T + A Lect Objs

• Thyroid gland


  • Right and left lobes that sit anterolaterally to the trachea
  • Normally the lobes are connected by an isthmus
  • The functional unit is the thyroid follicle, a spherical structure surrounded by a single layer of thyroid epithelial cells
  • The lumen is filled with colloid composed of thyroglobulin, which is secreted and iodinated by the thyroid epithelial cells
• Iodothyronines


  A class of hormones resulting from the coupling of two iodinated tyrosine molecules
• Thyroid hormones


  • T4 (thyroxine, 90% of thyroid output)
  • T3 (triiodothyronine, 10% of thyroid output)
  • rT3 (reverse T3, less than 1% of thyroid output)
• Thyroid hormone synthesis


  1. Amino acids assembled into thyroglobulin

  2. Iodide transported into gland by NIS

  3. Iodide transported into follicular lumen by pendrin

  4. Iodide oxidized and incorporated into tyrosine residues of thyroglobulin to form MIT and DIT

  5. Coupling of iodinated tyrosines to form T4 and T3

  6. Iodinated thyroglobulin stored in follicular lumen

  7. Secretion involves endocytosis of iodinated thyroglobulin and enzymatic degradation to release T4 and T3
• Thyroxine binding globulin (TBG)

  Synthesized in the liver, binds T4 and T3 to maintain a large circulating reservoir and prevent loss in urine
• Hypothalamic-pituitary-thyroid axis


  The most important regulator of thyroid gland function and growth, with TSH stimulating every aspect of thyroid function
• Circulating thyroid hormones


  Act on the pituitary gland to decrease TSH secretion, and on hypothalamic TRH-secreting neurons
• Iodide


  At low levels, the rate of thyroid synthesis is directly related to iodide available. At high levels (>2 mg/day), intraglandular iodide concentration suppresses the NIS and TPO genes (Wolff-Chaikoff effect)
• T4 and T3 entry into cells

  Occurs by a carrier-mediated energy dependent process, with most T4 converted to T3 (or rT3) within the cell
• Physiologic effects of thyroid hormone

  • Increases basal metabolic rate
  • Increases heart rate, cardiac output, and decreases systemic vascular resistance
  • Enhances substrate mobilization and synthesis
  • Essential for normal brain development and function
  • Regulates skeletal development and growth
  • Required for normal reproductive function
• Thyroid hormones consist of T4, T3, and rT3, and thyroid intermediates consist of MIT and DIT. T4 is the predominant hormone secreted by the gland, while T3 is the most potent at the receptor level
• Thyroid hormone synthesis and secretion

  1. Uptake

  2. Oxidation

  3. Iodination

  4. Coupling

  5. Endocytosis

  6. Proteolysis

  7. Secretion
• TSH


  Regulates the secretion of T3 and T4 via its actions on NIS, TPO, and proteolytic enzymes. Also causes enlargement of the thyroid gland
• Bound vs free T3 and T4

  Majority of T3 and T4 in the blood are bound to TBG, rendering them inactive. Some T3 and T4 are in the active free form
• Conversion of T4 to T3

  Majority of T4 entering cells is converted to T3 by 5'-monodeiodenase
• Thyroid hormone action


  Work via nuclear receptors and transcription/translation to increase protein synthesis, resulting in increased metabolic rate, heat production, and cardiac output. Also imperative for normal growth and development
• The most common cause of hypothyroidism is Hashimoto's thyroiditis, presenting with decreased metabolic rate, weight gain, fatigue, and a puffy face
• The most common cause of hyperthyroidism is Graves' disease, presenting with goiter, weight loss, sweating, heat intolerance, and exophthalmos
• The adrenal gland is composed of a cortex, of mesodermal origin and a medulla, of neuro-ectodermal origin. The cortex produces steroid hormones and the medulla produces catecholamines.
• Zona glomerulosa


  The thin, outermost zone of the adrenal cortex that produces the mineralocorticoid aldosterone which regulates salt and volume homeostasis
• The zona glomerulosa is primarily regulated by the renin-angiotensin system and to a much smaller degree, ACTH.
• The zona glomerulosa does not express 17-α-hydroxylase, therefore zona glomerulosa cells never make cortisol or androgens.
• Aldosterone


  Its primary mechanism of action is through binding to a specific intracellular receptor, the mineralocorticoid receptor (MR)
• Aldosterone's primary action


  Increase the reabsorption of Na+, followed by H2O in the distal nephron
• Zona fasciculata


  The largest and most active steroidogenic zone that produces the glucocorticoid hormone, cortisol
• Cortisol


  Transported in the blood predominantly bound to proteins like corticosteroid-binding globulin (CBG) and albumin. The free form exerts biological effects and feeds back on the pituitary and hypothalamus.
• Cortisol mechanism of action

  1. Cortisol-GR binding promotes dissociation of chaperone proteins

  2. Rapid translocation of cortisol-GR complex into the nucleus

  3. Dimerization and binding to glucocorticoid response elements

  4. Increase or decrease in transcription rate of targeted genes

  5. Phosphorylation and nuclear export or degradation of GR, terminating the signal
• Major actions of cortisol


  • Hyperglycemic
  • Gluconeogenic
  • Lipolytic
  • Protein catabolic
  • Insulin antagonist in muscle and adipose tissue
  • Inhibits bone formation, stimulates bone resorption
  • Necessary for vascular responses to catecholamines
  • Anti-inflammatory
  • Immunosuppressive
  • Inhibits ADH secretion and action
  • Stimulates gastric acid secretion
  • Necessary for integrity and function of GI tract
  • Stimulates RBC production
  • Alters mood and behavior
  • Permissive for lipolytic effects of catecholamines
• Zona reticularis


  The innermost zone that produces both cortisol and adrenal androgens, especially DHEA
• Several peripheral tissues (breast, adipose tissue) express enzymes that can convert DHEA and androstenedione to the potent androgens, testosterone and dihydrotestosterone or to the potent estrogen, estradiol.
• Addison's disease


  Adrenocortical insufficiency with symptoms like hypotension, hyperpigmentation, muscle weakness, anorexia, hypoglycemia and hyperkalemic acidosis
• Cushing's syndrome


  Results from hypercortisolemia, with symptoms like centripetal fat, muscle wasting, thin skin with abdominal striae, insulin resistance, polycythemia
• Cushing's disease


  Cushing's syndrome caused by increased pituitary ACTH secretion
• Congenital adrenal hyperplasia


  Results from congenital enzyme deficiency that blocks production of cortisol, leading to elevated ACTH and adrenal cortical growth and secretion of precursors produced before the block
• High Yield Concepts from Adrenal Glands

  • The adrenal gland is composed of a cortex and medulla
  • The zona glomerulosa produces aldosterone
  • The zona fasciculata and zona reticularis produce glucocorticoids and sex hormones
  • Major stimuli for cortisol secretion include stress, hypoglycemia, hemorrhage, and ACTH
  • Major actions of cortisol include increasing gluconeogenesis, lipolysis and proteolysis
  • Cushing's syndrome results from hypercortisolism
  • Addison's disease is adrenocortical insufficiency
  • Congenital adrenal hyperplasia results from a congenital enzyme deficiency