Differentiated thyroid cancer - A guide to survivorship care - RACGP
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Clinical
Differentiated thyroid cancer
A guide to survivorship care
Peter Watson-Brown, Daniel Anderson THYROID CANCER is becoming more promotion of a healthy lifestyle are
common in Australia because of important factors in the survivorship of
increasing incidence and decreasing all cancer patients.3
Background
Thyroid cancer diagnoses are increasing
mortality over the past 30 years.1 There Initial follow-up after primary treatment
in Australia. Increased detection and has been a fourfold increase in the annual for DTC is usually with a specialist thyroid
excellent prognosis of differentiated incidence of thyroid cancer in Australia surgeon and/or endocrinologist governed
thyroid cancers has led to a growing since 1982, with current estimates by published guidelines.4,5 Thereafter,
cohort of patients undergoing post- suggesting 1.2% of Australians will be appropriate patients with DTCs may be
treatment survivorship care. diagnosed with thyroid cancer by age returned to their general practitioner
Objective 85 years. Differentiated thyroid cancers (GP) for shared care or follow-up in
The aim of this article is to provide (DTCs) make up the majority of diagnoses primary practice alone. A Canadian study
an overview of the principles and and have an excellent overall survivorship, found patients with low-risk DTC had
modalities of differentiated thyroid with a >97% five-year survival rate.1 similar outcomes when followed up in
cancer survivorship care in adults and Differentiated thyroid cancers arise primary care when compared with thyroid
present a framework for follow-up within
from follicular cells, with papillary thyroid specialist care and additionally had an
general practice.
carcinomas (PTCs) and follicular thyroid economic benefit to the healthcare system.6
Discussion carcinomas (FTCs) by far the most
Surveillance for recurrent disease is an common types (Figure 1). Medullary
important component of survivorship Risk stratification
thyroid cancers (MTCs) arising from the
care and involves clinical assessment,
parafollicular C-cells are neuroendocrine The American Thyroid Association (ATA)
biochemical monitoring of serum
thyroglobulin and anti-thyroglobulin tumours that are associated with familial divides DTC into low, intermediate and
antibodies and ultrasonography. Thyroid‑ and multiple endocrine neoplasia high risk of recurrence based on histological
stimulating hormone suppression is (MEN) syndromes. MTCs are distinct subtype, size and extent of the primary
frequently used to reduce the risk of in their association with calcitonin and tumour and presence of distant metastases
recurrence. Clear communication between carcinoembryogenic antigen (CEA) tumour (Table 1).4 Within PTC, there are
the patient’s thyroid specialists and their
markers and have a different management numerous histological variants including
general practitioners is important to plan
and monitor effective follow-up.
guideline.2 A small proportion of cancers aggressive subtypes: tall cell, columnar,
are undifferentiated anaplastic carcinomas hobnail and solid. Conversely, non-invasive
that convey a very poor prognosis. follicular thyroid neoplasm with papillary
Survivorship care is an integrated, like features (NIFTP) is an indolent variant
patient-centred model that involves of PTC withClinical Differentiated thyroid cancer: A guide to survivorship care
Surveillance hemithyroidectomy) and both central and majority of recurrences occur within the
The principal modalities used for lateral cervical lymph node compartments. first five years,7 late recurrences are well
surveillance are clinical assessment, The ATA DTC guidelines4 provide documented, necessitating long-term
thyroid function tests, biochemical surveillance recommendations based on follow-up.4,8,9
markers of tumour recurrence variable levels of evidence and ultimately
and ultrasonography to assess for the follow-up algorithm is at the discretion
locoregional structural recurrence. of the thyroid specialist, taking into account Biochemical surveillance
Less than 10% of patients with DTC both patient and disease factors. Continued Serial monitoring of serum thyroglobulin
experience distant metastases, and half risk stratification should be undertaken (Tg) and anti-thyroglobulin antibodies
of these are identified at diagnosis.5 throughout the surveillance period to (TgAbs) is an important postoperative
Lungs and bone are the most prevalent provide individualised management tool to assess for residual and recurrent
sites and risk factors include aggressive recommendations to the patient. disease in DTC.4 Ultrasensitive assays
histological subtypes, vascular invasion, It is important for the thyroid specialist allow testing while on levothyroxine
advanced primary tumours and bulky to communicate to the GP the expected supplementation; however, consistent
nodal disease.4 frequency of investigations and follow-up, measuring at the same pathology provider
A consultation for thyroid cancer along with TSH targets and guidelines for is required to ensure accurate results.
surveillance involves a screen for when to re-refer. This cohort of patients Thyroglobulin is a protein made by
symptoms of recurrent disease in the with low- and-intermediate risk DTC who thyroid follicular cells and is a sensitive
thyroid bed, cervical lymph nodes and achieve an excellent response to initial marker for the presence of thyroid tissue in
upper aerodigestive tract (eg dysphonia, treatment should be surveilled six monthly the body.10 It does not distinguish between
dysphagia, pain, haemoptysis). for the first two years and then 12 monthly benign and malignant tissue and can be
Symptoms of hypo/hyperthyroidism thereafter (example in Table 2).4 Patients elevated in most thyroid diseases, so it is not
should also be elicited and correlated who achieve an incomplete or indeterminate recommended to be tested preoperatively.
with thyroid function tests. The anterior response to treatment should continue Thyroglobulin is influenced by both the
and lateral neck should be palpated follow-up with their thyroid specialist. serum TSH and TgAb levels and should be
to assess for disease in the thyroid There is no ATA recommendation considered in the context of these values.4
bed (and contralateral lobe in case of on duration of surveillance.4 While the After total thyroidectomy and adjuvant
Thyroid gland
Follicular Parafollicular cells
epithelial cells (C cells)
Differentiated Medullary thyroid
Undifferentiated cancer (MTC)
thyroid cancer
thyroid cancer
(DTC) ~1–2% cases
Papillary thyroid Follicular thyroid Other thyroid Anaplastic thyroid
carcinoma (PTC) carcinoma (FTC) cancers cancer (ATC)
~90% cases ~5% casesDifferentiated thyroid cancer: A guide to survivorship care Clinical RAI, Tg levels should become and remain Patients should have undetectable or recurrent disease of the thyroid bed. undetectable. Remnant normal thyroid down-trending Tg and TgAbs after initial The ATA recommends ultrasonography tissue may cause a low level of serum Tg treatment. Newly elevated or rising Tg 6–12 months after treatment to measure to persist postoperatively in some patients or TgAb titres raise the likelihood of the initial response, then ‘periodically’ treated with total thyroidectomy without persistent or recurrent disease.4 depending on recurrence risk, Tg and RAI, and is expected in patients treated clinical suspicion.4 with hemithyroidectomy alone. While it can Ultrasonography findings should be be considered,4 the current evidence does Structural surveillance considered in the context of the biochemical not support using Tg as a biomarker for Ultrasonography of the neck is a and clinical picture. Sonographically recurrence in hemithyroidectomy.11 highly sensitive tool for detecting suspicious lymph nodes ≥8–10 mm in Serum TgAbs are present in structural recurrence in the thyroid bed, smallest diameter should be considered approximately 25% of patients with contralateral lobe (in hemithyroidectomy) for fine-needle aspiration biopsy.4 Smaller thyroid cancer, especially in the setting and metastases to cervical nodal and benign appearing nodes can often of Hashimoto thyroiditis.4 The presence compartments.4 Whereas most be monitored with serial examinations in of TgAbs can interfere with the serum Tg recurrences of PTC are confined to the first instance.4 In patients treated with level, and they should be tested together the neck, FTC typically metastasises hemithyroidectomy, thyroid nodules in the to allow accurate interpretation.4 Positive distantly (to lungs and bone) and rarely contralateral lobe should be monitored for TgAbs frequently cause falsely low serum involves the cervical lymph nodes.10 growth or suspicious features and biopsied Tg levels, but can conversely cause false Therefore in FTC, ultrasonography in accordance with ATA guidelines for elevated readings with certain assays. serves mainly to exclude residual/ thyroid nodules.4 Table 1. Classification of risk of thyroid cancer recurrence, and recommended initial TSH targets4 Risk of recurrence Definition Initial TSH target* Low PTC with all of the following: Hemithyroidectomy or initial Tg (
Clinical Differentiated thyroid cancer: A guide to survivorship care
TSH suppression Only 10–15% of patients with normal serum Tg measured 6–12 weeks after total
Lifelong thyroid hormone preoperative thyroid function who thyroidectomy (Table 1). For long-term
supplementation (levothyroxine) is undergo hemithyroidectomy will develop follow-up, all patients at low- and
required following total and completion hypothyroidism requiring levothyroxine intermediate-risk patients with an excellent
thyroidectomy to prevent symptomatic supplementation.4 There is little evidence response to treatment (no structural or
hypothyroidism. Following surgery for to guide TSH targets or the use of the biochemical evidence of residual disease)
thyroid cancer, supraphysiological dosing levothyroxine for TSH suppression allow TSH target levels in the low end of
of levothyroxine is used to reduce TSH alone in patients who underwent the normal range (0.5–2 mU/mL; Table 2).
to below-normal levels via the pituitary hemithyroidectomy. Those with high risk of recurrence or
feedback loop. TSH has a trophic effect on Different guidelines recommend incomplete or indeterminate response to
DTC cells, upregulating cell growth and varying TSH targets based on their risk initial treatment are often recommended
production of proteins including Tg. By of recurrence and response to initial continued TSH suppression targets.4
controlling the TSH-driven proliferation treatment, and decisions will be made by Benefits of suppression must be
of DTC, levothyroxine suppressive the treating thyroid specialist.4,5 Initial weighed against the risk of complications
therapy is thought to decrease the risk TSH suppression is recommended for from subclinical hyperthyroidism
of disease recurrence and progression intermediate and high-risk DTC and for as a result of supraphysiological
postoperatively.12 cases of low-risk DTC with a detectable levothyroxine supplementation. These
include exacerbation of ischaemic heart
disease and atrial fibrillation, as well as
Table 2. Example of follow-up schedule for DTC patients with an excellent osteoporosis, especially in postmenopausal
response to initial treatment* women.13 A patient’s age, comorbidities
and risk of recurrence should be taken into
Example of long-term follow-up schedule for account when determining the degree of
Risk of patients with an excellent response to initial
TSH suppression.4 Maintaining appropriate
recurrence Initial treatment treatment*
thyroxine replacement dosing is one of
Low risk Hemithyroidectomy Likely suitable for GP follow-up: the challenges of long-term follow-up and
Clinical history and examination six monthly for should be reviewed at least yearly.
two years, then 12 monthly
Periodic ultrasonography of the neck
(eg 12–24 monthly); contralateral lobe nodules When to refer
should be monitored/investigated in accordance Referral to a thyroid cancer specialist for
with ATA guidelines
further investigation and management
Low/ Total thyroidectomy Likely suitable for GP follow up: (Box 1) is recommended for patients with
intermediate +/– RAI Clinical history and examination six monthly for suspected recurrent disease based on
risk two years, then 12 monthly clinical findings, ultrasonography or blood
TFTs 12 monthly (TSH target 0.5–2 mU/mL) tests.5 Patients presenting with upper
Tg and TgAb levels 12 monthly aerodigestive tract symptoms such as voice
Periodic ultrasonography of the neck change or difficulty swallowing should
(eg 12–24 monthly) be referred for endoscopic assessment.
Late recurrences do occur and should be
High risk Total thyroidectomy May be suitable for shared care or GP follow-up
+ RAI after 2–5 years:
Clinical history and examination 6–12 monthly for
five years, then 12 monthly Box 1. Red flags for thyroid cancer
TFTs 12 monthly (consider suppression TSH target recurrence
0.1–0.5 mU/mL for five years;† thereafter 0.5–2 mU/mL
if no concerns for recurrence) New aerodigestive tract symptoms
Tg and TgAb levels 6–12 monthly (eg dysphonia, dysphagia, haemoptysis)
Periodic ultrasonography of the neck Newly elevated or rising thyroglobulin or
(eg 6–12 monthly) anti-thyroglobulin antibody levels
Enlarging or suspicious masses in the
*Only for patients who have had an excellent biochemical and structural response to initial treatment. contralateral thyroid lobe, thyroid bed or
Patients who have an incomplete or intermediate response to treatment should continue management cervical lymph node chain
and follow-up with their thyroid specialist (refer to main text).
†TSH suppression targets are age and comorbidity dependent (refer to main text) Systemic symptoms of malignancy and
ATA, American Thyroid Association; RAI, radioactive iodine; TFTs, thyroid function tests; Tg, thyroglobulin; metastatic disease (especially lungs
TgAb, anti-thyroglobulin antibody; TSH, thyroid-stimulating hormone and bone)
50 Reprinted from AJGP Vol. 52, No. 1–2, Jan–Feb 2023 © The Royal Australian College of General Practitioners 2023Differentiated thyroid cancer: A guide to survivorship care Clinical
considered in any patient with thyroid Competing interests: None. J Clin Endocrinol Metab 2013;98(2):636–42.
Funding: None. doi: 10.1210/jc.2012-3401.
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Provenance and peer review: Not commissioned, 8. Mazzaferri EL, Jhiang SM. Long-term impact
irrespective of time since diagnosis. externally peer reviewed. of initial surgical and medical therapy on
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Correspondence to:
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are essential as part of the referral. Further peter.watsonbrown@uqconnect.edu.au
9343(94)90321-2.
investigation with fine-needle aspiration 9. Jeon MJ, Kim M, Park S, et al. A follow-up strategy
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© The Royal Australian College of General Practitioners 2023 Reprinted from AJGP Vol. 52, No. 1–2, Jan–Feb 2023 51You can also read
