The iatrogenic thyroid disease treatment

Diagnosis of thyroid diseases is often challenging with various manifestations that are non-specific such as lethargy, weight gain or loss, palpitations or weakness. A key factor in the diagnosis of thyroid disease such as hypothyroidism or hyperthyroidism, is accurate interpretation of thyroid hormone (TH i.e. T4, thyroxine; T3, triiodothyronine) and thyrotropin (TSH) concentrations that are commonly measured in a test called thyroid function test (TFT).¹ In a subgroup of patients, the interpretation of TFT is more challenging, either because the results appear to not correlate with the clinical picture i.e. a low TSH in patient with hypothyroid or normal TFT in patients is suspected to be strongly thyrotoxic.^1-2 In these patients, a structured approach that includes clinical reassessment of thyroid status, along with various potentiating factors [e.g. infection, stress, drug therapy] can help in identifying the possible solution to this discordant TFT. A referral to an endocrinologist is also warranted in certain cases. This is a case that correctly depicts the pitfall in the diagnosis and management of this condition.

Case report

A 70-years old man presented with weakness for two days to the neurologist. This has been a recurrent problem for the past two years. It typically occurs in clusters of a few days.

The patient has a background history of hypertension, diabetes and hypothyroidism. Both hypertension and diabetes were diagnosed about 10 years ago. His hypothyroid condition was diagnosed two years ago based on a low T4 and correspondingly high TSH at a primary care clinic.

His current medication is amlodipine 10mg daily, metformin 500mg daily and L-thyroxine 50 microgram. He was previously on L-thyroxine 75microgram which was adjusted based on a very low TSH level (<0.01 pmol/L).

He has seen many physicians over this past two years, but his underlying weakness is not improving. In fact, he has also been investigated for weight loss of 10kg over the past 2 years with various imaging methods and blood tumour markers, but without any positive lead.

On examination, he looks cachexic. He has mild pallor but otherwise has normal vital signs. His physical examination is also unremarkable including his physical examination. His latest HbA1c is 6.3%.

A list of investigation was ordered of which the most striking case was the TFT result. While the T4 results was within the normal range, TSH was 0.1. The thyroxine medication was stopped temporarily.

He was seen six week later. His TFT level recovered to normal. His weakness also improved on which he was very grateful to the treating physician. He gained 2 kg over this period of time. The neurologist attributed his symptoms as side effects due to iatrogenic thyroxin therapy. On further questioning, it was noted his thyroxine was started two years ago while he was having some upper respiratory illness.

Discussion

A small but significant number of patients may reveal TFT results that doesn’t correlate with their clinical status. In such scenarios, a careful search for confounding factors [e.g. physiological changes of age, pregnancy, intercurrent (non-thyroidal) illness or concomitant medication use] is required before jumping into further assessment is essential to avoid unnecessary waste and risk in unneeded investigation and treatment^.2 In particular, they may be a reduced physiological production of thyroid hormones and concurrent rise in TSH secondary to age which may not need treatment as noted in this case.²

Thyroid antibodies such as TPO-Ab and TRAb may help in diagnosis but not in all cases. In patients with Hashimoto’s thyroiditis, TPO-Ab is nearly always elevated.³ TRAb on the other hand helps in the differential diagnosis of hyperthyroidism.⁴ Only in very rare instances, acquired and genetic causes of discordant TFTs can be considered such as investigating for resistance to thyroid hormone and disorders of thyroid hormone transport or metabolism.^1,5 Looking ahead, the increasing availability of next generation sequencing will likely expand the reporting of genetic causes and disorders of TH transport, action and metabolism.²

The following (table 1) may help in delineating the cause of abnormal thyroid hormone levels but correlation with clinical condition is equally as important before a final diagnosis is reached.⁶

Conclusion

In conclusion, the treatment of thyroid disease may need more than just consideration of thyroid hormone levels to avoid any iatrogenic effect such as extreme weight loss and weakness.

Acknowledgement

The author would like to thank the patient for his kind informed consent in publishing of this case.

References

1. Koulouri O, Moran C, Halsall D, Chatterjee K, Gurnell M. Pitfalls in the measurement and interpretation of thyroid function tests. Best practice & research Clinical endocrinology & metabolism. 2013; 27(6):745-62.
2. Soh SB, Aw TC. Laboratory testing in thyroid conditions-pitfalls and clinical utility. Annals of laboratory medicine. 2019 ; 39(1):3-14.
3. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002; 87:489-99.
4. Barbesino G and Tomer Y. Clinical review: clinical utility of TSH receptor antibodies. J Clin Endocrinol Metab 2013; 98:2247-55
5. Singh BK and Yen PM. A clinician’s guide to understanding resistance to thyroid hormone due to receptor mutations in the TRα and TRβ isoforms. Clin Diabetes Endocrinol 2017; 3:8.
6. Sharma AN, Levy DL; Thyroid and Adrenal Disorders; in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice. St. Louis, Mosby; 2014:1676-93.

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