PANCE Blueprint Endocrinology (6%)

Goiter

Goiter is an abnormal enlargement of the thyroid gland, which may be diffuse or nodular, and can be associated with normal, hyper, or hypothyroid function

• Goiter is commonly caused by iodine deficiency worldwide, but in the United States, it is often due to Graves' disease, Hashimoto's thyroiditis, and multinodular goiter; certain medications (e.g., lithium) can also contribute
• Symptoms depend on the size and cause of the goiter and may include visible neck swelling, difficulty swallowing (dysphagia), shortness of breath (dyspnea) due to tracheal compression, and hoarseness if the recurrent laryngeal nerve is affected
• Thyroid function can be normal (euthyroid), hyperthyroid (toxic goiter), or hypothyroid

DX:

Diagnosis involves assessing thyroid function with TSH and free T4, imaging with ultrasound to evaluate gland size and nodule characteristics, and radioactive iodine uptake (RAIU) if hyperthyroidism is present

• Fine-needle aspiration (FNA) may be needed to evaluate suspicious nodules for malignancy

TX:

• Management depends on the cause and size:
  • Iodine supplementation for iodine deficiency
  • Antithyroid medications, radioactive iodine, or surgery for hyperfunctioning goiters
  • Thyroid hormone replacement for hypothyroid goiters
  • Surgical resection (thyroidectomy) is indicated for large goiters causing compressive symptoms, cosmetic concerns, or suspicion of malignancy
• Complications of untreated goiter include airway obstruction, dysphagia, and the risk of thyroid cancer in nodular goiters

Goiter with large palpable paratracheal nodule

Hyperthyroidism (ReelDx)

ReelDx Virtual Rounds (Hyperthyroidism)

Hyperthyroidism is the production of too much thyroxine hormone. It can increase metabolism and accelerate the body's metabolism, causing unintentional weight loss and a rapid or irregular heartbeat

Etiology: Grave’s disease (autoimmune). Toxic adenoma, thyroiditis, pregnancy, amiodarone

Presentation: Heat intolerance, palpitations, sweating, weight loss, tremor, anxiety, tachycardia

• Graves - Diffuse goiter with a bruit, exophthalmos, pretibial myxedema
• Thyroid storm - Fever, tachycardia, delirium

Diagnosis:

• TSH (best test): Decreased in primary disease (↓ TSH and ↑ Free T4), elevated in secondary disease (↑ TSH  and ↑ Free T4)
• T4 ⇒ elevated although may be normal
• Thyroid radioactive iodine uptake:
  • Graves: diffusely high uptake
  • Toxic multinodular: discrete areas of high uptake

Antibodies:

• Graves: Anti-thyrotropin antibodies (TSHR-Ab) - can be measured by either a TSI or TBII
  • Other antithyroid antibodies, such as antithyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies are also present in Graves disease but ⇒ levels tend to be even more elevated in autoimmune thyroiditis.

Treatment:

• Beta-blockers (symptomatic), methimazole/propylthiouracil, radioactive iodine, thyroidectomy
• Thyroid storm- prompt beta-blockers, hydrocortisone, methimazole/propylthiouracil, iodine
• Thyroidectomy- most likely complication is an injury to the recurrent laryngeal nerve (hoarseness)

Antithyroid drugs during pregnancy — Propylthiouracil used to be the drug of choice during pregnancy because it causes less severe birth defects than methimazole. But experts now recommend that propylthiouracil be given during the first trimester only. This is because there have been rare cases of liver damage in people taking propylthiouracil. After the first trimester, women should switch to methimazole for the rest of the pregnancy.

• For women who are nursing, methimazole is probably a better choice than propylthiouracil (to avoid liver side effects)

Hypothyroidism

Etiology: Hashimoto’s (chronic lymphocytic/autoimmune), previous thyroidectomy/iodine ablation, congenital

Presentation:

• Cold intolerance, fatigue, constipation, depression, weight gain, bradycardia
• Congenital: round face, large tongue, hernia, delayed milestones, poor feeding

Diagnosis:

Labs: TSH- elevated in primary disease. Low T4 (↑ TSH and ↓ Free T4)

• Hashimoto’s: antibodies to thyroid peroxidase (anti-TPO autoantibodies) and antithyroglobulin antibodies (anti-Tg)

Treatment: Levothyroxine. Follow up with serial TSH monitoring

Thyroid nodules

Thyroid Nodules are discrete masses within the thyroid gland, which may be benign or malignant and can affect thyroid function

• Common causes include benign adenomas, colloid nodules, Hashimoto's thyroiditis, and thyroid cancer (papillary, follicular, medullary, anaplastic)
• Symptoms: Most are asymptomatic and discovered incidentally; larger nodules may cause compressive symptoms such as dysphagia, hoarseness, or dyspnea. Functional nodules may present with hyperthyroidism
• Risk factors for malignancy: Radiation exposure, family history of thyroid cancer, male sex, rapid growth, vocal cord paralysis, or nodules >1 cm with suspicious features on imaging

DX:

• Thyroid function tests (TSH, free T4) to assess thyroid activity
• Ultrasound to evaluate nodule size, structure, and features (suspicious findings = microcalcifications, irregular margins, hypoechogenicity)
• Fine-needle aspiration (FNA) biopsy for nodules >1 cm or those with suspicious ultrasound findings to rule out malignancy
• Radioactive iodine uptake (RAIU) if hyperthyroidism is present

TX: Management depends on findings:

• Benign nodules: Monitor with periodic ultrasound and thyroid function tests
• Suspicious or malignant nodules: Surgical resection (lobectomy or total thyroidectomy)
• Functional nodules causing hyperthyroidism may be treated with radioactive iodine, antithyroid medications, or surgery
• Complications include compression of adjacent structures or progression to thyroid cancer in malignant cases

Thyroiditis

Thyroiditis is a general term that refers to “inflammation of the thyroid gland”. Thyroiditis includes a group of individual disorders causing thyroidal inflammation but presenting in different ways.

• Painful vs. Painless may be hypo or hyperthyroid

Hashimoto’s thyroiditis:

• Diffusely enlarged, painless, nodular goiter

Subacute thyroiditis (Quervain's thyroiditis):

• Young women, after a viral infection
• Painful enlarged thyroid with dysphagia, mild fever, neck pain
• DX: ↑ T4 and T3 and ↓ TSH concentrations. ↑ ESR, ↑ CRP.  Radioiodine or technetium imaging study will show low uptake
• TX: Aspirin or NSAIDs, propranolol
  • Thyroid function tests should be monitored every two to eight weeks to confirm the resolution of hyperthyroidism, detection of hypothyroidism, and subsequent normalization of function

Postpartum thyroiditis:

• 1-2 months of hyperthyroidism after delivery
• TX: Completely resolves, give propranolol for cardiac symptoms

Drug-induced: Thyroiditis can also be seen in patients taking certain drugs

• Antithyroid medications: methimazole and propylthiouracil
• Lithium - bipolar disorder
• Amiodarone - antiarrhythmic
• Interferon alpha
• Tyrosine Kinase Inhibitors (e.g. Sunitinib) - anti-cancer
• Checkpoint inhibitors (e.g. Nivolumab, Pembrolizumab)
• DX: TSH should be checked every 6-12 months
• TX: T4 therapy given right away

Infectious (suppurative) bacterial thyroiditis (rare) is often due to the hematogenous spread of staph or strep

• Its signs are the classic ones of inflammation: fever, heat, pain, redness, and swelling
• DX: ↑ WBC
• TX: Antibiotic/surgical drainage

Summary of thyroiditis: