Hyperthyroidism and Hypothyroidism

By SWA

Understanding Thyroid Values: The Significance of an Elevated fT3 Level Despite Normal Ultrasound Findings

The thyroid gland plays a crucial role in regulating the body’s metabolism through the production of hormones such as triiodothyronine (T3) and thyroxine (T4). These hormones affect nearly every tissue and organ system in the body. Proper interpretation of thyroid hormone levels is essential for diagnosing thyroid disorders, even when imaging techniques like ultrasound appear unremarkable.

Key Thyroid Hormones and Their Importance

The three main laboratory values used to assess thyroid function are:

  • TSH (Thyroid Stimulating Hormone): Produced by the pituitary gland to stimulate the thyroid to produce hormones.

  • Free T4 (fT4): The storage form of thyroid hormone with a longer half-life.

  • Free T3 (fT3): The active form of thyroid hormone, with a shorter half-life but greater physiological effect than T4.

Among these, T3 is considered more biologically active. According to medical research, T3 is approximately four times more potent than T4 in its physiological effects [1].

What Does an Elevated fT3 Value (>50) Indicate?

An fT3 value above 50 pmol/L—especially if it is significantly beyond the reference range of the testing laboratory—may be a strong indicator of thyroid overactivity (hyperthyroidism), even in the absence of abnormal ultrasound findings.

A normal ultrasound does not rule out biochemical thyroid dysfunction. In such cases, lab values provide essential insights that imaging alone cannot offer.

Possible causes for elevated fT3 include a inflammation of the thyroid, known as thyroiditis:

Thyroiditis:
This refers to inflammation of the thyroid gland, which can be caused by various factors, including viral infections, autoimmune conditions, or certain medications.

  • Early or subclinical hyperthyroidism

  • T3 toxicosis (isolated elevation of T3 with normal T4)

  • Exogenous intake of thyroid hormones

  • Thyroid nodules or toxic adenomas

  • Autoimmune disorders such as Graves’ disease (Morbus Basedow)

Reference Ranges and Interpretation

It’s important to interpret hormone levels in the context of reference ranges, which may vary between laboratories. For example:

  • TSH: 0.4–4.0 mU/L (normal for adults under 70)

  • fT3: Typically ranges from 3.1–6.8 pmol/L

  • fT4: Approximately 10–22 pmol/L

A TSH below the reference range (or suppressed TSH) with high fT3 supports a diagnosis of hyperthyroidism [2].

Contrasting Hyperthyroidism and Hypothyroidism

Hyperthyroidism Symptoms

Symptoms of thyroid overactivity can be systemic and include:

  • Rapid heartbeat and palpitations

  • Weight loss despite normal or increased appetite

  • Heat intolerance and sweating

  • Nervousness, tremors, and insomnia

  • Diarrhea and frequent bowel movements

  • Exophthalmos (protruding eyes) in Graves' disease

In some cases, the only biochemical sign may be an elevated fT3 level.

Hypothyroidism Symptoms

In contrast, a high TSH level with low fT3 suggests hypothyroidism. Symptoms include:

  • Fatigue, weight gain

  • Cold intolerance

  • Dry skin and brittle hair

  • Constipation

  • Depression and slow cognition

  • Bradycardia and muscle weakness

Types of Thyroid Diseases

Common thyroid disorders include:

  1. Struma (goiter) – enlargement of the thyroid

  2. Graves’ disease (Morbus Basedow) – autoimmune hyperthyroidism

  3. Hashimoto's thyroiditis – autoimmune hypothyroidism

  4. Thyroid cancer

  5. Hypothyroidism – underactive thyroid

  6. Hyperthyroidism – overactive thyroid

Disturbances in T4 to T3 Conversion

Even with normal TSH and T4 levels, deficient conversion of T4 to T3 can result in low T3 syndrome, causing hypothyroid symptoms. This may result from:

  • Genetic polymorphisms

  • Chronic illnesses

  • Certain medications, including:

    • Glucocorticoids

    • Heparin

    • Furosemide

    • St. John's Wort

    • Acetylsalicylic acid (Aspirin)

These substances can interfere with hormone binding, transport, or conversion [3].

Role of TSH Suppression

A suppressed TSH level (<0.01 mU/L) typically indicates hyperthyroidism, particularly when fT3 and/or fT4 levels are elevated. The most common causes include:

  • Graves’ disease – autoimmune stimulation of the thyroid

  • Toxic multinodular goiter

  • Autonomously functioning thyroid nodules

  • Medication-induced hyperthyroidism

Untreated hyperthyroidism can lead to serious complications such as atrial fibrillation, osteoporosis, and thyrotoxic crisis [4].

The Role of Thyroid Antibodies

Thyroid autoantibodies, including:

  • TRAb (TSH receptor antibodies)

  • TPO-Ab (thyroid peroxidase antibodies)

  • Tg-Ab (thyroglobulin antibodies)

can indicate autoimmune diseases such as Graves’ disease or Hashimoto’s thyroiditis. In Graves’ disease, antibodies stimulate the TSH receptor, increasing the release of T3 and T4, leading to hyperthyroidism and potentially causing exophthalmos [5].

Conclusion

An elevated fT3 level above 50 pmol/L, even with a normal ultrasound, should not be dismissed. It may indicate early or subclinical hyperthyroidism, which can progress and cause significant health issues if left untreated. Clinical correlation, further testing (including antibodies), and careful evaluation by an endocrinologist are crucial for accurate diagnosis and treatment planning.

References

  1. Brent, G. A. (2012). Mechanisms of thyroid hormone action. The Journal of Clinical Investigation, 122(9), 3035–3043. https://doi.org/10.1172/JCI60047 https://www.jci.org/articles/view/60047

  2. Ross, D. S., et al. (2016). 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism. Thyroid, 26(10), 1343–1421. https://doi.org/10.1089/thy.2016.0229 https://www.liebertpub.com/doi/10.1089/thy.2016.0229

  3. De Groot, L. J., & Chrousos, G. (2000). Thyroid hormone resistance. In: Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc. https://pubmed.ncbi.nlm.nih.gov/25905160/

  4. Bahn, R. S. (2010). Graves’ ophthalmopathy. The New England Journal of Medicine, 362, 726–738. https://doi.org/10.1056/NEJMra0905750 https://www.nejm.org/doi/full/10.1056/NEJMra0905750

    Hyperthyroidism and Graves’ Disease: https://www.uofmhealth.org/conditions-treatments/endocrinology-diabetes-and-metabolism/hyperthyroidism-and-graves-disease

Reference in German: 

Kapitel 19 – Ein Update zur Entwicklung fortschrittlicher Arzneimittelverabreichungssysteme zur Behandlung von Hyperthyreose https://www-sciencedirect-com.translate.goog/science/article/abs/pii/B9780323996167000037?_x_tr_sl=en&_x_tr_tl=de&_x_tr_hl=de&_x_tr_pto=sge

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742


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