PANCE Blueprint Endocrinology (7%)

Thyroid neoplastic disease (Lecture)

Patient will present as → a 40-year-old woman who is otherwise healthy presents to your office complaining of a lump in her neck. On examination, she is found to have a firm 2-cm nodule associated with the left lobe of the thyroid gland.

The most common risk factor for thyroid carcinoma is radiation exposure

  • Papillary carcinoma (80%) is the most common, remember: PAPILLARY IS POPULAR
  • Most common in young females 40-60 years old.
  • You may (not always) feel a Palpable thyroid nodule/mass

Solitary thyroid nodule: 

  • A solitary thyroid nodule is common in the general population and affects women more often than men. One in 12 to 15 young women has a thyroid nodule
  • Nodules must generally be over 1 cm in diameter to be palpated. Most are asymptomatic and are discovered incidentally via physical exam or through imaging. The presence of one palpable nodule increases the risk of additional nodules
  • Thyroid adenoma is the most common benign nodule. Only 5% of palpable nodules are malignant

Thyroid cancer risk factors: 

  • Prior radiation (head or neck)
  • Family history of thyroid cancer
  • Being > 65 y/o or < 20 y/o
  • Having additional symptoms such as voice changes, hoarse voice, difficulty breathing, or difficulty swallowing indicate invading of adjacent tissues

Physical exam risk factors

  • Firm and hard on palpation
  • Fixed during swallowing
  • Swollen lymph node in the neck region and only on one side

Lab and ultrasound finding risk factors

  • Nonfunctional nodules –  normal or high TSH and normal thyroid hormone level
  • Solid an echogenic, irregular margins, microcalcifications, > 1 cm

If you think you have a mass you will need to confirm by ultrasound

  • Lesions larger than 1 cm should be biopsied
  • Smaller lesions and those with benign histology can be followed and reevaluated if they grow

Ultrasound characteristics that put a nodule at high risk of malignancy are:

  • microcalcifications, hypoechogenicity, a solid nodule, irregular nodule margins, chaotic intranodular vasculature, and a nodule that is more tall than wide. 

You must identify if the mass is benign or malignant. To do this you can order a thyroid uptake scan

  • A cancerous lesion does not make hormone and will not take up iodine from a radioactive thyroid scan. (COLD NODULE)
  • A non-cancerous lesion does make hormone and will take up iodine at either a normal rate or a quicker rate. (HOT NODULE)

Remember: COLD = CANCER

Once you see a cold nodule you must rule out cancer. To do this you will need a FINE NEEDLE ASPIRATION

Treatment depends on the type of cancer and prognosis depends on staging, with a 99% 5-year survival with locally confined, less than 1 cm papillary carcinoma

  • Always involves complete or partial removal of the thyroid with chemotherapy and external beam radiation reserved for anaplastic thyroid cancer

Evaluation of a thyroid nodule

Suggested diagnostic and treatment approach for thyroid nodules (AAFP) Click Here

Palpable nodule

Childhood irradiation to head and neck confers a 25-fold increase in thyroid cancer

Confirm by Ultrasound

Microcalcifications, hypoechogenicity, a solid nodule, irregular nodule margins, chaotic intranodular vasculature, and a nodule that is more tall than wide.

Review TSH

Is the TSH normal, subnormal, or elevated?

TSH normal or elevated

Meets sonographic criteria for FNA?

Fine needle aspiration

Proceed to FNA If nodule is nonfunctional on uptake scan and meets sonographic criteria for FNA

Monitor

If nodule is nonfunctional on uptake scan and does not meet sonographic criteria for FNA

Thyroid nodules that do not meet sonographic criteria for FNA should be monitored with periodic ultrasonography. The frequency of evaluation (ranging from 6 to 24 months) depends upon the sonographic features of the nodules.

TSH subnormal/low

Proceed to radionuclide thyroid uptake scan

Thyroid uptake scan

Also measure FT4, T3

A cancerous lesion does not make hormone and will not take up iodine from a radioactive thyroid scan. (COLD NODULE)

A non-cancerous lesion does make hormone and will take up iodine at either a normal rate or a quicker rate. (HOT NODULE)

Fine needle aspiration

If nodule is nonfunctional on uptake scan and meets sonographic criteria for FNA

Thyroid nodules that do not meet sonographic criteria for FNA should be monitored with periodic ultrasonography. The frequency of evaluation (ranging from 6 to 24 months) depends upon the sonographic features of the nodules.

FT4 and FT3

FT4 and T3 Normal = subclinical hyperthyroidism ⇒ can be observed in most cases

FT4 and/or T3 high = overt hyperthyroidism ⇒ treat

osmosis Osmosis
Picmonic
Thyroid nodules

IM_MED_ThyroidNoduleAssessment_v1.2

Thyroid nodules can be identified on physical exam or incidentally on imaging for another indication. There are various etiologies for thyroid nodules, some benign and some malignant, so it is important to investigate further when they are discovered. Initial work-up includes a serum thyroid-stimulating hormone (TSH) and an ultrasound of the thyroid gland. Depending on the findings, further testing may include fine-needle aspiration (FNA), radioactive iodine uptake (RAIU), and serum triiodothyronine (T3) and thyroxine (T4). Routine monitoring of a thyroid nodule is recommended with ultrasound 6-18 months after diagnosis.

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Thyroid cancer

There are four main types of thyroid cancer, listed in descending order of prevalence are papillary, follicular, medullary, and anaplastic.

1. Papillary Carcinoma

IM_MED_PapillaryCarcinoma_V1.7_ASSETS_

Papillary thyroid carcinoma is the most common, carries the best prognosis, is characterized by lymphatic spread and distinct histological findings like Orphan Annie nuclei and psammoma bodies. Risk factors for papillary carcinoma include head and neck radiation, RET and BRAF gene mutations, as well as Gardner and Cowden’s syndrome.

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2. Medullary Carcinoma

Medullary Carcinoma Picmonic, the third most common type of thyroid cancer is divided into sporadic and familial types. This cancer arises from parafollicular C cells, may produce calcitonin and manifest with hypocalcemia or produce ACTH and manifest with Cushing syndrome. It is characterized histologically by amyloid-staining sheets of cells and will exhibit calcitonin release with pentagastrin administration. Two major risk factors for medullary carcinoma are a history of head and neck radiation and a family history of MEN 2A and 2B.

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3. Follicular Carcinoma

Follicular thyroid carcinoma, the second most common type, commonly presents as a solitary thyroid nodule with a good prognosis. It is characterized by hematogenous spread, thyroid capsule invasion, and histological findings like uniform follicles. A major risk factor for follicular carcinoma is a history of head and neck radiation, and women are more commonly affected than men.

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5. Anaplastic Thyroid Cancer

Anaplastic Thyroid Cancer is the least common, is rapidly progressive, and has a grave prognosis. A common presenting symptom of this tumor is a hoarse voice and diagnostic examination will show the invasion of local structures and a mixed cellular morphology. Major risk factors for anaplastic carcinoma are old age, the presence of multinodular goiter, and a history of previous thyroid disease or malignancy.

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Question 1
A 38-year-old woman is seen in your office for a complete baseline health assessment. You have never seen this patient before. She feels well and tells you that she is “wonderfully healthy.” She has had no weight loss or gain; no sweating, no tremors, no diarrhea or constipation; no anxiety or depression; no irritability; and no other symptoms. On examination, she is found to have a 2-cm nodule in the left lobe of the thyroid gland. Her blood pressure is 120/ 70 mm Hg. Her pulse is 90 beats/ minute and regular. What is the first test that should be ordered to evaluate the patient’s physical examination abnormality?
A
magnetic resonance imaging (MRI) scan of the thyroid
B
thyroid ultrasound study
C
radioactive iodine uptake scan
D
FNA of the nodule
E
computed tomography (CT) scan of the thyroid
Question 1 Explanation: 
The initial procedure of choice is thyroid ultrasound examination. Despite the presence of a palpable nodule, there may be other nodules that are not clinically evident. The decision to perform FNA should not be made on size alone. A thyroid ultrasound study may uncover other nodules not palpated that may have features putting them at high risk of malignancy and that should receive FNA in addition to the palpable nodule. Among those receiving ultrasound examination for a clinically suspected thyroid nodule, 20% will have another, clinically inapparent nodule, and 10% of those will have no nodule found sonographically. Radioactive iodine uptake scanning can indicate whether the nodule is functioning, but it does not provide as much information about the presence of other nodules or their internal features. CT and MRI scanning have limited value in the investigation of thyroid nodules.
Question 2
Two suspicious thyroid nodules are identified after the appropriate primary test is ordered. What is the next test in the evaluation of the patient’s thyroid nodules?
A
serum T4
B
radioactive iodine uptake thyroid scan
C
FNA of the nodules
D
thyroid ultrasound study
E
CT scan of the thyroid
Question 2 Explanation: 
After suspicious nodules are identified, FNA should be performed to further evaluate for thyroid carcinoma. Although FNA may be done blindly, the use of ultrasound-guided FNA is increasing. This allows direct visualization of the needle in the nodule, permitting accurate sampling of the desired area. This also helps avoid accidental damage to surrounding neck structure, such as the trachea and the neurovasculature. Results of FNA are reported as positive, negative, suspicious, or nondiagnostic for malignant cells. Refer to the Solution to the Clinical Case Management Problem for complete details on the management of thyroid nodules.
Question 3
Which of the following statements regarding “hot nodules” and “cold nodules,” found on radioactive iodine scan, is true?
A
cold nodules are more likely than hot nodules to be benign
B
cold nodules need not be investigated any further
C
cold nodules are more likely than hot nodules to be associated with signs and symptoms of hyperthyroidism
D
cold nodules always require further investigation to differentiate benign from malignant status
E
all nodules, whether hot or cold, require further investigation to differentiate benign from malignant status
Question 3 Explanation: 
Cold nodules require further investigation because they carry a 5% to 15% risk of malignancy. Hot nodules are extremely unlikely to be malignant and do not require FNA.
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