5.3 Thyroid and parathyroid glands

The thyroid and parathyroid glands play crucial roles in regulating metabolism and calcium levels. These small but mighty organs produce hormones that affect nearly every cell in your body, influencing energy production, growth, and bone health.

Understanding how these glands work is key to grasping the endocrine system's complexity. From thyroid hormones controlling metabolism to parathyroid hormone managing calcium balance, these glands showcase the intricate hormone networks keeping your body in check.

Thyroid and Parathyroid Anatomy

Thyroid Gland Location and Structure

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• The thyroid gland, a butterfly-shaped endocrine gland, is situated in the anterior neck, inferior to the larynx and wrapped around the trachea, consisting of two lobes connected by an isthmus
• Follicles, the functional units of the thyroid gland, are spherical structures lined by follicular cells that produce and store thyroid hormones (thyroxine and triiodothyronine)
• Parafollicular cells (C cells) are found between follicles and secrete calcitonin, which helps regulate calcium homeostasis by lowering blood calcium levels

Parathyroid Gland Location and Structure

• The parathyroid glands, four small, oval-shaped endocrine glands, are embedded in the posterior surface of the thyroid gland, with two glands located on each lobe
• Parathyroid glands are composed of chief cells that produce and secrete parathyroid hormone (PTH) and oxyphil cells with an unknown function
• The small size of the parathyroid glands (approximately 3-6 mm in diameter) makes them difficult to locate and distinguish from the surrounding thyroid tissue

Thyroid and Parathyroid Hormones

Thyroid Hormones and Their Functions

• The thyroid gland produces and secretes two main hormones: thyroxine (T4) and triiodothyronine (T3), which are synthesized from the amino acid tyrosine and the mineral iodine
  • T3 and T4 regulate basal metabolic rate, growth and development, protein synthesis, and the activity of other endocrine glands (adrenal glands and gonads)
  • Thyroid hormones are essential for normal brain development during fetal life and early childhood, and deficiency can lead to intellectual disability (cretinism)
• Calcitonin, secreted by the parafollicular cells, helps regulate calcium homeostasis by lowering blood calcium levels through inhibiting bone resorption and increasing calcium excretion in the kidneys

Parathyroid Hormone and Its Functions

• The parathyroid glands secrete parathyroid hormone (PTH), which is the primary regulator of calcium homeostasis in the body
  • PTH increases blood calcium levels by stimulating bone resorption, increasing calcium reabsorption in the kidneys, and indirectly increasing calcium absorption in the intestines through the activation of vitamin D
  • PTH also decreases blood phosphate levels by inhibiting phosphate reabsorption in the kidneys, leading to increased phosphate excretion in the urine
• Parathyroid hormone-related protein (PTHrP), produced by various tissues, has similar effects to PTH and plays a role in regulating bone metabolism and fetal calcium homeostasis

Regulation of Thyroid Hormone

Hypothalamic-Pituitary-Thyroid Axis

• Thyroid hormone synthesis and secretion are regulated by a negative feedback loop involving the hypothalamus, anterior pituitary gland, and thyroid gland, known as the hypothalamic-pituitary-thyroid (HPT) axis
• The hypothalamus secretes thyrotropin-releasing hormone (TRH), which stimulates the anterior pituitary gland to produce and secrete thyroid-stimulating hormone (TSH)
• TSH binds to receptors on the follicular cells of the thyroid gland, stimulating the synthesis and secretion of T3 and T4
• Elevated levels of T3 and T4 in the blood provide negative feedback to the hypothalamus and anterior pituitary, suppressing the release of TRH and TSH, respectively, to maintain homeostasis

Iodine and Thyroid Hormone Synthesis

• Iodine is essential for the synthesis of thyroid hormones, and the thyroid gland actively transports iodide ions from the blood and incorporates them into thyroglobulin, a protein produced by follicular cells, to form T3 and T4
• Iodine deficiency can lead to goiter (enlargement of the thyroid gland) and hypothyroidism, while excessive iodine intake can cause hyperthyroidism (Jod-Basedow phenomenon)
• The enzyme thyroid peroxidase (TPO) catalyzes the oxidation of iodide and its incorporation into tyrosine residues of thyroglobulin, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT), which are then coupled to form T3 and T4

Parathyroid Hormone in Calcium Homeostasis

Regulation of Parathyroid Hormone Secretion

• Parathyroid hormone (PTH) is the primary regulator of calcium homeostasis, maintaining blood calcium levels within a narrow range (8.5-10.5 mg/dL)
• PTH secretion is regulated by the calcium-sensing receptors on the chief cells of the parathyroid glands, with low blood calcium levels stimulating PTH secretion and high blood calcium levels inhibiting it
• Vitamin D (calcitriol) also provides negative feedback on PTH secretion, as it increases calcium absorption in the intestines and reduces the need for PTH-mediated calcium mobilization

Mechanisms of Parathyroid Hormone Action

• PTH increases blood calcium levels through three main mechanisms:
  • Stimulating osteoclast activity in bones, leading to increased bone resorption and release of calcium into the bloodstream (osteolytic effect)
  • Enhancing calcium reabsorption in the kidneys, reducing urinary calcium excretion, by increasing the expression of calcium-binding proteins in the renal tubules
  • Indirectly increasing calcium absorption in the intestines by stimulating the activation of vitamin D (1,25-dihydroxyvitamin D) in the kidneys, which promotes calcium uptake by intestinal cells
• PTH also decreases blood phosphate levels by inhibiting phosphate reabsorption in the proximal renal tubules, leading to increased phosphate excretion in the urine (phosphaturic effect)
• Calcitonin, secreted by the thyroid gland, acts as an antagonist to PTH by lowering blood calcium levels through inhibiting bone resorption and increasing calcium excretion in the kidneys, providing a counterbalance to the effects of PTH