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Euthyroid Conversion

Authors: Sanjay Kalra, Ahmed Hussein Rahoma, Yashdeep Gupta

Thyroidology is a vast field, which continues to expand and evolve. The science of thyroidology has been enriched by cross-disciplinary contact between endocrinology, surgery, radiology, nuclear medicine and pathology. Though professionals from these subjects may differ in their approach, they are united in their aim to achieve euthyroid health for all.

Based upon their expertise, some medical professionals may have limited contact with a person living with thyroid dysfunction. Others, however, may be engaged in long-term or chronic care of thyroid disease. Availability of, or access to, modern screening, diagnostic, monitoring, and therapeutic techniques and interventions may vary according to the healthcare setting. These factors contribute, in no small measure, to the subtle interdisciplinary differences noted in approaches to thyroid management. While endocrinologists tend to focus more on the function of the thyroid gland, surgeons are more concerned with its anatomy. Both function and structure, however, are intertwined.

Euthyroid conversion

One aspect that needs clarification is the concept of euthyroid conversion. Though frequent in endocrine surgical circles (personal communication: Prof Ahmed Hussein Rahoma, Malaysia), this term is not popular in endocrine medicine. We explore the meaning of this phenomenon, list its differential aetiology, and expand upon its rational use in modern thyroidology.

The adjective “euthyroid” or the noun “euthyroidism” can be taken to describe normal thyroid structure and function. Though this is the accurate meaning of euthyroidism, modern endocrinology tends to view euthyroidism as a term that conveys normal thyroid function.1 This is evident from phraseology such as euthyroid goiter or euthyroid nodular goiter. This means that the term euthyroid conversion may be taken to refer to having, or restoration to, normal thyroid function, with or without change in gross anatomy, imaging findings or microscopic features. Euthyroid conversion may therefore be defined as a phenomenon in which euthyroid functional status is attained, temporarily or permanently, without the need for ongoing medical therapy, in a person with reliably documented thyroid dysfunction. Euthyroid conversion may occur in people with hypo- or hyperthyroidism of varying aetiologies. Some situations where such conversion may occur are listed in Table 1. The ambit of euthyroid conversion excludes patients with autoimmune thyroid disease who report euthyroid function while on maintenance levothyroxine or antithyroid drug therapy. It also excludes people who may have had “abnormal” thyroid function tests due to sampling or laboratory errors – or unverified history of thyroid abnormality.

At the same time, euthyroid conversion includes patients who recover from curable causes of hypo- or hyperthyroidism and those who achieve remission (whether spontaneous or drug-facilitated) from chronic thyroid dysfunction.

Classification of conversion

We may study euthyroid conversion according to the aetiology of thyroid dysfunction or the aetiology of euthyroid conversion. Both methods provide an easily understandable overview of the phenomenon and are best studied concurrently (see Table 1).

Conversion to a euthyroid state can occur in settings of both hypo- and hyperthyroidism. Euthyroid conversion in hypothyroidism may be spontaneous (e.g. in Hashimoto’s thyroiditis) due to nonpharmacological intervention (e.g. discontinuation of dietary or drug-based goitrogens). A case report of conversion of hypothyroidism due to the occurrence of Graves’ disease in a girl with congenital ectopic thyroid has been reported.2 Another publication describes euthyroid conversion in Graves’ disease after renal transplantation.3

In hyperthyroidism, euthyroid conversion may be spontaneous, or due to medical, surgical, or nuclear medicine interventions. Thyroiditis, in which destruction of thyroid cells causes release of thyroid hormones into the circulation, is implicated in about 10% of thyrotoxicosis cases.4 Examples of spontaneous achievement of euthyroidism may be noticed in the self-limiting natural history of subacute thyroiditis and postpartum thyroiditis.5 More often, however, euthyroidism occurs due to medical, surgical, or nuclear intervention in people with hypothyroidism.

Hashimoto’s thyroiditis can also be associated with transient hypothyroidism. Generally, the progression from euthyroidism to hypothyroidism has been considered an irreversible process due to thyroid cell damage and loss of thyroidal iodine stores. However, it is now clear that up to one-quarter of patients who are hypothyroid may spontaneously return to normal function over the course of several years. This sequence may reflect the initial effect of high titers of thyroid stimulation-blocking antibodies, which fall with time and allow thyroid function to return.6

Relevance of euthyroid conversion

The terms ‘remission’ and ‘cure’ are not popular in discussions on the surgical management of thyrotoxicosis. However, they are routinely used with reference to successful medical management of Graves’ disease.7 The success of radioiodine ablation is studied not in the context of euthyroid conversion, but rather in terms of prevention of long-term hypothyroidism.8 Hence, the phrase ‘euthyroid maintenance’ rather than ‘conversion’ would be better suited to an assessment of efficacy of radioiodine ablation.

It is in thyroid surgery, the term ‘thyroid conversion’ gains traction. Thyroid surgery has made dramatic advances in recent years, with minimally invasive thyroid surgery gaining ground.9,10 Tissue preservation is a cardinal principle of modern thyroid surgical practice, which aims to limit excision of toxic or dysplastic tissue to the minimum.9 In such a situation, the operating surgeon faces a therapeutic dilemma. On one hand, he or she aims to achieve euthyroidism, while on the other, he or she strives to preserve as much thyroid tissue as possible.11 This makes it difficult to strike a balance between postoperative hypothyroidism (due to excessive gland tissue removal) or surgical failure (caused by inadequate removal of thyroid mass). This is even more challenging in patients with toxic nodular goiter, where the decision to perform a nodule excision or a hemi thyroidectomy can be difficult. Large goiters also present a therapeutic challenge, as the operation surgeon has to balance clinical concerns with aesthetic ones. Clinical issues are multifaceted in themselves, with the surgeon, endocrinologist and anaesthesiologist having different opinions about what defines an adequate and safe surgery.

Euthyroidism is a desirable endpoint in any thyroid dysfunction. It stands to reason, therefore, that one must aim to maximise euthyroid conversion in patients undergoing thyroid surgery. Published data suggest that euthyroid conversion can be achieved with surgery, with a low risk of complications.10,12

 Conclusion

Euthyroid conversion is the aim of therapeutic intervention in thyroid dysfunction. Different terms, including remission, cure and maintenance, have been used in the context of medical and radioactive therapy. In thyroid surgery, however, the definition of an optimal surgery is open to debate. Surgical, medical, aesthetic and anaesthesiological concerns  have to be balanced by the treating team. This article aims to highlight the phrase “euthyroid conversion” and stimulate cross-disciplinary debate about its appropriate use in thyroidology.

Table 1: Spectrum of euthyroid conversion

In hyperthyroidism
  • Graves’ disease

o   Drug induced

o   Postsurgical

o   Post-radioiodine ablation

  • Toxic nodular disease

o   Postsurgical

o   Post-radioiodine ablation

  • Cure of other causes of hyperthyroidism

o   Discontinuation of offending therapy e.g. amiodarone

o   Correction of cause, e.g. struma ovarii, subacute thyroiditis

  • Self-limiting course, e.g. gestational thyrotoxicosis
  • Spontaneous, e.g. thyroiditis
In hypothyroidism
  • Remission of immune thyroid disease

o   Spontaneous

  • Cure of other causes of hypothyroidism

o   Discontinuation of offending therapy, e.g. amiodarone, lithium

o   Correction of cause, e.g. thyroid hormone resistance due to obesity

  • Self-limiting course of disease, e.g. hypothyroidism treated during preconception/gestation

References

  1. Euthyroid, Available at: https://www.dictionary.com/browse/euthyroid?s=t (accessed August 15, 2018).
  2. Szczepanek-Parulska E, Ruchala M, Hernik A. Unexpected conversion from hypothyroidism to an euthyroid state due to Graves’ disease in a patient with an ectopic thyroid. Endocrine. 2014;46:684–5.
  3. Lee Y, Butani L, Glaser N, Nguyen S. Resolution of Graves’ disease after renal transplantation. Pediatr Transplant. 2016;20:590–3.
  4. Franklyn JA, Boelaert K. Thyrotoxicosis. Lancet. 2012;379:1155–66.
  5. Prajapati S, Hernandez-Prera JC. Putting All the Pieces Together: Clinical, Macroscopic and Microscopic Characteristics of Subacute Thyroiditis. Head and neck pathology. 2018 Feb 9:1-4. doi: 10.1007/s12105-018-0890-x. [Epub ahead of print]
  6. Takasu N, Yamada T, Takasu M, et al. Disappearance of thyrotropin-blocking antibodies and spontaneous recovery from hypothyroidism in autoimmune thyroiditis. N Engl J Med. 1992;326:513–8.
  7. Burch HB, Cooper DS. Management of Graves’ disease: a review. JAMA. 2015;314:2544–54.
  8. Smith TJ, Hegedüs L. Graves’ disease. N Engl J Med. 2016;375:1552–65.
  9. Aggarwal V, Kiran RB, Garg M, Khandelwal D. Transoral thyroidectomy, vestibular approach using two ports: A novel technique. Thyroid Research and Practice. 2017;14:75.
  10. Lombardi CP, Carnassale G, D’Amore A, et al. Morbidity from minimally invasive video-assisted thyroidectomy: a general review. Gland Surg. 2017;6:488­–91.
  11. Feroci F, Rettori M, Borrelli A, et al. A systematic review and meta-analysis of total thyroidectomy versus bilateral subtotal thyroidectomy for Graves’ disease. Surgery. 2014;155:529–40.
  12. Liu Y, Liu B, Liu RL, et al. A new method of subtotal thyroidectomy for Graves’ disease leaving a unilateral remnant based on the upper pole. Medicine. 2017;96:e5919.
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