Investigating and managing thyroid nodules.

Introduction

Thyroid nodules are becoming more common, mainly due to increased incidental detection with medical imaging. Palpable nodules are estimated to occur in about 4-7% of the population¹.

When ultrasound detected nodules in healthy adults are included, the prevalence can be up to 60%². Thyroid nodules occur more frequently in women and are more common with advancing age. About 50% of people over the age of 60 will have thyroid nodules³.

Approximately 1 in 20 thyroid nodules are cancerous⁴, therefore it is important to determine which nodules are suspicious and investigate appropriately.

Thyroid cancer is a relatively uncommon disease with an excellent prognosis especially if detected early. There are many other causes of thyroid nodules which are shown in Table 1. Often when a single nodule is palpated, ultrasound will reveal there are multiple nodules.

History and examination

Features that may raise the suspicion of malignancy are:

1. previous history of childhood head and neck irradiation or total body irradiation for bone marrow transplantation
2. family history of thyroid carcinoma or thyroid cancer syndrome
3. exposure to ionizing radiation in childhood or adolescence (including living in Europe during Chernobyl)
4. rapid growth or hoarseness of voice.

A family history of multinodular goitre or growing up in an area of endemic goitre is reassuring as likelihood of malignancy in these situations is low. A nodule that has been present for a long period of time without any change is also less likely to be malignant. 

A nodule in a person who has signs and symptoms of hyperthyroidism suggests it is hyperfunctioning.  A hyperfunctioning nodule usually requires no further cytological assessment as the risk of malignancy is extremely low.  

Physical findings that increase the likelihood of malignancy include a firm hard, irregular nodule adherent to surrounding structures, paralysis of the vocal cords and cervical lymphadenopathy.

Investigations

A low TSH suggests the nodule is hyperfunctioning. This should be confirmed by a radionucleotide uptake scan. There is a common misconception that an ultrasound is the most appropriate investigation in all types of thyroid disease, however if the issue is one of “function” of the gland then the most appropriate form of imaging is a nucleotide scan. If the issue is one of “structure” then an ultrasound should be the initial investigation.

In conjunction with a serum TSH an ultrasound of the thyroid is recommended. Ultrasonography can accurately detect and estimate the size of nodules and differentiate between cystic and solid component.

There are a number of features detected by ultrasonography which increase suspicion of malignancy, see Table 2. A predominantly cystic nodule or spongiform appearances of the nodule on ultrasound are strong predictors of a benign nodule.  

A nodule greater than 10mm in diameter with any of the above features should be biopsied under ultrasound guidance. A pathologist ideally should be present at the time of FNAB to ensure an adequate sample is retrieved. Where there are multiple nodules present, evidence supports biopsy of up to four nodules⁶.

Management

"Hot' nodules

Nodules that light up on a radionucleotide study with suppression of the surrounding tissue are termed "hot" nodules and indicate the nodule is hyperfunctioning, Patients may be unaware that the nodule is hyperfunctioning and only have biochemical evidence of increased activity with a suppressed TSH and a fT4 and fT3 that may remain in the laboratory normal range although these values are likely to be elevated for that patient.  Other patients may be clinically and biochemically hyperthyroid.  The aim of therapy is to ablate the ‘hot" nodule and render the patient clinically and biochemically euthyroid.  The recommended treatment is radioactive iodine (I¹³¹ ).

Thyroid cancer

If cancer is detected on a FNAB, management consists of surgically removing the thyroid gland, usually both lobes with clearance of lymph nodes.  Depending on the stage and severity of the cancer, further ablative I¹³¹ treatment is given to reduce the risk of recurrences.

Nondiagnostic FNAB

Nodules in which the FNAB did not yield enough cells for an adequate diagnosis should  have  a repeat FNA performed soon after.  If the second FNA fails to reveal a diagnosis then the options are either surgery to remove the nodule or ongoing surveillance, with clinical examination and imaging.   

Benign nodules

Cytologically benign nodules do no require further treatment or diagnostic studies. 

Indeterminate nodules; follicular or Hürthle cell neoplasm

A FNA that comes back with follicular cells or Hürthle cells may be benign or malignant. Management is guided by the size of the nodule and other clinical indicators of suspicion.  Older patients, male sex and nodules greater than 4cm increase the risk of malignancy.  There are a number of molecular markers that can improve the diagnostic accuracy, but at this time still remain as research tools. 

Thyroid nodules are a common occurrence and assessment and management centres on determining which nodules are likely to be cancerous.  The main investigations to assist in diagnosis are TSH, ultrasound and FNAB.  An algorithm for workup of patients can be seen in  Figure 1.

Figure 1. Work up of a thyroid nodule

 Talking Women Thyroid nodules 256.43 Kb

References

1. Singer PA, Cooper DS, Daniels GH, et al. Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. Arch Intern Med 1996;156:2165-72

2. Ezzat S, Sarti DA, Cain DR, Braunstein GD. Thyroid incidentalomas.  Prevalence by palpation and ultrasonography.  Arch Intern Med 1994;154:1838-40

3. Hegedüs L, Bonnema SJ, Bennedbaek FN.  Management of simple nodular goiter: current status and future perspectives. Endocr Rev 2003;24:102-32

4. Mazzeferri EL.  Management of a solitary thyroid nodule.  N Engl J Med 1993;328:553-59

5. Cooper D, Doherty G, Haugen B, Kloos R, Lee S, Mandel S, et al. Revised Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2009:19(11);1167-214.

6. Frates MC, Benson CB, Doubilet PM et al.  Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography.  JCEM 2006;91:3411-17

See also Medical Observer http://www.medicalobserver.com.au/

Content Updated June 18, 2010