Forcep

What are the2 diff blades? cephalic and pelvic curve. cephalic curve has Shape of fetal head while pelvic curve is the axis of birth canal What are 2 most important discriminators for mother and infant: station and rotation What are the 3 diff classifcations? Outlet, low, midpelvic. What is outlet: Outlet is the scalp visible in introius without separating labia. The fetal skull has reached the pelvic floor and sagitall sutures in AP/R LOA/R-LOP; fetal head at or near perineum; rotation not exceed 45 degree Wht is low? Leading point of fetal scalp at station > +2 and not on pelvic floor; rotation <45 degree L/R OA to OA, L/R OP to OP What is midpelvic station: station above 2 plus, head enaged, high, not included. What are the effects of anesthesia? 2 fold increase rate of forcep delivery; associated with failure of spon rotation to OA, slowing 2nd stage labor, decrease maternal expulsive forces What r fctn forcep? Most impt is traction, roation What is the simpson used for? Delivery fetus with molded head What is tucker mclane? Used for round headed; usually mutiparas What are indications for forceps? Maternal: exhausted, prolonged 2nd stagelabor, fetal is prolapse umbilical cord, premature sep placenta, nonreassuring FHR What are pre req for forcep application? head must be engaged, fetus in vertex or face presentation, position fetal head must be precise, cervix dilated, membrane must be ruptured , no suspected CPD Whatismost common forcep used: simpson What is the forcepf or occiput transverse/occiput oblique posterior? Tucker mclane What is the idea for rotating head and occiput transfer/occiput obliue posterior? Keilland What is rotation of head in transverse arrest and ideal for cases of marked asynctism? Barton Which is for aftercomming in breech postion?piper What is morbidity from forceps operations? Maternal is lacerations, urinary rectal incon, postpartum mertitis, bladder atony What is morbidity of fetus? intracranial hemorrhage, facial nerve palsy, brachial plexus injury What is conclusion for morbid from forceps? Less than 45 degree associated with lil increase in maternal morbid What are vaccum extraction advantages? To avoid insertion of space occupying steel blades within the vagina and of req for precise positioning over fetal head; ability to rotate w/out impinging soft tissue, decrease ICP during traction, soft cup lower incidence scalp injury andhigher failure rate, complication more common metal than soft cups, indication and pre req same as for forcep delivery Which is a reusable instrument? Silastic cup What uses a disposable 60 mm cup? Mityvac instrument

What is the technique for cup? Proper cup placement is most important deterimnent of success. Center of cup should be over sagittal suture, 3 cm in front of post fontanelle; full circumference of cup shud be palpated before and ater vaccum is created prior to traction; intermittent and coordinated with maternal expulsive forces; progressive descent accompany each traction attempt What is comparision of forceps and vacuum? Forceps has higher freq of maternal trauma and blood loss, more than 3rd and 4th degree lacerations; infants have more marks and bruising. Vaccum has increased incidence of neonatal jaundice with shoulder dystocia and cephalhematoma are doubled. Associated with less maternal but more fetal trauma

Abnorma of placenta, cord, fetalmembrane What is a placenta biparta or bilobota? Division of lobes are incomplete, fetal vessels extend from 1 lobe to the other being uniting to form the umbilical cord; What is placenta duplex or triplex? 2 or 3 distinct lobes separated entirely; vessels remain distinct What is succenturiate lobes? 1 or more accessory lobes that develop at a distance from periphery of main placenta; it is a small version of bilobated What is membranceous placenta? All fetal membranes covered by functioning villi; placenta develop as thin membrane structure occupying entire periphery of chorion; associated with placenta previa or accrete What is a ring shaped placenta? Annular shape, variant of membranaceous placenta; associated with antepartum and postpartum bleeding, fetal growth restriction What is fenestrated placenta? Central portion of discoidal placenta is missing; only involves VILLOUS tissue with chorionic plate intact; mistakenly considered as retained placenta Explain extrachorial placentation? Chorionic plate fetal is smaller than the basal plate maternal; placental periphery is uncovered; some complications are antepartum hemorrhage from placental abruption and fetal he, preterm delivery, perinatal mortality, fetal malformations What is circumvallate placenta? It is fetal surface presents with central depression with double fold ring of aminon and chorion with degenerated decidua and fibrin in btwn What has +ring aminon and chorion and no central depression? Circummarignate placenta What is trophoblastic tissue invade mymometrium to varying depths? Placenta accrete, increta, percreta. It is associatd with placenta previa, and prior uterine incision or perforation. What are degenerative placental lesions? Deposition calcium salts, results from trophoblast aging and infarction. Common smokers, increase preg progress What is most common placental lesion? Placental infarction; 90% located at placental margin; it results from occlusion of maternal uteroplacental circulation; normal aging process What are complications of placental infarction? Uteroplacental insuffi, placental abruption What is associatd with placental infarctions? Pre-eclampsia, lupus anticoagulant

What is thehistopath for placental infarction? Fibrinoid degen of trophoblast, calcification, ischemic infarction How does it happen? Occlusion decidual artery, interrupt flow to intervillous space, ischemia What is found underneath the chorionic plate and extends downward toward intevillous space subchorionic infarct What has no large area of villous infarction, fibrnoid deposition within decidua basalis, and confined to the placental floor and fibrin extend to intervillous space? Maternal floor infarction What are associated with maternal floor infarction? Thrombophilia, fetal growth restriction, abortion, still births What is a stem artery from fetal circulation in placenta that is occluded producing sharply demarcated area of avascularity? Placental vessel thrombosis; its complications are fetal growth restriction and stillbirth What is associatd with striking enlargement of chorionic villi? Severe erythroblastosis, fetal hydrops, maternal diabetes, Fetal CHF maternal fetal syphilis. This is called hypertrophic lesions of chorionic villi. What are clumps of syncytial nuclei project into the intervillous space beginning after 32 weeks and respresents apoptosis? Syncytial knots Is it normal that cytrophoblatic cells become progress reduce as pregn advance? True What are maternal fetal disorder with numerous cytotrophoblastic cell in placenta? Gestational hypertension, diabetes, erythroblastosis fetalis What is placental inflammation? Characterized by degenerative and necrotic changes; bacteria invade fetal surface placenta; associated with pre term and prlonged membrane rupture What are components resemble BV and stroma of chorionic villus and ONLY beningtumor? Has hamartomas? Chorioangioma Is small growth asymptomatic ? yes What is large growth associated with? Hydraminos, antepartum hemorrhage; can provide AV shunt lead to fetal heart failure What is correlated with? Low birthweight, and severe anemia What tumors mets to placenta? 1/3 melanoma, leukemia/lymphoma 1/3; tumors confined to intervillous space. Fetus will hve metastasis in of cases What is usually described with traumatic delivery? Embolic fetal brain tissue. Located where? Fetal lung and placenta Describe charteristics of meconium staining? Its uncommon preterm, risk increase 25-30% after 42 weeks. (+) staining of amnion=1-3hrs. What is associated with meconium staining? Severe fetal academia, doubling of CS delivery rate; 10 % develop meconium aspiration syndrome. What are maternal complications of meconium staining? Meconium associated aminontic fluid embolism, cardioresp failure, consumptive coagulopathy, maternal moratliy, Wht has 4 fold risk of puerperal metritis? Meconium staining What is manifestation intrauterine infection? Chorioamnionitis; associated with prolonged membrane rupture and long labor

What is grossly characterized by clouding of membranes and foul oder? Chorioaminoitis Characterized aminoitis versus funisitsi? Amniotisis is amniotic fluid while funists is umiblica cord, both are fetal orgin; antibiotic therapy and expedient delivery What result from fusion aminonic fluid, with subsequent fluid rentation? Small amnionic cyst What is light tan, creamy nodule in aminon? Aminon nodosum? What is made up of? Vernix caseosa with hair, degenerated squames, sebum; what result from? Oliohydraminos What is aminon nodum most common in? fetal renalagensis, prolonged PPROM, placenta of donor fetus What are formed from disruption of aminon? Aminoinic bands; whtis the consequence intrauterine amputation! What is diff of short vs long cord? Short cord fetal growth restrict, congential malformation, intrapartum distress, 2 fold risk of death, long cord: maternal systemic disease, delivery complciations, cord entanglement, fetal distress, fetal anomalies, resp distress, 3 fold increase of perinatal mortality What is mean cord length? 37 cm What is exclusively long cord?70 cm What is cord length influenced positively by? Amnioticfluidvolume, fetal mobility, heredity What are conditions producing short cord? Oligiohydraminos, decreased fetal movement. What associated with hypocoiled cord? Meconium staining, preterm birth, fetal distress What associated with hypercoiled cord? Preterm delivery, cocaine abuse What is single umbilical artery? 2 vessel cord associated with congenital anomalies in of affected infants; increased incidence in who? Maternal diabetes, epilepsy, pre eclampsia, antepartum hemorrhage, oligohydraminos, hydraminos What is single umbilical artery associatd with spontenous abortion How many weeks is # of cord vesels quantified by UTZ? 17-36 weeks What are associatd anomalies in single umbilical artery?renal aplasia, limb reduction defects, atresia hollow organs. Doppler velocimetry indices? Lower. VOlumeteric blood flow? Equal to normal What is umbilical separate from cord substance before their inserstion into placenta? Furcate insertion; prone to twisting and thrombosis! What is the battledore placenta? Marginal insertion. What is clinical significance? Cord pulled off during placental delivery What is umbilical vessel separate in membranes at distance from placental margin and surrounded only by a fold or amnion and most frequent in twins? Velamentous insertion. What is fetal vessels cross cervical os below presenting fetal part and associatd with velamentous insertion? Vasa previa. How do you dx it? Color Doppler exam What is fetal danger of vasa previa? Membrane rupture and tearing of fetal vessels with exsanguination. What are risk factors for vasa previa? Low lying placenta, bilobed or succenturiate placenta, multifetal placenta, and preg in vitro fertilization

How is itdx? TVS with color Doppler. Echogenic parallel or circular line near cervix; fetal death instant. What results from kinking of vessels to accommodate length of cord? False knot What result active fetal movement? High incidence of monoamniotic twins? True knots Which has high incidence of venous stasis, mural thrombia fetal hypoxia, death/neuro abnorm and still birth? True knots What do loops usually occur? Around neck; likely longer cor; may cuase intrapartum complications; fetal descent and contraction, compress cord vessels, mod deceleration What has more likely lower umbilical artery ph? Loops What results from fetal movement and compromises fetal circulation? Torsion What is more serious and most are stillborn and assoc with extreme focal deficiency in whartons jelly? Stricture What is accum of blood and assoc with shortcord, trauma, and entanglement? Hematoma What is derived from remnants of umbilical vesicle or allantosis ? true cyst which is small What is result of liquefaction of whartons jelly? False cyst large Management of normal labor and delivery

What is dif btwn true versus false labor? True labor has reg contraction, reg interval and shorter intensity, increase discomfort, cervical dilation back and abdomen, neg relief sedation. False labor has irreg interval, ireg intensity, long intensity, no discomfort, cervi dilation chiefly lower abdomen, sedation has relief How long is preadmi and admi electronic FHR monitoring for? Atleast 1 hr before discharge with low risk preg When is vaginal examine preformed? Preformed unless there is bleeding in excess of bloody show; number of vag exam labor correlates with infectious morbidity What is impt to detect rupture membrane? Possible cord prolapse, labor likely to begin, infection likely if delayed >24 hrs What is conclusive dx for rupture membrane? + pooling of amniotic fluid on speculum exam What are other tests to dx rupture membrane? Nitrazine test: ph >6.5 consistent with rupture membrane; normal ph vagina 4.5-5.5; amniotic fluid ph is 7-7.5 What is ferningof vaginal fluid due to? Nacl, CHON, and CHO of amniotic fluid What are other 2 tests? AFP in vaginal valt and transabdomina dye infection:indigo carmine dye least favored cuz invasive What is 100% effaced cervix? Cervix as thin as adjacent lower uterine segment.2-2.5 cm avg unefacted 0% What are positions of cervix which relationship cervical os to fetal head? Posterior, midposition, anterior. Anterior indicates the baby is ready to deliver Where is station located ? relation to ischial spine cuz midway b/w inlet and outlet Where is lowermost portion of fetal presenting part at level of ischial spine? Station 0 Where is engaged leading part located? Station 0 or below

What is biparietal plane pelvic diameter that cross pelvic inlet? Engaged What cuase a molding or caput succedaneum? Fault forcep delivery What station is intrious visible? Station 5 What 5 characteristic of bishop scoring? Cervical dilatation, effacement, consistency, position, and fetal station What is uterine contraction to full cervical dilation ? management of 1st stage of labor.it has longest duration What is the way to monitor Fetal heart rate? Low risk preg, every 30 min 1st stage, then every 15 mins 2nd stage. For high risk, every 15 min 1st stae, then every 5 min 2nd stage Whenyou should monitor fetal well being? Nulliparous 7 hrs, multiparous, 4 hrs When is fetal HR monitored? After every uterine contraction; norm preg every 30 min, high risk every 15 min; vaginal exam 2-3 hr interval Where is FHR assessed? Lower ab quad What are good uterine contractions? Every 2-3 mins to detect dystocia What is normal duration of uterine ex? 40-60 sec What is tachsystole or tetanic contraction? >90 How often evaluate maternal vital sign? Every 4 hr, prolonged rupture >18 hrs, evaluate tmp every hr, antimicob prophylaxis for group b strep What is oral intake during labor and delivery ? NPO, antipation of analgesia dueto aspiration and vomiting When IV fluids needed? Immediate puerperium or prolonged labor to prevent dehydration and acidosis from prolonged fasting; admin oxytocin; admin glucose, sodium water to fasting parturient at 60 to 120 ml/hr prevent acidosis and dehydration What is most comfortable position during labor ? lateral recumbency What is benefit of amniotomy ? more rapid labor, early detection of meconium stain amniotic fluid; apply electrode to fetus; accelerate labor 1-2 hr/ assted with significantly shorter labor by 4 hrs What complications of aminotomy? Chorioamnioitis, cord compression patterns. What is the fetal HR monitoring for 2nd stage of labor? Low risk every 15 min, high risk every 5 mins What is better open or closd glottis? Open Changes in FHR during contraction? Slows down but goes to normal What is encirclement of largest head diameter by vulvuar ring? Crowning What is the prep for delivery in primpara and multipara in 2nd stage labor primpara is 50 min while multipara is 20 min What is dorsal lithotomy position anatomic basis? Upward gliding movement of sacroiliac joint giving additional 1.5-2 cm room for passage of the baby. Legs may cramp cuz fetal head compress pelvic nerves In spon delivery, what is the ritgen maneveur? Allow control delivery of fetal head ; favor neck extension toward maternal symph pubis so smallest diameter pass via intrious; assoc with 3rd degree lacerations and episotomy.

What is handpoised method? Attendant didnt touch perineum; similar laceratino of ritgens, but lower incidence of 3rd degree tear What should be done in delivery of shoulders? After delivery the occiput turns toward one of the maternal thigs and head assumes the transverse position. Gentle downward tration applied until shoulder appear under pubic arch; then upward movme, the posterior shoulder delivered What is the bisacromial diameter has rotation into the AP diameter of pelvis? External rotation/restitution. Why should nasopharyx be cleared? To minimize aspiration of amniotic fluid particulate mater, and blood once the thorax is delivered and newborn can inspire What is slipped over head if loose and cut btwn 2 clumps if tiht? Nuchal cord What is cut btwn 2 clamps placed 4-5 cm from fetal abdomen and later an umbilical cord clamp is applied 2-3 cm from fetal abdomen? Cord clamping In mgt of 3rd stage of labor, what are signs of placental separation? 1-5 min after delivery of newborn, uterus becomes firm and globular, there is sudden gush of blood and uterus rises in abdomen. Umbilical cord protrudes farther out of the vagina. What is sudden gush of blood cuz placental detachement occurs in periphery ? Duncan What is no blood comes out d/t placental separation occurs first at center? Schultz What is a complication associated with premature placental delivery esp when traction? Uterine inversion What should be done during delivery of placenta? Push fundus toward maternal head, traction of umbilical cord must not be used to pull placenta out of uterus; inversion of uterus is grave complication What are 2 maneuveur to separate placenta? Modified credes maneuveur and brandt Andrew maneuveur Never grasp placent til separated; hand covered with antiseptic creame introduced vagina following the ocord. Locate margin placenta and insinuate ulnar border hand btwn it and placenta like separating book pages What is active management of third stage? 5 units of oxytocin wit .5 mg of ergometerine; SE: nausea, vomiting, blood pressure elevation Explain 4th stage of labor ? hour immediately following delivery uterine atony more likely; maternal vital signs every 15 mins. When is postpartum hemorrhage more likey? 4th stage labor How to control hemostasis? Oxytocic agent; uterine massage and oxytoci agent What causes ADH effect? Oxytocin; there is fall in BP followed by increase CO. Whatproduce sustain myometerial contraction? Ergonovine/methylergonovine; effective postpartum but dangerous to deliver; may intiate transient but severe hypertension What not used routinely and reseverd for hemorrhage? Prostaglandin What involves fourcheete, perianal skin, vaginal mucus membrane not muscle or fascia? 1st degree lac What has fascia and muscle but no anal spincther? Second degree What has skin, mucus membrane, perineal body and anal spinchter? 3rd degree lac

What extends via rectal mucosa to express the lumen of rectum? 4th degree In epistomy, what can cause 3rd or 4th degree laceration and more superior than mediolat episotomy? Median/midline When is it done ?with shoulder dystocia, breech delivery, forcep vacuum extraction, occiput posterior What prevents pelvic relxation? Cystocele, rectocele, urinary incompetence When is timing episotomy? When head is visible during contraction of diameter of 3-4 cm; performed after application of blades during forcep delivery Compare midline vs mediolaterl? Mediolateral difficult,faulty healing, post op pain, loss anatomic fct, more bleeding, dyparenuia, uncommon extension

Recurrent spon preg loss What def? 3 or more preg loss before 20 weeks; most common complication preg Occurs 1/300 preg After 4 sponteanous abortion risk is 40-50 % What is most common error? Parental chromosomal balance translocation What provides insight to new parental genetic abnormalties? Molecular cytogenetic technique What are congential anomlaies? Incomplete mullerian duct fusion, sepetum resportion defect, DES exposure, uterine cervical anomalies In intrauterine septum, where is it most common? 2nd tri What can in utero DES exposure cause? Hypoplasia contributing to 1st and 2nd tri spontaneous abortion, incompetent cervix, premature labor What are acquired defect? Cervical incompetence, synechie, leiomyoamas, adenomycosis; ithappens by interference with blood supply in adhesion and leiomyoma and immune phenomenon potentially with endometriosis What does abnormal LH secetion cause: direct effect oocyte causing premature aging; dyssynchourous onendometerium maturation; elevate test level What compromise blood flow uterus? DM; increase Hbg A1c What is most common materal infection? Ureaplasma urilyticum Immune response genes What are MHC I impt for? Recog structure in rejection rezones mediated by cytotoxic T lymphocytes What are MHC II impt for? Dtermin immune compati of tissues Immunity is specific regulatd by CD4 What are TH1 cyotkins? IFN-Y, TNFb Whatare TH2 cytoines? IL10, IL4, IL5, IL6 Humoral ab What are some humora ab dises? Antiphosphlipid ab to either cardiolipin or phosphatidylserine; Igg or IGM directed against neg charged phospholipid

What characterized APAS? Prolonged phospholipid coagulation test, Aptt, russel viper venom nad thrombosis in vitro What mech of APAS? Increase TXA2 and decrease PGI; platlet adhesion with placental vessel in vitro vs phosphatidylserine inhibt formation of syncytial trophoblsat In postconcep evaluation, what is gold stand monitor early preg? UTZ; b hcg helpful until UTZ can be done until 1,500 mU/ml How often UTZ done? Evey 2 weeks When is maternal serum a fetal protein? 16-18 weeks What is used in testing neural tube defects and assess fetal karyotype and preg progress past the time of prior los? Aminocentesis When is tx indicated in chromosomal aberration? Robertsonian translocation then donor oocyte or sperm can be used When is hysterscopic resection of intrauterine defects used? Submucus leiomyomas, intrauterine adhesion, intrauterine septa When should cervical cercalage be considered after 1 tri ? its for women with DES asscoited uterine abnormalties For endometerisosi what should be used? Resected laproscopically. For APAS, wht is tx? Heparin and asprin What can progesterone do? Wit immunosuprresive effect can inhibt in viro TH1 immunity to trophoblast

Hyperandrogenism What is vellus hair? Fine texture short, languo What is terminal hair? Coarse, longer, darkly pigmented What is the growth phase? Anagen What is the involution phase? Catagen What is the resting phase? Telogen What are both variable in length? Growth and resting phase What is short angaen phase whc include extremities, eyebrow, eyelash? Short hair What is extended anagen phase followed by short telogen phase(scalp)? Long hair What is low level of androgens in both genders? Axilla, lower pubic triangle, forearms, legs, Whatis final hair growth dependnat on? Level circulating androgens, sensitivity to hair follicles to androgens What is hirustism due to? Increase 5 alpha reductase The total daily production of testosterone in women is normally about 0.35 mg The length of the anagen phase is prolonged = the hair becomes thicker Excessive 5 alpha reductase activity also may lead to acne as well as scalp hair loss (alopecia) Hirsutism:

Presence of hair in location where it is not normally found in a woman, specifically in the midline of the body (upper lip, chin, back and intermammary region)

Hypertrichosis: A generalized increase in the amount of body hair in its normal location Hirsutism: Testosterone o <1.5 ng/mL: hirsutism without other signs of virilization; is a/w relatively mild disorders of androgen production or increased 5alpha-reducatase activity o Hirsutism has a gradual onset and not caused by a severe enzymatic defect or a neoplasm In the milder forms hair is found only on the upper lip and chin In severe forms it appears on the cheeks, chest (intermammary), abdomen (superior to the umbilicus), inner aspects of thigh, lower back, and intergluteal areas 5alpha-reductase testosterone DHT 3a diol. Women with hirsutism can have normal ovulatory menstrual cycles, oligoamenorrhea, or amenorrhea. >= 2ng/mL: presence of virilization; develops over a short time; nearly always amenorrheic; suspect androgen secreting neoplasm; virilization due to both the masculinising and defeminising (antiestrogenic) action of testosterone and include: o temporal balding o Decrease breast size o Increased muscle mass o Clitoral hypertrophy o Dryness of the vagina. Physiology: Sources of androgen production: 1. Ovaries; major androgen produced is testosterone: other androgen secreted are androstenedione & DHEA 2. Adrenal glands: major androgen produced is DHEA-S: also secretes androstenedione & DHEA 3. Peripheral compartment: extrasplanchnic & nonglandular areas of production; includes the skin; modulates androgens produced by the ovaries & adrenals; where conversion of androstenedione & DHEA to testosterone occurs The normal adrenal gland secretes little testosterone, although some uncommon adrenal tumors may secrete testosterone directly. Androstenedione and DHEA do not have androgenic activity but are peripherally converted at a slow rate to the biologically active androgen, testosterone The total daily production of testosterone in women is normally about 0.35 mg Two thirds of the daily testosterone produced in a woman originates from the ovaries. Thus increased circulating levels of testosterone usually indicate abnormal ovarian androgen production For practical purposes circulatory levels of DHEA-S reflect an adrenal source of production Testosterone o SHBG bound: 85%

o Albumin bound: 10 to 15%: biologically active o Free/unbound 1 to 2% biologically active Serum testosterone can be measured either as the total amount. The amount that is believed to biologically active (non-SHBG bound) and as the free form. Peripheral target tissue: o 5 alpha reductase diagram: testosterone DHT = 3 adiol biologic activity Even with normal circulatory levels of androgen, increased 5 alpha reductase activity in the pilosebaceous until will result in increased androgenic activity, producing hirsutism. 3alpha diol-G level- A metabolite of 5 alpha reductase conversion of testosterone (T) to dihydrotestosterone (DHT), the most accurate indicator of the degree of peripheral androgen metabolism Serum levels of total testosterone are similar in normal and hirsute women Markers of androgen production: o Ovary: testosterone o Adrenal gland: DHEAS o Periphery: 3 alpha-diol-G Etiology: 1. Androgenic medication: a. Steroids b. 19-norprogestins c. danazol 2. Abnormal gonad development: with external sexual ambuguity or primary amenorrhea in addition to androgen excess findings & Y chromosome 3. Androgen secreting tumors in pregnancy a. Luteoma of pregnancy: solid ovarian tumor b. Hyperreactio luteinalis: bilateral cystic enlargement i. How do you manage this? Table 1: differential diagnosis of hirsutism and virilization: Source = diagnosis Nonspecific o Exogenous/iatrogenic o Abnormal gonadal or sexual development Pregnancy o Androgen excess in pregnancy: luteoma or hyperreactio luteinalis Periphery o Idiopathic hirsutism Ovary o Polycystic ovary syndrome o Stromal hyperthecosis o Ovarian tumors Adrenal gland o Adrenal tumors o Cushing syndrome o Adult-onset congenital adrenal hyperplasia @@ Idiopathic hirsutism (peripheral disorder of androgen metabolism)

Is manifested by signs of hirsutism and regular menstrual cycles in conjunction with normal circulatory levels of androgens (both testosterone and DHEA-S) Because this type of disorder is frequently present in several individuals in the same family, it has also been called familial, or constitutional, hirsutism. Since neither ovarian nor adrenal androgen production is increased in these individuals, the cause of the androgen excess was not determined until recently, hence the term idiopathic hirsutism. Is a very common cause of hirsutism and is second in frequency only to polycystic ovary syndrome (PCOS) Individuals have increased levels of 3 alpha diol-G, indirectly indicating that the cause of hirsutism is increased 5 alpha reductase activity (5alpha RA) Is actually a disorder of peripheral androgen metabolism in the pilosebaceous apparatus of the skin and is possibly genetically determined although it is also possible that early exposure to androgens can program increased 5 alpha RA Antiandrogens that block peripheral testosterone action or interfere with 5 alpha RA are effective therapeutic agents for this disorder. Cryptic hyperandrogenism: elevated levels of circulatory androgens without clinical manifestations of hirsutism or acne. It is usually accompanied by anovulation. Stromal hyperthecosis: Is an uncommon benign ovarian disorder in which the ovaries are bilaterally enlarged to about 5 to cm in diameter Histologically there are nests of luteinized theca cells within the stroma Disorder has a gradual onset and is initially associated with anovulation or amenorrhea and hirsutism With increasing age the ovaries secrete steadily increasing amounts of testosterone. Thus when women with this disorder reach the forth decade of life, the severity of the hirsutism increases, and signs of virilization, such as temporal balding, clitoral enlargement, deepening of the voice, and decreased breast size, appear and gradually increase in severity. By this time serum testosterone levels are usually greater than 2 ng/mL, similar to levels found in ovarian and adrenal testosterone-producing tumors. (however, with the latter conditions the symptoms of virilization appear and progress much more rapidly than with ovarian hyperthecosis, in which symptoms progress gradually over many years. Androgen-producing tumors: Ovarian neoplasms: o Cystadenomas o Brenners tumors o Krukenbergs tumors o Germ cell tumors o Sertoli-leydig cell tumors o Hilus cell tumors o Lipoid cell (adrenal rest) tumors o Granulosa/theca cell tumors Androgen-producing ovarian tumors usually produce rapidly progressive signs of virilization Adrenal tumors: Nearly all the androgen-producing adrenal tumors are adenomas or carcinomas that generate large amount of the C19 steroids normally produced by the adrenal gland: DHEA-S, DHEA, and androstenedione.

Although these tumors do not usually directly secret testosterone, testosterone is produced by extraglandular conversion of DHEA and androstenedione. Women with these tumors usually have markedly elevated serum levels of DHEA-S (>8ug/mL) Women with these laboratory findings and a history of a rapid onset of signs of androgen excess should undergo a CT scan or MRI of the adrenal glands to confirm the diagnosis An adrenal adenoma is highly likely when DHEA-S levels are greater than 8 ug/mL and testosterone levels are more than 1.5 ng/mL Late-onset 21 hydroxylase deficiency: Congenital adrenal hyperplasia (CAH)_ is an inherited disorder caused by an enzymatic defect (usually 21-hydoxylase (21-OHase) or less often 11Beta-hydroxylase, resulting in decrease cortisol biosynthesis. As a consequence, adrenocorticotropic hormone (ACTH) secretion increases and adrenal cortisol precursors produced proximal to the enzymatic block accumulate and are converted mainly to DHEA and androstenedione. These C19 steroids are in turn peripherally converted to testosterone, which produces signs of androgen excess. Because the enzymatic defects are congenital, the classic severe form (complete block) usually becomes clinically apparent in fetal life by producing masculinization of the female external genitalia. The severe form of CAH is the most common cause of sexual ambiguity in the newborn. The more attenuated (mild) block of 21-OHase activity usually does not produce physical signs associated with increased androgen production until after puberty. Thus this condition, termed late-onset 21-hydroxylase deficiency (LOHD) or late-onset congenital adrenal hyperplasia, is associated with the development of signs of hyperandrogenism in a woman in the second or early third decade of life. Also called nonclassic congenital adrenal hyperplasia attenuated, or acquired adrenal hyperplasia. LOHD: is probably the most frequent autosomal genetic disorder in humans Both classic CAH and LOHD are transmitted are transmitted in an autosomal recessive manner at the CYP21B locus and are linked to the HLA-B locus LOHD is a phenotype that is symptomatic after adolescence LOHD is also usually associated with menstrual irregularity. the mechanism for anovulation is similar to that which occurs with PCOS. The increased levels of androgen lower SHBG levels, thus increasing the amount of biologically active circulating estradiol. The increased estradiol stimulates tonic LH release, which increases ovarian androgen production and locally inhibits follicular growth and ovulation. Thus women with this disorder present with postpubertal onset of hirsutism and oligomenorrhea or amenorrhea, similar to women with PCOS. However, women with LOHD, unlike those with PCOS, commonly have a history of prepubertal accelerated growth (ages 6 to 8 years) with later decreased growth and a short ultimate height. A history of this growth pattern, a family history of postpubertal onset of hirsutism, and findings of mild virilization are indicators of the presence of CAH.

To differentiate LOHD from PCOS, measurement of basal (early-morning) serum 17-OHP levels should be performed. If basal levels of 17-OHP are greater than 8 ng/mL, the diagnosis of LOHD is established.

If 17-OHP is above normal (2.5 to 3.3 ng/mL) but less than 8 ng/mL, an ACTH stimulation test should be performed. A baseline 17-OHP should be measured and 0.25 mg of synthetic ACTH infused as a single bolus. One hour later another serum sample of 17-OHP should be measured. If the level of 17-OHP increases more than 10 ng/mL, the diagnosis of LOHD is established ( Fig. 40-22 ). Individuals with LOHD should be treated with continuous corticosteroids to arrest the signs of androgenicity and restore ovulatory menstrual cycles. Cushing's Syndrome Excessive adrenal production of glucocorticoids due to increased ACTH secretion (Cushing's disease) or adrenal tumors produces the signs and symptoms of Cushing's syndrome. These findings include hirsutism and menstrual irregularity in addition to the o Signs/symptoms: Hirsutism Menstrual irregularity o classic findings of central obesity, dorsal neck fat pads, abdominal striae, and muscle wasting and weakness. Can be easily differentiated from PCOS by performing an overnight dexamethasone suppression test. If the cortisol level is less than 5 g/100 mL, Cushing's syndrome is ruled out. If the cortisol level fails to suppress to this degree, the diagnosis of Cushing's syndrome is not established. It is necessary to perform a complete dexamethasone suppression test (Liddle's test) or measurement of urinary free cortisol and plasma ACTH to determine whether Cushing's syndrome exists. DIFFERENTIAL DIAGNOSIS testosterone and DHEA-S to determine if there is an ovarian or adrenal source Measurement of total testosterone: most cost effective Serum testosterone levels greater than 2 ng/mL with normal DHEA-S levels indicate the probable presence of an ovarian tumor. The diagnosis can be confirmed by bimanual pelvic examination and ultrasonography, CT scan, or MRI. Women with a rapid progression of virilization and DHEA-S levels greater than 8 g/mL most likely have an androgen-producing adrenal adenoma, and the diagnosis can be confirmed by CT scan or MRI. A long history of gradually increasing hirsutism, even if accompanied by virilization, is not consistent with the diagnosis of adrenal or ovarian tumors. The diagnosis of ovarian stromal hyperthecosis should be suspected for individuals with these signs and testosterone levels greater than 1.5 ng/mL. Women with physical findings consistent with Cushing's syndrome should have the diagnosis ruled out. PCOS, LOHD, and idiopathic hirsutism may be associated with a similar history and findings at physical examination. Menstrual irregularity, however, is uncommon among women with idiopathic hirsutism, and testosterone and DHEA-S levels are normal. Women with LOHD commonly have a family history of androgen excess, and often belong to an ethnic group with a higher gene frequency for an abnormality. The diagnosis of LOHD is established by measurement of 17-OHP either by an early-morning serum sample or following ACTH stimulation. Treatment of hirsutism depends on whether the androgen excess is ovarian, adrenal, or peripheral. MANAGEMENT Ovarian and Adrenal Tumors

 USO/TAH-BSO adrenalectomy Late-Onset 21-Hydrolase Deficiency glucocorticoids such as o hydrocortisone (15 to 20 mg), o prednisone (5 to 7.5 mg), or o dexamethasone (0.5 to 0.75 mg) in divided doses. The aim of treatment is to suppress androstenedione and bring 17-OHP and progesterone levels into the normal range. Idiopathic Hirsutism An agent that inhibits peripheral androgen activity should be administered Because of the length of the hair growth cycle, responses to treatment should not be expected to occur within the first 3 months of therapy. Objective methods of assessing changes of hair growth, such as photographs, are useful. Remaining excess hair can be removed by electrolysis. Treatment should be continued for 4 years and then stopped to determine if hirsutism recurs. If so, therapy can be reinitiated. Many agents are available to inhibit the various sources of androgen production that may lead to hirsutism. OCs suppress LH and ovarian testosterone production by o the inhibitory action of the progestational component. The estrogenic component in OCs increases SHBG levels in the circulation, which decreases free testosterone levels. The progestins in the OCs also inhibit 5reductase activity in the skin. Women in whom OCs are contraindicated or produce side effects may be treated with medroxyprogesterone acetate. o This agent also inhibits LH, which causes decreased testosterone production, although to a lesser extent than occurs with combined OCs. Treatment with GnRH agonists is expensive and reserved for severe clinical manifestations of ovarian hyperandrogenism, not hirsutism alone. Ketoconazole: blocks adrenal and gonadal steroidogenesis by inhibiting cytochrome P-450dependent enzyme pathways, has been used in dosages of 200 mg twice a day to treat hyperandrogenism associated with PCOS and idiopathic hirsutism. o This potent drug effectively decreases hair growth and acne, but major side effects and complications (including hepatitis) occur in the majority of women treated. These problems limit the use of ketoconazole to very select women, who require careful monitoring. In these severe cases it is probably preferable to use a GnRH agonist. Spironolactone: considered the treatment of choice for idiopathic hirsutism as well as many with PCOS. This agent, in addition to being an androgen receptor blocker, also decreases ovarian testosterone production and inhibits 5RA. o a dose of 200 mg/day of spironolactone is more effective than 100 mg/day. o Side effects: irregular uterine bleeding Finasteride, a 5reductase inhibitor (5 mg/day), flutamide, a nonsteroidal antiandrogen (250 to 500 mg/day) o doses should be kept as low as possible and liver function tests should be obtained regularly. Antiandrogen therapy has been shown to be the most important modality for hirsutism treatment.

What can be secreted by both? TNF b but more so from TH1 whatis