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Endometriosis treated with prolonged estrogen and progesterone combination therapy exhibits which of the following histologic characteristics Luteectomy before 42 days’ gestation is most likely to asthma when to go to the hospital cheap ventolin 100 mcg line result in which of the following Her pelvic examination demonstrates tenderness and nodularity over her uterosacral ligaments and a 4-cm right ovarian cyst asthmatic bronchitis viral or bacterial ventolin 100 mcg low cost. A 65-year-old woman G3P3 is being counseled regarding the risks of having a Burch operation for stress incontinence asthma wheezing discount 100mcg ventolin with mastercard. A vigorous 79-year-old woman with worsening urinary incontinence over the past year comes to asthmatic bronchitis and sinus infection generic ventolin 100 mcg visa see you. She denies neurologic symptoms, stress incontinence symptoms, or voiding problems. She generated a low-level detrusor contraction with voiding but has incomplete bladder emptying with residuals around 200 mL. Transvaginal sonography shows a 4-cm unilocular smooth ovarian cyst without internal excrescences. A transabdominal ultrasound shows an enlarged uterus containing five viable fetuses. You advise her that the optimal outcome can be achieved only with which of the following A 69-year-old woman presents with a 2-cm firm nodule in the right labium majus without signs of inflammation. It extends from the basal layer to a little more than one-half the thickness of the epithelium. A patient is referred to you from her primary care provider because of the finding of a large cystic structure in the vagina that prevented visualization of the cervix and the performance of a Pap smear. You biopsy the wall of the cyst for diagnostic confirmation and to decompress the cyst so a Pap can be done. The pathology returns with the description that the cyst wall is lined with cuboidal, nonciliated epithelium. A 62-year-old obese woman on unopposed estrogen develops abnormal vaginal bleeding. A 35-year-old G5P5 patient who is using a tubal ligation as contraception for the past 5 years is noting increasing dysmenorrhea over the past year. Her examination 2 days prior to her menses reveals a large boggy mobile uterus that is tender. Which of the following is the best therapy for secondary dysmenorrhea thought to be due to adenomyosis A19-year-old woman is seen in the emergency room with a history of amenorrhea for 8 weeks, and 1 week of unilateral adnexal pain. On physical examination, she is found to have a diffuse tenderness and fullness in the right ad-nexa. Laboratory evaluations reveal a hematocrit that is roughly normal, and a positive pregnancy test. Which of the following is the most appropriate imaging modality to establish a diagnosis in this case A 56-year-old woman has gradual virilization and is found to have a 5-cm left ovarian mass, which contains nests of luteinized thecal cells within the stroma. Currently many screening tests are being evaluated for the most cost-effective population that should receive the test and what interval it should be done. Currently mammograms are being recommended by some to be done only every 2 years in the low-risk woman who is between 50 and 65 years of age with annual clinical examinations. This means that the provider must determine during the clinical examination whether the patient is potentially at more high risk for an early can and should be screened annual. Which of the following findings in a patient would be the most suspicious for an increased risk of a breast carcinoma A 32-year-old woman (G2P0101) who had a classical C-section with her last pregnancy due to cord prolapse with spontaneous rupture of membranes and a transverse lie at 34 weeks. What is the best method for determining the extent and severity of uterine damage when uterine rupture is suspected A 21-year-old college student presents to the student health clinic with complaints of increasing nervousness, fatigue, weight loss, and palpitations. Her examination is remarkable for a documented 10-lb weight loss since her last clinic visit 6 months ago, warm skin, no goiter, and tachycardia without a murmur or click. When making a lower midline abdominal incision, where would you find the lower border of the posterior rectus fascia sheath A 21-year-old G1P0 patient has made it to second stage after a slightly prolonged active phase. As you evaluate for reasons that are preventing descent you check for the positioning of the vertex presentation. This is important since there is great variation in the diameter of the vertex depending on the positioning and in turn the fetal ability to negotiate the pelvic axis and descend in second stage. You are going back to do a C-section for a patient with a fetus in a back down transverse lie. To aid in delivery relaxation of the uterus can facilitate an atraumatic delivery from this abnormal lie. Which of the following anesthetic techniques will produce the greatest uterine relaxation A 25-year-old healthy woman complains of breast tenderness and amenorrhea of 6 weeks’ duration. Examination demonstrates a whitish breast discharge with milk-containing fat droplets on microscopic examination. The next step in the management of this patient should be to obtain radiologic assessment of which structure(s) The relationship of the long axis of the fetus to the long axis of the mother is called which of the following An unregistered obstetric patient with no prenatal care presents with active labor and a history consistent with estimated gestational age of 37 weeks and an 8-hour history of spontaneous rupture of the membranes. About 8 hours after delivery, her infant develops septic shock, pneumonia, and a positive Gram’s stain is obtained from the infant’s blood. The clinical picture in this infant is most consistent with which of the following Physical examination shows grape like lesions protruding from the vaginal introitus. A 31-year-old woman (gravida 6, para 0–2-3–1) comes to you at 10 weeks’ gestation with the history of having had progressively earlier deliveries, all without painful contractions. Her first child was born at 34 weeks and survived, the next delivered at 26 weeks, the next two at 22 weeks, and the last one at 20 weeks. With this information, your first diagnosis is intrauterine gestation and which of the following She asks you if there is anything in particular that you would recommend in this pregnancy. A patient after a prolonged second stage delivers the vertex with an immediate turtle sign with the head retracting against the perineum. Which of the following would be a helpful maneuver in managing this shoulder dystocia She is currently on supplemental T4 secondary to hypothyroid condition brought on after radioactive iodine for Graves’ disease. A patient who is a G2P1001 has been pushing for 3 hours and is exhausted after a long labor. You feel that a vacuum-assisted vaginal delivery is an indicated option to expedite delivery. In your counseling of the patient, you tell her that the most severe fetal complications of vacuum extraction for the fetus include which of the following A patient presents with a complaint that prompted an assessment of the prolactin level. Which of the following is a normal physiologic reason for an elevated prolactin without associated pathology The three signs of placenta separation after delivery include which of the following A 26-year-old nulligravida complains of bilateral, spontaneous milky nipple discharge that has been present for the last 3 months. You offer her one of the newer antidepressant medications but warn her that side effects are common.

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The examination should focus on the nor of fetal anatomy asthma definition volume buy ventolin 100mcg amex, and even probe features [14 asthma treatment budesonide ventolin 100mcg for sale, 42] asthma symptoms in children age 5 cheap 100mcg ventolin. At 11 to asthma definition diagnosis discount ventolin 100 mcg online 13 weeks and 6 days, the malities into three groups according to the possibility ultrasound aspect of the brain is characterized by the of detection during the frst-trimester examination: two prominent lateral ventricles that are flled with always detectable, potentially detectable, and unde the choroid plexuses. The two cerebral hemispheres are symmetrical in the “always detectable” abnormalities are those size divided by the falx, and the cortex is thin. Posterior already present in the frst trimester, and causing clearly fossa should be visualized in the axial and midsagittal visible alterations of the fetal structures even before view, with evaluation of the brain stem, fourth ven 13 weeks and 6 days. In order to complete the usually are manifested only during the second or third examination of the central nervous system, it is nec trimester of pregnancy (Table 1. The detection of these abnormalities could depend on • Acrania–exencephaly–anencephaly. Already in the the expertise of the operator; the aims, indications, and 1990s it was shown to be possible to detect up to standardization of the ultrasound examination; the time 97% of cases of anencephaly during the second allocated for the scan; the equipment used; the presence trimester anomaly scan. The most recent publications of direct or indirect ultrasound markers of the malfor show how it is possible to obtain such a detection mation; and the evolution in the phenotypic expression rate already during the frst-trimester scan [14, 43]. Cranial vault is absent hernia and the brain is covered only by meninges (arrowheads). This is characterized by protrusion Gastroschisis +++ +++ ++ of intracranial structures through a cranial bone Bilateral renal + +++ defect. Sonographic Posterior urethral +++ ++ ++ diagnosis is based on the recognition of a cystic valves (meningocele) (Figure 1. Another malformation that not possible; +++: more common; ++: average; confdently may be diagnosed in the frst trimester is +: less common;: extremely rare. It is caused by the impaired midline cleav Acrania–exencephaly–anencephaly (see Chapter 2) age of the embryonic forebrain [43, 45]. Most of the skull, and in of alobar and semilobar holoprosencephaly, can be particular parietal and occipital bones, are identif reliably detected. The transverse view of the head will able as echoic calcifed structures from 11 completed not show the typical butterfy sign (Figure 1. Therefore, it is possible to assess quite clearly but the fusion of the brain midline structures and of the skull shape and profle between 11 and 14 weeks. It is also important to take nial vault (acrania), resulting in abnormal shape of into account the strong correlation of this abnormal the exposed brain (exencephaly) should lead to the ity with trisomy 13 (about 66% of the cases diag early diagnosis of acrania–exencephaly (Figure 1. Axial view of the head showing the normal calcifcation of the skull; the falx and the two choroid plexuses (“butterfy sign”) are normal. It is possible to visualize at appearance during the frst trimester cannot exclude 11 to 13 weeks and 6 days, three spaces within the open spina bifda, because the defect would not be posterior fossa, between the sphenoid and the occip suffciently evident at this stage. However, it obliteration and disappearance of the intracranial should be kept in mind that, in this case, the diag translucency/fourth ventricle, and the enlargement nostic suspicion should be subsequently confrmed of the anechoic space representing the brain stem by a later scan, usually beyond 18 weeks of gestation. According to the most recent lit As mentioned above, in the case of spina bifda, erature [48], it could be useful to measure the ratio the ratio between the brain stem and the fourth ven between the brain stem and the fourth ventricle/ tricle/cisterna magna complex is abnormal (brain cisterna magna complex in cases of suspected spina stem/brain stem-occipital bone diameters ratio is bifda (brain stem/brain stem-occipital bone diame higher in fetuses with open spina bifda than in ters ratio is higher in fetuses with open spina bifda normal fetuses). Ventriculomegaly may ance or measurement of the structures of the poste be secondary to brain destruction (congenital infec rior fossa, the operator could be alerted to accurately tion or a vascular mechanism); malformations; examine the anatomy of the spine, aiming for direct hydrocephalus; neoplasms; or a combination of two visualization of any spinal defects (Figure 1. Development are usually related to a second or third-trimester of the posterior fossa structures is ongoing during ventriculomegaly, rather than a frst-trimester one. In particular, the cerebellar ver the frst trimester, has been reported [14, 43, 50]. Midsagittal view of the face; trans normal development of the cerebellum is not taken verse view at the level of the orbits and of the upper lip/ into consideration. Even if the correct diagnosis of hard palate; coronal view, to visualize the hard palate these abnormalities cannot be made this early, the and retronasal triangle [51]. The examination of the fetal profle orbits may show the two orbits, symmetric and normal in the midsagittal view of the face may show a chin in size/position. This fnding is arch-shaped calcifed palate and the upper lip above it usually not easily detected, because the size of the should be visualized, without any evident disruption. This fnding should raise suspicions of chromosomal abnormalities (mainly trisomy 18) and genetic syndromes. When diagnosed, a detailed exam ination of the fetal anatomy should be encouraged. The routine examination of the pal ate and lip could lead to an improved detection of facial cleftings. The usually diffcult visualization of the lip and the small dimensions of these struc tures make the diagnosis possible only for the major defects (Figure 1. In selected cases, the transvag inal approach may contribute to improve the detec tion of these defects. Thorax and Heart the thorax, and several basic features of cardiac anat omy, can be evaluated during the frst trimester. The chest normally contains lungs of homogeneous echo genicity on ultrasound, without evidence of cystic or solid masses. Routine examination of some ultrasound markers for chromosomal abnormali ties has recently improved the early detection rates of fetal cardiac anomalies. The lumen of right and left ventricle separated by the interventricular septum can be clearly identifed. This transverse view provides important information on the direction of blood fow in the two arches and on the location and dimension of the aortic arch. In this frst trimester and require further evaluation after a view, the assessment of the cardiac situs and its rela few weeks [13, 56]. The four-chamber view Also, an evaluation of the two atrioventricular con could reveal an abnormal position of the heart, due nections by two-dimensional ultrasound and color to compression by bowel loops or stomach or liver fow mapping should be performed; in case of congenital diaphragmatic hernia. The transverse view of the the cases of diaphragmatic hernia had been diag chest, with the examination of the four-chamber nosed in the frst trimester [14] (Figure 1. In order of the abdomen, including the visualization of the to confrm the situs solitus, it is also important to stomach, the outline of the abdominal wall, and cord check whether the fetal stomach is on left side of the insertion. Situs abnormalities could, therefore, already be detected in the frst trimester, if we were to assess Method. The stomach must be shown in a transverse these structures and their position routinely. Color Doppler image at 13 weeks demonstrating, in the fve-chamber view, the ventricular septal defect with an overriding aorta (arrow). However, care should be taken in diagnosing an exomphalos before 12 weeks, because the physiologic herniation of the bowel in the cord completely regresses only at the end of 11 weeks. Therefore, if an exomphalos containing only bowel loops is suspected at this gestational age, it is safer to wait 1 week in order to get a confr mation of the diagnosis. Sometimes, cord loops could give the impression of a bowel hernia tion and the color Doppler could be helpful in the differential diagnosis. It is important to differenti ate between exomphalos and gastroschisis because of the strong association between exomphalos and chromosomal abnormalities, like trisomy 18 and 13 (about half of the cases) [46, 57]. The heart (H) is shifted to the right by intra dition could resolve spontaneously, if there is just thoracic viscera. If herniation of the liver is already visi well as the normal size and position within the abdo ble in the frst trimester and the exomphalos does men. The cord insertion can be visualized either in a not resolve spontaneously, surgery is required after transverse view or in a midsagittal one. Gastroschisis is not usually correlated with view, the outline of the abdominal wall can be assessed increased risk for chromosomal abnormalities, but to exclude any abdominal wall defects. Transverse view of the fetal abdomen showing herniation of the liver in the sac (arrows). The kidneys are already visible in nosis is based on two of the three features below: the frst trimester, but they have similar echogenicity exencephaly/cephalocele, abdominal wall defect/ to the surrounding tissue; therefore, visualization is thoracoschisis, and limb defect. The visualization could be improved by num, but no other defects usually are associated. Midsagittal view of a fetus at 13 weeks showing massive dilatation of the bladder, occupying almost all the abdominal cavity. This fnding is cor enough time to allow the bladder to fll up, it is man related with chromosomal abnormalities (mainly datory to clearly visualize the kidneys either trans trisomy 13 and 18) in a signifcant number of cases abdominally or, if necessary, transvaginally. We need to classify at least two different kidneys are not visible, bilateral renal agenesis con types of megacystis, both visible in the frst trimes dition has to be suspected, and a further confrma ter.

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There is no reason to asthma symptoms in adults purchase ventolin 100 mcg mastercard believe that this is a factor in ovulatory women with recurrent miscarriages asthma definition humble generic 100 mcg ventolin visa. An endocrine abnormality that may cause recurrent miscarriages is the inadequate luteal phase asthma treatment 4x4x4 purchase ventolin 100mcg free shipping. Studies of the role of hormone deficiency as a cause of recurrent miscarriage have largely focused on deficiencies of progesterone or its metabolites asthma 9 months trusted 100mcg ventolin. Attempts to implicate low progesterone or pregnanediol levels in early pregnancy 40, 41 as a cause for miscarriage, and, as a corollary, to treat with exogenous progesterone or progestins have been fruitless. Another approach has been to diagnose an inadequate luteal phase during the nonpregnant state and to initiate treatment with progesterone a few days after 42 ovulation. Jones and Delfs claimed that 30% of women with pregnancy wastage had an inadequate luteal phase, whereas more recent studies have found that 14, 15, 16, 17, 18and 19 20–25% of women with recurrent miscarriages have an inadequate luteal phase. Indeed, a meta-analysis of randomized trials of pregnancies treated with progestational agents failed to find any evidence for a positive effect on the 41 maintenance of pregnancy. Nevertheless, clinicians continue to report, as we have noted, a significant incidence of luteal phase inadequacy in their series of 18, 43, 44 patients with recurrent miscarriages. The uncertainty that plagues physicians in dealing with the inadequate luteal phase in infertility, therefore, is also apparent when considering recurrent miscarriages. If repetitive endometrial biopsies indicate a lag in histologic development of more than 2 days or if the basal body temperature chart shows a luteal phase of less than 11 days, it is reasonable to treat with clomiphene or progesterone (Chapter 26) and with a dopamine agonist if galactorrhea or an elevated prolactin is present. In the absence of galactorrhea or hyperprolactinemia, we prefer clomiphene because this avoids the situation of a prolonged luteal phase due to progesterone treatment, a false expectation of pregnancy, and a more difficult time for the couple in coping with the results of a negative pregnancy test. Should clomiphene be offered empirically (for 6 cycles) when no other cause for recurrent miscarriages can be identified Placebo treatment may be useful in maintaining a clinician-patient relationship in which the patient derives needed psychologic sustenance. Furthermore, there is no evidence of any major harmful consequences with clomiphene treatment (see Chapter 30). In view of the difficulty in establishing the diagnosis of an inadequate luteal phase and the uncertainties that surround this diagnosis, we believe there is a place for empirical treatment. It must be remembered, however, that there is a reasonable cure rate in unexplained recurrent miscarriage, even without treatment. Anatomical Causes Uterine abnormalities can result in impaired vascularization of a pregnancy and limited space for a fetus due to distortion of the uterine cavity. Approximately 12–15% of women with recurrent miscarriages have a uterine malformation, and this can be best diagnosed by vaginal ultrasonography (especially with saline instillation), and 45 confirmed by magnetic resonance imaging. Hysterosalpingography is relatively inaccurate and decisions should not be based upon hysterosalpingography alone. Surgical repair of these defects, often by hysteroscopy, is rewarded with delivery rates in the 70–80% range; however, this high rate of success must be tempered by the realization that it is not derived from randomized clinical trials. The septate uterus is the most frequent anatomic abnormality associated with recurrent early spontaneous miscarriages, and 46 the results with hysteroscopic repair have been impressive. Repeat procedures are occasionally necessary; the surgical result should be evaluated several weeks postoperatively by hysterosalpingography (which is sufficiently accurate for this purpose) or office hysteroscopy. Surgery is unlikely to make a difference in a patient 47 who has successfully delivered a live born term infant. The prophylactic use of cervical cerclage has not been supported by results from randomized trials. If an appropriate predisposing factor, such as uterine curettage or a severe uterine infection, can be identified, diagnostic hysterosalpingography or hysteroscopy should be performed. Infectious Causes Despite periodic reports that have implicated specific infectious agents as etiologic factors in recurrent miscarriages, there currently is no hard evidence that bacterial or viral infections cause recurrent pregnancy losses. An impressive incidence of antichlamydial antibody has been reported in women with 3 or more spontaneous miscarriages, but it is not certain whether this an association with Chlamydia trachomatis or whether this is a marker of a different immune response in women with 48 49 recurrent miscarriages. In a prospective study, no association could be detected between antichlamydia antibodies and spontaneous miscarriage. Other organisms that have been implicated, but not substantiated, include Toxoplasma gondii, Listeria monocytogenes, Mycoplasma hominis, herpes virus, and cytomegalovirus. It is more cost-effective and time efficient to prescribe both partners a course of doxycycline (100 mg bid for 14 days) or erythromycin (250 mg qid for 14 days) than to pursue multiple and repeated cultures. Thrombophilia the major cause of thrombosis in pregnancy is an inherited predisposition for clotting, especially the factor V Leiden mutation. Mutations in the prothrombin gene and the factor V 51 Leiden mutation are the most common inherited causes of venous thromboembolism. An inherited resistance to activated protein C has been identified as the basis 52, 53 for about 50% of cases of familial venous thrombosis, due in almost all cases to a gene alteration recognized as the factor V Leiden mutation. The factor V Leiden 54 mutation is found in approximately 30% of individuals who develop venous thromboembolism. One of the 3 cleavages sites in factor V is the precise site of a mutation (known as the factor V Leiden mutation) that substitutes glutamine instead of arginine at 54 this site (adenine for guanine at nucleotide 1691 in the gene). This mutation makes factor V resistant to degradation (and activation in fibrinolysis). Heterozygotes for the factor V Leiden mutation have an 8-fold increased risk of venous thrombosis, and homozygotes, an 80-fold increased risk, and this risk appears to be further enhanced by oral contraceptive use. The highest prevalence (3–4% of the general population) of factor V Leiden is found in Europeans, and its occurrence in populations not of European descent is very rare, perhaps explaining the low frequency of thromboembolic disease in Africa, Asia, and in native 55 56 Americans. The mutation is believed to have arisen in a single ancestor approximately 21, 000 to 34, 000 years ago. The next most common inherited disorder (after the factor V Leiden 51, 57 mutation) is a mutation a guanine to adenine change in the gene encoding prothrombin. The prevalence of this abnormality in the white population is estimated to 58 range from 0. In a group of 39 women with recurrent miscarriages, the factor V Leiden mutation was identified in nearly half, and 5 women treated with anticoagulation had normal 59 term deliveries. Others have found an increased incidence of the factor V Leiden mutation in women with second-trimester losses, but either not at all or only a slight 60, 61, 62and 63 increase in women with first-trimester losses. In a prospective 65 cohort study, inherited deficiencies were associated with increased risks of late loss, but not for early miscarriage. Elevated homocysteine levels are a risk factor for 66 venous thrombosis, and this condition has also been suggested to be a factor in recurrent early pregnant losses. In view of the new recognition for the clinical importance of inherited disorders that predispose to venous thrombosis, we believe that women with recurrent miscarriages who have no obvious identified cause should consider hematologic screening. This is definitely necessary in women with a previous episode or a close family history (parent or sibling) of thromboembolism. A positive result warrants treatment with low molecular weight heparin after pregnancy is diagnosed. The lupus anticoagulant and anticardiolipin antibodies are antiphospholipid antibodies, which arise as the result of an autoimmune disease. The lupus anticoagulant is present in a variety of clinical conditions, not just with lupus erythematosus. The antiphospholipid antibodies are directed against platelets and the vascular endothelium and cause thrombosis, spontaneous miscarriage, 67 and fetal wastage. These antibodies block prostacyclin formation, which results in unbalanced thromboxane activity, leading to vasoconstriction and thrombosis. In 68 several series, 10–16% of women with recurrent miscarriages have had antiphospholipid antibodies. These antibodies are also associated with fetal growth retardation and fetal death in addition to recurrent miscarriages, and when present, there is a high rate of second-trimester fetal deaths. The mechanism of pregnancy loss is probably decidual and placental insufficiency due to the thrombotic tendency. Annexin-V is a phospholipid-binding protein that inhibits coagulation; the levels 69 of annexin-V on trophoblasts and endothelial cells are reduced in the presence of antiphospholipid antibodies. Despite activating thrombosis, the antiphospholipid antibodies prolong the prothrombin time and the partial thromboplastin time. The activated partial thromboplastin time is a relatively sensitive screening test, but we also obtain a kaolin clotting time. The anticardiolipin antibody and lupus anticoagulant can be identified and titered 70 by specific immunoassays; other individual antiphospholipid antibodies have not been associated with recurrent miscarriages. The antiphospholipid antibodies all produce the same clinical impact and have identical effects on clotting tests. Although the prevalence is uncertain, patients with recurrent miscarriages should be 71, 72, 73, 74and 75 screened with the activated partial thromboplastin time, a kaolin clotting time, lupus anticoagulant, and the anticardiolipin antibody. Our preferred treatment for significant titers of antiphospholipid antibodies consists of the combination of low-dose aspirin (80 mg daily) and low-dose heparin as soon 76, 77 78 as pregnancy is diagnosed.

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Demonstration of growth stops symptoms asthma 11 month old ventolin 100 mcg overnight delivery, but truncal development continues asthma management discount ventolin 100mcg otc, the elevated levels of 17-hydroxyprogesterone in amniotic characteristic appearance being a short child with a well uid at 14–16 weeks of gestation allows prenatal detec developed trunk asthma symptoms go away quality 100 mcg ventolin. Hypertension and hypokalemia occur because de cits in both cortisol and aldosterone secretion asthma definition 24 buy generic ventolin 100 mcg on-line. Steroid precursors are ing increased levels of 11-deoxycortisol in the blood or shunted into the androgen pathway. Female patients have high basal level of a precursor of cortisol biosynthesis primary amenorrhea and lack of development of secondary (such as 17-hydroxyprogesterone, 17-hydroxypregnenolone, sexual characteristics. Adrenal treatment with appropriate gonadal steroids results in sexual androgen output is easily suppressed by the standard maturation. The dosage schedule is gov or ion channels important in mediating or mimicking erned by repetitive analysis of the urinary 17-ketos aldosterone’s action. Skeletal growth and maturation must Hypermineralocorticoidism also be monitored closely, as overtreatment with gluco Low Plasma Renin Activity corticoid replacement therapy retards linear growth. Rarely, hypermineralocorticoidism is due to a defect in cortisol biosynthesis, speci cally 11 or 17-hydroxylation. In some patients, the adrenal Glucocorticoid administration can also ameliorate insuf ciency is associated with achalasia and alacrima— hypertension or produce normotension even though a Allgrove’s, or triple A, syndrome. Thus, aldosterone synthase steroids—cortisol, aldosterone, and adrenal androgens—as activity is ectopically expressed in the zona fasciculata well as gonadotropin de ciency. Screening for this defect tisol resistance due to mutations in the glucocorticoid recep is best performed by assessing the presence or absence of tor. Individuals with sup Miscellaneous Conditions pressed plasma renin levels and juvenile-onset hyper Adrenoleukodystrophy causes severe demyelination and tension or a history of early-onset hypertension in early death in children, and adrenomyeloneuropathy is rst-degree relatives should be screened for this disorder. Auto with glucocorticoid administration or antimineralocor somal recessive mutations in the steroidogenic acute ticoids, i. A combi terized by adrenal insufficiency and defective gonadal nation approach is often necessary. In genetic females, sexual differentiation High Plasma Renin Activity is normal but there is premature ovarian failure. Renal biopsy shows juxtaglomerular aldosterone secretion, elevated plasma renin levels, and hyperplasia. Bartter syndrome is caused by a mutation in elevated levels of the intermediates of aldosterone biosyn the renal Na-K-2Cl co-transporter gene. The renal loss of sodium is thought to somal recessive disorder that is seen in the neonatal stimulate renin secretion and aldosterone production. In hypokalemia further elevates prostaglandin production contrast to the gain-of-function mutations in the and plasma renin activity. In contrast to Bartter’s need for a thorough understanding of the metabolic syndrome, urinary calcium excretion is reduced. Before adrenal hormone therapy syndrome results from loss-of-function mutations of the is instituted, the expected gains should be weighed renal thiazide-sensitive Na-Cl co-transporter. First, how Increased Mineralocorticoid Action serious is the disorder (the more serious, the greater the Liddle’s syndrome is a rare autosomal dominant disorder that likelihood that the risk-versus-bene t ratio will be posi mimics hyperaldosteronism. Second, how long will therapy be required (the encoding the or subunits of the epithelial sodium longer the therapy, the greater the risk of adverse side channel. Third, does the individual have preexisting con to the constitutively activated sodium channel and the ditions that glucocorticoids may exacerbate (Table 5-9) Fourth, also termed apparent mineralocorticoid excess syndrome, is which preparation is best Patients can be identi account in deciding which steroid preparation to use: ed either by documenting an increased ratio of cortisol to cortisone in the urine or by genetic analysis. The ingestion of candies or chewing tobacco contain Presence of tuberculosis or other chronic infection (chest ing certain forms of licorice produces a syndrome that x-ray, tuberculin test) mimics primary aldosteronism. The diagnosis is established or (bone density assessment in organ transplant recipients excluded by a careful history. In general, the more potent Restrict sodium intake to prevent edema and minimize the steroid, the longer its biologic half-life. Cortisone and Patients receiving steroid therapy over a prolonged prednisone have to be converted to biologically period (months) should have an appropriate increase active metabolites before anti-in ammatory effects in hormone level during periods of acute stress. Because of this, in a condition for which rule of thumb is to double the maintenance dose. Prednisone Ensure adequate calcium intake (should be ~1200 mg/d is the least expensive of available steroid preparations. Consider administering bisphosphonate prophylactically, effects by increasing their hepatic inactivation if they orally, or parenterally in high-risk patients. Short-acting preparations have a biologic half-life <12 h; long-acting, >48 h; and intermediate-acting, between 12 and 36 h. Sodium retention is insigni cant for commonly employed doses of methylprednisolone, triamcinolone, paramethasone, betamethasone, and dexamethasone. These tumors vascularized tumors that arise from cells derived from the may arise sporadically or be inherited as features of sympathetic. The diagnosis of the name pheochromocytoma re ects the black-colored pheochromocytomas provides a potentially correctable staining caused by chromaf n oxidation of catecholamines. The clinical presen describe these tumors, most clinicians use the term tation is variable, ranging from an adrenal incidentaloma pheochromocytoma to describe symptomatic catecholamine to a patient in hypertensive crisis with associated cere producing tumors, including those located in extraadrenal brovascular or cardiac complications. Classically, patients have episodic hypertension, but sustained hypertension is also frequent. During episodes of hormone release, which mocytoma has been termed “the great masquerader” can occur at very divergent intervals, patients are anxious (Table 6-1). Among the presenting symptoms, episodes and pale, and they experience tachycardia and palpita of palpitations, headaches, and profuse sweating are typi tions. These paroxysms generally last less than an hour and cal and constitute a classic triad. The presence of all may be precipitated by surgery, positional changes, exercise, three of these symptoms, in association with hyperten pregnancy, urination (particularly bladder pheochromocy sion, makes pheochromocytoma a likely diagnosis. Both are of equal importance, although mea Headaches Weight loss surement of catecholamines is traditionally the rst step. Sweating attacks Paradoxical response to Palpitation and tachycardia antihypertensive drugs Hypertension, sustained or Polyuria and polydipsia Biochemical Testing paroxysmal Constipation Pheochromocytomas and paragangliomas synthesize and Anxiety and panic attacks Orthostatic hypotension store catecholamines, which include norepinephrine Pallor Dilated cardiomyopathy Nausea Erythrocytosis (noradrenaline), epinephrine (adrenaline), and dopamine. Ele Abdominal pain Elevated blood sugar vated plasma and urinary levels of catecholamines and the Weakness Hypercalcemia methylated metabolites, metanephrines, are the cornerstone for the diagnosis. The hormonal activity of tumors uctuates, resulting in considerable variation in serial catecholamine levodopa, labetalol, sympathomimetics) that increase cate 135 measurements. Thus, there is some value in obtaining tests cholamines can still confound testing. On the other hand, are relatively rare, borderline elevations are likely to be most tumors continuously leak O-methylated metabolites, false positives. In this circumstance, repeated testing, often which are detected by metanephrine measurements. The pattern of catecholamines can help in cious for pheochromocytoma, when values are increased localizing the tumor, as epinephrine is virtually never two to three times the upper limit of normal, a increased in extraadrenal pheochromocytomas. When an asymptomatic adrenal mass is identi ed, Total metanephrines +++ ++++ likely diagnoses other than pheochromocytoma include a Plasma tests nonfunctioning adrenal adenoma, aldosteronoma, and Catecholamines +++ ++ cortisol-producing adenoma (Cushing’s syndrome). Adequate alpha blockade generally requires Treatment of malignant pheochromocytoma or para 10–14 days, with a typical nal dose of 20–30 mg ganglioma is challenging. Before surgery, the apy protocol includes dacarbazine (600 mg/m2 days 1 and blood pressure should be consistently below 160/90 2), cyclophosphamide (750 mg/m2 day 1), and vincristine mmHg, with moderate orthostasis. Palliation (stable disease to shrinkage) is achieved after starting alpha blockers, and increased as needed, if in about half of patients. Because beta blockers can induce a ment using 200-mCi doses at monthly intervals, over paradoxical increase in blood pressure in the absence of three to six cycles. The prognosis of metastatic pheochro alpha blockade, they should be administered only after mocytoma or paraganglioma is variable, with a 5-year effective alpha blockade. Blood pressure can be labile to sixth month of gestation, is possible and can be fol during surgery, particularly at the onset of intubation or lowed by uneventful childbirth. Nitroprusside infusion is families with inherited pheochromocytomas provides an useful for intraoperative hypertensive crises, and opportunity to identify and remove asymptomatic hypotension usually responds to volume infusion. Atraumatic endoscopic surgery was introduced in the About 25–33% of patients with pheochromocytoma or early 1990s and has now become the method of choice. An adrenocorticotropic hormone test functions as a tumor suppressor by regulating the ras signal should be used to exclude cortisol de ciency when bilateral ing cascade.

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