Exam 2 Diseases PDF

Disease Cause Symptoms *X monosomy (only X instead of XX) → no full ovarian development Orthodontic anomalies Treatment/ Notes Female Reproductive Turner syndrome Thyroid Hypothyroidism Hypothyroidism in children (pre and postnatal development) iodine insufficiency→ lack of thyroid hormone...

Disease Cause Symptoms *X monosomy (only X instead of XX) → no full ovarian development Orthodontic anomalies Treatment/ Notes Female Reproductive Turner syndrome Thyroid Hypothyroidism Hypothyroidism in children (pre and postnatal development) iodine insufficiency→ lack of thyroid hormone production -maternal iodine insufficiency ● ● ↓ thyroid hormone production Goiters Cretinism→ mental retardation, dwarfism, deaf-mutism, and other physical abnormalities -if the thyroid H insufficiency comes from a FETAL issue→ material T3/ T4 will compensate during pregnancy→ after birth can be treated and live a normal life -disease of thyroid -low metabolic rate -disease of hypothalamus/ pituitary -always feeling cold How to tell if someone has thyroid issue or hypothal/pitu issue: -fetal abnormalities of thyroid or pituitary or hypothalamus -maternal anti-thyroid antibodies that cross the placenta and damage the fetal thyroid gland Hypothyroidism in adults -dry and yellow skin -iodine deficiency -thinning hair -mental/ cognitive issues -if the cause is iodine deficiency→ goiter (below) Iodine deficiency goiter (hypothyroidism) Iodine deficiency *hypothal/ Pitu issue→ they have low TRH and TSH - Inject them with TSH→ their thyroid hormone levels will go back to normal *thyroid gland issue→ inject them with TSH→ still have low T3/ T4 levels -no iodine→ can’t make T3/T4 but the adrenal gland is constantly sending TSH to stimulate it→ so you get buildup of thyroglobulin in the colloid tissue Hashimoto’s Thyroiditis Autoimmune disease that attacks the follicular cells Destruction of the follicles→ infiltration of the lymphocytes into the colloid→ causes excessive swelling and excess tissue of the goiter Hyperthyroidism Too much T3/T4 -high basal metabolic rate - - Pituitary tumor→ too much TSH released→ over stimulation Graves disease -easily overheated→ sweating -increased food intake -weight loss -nervousness (bc high T3/T4 increase catecholamine sensitivity→ nervousness) Small follicular cells Large colloid Graves disease (hyperthyroidism) Autoimmune - Antibodies that targets TSH receptor Bulging eyes→ (antibodies cause inflammation and swelling) goiter Antibody mimics effects of TSH→ overstimulation of thyroid gland→ too much T3/T4 released - -thyroid does NOT get negative feedback bc the antibody does not respond to TRH - Very large follicular cells Low colloid Pancreas Hypoglycemia Low blood glucose Most common cause: excess insulin injection Type 1 diabetes (hyperglycemia) Loss of beta cells Weight loss (autoimmune) → not enough insulin secreted Ketoacidosis (insulin dependent diabetes mellitus) Type 2 diabetes (insulin independent diabetes mellitus) Insulin injections Polyurea→ excessive urination Polydipsia→ excessive thirst Polyphagia→ excessive eating Hyperglycemia Glycosuria→ glucose in urine Decreases insulin sensitivity in tissues Reduced insulin secretion Obestity NOT insulin injections Polyurea→ excessive urination Polydipsia→ excessive thirst Polyphagia→ excessive eating Hyperglycemia Glycosuria→ glucose in urine Sulfonylureas→ block K channels on beta cells→ allows cell to depolarize→ stimulate insulin secretion Metformin→ decreases glucose output from the liver Diabetes insipidus Low vasopressin (ADH) Metabolic syndrome Polyurea polydipsia Risk factors: Abdominal obesity Low LDL, high HDL High blood glucose Insulin resistance High BP Increases risk for: Type 2 diabetes Coronary artery disease stroke Parathyroid Hypocalcemic tetany Blood becomes more BASIC→ more Ca binds to albumin→ low free Ca in blood→ Hyperexcitability of cells Numbness and tingling Muscle spasms Na channels not stabilized by Ca→ depolarize all the time→ muscles contract constantly Ex. hyperventilation Rickets Vitamin D deficiency Osteoporosis prolonged excess bone reabsorption (prolonged net bone loss) Too much osteoclast activity, too little osteoblast activity Other causes: inactivity, low gravity (spaceships) Lack of estrogen→ common in postmenopausal women Adrenal cortex Weakness and bowing of weight bearing bones Estrogen suppresses RANKL (which triggers osteoclast activity) So no estrogen= too much RANKL→ too much osteoclast activity Also increases cytokines that increase bone resorption Primary hyperparathyroidism Excess PTH→ causes hypercalcemia Most common cause: benign parathyroid neoplasm (adenoma) that secretes PTH Symptoms are mild bc high Ca levels combat the bad effects of high PTH (too much bone loss→ but high Ca so it can just be deposited back onto it) Both PTH and Ca are high Caused by issue w/ parathyroid gland Secondary hyperparathyroidism Cause: chronic hypocalcemia From renal disease or rickets PTH levels are high, Ca levels are low NOT caused by an issue w/ parathyroid gland Low Ca levels→ chronic stimulation of parathyroid glands→ hypertrophy parathyroids Primary hypoparathyroidism loss of parathyroid glands (surgery/ injury/ autoimmune disease) nerve and muscle hyperexcitability, hypocalcemic tetany Cushing’s syndrome Excess glucocorticoids (same symptoms as below) Low levels of PTH Low levels of Ca High levels of phosphate Ex. using steroids to treat inflammation Cushing’s disease If you know what the actual cause is *tumor anterior pitu→ excess ACTH and androgens *tumor adrenal Red cheeks Receding hairline Striae (stretch marks) → bc no elasticity in the skin Moon face Pendulous abdomen Poor muscle development Poor wound healing Weight gain and central obesity Hypertension Bc excess cortisol→ cant all be converted to cortisone in kidney→ stimulates MR aldosterone receptor→ increases blood pressure cortisol→ makes too much cortisol Bruisability Also bc it increases vascular tone Diabetes mellitus= impaired glucose tolerance Bc cortisol has anti-insulin factor Striae Loss of elasticity in skin→ bc cortisol decreases fibroblast formation and synthesis osteopenia/ osteoporosis Bc cortisol decreases osteoblast formation Proximal myopathy Bc cortisol stimulates protein break down into amino acids→ excess cortisol can cause muscle wasting Hypoadrenalism 99% of cases: abruptly stop taking glucocorticoid medication 1% of cases→ addison's disease or secondary adrenal insufficiency Need to taper off No ACTH production glucocorticoids→ bc high levels of exogenous glucocorticoids the adrenal cortex basically shuts off bc the high levels inhibit ACTH production→ need to taper so adrenal cortex has enough time to start working again No ACTH production Addison's disease (primary adrenal insuff, hypoadrenalism) Issue w/ adrenal cortex High levels of ACTH bc there is no cortisol being produced so there is no negative feedback to stop it Weakness Weight loss Increased pigmentation High ACTH→ ACTH also contain melanocyte stimulating hormone (MSH) → so you also have high levels of MSH *pigmentation will go away with tx of glucocorticoids* Postural hypotension Anorexia High ACTH production Secondary adrenal insufficiency any pituitary or hypothalamic disease causes hypopituitarism→ CRH or ACTH deficiency Adrenal medulla Pheochromocytoma Tumor of adrenal medulla Too much catecholamines released Headaches Chest pain Extreme anxiety Cold perspiration High BP Tachycardia Male reproductive 5 alpha reductase deficiency (Hermaphroditism) No DHT No development of urogenital sinus and external genitalia (males) AR deficiency Mutation in androgen receptor→ insensitivity to androgens less androgens bind to the receptors than normal and their effects are decreased→ causes issues w/ internal and external genitalia Boys: testosterone still produced but it can not activate the AR→ appears female Mullerian duct will still regress bc it is not caused by an androgen But wolffian duct will be present But it won’t develop into epididymis and vas deferens bc testosterone is not working Female reproductive Turner syndrome (X-monosomy) XO No full ovarian development -orthodontic anomalies Pts look like a girl at birth Hypothal/ Pituitary Diabetes insipidus No vasopressin (ADH) Excess urination without loss of water -polydipsia (drinking a lot of water) -frequent urination acromegaly Excess growth hormone in adults -tumor of pituitary 21 hydroxylase deficiency Can’t get past progesterone to DOC or 11-deoxycortisol→ can not make aldosterone or cortisol Loss of sodium→ low blood pressure Increase in androgen production!!!--> bc it is the only thing you actually can make 11- beta hydroxylase deficiency → apparent mineralocorticoid excess Congenital adrenal hyperplasia No aldosterone (but it looks like their is bc everything is there) Cant get past DOC→ DOC accumulates→ DOC has mineralocorticoid activity→ increases salt retention No 21 hydroxy or no 11 beta hydroxy→ can’t make cortisol Cortisol conc. Never gets high enough to trigger – feedback to hypo to decrease ACTH production HIGH MINERALOCORTICOID ACTIVITY→ high blood pressure High levels of androgens→ bc no negative feedback from cortisol to hypothalamus Overproduction of androgens Pregnant w/ a girl→ excess androgen causes ambiguous genitalia Granulosa cells→ estradiol Theca cells→ progesterone Theca cells Granulosa cells Fetus Placenta Key enzyme 17 alpha hydroxylase P450 aromatase 17 alpha hydroxylase P450 aromatase Stimulated by LH only Both LH and FSH What is CAN make testosterone secretions Estradiol DHEA (diffuses into placenta to be converted to estradiol) Estradiol (and obvi progesterone) Inhibin→ inhibits production of FSH Wolffian duct= male Mullerian duct= female ovulation= day 14 Inhibin→ made by granulosa cells→ inhibits production of FSH Most important hormone for early development→ thyroid hormone Do not eat: dopamine→ norepinephrine→ epinephrine ● TSH→ causes follicular cell height to increase ○ Too much TSH→ swelling of thyroid→ presence of goiter - Changing the actual number of receptors on the surface= receptor down regulation→ changes hormone responsiveness/ maximal response Changing the receptor's affinity for the hormone= changing the sensitivity→ ex. done by phosphorylating the receptor - Islets of langerhans cells - alpha= glucagon - beta= insulin - delta= somatostatin - F cells= pancreatic polypeptide **byproduct of breaking down amino acids= ketone bodies C chain→ used to measure Beta cell function in pts with diabetes who are being injected with insulin (they only inject A and B chain) Insulin in secretory vesicles→ stored with zinc→ stabilizes stored hormones - In beta cells→ GLUT2 and glucokinase have a LOW AFFINITY for glucose→ they need a shit ton of glucose in order to be activated→ so they only respond/ make ATP at HIGH glucose levels - Beta cells have a low basal metabolic rate GLUT2= glucose receptor on beta cells - regulated by glucose→ has a low affinity for it - In Beta cells in pancreas GLUT4= glucose transporter on peripheral tissue cells - Regulated by insulin - Found in insulin sensitive tissues→ muscle, fat Sulfonylureas→ blocks K channels→ prevents them from opening→ causes cell to depolarize→ triggers secretion/ exocytosis - This is why it STIMULATES insulin secretion Diazoxide→ opens K channels→ makes the membrane more hyperpolarized→ does not trigger AP/ v-gated Ca channels from opening→ no exocytosis/ secretion - BLOCKS insulin secretion Catecholamines→ (a-adrenergic agonists) inhibit insulin secretion - To increase blood glucose levels for fight or flight Somatostatin→ inhibits insulin secretion Glucagon secretion - Stimulators - Amino acids (esp. Glucogenic AAs→ alanine, serine, glycine) - Acetylcholine - Catecholamines (B- adrenergic) - Cortisol - Exercise - Inhibitors - Glucose - Fatty acids - Somatostatin - (ketones) - Insulin High glucagon= high keto acids in blood Somatostatin→ triggered by high glucose and high amino acids ● Somatostatin function: ○ Main: inhibit insulin and glucagon ■ Does this via paracrine action→ works within a single islet of langerhans ○ In GI tract: decrease glucose transport and decrease blood flow ○ In pituitary: suppresses prolactin cortisol= long term metabolism regulation epi/ norep= short term ● Cortisol ○ Long term regulation of metabolism ○ Stimulates the mobilization of amino acids in muscle to be converted to glucose in the liver ○ Has anti-insulin effects ■ Reduces glucose uptake ■ Decreases lipogenesis ■ Decreases amino acid and glucose uptake in muscle ■ BUT→ it increases glycogen formation→ diff than you would expect ○ Is hyperglycemic (increases blood glucose) ■ But it is different than other short term hormones that do this bc it does NOT stimulate the break down of glycogen→ glucose, it still increases glucose→ glycogen formation Insulin→ increase proteins Insulin→ INCREASES GLYCOLYSIS Glucagon→ NO CHANGE TO GLUCOSE UPTAKE→ ONLY IMPACTS THE LIVER TO INCREASE GLUCONEOGENESIS Epi→ NO IMPACT ON AA/ PROTEINS Epi→ INCREASES GLYCOLYSIS Cortisol→ INCREASE GLYCOGEN SYNTHESIS, DECREASES GLYCOLYSIS Leptin - Peptide hormone made by adipose tissue - More adipose tissue= more leptin secreted - Tells hypothalamus how much fat we have - Triggers behavioral and metabolic changes: - Decreases appetite, increases energy expenditure - Thermogenesis - Secretion of hormones to decrease lipogenic activity in adipose tissue - K/O mice - Mouse with no leptin→ constant eating - Bc no feedback to hypothal to decrease appetite - - Glucagon and epi do all the same EXCEPT: - Glycolysis - glucagon= decreases - epi= increases Glucagon and cortisol do all the same EXCEPT - Glycogen synthesis - glucagon= decreases - cortisol= increases - Glycogenolysis (breakdown of glycogen→ just opp of what is above) - glucagon= increases - cortisol= decreases Diabetes person→ glucose tolerance test→ blood glucose will stay high much longer than it should Other way to diagnose diabetes: Hb1AC - High blood glucose levels→ increases rate of Hb1AC formation - RBCs live 2-4 months→ so measuring Hb1AC tells you average amount of blood glucose over the last 3 months - normal= 4.5-5.6 % - diabetic= over 6.5% Parathyroid - Chief cells - active= 84 AA or 34 AA - Calcium receptor - High calcium→ ACTIVE→ BLOCKS pth - (bc it inhibits adenyl cyclase) - Low calcium→ INACTIVE→ increases PTH ● Max secretion at 1.2mM ca in blood, max= 1.3 mM Vitamin D= inhibits PTH - Independent of Ca levels Epi, histamine, dopamine= increase PTH Ca binding is dependent on pH ○ More basic= more Ca binds to proteins= free Ca goes down ○ More acidic= less Ca binds to proteins= free Ca is higher Phosphate→ more absorbed in gut than Ca, more excreted through urine than feces Osteocytic osteolysis→ osteocytes, extracts Ca without the loss of bone mass Transcalciferin→ vitamin D carrier protein Vitamin D→ negative feedback to parathyroid to decrease PTH secretion Vitamin D in gut: Increases expression of Ca binding proteins and Ca pumps in enterocytes that pump the calcium into the blood→ increases Ca absorption - (Ca enters enterocyte thru passive diffusion down conc. gradient) - Also increases PO4 and Mg absorption The net effect of PTH actions is hypercalcemia and hypophosphatemia, and hypocalciuria and hyperphosphaturia Adrenal gland Cholesterol→ not soluble→ needs LDL to get into cell cortex= steroids, medulla= catecholamines Cool pregnant professors don't call administration Enzymes in mitochondria= p450 ssc, 11B-hydroxylase, aldosterone synthase Zona fasciculata→ makes BOTH cortisol AND androgens transporters/ half life - cortisol= CBG and and transcortin - High affinity→ low cortisol in blood - LONG HALF LIFE - Aldosterone - Albumin→ low affinity (and also low affinity for CBG) - SHORT HALF LIFE A lot more cortisol in blood than aldosterone **PIC OF PATH OF RENIN/ ANGIOTEN/ CGMP FOR ALDOSTERONE** If you block aldosterone secretion→ hyperkalemia (too much K in blood) Cortisol has anti-insulin effects by blocking GLUT4 Cortisol→ inhibits inflam. And immune responses→ that is why glucocorticoids are prescribed for inflammation Production of cortisol= hypothal CRH→ anterior pitu makes ACTH—> adrenal gland makes cortisol *ACTH levels will always peak BEFORE cortisol levels* How ACTH controls cortisol syn: ● ACTH binds to the melanocortin 2 receptor= GPCR that activates adenyl cyclase/ increases cAMP→ cAMP activates PKA→ triggers releases of cholesterol esters from lipid droplets (storage) → they get hydrolyzed back into cholesterol ● ACTH stimulates transfer of cholesterol into the outer mitochondrial membrane, and then also into the inner mitochondrial membrane ● ACTH stimulates P450 to convert cholesterol into pregnenolone Adrenal medulla= in the middle - Chromaffin cells - Sympathetic NS - Enzymes in catecholamine production - TADP - Tyrosine hydroxylase→ RATE LIMITING STEP - AAD - DBH - PNMT - Catechol production: - Tyrosine→ DOPA→ dopamine→ norep→ epi - Requires ATP epi= beta receptors - Gs→ increases aden. Cyc→ increases cAMP norep= alpha receptors - Alpha 1→ Gq→ PLC/ DAG/ IP3→ inc. calcium levels - Alpha 2→ Gi→ inhibits aden cyc→ decreases cAMP Catecholamine effects: - Inc. glucose production - - Inc. lipolysis (only epi) Dilation of bronchioles (smooth muscle relax) (only Epi) Inc. force and rate of contract in heart ONLY ONE THAT IS NOREP: constriction of blood vessels→ increases BP - (the rest are all either just E or E>NE) - This is also E but to a lesser extent Increase renin release from kidney→ increases BP Hypoglycemia→ triggers sympathetic NS→ triggers catecholamine release Epi is a vasoconstrictor ● Beta-blockers→ antagonists of epi (compete with catecholamines for binding to adrenergic receptor, but they dont actually stimulate it) ○ Used to tx hypertension ● Amphetamines→ agonists of epi→ stimulate the adrenergic receptor ○ Mimics effects of epi Testes germinal= make spermatids leydig= makes testosterone sertoli= makes estrogen and DHT→ has p450 aromatase and 5 alpha reductase Germinal and sertoli cells→ inside seminiferous tubules Leydig→ between the tubules Testosterone→ binds to androgen receptor (AR)--> dimerizes, releases HSP→ AR binds to estrogen like binding element→ gene transcrip. Adrongens effect - Somatic tissues= anabolic→ increase syn, dec. breakdown of proteins - Androgenic on male repro tract - NOT STEROIDS HAVE BEEN MADE THAT ONLY HAVE THE ANABOLIC EFFECTS→ women athlete takes testosterone to increase muscle→ she will also develop male characteristics Spermatogenesis→ under control of leydig cell testosterone LH→ leydig - Inc. testosterone FSH→ sertoli - Inc. produc of inhibin→ neg feedback to stop FSH NOS makes NO→ increases cGMP→ vasodilation→ erection Phosphodiesterase→ converts cGMP→ GMP→ no erection Viagra: inhibits phosphodiesterase Female reproductive Primordial→ primary= no hormones, just growing Primary→ secondary→ graafian= hormone dependent Puberty→ inc. GNRH→ inc. FSH→ development of secondary follicle FSH increases p450 aromatase in granulosa cells ■ When estradiol levels peak→ exerts positive feedback on hypothal→ increased GNRH→ LH surge ● FSH levels also increase but not as much as LH bc of the inhibin that is produced by granulosa cells inhibits FSH secretion ● Menstrual cycle ○ Day 0-8= first part of follicular phase ■ Estrogen produced has negative feedback to both anterior pitu and hypothal (less GNRH, LH, FSH) ■ But the # of G cells is increasing→ steady increase the amount of estrogen produced ○ Day 8-13= second part of follicular phase ■ # of G cells and T cells increasing→ follicle is getting bigger and bigger→ more and more estradiol produced ■ When estradiol levels peak→ exerts positive feedback on hypothal→ increased GNRH→ LH surge ● FSH levels also increase but not as much as LH bc of the inhibin that is produced by granulosa cells inhibits FSH secretion ○ Day 14= ovulation ○ Day 15-28= Luteal phase ■ Early luteal phase: ● Still have high levels of LH (but decreasing) → triggers theca and granulosa cells to form corpus luteum ■ Corpus luteum secretes: progest, estradiol, inhibin ● Progesterone & Estradiol→ (–) feedback to hypothal ↓ GNRH→ ↓ FSH, ↓ LH ● Inhibin→ ↓ FSH ● progesterone>>> estradiol ○ Bc need p450 aromatase to make estradiol, and aromatase needs FSH ○ ○ ● ■ ↓ FSH= ↓ estradiol ○ Overall more progesterone is produced If no fertilization: ↓ LH→ triggers corpus luteum to → corpus albicans ■ Corpus albicans= no granulosa/ theca cells→ NO HORMONES ● No granulosa cells→ no inhibin & no estrogen ○ No more (–) feedback to anterior pitu to ↓ FSH→ now there is an ↑ FSH→ starts new cycle ■ ↓ estradiol→ spiral arteries collapse→ endometrium sheds→ menstruation If there IS fertilization: meiosis→ mitotic divisions→ blastocyst implants into wall at day 7 ■ Blastocyst has trophoblast (future placenta) ■ Trophoblast secretes HCG ■ HCG mimics LH→ keeps corpus luteum alive even though ↓LH ■ Corpus luteum keeps making progesterone and estradiol ● Progesterone→ stimulates endometrial glands→ prevents it from making the endometrial lining shed→ allows implantation ■ Week 6→ placenta starts to make progesterone and estradiol from cholesterol ● Important to have ↑ cholesterol during pregnancy ● Placenta→ has p450 aromatase, no 17A hydroxylase ○ CAN’T: progesterone → DHEA ○ CAN: DHEA → estradiol ● Fetus→ has 17A hydroxylase, no p450 aromatase ○ CAN’T: DHEA → estradiol ○ CAN: progesterone → DHEA ● SO: ○ Mom gives cholesterol to placenta ○ Placenta to turns it into pregnenolone and progesterone ○ Pregnenelone and progesterone go into fetus ○ In the fetus: ■ Pregnenelone→ DHEA ■ Progesterone→ cortisol and aldosterone (thru fetal adrenal glands) ○ DHEA goes into the placenta ○ In the placenta: ■ DHEA→ estradiol Somatic effect of estradiol ○ Vasodilation by: ■ Increasing 2 vasodilators: ● NO ● Prostaglandin E2 ■ ○ ○ Decreasing 1 vasoconstrictor: ● Endothelin-1 Mammary gland development Antiresorptive effect on bone Hypothalamus / pituitary Posterior pitu - Hormones made in hypothal, releases it in the blood supply of the posterior pitu Anterior pitu - Hypo releases hormones into median eminence 2 major products of posterior pitu= vasopressin and oxytocin Vasopressin (ADH) - Increases water retention in kidney - Increases thirst - Released if blood is hyperosmotic Oxytocin→ controls lactation and contraction of uterus - Increases milk ejection (signal= suckling) - Increases uterine contraction (signal= stretch of uterus) - Both have afferent sensory neurons that go to hypothalamus to trigger the release Anterior pitu GHRH (growth hormone releasing hormone)--> Progesterone→ peaks during luteal ACTH→ stimulates secretion and growth of zona fasiculata and zona reticularis Somatostatin→ released from HYPOTHALAMUS Growth hormone - Inc. secretion of somatomedin (IGF) → does negative feedback→ blocks GHRH from hypothal and increases somatostatin secretion - somatomedin= insulin like growth factor (IGF) - Secreted by liver - Does everything GH does but it works like insulin and increaese glucose uptake and increases liponeogenesis - Function: increase growth, but too much GH can cause elevated blood glucose - Bc it inhibits glucose uptake and inc lipolysis→ GH is diabetogenic Prolactin - Mammotroph cells in anterior pitu - Function: increase milk production - Regulation - increase= estrogen - decrease= dopamine, PIF Thyroid Secondary active transport→ brings iodine (i-) into cell (I/ Na symport) DIT+DIT= T4 MIT+DIT= T3, and small amounts of rT3 ○ ● ● ● ● Deiodinases→ need selenium to work ■ No selenium→ no converted T4 into either T3 or rT3 2 possible steps: (T4 can become 2 things: T3 or rT3) ○ Activation step: ■ More active/ potent than T4 ■ Enzyme: 5’-deiodinase: T4→ T3 ○ Deactivation step: ■ Enzyme: 5-deiodinase: T4→ rT3 main= thyroxine binding globulin (TBG) ○ High affinity for T4 ○ Low affinity for T3 Low temp= thyroid increases activity ○ Thyroid increases metabolism→ breaks down sugar→ generates energy→ can be used as heat cochlea formation ○ Hypothyroidism in children→ deafness