Endocrine System Lecture Notes PDF

ENDOCRINE SYSTEM Copyright Pass NPLEX 2018 1  ENDOCRINE SYSTEM ▪ Embryology & Anatomy ▪ Physiology ▪ Biochemistry ▪ Pathology SAMPLE CASE 1 A 32-year-old female presents with galactorrhea, frequent he...

ENDOCRINE SYSTEM Copyright Pass NPLEX 2018 1  ENDOCRINE SYSTEM ▪ Embryology & Anatomy ▪ Physiology ▪ Biochemistry ▪ Pathology SAMPLE CASE 1 A 32-year-old female presents with galactorrhea, frequent headaches, and decreased vision in her left eye. She has a year-long history of amenorrhea. Radiologic studies confirm a pituitary adenoma. 1. Loss of vision in her left monocular visual field could be explained by damage to nerve fibers in the _________. A. Left optic tract B. Right optic tract C. Right frontal lobe cortex D. Left occipital lobe cortex 4 Copyright Pass NPLEX 2018 2  ▪ Answer: B – right optic tract Image: Wikimedia Commons – Author: Mads00 5 SAMPLE CASE#2 30-year-old female presents with, fatigue, weakness, muscle and joint pain. She mentions that she has been more thirsty than usual lately. Lab test results show elevated serum calcium and calciuria. She is diagnosed with primary hyperparathyroidism. 1. Which hormone counteracts the effects of parathyroid hormone? A. Calcitriol B. ADH C. Aldosterone D. Calcitonin 6 Copyright Pass NPLEX 2018 3  ▪ Answer: D - Calcitonin ▪ Calcitonin is secreted in response to increased plasma calcium levels. Calcitonin counteracts most of the effects of PTH in response to rising Ca2+ levels. ▪ Calcitriol is a form of vitamin D ▪ ADH stimulates sodium, potassium, and water retention in order to concentrate urine. ▪ Aldosterone decreases sodium removal from the body by stimulating the distal tubule to reabsorb sodium and secrete potassium. 7 EMBRYOLOGY & ANATOMY Copyright Pass NPLEX 2018 4  EMBRYOLOGY Endoderm ▪ Foramen cecum → Thyroid follicles ▪ 3rd, 4th pharyngeal pouches → Parathyroids ▪ Foregut → Parathyroid glands (4) Mesoderm ▪ Adrenal cortex ▪ Ovaries ▪ Testicles Ectoderm ▪ Diencephalon (sulcus) → Hypothalamus ▪ Infundibulum → Neurohypophysis (posterior pituitary) ▪ Rathke’s pouch → Adenohypophysis (anterior pituitary) ▪ Diencephalon (caudal) → Pineal gland ▪ Neural crest → Thyroid C cells ▪ Neural crest → Adrenal medulla HYPOTHALAMUS ▪ Interface between endocrine and neurological systems ▪ Made of nuclei that have multiple functions Copyright Pass NPLEX 2018 5  PITUITARY ▪ Master gland of the endocrine system that contains two-lobes ▪ Sits in the fossa of the sella turcica of the sphenoid bone Adenohypophysis (anterior pituitary) ▪ Attached to the neurohypophysis ▪ Secretes: ▪ ACTH, TSH, GH, LH, FSH, prolactin Pars intermedia divides the anterior and posterior sections ▪ Produces melanocyte stimulating hormone (MSH) Neurohypophysis (posterior pituitary) ▪ Hangs from the hypothalamus by the infundibulum ▪ Secretions originate in the hypothalamus: ▪ ADH (also known as vasopressin) oxytocin Anterior Lobe ▪ Chromophobe ▪ Clear (C) → non-differentiated/non-secretory ▪ Acidophil (alpha) ▪ Somatotrope → somatostatin ▪ Mammotrope → prolactin ▪ Basophil (beta) ▪ Thyrotrope → TSH ▪ Gonadotropes → FSH, LH ▪ Corticotropes → ACTH Intermediate Lobe ▪ Basophile → melanocyte-stimulating hormone Posterior Lobe ▪ PV/SO neurons → oxytocin, ADH Copyright Pass NPLEX 2018 6  PINEAL GLAND ▪ Attached to the roof of the third ventricle ▪ Located posterior to the thalamus and superior to the midbrain ▪ Pinealocytes secrete: ▪ Melatonin (at night) ▪ Serotonin (during the day) PARATHYROID GLANDS ▪ Generally four glands located on the posterior surface of the thyroid ▪ Blood supply primarily from branches of the inferior thyroid arteries ▪ Also can be supplied by the superior thyroid arteries, tracheal artery, esophageal artery, or laryngeal artery. ▪ Parathyroid veins drain these glands. ▪ Lymphatics drains to the deep cervical and paratracheal lymph nodes. ▪ Innervated by the thyroid branches of the cervical sympathetic ganglia. ▪ Chief cells ▪ Contain lipofuscin pigment and PTH ▪ Oxyphil cells ▪ Unknown function Copyright Pass NPLEX 2018 7  THYROID ▪ Largest endocrine gland located between C5-T1 below the sternohyoid and sternothyroid muscles. ▪ Right and left lobes attached via the isthmus (located over the 2nd & 3rd tracheal rings) ▪ Under control of TSH ▪ Secretes ▪ Thyroxine (T4) and 3,5,3’-triiodothyronine (T3) ▪ Stored in the lumen of follicular cells and stimulates the metabolic rate ▪ Calcitonin ▪ Stored in the parafollicular cells and stimulates calcium storage in the bones ▪ Supplied by the superior and inferior thyroid arteries ▪ Drained by the superior, middle, and inferior thyroid veins. ▪ Paratracheal lymph nodes and the prelaryngeal, pretracheal, and inferior deep cervical lymph nodes. ▪ Innervated by the superior, middle, and Image: Wikimedia Commons – Author: CFCF inferior cervical sympathetic ganglia. ▪ Follicles composed of simple cuboidal epithelium lining a cavity of gelatinous colloid ▪ Colloid serves as a reserve of thyroglobulin and iodine ▪ Parafollicular (C cells) are located between follicles Image: Wikimedia Commons – Author: Henry Gray Copyright Pass NPLEX 2018 8  ADRENAL GLANDS ▪ Located superior to the kidneys and encased in perirenal fat and a fibrous capsule. Cortex (outer → inner) ▪ Zona glomerulosa ▪ Mineralcorticoids ▪ Zona fasciculata ▪ Glucocorticoids ▪ Zona reticularis ▪ Androgens, glucocorticoids Medulla ▪ Contains sinusoids and capillaries ▪ Chromaffin cells → catecholamines ▪ Sympathetic ganglion cells ENDOCRINE PANCREAS ▪ Retroperitoneal digestive gland that lies near the descending duodenum (head) and posterior to the stomach (tail). ▪ Body contacts the stomach and left kidney and the tail contacts the spleen ▪ Contains islets of Langerhans ▪ Alpha → glucagon ▪ Beta → insulin ▪ PP (F) → pancreatic polypeptide ▪ Delta → somatostatin ▪ Epsilon → ghrelin Copyright Pass NPLEX 2018 9  ▪ Hepatopancreatic ampulla is formed by the joining of the bile duct and main pancreatic duct. ▪ Opens into the duodenum at major duodenal papilla and contains the sphincter of hepatopancreatic duct (aka sphincter of Oddi) ▪ Accessory pancreatic duct may connect with the main pancreatic duct. ▪ Opens at the minor duodenal papilla in the duodenum ▪ Pancreatic arteries supply the body and tail. ▪ Superior and inferior pancreaticoduodenal arterties supply the head. ▪ The pancreatic veins empty into the splenic vein. ▪ Pancreaticosplenic lymph nodes drain into the celiac, hepatic, and superior mesenteric lymph nodes. ▪ Innervated by the vagus and thoracic splanchnic nerves. ▪ Parasympathetics and sympathetics via the superior mesenteric and celiac plexi. PHYSIOLOGY Copyright Pass NPLEX 2018 10  PHYSIOLOGY ▪ Hypothalamus & pituitary hormones ▪ Peptide hormones ▪ Steroid hormones HYPOTHALAMUS & PITUITARY HORMONES Hypothalamic ▪ GnRH → increases FSH & LH secretion ▪ CRH → increases ACTH secretion ▪ TRH → increases TSH secretion ▪ GHRH → increases GH secretion ▪ DA → inhibits prolactin secretion from the anterior pituitary Posterior Pituitary ▪ ADH/vasopressin → increases renal H2O reabsorption; vasoconstriction ▪ Oxytocin → milk secretion, increased uterine contraction Copyright Pass NPLEX 2018 11  Anterior Pituitary ▪ LH → induces ovulation (female); increases testosterone secretion by Leydig cells (male) ▪ FSH → increases follicle growth and its estrogen secretion (female); increases spermatogenesis by Sertoli cells (male) ▪ ACTH → increases cortisol and aldosterone secretion ▪ TSH → increases thyroid hormone production ▪ GH → increases free fat mobilization, muscle glucose uptake, growth ▪ PRL → increases milk production Image: Wikimedia Commons – Author: OpenStax College Copyright Pass NPLEX 2018 12  Image: Wikimedia Commons – Author: LadyofHats PEPTIDE HORMONES ▪ Insulin ▪ Glucagon ▪ Somatostatin ▪ TSH ▪ T4 & T3 ▪ PTH & Calcitonin ▪ Renin-Angiotensin ▪ ADH ▪ Natriuretic hormones Prolactin Copyright Pass NPLEX 2018 13  INSULIN ▪ Made by beta cells in islets of Langerhans found in the endocrine pancreas ▪ Lowers serum glucose levels by increasing membrane glucose transport into the cells. ▪ Inhibits glycogenolysis and gluconeogenesis. ▪ Insulin binding promotes glycolysis, glycogenesis, lipogenesis, amino acid uptake, and protein synthesis in muscles. ▪ Somatostatin directly suppresses insulin secretion. Image: Wikimedia Commons – Author: XcepticZP Image: Wikimedia Commons – Author: Fred the Oyster Copyright Pass NPLEX 2018 14  GLUCAGON ▪ Made by alpha cells within the islets of Langerhans in the endocrine pancreas ▪ Promotes gluconeogenesis, glycogenolysis, and the release of glucose from storage cells in the liver. ▪ Release is stimulated by low blood glucose levels and increasing amino acid levels. ▪ Somatostatin and increasing blood glucose levels inhibit glucagon release. SOMATOSTATIN ▪ Made by delta cells in the islets of Langerhans in the endocrine pancreas, small intestines, stomach, and in the hypothalamus. ▪ Inhibits glucagon and insulin secretion from the alpha and beta cells, GH and TSH release from the anterior pituitary, gastrin, CCK, secretin, motilin, VIP, and GIP secretion. ▪ Secretion is stimulated by hypoglycemia, glucagon, the presence of fatty acids and amino acids, and beta-adrenergic agonists. Copyright Pass NPLEX 2018 15  TSH & THYROID HORMONES ▪ Synthesized in the anterior pituitary due to stimulation by TRH. ▪ Receptors are found on the thyroid follicle cells. ▪ Stimulates the synthesis and secretion of thyroid hormones (T4 & T3) ▪ Thyroid hormones are synthesized in thyroid follicles. ▪ T4 and T3 increase metabolic rate, body heat production, promotes CNS development, nerve conduction, protein synthesis and degradation, and increase the body’s response to sympathetic stimulation. Image: Wikimedia Commons – Author: Mikael Häggström Image: Wikimedia Commons – Author: Mikael Häggström Copyright Pass NPLEX 2018 16  PARATHYROID HORMONE & CALCITONIN PTH ▪ Synthesized in the parathyroid glands ▪ Released in response to declining plasma Ca2+ levels. ▪ Receptors are found in renal tubules, small intestinal epithelium, and osteoclasts. ▪ Increases bone resorption by osteoclasts ▪ Increases Ca2+ and decreases phosphate reabsorption by the kidney tubules ▪ Increased Ca2+ absorption by the small intestine via vitamin D Calcitonin ▪ Synthesized by the parafollicular cells of the thyroid. ▪ It is released in response to increased plasma Ca2+ levels Image: Wikimedia Commons – Author: OpenStax College Image: Wikimedia Commons – Author: Mikael Häggström Copyright Pass NPLEX 2018 17  RENIN & ANGIOTENSIN ▪ Renin is synthesized in the juxtaglomerular apparatus. ▪ Angiotensin is synthesized in the liver ▪ Angiotensin II is the receptor found on renal tubules, adrenal cortex, vascular smooth muscle, and the posterior pituitary. ▪ Angiotensinogen is converted to angiotensin I by Renin ▪ Angiotensin I is convered into Angiotensin II by Angiotensin Converting Eynzyme (ACE), which results in vasoconstriction (increased blood pressure), aldosterone secretion (Na & H2O reabsorption) and ADH secretion ▪ Renin secretion is stimulated by decreased blood pressure. Image: Wikimedia Commons – Author: A. Rad Copyright Pass NPLEX 2018 18  ANTIDIURETIC HORMONE ▪ Synthesized in the hypothalamus via the posterior pituitary ▪ Stimulates Na+, K+, and water retention which causes urine concentration and thirst. ▪ Stimulation is secreted in response to high plasma oncotic pressure and low plasma volumes. NATRIURETIC HORMONES ▪ Atrial natriuretic factor (ANF) ▪ Ouabain-like hormone (OLH) ▪ Synthesized in the atria of the heart and secreted in response to hypernatremia and volume expansion. ▪ Receptors are found on vascular smooth muscle and kidneys ▪ Causes peripheral vasodilation, inhibition of renin and aldosterone secretion, increased sodium excretion, and increased GFR with diuresis. Copyright Pass NPLEX 2018 19  MELATONIN ▪ Synthesize in the pineal gland ▪ Regulates diurnal behaviour ▪ It is an antioxidant and immunologically active. ▪ Connected via adrenergic nerves. ▪ NE from postganglionic neurons projecting from superior cervical ganglia stimulates beta-receptors in the pineal gland to produce melatonin. GROWTH HORMONE ▪ Synthesized in the anterior pituitary ▪ Receptors are found on most cells especially hepatocytes ▪ Stimulates the productions of IGF-1 by the liver and other tissues ▪ Promotes linear growth and beta-oxidation and stimulates collagen and protein synthesis, muscle growth, fat mobilization, and lipolysis. ▪ GHRH and ghrelin stimulate secretion. ▪ Somatostatin inhibits secretion. Copyright Pass NPLEX 2018 20  PROLACTIN ▪ Synthesized in the anterior pituitary. ▪ Receptors are found primarily on breast cells and most other cells. ▪ Promotes breast milk production, increases breast size, suppresses fertility and libido, elevates PGE2 levels, and has immunomodulatory action ▪ Dopamine inhibits secretion and synthesis. OXYTOCIN ▪ Synthesized in the hypothalamus via the posterior pituitary ▪ Receptors are found on cells in the breast, uterus, male reproductive tract, and brain ▪ Release results in the let-down of milk into mammary ducts, uterine contractions, and contributes to feeling of love, trust, and orgasm. Copyright Pass NPLEX 2018 21  GONADOTROPINS ▪ LH, FSH – synthesized in the anterior pituitary ▪ HCG – synthesized in the placenta ▪ Receptors are found on the ovaries, testes, and many other cells ▪ LH stimulates ovulation ▪ LH stimulates testosterone synthesis by Leydig cells and corpus luteum formation and progesterone synthesis. ▪ FSH supports spermatogenesis and other function of the Sertoli cells ▪ hCG maintains the corpus luteum ▪ GnRH stimulates the synthesis of FSH and LH. ▪ Estrogen, testosterone and FSH inhibit FSH and LH synthesis. GASTROINTESTINAL PEPTIDE HORMONES Gastrin ▪ G cells found in the antrum of the stomach and duodenum ▪ Increases gastric HCl ▪ Secretion is increased by food and decreased by HCl and somatostatin Ghrelin ▪ P/D1 cells in the fundus of the stomach and εcells in the pancreas ▪ Increases hunger, GI motility, and GH ▪ Secretion decreased by leptin and increased by empty gut CCK ▪ I cells in the duodenum and jejunum ▪ Increases gallbladder contraction and digestive enzymes, decreases hunger ▪ Secretion stimulated by food Copyright Pass NPLEX 2018 22  Motilin ▪ M cells in the duodenum and jejunum ▪ Increases GI motility and pepsin Secretin ▪ S cells in the duodenum and jejunum ▪ Increases bicarbonate secretion from the pancreas ▪ Secretion stimulated by the presence of acid in the duodenum VIP ▪ Enteric neurons ▪ Causes vasodilation and decreases GI motility and secretion ▪ Secretion is increased by parasympathetic stimulation LEPTIN ▪ Synthesized primarily in white adipose tissue ▪ Receptors are found in the CNS especially the hypothalamus ▪ Decreases hunger and insulin ▪ Synthesis is stimulated by glucocorticoids and insulin and inhibited by fasting. Copyright Pass NPLEX 2018 23  INCRETINS ▪ Synthesis occurs in the jejunum and duodenum ▪ L cells synthesize GLP-1 ▪ K cells synthesize GIP ▪ Receptors are located on beta cells ▪ GLP-1 and GIP stimulates insulin secretion GLP-1 ▪ Increases insulin sensitivity ▪ Inhibits glucagon secretion ▪ Inhibits gastric HCl secretion and gastric emptying ▪ Increases satiety GIP stimulates lipoprotein lipase in adipocytes CATECHOLAMINES ▪ Synthesized in chromaffin cells in the adrenal medulla secrete epinephrine and norepinephrine ▪ Stressor stimulates the sympathetic nervous system causing the release of NE and Epi. ▪ NE binds primarily with alpha-receptors and Epi bind with both alpha and beta- receptors. ▪ Increase HR, peripheral vasoconstriction and increase BP, vasoconstriction in the kidneys, digestive tract, and spleen, glycogenolysis, lipolysis, bronchodilation, increased brain arousal/alertness, pupil dilation ▪ Parasympathetic stimulation decreases catecholamine release. Copyright Pass NPLEX 2018 24  STEROID HORMONES ▪ Cortisol ▪ Aldosterone ▪ Testosterone ▪ Progesterone ▪ Vitamin D CORTISOL ▪ Synthesized in the zona fasciculata and reticularis of the adrenal cortex ▪ Primarily involved in immune and inflammation suppression and catabolic effect on protein and lipids. ▪ ACTH stimulates its synthesis in response to stressors and cortisol feedbacks to inhibits its production. Copyright Pass NPLEX 2018 25  ALDOSTERONE ▪ Synthesized in the zona glomerulosa of the adrenal cortex ▪ Receptors are found on the collecting ducts and renal distal tubules ▪ Stimulates the distal tubule to reabsorb Na+ and secrete K+. ▪ Stimulated by ACTH, hyperkalemia, angiotensin II Blood pressure/plasma osmolarity decreases → renin secreted → angiotensin II and aldosterone formed TESTOSTERONE ▪ Synthesized in the testes and zona reticularis of the adrenal cortex ▪ Induces male reproductive organs growth and secondary sex characteristics as well as function. ▪ Stimulates protein anabolism and promotes and stops bone growth ▪ Required for spermatogenesis and sex drive. ▪ Testes secrete testosterone at a constant rate. ▪ GnRH is secreted from the hypothalamus in pulses → FSH and LH → testosterone Copyright Pass NPLEX 2018 26  ESTROGEN ▪ Synthesized by granulosa cells in the ovaries, adrenal cortex, and testes ▪ Stimulates the growth of the ovary, follicles, and smooth muscles and the proliferation of epithelial linings of the reproductive tract. ▪ Increases uterine and fallopian tube contraction and epithelial cell layers in the vagina. ▪ Stimulates cervical mucus secretion, external genitalia growth, fat deposition, and pubic hair pattern. ▪ Stimulates bone growth and calcium deposition, stops bone growth and is involved in the closure of the epiphyseal plates, and protects against osteoporosis. ▪ Increases HDL and decreases LDL. PROGESTERONE ▪ Secreted from the corpus luteum, ovaries, and adrenal cortex ▪ Stimulates the endometrium to secrete a substance rich in glycogen and protein that supports the implanted embryo. ▪ Antagonizes estrogen and decreases contractions of the myometrium and uterine tubes. ▪ Decreases the proliferation of vaginal epithelial cells. ▪ Stimulates breast growth and inhibits prolactin. ▪ Responsible for the rise in basal body temperature after ovulation. ▪ FSH and LH stimulates the formation of corpus luteum and secretion of progesterone. Copyright Pass NPLEX 2018 27  VITAMIN D ▪ Active form is 1,25-dihydroxy vitamin D3 (aka calcitriol) ▪ Active calcitriol is made from ergosterol and from 7- dehydrocholesterol (in the skin) ▪ Ergosterol → ergocalciferol (vitamin D2) (via UV light) ▪ 7-dehydrocholesterol → cholecalciferol (vit D3) (via UV light) ▪ Cholecalciferol or ergocalciferol is absorbed in the intestine and is transported to the liver where it is hydroxylated to 25- hydroxy-D3 by D3-25-hydroxylase. ▪ 25-OH-D3 is converted to calcitriol in the proximal convoluted tubules in the kidneys, bone, and placenta. ▪ Can also be hydroxylated at the 24th position by another enzyme found in the kidneys, intestine, cartilage, and placenta. ▪ Increases Ca2+ and phosphate absorption in gut, antineoplastic, antimicrobial, immunomodulating ▪ PTH stimulates the activation of vitamin D Image: Wikimedia Commons – Author: OpenStax College BIOCHEMISTRY Copyright Pass NPLEX 2018 28  BIOCHEMISTRY ▪ Tyrosine is a precursor for both dopamine and thyroid hormones Notable Reactions Tyrosine hydroxylase (tyrosine → DOPA) ▪ Cofactor: tetrahydrobiopterin L-amino acid decarboxylase (DOPA → dopamine) ▪ Cofactor: vitamin B6 Dopamine beta-hydroxylase (dopamine → NE) ▪ Cofactors: vitamin C and copper 5’-deiodinase (T4 → T3) ▪ Cofactor: iron, selenium Cofactors: Cofactors: B3, Fe, Biopterin B6, B1 Phenyl- hydroxylase Cofactors: B3, Fe, Biopterin Phenylalanine Cofactors: SAMe, B12, folate (+) by: Cu, vit C (-) by: Glu, Cys, B5 Image: Wikimedia Commons – Author: Boghog2 Copyright Pass NPLEX 2018 29  SYNTHESIS AND DEGRADATION OF HORMONES ▪ Thyroid hormones ▪ Insulin ▪ Sex steroids ▪ Melatonin SYNTHESIS Thyroid Hormones ▪ Iodide is sequestered into thyroid follicles and then secreted into the colloid. ▪ Thyroid peroxidase oxidizes I- to I2 which is then attached to tyrosine. Insulin ▪ Proinsulin → insulin + C peptide (carboxypeptidase E, prohormone convertases 1&2) ▪ Insulin has two peptide chains bound together by two disulfide bridges ▪ C peptide is physiologically inert Copyright Pass NPLEX 2018 30  STEROID HORMONE SYNTHESIS Image: Wikimedia Commons – Author: Stannered Image: Wikimedia Commons – Author: Boghog2 Image: Wikimedia Commons – Author: David Richfield & Mikael Häggström. DEGRADATION OF MELATONIN ▪ Degraded in the liver primarily via CYP450 enzymes ▪ Hydroxylation at C6 then sulfation or glucouronidation ▪ 6-sulfatoxymelatonin is the main metabolite. Copyright Pass NPLEX 2018 31  PATHOLOGY PATHOLOGY ▪ Hyperfunction of endocrine organs ▪ Hypofunction of endocrine organs ▪ Inflammatory endocrine diseases ▪ Metabolic endocrine diseases ▪ Congenital endocrine disease ▪ Endocrine vascular diseases ▪ Endocrine neoplasms ▪ Infectious endocrine diseases Copyright Pass NPLEX 2018 32  HYPERFUNCTIONING ▪ Hyperadrenalism ▪ Cushing’s Syndrome ▪ Conn’s Syndrome ▪ Congenital Adrenal Hyperplasia ▪ Hyperparathyroidism ▪ Primary ▪ Secondary ▪ Hyperpituitarism ▪ Acromegaly ▪ Gigantism ▪ Hyperthyroidism (Thyrotoxicosis) ▪ Graves disease ▪ Toxic multinodular goiter CUSHING’S SYNDROME ▪ Increased circulating cortisol resulting in body fat redistribution. ▪ Causes: ▪ Increased ACTH from the anterior pituitary ▪ Iatrogenic due to exogenous corticosteroid administration ▪ Pituitary or ectopic ACTH-secreting adenoma or cancer (ex: small cell lung cancer) ▪ Adrenal cortisol-secreting adenoma ▪ Complications include osteoporosis, hypertension, recurrent skin infections, heart disease, diabetes, death ▪ Moon face, dorsal buffalo hump, hirsutism, muscle weakness, thin extremities due to muscle atrophy, osteoporosis, amenorrhea, skin atrophy, easy bruising, purple striae, hypertension, hyperglycemia, psychiatric dysfunction. Copyright Pass NPLEX 2018 33  CONN’S SYNDROME Excess aldosterone causing excessive K+ loss and sodium and water retention Primary aldosteronism ▪ Hyperproduction of adrenal mineralcorticoids due to a adrenocortical adenoma or hyperplasia of the zona glomerulosa Secondary aldosteronism/pseudohyperaldosteronism ▪ Caused by consuming excessive amounts of Glycyrrhiza glabra (glycyrrhetinic acid) ▪ Hypertension, sodium & water retention, hypokalemia, fatigue, decreased serum renin ▪ Complications include renal failure, rhabdomyolysis, hypertension, and death CONGENITAL ADRENAL HYPERPLASIA ▪ Mutation of genes for enzymes involved in steroidogenesis (autosomal recessive) ▪ Most commonly 21-hydroxylase deficiency ▪ Results in decreased cortisol production and compensatory increase in ACTH ▪ Altered primary and/or secondary sex characteristics, menstrual irregularity, anovulation, infertility, hirsuitism. ▪ Severe 21-hydroxylase deficiency results in salt wasting leading to vomiting or dehydration. ▪ Can result from an adrenal cortex tumor as well Copyright Pass NPLEX 2018 34  HYPERPARATHYROIDISM Elevated PTH → calcium mobilization from bone and hypercalcemia & hypercalciuria Primary ▪ Involves one or more parathyroid adenomas ▪ Elevated calcium ▪ Also can be due to ectopic production by non-parathyroid malignant tumors (bronchogenic squamous cell carcinoma or renal cell carcinoma or MEN type I and IIa) Secondary ▪ Chronic renal failure → impaired renal hydroxylation of 25-OH-D3 → hypocalcemia → elevated PTH ▪ Low serum calcium (reactive) ▪ Hyperplasia due to vitamin D deficiency, renal failure, hyperphosphatemia, hypocalcemia ▪ Paraneoplastic secretion of PTH-like protein (lung, kidney, T cell lymphoma, ovarian, and breast cancers) ▪ Risk factors include multiple endocrine neoplasia type I or 2A and familial hyperparathyroidism ▪ Hypercalcemia, hypophosphatemia, hypercalciuria, fatigue, weakness, myalgia, depression, arthralgia, polyuria, polydipsia, impaired appetite, arthralgia, cognitive impairment ▪ Elevated alkaline phosphatase and serum PTH levels, decreased serum phosphorus ▪ Complications include urolithiasis, osteoporosis, renal osteodystrophy Copyright Pass NPLEX 2018 35  PITUITARY ADENOMAS ▪ Benign monoclonal tumors from any of the five anterior pituitary cell types resulting in hypersecretion of any of the pituitary hormones (hyperpituitarism) ▪ Headache, bitemporal hemianopsia, diplopia, ptosis, decreased facial sensation, opthalmoplegia, weakness, nausea, amenorrhea, erectile dysfunction, decreased libido Prolactinomas – MC; due to hypothalamic lesion or medication ▪ Men – hypogonadism, galactorrhea ▪ Women – amenorrhea, galactorrhea, infertility Somatotropic adenomas (GH excess) ▪ Acromegaly/gigantism hyperhidrosis, athropathy, mandibular enlargement, enlarged thyroid, macroglossia, hypertension, diabetes mellitus Corticotropic adenomas (ACTH excess) ▪ Cushing’s disease and Cushing’s syndrome Thyrotropic adenoma (TSH excess) ▪ Goiter, visual field deficits, hyperthyroidism, headaches, diminishing visual acuity Posterior pituitary adenoma ▪ Diabetes insipidus Chromophobe adenoma (non-secreting pituitary adenoma) ▪ Due to local pressure ▪ Hypothyroidism, headaches, visual disturbances, cranial nerve palsies Gonadotropic adenomas ▪ Increased FSH and LH Copyright Pass NPLEX 2018 36  HYPERTHYROIDISM ▪ Excess thyroid hormone secretion ▪ Palpitations, rapid pulse/tachycardia, fatigue, weight loss despite increased appetite, nervousness, feeling hot, sweating, hair loss/fine hair, emotional lability, loose stools, menstrual changes (oligomenorrhorea or amenorrhea), tremor, eyelid retraction, heat intolerance, muscle wasting ▪ Increase in T3 and T4, decreased TSH ▪ Thyroid storm occurs when an another illness or extreme stress occurs. ▪ Hyperpyrexia, vomiting, diarrhea, dehydration, extreme tachycardia ▪ Can lead to coma or death Graves disease (most common) ▪ Diffuse toxic goiter due to autoimmune stimulation of the thyroid gland and attack on its tissues ▪ Autoantibodies against the TSH receptor active thyroid hormone release regardless of TSH levels ▪ General hyperthyroidism and exopthalmos ▪ Risk factors include HLA-DR3, autoimmune diseases ▪ Complications include other autoimmune disease and osteoporosis Toxic multinodular goiter ▪ Inactive nodules develop and enlarge over time before becoming hyperactive causing hyperthyroidism ▪ Can occur with Graves disease, Hashimoto’s thyroiditis ▪ Nodules are more prevalent in iodine-replete populations ▪ Complication include osteoporosis and thyroiditis Copyright Pass NPLEX 2018 37  NON-SECRETORY ENDOCRINE TUMORS Adrenal cortical adenoma ▪ Non-secreting (non-functioning) adrenal adenomas ▪ Symptomatic adenomas produce either Conn or Cushing syndromes ▪ Ganglioneuromas and myelolipomas Cold thyroid tumors ▪ Non-functional, benign thyroid nodules INSULINOMA ▪ Beta cell tumor ▪ Benign or malignant ▪ Increased in insulin secretion → hypoglycemia ▪ Whipple’s triad: CNS dysfunction (anxiety, stupor, convulsions, confusion, coma), episodic hypoglycemia, reversal of CNS symptoms with glucose administration Copyright Pass NPLEX 2018 38  CRANIOPHARYNGIOMA ▪ AKA adamantinoma ▪ Benign childhood tumor from Rathke’s pouch ▪ Not a true pituitary tumor ▪ Calcification can be seen on X-ray THYROID NEOPLASMS ▪ Papillary, follicular, anaplastic, medullary ▪ Differentiated (most common, good prognosis) ▪ Follicular carcinoma has a worse prognosis and is less common than papillary ▪ Poorly differentiated (rare, poor prognosis) ▪ Medullary (from parafollicular or C cells) and anaplastic ▪ Single painless thyroid nodule (cold on radioactive iodine scan), anorexia, fever, weight loss, fatigue, lymphadenopathy, metastatic disease ▪ Complications include local extension, metastasis, death Copyright Pass NPLEX 2018 39  MULTIPLE ENDOCRINE NEOPLASIA TYPE I & II ▪ More than one endocrine gland is hyperfunctional and is assocaited with hyperplasia or tumors. Type I ▪ Autosomal dominant ▪ Parathyroid adenoma or hyperplasia, pancreatic islet cell adenoma, hyperplasia or carcinoma, pituitary adenoma or hyperplasia, chrommafin cell tumors Type II ▪ Overactivity of thyroid, parathyroid, and adrenal glands ▪ Medullary thyroid carcinoma ▪ Pheochromocytoma can develop ▪ Type II a – Sipple’s syndrome ▪ Due to pheochromocytoma, medullary carcinoma of the thyroid and hyperparathyroidism ▪ Type II b – does not induce hyperparathyroidism GASTRINOMA ▪ Gastrin-secreting tumor of the pancreas or intestinal wall ▪ Can result in peptic ulcer, esophagitis, Barrett’s esophagus, esophageal stricture ▪ Associated with Zollinger-Ellison syndrome ▪ Extreme hyperchlorhydria with severe reflux esophagitis and peptic ulceration, extreme hypergastrinemia Copyright Pass NPLEX 2018 40  PHEOCHROMOCYTOMA ▪ Tumor of the adrenal medulla from chromaffin cells ▪ Secretes catecholamines ▪ Most commonly benign ▪ Paroxysmal or persistent severe hypertension with flushing, arrhythmias, hyperglycemia, hypermetabolism due to the release of norepinephrine and epinephrine. ▪ Increased urinary excretion of catecholamines and their metabolites HYPOFUNCTION OF ENDOCRINE ORGANS ▪ Diabetes insipidus ▪ Hypoadrenalism ▪ Hypoparathyroidism ▪ Hypopituitarism ▪ Hypothyroidism ▪ Congenital hypothyroidism Copyright Pass NPLEX 2018 41  DIABETES INSIPIDUS Decreased ADH → polydipsia and polyuria ▪ Due to tumor, trauma, inflammatory of the hypothalamus or neurohypophysis, lipid storage diseases ▪ Cannot concentrate urine, thirst wakes them from sleep Neurogenic ▪ Decreased ADH production Nephrogenic ▪ Vasopressin-resistant Dipsogenic ▪ Excessive water intake Gestagenic ▪ Decreased ADH production due to pregnancy HYPOADRENALISM ▪ Cortisol deficiency often with mineralcorticoid deficiency Primary hypoadrenalism (Addison’s disease) ▪ Failure of the adrenal glands to produce cortisol, aldosterone, androgens ▪ Can be due to autoimmune adrenalitis, TB, infections ▪ Fatigue, dizziness on standing, lethargy, hypotension, hyperpigmentation, hyperkalemia, salt craving, hyponatremia, hypochloremia, hypoglycemia, metabolic acidosis ▪ Complications: ▪ Addisonian crisis (profound hypotension, vomiting, diarrhea, weakness, dehydration, hypoglycemia, psychosis, dehydration, confusion, lethargy, convulsions, fever, hypercalcemia, death) triggered by acute stress, chronic hypoadrenalism Secondary adrenocortical insufficiency ▪ Anterior pituitary disease resulting in the failure to secrete ACTH ▪ Exogenous steroid therapy causing inhibition of ACTH production Copyright Pass NPLEX 2018 42  HYPOPARATHYROIDISM ▪ Low serum calcium and high serum phosphate ▪ Chvostek’s sign, Trousseau’s sign ▪ Most commonly occurs during error during a thyroidectomy ▪ Rarely due to DiGeorge’s syndrome ▪ Severe hypocalcemia → neuromuscular tetany and excitability HYPOPITUITARISM Low levels of secretion of one or more anterior pituitary hormones ▪ Lesions of the hypothalamus or adenohypophysis ▪ Adenoma putting pressure on the pituitary, loss of blood supply. Congenital agenesis, metastatic cancer ▪ When 75% of the lobe is destroyed symptoms manifest. ▪ Loss of LH and FSH → amenorrhea, ovarian or testicular atrophy ▪ Loss of TSH and ACTH Chromophobe adenomas ▪ Tumors of the hypophysis may compress the optic chiasm or pituitary gland causing hypopituitarism Empty sella syndrome ▪ Hypopituitary syndrome (agenesis of pituitary) ▪ Primary form → obesity and hypertension ▪ Secondary form → Sheehan’s syndrome Craniopharyngiomas ▪ Cystic tumors on the pituitary stalk ▪ Intrasellar lesions → hypopituitary syndromes (diabetes insipidus, pituitary hypothyroidism, amenorrhea, impotence, growth failure) ▪ Suprasellar lesions → visual disturbances Copyright Pass NPLEX 2018 43  HYPOTHYROIDISM ▪ Insufficient thyroid hormone secretion ▪ Myxedema (adults) or cretinism (newborns) ▪ Causes include deficiency of thyroid tissue, drug suppression, autoimmune thyroid destruction (Hashimoto’s), iodine deficiency, hypopituitarism with insufficient TSH ▪ Coarse hair and skin, hand and face edema, memory loss, pale cold dry skin, slow speech, lethargy, reduce HR and SV, irregular menstrual cycle (menorrhagia), constipation, weight gain (decreased BMR), puffy eyelids, face, and hands, goiter (if significant iodine deficiency), reduced DTRs ▪ Elevated serum TSH, decreased T3 and T4 levels, elevated serum cholesterol, and reduced T3 resin uptake ▪ Complications include dyslipidemia and atherosclerosis CONGENITAL HYPOTHYROIDISM ▪ Insufficient maternal iodine intake, deficiency of thyroid synthesis enzymes, improper development of the thyroid gland, transplacental transfer of maternal thyroid Ab ▪ Dwarfism, lethargy, decreased arm span:height ratio, hypothermia, somnolence, feeding difficulties, large tongue, protuberant abdomen, mental retardation ▪ The child is poor functioning and has a shortened life span Copyright Pass NPLEX 2018 44  INFLAMMATORY ENDOCRINE DISEASES ▪ Hashimoto’s thyroiditis ▪ Subacute thyroiditis HASHIMOTO’S THYROIDITIS ▪ Autoimmune inflammation of the thyroid generally associated with hypothyroidism ▪ Associated with Turner’s, Down’s, or Klinefelter’s syndrome, or other autoimmune diseases (pernicious anemia, diabetes mellitus type I, Sjogren’s syndrome); HLA- DR5 ▪ Painless thyroid enlargement (smoother, nodular, rubbery or firm), episodic hyperthyroid symptoms with general hypothyroid symptoms, elevated serum anti- thyroid peroxidase (antimicrosomal) and anti-thyroglobulin autoIgs ▪ Euthyroid → hyperthyroidism → hypothyroidism (once damaged) ▪ Often associated with other autoimmune conditions Copyright Pass NPLEX 2018 45  THYROIDITIS ▪ Painful enlargement of the thyroid gland ▪ Due to strep, staph, viruses, salmonella, sarcoidosis, or autoimmune conditions (Hashimoto’s thyroiditis) SUBACUTE THYROIDITIS AKA de Quervain’s thyroiditis Phase 1: Thyrotoxicosis/hyperthyroid ▪ Partial destruction of thyroid follicles (releases preformed thyroid hormone) Phase 2: Hypothyroidism ▪ Thyroid recovers from phase 1 Phase 3: Euthyroid ▪ Some never fully recover and stay in the hypothyroid state Granulomatous (painful), subacute (painless, silent), and postpartum ▪ Post viral infections (granulomatous and silent subacute) ▪ Associated with autoantibodies (silent and postpartum) Copyright Pass NPLEX 2018 46  METABOLIC ENDOCRINE DISEASES ▪ Diabetes Mellitus Type I ▪ Diabetes Mellitus Type II DIABETES MELLITUS TYPE I ▪ Autoimmune destruction of beta cells of the pancreas → inability to produce insulin without insulin resistance ▪ Dawn phenomenon ▪ Insulin cleared efficiently by the liver in the morning resulting in carbohydrates being less tolerated at breakfast ▪ Basal insulin ▪ Loss of basal insulin which must be replaced along with prandial insulin ▪ Mature-onset diabetes of the young (MODY) ▪ Autosomal dominant causing a mild form and results in hyperglycemia and low insulin without ketoacidosis ▪ Symptoms present in childhood with ketoacidotic coma (extreme hyperglycemia, metabolic acidosis, loss of consciousness) or polyuria, polydipsia, hunger, weight loss despite intake, hyperglycemia, decreased serum insulin ▪ Coma and death occur if insulin not replaced ▪ Complications include neuropathies, delayed gastric emptying, chronic renal failure, cataracts, retinopathy, skin ulcers, accelerated atherosclerosis, death Copyright Pass NPLEX 2018 47  DIABETES MELLITUS TYPE II ▪ Insulin resistance ▪ Latent autoimmune diabetes of the adult (LADA, type 1.5 diabetes) ▪ Autoimmune pancreatic destruction (anti-islet cell, anti-insulin, anti-glutamic acid decarboxylase (GAD) antibodies) ▪ Hyperglycemia, sugar hunger, obesity, polyphagia, elevated serum insulin ▪ Complications include neuropathies, chronic renal failure, delayed gastric emptying, retinopathy, cataracts, skin ulcers, accelerated atherosclerosis, death CONGENITAL ENDOCRINE DISEASE Thyroglossal duct cyst ▪ Result of persistent remnants of the thyroglossal duct tract ▪ Asymptomatic midline masses ▪ Can become infected to form an abscess and draining fistulas ▪ Elevates swallowing or tongue protrusion Copyright Pass NPLEX 2018 48  ENDOCRINE VASCULAR DISEASES Sheehan’s necrosis ▪ Infarction and necrosis of the pituitary usually due to postpartum hemorrhage with severe hypotension ▪ Mild forms results in hypoglycemia or failure to lactate ▪ Severe forms can result in hemodynamic instability, hypotension, and tachycardia and can be life threatening ▪ Chronic Sheehan’s results from less severe infarction and endocrine deficiencies that can be persist. ▪ Amenorrhea, loss of libido, partial or complete diabetes insipidus, and adrenal insufficiency INFECTIOUS ENDOCRINE DISEASE Infectious thyroiditis ▪ Painful enlargement of the thyroid gland due to staph, strep, salmonella, fungal infection, and viruses (cytomegalovirus and rubella) ▪ Fever, chills, malaise, pain and swelling of the anterior neck Waterhouse-Friderichsen syndrome ▪ Adrenal insufficiency and vascular collapse due to hemorrhagic necrosis of the adrenal gland ▪ Often due to DIC from meningococcemia Copyright Pass NPLEX 2018 49  KEY POINTS ▪ Hormones ▪ Where, what, how ▪ Stimulation/Inhibition ▪ Feedback loops ▪ Pathologies of thyroid, pituitary, parathyroid PRACTICE QUESTIONS 1. Which cofactor is needed by 5’-deiodinase? A. Selenium B. Copper C. Chromium D. Zinc 2. Which of the following is a key intermediate for synthesizing adrenal hormones? A. DHEA B. Progesterone C. Aldosterone D. Pregnenolone Copyright Pass NPLEX 2018 50  ANSWERS 1. A – selenium ▪ Iron and selenium are both needed by 5’-deiodinase 1. D – Pregnenolone IN THE NEXT SECTION… ▪ Section 4: Gastrointestinal System Copyright Pass NPLEX 2018 51