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• Thyroid Gland


  • Positioned in the lower anterior neck, shaped like a butterfly
  • Made up of two lobes, resting on each side of the trachea, bridged by the isthmus
• Thyroid Hormone


  Critical in regulating body metabolism, neurologic development, tissue growth, heat production, control of oxygen consumption, energy conservation
• Parathyroid Gland


  Posterior to the thyroid gland, regulate serum calcium levels
• Thyroid Hormone Synthesis


  1. Iodine (found in seafood, dairy products, and vitamins) is a key determinant in thyroid function

  2. Neuroendocrine system regulates the production and secretion of thyroid hormones

  3. Majority of thyroid hormones are bound to carrier proteins (Thyroxine-binding globulin, Thyroxine-binding prealbumin, Albumin)
• Thyroid Hormones


  • Thyroid Stimulating Hormone
  • Thyroxine (T4)
  • Triiodothyronine (T3)
  • Free Thyroxine (FT4)
  • Free Triiodothyronine (FT3)
• Thyroid Stimulating Hormone (TSH)

  • Origin: Anterior Pituitary Gland
  • Classification: Protein
  • Regulators: TRH and thyroid hormones
  • The most useful test in assessing thyroid function
  • Determination: First-generation, Second-generation, Third-generation, Fourth-generation
• Thyroxine (T4)


  • Principal secretory product of the thyroid gland
  • Its plasma concentration is a good indicator of the thyroid secretory rate
  • In the peripheral tissue, T4 is converted to T3
  • Reference range: 0.4-4.0 mIU/L
• Triiodothyronine (T3)


  • 20% produced by thyroid gland, 80% derived from the deiodination of T4
  • More biologically active thyroid hormone, more potent than T4 with shorter half-life
  • Total T3 is composed of both bound and free fractions, majority are bound to carrier proteins
  • Reference range: 80-200ng/dL
• Free Thyroxine (FT4)


  • Biologically active fraction of T4
  • Used as a second-line test in the evaluation of suspected thyroid disorders
  • Increased values suggest hyperthyroidism or excess thyroid hormone replacement, decreased values suggest hypothyroidism
  • Levels may be affected by abnormal TBBG and/or albumin, interfering substances: thyroid autoantibodies, biotin, and human anti-mouse antibodies (HAMA)
  • Reference range: 0.9-1.7 ng/dL
• Free Triiodothyronine (FT3)


  • Approx. 99.7% of total T3 is bound, remaining 0.03% is unbound
  • Biologically active form
  • Measured less frequently due to low fraction
  • Third-level test of thyroid function, may be required to evaluate clinically euthyroid patients (with abnormal thyroid binding proteins)
  • Increased values commonly associated with hyperthyroidism or with excess thyroid hormone replacement
• Other Tests for Thyroid Function

  • Thyroglobulin
  • Thyroid Autoimmunity (Thyroglobulin autoantibodies, Thyroperoxidase Antibody, Thyrotropin Receptor Antibody)
• Thyroglobulin


  Protein synthesized and secreted exclusively by thyroid follicular cells, proof of the presence of thyroid tissue, ideal tumor marker and post-treatment thyroid cancer surveillance test, can be measured by various methods
• Thyroid Autoimmunity


  Antibodies directed at thyroid tissue, including Thyroglobulin autoantibodies, Thyroperoxidase Antibody, and Thyrotropin Receptor Antibody
• Thyroglobulin Autoantibodies


  Most commonly associated with Hashimoto's thyroiditis, 35-60% of patients with hypothyroidism due to autoimmune disease have anti-Tg autoantibodies, reference range: <4.0 IU/mL
• Thyroperoxidase Antibody


  Most sensitive test for detecting autoimmune thyroid diseases, used as a diagnostic tool in deciding whether to treat a patient with subclinical hypothyroidism, inversely proportional to FT4 levels, thyroperoxidase catalyzes the binding of tyrosine residues, reference range: <9.0IU/mL
• Thyrotropin Receptor Antibody (TRAb)


  Most closely associated with disease pathogenesis, Long-acting thyroid stimulator (LATS), Thyroid-stimulating immunoglobulins (TSI) can cross placenta = neonatal thyrotoxicosis, reference range: ≥1.75 IU/L
• Other Tools for Thyroid Evaluation

  • Nuclear Medicine evaluation (Radioactive iodine, Radioactive iodine uptake)
  • Thyroid ultrasound
  • Fine Needle Aspirate Biopsy (FNAB)
• Nuclear Medicine Evaluation


  • Radioactive iodine useful in assessing the metabolic activity of thyroid tissue, assists in the evaluation and treatment of thyroid cancer
  • Radioactive iodine uptake (RAIU) - percentage of the dose taken up by the thyroid gland, high uptake indicates a metabolically active gland, low uptake indicates an inactive gland
• Thyroid Ultrasound


  A noninvasive procedure that uses high frequency sound waves to produce image, assessment of thyroid anatomy and characterization of palpable thyroid abnormalities, able to detect non-palpable thyroid nodules
• Fine Needle Aspirate Biopsy (FNAB)


  Often first step and most accurate tool in the evaluation of thyroid nodules in the absence of hyperthyroidism, commonly used with ultrasound-guided imaging, allows prompt identification and treatment of thyroid malignancies, cells are aspirated for cytologic evaluation and reported by the pathologist (Bethesda System for Reporting Thyroid Cytopathology)
• Disorders of the Thyroid

  • Hypothyroidism
  • Thyrotoxicosis
  • Hyperthyroidism
  • Drug-Induced Thyroid Dysfunction
  • Subacute Thyroiditis
  • Nonthyroidal Illness
  • Thyroid Nodules
• Hypothyroidism


  Defined as low FT4 with normal or high TSH, one of the most common disorders of the thyroid gland, symptoms include cold intolerance, fatigue, dry skin, constipation, hoarseness, dyspnea on exertion, cognitive dysfunction, hair loss and weight gain, divided into primary (thyroid gland dysfunction), secondary (pituitary dysfunction), and tertiary (hypothalamic dysfunction), most common cause is Hashimoto's thyroiditis, other common causes include thyroid surgery, radiation therapy, radioactive iodine treatment for hyperthyroidism, and medications
• Thyrotoxicosis


  Group of syndromes caused by high levels of free thyroid hormones in the circulation, can be the result of excessive thyroid hormone ingestion, leakage of stored thyroid hormone from thyroid follicles, or excessive thyroid gland production of thyroid hormone
• Hyperthyroidism


  Refers to an excess of circulating thyroid hormones, most common cause is Graves' disease (autoimmune disease in which antibodies are produced that activate the TSHR, features include thyrotoxicosis, goiter, ophthalmopathy, dermopathy, strong familial disposition, women are more likely to develop it than men, laboratory results show increased FT4 and/or T3 with decreased or undetectable TSH, TSI and TRAb are usually positive, elevated RAIU), other causes include toxic adenoma and multinodular goiter (caused by autonomously functioning thyroid tissue)
• Drug-Induced Thyroid Dysfunction


  Amiodarone-induced thyroid disease (fat-soluble drug with long half-life used to treat cardiac arrhythmias, interferes with normal thyroid function and blocks T4 to T3 conversion, patients taking this medication long-term can develop hyperthyroidism)
• Subacute Thyroiditis


  Conditions associated with a thyrotoxic phase when thyroid hormone is leaking into the circulation, a hypothyroid phase when the thyroid is repairing itself, and a euthyroid phase when the gland is repaired, includes post-partum thyroiditis (most common form, strongly associated with presence of TPO antibodies and chronic lymphocytic thyroiditis, patients may experience thyrotoxicosis) and painless thyroiditis (similar characteristics to post-partum thyroiditis but without pregnancy), painful thyroiditis (also called subacute granulomatous / subacute nonsuppurative thyroiditis / De Quervain's thyroiditis, characterized by neck pain, low-grade fever, myalgia, tender diffuse goiter, negative TPOAb, increased ESR and thyroglobulin)
• Nonthyroidal Illness


  Refers to abnormalities in the thyroid function tests without thyroid dysfunction, also known as euthyroid sick syndrome, laboratory pattern shows normal or low TSH, low T3 and low FT4, illness decreases 5'-monodeiodinase activity leading to less conversion of T4 to T3
• Thyroid Nodules


  Only 6-9% of nonpalpable nodules proved to be thyroid cancer, FNAB is the routine procedure to distinguish nodules
• Parathyroid glands


  • Ovoid or bean-shaped and measure approx. 3mm in size
  • Superior parathyroid glands are smaller than the inferior pair
  • Have specialized calcium-sensing receptors (CSRs) that respond to rising or falling calcium levels by increasing or decreasing PTH secretion
• Vitamin D

  • Steroid hormone that is synthesized in the skin from cholesterol following exposure to UVB rays from the sun
  • Two forms: Vitamin D2 and Vitamin D3
• For calcium to be maintained at optimal levels, Vitamin D and PTH work in conjunction with GI tract, kidneys, and bones
• Hypercalcemia

  When blood calcium levels are above the reference range
• Symptoms of hypercalcemia

  • Lethargy, stupor, and coma
  • Moderate increase - intellectual weariness, personality changes, nausea, anorexia, polyuria, kidney stones, hypertension, and ECG changes
• Primary hyperparathyroidism (PHPT)

  • Most common cause of hypercalcemia
  • Hallmark: autonomous overproduction of PTH
  • Caused by single adenoma, multiple gland hyperplasia, or parathyroid carcinoma
• Management of PHPT

  • Surgery: Parathyroidectomy
  • Medical management: Bisphosphonates, Selective estrogen receptor modulators, Estrogen, Cinacalcet
• Secondary Hyperparathyroidism


  • Compensatory rise in PTH secretion in response to factors that would lower blood calcium
  • Notable for the normal response of the parathyroid glands with appropriate and vigorous secretion of PTH
  • CKD: fails to excrete phosphate = impaired formation of 1,25(OH)2 D
• Tertiary Hyperparathyroidism


  Excessive secretion of PTH after prolonged secondary hyperparathyroidism with development of sustained hypercalcemia
• Familial Hypocalciuric Hypercalcemia (FHH)


  • Benign condition that results from germline mutation involving the CSR
  • Inheritance of autosomal dominant with 100% penetrance among carriers
  • PTH production and calcium elevation are not progressive and result to stable mild hypercalcemia
• Surgery is not advised for FHH - end-organ dysfunction is uncommon
• Hyperthyroidism


  Patients have increased bone resorption and hypercalcemia = PTH are low in these patients