Endocrine System Lecture 20 PDF

The Endocrine System Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives Explain the normal physiologic functions of the pituitary hormones. Name the common endocrine disturbances, and describe the methods of treating each disturb...

The Endocrine System Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives Explain the normal physiologic functions of the pituitary hormones. Name the common endocrine disturbances, and describe the methods of treating each disturbance. 2. Describe the major disturbances of thyroid function and their clinical manifestations, and explain the methods of treatment. 3. Explain the normal physiologic functions of the adrenal cortex and medulla. Name the common endocrine disturbances resulting from dysfunction, and describe methods of treatment. 4. Define the causes and effects of parathyroid dysfunction, and describe the methods of treatment. 5. Understand the concept of ectopic hormone production by nonendocrine tumors. 6. Explain how stress affects the endocrine system. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com 1. Endocrine Glands Autocrine: cell products act on itself Paracrine: localized action around production site (short distance) Endocrine: products secreted into blood stream to have action at distant sites (long distance) FIGURE 24-1 Endocrine organs and tissues. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Major endocrine glands (produce hormones) ▪ Hypothalamus (control center) ▪ Pituitary (directed by hypothalamus to secrete hormones to control endocrine gland function) ▪ Thyroid (metabolism, growth) ▪ Parathyroid -mineral regulation (Ca, P) ▪ Adrenal (metabolism/blood pressure) ▪ Pancreatic islets (glucose regulation) ▪ Ovaries and testes (sex, reproduction) ▪ Pineal (sleep – melatonin) Normal Mechanisms Controlling Elaboration of Tropic Hormones by Pituitary Gland Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com FIGURE 24-2 Normal mechanisms controlling elaboration of tropic hormones by the pituitary gland. Endocrine Glands Have effects/ controls on digestion, metabolism, sleep, growth, development, reproduction Hypothalamus – neural control center for all endocrine system Negative feedback – increased levels stimulate decreased production (pituitary hormones) Clinical disorders of endocrine glands result in Hyper or hyposecretion of hormones caused by gland abnormalities or abnormality in gland activity Determination of clinical effects (barely noticeable to extreme in outcome) ▪ Degree of dysfunction ▪ Age and sex of affected individual Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Hormones are synthesized either :in response to level of hormone in circulation (pituitary hormones), or in response levels of substances in the blood (glucose) Pituitary Gland Produces tropic hormones (regulates other endocrine glands) ▪ Regulated by level of hormone (detected by cells in hypothalamus) that is produced by the target gland – maintains uniform levels (self regulation) ▪ Composed of a variety of cells – each can produce a different tropic hormone when signaled by hypothalamus ▪ Signal from hypothalamus can stimulate production of one or many tropic cell types to stimulate (most)/inhibit (prolactin): ▪ Prolactin secretion controlled by prolactin inhibitory factor (inhibitory) ▪ Thyroid stimulating hormone stimulates release of prolactin and thyroid hormones (stimulatory) ▪ Hormones from hypothalamus/pituitary tend to be produced in pulses (rather than continuously –like HVAC system) ▪ Hormone levels fluctuate – once they fall below a set point – stimulates more production (pulsing) ▪ “Set point” varies between individuals - production can also be influenced by emotion, stress, anger, fear (due to hypothalamus response to cerebral function) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Suspended by stalk from hypothalamus at base of brain ▪ Anterior lobe ▪ Intermediate lobe: Rudimentary structure (vestigial in humans) ▪ Posterior lobe Pituitary Gland Hormones Posterior lobe hormones ▪ Antidiuretic hormone (ADH): Causes more concentrated urine (increased water reabsorption) – regulated in response to sodium ion conc in blood (detected by receptors in hypothalamus) ▪ Oxytocin: Stimulates uterine contractions and milk secretion Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Anterior lobe hormones ▪ Growth hormone(GH): Stimulates growth of tissues ▪ Prolactin: Stimulates milk production ▪ Thyroid-stimulating hormone (TSH) – stimulates secretion of thyroid hormones ▪ Adrenocorticotrophic hormone (ACTH) – simulates release of adrenal hormones ▪ Follicle-stimulating hormone (FSH), Luteinizing hormone (LH) regulate sexual growth/development, fertility Hypothalamic Hormones and Their Targets Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Pituitary Gland Abnormalities - hypofunction Anterior: Can lead to Pituitary dwarfism (deficiency of growth hormone, with stunted growth and development (can supplement with GH) Posterior: Can also lead to Diabetes insipidus from failure of posterior lobe to secrete ADH inability to absorb H2O causes excretion of large amounts of diluted urine (supplement with ADH, increased fluid intake) ▪ Can also occur if there is a defect in kidney – not responsive to ADH (nephrogenic diabetes) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Panhypopituitarism ▪ Anterior lobe fails to secrete all hormones ▪ Can be caused by tumor/destruction, neurologic injury, ischemia from reduced blood supply or rare congenital defects Pituitary Gland Tumors Many pituitary endocrine disturbances caused by anterior lobe pituitary tumors Nonfunctional tumors: Do not produce hormones but exert other effects from tumor encroachment Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Clinical manifestations depend on size of tumor, age of patient and the hormone produced, degree of effect Functional tumors: Produce hormones that cause clinical manifestations (most commonly affects growth hormone and prolactin production) ▪ Majority are adenomas (benign glandular tumor – do not metastasize) ▪ Still associated with significant disease through effects on hormone imbalance and/or neurological abnormalities ▪ May encroach on important structures adjacent pituitary (optic chiasm and nerves) – may also disrupt hormone-producing functions of anterior lobe cells Pituitary Gland Tumors Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Treatment determined by type, size of tumor, and hormone produced by tumor ▪ Drugs can be used to suppress tumor growth ▪ Excess hormone can be counteracted with inhibitor drug ▪ –Surgical resection: Usual surgical approach is through the nasal cavity (transsphenoidal resection) Pituitary Gland Hormone Overproduction Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Growth hormone overproduction ▪ Caused by pituitary adenoma ▪ Causes gigantism in children (excessive growth of long bones) ▪ Causes acromegaly in adult onset (since bones are not longer growing – they thicken and coarsen) ▪ Large jaws, large, thickened fingers – not taller ▪ May cause visual disturbances from tumor encroachment in optic chiasm ▪ Tumor encroachment can also manifest in headaches, neurological deficits ▪ Curable with surgery Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Prolactin overproduction ▪ Result of small pituitary adenoma and or conditions affecting function of hypothalamus ▪ Increased prolactin stimulates galactorrhea (milk secretion from breasts of women who are not pregnant) ▪ Increased prolactin inhibits FSH/LH - causes anovulation/amenorrhea (loss of menstrual periods) ▪ In males – infertility, hypogonadism, sexual dysfunction ▪ Tumor encroachment can also manifest in headaches, neurological deficits ▪ Can be inhibited by dopamine agonist (for small tumors) to suppress prolactin production ▪ Curable with surgery Thyroid Gland Actions ▪ Controls rate of metabolic processes ▪ Required for normal growth and development Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Structure ▪ Two lateral lobes connected by isthmus ▪ Composed of thyroid follicles that produce colloid and store hormones ▪ Colloid – precursor thyroid hormones (thyroglobulin, T1,T2) ▪ Produce thyroid hormone T3 (triiodothyrine) and T4 (thyroxin) ▪ Hormone production regulated by TSH from pituitary ▪ Most is bound to carrier proteins in inactive state Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Dysregulation leads to hypo- or hyper-thyroidism Goiter Causes ▪ Iodine deficiency (required to produce T3, T4 hormones) ▪ Enzyme deficiency or inefficient enzyme function– unable to produce hormones (drugs, some foods like turnips and cabbage interfere with synthesis) ▪ Increased hormone requirements (puberty, pregnancy, stress) Treatment: Administer thyroid hormone – will suppress TSH thorough negative feedback and goiter should regress Large nodular goiter may need surgical removal (compresses trachea, interferes with respiration of circulation in the neck Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Enlargement of the thyroid gland (non-toxic goiter: no increase in thyroid hormone) Enlargement is in response to TSH stimulation due to insufficient thyroid hormone. Hyperthyroidism Excess secretion of thyroid hormone Caused by antithyroid antibody (Thyroid stimulating Immunoglobulin -TSI) that stimulates gland Mimics effects of TSH but not subject to normal control mechanisms Autoimmune disease (T cells) also attacks fat, connective tissue and muscles that control eye movements – inflammation/swelling pushes eyes forward Treatment ▪ Antithyroid drugs, thyroidectomy of portion of thyroid, large doses of radioactive iodine, to destroy part of thyroid gland Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Can be caused by thyroid adenoma or most commonly by Graves disease (autoimmune disease) Hypothyroidism In infants (congenital – historically called cretinism) ▪ Caused by failed thyroid gland development or thyroid enzyme deficiency ▪ Appears normal at birth – maternal thyroid hormone compensates ▪ Months after birth – hypometabolic rate ▪ If not detected early - causes impaired growth and impaired central nervous system development ▪ Early detection (low thyroid hormone and elevated TSH) and treatment required for normal development ▪ Still important source of childhood physical and mental impairment in areas with iodine diet deficiency (developing world) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com In adults (Myxedema) ▪ Causes metabolic slowing ▪ Have high levels of TSH, low levels of thyroid hormones ▪ Treatment: administration of thyroid hormone Chronic Thyroiditis Thyroiditis can be caused by acute viral or bacterial infection ▪ Results decreased thyroid hormone production, hypothyroidism ▪ Enlarged thyroid gland from infiltration/inflammation Treatment: administration of thyroid hormone Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Hashimoto Thyroiditis: Autoantibodies and T cells destroys thyroid tissue and TSH receptors (Graves – autoimmune stimulates) Thyroid Tumors Benign encapsulated nodules are common and may progress to malignancy Radiation: Increases incidence of benign and malignant thyroid tumors after latent period of 5 to 10 years after cancer treatments (side effect) Most tumors are well-differentiated and easily treated Persons who received head or neck radiation should have periodic follow-up examinations Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Typically present as benign adenomas (glands) – common (present in 50% of autopsies), and several types of carcinoma (tissues) Thyroid Tumors 2. Poorly differentiated follicular carcinomas – closely resembles thyroid tissue. Poor prognosis; rapidly growing metastasizing cancers 3. Undifferentiated (anaplastic) carcinoma Uncommon – older adults , rapidly growing cells, poor prognosis Treatments: surgery (partial/total resection), radiation, chemotherapy Medullary carcinoma (calcitonin secreting parafollicular cells) ▪ Rare, secretes increased calcitonin (unregulated) ▪ Poor bone health (calcium scavenging), kidney stones, heart/ brain effects Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Thyroid Carcinoma (3 main types of follicular cell carcinoma) 1. highly-differentiated follicular and papillary carcinoma (Assoc with radiation exposure in children) ▪ Good prognosis in young – more aggressive in adults; treatment by surgical resection Parathyroid Glands Located on posterior surface of lateral lobes of thyroid (commonly 4) ▪ Calcium and phosphate are required for muscle contraction, nerve impulse transmission Calcium and Phosphate levels are regulated by parathyroid glands (secreting PTH) – in response to calcium blood levels. ▪ regulating release of calcium from bones ▪ Absorption of calcium from intestine ▪ Rate of calcium excretion in kidneys PTH secretion (direct – no tropic mediator) is regulated directly in response to blood calcium levels (high – decrease/ low – increase) tightly regulated: need to be kept in narrow range In contrast, PTH reduces reabsorption of phosphate and stimulates excretion in urine https://en.wikipedia.org/wiki/Parathyroid_gland Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Blood calcium levels are kept in equilibrium with calcium in the bones (half of blood calcium in bound by carrier protein – inactive) Hyperparathyroidism Relatively common disease that is usually caused from a hormone-secreting parathyroid adenoma ▪ Treatment: surgical removal of tumor Secondary Hyperparathyroidism: can result from chronic renal disease when too much calcium is lost Tertiary: chronic hyperparathyroidism (over 2y) – parathyroid becomes unresponsive to chronic low blood calcium levels and releases PTH constantly Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Effects ▪ Hypercalcemia: Blood calcium rises ▪ Renal calculi: From excessive calcium excreted in urine ▪ Calcium deposition in tissues (kidney, lung etc.) causing functional impairment ▪ Decalcification of bone: From excessive calcium withdrawn from bone ▪ Neurologic effects and heart arrythmias Hypoparathyroidism Can also occur from autoimmune disease or congenital abnormality (DiGeorge syndrome) or genetic conditions where tissues are resistant to PTH Effects ▪ Hypocalcemia: Blood calcium falls precipitously ▪ Leads to neuromuscular excitability and tetany/ cramping ▪ Paresthesia Serious complications: Seizures, irregular heart rhythms, respiratory spams/ failure Treatment: Raise calcium levels - excess dietary calcium, increased risk of renal failure ▪ High-calcium diet/ supplements ▪ Supplementary vitamin D ▪ Recombinant PTH Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Usually from accidental removal of parathyroid glands or blood supply to glands during thyroid surgery/ treatment of goiter Adrenal Glands: Adrenal Cortex Adrenals: Paired glands above kidneys – two set of adrenal glands (inner – medulla, outer- cortex) 2. Mineralocorticoids – regulate electrolyte and water balance (Aldosterone) ▪ Promotes retention of sodium and water (maintain blood volume, BP) ▪ Renin–angiotensin system is main stimulus, responds to decreased BP or decreased renal blood flow 3. Gonadocorticoids: Sex hormones – produces testosterone/estrogen precursors (DHEA) that are converted in the gonads Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ACTH (adrenocorticotropic hormone) from pituitary controls secretion mainly for sex hormones and 3 main Hormone categories secreted by adrenal cortex glucocorticoids – Aldosterone to a lesser extent 1. Glucocorticoids (raise blood glucose – promote fat and protein breakdown) also suppress inflammation (cortisol). Basal secretion is increased by ACTH Disturbances of Adrenal Cortical Function: Addison Disease An adrenal cortical hypofunction caused by atrophy or destruction of adrenal glands Results in deficiency of all steroid hormone production ▪ Glucocorticoid deficiency: Hypoglycemia ▪ Mineralocorticoid deficiency: Low blood volume and low blood pressure ▪ Absent or irregular menstrual cycle ▪ Confusion/lethargy/convulsions Hyperpigmentation: From increased ACTH due to loss of feedback inhibition Treatment: Administration of corticosteroids Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com usually autoimmune destruction is the cause – can also be due to TB , cancer or rare genetic defect Cushing Disease Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Hyperfunction - excessive production of adrenal corticosteroids ▪ Glucocorticoid excess: Disturbed carbohydrate, fat, and protein metabolism (elevated blood glucose) ▪ Increased breakdown of protein – muscle wasting/weakness ▪ Mineralocorticoid excess: High blood volume and high blood pressure, osteoporosis 4 main Causes: ▪ ACTH Hormone-producing pituitary microadenoma (Cushing disease – most common) ▪ Corticosteroid -producing adrenal cortex adenoma (adrenal Cushing syndrome) ▪ Hyperplastic adrenal glands or tumor (secreting ACTH) ▪ Administration of large amounts of corticosteroid – used in immune suppression for autoimmune or transplant treatments (exogenous Cushing syndrome) Overproduction of Other Adrenal Cortex Hormones Overproduction of aldosterone – promotes absorption of salt and water in kidneys and elimination of potassium Regulated by renin- angiotensin- aldosterone ▪ Commonly from aldosterone-producing tumor of adrenal cortex (Conn syndrome) ▪ High sodium, increased blood volume = increased blood pressure ▪ Low potassium level leading to neuromuscular manifestations (muscular weakness) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Overproduction of adrenal sex hormones ▪ Congenital adrenal hyperplasia (CAH) – deficiency of enzymes required for synthesis of aldosterone/cortisol ▪ Results in increased ACTH secretion in response to low cortisol ▪ Causes increased androgen synthesis (testosterone) - varies depending on degree of enzyme deficiency ▪ Early sexual development in males – stunted development of puberty in females (virilization/masculinization, ambiguous genitalia, infertility) ▪ Also causes hypoglycemia, elevated BP (and other effects from lack of cortisol/aldosterone) Adrenal Glands: Adrenal Medulla Pheochromocytoma: rare tumor (benign) that results in increased secretion of catecholamines (large amounts) ▪ Produces pronounced cerebrovascular effects ▪ May cause cerebral hemorrhage from hypertension ▪ Treatment: Tumor resection ▪ Most occurs sporadically or can be associated with inherited susceptibility (gene mutations in MEN1 and 2 (Multiple Endocrine Neoplasia Syndrome) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Produces catecholamines that stimulate the sympathetic nervous system ▪ Norepinephrine (noradrenaline) ▪ Epinephrine (adrenaline) They are released into the blood stream in response to sympatric stimulation (emotional stress, fear, anger, anxiety, exercise) ▪ Increased HR and contraction strength, BP, respiratory rate, muscle responsiveness (fight or flight response) Nonendocrine Tumors Ectopic hormones: Hormones secreted by nonendocrine tumors that are identical with or mimic action of true hormones (ACTH, TSH, gonadotropins, ADH, PTH and insulin) Usual origin: Produced by malignant tumors of the lung, pancreas, kidneys, connective tissue – referred to as paraneoplastic syndrome Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Sometimes tumors (non-endocrine) can secrete hormones or hormone like molecules Pancreatic Islets (Islets of Langerhans) Produces hormones – glucose regulation/digestion ▪ Beta cells: Insulin production – glucose metabolism (in response to high blood glucose) ▪ Alpha cells: Glucagon – raises blood glucose (stimulates conversion of glycogen to glucose in the live) and fatty acid concentration in response to low blood glucose or stress (adrenaline) ▪ Delta cells: Somatostatin reduces acid secretion (also present in several locations in the digestive system) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Pancreatic tissues have digestive functions but also has endocrine function Gonads (Ovaries, Testis) Required for sexual development, fertility Tumors of gonads may develop that secrete hormones – no clinical symptoms for over secretion of proper hormones – (masculinization/feminization of opposite) ▪ Treatment: Surgical excision (usually benign) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Also serve dual function 1. Production and development of germ cells (sperm or ovum) 2. Endocrine function: Production of sex hormones: (testosterone, progesterone, estrogen) Controlled by gonadotropic hormones of pituitary gland FSH and LH Production of FSH and LH is controlled by tropic hormone GnRH – (Gonadotropin releasing hormone) from the hypothalamus Stress and the Endocrine System Homeostasis: Maintenance of steady state in internal control system – can be affected by stress and its impact on the endocrine system 2 distinct overlapping systems respond to short and long-term stresses: ▪ Long-term stress response: Dampens inflammatory response (immunity), increases growth and thyroid hormone – mediated through many endocrine glands with the adrenal cortex playing a major role Eventually short-term protective response leads to chronic damage – chronic stimulation of endocrine system takes it toll – leading to predisposition to illness (cardiovascular and other organ systems, immune suppression) ▪ Increased thyroid and growth hormone (increased metabolism and growth) ▪ Increased cortisol disturbs fat, glucose and protein metabolism and suppresses immune function ▪ Increased aldosterone – elevated BP (retention of water and sodium) - CAD ▪ suppress gonadotropic hormones – impairs gonadal function (amenorrhea, decreased sex drive) reproductive/sexual health Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Acute stress response: Fear, fight, flight – mediated by sympathetic NS though the adrenal medulla (Epinepherine/norepinepherine) Endocrine system Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com.