Thyroid nodules: Clinical sciences

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Introduction0:00–0:46

Thyroid nodules are discrete, solid, or fluid-filled lumps in the thyroid gland, often found incidentally on exam or imaging.
Thyroid nodules are common and usually benign, though some can be malignant. When evaluating a thyroid nodule, you will want to determine if the patient has thyroid dysfunction and obtain a thyroid ultrasound.
Patients who are hypothyroid or euthyroid require further work up based on concerning features on ultrasonography, while patients who are hyperthyroid will require a radioactive iodine uptake or RAIU test.
Alright, when a patient presents with chief concern suggesting thyroid nodule, you should first perform a focused history and physical examination.

History and physical examination0:46–2:49

Most patients with thyroid nodules are asymptomatic and the nodule is found on a routine exam or incidentally on imaging.
If the patient does have symptoms, they may have signs of hyperthyroidism, such as tachycardia, weight loss, muscle weakness, heat intolerance, anxiety, or irritability; or signs of hypothyroidism like dry skin, depression, cold intolerance, fatigue, and constipation.
Very rarely, if the nodule is large enough, it can put pressure on surrounding structures and cause symptoms, like a feeling of fullness in the throat or difficulty swallowing.You should also assess for personal or family history of syndromes that increase the risk of developing cancer.
This includes Cowden disease; familial adenomatous polyposis or FAP; multiple endocrine neoplasia or MEN II; Carney complex; or Werner syndrome, also called progeria.
Meanwhile, on physical examination, you may feel the nodule as a palpable mass at the front of the neck, over the thyroid.
Remember, the thyroid moves upward when the patient swallows, so if the nodule you feel also moves upward, you know it is part of the thyroid.
If the nodule doesn’t move upward with swallowing, then it’s another type of neck mass. Now, in some cases, you may feel more than one nodule, what’s known as a multinodular thyroid, and you might even find palpable cervical lymph nodes.
Alright, if you see these findings, you should next assess for thyroid dysfunction by ordering TSH and obtain a thyroid ultrasound.
Okay, let’s start with patients who are hypothyroid, meaning their TSH is elevated, and patients who are euthyroid, meaning their TSH is within reference range.

Hypothyroid/Euthyroid2:49–6:10

In these cases, the nodule is not producing thyroid hormone, so it’s a non-functioning thyroid nodule. If this is the case, you will want to assess your ultrasound results to help you determine the risk for malignancy.
If the ultrasound shows a cystic mass that’s smaller than 1 cm in size, you should have a low suspicion for malignancy, and can consider the nodule a benign thyroid nodule.
Benign nodules are commonly found in some thyroid conditions like Hashimoto thyroiditis, subacute thyroiditis, colloid nodules, and follicular adenomas.
These patients need a repeat ultrasound at 12 to 24 months for follow up. Now, here’s a high-yield fact!
If an ultrasound shows a cystic lesion with solid components, this is more likely to be malignancy, and so you should proceed with a fine needle aspiration, or an FNA.On the other hand, if the ultrasound shows a hypoechoic, solid mass, that’s 1 cm in size or larger, with microcalcifications, irregular margins, hypervascularity, evidence of extrathyroidal extension, and a taller than wide shape, you should have an intermediate to high suspicion for malignancy.
In this situation, you need to order an FNA for cytological analysis. Here’s a clinical pearl!
FNA cytology uses the Bethesda System for cytopathology. There are six classifications based on cytology results, including nondiagnostic or unsatisfactory; benign; atypia or follicular lesion of undetermined significance, also called AUS or FLUS respectively; follicular neoplasm or suspicious for follicular neoplasm; suspicious for malignancy; and lastly, malignant.If the FNA cytology demonstrates benign cells, you can diagnose a benign thyroid nodule.
In these cases, because of the suspicion based on ultrasound, you should repeat an ultrasound and FNA within 12 months. You will also want to repeat the ultrasound and FNA within 12 months for nondiagnostic and indeterminate FNA results.
If the FNA cytology shows malignant cells, this is consistent with a malignant thyroid nodule. Your next step will be to determine the type of cancer using histology and then treat accordingly, most often with surgical resection of the thyroid.
Remember, any patient who has their thyroid resected will then need thyroid hormone supplementation. Additional therapies include lymph node dissection, radiotherapy, and chemotherapy.Now that we’ve discussed what to do for patients who are hypothyroid or euthyroid, let’s discuss patients with evidence of hyperthyroidism.

Hyperthyroid6:10–6:54

These patients will have low TSH. In these cases, the thyroid nodule may or may not be the source of the thyroid hormone, so we need to do a radioactive iodine uptake test, or RAIU, to help us be sure.
The RAIU tests thyroid function by using radioactive isotopes such as iodine-123 or Technetium 99m pertechnetate, also called Tc-99, which are absorbed in follicular cells that are producing thyroid hormone.So let’s say that there is minimal or insignificant Iodine-123 or Tc-99 uptake on RAIU.

Hypofunctioning nodule6:54–7:59

This represents a hypofunctioning or “cold” nodule. Cold nodules have a higher likelihood of malignancy, so you’ll need to review your ultrasound results to determine your next step.
As in the case with non-functioning nodules, those with low suspicion on ultrasound can be classified as benign thyroid nodules and followed up with an ultrasound in 12 months.
Those that have intermediate or high suspicion on ultrasound should undergo an FNA for cytology review. If the cytology reveals benign cells, you can again diagnose a benign thyroid nodule and repeat the ultrasound and FNA in 12 months.
If there are malignant cells, you will want to differentiate the type of cancer, surgically resect the thyroid, and consider additional medical management.
Now, let’s go back to the RAIU and consider a thyroid nodule that is producing thyroid hormone. In these cases, there will be significant uptake, resulting in a hyperfunctioning or “hot” nodule appearance.

Functioning nodule7:59–10:01

In these cases, the uptake will either show a patchy, multifocal uptake, signifying toxic multinodular goiter, also called Plummer disease; or a solitary focus of uptake, signifying a solitary toxic nodule.
In cases where there is multifocal uptake, you will want to compare your ultrasound against the RAIU. If the ultrasound is nonconcordant, meaning there are nodules that seem suspicious on ultrasound but do not have uptake on RAIU, you will want to obtain an FNA and further evaluate for malignancy as noted above.
If the ultrasound is concordant, meaning all of the nodules on ultrasound also have uptake on RAIU, then you can proceed to treat the hyperthyroidism.
This can include antithyroid medications like methimazole; as well as beta-blockers like propranolol if the patient presents with adrenergic symptoms, such as palpitations, tremors, and anxiety.
Lastly, consider surgical resection or radioiodine therapy, depending on the case. Here’s a clinical pearl!
Hyperfunctioning nodules, also called toxic nodules, are often treated by treating the hyperthyroidism with either methimazole or propylthiouracil.
In some cases, the nodule can be big enough that it causes symptoms of compression, like dysphonia, dysphagia, and dyspnea.
These patients can be treated with a thyroidectomy, which can result in hypothyroidism and requires further treatment with levothyroxine.
Alright, as a quick recap… Most thyroid nodules are asymptomatic and found incidentally on physical examination or imaging.

Review10:01–11:17

The first step is to evaluate for thyroid dysfunction and obtain an ultrasound. Hypothyroid or euthyroid cases have non-functioning nodules, which are more likely malignant.
If ultrasound findings are suspicious for malignancy, obtain an FNA. Malignant nodules require surgical resection and thyroid hormone replacement.
Benign nodules require repeat evaluation with ultrasound, and you may need to repeat the FNA. Hyperthyroid cases require an RAIU test, and nodules will either be hypofunctioning or hyperfunctioning.
Hypofunctioning nodules require similar evaluation and treatment as non-functioning nodules. Hyperfunctioning nodules should be assessed based on the pattern of uptake.
If there’s patchy uptake, check the ultrasound for concordance. Nonconcordant nodules require further evaluation with FNA.
Concordant nodules, or those with a solitary uptake focus, don’t need further evaluation. You should treat hyperthyroidism and consider