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Thyroid Nodules: Growth In Our Knowledge: Part I
by Susan J. Mandel
Lecture related to:
Chapter 320: Disorders of the Thyroid Gland
Slide 1: Thyroid Nodules: Growth in Our Knowledge
This is a review of the evaluation and management of thyroid nodules entitled “Thyroid Nodules: Growth in our Knowledge.”
Susan J. Mandel, MD, MPH
The Divisions of Endocrinology, Diabetes and Metabolism
University of Pennsylvania School of Medicine
Slide 2: Iodine Deficiency As A Worldwide Cause of Thyroid Nodules
Worldwide, the most common cause of thyroid nodules is odine deficiency that affects about 800 million people.
Slide 3: Salt Has Been Iodized in the United States Since the 1920s
However, in the United States, iodine deficiency does not exist to the same scale, because in 1923 we began to iodize our salt. Therefore, iodine deficiency as a cause for thyroid nodule is not necessarily present in the United States.
Slide 4: Prevalence of Thyroid Nodules in the United States
Determining the prevalence of thyroid nodules depends upon the method of detection. As shown, green is the prevalence of thyroid nodules as determined by palpation and pink as determined by the more sensitive technique of ultrasound. Overall, from the Framingham Study, palpable nodules are present in about 6% of women and 1.5% of men in the middle decades. And the annual incidence of detecting new nodules is about 1 in a 1000. Nodules are more common in older people and in women than in men, although the influence of parity in genetic susceptibility is unclear.
Slide 5: Differential Diagnosis of Thyroid Nodules
The reason we are trying to devise an effective method for evaluating and managing patients with thyroid nodules is that between 5 and 10% of nodules are malignant, the most common cancer being papillary follicular cancer. Fortunately, about 90% of nodules are benign and sometimes what we feel is a nodule is not truly a nodule, but a developmental abnormality.
Slide 6: Clinical Evaluation of Patients with Thyroid Nodules (History)
Unfortunately, elements from history and physical exam may not be that helpful in identifying to identify patients who have a higher risk of thyroid cancer. Certainly, adults who have children, had a history of head or neck irradiation, for benign conditions like acne and thymic hyperplasia, have a higher risk of thyroid cancer. Some patients do have a family history of thyroid cancer. Older and younger patients are more likely to have malignancy, as are men. However, with the exclusion of gender, these clinical scenarios are quite uncommon; and factors like the duration of the nodule, hoarseness or even rapid growth, which often represents hemorrhage into a nodule, that is either benign or malignant, do not help us in trying to figure out whether our patient is more likely to have thyroid cancer. In addition, whether a patient has coincident hyper- or hypothyroidism does not change the likelihood of cancer.
Slide 7: Cancer Rates For Patients with Solitary & Multiple Thyroid Nodules
Although in the past it was thought that patients with multiple nodules were less likely to have cancer than those with single nodules, this slide summarizes seven very well-done studies that have reported the cancer rates in patients with solitary nodules or multiple thyroid nodules, where the definition of nodularity has either been radiologic or histologic, and fine needle aspiration has been done. As you can see in all of the studies, the cancer rate per patient is the same for patients with one or multiple nodules, although there are some differences between the cancer rates in the different studies. But again, the cancer rates for one or multiple nodules are the same.
Slide 8: Clinical Evaluation of Patients with Thyroid Nodules (Physical Exam)
Unfortunately, physical examination is also not that sensitive for detecting patients with thyroid nodules. Although fixation to adjacent structures and adenopathy may be more likely to be associated with malignancy, these are quite uncommon. And nodule consistency does not help us in trying to decide whether a patient has a cancerous or noncancerous nodule.
Slide 9: Radionuclide Thyroid Scan
Historically, the initial test in the diagnostic evaluation of the patient with a thyroid nodule was the performance of a nuclear medicine scan to determine whether the nodule was functioning or not. This is based on the fact that malignancy is unlikely in functioning nodules, but for nonfunctioning nodules, 5 to 10% of these are thyroid cancers. The procedure for doing a thyroid scan is shown.
Slide 10: Hyperfunctioning "Hot" Left Nodule
This is a scan of a hyperfunctioning or hot left nodule. These are the nodules that do not need to be aspirated. As you can see, the remaining thyroid on the left and the upper pole on the right side is not functioning, as the nodule is making too much thyroid hormone. These nodules, however, are not very common.
Slide 11: Hypofunctioning
Ninety percent of nodules are hypofunctioning, or cold, and these are the nodules that need to be aspirated because there is a 10% chance of malignancy.
Slide 12: Initial Diagnostic Evaluation of Patients with Thyroid Nodules
How can we screen for the hyperfunctioning nodule, without doing thyroid scans in all patients since only about 5-10% of nodules are hyperfunctioning? This leads to the recommendation that the first step is the TSH level. It is not indicated to do a radionucleide scan as a first test, a CT or an MRI, antithyroid antibodies, or other tests of thyroid function.
Slide 13: Fine Needle Aspiration Biopsy
If the TSH is normal, we proceed directly to doing a fine needle aspiration biopsy. This simply consists of attaching a 25-gauge needle to a syringe and placing it in the nodule. The slide is actually from a British textbook where there are no OSHA guidelines and we obviously do this procedure with gloves.
Slide 14: Fine Needle Aspiration Cytology Results
However, a fine needle aspiration is not a perfect test. The nodule either is or is not cancerous, but there are actually four readings that can be obtained. Benign or malignant, we can also get a nondiagnostic reading and it is very important to look for these characteristics: rare, scant, few, or scattered. The technique is highly operator-dependent where 5 FNAs should be done a month, and there are very strict criteria for adequacy – 6 groups of 10 to 15 cells. However, there is a reading that occurs 20% of the time, which is an indeterminate reading, follicular neoplasm.
Slide 15: Indeterminate Follicular Cytology
The problem with the follicular neoplasm reading is that it is indeterminate and we cannot know if the nodule is a benign follicular adenoma or a follicular cancer. This distinction is made by histology, which often requires surgery, where the pathologist looks for capsular and vascular invasion.
Slide 16: Hypofunctioning "Cold" Right Lower Pole Nodule
Therefore this is the time when we would consider doing a thyroid scan. If the thyroid scan in the euthyroid patient shows that a nodule’s follicular cytology is cold, as shown in the right lower pole, the patient would require surgery because there is a 20% chance of cancer.
Slide 17: Right Lower Thyroid Nodule
However, if the scan shows that the nodule is actually accumulating radioiodine as shown in the right lower pole nodule, then the patient would not need surgery. This is a scan in a patient who does have a follicular neoplasm cytology. The nodule in the right lower pole has relatively more accumulation of I-123 tracer than the surrounding thyroid. The TSH is normal so you do see uptake of I-123 in the surrounding thyroid.
Slide 18: Surgery Indicators - Summary
However, as summarized in the slide, nodules with a follicular cytology that are hyperfunctioning on I-123 scans, compared to the surrounding thyroid, do not require surgery. All others must be removed because there is a 20% chance of malignancy.
Slide 19: Fine Needle Aspiration
Fine needle aspiration (FNA) cytology is a good diagnostic screening test for thyroid nodules. Estimates of sensitivity and specificity are based on several factors, but the medium sensitivities and specificities are quite high.
Slide 20: Triage of Nodule Management by Cytology
The slide summarizes the management of nodules by cytology. For nondiagnostic cytology, if FNA is repeated usually with ultrasound, malignant nodules go to surgery. Follicular neoplasms undergo an I-123 thyroid scan, which, if the nodule is hyperfunctioning compared to the surrounding thyroid, leads to observation. But if the nodule is hypofunctioning, which the majority are, these patients need to have surgery because of the 20% chance of thyroid cancer. But what about benign nodules?
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