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Authors: Arthur S. Tischler, M.D., Anastassios G. Pittas, M.D.

1. Case 1

A 22-year-old woman complained of fatigue and amenorrhea since the birth of her 2nd child 1 year ago. She did not breast feed. She doesn't remember being this tired after the birth of her first child but attributes the fatigue to being older. In addition to fatigue, she often feels cold when others around her feel warm and she has noticed puffiness of the face and hands and paresthesias of hands and feet. She has not been able to lose the 20 extra pounds of weight she gained during pregnancy.

Physical examination revealed a pale, good-humored woman with some facial puffiness. Weight was 143 pounds, pulse 56, and blood pressure 100/70 without postural change. The skin was dry, coarse and cold. The thyroid was twice enlarged, very firm but without discrete nodules. Body and scalp hair seemed normal in texture and amount. The deep tendon reflexes had a brisk contraction phase but relaxation was perceptibly slow.

  1. You suspect thyroid dysfunction. What tests would you order?
    1. TSH
    2. TSH, Free T4 index
    3. TSH, Free T4 index and thyroid antibodies

      Laboratory evaluation revealed: Serum T4: 1.0 mcg/dl (normal 5-12 mcg/dl); serum T3: 85 ng/dl (normal 80-180 ng/dl); serum TSH: 84 mcU/L (normal 0.35-4.6 mcU/ml). Thyroglobulin and Thyroid Peroxidase (TPO) antibody titers were both elevated.
  2. The patient has
    1. Primary hypothyroidism
    2. Secondary hypothyroidism
    3. Tertiary hypothyroidism
  3. The mechanism most likely involved in her amenorrhea is
    1. Increased prolactin
    2. Increased testosterone
    3. High hCG D. Stress
      The patient was treated with T4, initially 50 mcg daily, increasing the dosage at monthly intervals until a maintenance dose of 150 mcg daily was reached.

      On this regimen, there was considerable subjective improvement (six-pound weight loss, pulse 70, and more vigor). Four months after the start of therapy, she had her first menstrual period since the birth of her baby.
  4. Will she require life-long thyroid hormone therapy? Why or why not?
  5. PATH - What are the histological findings characteristic of this disease?
  6. PATH - What would this disease typically look like in a thyroid fine needle aspirate?
  7. PATH - How would you distinguish this disease from a thyroid neoplasm histologically and at fine needle aspiration?

2. Case 2

A 48-year old woman presents to your office with palpitations and nervousness for the last few weeks. She also has had a large neck for years. She is healthy otherwise, and she takes no medications. Her family history is significant for a sister and maternal aunt with hypothyroidism.

Physical examination revealed: weight 134 pounds, pulse 110, and blood pressure 110/80. Patient was anxious and apprehensive. Skin was warm and moist. There was no proptosis or conjunctival chemosis. Lid lag was noted on exam. Thyroid gland was enlarged with multiple nodules; one nodule on the right was more prominent. Cardiac exam was remarkable only for tachycardia. Muscle strength was normal. A mild fine tremor was noted.

Laboratory evaluation revealed:

  • Serum T4 = 20.4 mcg/dl
  • THBR, 1.30 (normal 0.8-1.2)
  • Free T4 Index 26.5 (normal 5-12)
  • T3 220 ng/dl • TSH <0.05 mcU/ml)
  • Anti-TPO antibody titer <1
  1. Based on what we know so far, the patient has?
    1. Primary hyperthyroidism
    2. Secondary hyperthyroidism
    3. Tertiary hyperthyroidism
  2. What are the most common causes of hyperthyroidism?
  3. In addition to her lid lag, the patient is at risk for other thyroid eye disease such as proptosis and chemosis
    1. True
    2. False
  4. The most likely cause for her hyperthyroidism is:
    1. Graves’ disease
    2. Toxic Multinodular Goiter
    3. Toxic Adenoma
    4. Subacute Thyroiditis

      Discuss how you would confirm your clinical suspicion.

      A thyroid I-123 scan and uptake was performed. Uptake was 44% at 24 hours (normal 15-25%). A "cold" nodule was seen in the right thyroid lobe.
  5. How is this additional information useful?

    Because of the dominant nodule that appeared "cold" on the scan, a thyroid biopsy was done and based on the result, thyroidectomy was done.
  6. PATH - What is your differential diagnosis for this nodule based on the pathology?
  7. PATH - What criteria would you use to differentiate an adenomatous nodule from a follicular adenoma?
  8. PATH - How would you best distinguish a thyroid follicular adenoma from a well-differentiated thyroid follicular carcinoma?
    1. Extensive sampling of the capsule of the tumor
    2. Look for mitoses
    3. Look for hemorrhagic necrosis
    4. Stain for thyroglobulin
    5. Do a bone scan on the patient
  9. PATH - What is the prognosis in this case?

3. Case 3

A 34-year-old married woman was referred to you because of a thyroid nodule. The patient denied being aware of any thyroid disease or a "lump in the neck." She had not experienced any symptoms related to the thyroid, but had noticed some "choking" sensation recently. Past medical history was notable for Hodgkin's lymphoma for which she received chemotherapy and external radiation 15 years ago. Her family history is negative for thyroid disease.

Physical examination: Pulse 76, BP 120/70, and no ocular signs. There was a 2 x 3 cm firm nodule in the right lobe of the thyroid. The nodule was movable and non-adherent to adjacent tissues. There was no lymphadenopathy.

  1. What would you do next?
    1. TSH measurement
    2. Thyroid scan and uptake with I-123
    3. CT of the neck
    4. Surgical removal given her history of radiation exposure
    5. No evaluation is needed

      Laboratory evaluation revealed: Serum T4 = 7.8 ug/dl, free T4 index = 7.7, Serum TSH = 3.1 mU/L (0.35-4.5 mU/L).

      The patient had a fine needle aspiration of the nodule which showed papillary thyroid cancer. She underwent total thyroidectomy.
  2. PATH - Slide G-61 (will be shown in class) shows:
    1. Medullary thyroid cancer
    2. Papillary thyroid cancer
    3. Anaplastic thyroid cancer
    4. Lymphoma

      Pathology showed a 1.8 x 2.3 cm papillary carcinoma. One perithyroidal lymph node was noted to be enlarged and it also contained papillary thyroid cancer
  3. PATH - What are the distinctive characteristics of this lesion histologically?
  4. PATH - What is the relevance of irradiation to the development of this lesion?
  5. PATH - The patient’s long-term prognosis is best summarized as follows:
    1. 1% mortality at 20 years
    2. 5 % mortality at 20 years
    3. 20 % mortality at 20 years

4. Case 4

A 54-year old man comes to your office with a right neck mass. He noted the mass to be present for at least 10 years but over the last 6 months, the mass has increased in size. He feels well otherwise. He takes no medications. He does not know his family history as he was adopted. TSH was normal. A fine needle aspiration of the thyroid was done. Cytology was suspicious for malignancy so a total thyroidectomy was done.

  1. PATH - How would you describe this lesion?
  2. PATH - What is the pink amorphous material between the tumor cells?
  3. PATH - In immunohistochemical studies, this tumor would be positive for
    1. Chromogranin
    2. Calcitonin
    3. Both
    4. Neither
  4. PATH - What is the origin of this tumor?
  5. How might the family history be significant?
  6. What underlying molecular abnormalities may be present in patients who develop this type of tumor?