USMLE 2024 Endocrine System PDF

HIGH-YIELD SYSTEMS Endocrine “If you skew the endocrine system, you lose the pathways to self.” ` Embryology 330 —Hilary Mantel ` Anatomy...

HIGH-YIELD SYSTEMS Endocrine “If you skew the endocrine system, you lose the pathways to self.” ` Embryology 330 —Hilary Mantel ` Anatomy 331 “Sometimes you need a little crisis to get your adrenaline flowing and help you realize your potential.” ` Physiology 332 —Jeannette Walls, The Glass Castle ` Pathology 342 “Chocolate causes certain endocrine glands to secrete hormones that affect your feelings and behavior by making you happy.” ` Pharmacology 358 —Elaine Sherman, Book of Divine Indulgences The endocrine system comprises widely distributed organs that work in a highly integrated manner to orchestrate a state of hormonal equilibrium within the body. Generally speaking, endocrine diseases can be classified either as diseases of underproduction or overproduction, or as conditions involving the development of mass lesions—which themselves may be associated with underproduction or overproduction of hormones. Therefore, study the endocrine system first by learning the glands, their hormones, and their regulation, and then by integrating disease manifestations with diagnosis and management. Take time to learn the multisystem connections. 329 330 SEC TION III ENDOCRINE ` ENDOCRINE—EMBRYOLOGY ` ENDOCRINE—EMBRYOLOGY Thyroid development Thyroid diverticulum arises from floor of primitive pharynx and descends into neck. Connected to A tongue by thyroglossal duct, which normally disappears but may persist as cysts or the pyramidal lobe of thyroid. Foramen cecum is normal remnant of thyroglossal duct. Most common ectopic thyroid tissue site is the tongue (lingual thyroid). Removal may result in hypothyroidism if it is the only thyroid tissue present. Thyroglossal duct cyst A presents as an anterior midline neck mass that moves with swallowing or protrusion of the tongue (vs persistent cervical sinus leading to pharyngeal cleft cyst in lateral neck). Thyroid follicular cells B derived from endoderm. B Parafollicular cells arise from 4th pharyngeal pouch. Foramen cecum Hyoid bone Thyrohyoid membrane Internal carotid artery Thyroglossal duct External carotid artery Thyroid cartilage Superior thyroid artery Thyroid Inferior thyroid artery Trachea Thyrocervical trunk Left subclavian artery Brachiocephalic artery  ENDOCRINE ` ENDOCRINE—ANATOMY SEC TION III 331 ` ENDOCRINE—ANATOMY Pituitary gland Anterior pituitary Secretes FSH, LH, ACTH, TSH, prolactin, Proopiomelanocortin derivatives—β-endorphin, (adenohypophysis) GH, and β-endorphin. Melanotropin (MSH) ACTH, and MSH. Go pro with a BAM! secreted from intermediate lobe of pituitary. FLAT PeG: FSH, LH, ACTH, TSH, PRL, GH. Derived from oral ectoderm (Rathke pouch). B-FLAT: Basophils—FSH, LH, ACTH, TSH. ƒ α subunit—hormone subunit common to Acid PiG: Acidophils — PRL, GH. TSH, LH, FSH, and hCG. ƒ β subunit—determines hormone specificity. Posterior pituitary Stores and releases vasopressin (antidiuretic (neurohypophysis) hormone, or ADH) and oxytocin, both made in the hypothalamus (supraoptic and paraventricular nuclei) and transported to posterior pituitary via neurophysins (carrier proteins). Derived from neuroectoderm. Adrenal cortex and Adrenal cortex (derived from mesoderm) and medulla (derived from neural crest). medulla HORMONE 1˚ HORMONE ANATOMY HISTOLOGY 1˚ REGULATION BY CLASS PRODUCED Zona Glomerulosa Angiotensin II Mineralocorticoids Aldosterone Adrenal gland CORTEX Zona Fasciculata ACTH, CRH Glucocorticoids Cortisol Capsule ACTH, CRH Androgens DHEA Zona Reticularis Preganglionic Superior surface Catecholamines Epi, NE MEDULLA Chromaffin cells sympathetic fibers of kidney GFR corresponds with salt (mineralocorticoids), sugar (glucocorticoids), and sex (androgens). Endocrine pancreas Islets of Langerhans are collections of α, β, and Capillary cell types δ endocrine cells. Islets arise from pancreatic buds. α cell α = glucαgon (peripheral) β cell β = insulin (central) δ = somatostatin (interspersed) δ cell 332 SEC TION III ENDOCRINE ` ENDOCRINE—PHYSIOLOGY ` ENDOCRINE—PHYSIOLOGY Hypothalamic-pituitary hormones HORMONE FUNCTION CLINICAL NOTES ADH  water permeability of distal convoluted tubule Alcohol consumption Ž  ADH secretion and collecting duct cells in kidney to  water Ž polyuria and dehydration reabsorption CRH  ACTH,  MSH,  β-endorphin  in chronic glucocorticoid use Dopamine  prolactin,  TSH Also called prolactin-inhibiting factor Dopamine antagonists (eg, antipsychotics) can cause galactorrhea due to hyperprolactinemia GHRH  GH Analog (tesamorelin) used to treat HIV-associated lipodystrophy GnRH  FSH,  LH Suppressed by hyperprolactinemia Tonic GnRH analog (eg, leuprolide) suppresses hypothalamic–pituitary–gonadal axis. Pulsatile GnRH leads to puberty, fertility MSH  melanogenesis by melanocytes Causes hyperpigmentation in Cushing disease, as MSH and ACTH share the same precursor molecule, proopiomelanocortin Oxytocin Causes uterine contractions during labor. Modulates fear, anxiety, social bonding, mood, Responsible for milk letdown reflex in response and depression to suckling. Prolactin  GnRH Pituitary prolactinoma Ž amenorrhea, Stimulates lactogenesis. osteoporosis, hypogonadism, galactorrhea Breastfeeding Ž  prolactin Ž  GnRH Ž delayed postpartum ovulation (natural contraception) Somatostatin  GH,  TSH Also called growth hormone inhibiting hormone (GHIH) TRH  TSH,  prolactin  TRH (eg, in 1°/2° hypothyroidism) may increase prolactin secretion Ž galactorrhea Hypothalamus CRH GnRH TRH GHRH DA Anterior pituitary ACTH LH FSH TSH GH Prolactin Somatostatin Basophils (basophilic) Acidophils (eosinophilic)  ENDOCRINE ` ENDOCRINE—PHYSIOLOGY SEC TION III 333 Growth hormone Sleep, hypoglycemia, stress, Aging, obesity, Also called somatotropin. Secreted by anterior puberty, exercise hyperglycemia pituitary. GHRH Somatostatin Stimulates linear growth and muscle mass through IGF-1 (somatomedin C) secretion by liver.  insulin resistance (diabetogenic). Released in pulses in response to growth hormone–releasing hormone (GHRH). Secretion  during sleep, hypoglycemia, stress, Posterior puberty, exercise. Anterior pituitary pituitary Secretion  with aging, obesity, hyperglycemia, somatostatin, somatomedin (regulatory molecule secreted by liver in response to GH acting on target tissues). Growth hormone Excess secretion of GH (eg, pituitary adenoma) may cause acromegaly (adults) or gigantism (children). Treatment: somatostatin analogs (eg, octreotide) or surgery. Amino acid uptake IGF-1 Amino acid uptake Glucose uptake Protein synthesis Protein synthesis Lipolysis DNA and RNA synthesis Chondroitin sulfate Collagen Cell size and number Antidiuretic hormone Also called vasopressin. SOURCE Synthesized in hypothalamus (supraoptic and paraventricular nuclei), stored and secreted by posterior pituitary. FUNCTION Regulates b1ood pressure (V1-receptors) and ADH level is  in central diabetes insipidus (DI), serum osmolality (V2-receptors). Primary normal or  in nephrogenic DI. function is serum osmolality regulation (ADH Desmopressin (ADH analog) is a treatment for  serum osmolality,  urine osmolality) via central DI and nocturnal enuresis. regulation of aquaporin channel insertion in Vasopressin is a potent vasopressor that can be principal cells of renal collecting duct. used to increase organ perfusion in septic shock. REGULATION Plasma osmolality (1°); hypovolemia. serum osmolality serum osmolality Hypothalamus serum volume serum volume urine osmolality ADH urine volume Posterior Medullary collecting duct pituitary Aquaporin channels (storage) ADH 334 SEC TION III ENDOCRINE ` ENDOCRINE—PHYSIOLOGY Prolactin SOURCE Secreted mainly by anterior pituitary. Structurally homologous to growth hormone. FUNCTION Stimulates milk production in breast; inhibits Excessive amounts of prolactin associated with ovulation in females and spermatogenesis  libido. in males by inhibiting GnRH synthesis and release. REGULATION Prolactin secretion from anterior pituitary Dopamine agonists (eg, bromocriptine, is tonically inhibited by dopamine from cabergoline) inhibit prolactin secretion and tuberoinfundibular pathway of hypothalamus. can be used in treatment of prolactinoma. Prolactin in turn inhibits its own secretion Dopamine antagonists (eg, most antipsychotics, by  dopamine synthesis and secretion from metoclopramide) and estrogens (eg, OCPs, hypothalamus. TRH  prolactin secretion (eg, pregnancy) stimulate prolactin secretion. in 1° or 2° hypothyroidism). Dopamine has stronger effect on prolactin regulation than TRH does. Sight/cry of baby Higher cortical centers Hypothalamus Medications Chest wall injury (via ANS) Dopamine TRH 1°/2° hypothyroidism Nipple stimulation Posterior Anterior pituitary pituitary Estrogen Pregnancy Reduced prolactin elimination FSH Ovulation Renal failure Prolactin GnRH Spermatogenesis LH Milk production  ENDOCRINE ` ENDOCRINE—PHYSIOLOGY SEC TION III 335 Thyroid hormones Thyroid produces triiodothyronine (T3) and thyroxine (T4), iodine-containing hormones that control the body’s metabolic rate. SOURCE Follicles of thyroid. 5′-deiodinase converts T4 (the major thyroid product) to T3 in peripheral tissue (5, 4, 3). Peripheral conversion is inhibited by glucocorticoids, β-blockers, and propylthiouracil (PTU). Reverse T3 (rT3) is a metabolically inactive byproduct of the peripheral conversion of T4 and its production is increased by growth hormone and glucocorticoids. Functions of thyroid peroxidase include oxidation, organification of iodine, and coupling of monoiodotyrosine (MIT) and diiodotyrosine (DIT). Inhibited by PTU and methimazole. DIT + DIT = T4. DIT + MIT = T3. Wolff-Chaikoff effect—protective autoregulation; sudden exposure to excess iodine temporarily turns off thyroid peroxidase Ž  T3/T4 production. FUNCTION Only free hormone is active. T3 binds nuclear receptor with greater affinity than T4. T3 functions —7 B’s: ƒ Brain maturation ƒ Bone growth (synergism with GH and IGF-1) ƒ β-adrenergic effects.  β1 receptors in heart Ž  CO, HR, SV, contractility; β-blockers alleviate adrenergic symptoms in thyrotoxicosis ƒ Basal metabolic rate  (via  Na+/K+-ATPase Ž  O2 consumption, RR, body temperature) ƒ Blood sugar ( glycogenolysis, gluconeogenesis) ƒ Break down lipids ( lipolysis) ƒ Stimulates surfactant synthesis in Babies REGULATION TRH Ž ⊕ TSH release Ž ⊕ follicular cells. Thyroid-stimulating immunoglobulin (TSI) may ⊕ follicular cells in Graves disease. Negative feedback primarily by free T3/T4: ƒ Anterior pituitary Ž  sensitivity to TRH ƒ Hypothalamus Ž  TRH secretion Thyroxine-binding globulin (TBG) binds most T3/T4 in blood. Bound T3/T4 = inactive. ƒ  TBG in pregnancy, OCP use (estrogen Ž  TBG) Ž  total T3/T4 ƒ  TBG in steroid use, nephrotic syndrome T3 and T4 are the only lipophilic hormones with charged amino acids and require specific transporters to diffuse into the cell (facilitated diffusion). Follicular lumen Thyroid follicular epithelial cell Blood Effector organs Hypothalamus TG TG + I₂ I- I- Downstream thyroid Na+ function Anterior pituitary Thyroid Organification, peroxidase coupling T₃ TSI Thyroid gland T₃ (follicular cells) TG TG T₃