PANCE Blueprint Endocrinology (7%)

Thyroid Disorders (PEARLS)

Thyroid test What it measures Normal range Associated thyroid condition(s) How levels are affected
Thyroid-stimulating hormone (TSH) The amount of TSH in the blood 0.3-4.0 mIU/L Hypothyroidism, hyperthyroidism High TSH levels indicate hypothyroidism, while low TSH levels indicate hyperthyroidism.
Free thyroxine (T4) The amount of free T4 in the blood 0.8-1.8 ng/dL Hypothyroidism, hyperthyroidism Low T4 levels indicate hypothyroidism, while high T4 levels indicate hyperthyroidism.
Free triiodothyronine (T3) The amount of free T3 in the blood 2.3-4.2 pg/mL Hypothyroidism, hyperthyroidism Low T3 levels indicate hypothyroidism, while high T3 levels indicate hyperthyroidism.
Thyroid peroxidase antibodies (TPOAb) The presence of antibodies to thyroid peroxidase <1.0 IU/mL Hashimoto's thyroiditis, Graves' disease High TPOAb levels can be present in people with Hashimoto's thyroiditis and Graves' disease.
Thyroglobulin antibodies (TgAb) The presence of antibodies to thyroglobulin <0.4 kIU/L Hashimoto's thyroiditis, Graves' disease High TgAb levels can be present in people with Hashimoto's thyroiditis and Graves' disease.
Thyroglobulin (Tg) The amount of Tg in the blood 3-40 ng/mL Thyroid cancer High Tg levels may be present in people with thyroid cancer.
Anti-thyrotropin antibodies (TSHR-Ab) The presence of antibodies to the thyrotropin receptor Negative Graves' disease High TSHR-Ab levels are present in people with Graves' disease.

Hyperthyroidism (ReelDx)

ReelDx Virtual Rounds (Hyperthyroidism)
Patient will present as → a 34-year-old female complaining of irritability and nervousness, heat intolerance with increased sweating, and weight loss despite an increase in appetite.

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)

Thyroid system


Hypothyroidism

Patient will present as → a 28-year-old woman with increased fatigue and a 10-lb weight gain over the last 2 months. She states that she “feels cold” all the time, has decreased energy, and is experiencing worsening constipation. The patient has a tender thyroid, increased TSH, elevated antimicrosomal antibodies, and increased antithyroglobulin antibodies.

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


Thyroiditis

Patient will present as → a 37-year-old female with a 2-week history of a painful mass in her neck after having a sore throat and fever for 3 days. The patient reports the mass has slowly been enlarging over that time span and has become more painful to the touch. She also reports feeling hot, even when her coworkers feel cold, and reports loose stools over the past week. The patient’s vital signs are T 98.6F, BP 140/90, Pulse 110 bpm, and SpO2 100%. On exam, you note a diffusely enlarged thyroid that is painful to the touch. TSH is decreased, T4/T3 is elevated, and radioactive iodine uptake and scan at 24 hours reveals an uptake of 3% (normal 8-25%).

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:

Type Cause Features Diagnosis Duration and resolution
Hashimoto’s thyroiditis Anti-thyroid antibodies, autoimmune disease Hypothyroidism, rare cases of transient thyrotoxicosis Thyroid function tests, thyroid antibody tests Hypothyroidism is usually permanent
Subacute thyroiditis (de Quervain’s thyroiditis) Possible viral cause Painful thyroid, thyrotoxicosis followed by hypothyroidism Thyroid function tests, sedimentation rate, radioactive iodine uptake Resolves to normal thyroid function within 12-18 months, 5% possibility of permanent hypothyroidism.
Silent thyroiditis, Painless thyroiditis Anti-thyroid antibodies, autoimmune disease Thyrotoxicosis followed by hypothyroidism. Thyroid function tests, thyroid antibody tests, radioactive iodine uptake Resolves to normal thyroid function within 12-18 months, 20% possibility of permanent hypothyroidism.
Postpartum thyroiditis Anti-thyroid antibodies, autoimmune disease Thyrotoxicosis followed by hypothyroidism Thyroid function tests, thyroid antibody tests, radioactive iodine uptake (contraindicated   if the hypothyroid woman is breastfeeding) Resolves to normal thyroid function within 12-18 months, 20% possibility of permanent hypothyroidism
Drug-induced Drugs include amiodarone, lithium, interferons, cytokines Either thyrotoxicosis or hypothyroidism. Thyroid function tests, thyroid antibody tests Often continues as long as the drug is taken
Radiation-induced Follows treatment with radioactive iodine for hyperthyroidism or external beam radiation therapy for certain cancers. Occasionally thyrotoxicosis, more frequently hypothyroidism Thyroid function tests Thyrotoxicosis is transient, hypothyroidism is usually permanent
Acute thyroiditis, Suppurative thyroiditis Bacteria mainly, but any infectious organism Occasionally painful thyroid, generalized illness, occasional mild hypothyroidism Thyroid function tests, radioactive iodine uptake, fine-needle aspiration biopsy Resolves after treatment of infectious cause, may cause severe illness
osmosis Osmosis
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Thyroid Gland Overview

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The thyroid gland is a large endocrine gland that is located in the neck. It releases T3 and T4 hormones, which help the body regulate metabolism. T3 and T4 stand for triiodothyronine (T3) and thyroxine, which can sometimes be referred to as tetraiodothyronine (T4). In addition, the thyroid gland has a blood calcium sensor that helps it detect when blood calcium levels are elevated, to which it responds. The thyroid gland releases calcitonin, which builds bone, resulting in an absorption of calcium from the bloodstream. Osteoblasts are the cells responsible for bone formation.

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Thyroid Function Screening Tests

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When a patient is suspected of having an underlying thyroid condition, there is a stepwise approach to ordering thyroid function tests. The initial screening test of choice is the measurement of thyroid stimulating hormone or TSH. Depending on the value determined, measurements of thyroid hormones (serum free T3 and free T4) may be taken, with the addition of a total T4 measurement to provide further evidence towards the underlying cause. Regardless of etiology, screening tests are not always reliable in a severely ill inpatient population, and special circumstances, like pregnancy, may alter the measured value of these tests.

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