Hormones and Endocrine - Endocrinology and Diabetes Course

Metformin is first-line, decreasing hepatic glucose production and insulin resistance to reduce cardiovascular risk in type 2 diabetes. The lecture summarizes classes and mechanisms, including GLP-1 analogues and SGLT inhibitors.

Metformin treats type 2 diabetes by inhibiting gluconeogenesis via mitochondrial glycerol-3-phosphate dehydrogenase, boosting glycolysis and glucose uptake with weight loss; use cautiously in renal impairment due to lactic acidosis risk.

Sulfonylureas block potassium channels in beta cells to trigger insulin release, requiring functioning beta cells; two generations include chlorpropamide to glimepiride, with hypoglycemia risk, weight gain, and disulfiram-like reactions.

Explore alpha-glucosidase inhibitors, including acarbose and miglitol, that treat type two diabetes by blocking intestinal alpha-glucosidase, keeping glucose in the lumen and causing GI symptoms.

GLP-1 analogues mimic natural GLP-1 to boost insulin, reduce glucagon, slow gastric emptying, and enhance satiety. DPP-4 inhibitors raise GLP-1 levels to similar effects without proven cardioprotection.

Insulin stimulates tyrosine kinase insulin receptor to regulate liver glycogen, muscle protein, and fat storage. It comes in rapid, short, intermediate, and long acting forms, lispro, regular, NPH, and glargine.

Meglitinides bind the beta cell potassium channel allosteric site, triggering insulin release. They are used with metformin for type 2 diabetes, postprandial, with thyroid and liver tumors, renal failure contraindication.

Explore SGLT2 inhibitors, gliflozin drugs that treat type 2 diabetes by inhibiting renal glucose reabsorption, causing glucosuria and potential dehydration, UTIs, and ketoacidosis risk.

Thiazide diuretics inhibit sodium chloride reabsorption in the distal tubules and alter calcium handling, promoting diuresis and making them useful for hypertension, heart failure, osteoporosis-related hypertension, and hypercalciuria.

Order TSH and T4 levels to distinguish cold versus hot nodules, then perform ultrasound and fine-needle aspiration for nodules over 1 cm or with malignant features, followed by radioiodine uptake.

Use the corticotropin-releasing hormone stimulation test to differentiate Cushing disease from Cushing syndrome: pituitary tumors show increased ACTH and cortisol in response to CRH, while ectopic ACTH does not respond.

Use a low-dose dexamethasone suppression test to distinguish cushing disease from cushing syndrome. Suppression indicates pituitary ACTH and cortisol source; no suppression points to outside-pituitary causes, such as paraneoplastic tumors.

The metyrapone stimulation test inhibits 11 beta hydroxylase, blocking cortisol synthesis and raising 11 deoxycortisol in normal patients, triggering increased ACTH; in adrenal insufficiency, 11 deoxycortisol and cortisol stay low.

Trace how angiotensinogen from the liver converts to angiotensin II via renin and ACE from the lungs, driving vasoconstriction and aldosterone-mediated sodium reabsorption that raise blood pressure.

Explore respiratory and metabolic acid-base balance by analyzing arterial PCO2 and bicarbonate, define alkalosis and acidosis, and use nacho, mud piles, and hardness to classify anion-gap status.

The lecture explains how prolactin drives milk production and oxytocin enables milk letdown, with prolactin blocked by estrogen and progesterone during pregnancy and released after delivery, maintained by suckling.

Maps hypothalamus anatomy near the optic chiasm and anterior commissure, outlines nuclei roles—supraoptic with oxytocin, suprachiasmatic circadian rhythm, cooling, posterior heating, lateral hunger, medial satiety—osmotic pressure sensing input and vomiting.

Explain the GnRH axis from hypothalamus to LH, testosterone, and dihydrotestosterone via 5 alpha reductase, and how leuprolide, spironolactone, ketoconazole, finasteride, and the CSF group affect it.

Use carbonic anhydrase to convert bicarbonate and hydrogen in the lumen to carbon dioxide and water. Reverse reaction in proximal tubule cells to form hydrogen and bicarbonate, absorbed into blood.

Explore how carbon dioxide is transported: most as bicarbonate via carbonic anhydrase in red blood cells, with chloride exchange, Bohr effect and Haldane effect, and eventual exhalation.

Learn how iodine deficiency makes the thyroid hypersensitive to iodine, triggering thyroxine synthesis and a thyroxine storm, especially when iodine intake becomes normal or slightly higher.

Explore how the Wolff-Chaikoff effect shows that excess iodine downregulates thyroid receptors, altering thyroxine production and the body's response to iodine intake.

Identify how aldosterone from the zona glomerulosa reabsorbs sodium, excretes potassium, and retains water, raising plasma volume and blood pressure; distinguish Addison's disease and Conn's syndrome from secondary, renin-driven hyperaldosteronism.

cortisol releases from the zona fasciculata via hypothalamic crh to the pituitary and adrenal cortex; feedback and binding globulin regulate it, with cortisol causing catabolic effects and cushing's or addison's.

Examine androgens from androstenedione to dihydrotestosterone, their conversion by five alpha reductase and aromatase to estrogen, and effects on testosterone therapy, fertility, growth, lipids, and abuse risks.

Regulate body fluid via hypothalamic osmoreceptors controlling antidiuretic hormone release. V1 vasoconstricts; V2 raises blood volume; desmopressin treats diabetes insipidus and nocturnal enuresis; demeclocycline and reptons correct hyponatremia.

Explore how cholecystokinin triggers gallbladder contraction and bile release, promotes pancreatic juice secretion and sphincter of Oddi relaxation, and delays gastric emptying, summarized by the GPUs memory.

Explore estrogen's mnemonic and its effects on myocyte excitability via receptor activation and nuclear gene modification. Review estradiol potency, placental estriol, aromatase, and estrogen's protection against osteoporosis and CAD.

Gastrin, released by g cells in the stomach and first part of the duodenum, increases gastric motility, acid secretion by parietal cells, and mucosal growth.

Glucagon from pancreatic alpha cells raises glucose through gluconeogenesis and glycogenolysis. It also boosts ketone production via ketogenesis and lipolysis in the liver, rising during fasting and hypoglycemia.

Explain how ace inhibitors block ace enzyme, lower angiotensin ii, raise bradykinin, and lower blood pressure, while protecting kidneys in diabetes and causing dry cough or angioedema.

Angiotensin II receptor blockers, the sartan class, lower blood pressure by blocking the receptor, have no bradykinin cough, protect against diabetic nephropathy, may raise creatinine, hyperkalemia, and are teratogenic.

Acetazolamide inhibits renal carbonic anhydrase, depleting bicarbonate and alkalizing urine to treat aspirin overdose, altitude sickness, and pseudotumor cerebri; glaucoma may follow, with sulfur allergy and metabolic acidosis.

Explore potassium-sparing diuretics such as spironolactone, eplerenone, triamterene, and amiloride that block collecting-duct sodium channels to promote diuresis and treat hyperaldosteronism, heart failure, and hyperandrogenism, with hyperkalemia and gynecomastia risks.

Loop diuretics inhibit the Na-K-2Cl cotransporter in the ascending loop of Henle, promoting diuresis and decreasing renal medullary tonicity, with use in edema, hypertension, and hypercalcemia.

Learn thiazide-like diuretics that act on the distal tubules to promote diuresis by altering sodium and calcium handling, useful for hypertension and heart failure, with osteoporosis and hypercalciuria considerations.

Fludrocortisone is a synthetic aldosterone analogue with glucocorticoid effects, used to replace adrenal function in primary adrenal insufficiency; it causes hypervolemia, edema, hyperpigmentation, and infection risk.

Identify diabetes criteria: A1C above 6.5%, fasting glucose above 126 mg/dl, or glucose tolerance test above 200 mg/dl. Distinguish type 1 autoimmune beta cell destruction from type 2 insulin resistance with amyloid, and note DKA and HHNS as key complications.

Understand euthyroid sick syndrome, where stress increases organ conversion of T4 to T3 in situ, creating high T3 demand while TSH and T4 stay normal.

Analyze how preload, cardiac output, and afterload determine shock states, including cardiac shocks from heart damage, hypovolaemic shock with reduced volume, and high output heart failure from fistulas.

Unpack congenital adrenal hyperplasia, detailing 21 hydroxylase, 11 beta hydroxylase, and 17 alpha hydroxylase deficiencies, their effects on aldosterone, cortisol, and sex hormones, with salt wasting, hypertension, and ambiguous genitalia.

Explain the adrenal steroid pathways from cholesterol to aldosterone, cortisol, and sex hormones, highlighting pregnenolone as the first step and enzymes 21-hydroxylase, 11 beta-hydroxylase, 17-hydroxylase, and aromatase.

Distinguish central diabetes insipidus from nephrogenic diabetes insipidus caused by brain damage or kidney receptor defects; diagnose with imaging and therapy response, and treat with ph analogs, hydration, and amiloride.

Breastfeeding jaundice results from immature bilirubin conjugation, causing indirect bilirubin buildup in week 1 and dehydration from milk; continue breastfeeding with phototherapy at 20 and exchange therapy at 25.

Manage bedwetting in children over five by ruling out cystitis with urine analysis, then address sleep and urine hygiene, use an enuresis alarm, and desmopressin to reduce urine output.

Identify the slow onset of type two diabetes and symptoms like thirst, frequent urination, and weight loss. Diagnose with HbA1C, fasting glucose, or oral glucose tolerance, and emphasize lifestyle changes.

Explain syndrome of inappropriate antidiuretic hormone secretion, causing euvolemic hyponatremia with high urine osmolality, diagnosed by water deprivation test and treated with salt, fluid restriction, and hypertonic saline if needed.

Learn about Escherichia coli types, including hemorrhagic E coli 0157 and pathogenic strains causing pediatric and traveler's diarrhea, plus dysentery and toxin-mediated disease; note antibiotic treatments with penicillins and cephalosporins.

Explore Staphylococcus aureus, a gram-positive, beta-hemolytic, catalase- and coagulase-positive bacterium with protein A and hemolysin, including MRSA, causing skin infections, toxic shock syndrome, endocarditis, and food poisoning.

Streptococcus forms long chains, produces toxins and pus, and modulates immunity, causing scarlet fever, necrotizing fasciitis, toxic shock-like syndrome, rheumatic fever via M protein mimicry, post-streptococcal glomerulonephritis, and pyogenic infections.

Block beta-1 receptors with beta blockers like propranolol, atenolol, labetalol, and esmolol to slow the heart and treat angina, SVT, and hypertension, while noting beta-2 mediated bronchoconstriction risk in asthma.

Cinacalcet sensitizes the parathyroid gland to calcium, lowering parathyroid hormone and risking hypercalcemia, with indications including primary hyperparathyroidism, failed parathyroidectomy, parathyroid carcinoma symptoms, and secondary hyperparathyroidism in CKD on hemodialysis.

Learn levothyroxine therapy for hypothyroidism, covering T4 and T3 forms, the four B's: bone growth, brain maturity, beta receptor activation, and basal metabolic rate, plus pregnancy dosing considerations.

Metoclopramide blocks central and peripheral dopamine D2 receptors, delivering prokinetic and antiemetic effects. It increases gastric motility and LES tone for gastroparesis and nausea.

Ondansetron and related anti-emetics block serotonin receptors on the vagus nerve to prevent vomiting via central and peripheral mechanisms, with side effects including serotonin syndrome, interval prolongation, constipation, and headache.

Sympathomimetics mimic sympathetic stress via direct receptor agonists and indirect mechanisms. Dobutamine raises heart function (beta-1); beta-2 agonists dilate bronchioles; epinephrine activates beta and alpha receptors.

Thioamides inhibit thyroid peroxidase to reduce thyroxine production, treating hypothyroidism. They may inhibit T4 to T3 conversion and carry risks of hepatotoxicity, teratogenicity, and agranulocytosis, necessitating stopping if it occurs.

Explore how aspirin irreversibly inhibits COX-1 at low doses to thin blood and COX-2 at high doses for anti-inflammatory effects, with risks like Reye’s syndrome, ulcers, tinnitus, and kidney injury.

Understand delta, kappa, and mu opioid receptors and how agonism reduces pain signaling, and review key opioids like pentazocine, butorphanol, tramadol, morphine, and fentanyl with withdrawal risks and side effects.

Nonsteroidal anti-inflammatory drugs block COX-1 and COX-2, inhibiting prostaglandin synthesis, with analgesic and antipyretic effects; they risk gastric mucosa damage, PDA dependency in certain heart diseases, and renal injury.

Paracetamol inhibits central nervous system cyclooxygenase, producing fever-reducing antipyretic and mild analgesic effects but no peripheral anti-inflammatory action. Overdose forms Napqi oxidant; hepatic glutathione detoxifies, and acetylcysteine regenerates glutathione.