Peripheral Endocrine Function PDF

**Peripheral Endocrine Function** **GH, PRL, ADH, T3/4, PTH, Adrenal, &ADH** PA Medical Physiology +-----------------------------------+-----------------------------------+ | **Peripheral Endocrine Function** | 1. **[In general:]** | | | What would be the ef...

**Peripheral Endocrine Function** **GH, PRL, ADH, T3/4, PTH, Adrenal, &ADH** PA Medical Physiology +-----------------------------------+-----------------------------------+ | **Peripheral Endocrine Function** | 1. **[In general:]** | | | What would be the effect of | | **GH, PRL, ADH, T3/4, PTH, | each of the endocrine | | Adrenal (Cort, Aldo, androg), | disorders on the body? 'Too | | &ADH** | much or too little X hormone | | | leads to ABC symptoms" | | | | | | a. Are there blood glucose | | | effects? If so, how does | | | that happen? What effect | | | does the pathology have | | | on gluconeogenesis, | | | glycogenolysis, | | | glycogenesis, lipolysis, | | | are there | | | anabolic/catabolic | | | effects? | | | | | | b. Too much or too little of | | | X hormone would have what | | | kind of effects on: Blood | | | pressure, heart rate, | | | Na+, K+, urine output, | | | growth effects, Ca+, | | | Phosphate, skin pigment, | | | metabolism, breast | | | development and function, | | | secondary sex | | | characteristics, the | | | body's response to | | | stress. | | | | | | i. GH, Prolactin, | | | Thyroid hormones, | | | PTH, Calcitonin, | | | adrenocortical | | | hormones | | | (Glucocorticoids=Cort | | | isol, | | | Mineralocorticoids = | | | Aldosterone, | | | Androgens = | | | Testosterone, DHT | | | mainly which are | | | precursors to | | | Estrogen), ADH, and | | | adrenal medulla | | | hormones. | | | | | | c. What is the treatment for | | | too much or too little X | | | hormone? | | | | | | d. Name some of the causes | | | of hyper/hypo secretion | | | of each of the hormones. | | | | | | | | | | | | 2. How can primary and secondary | | | endocrine disorders be | | | differentiated? (reviewed in | | | previous chapter, practice it | | | here with each endocrine | | | axis). | | | | | | 3. Cite possible causes for | | | dysfunction of the | | | hypothalamic-pituitary | | | system. | | | | | | 4. What are the symptoms, | | | treatments, and causes of | | | hyposecretion disorders of | | | each of the endocrine axes? | | | (GH, Thyroid axis, | | | PTH/Calcitonin, Cortisol, | | | Aldosterone, Gonadal axis | | | hormones, NE/EPI form the | | | adrenal medulla, ADH (central | | | vs nephrogenic DI). | | | | | | 5. What are the symptoms, | | | treatments, and causes of | | | hypersecretion disorders of | | | each of the endocrine axes? | | | (GH, Thyroid axis, | | | PTH/Calcitonin, Cortisol, | | | Aldosterone, Gonadal axis | | | hormones, NE/EPI from the | | | adrenal medulla, ADH (SIADH). | | | | | | e. How are hypothyroidism | | | and hyperthyroidism | | | different. How are each | | | of the following | | | affected: | | | | | | f. basal metabolic rate, | | | sympathetic nervous | | | system response, weight, | | | temperature tolerance, GI | | | function, cardiovascular | | | function, respiratory | | | function, muscle tone and | | | reflexes, general | | | appearance, and general | | | behavior | | | | | | 6. Compare and contrast the | | | disorders of hyperthyroidism | | | to include cause, | | | manifestations, treatment, | | | and complications: especially | | | Grave's disease -- how is it | | | similar or different than | | | other causes of | | | hyperthyroidism? | | | | | | 7. Discuss the similarities and | | | differences of the disorders | | | of hypothyroidism: Hashimoto | | | disease (autoimmune | | | thyroiditis), & Lithium | | | toxicity | | | | | | 8. Discuss the manifestations of | | | a primary pituitary adenoma; | | | relate the HGH levels to | | | acromegaly and giantism. | | | | | | 9. Describe the causative factor | | | and manifestations for the | | | hypersecretion of prolactin. | | | | | | 10. Distinguish between primary | | | and secondary | | | hyperparathyroidism and | | | hypoparathyroidism. What | | | hormones in that axis would | | | be increased/decreased? | | | | | | 11. Describe the clinical | | | manifestations of | | | hyperparathyroidism and | | | hypoparathyroidism to the | | | respective blood calcium | | | levels. | | | | | | 12. Be able to describe the | | | production and regulation of | | | mineralcorticoids, | | | glucocorticoids, and androgen | | | and the key hormones/triggers | | | that stimulate each pathway's | | | activation. | | | | | | g. How is the RAAS system | | | regulated? What is the | | | main stimulation? What is | | | the overall effect? How | | | does this work in a | | | negative feedback loop? | | | | | | ii. Why is aldosterone | | | largely unaffected by | | | altered levels of | | | ACTH? | | | | | | iii. What if there was a | | | tumor secreting too | | | much X hormone in the | | | RAAS system -- over | | | all body effects? | | | | | | iv. What if there was | | | damage to an organ of | | | the RAAS system? How | | | would the rest of the | | | system be affected? | | | How would K+, Na+, | | | blood pressure be | | | affected? | | | | | | 13. Describe the etiology, | | | pathogenesis, and | | | manifestations of | | | hyperfunction and | | | hypofunction of the adrenal | | | cortex: Cushing disease, | | | Cushing syndrome, primary | | | hyperaldosteronism (Conn | | | disease), secondary | | | hyperaldosteronism, | | | feminization, virilization, | | | and Addison disease. | | | | | | 14. Describe the cause, clinical | | | manifestations, and treatment | | | for adrenal medulla | | | hyperfunction. | | | | | | 15. Generate comparative diagrams | | | of SIADH and diabetes | | | insipidus, including | | | causative factors, cellular | | | pathophysiology, | | | manifestations, treatment, | | | and prognosis. | | | | | | 16. Compare central and | | | nephrogenic diabetes | | | insipidus. What are the | | | effects on the kidney, blood | | | volume, blood pressure, urine | | | and blood tonicity. What are | | | the treatments for each? How | | | would those treatments be | | | administered? | +-----------------------------------+-----------------------------------+ I. Endocrine control of growth A. Factors influencing growth 1. Genetic determination of an individual's maximum growth capacity 2. An adequate diet 3. Freedom from chronic disease and stressful environmental conditions 4. Normal levels of growth-influencing hormones i. Thyroid hormone, insulin, sex hormones B. Evaluation of growth 5. See growth charts from powerpoint II. GH disorders C. Regulation and actions of GH 6. Hypothalamus role: ii. Secretes GHRH which activates Ant. Pit cells to secrete GH. iii. Secretes Somatostatin which inhibits the Ant Pit release of GH. iv. Follows circadian cycle v. Greatest secretion in adolescence. 7. GH actions vi. Anabolic -- uses energy to build molecules (muscle, cartilage, bone, liver, kidney, nerves, skin, and lungs, etc). a. Increases protein synthesis b. Increases mitosis c. Decreases protein and carbohydrate breakdown d. Stimulates liver to make IGF-1 (Insulin like growth factor). i. Causes glucose uptake to tissues as a fuel for growth. e. Causes liver to make some small amounts of insulin (insulin is also anabolic) vii. Increases fuel for that growth f. Glycogenolysis g. Gluconeogenesis h. lipolysis = Mobilizes fats -- breaks them down for energy 8. GH regulation viii. GHRH from hypothalamus ix. Somatostatin from hypothalamus, stomach, liver, pancreas, etc. x. IGF1 (insulin like Growth factor....aka somatomedin) -- similar effect of GH. i. Secreted from the liver *(and perhaps other target tissue of GH).* D. GH deficiency 9. Etiology xi. can be caused by midline brain tumors impinging on hypothalamus *(secondary GH deficiency)* or pituitary *(primary).* xii. Radiation or chemotherapy can damage hypothalamus and/or pituitary. xiii. Trauma to sella turcica 10. Clinical Manifestations xiv. Children j. Hypoglycemia --GH normally increases blood glucose ii. especially dangerous in infants because it more easily leads to seizures and brain damage k. Male infants -- undescended testicle or micropenis l. Delayed tooth development m. Poor hair and nail growth n. Delayed puberty o. *Overweight* p. Poor bone development -- short stature (Dwarfism) xv. adults q. more rare to have onset in adulthood r. most occur after trauma or pituitary tumor removal iii. they are normally evaluated for hormonal changes so symptoms rarely progress. s. Sx -- iv. Decreased lean body mass v. Hypercholesterolemina vi. Decreased bone density. xvi. Treatment t. Hormone replacement therapy injections E. GH excess 11. Etiology xvii. Normally caused by malignant hypersecretion of both GH and its action on IGF1 12. Children xviii. rapidly exceed the 95^th^ percentile on pediatric growth charts. xix. If it occurs before the epiphyseal plates close the child can grow to 8+ feet tall. xx. Cardiovascular problems normally result and lead to an early death. 13. **Acromegaly** xxi. Normally occurs [after] epiphyseal plates close -- but bones still grow u. Distinct facial features -- over growth of facial bones into adulthood. xxii. Normally due to a slow growing tumor. xxiii. Widespread growth of tissues (ring size, shoe size, etc all increase). v. Goiter -- hypertrophy of thyroid w. Headache, visual disturbances x. Hyperglycemia y. Increased bone and soft tissue z. Cardiomegaly -- hypertrophy of heart vii. The normal cause of death in people with acromegaly a. Sleep apnea due to enlarged tongue. viii. Also a major problem in people with acromegaly 14. Treatment xxiv. surgical removal of tumor - Hypophysectomy xxv. Synthetic somatostatins (anti GH effect) -- "Octreotide" III. Prolactin (PRL) disorders F. Regulation and actions of PRL 15. Actions: xxvi. Major hormone of lactogenesis b. Stimulates milk production at breast tissue. xxvii. Cohormonal action at the breast with estrogen -- they work together. xxviii. Structurally similar to GH (hence the 'cross specificity' of GH at the PRL ®) xxix. Inhibits ovulation/spermatogenesis by decreasing synthesis of GNRH c. 'natural birth control' mechanism for nursing mothers. d. Doesn't always work. 90% effective in 1^st^ month decreasing after that. 16. Regulation xxx. Hypothalamic control by dopamine (inhibits PRL release from Ant. Pituitary). e. 'Tonic inhibition' by dopamine therefore PRL release is via dopamine inhibition. xxxi. Negative feedback of PRL by stimulation of hypothalamic dopamine. xxxii. PRL release stimulated by TRH. G. PRL deficiency 17. Usually occurs with damage to ant. Pit. 18. Failure to lactate H. PRL excess 19. Etiology xxxiii. Usually due to hypothalamic damage (no more dopamine inhibition) without damage to pituitary -- rare. xxxiv. Can be due to PRL secreting tumors -- "prolactinomas" xxxv. excess TRH can lead to mild PRL excess?- 'secondary' PRL excess 20. Sx xxxvi. failure to ovulate xxxvii. Galactorrhea is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing xxxviii. amenorrhea (absence of a menstrual period in a woman of reproductive age). f. Due to inhibition of GnRH release. xxxix. Gynecomastia in men -- formation of breast tissue in men g. h. *Can occur as a side effect of Rx dopamine blockers for which disorder?* ix. *What disorder uses dopamine blockers as a treatment:* 21. Tx -- Bromocriptine -- dopamine agonist ➔ decreases PRL release. xl. *What side effects would you expect to see?* i. *Schizophrenic side effects* j. *Leukopenia (inhibits T cell formation)* k. *others* IV. Thyroid disorders I. Regulation and actions of Thyroid hormone 22. Production of thyroid hormone xli. *Thyroglobin made by thyroid cell.* xlii. *Iodine is pumped into the thyroid follicular cells where....* xliii. *Iodine is oxidized (peroxidase enzyme) and bound to [thyroglobin] which contains the amino acid tyrosine.* xliv. *This complex is stored in the thyroid until TSH causes...* xlv. *Thyroglobulin to be broken down thereby releasing T3 (triiodothyronine) or T4 (thyroxine) forms of thyroid hormone into circulation.* xlvi. T3/T4 are bound to Thyroid Binding Globulin (TBG) in the circulation. l. T4 can be converted into the more active form 'T3' in many tissues. 23. Thyroid hormone release stimulated by ant pit release of TSH xlvii. Trophic hormone to thyroid - activates both secretion and production of thyroid hormone [and thyroglobulin] xlviii. T3 causes decreased TRH ® [number and sensitivity] on the anterior pituitary cells 24. Actions of thyroid hormone xlix. **BMR -- basal metabolic rate** m. Generally, increases metabolism in a number of tissues. n. Increases Na/K ATPase production o. Increases fuel for metabolism: Increases glucose absorption from GI tract, gluconeogenesis, glycogenolysis, fat oxidation. l. Cardiopulmonary effects p. Boosts both cardiac output and respirations to supply O2 to tissues for metabolism. li. ANS (autonomic nervous system) q. Similar effects as the SNS- up regulates Beta adrenergic ® in the heart r. Can use Beta blockers to treat hyperthyroidism symptoms lii. Aids in bone formation and maturation (with GH) in youth and adolescence. liii. CNS development s. Essential for proper CNS maturation in prenatal period x. Important to check thyroid hormone levels in pregnant women 25. Standard thyroid hormone evaluation liv. T3/T4 lv. TSH lvi. TBG lvii. Hard to measure TRH from the hypothalamus (hard to get to.... Exceptionally low concentrations in the peripheral circulation) J. Thyroid hormone deficiency (hypothyroidism) 26. Etiology lviii. May be due to problem in any one of the enzymes used to produce T3/T4. lix. Liver diseases that causes decreased TBG production t. Thyroid hormone can't be carried in the blood. lx. Iodine nutritional deficiency -- causing low production of thyroid hormone u. 'iodonized salt'. lxi. Usually primary hypothyroidism v. **Hashimoto's Thyroiditis** (Autoimmune) xi. Destruction of thyroid by autoimmune antibodies. xii. Anti-thyroid *(anti-microsomal)* IgG are present. w. Lithium toxicity xiii. For Bipolar disorder treatment. lxii. Sx x. Decreased BMR xiv. Obesity xv. Sensitive to cold 1. Can't generate enough of their own heat to be comfortable in a cold room. xvi. Lethargy/Fatigue y. Cognitive disfunction xvii. Cognitive dysfunction xviii. Intellectual disability (if infantile onset) z. Amenorrhea (women) xix. likely mechanism: increased TRH➔ stimul PRL ® ➔ GnRH inhibition ➔ decreased LH/FSH➔ decreased Est/Progest a. Constipation b. Poor reflexes due to poor Autonomic nervous system stimulation c. Cardiopulmonary effects xx. ltd up regulation of beta adrenergic ® (less heart stimulation so lower CO)- so you would expect lower BP xxi. but also mild hypertension, because of an increase in peripheral vascular resistance. Maybe b/c lower cholesterol metabolism and subsequent atherosclerosis? xxii. So cardiac effect vary by patient. d. **Goiter** xxiii. Overgrowth of thyroid gland. xxiv. increased TSH levels 2. **why high TSH???? \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** xxv. Goiter occurs usually with primary hypothyroidism. 3. if 2ndary then it would be due to ant pit hyposecretion of TSH (no goiter). e. *Accumulation of matrix glycosaminoglycans in the interstitial spaces of many tissues. This can lead to coarse hair and skin, puffy facies, enlargement of the tongue, and hoarseness* f. *Anemia -- poor stimulation of RBC production.* lxiii. Tx -- g. SLOWLY return thyroid hormones to normal xxvi. [hyperthyroid crisis] (Thyrotoxic Storm): 4. can occur if you have acute elevation in thyroid hormones a. cardiovascular activation (dangerous). b. cognitive effects (T3/4 affects brain) =\> coma and death. h. Levothyroxine = thyroid hormonal replacement i. Synthetic T4 (Synthroid) j. Monitor TSH level xxvii. Long-term untreated hypothyroid may have asymptomatic coronary artery disease. xxviii. if TSH too low, reduce replacement dose lxiv. Lab med stuff - how to evaluate k. TSH is a better indicator of hypothyroid xxix. Primary hypothyroid: ***\_\_\_\_high/low\_\_\_\_\_\_\_\_*** TSH xxx. Secondary hypothyroid: ***\_\_\_\_\_\_ high/low \_\_\_\_\_\_\_***TSH K. Thyroid hormone excess (hyperthyroidism) 27. Etiology -- lxv. primary hyperthyroidism (more common) l. Thyroid tumor (rare) m. **Grave's Disease** (much more common) xxxi. Antibodies produced to TSH receptor on the thyroid cells that over stimulate it. 5. This causes excess T3/T4 release and subsequent amplification of negative feedback on the rest of the thyroid access. xxxii. More common in women xxxiii. Goiter -- TSH is a trophic hormone (causes growth) n. Pregnancy normally causes Thyroid binding globulin (TBG) increase xxxiv. increased levels of thyroid hormone in storage (but normal levels of free thyroid hormone.). lxvi. Secondary hyperthyroid o. usually due to excess TSH -- p. leads to overgrowth of thyroid = goiter. xxxv. caused by trophic effect of TSH 28. Sx lxvii. **Increased BMR** q. Hyper-excitability r. irritability s. weight loss t. increased heat production (sweating) u. Sensitive to warm environments -- Generating lots of heat on their own so they prefer cooler environments and don't like warm places. lxviii. Increased Cardiopulmonary function v. Increased HR, RR and increased BP lxix. **Goiter** w. if secondary hyperthyroidism (excess TSH) lxx. **Exophthalmos** -- (\"ek-säf-\'thal-mas) x. bulging of the eye anteriorly out of the orbit y. due to abnormal connective tissue deposition in the orbit and extraocular muscles 29. **Diagnosis** lxxi. **Elevated T4/T3** z. With low TSH = primary hyperthyroidism a. With high TSH: pituitary (secondary hyperthyroidism) b. With anti-TSH IgG: Graves' disease lxxii. Inject radioactive Iodine to see if thyroid is only organ that takes is up c. eliminate the possibility of a thyroid hormone secreting tumor that way d. Also allows you to see how much thyroid hormone is being made (more iodine uptaken the more T3/T4 being made). 30. Tx (usually long term -- years) lxxiii. Thionamides -- decrease production of thyroid hormones and conversion of T4 to T3. lxxiv. Iodides and lithium are used effectively to block the release of thyroid hormone e. *Iodides = solutions containing potassium iodide that inhibit the release of *T3/T4 lxxv. Beta blockers (propranolol) to decrease CV effects. lxxvi. Corticosteroids -- block T4 to T3 conversion. lxxvii. Irradiated Iodine -- permanent ablation of thyroid f. given to target and specifically kill thyroid gland cells. g. Thyroid is primary organ to uptake I- so it's a good way to target the destruction of thyroid cells. h. Will need thyroid replacement therapy after thyroid ablation. lxxviii. Surgical removal of thyroid may cause ablation of parathyroid so it's rarely done. V. Parathyroid and Calcitonin -- Regulation of Bone (not much in your text on this subject) L. Regulation and actions of Parathyroid hormone 31. PTH, Calcitonin and Vitamin D = All about Calcium (Ca^++^) homeostasis 32. Actions lxxix. **PTH -- increases blood Calcium** and decreases Phosphate i. Indirectly stimulates osteoclasts to breakdown bone xxxvi. Osteoclasts -- cut bone down into Ca^++^ and Phosphate ions which then are moved into the blood j. Stimulates Ca^++^ reabsorption from the kidney. k. Stimulates Ca^++^ absorption from the GI tract. l. Phosphate is normally excreted by kidney so net effect of PTH is increased plasma Ca^++^ lxxx. **Calcitonin** m. Inhibits bone resorption (inhibits osteoclasts) n. Promotes bone formation (stimulates osteoblasts) xxxvii. Osteoblasts -- build bone o. Secreted from "C" cells in thyroid gland in response to increased serum Ca^2+^ lxxxi. **Vitamin D** p. Helps to absorb intestinal and renal Ca^2+^. q. Low vitamin D can lead to hypocalcemia. 33. Regulation lxxxii. PTH r. Decreased plasma Ca^++^ increases PTH secretion lxxxiii. Calcitonin s. Increased plasma Ca^++^ increases Calcitonin secretion from thyroid lxxxiv. Vitamin D t. Stimulated by PTH to help absorb intestinal and renal Ca^++^ M. Parathyroid hormone excess (hyperPTH) 34. Primary hyperparathyroidism lxxxv. usually due to parathyroid adenoma 35. Sx lxxxvi. normally a slow onset -- may be asymptomatic lxxxvii. increased plasma Ca^++^ u. kidney stones lxxxviii. decreased plasma Phosphate lxxxix. Increased urinary Ca^++^ (kidney can't reabsorb all of the Ca^++^) xc. bone resorption (osteoporosis) 36. Tx xci. Surgical removal of parathyroid v. Then treat for hypoparathyroid (which is easier) xcii. Medical management in mild cases -- w. Low Ca^++^ diets x. Hydration to prevent kidney stones y. *Alendronate* (**Fosamax)** to prevent bone resorption. z. *Parsabiv™ (etelcalcetide)* xxxviii. Calcimimetic agent (mimics Calcium at the PTH... by telling the gland that there is already enough calcium in the body) 6. activate the calcium-sensing receptor in the parathyroid gland, thereby inhibiting PTH secretion xxxix. *IV infusion* a. If severe: dialysis to restore Ca^++^ levels to where they should be 37. [Chronic Renal Failure] can cause Secondary hyperparathyroidism xciii. Decreased kidney function causes retention of Phosphate b. Failing nephron cannot excrete Phosphate c. Blood Phosphate levels increase xl. So **PTH increases** to try and rid body of phosphates (but it cant) xciv. Ca^++^ levels decrease d. Phosphate binds to free Ca^++^ e. Vit D is also made by the kidney and is a cofactor in Ca+ reabsorption from the GI tract. Without it serum Ca+ levels decrease further increasing the stimulus for PTH release. xcv. The excess phosphates and decreased free Calcium further stimulates PTH release. N. Parathyroid hormone deficiency (hypoPTH) 38. Normally due to damage to parathyroid (thyroid surgery) xcvi. Sx f. low plasma Ca^++^ g. Muscular problems xli. muscle cramps (need Ca^++^ to contract) xlii. parasthesias of distal extremities. 7. *An abnormal sensation of the skin, such as numbness, tingling,* xliii. Fatigue xliv. Laryngospasm (if very serious) h. Cardio changes xlv. EKG alterations i. CNS alterations xlvi. Anxiety, irritability xlvii. Seizure (if serious) xcvii. Tx -- j. Mild- PTH hormone replacement, Ca^+^ and Vitamin D supplements. k. Severe -- IV Ca^+^ and Calcitrol (active form of Vit D). VI. Adrenal Cortex O. Adrenal gland made of a 'cortex' and a 'medulla' which produce very different hormones 39. Medullary hormones: Catecholamines xcviii. **Epinephrine** xcix. Norepinephrine 40. Cortical hormones: - steroids c. Glucocorticoids - Cortisol ci. Sex steroids -- androgens (testosterone, estrogen) cii. Mineralcorticoids -- Aldosterone P. Regulation and actions of Adrenocortical hormones 41. Adrenal gland regulated by hypothalamic CRH and consequent anterior pituitary ACTH release. 42. Production of Adrenocortical hormones ciii. [figure is pasted below]. It has the enzymes responsible for the manufacture of adrenocortical hormones. civ. Enzymes important in adrenocortical hormone production l. [21 Hydroxylase] -- helps to make mineralocorticoids and glucocorticoids from precursor steroid hormones. m. [Aromatas]e -- helps convert testosterone in to estrogens. n. Which levels of which hormones would be increased/decreased with each enzyme dysfunction? ("Enzymatic Block") 43. Glucocorticoids (Cortisol) cv. Functions (**Stress hormone**) o. Glucose regulation (hence 'glucocorticoid') -- xlviii. anti- insulin effect 8. blocks uptake of glucose into cells 9. blocks glycogenesis -- making new glycogen from glucose 10. stimulates glycogenolysis -- breaking down glycogen into glucose. xlix. stimulates gluconeogenesis -- making new glucose from a variety of sources (including protein) l. protein breakdown (catabolic), lipid breakdown 11. hyper proteinemia -- bad for kidney 12. hyperlipidemia -- bad for vascular system (atherosclerosis) li. **raise blood sugar 'at all costs'** p. Immunosuppression (sometimes with poor consequences). lii. Lots of mechanisms have been proposed for how cortisol is immunosuppressive. 13. *Inhibits leukotriene, interleukin, and prostaglandin production and histamine release.* q. Permissive effect for norepinephrine (NE) -- increased alpha 1 adrenergic ® in vasculature -- allowing for greater vasoconstriction with NE release. cvi. Regulation via ACTH from anterior pituitary in the standard "H'thal -- ant pituitary -- ad Ctx" axis. 44. Mineralocorticoids (Aldosterone) cvii. Functions r. Salt and water balance s. Cause kidneys to retain Na^+^ (at the expense of excreting K^+^) t. Retention of water by kidneys ("where Na^+^ goes H~2~O goes") liii. this increases blood volume and therefore BP increases cviii. Regulation of Aldosterone u. **Primary path =** **RAS system (Renin -- Angiotensin System**) liv. Renin stimulated by 14. Low blood volume at kidney 15. low blood pressure at kidney 16. Low plasma Na^+^ 17. High plasma K^+^ = secondary stimulus 18. Circadian rhythm and age can affect Renin release lv. Renin hormone causes angiotensinogen to be made into angiotensin I (Ang I). lvi. The lungs enzymatically convert Ang I to Ang II 19. Done by angiotensin converting enzyme (ACE) c. ACE inhibitors used to treat hypertension (see cardio section) lvii. Ang II causes aldosterone release from adrenal cortex. lviii. Na^+^ is retained (Water follows) while K^+^ is excreted and blood volume increases. 20. "K^+^ wasting effect" of aldosterone v. Aldosterone is unresponsive to ACTH release [in normal concentrations]. 45. Androgens (testosterone, estrogen) cix. Functions = Minor role in secondary sex characteristics (those duties mostly done by gonads). cx. Regulation: not directly linked to ACTH from anterior pituitary. However, if ACTH is in excess it CAN activate androgen production. VII. Adrenocortical disorders Q. Hyperaldosteronism = "Conn's Syndrome" 46. Etiology cxi. Hypersecreting adrenal tumor made up of aldosterone-secreting cells w. Primary hyperaldosteronism or Conn's syndrome cxii. Inappropriately high activity of the renin-angiotensin system x. Secondary hyperaldosteronism 47. Sx -- cxiii. Hypernatremia (high Na^+^ in plasma) =\> hypervolemia =\> hypertension cxiv. Hypokalemia cxv. Decreased renin release. 48. Tx -- cxvi. *Spironolactone* is an aldosterone antagonist. y. **Watch K+ levels** cxvii. Salt restricted diet z. To prevent hypertension R. Hypoaldosteronism 49. See Addison's disease below. S. Adrenocortical hormone Insufficiency (Cortisol) 50. **Addison's Disease** -- Primary adrenocortical insufficiency 51. *Side note; JFK had this.* cxviii. Etiology a. Decreased levels of mineralocorticoids, glucocorticoids (very serious problem), and androgens. b. Adrenal cortex is damaged. lix. Autoimmune disease, trauma, tuberculosis, etc cxix. Sx c. From low cortisol lx. Elevated ACTH (no neg feedback from cortisol) lxi. Hypoglycemia lxii. *Anorexia, Weight loss, fatigue* 21. *Why???* lxiii. Hypotension 22. not as robust a response to NE in vasculature lxiv. Hyperpigmentation (Melanocyte stimulating hormone (MSH) is left over after ACTH is made. Activated melanin production. d. From low androgens lxv. Decreased axillary and pubic hair growth (especially in women). lxvi. Adrenal androgen not a major player in determination of secondary sex characteristics. e. From low aldosterone lxvii. Hypotension 23. hypovolemia =\> dehydration lxviii. Hyperkalemia (elevated K^+^) -- can lead to cardiac and neural problems. lxix. Salt cravings (not reabsorbing Na^+^) lxx. Renin increased lxxi. *Metabolic acidosis (aldo causes K^+^ secretion, without it K+ remains in blood and H+ doesn't get secreted by intercalated cells).* 52. Secondary adrenocortical insufficiency. cxx. Problem is a lack of ACTH. cxxi. Caused by f. chronic corticosteroid meds *(RA, asthma etc)* lxxii. Perpetual neg feedback on ACTH release =\> hard to 'jump start' the system again after prolonged corticosteroid treatment. lxxiii. Can be dangerous to stop these meds too quickly -- lack of a cortisol response to stress. g. Damage to Ant Pit-- no ACTH secretion cxxii. Similar presentation as Addison's except..... h. No Hyperpigmentation ([low ACTH] so low MSH) i. No aldosterone deficiency effects lxxiv. Aldo doesn't normally respond to ACTH changes j. less chance for hypotension or Hyperkalemia. lxxv. Aldosterone levels are OK but.... lxxvi. some risk for hypotension due to NE ® decrease in vasculature (cortisol permissive for NE ®) k. No androgen deficiency effects cxxiii. Tx = hormone replacement of glucocorticoids 53. **In primary adrenal insufficiency (Addison's) mineral/glucocorticoids and androgens are all hyposecreted. However, in secondary adrenal insufficiency only glucocorticoids are hyposecreted because the mineralocorticoids and androgens are activated by separate mechanisms.** 54. **Dx adrenal insufficienc**y cxxiv. **Cortisol levels** cxxv. **ACTH test --("*cosyntropin"* = synthetic ACTH)** l. **IV injection and measure cortisol response. If cortisol increases, then the ad ctx [can] be stimulated, it just isn't being stimulated suggesting 2ndary hypocortisolism. If no cortisol response, then the ad ctx is damaged and it may be primary hypocortisolism** cxxvi. **CT scan of abdomen -- look at adrenals** m. **Small -- autoimmune destruction** n. **Lg -- tumor, hemorrhage, tuberculosis** 55. Tx cxxvii. hormone replacement of glucocorticoids (*hydrocortisone, prednisone, dexamethasone*) and mineralocorticoids *(fludrocortisones acetate -- Florinef*) T. "Addisonian crisis" 56. = "acute adrenal insufficiency" 57. Secretion of glucocorticoids is OK for normal demands of life but when a stress arises the body cannot respond because of a lack of glucocorticoids release. 58. True med emergency 59. Anything that slowly diminishes ACTH or cortisol secretion can lead to increased risk for this cxxviii. Chronic corticosteroid administration with sudden withdrawal. U. Diagnosing adrenal insufficiency 60. Cortisol levels 61. ACTH test --("*cosyntropin*" = synthetic ACTH) cxxix. IV injection and measure cortisol response. 62. CT scan of abdomen -- look at adrenals cxxx. Small -- autoimmune destruction cxxxi. Lg -- tumor, hemorrhage, tuberculosis *(scarring & calcification),* etc. V. Hypercortisolism 63. **Cushing's Syndrome** = generic term for any hypercortisolism most often associated with Primary hypercortisolism cxxxii. primary hypercortisolism o. excess cortisol secretion from adrenal (tumor perhaps?) p. more common than 'secondary'. q. Can be due to over dosage of chronic corticosteroid meds *(RA, asthma etc)* 64. **Cushing's Disease** = hypercortisolism due to pituitary dysfunction (secondary hypercortisolism). cxxxiii. Normally caused by pituitary adenoma r. Hypersecretion of ACTH. 65. Sx: - cxxxiv. Appearance is specific for hypercortisolism s. "Moon" face t. Truncal obesity (central deposition of fat) u. Buffalo hump in upper back v. Hirsutism (Her -- soot - ism) - male pattern of body hair in women w. Striae especially on abdomen (skin breakdown) x. Poor healing y. Hypertension (increased NE ® in vasculature from cortisol effects) z. If ACTH is high ("secondary" etiology) -- hyperpigmentation. a. hyperglycemia cxxxv. If there is excess aldosterone released too from either adrenal tumor (primary hypercortisolism) or from residual mineralocorticoid action of cortisol (yes, cortisol can act like aldosterone at high concentrations) b. Hypertension can be even more pronounced c. Hypokalemia d. Water retention e. Cortisol has a mild mineralcorticoid action in high doses. So, Cushings Dis ➔ high ACTH which stimulates both Aldo and Cortisol and Cortisol mimics Aldo at high concentrations. Hence, you CAN get some hyperaldosteronism effects from Cushing's disease. 66. Diagnosis -- cxxxvi. look at cortisol levels (24 hour levels due to circadian changes.) cxxxvii. Can test cortisol response with synthetic corticosteroid (dexamethosone) injections f. if ACTH levels do not decrease the problem is likely a pituitary tumor secreting ACTH. If ACTH does decrease then it is probably a primary hypercortisolism. 67. Tx: cxxxviii. If secondary (pituitary tumor) -- surgical removal of tumor cxxxix. If primary - g. surgical removal of tumor h. *Ketoconazole* (inhibits steroid hormone synthesis) -- be careful so supplement with needed mineral and glucocorticoids. THE DISORDERS OF CORTISOL SECRETION ---------------------------------------------------------------- --------------------- ----------------- **Plasma Cortisol** **Plasma ACTH** **Primary Hypercortisolism** (Cushing\'s syndrome) **↑** **↓** **Secondary Hypercortisolism** (pituitary, Cushing\'s disease) **↑** **↑** **Primary Hypocortisolism** (Addison\'s disease) **↓** **↑** **Secondary Hypocortisolism** (pituitary) **↓** **↓** ---------------------------------------------------------------- --------------------- ----------------- VIII. Adrenal Medulla W. Part of **sympathetic nervous system** 68. Really a glorified SNS ganglion X. **Primary stimulus for increased secretion is activation of sympathetic nervous system by stress** Y. Releases the catecholamines epinephrine (80%) and norepinephrine (20%) 69. Maintenance of arterial blood pressure *(how?)* 70. increased fuel for fight or flight cxl. Increases blood glucose and blood fatty acids -- cxli. Promotes **glycogenolysis** and **gluconeogenesis** in the liver cxlii. Promotes **lipolysis** Z. Pheochromocytoma 71. Etiology cxliii. excessive secretion of catecholamines due to adrenal tumor 72. Sx- excess SNS stimulation cxliv. Hypertension (vascular constriction, stimulation of heart) cxlv. Tachycardia cxlvi. Headache 73. Diagnosis cxlvii. may have to wait until symptoms worsen before attributing symptoms to this rare condition cxlviii. CT scan of adrenal tumor can confirm it. 74. Tx cxlix. surgical removal of tumor cl. beta blockers (propranolol) until surgery can be done cli. High risk of recurrence in remaining adrenal. 75. See [[http://www.mc.vanderbilt.edu/reporter/index.html?ID=5470]](http://www.mc.vanderbilt.edu/reporter/index.html?ID=5470) IX. Anti diuretic hormone disorders *(good transition to diabetes)* A. Regulation and actions of ADH 76. Released when serum osmolality increases. 77. Causes aquaporin formation in late distal tubules and collecting ducts of kidney (increased water permeability)(V2 receptors). clii. Retention of water. 78. Higher concentrations can stimulate V1 receptors in vascular smooth muscle causing increased peripheral resistance =\> increased BP. B. ADH deficiency (Diabetes Insipidus) 79. Types cliii. Central DI. Also called Neurogenic DI -- hyposecretion of ADH i. hyposecretion of ADH j. Caused by damage to osmoreceptor cells in h'thal cliv. Nephrogenic DI -- hyporesponsiveness of ADH k. Caused by problem at kidney (V2 receptors). l. Chronic renal disease m. Lithium toxicity n. Electrolyte abnormalities o. ADH secretion may be normal to high 80. Sx -- clv. **Polyurea** (lg urine output) p. \_\_*hypo/hyper*\_\_\_\_\_smotic urine (dilute urine compared to plasma clvi. **Polydipsia** (excessive thirst) -- triggered by hypothalamic thirst center clvii. Dehydration (can't ingest enough water to balance water loss). q. Skin dehydration and dried mucus membranes and poor sweat function. clviii. Hypernatremia (losing water but not sodium) clix. Hyperosmolality of plasma clx. **[Neurological symptoms]** because cells shrink (intracellular fluids move to ECF) 81. Treatment clxi. Tx for central DI = supplement with synthetic ADH. clxii. Tx for Nephrogenic DI = r. Carefully regulate fluid levels in the body. Fluids consumed should approximately equal the volume of urine produced. s. Reduction or discontinuation of medications that may cause nephrogenic DI may improve symptoms. C. ADH excess (SIADH -- Syndrome of Inappropriate ADH) 82. Sx clxiii. water retention clxiv. concentrated (hyperosmotic) urine clxv. Hypotonicity of plasma (serum osmolality is low) t. hyponatremia -- retaining so much water you are diluting the solutes (like Na^+^) u. Cellular swelling (osmosis of water from blood into cells) v. Neurological problems -- neuronal swelling clxvi. Increased plasma volume clxvii. Hyponatremia (because blood is 'diluted' -- Na+ amount hasn't changed but the volume has increased) 83. Tx clxviii. Fix the cause (*tumor, meningitis induced damage to h'thal, side effect of another medication (common)*) clxix. Salt tablets or IV hypertonic saline to restore Na+ levels clxx. Vasopressin ® blockers clxxi. Sx management w. Fluid restriction