodine uptake in various thyroidal illnesses. Adapted from NucRadShare.

5. Approach to Treatment

In general, my approach to treatment of thyrotoxicosis is: treat the symptoms, and treat the illness. Remember the following pearls we discussed:

  • Beta blockade should be started if there is any evidence of cardiovascular symptoms (tachycardia, palpitations). Our medication of choice is usually propranolol 20-40 mg TID
  • Definitive treatment is directed at the underlying cause of thyrotoxicosis:
    • Graves’ Disease: Treatment options include antithyroidal drugs (methimazole > PTU), radioactive iodine therapy, or thyroidectomy.
      • PTU is preferred over methimazole in the first trimester of pregnancy (methimazole causes cleft lip and aplasia cutis)
      • PTU is preferred over methimazole in thyroid storm (inhibits conversion of T4 to T3)
      • Both PTU and methimazole can cause hepatotoxicity and agranulocytosis, among other side effects. Careful counselling of patients is key!
    • Subacute Thyroiditis: NSAIDs (typically naproxen) should be started for subacute/painful thyroiditis for analgesia and to decrease associated inflammation of the thyroid gland. Steroids may occasionally be needed if symptoms are not abated with NSAIDs. Patients must be counselled about the expected trajectory of subacute thyroiditis: hyperthyroid state, followed by possible hypothyroid state that requires levothyroxine replacement, and hopefully eventual euthyroid state
    • Infectious: Treat the infection
    • Drugs: Withdraw the offending agent

6. Further reading

This Lancet review article on Hyperthyroidism is very high-yield. Strongly recommended!

I hope you enjoyed this Morning Report! As always, please send all questions/comments to

Note: These recaps are based on real-life cases presented during weekly Morning Report; however, no real patient information/investigations/images/identifying details are presented. Any clinical information presented has been modified and completely de-identified for privacy.

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