BACKGROUND
Papillary thyroid cancer is common and overall has an excellent prognosis. This is especially true of small papillary thyroid cancers (< 1 cm), called papillary thyroid microcarcinomas. These small cancers can often be monitored without the need for surgery or other treatment. This is called active surveillance. We know that in some patients, the small cancers will grow and surgery may eventually be needed.

One question is whether there is a role of levothyroxine therapy in the management of papillary thyroid microcarcinomas undergoing active surveillance. It is clear that levothyroxine therapy to keep TSH levels in the low normal to low range in patients that have undergone surgery for papillary thyroid cancer improves prognosis. Also, previous studies have suggested that a low normal TSH level may be associated with less cancer growth in younger patients with papillary thyroid microcarcinomas. However, to date, there is no study examining the use of levothyroxine therapy in papillary thyroid microcarcinomas undergoing active surveillance.

The current investigators looked back at their extensive experience in patients with papillary thyroid microcarcinomas undergoing active surveillance to evaluate the effect of levothyroxine therapy to decrease TSH levels to see how this influenced cancer growth.

THE FULL ARTICLE TITLE
Yamamoto M et al 2023 Active surveillance outcomes of patients with low-risk papillary thyroid microcarcinoma according to levothyroxine treatment status. Thyroid 33:1182–1189. PMID: 37310904.

SUMMARY OF THE STUDY
The authors identified 2,509 patients with papillary thyroid microcarcinomas undergoing active surveillance who were ≥20 years of age and had undergone at least four ultrasound neck surveillance studies.

Patients were first divided into two groups. Group I – not on thyroid hormone at the time of diagnosis and Group II – on thyroid hormone at the time of diagnosis and remained on it. Group I was further subdivided into IA – those who remained off thyroid hormone and IB – those who were started on thyroid hormone during active surveillance. Disease progression was defined as growth of the papillary thyroid microcarcinoma of at least 3 mm compared to baseline or the development of spread to the lymph nodes. Group II (322 patients) were younger, had larger cancers and had a higher baseline TSH than Group I (2,187 patients). Group II had a lower rate of surgery during follow up (4% vs 8.3%).

There were 252 patients who began levothyroxine treatment during observation (Group IA) while 1,935 patients remained off levothyroxine (Group IB). Group IA patients had significantly larger cancers, faster cancer growth and higher TSH levels. The percentage of patients in Group IA with cancer growth decreased from 26.8% to 12.5% after starting levothyroxine and cancer regression was seen in 59.8% vs 41.7% before starting levothyroxine. TSH levels by themselves did not predict disease progression or development of spread to the lymph nodes.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The authors concluded that levothyroxine treatment of patients with papillary thyroid microcarcinomas decreased the rate of disease progression and may be useful in following patients with active surveillance. However, if we think that the mechanism of levothyroxine slowing disease progression is to decrease TSH, we would expect to see lower TSH levels in patients with slower growth. This was not identified. There is no information on TSH goals to guide treatment. While this is an interesting study, further studies will be needed to determine whether the routine use of levothyroxine is warranted in patients with papillary thyroid microcarcinomas undergoing active surveillance.

— Marjorie Safran, MD

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