Untitled Quiz

Thyroid Gland Anatomy

• The thyroid gland has two lobes (left and right) connected by an isthmus, a thin band of tissue.
• A pyramidal lobe may sometimes be present above the isthmus.
• The thyroid gland is located behind the larynx and thyroid cartilage.
• The trachea is situated behind the isthmus of the thyroid.

Thyroid Blood Supply

• The superior thyroid arteries originate from the external carotid artery.
• The inferior thyroid arteries arise from the thyrocervical trunk, which branches off the subclavian artery.
• The hyoid bone plays a role in the superior thyroid artery's location.
• The common carotid arteries supply blood to the thyroid gland.

Thyroid Embryology

• The thyroid gland develops from the floor of the pharynx, specifically from epithelial cells.
• During development (24-28 days old embryo), the thyroid gland originates from the floor of the pharynx.
• It initially maintains a connection to the tongue via the thyroglossal duct.
• At later stages of development, the thyroglossal duct disappears.
• Two remnants from the duct in child/adult remain. Including the pyramidal lobe of the thyroid and the foramen cecum of the tongue

Thyroglossal Duct Cysts

• A persistent remnant of the thyroglossal duct can result in a midline neck mass.
• These cysts are generally painless and often discovered in childhood.
• They are classically movable upward with swallowing or tongue protrusion.
• Some may contain thyroid tissue.

Ectopic Thyroid

• Functioning thyroid tissue outside the typical gland location.
• The most common location is the base of the tongue.
• It's commonly detected during puberty or pregnancy due to increased hormone demand.
• The ectopic tissue may be the only functioning thyroid tissue causing potential hypothyroidism.
• ↑TSH may stimulate growth of ectopic tissue.

Thyroid Histology

• The thyroid gland consists of follicles filled with colloid (protein material).
• Follicular cells form a single layer lining each follicle.
• The hormones are synthesized by follicular cells within these follicles.

Thyroid Hormones

• Thyroid hormones contain the element iodine.
• Iodized table salt (NaCl) is added with a minute amount of iodine to prevent iodine deficiency.
• Iodized salt was added to salt in the US in 1924.
• Two main hormones: T3 and T4.
• Synthesized from tyrosine and iodine.

Thyroglobulin

• Thyroglobulin is a large protein produced by follicular cells in the thyroid.
• It contains numerous tyrosine molecules.
• Tyrosine molecules are important for creating thyroid hormones.

Iodine

• Iodine (I) is a chemical element with atomic number 53.
• Iodine exists as iodide (I−) in plasma.
• In the thyroid, iodide needs to be taken up by follicular cells.
• Oxidized into I₂ through the process of “oxidation”
• "Organification" involves adding iodide to organic carbon structures.
• NIS is important for transporting iodide into the follicular cells.

Thyroid Hormone Regulation

• TSH (thyrotropin) is released by the anterior pituitary.
• It binds to receptors on follicular cells, stimulating a cAMP/PKA second messenger system that increases T3/T4 release.
• The rate of proteolysis of thyroglobulin is also increased, accelerating the release of T3/T4.
• The release of TSH is regulated by negative feedback loops involving the hypothalamus.
• Hypothalamus releases TRH which stimulates the pituitary's release of TSH.

Pregnancy and Thyroid Hormones

• Thyroid hormone production is affected during pregnancy.
• Total plasma T4/T3 levels rise due to increased TBG levels stimulated by estrogen.
• hCG may also stimulate the thyroid gland (shares the same alpha subunit as TSH).
• Free T4 increases, leading to decreased TSH.

Thyroid Panel

• Four standard measurements for assessing thyroid function:
• TSH (0.4-5.0 mU/L)
• Total T4 (60-145 nmol/L)
• Total T3 (1.1-3 nmol/L)
• Free T4 (0.01-0.03 nmol/L)
• Total T4 is primarily bound to TBG, therefore a higher level compared to free T4 Important Note: T4 is often higher than T3.

Calcitonin

• Calcitonin is a hormone synthesized by parafollicular cells (C-cells) of the thyroid gland.
• It has the function of lowering serum calcium, among other roles in calcium homeostasis.

Thyroid Disorders

• Thyroid disorders can be categorized into hyperthyroidism, hypothyroidism, and thyroiditis (inflammation).
• Some general considerations and examples of thyroid disorders will be provided.

Hypothyroidism

• Metabolism slows down, causing symptoms like lethargy, fatigue, cold intolerance, weight gain, constipation, and bradycardia.
• Symptoms of hypothyroidism often include reduced metabolism, leading to fatigue, impaired tolerance to cold temperatures, increased sensitivity to cold, constipation, and decreased heart rate.
• The classic hypothyroid symptom is that of a "cold intolerance".

Hyperthyroidism

• Metabolism speeds up, causing symptoms like hyperactivity, heat intolerance, weight loss, diarrhea, hyperreflexia, warm moist skin, and fine hair.
• Tachycardia and atrial fibrillation are also potential considerations.

Thyroid Storm

• Life-threatening hyperthyroidism that is typically precipitated by an acute event such as infection, surgery, trauma, or stress response to illness.
• Symptoms include fever, delirium, tachycardia, arrhythmias, and potentially fatal conditions such as hyperglycemia and hypercalcemia.

Goiter

• Enlarged thyroid gland, often from high TSH levels and the thyroid's inability to produce enough T3/T4.
• Thyroid-stimulating antibodies (Graves') can trigger goiter.

Radioiodine Uptake

• A diagnostic test for thyroid nodules.
• A small oral dose of iodine-131 is given, and a scanner measures the uptake.
• "Hot" nodules take up iodine strongly, often benign.
• "Cold" nodules show low uptake, potentially cancerous, requiring biopsy.

Thyroid Cancer

• Thyroid cancer, which usually presents as a nodule, doesn't often cause noticeable hyper/hypothyroidism symptoms.
• Biopsy by fine-needle aspiration is commonly used to distinguish benign nodules from cancerous ones.
• Thyroid cancer often detected on imaging using techniques like ultrasound.
• Common thyroid cancers include papillary, follicular, medullary, and anaplastic cancers.

General Principles

• Thyroid cancer typically doesn't elicit hyper or hypothyroidism symptoms.
• Often presents as a nodule requiring further investigation.
• Differential diagnosis includes benign adenoma vs. cancer.
• Fine-needle aspiration (FNA) biopsy is frequently used in evaluation.

21-a Hydroxylase Deficiency

• A very common cause of Congenital Adrenal Hyperplasia (CAH).
• It affects the production of cortisol and aldosterone, leading to a variety of symptoms, especially ambiguous genitalia in females, and precocious puberty in males.

11-ẞ Hydroxylase Deficiency

• Similar to 21-a hydroxylase deficiency but often leads to elevated mineralocorticoid activity.
• This can cause hypertension and hypokalemia, while cortisol production remains low.

17-a Hydroxylase Deficiency

• Low cortisol and mineralocorticoids, resulting in hypertension, and low androgens.
• Males typically present with ambiguous genitalia and undescended testes, while females may have delayed or absent puberty.

3-ẞ Hydroxysteroid Dehydrogenase Deficiency

• Deficiency affects cortisol and aldosterone production, leading to varied clinical presentations.
• Often presenting with ambiguous genitalia and early puberty.

Adrenal Insufficiency

• Insufficient cortisol (or cortisol and aldosterone in primary).
• Symptoms can include hypoglycemia, fatigue, weight loss, and hypotension.
• Diagnosis usually involves serum cortisol and ACTH levels as well as stimulation tests like ACTH testing.
• Treatment often includes glucocorticoid replacement therapy.

Adrenal Crisis

• Acute form of adrenal insufficiency.
• Abrupt onset, presenting as shock, nausea, vomiting, fatigue, and potentially life-threatening consequences.
• High-dose glucocorticoids are often given for management.

Adrenal Adenomas

• Often discovered incidentally during imaging of other abdominal processes.
• They are typically benign but can potentially secrete cortisol or aldosterone.

Pheochromocytoma/Paraganglioma

• Tumor of adrenal medulla tissue often causing episodic hypertension, headaches, palpitations, and sweating.
• Diagnosis involved measuring catecholamine metabolites in 24-hr urine samples.
• Management often involves surgical removal.

Neuroblastoma

• Tumor arising from sympathetic ganglion cells.
• Often found in children in the abdomen or adrenal glands.
• Symptoms can include abdominal pain and synthesis of catecholamines.
• Common clinical feature is Opsoclonus-myoclonus-ataxia (OMA).
• Prognosis depends on age at diagnosis and tumor staging. Early infant diagnosis typically associated with higher rates of cure.
• Specific biomarkers such as MIBG can be used in diagnostics.

Goitrogens

• Substances that inhibit thyroid hormone production.
• Iodine is a common goitrogen, along with certain foods like cassava and millet, and lithium.

Ketoconazole

• Antifungal, affecting steroidal synthesis, used in Cushing's syndrome treatment.
• Blocks ergosterol synthesis in fungi; also blocks steroid hormone synthesis.
• The side effects include gynecomastia.

Congenital Adrenal Hyperplasia (CAH)

• Genetic disorders causing adrenal insufficiency.
• Often present early in childhood, sometimes with ambiguous genitalia or precocious puberty.
• Treatment involves glucocorticoid replacement therapy to manage symptoms.
• Newborn screening programs measure 17-Hydroxyprogesterone to detect CAH, particularly 21-α hydroxylase deficiency.

Cushing's Syndrome

• Excess cortisol production, manifesting in various symptoms such as hypertension, hyperglycemia, and central obesity.
• Different etiologies can cause Cushing's syndrome, including the administration of steroids.
• Diagnosis often involves hormone tests like 24-hour urine free cortisol or low-dose dexamethasone suppression tests.
• Treatment depends on the underlying cause, typically involving surgical removal of tumors or the adjustment of steroid use.