Discrepant TFT’s
| HOSP # | WARD | Endocrine Clinic (OPD) | |
| CONSULTANT | Dr. Jody Rusch | DOB/AGE | 32 Year female |
Abnormal Result
The clinician, an endocrinologist, phoned about discrepant results: Suppressed TSH, Low Free T4 and Normal (upper end of reference interval) Free T3.
| Date | 09/12/2020 |
| TSH (mIU/L) | 0.05 L |
| Free T4 (pmol/L) | 4,8 L |
| Free T3 (pmol/L) | 6,4 |
Presenting Complaint
The patient was known with Graves Disease complicated by quite severe Graves Eye Disease (orbitopathy).
History
Known with Graves disease with positive antibodies to TSH-receptors.
Examination
The clinical examination for this patient is not available, but the following is important:
Interestingly, patients may have no ocular symptoms at all, but may sometimes be distressed by the appearance of their eyes. The major ocular symptoms include:
- A gritty or foreign object sensation
- Excessive tearing that is often made worse by exposure to cold air, wind, or bright lights
- Eye or retroocular discomfort or pain
- Blurring of vision
- Diplopia
- Color vision desaturation
- Loss of vision in severe cases
The characteristic signs of Graves’ orbitopathy are proptosis (exophthalmos), tearing, and periorbital edema. In more severe disease, there may be severe conjunctival inflammation and ulceration from over exposure.
Laboratory Investigations
| Date | 09/12/2020 | 11/05/2020 | 08/11/2019 | 24/05/2019 | 29/01/2019 | 10/12/2018 |
| TSH (mIU/L) | 0.05 L (Rerun 0.05) | 0.02 L | <0.01 L | <.01 L | <.01 L | |
| Free T4 (pmol/L) | 4,8 L (Rerun 4.9) | 65,7 H | δ+>100.0 H | 48,4 H | 42,7 H | 44 H |
| Free T3 (pmol/L) | 6,4 (Rerun 6.4) | 19,6 H |
As above, the history of Graves disease is clear, which includes a suppressed TSH and raised Free T4 and Free T3.
Other Investigations
The Free T4, Free T3 and TSH was re-run on 10/12/2020, QC checked on these three analytes (all was within normal range) and pre-analytical labeling errors excluded as far we could.
Final Diagnosis
Graves eye disease, now with hypothyroidism.
Take Home Message
In Graves’ disease, the main auto-antigen is the thyroid-stimulating hormone (TSH) receptor (TSHR), which is expressed primarily in the thyroid but is also expressed in adipocytes, fibroblasts, and a variety of additional sites and appears to be closely aligned with the insulin-like growth factor 1 (IGF-1) receptor. TSHR antibodies and activated T cells also play an important role in the pathogenesis of Graves’ orbitopathy by activating retro-ocular fibroblast and adipocyte TSHR and IGF-1 receptors and initiating a retro-orbital inflammatory environment.
The retro-orbital tissue (and ocular muscles) increase in volume due to this inflammatory milieu, fibroblast proliferation and the accumulation of hydrophilic glycosaminoglycans (GAG’s), most notably hyaluronic acid.
Sometimes orbitopathy occurs in patients with hypothyroidism (high TSH, low free T4) due to classical chronic autoimmune thyroiditis (Hashimoto’s disease), and these patients may have stimulating TSH receptor (TSHR) antibodies but inadequate thyroid reserve.
In summary, the most important factors for development of Graves Eye Disease (orbitopathy) seems to be:
- Graves Orbitopathy antigen (which is the TSH-receptor): these are expressed extra-thyroidally, especially retro-orbitally.
- Role of TSH receptor antibodies
- Role of T-cells: Retroocular fibroblasts secrete GAG in response to cytokines such as interferon gamma and tumor necrosis factor (TNF)-alpha secreted by helper (CD4+) T cells of the Th1 type.
In cases of hypothyroidism, the action of deiodinase is increased to protect against the effects of hypothyroidism, likely the explanation of the increased Free T3 in this patient (compared to the low Free T4).