Clare E. Close, MD

• Associate Clinical Professor of Surgery and Pediatrics,
• University of Nevada School of Medicine, Las Vegas, Nevada

Although patients may complain of neck tight ness medications to treat anxiety requip 0.25 mg with amex, pain and tenderness are not usually present symptoms nerve damage buy requip with a visa. About 10% of cases are atrophic symptoms chlamydia discount requip 0.5 mg visa, the gland being fibrotic symptoms dizziness nausea requip 0.5 mg discount, particu larly in elderly women treatment jammed finger purchase requip 2 mg mastercard. However medications known to cause tinnitus order requip 0.25mg online, depression and chronic fatigue are more common in such patients, even after cor rection of hypothyroidism. About one-third of patients have mild dry mouth (xerostomia) or dry eyes (keratocon junctivitis sicca) related to Sj ogren syndrome. Asso ciated celiac disease can produce fatigue or depression, often in the absence of gastrointestinal symptoms. Postpartum thyroiditis is typically manifested by hyperthyroidism that begins 1 - 6 months after delivery and persists for only 1 -2 months. Thyrotoxic symptoms in painless sporadic thyroiditis are usually mild; a small, nontender goiter may be palpated in about 50% of such patients. Subacute thyroiditis presents with an acute, usually painful enlargement of the thyroid gland, often with dys phagia. The manifestations may persist for weeks or months and may be associated with malaise. Thyrotoxicosis develops in 50% of affected patients and tends to last for several weeks. Normal thyroid func tion typically returns within 12 months, but persistent hypothyroidism develops in 5% of patients. Patients with infectious thyroiditis usually are febrile and have severe pain, tenderness, redness, and fluctuation in the region of the thyroid gland. In Riedel thyroiditis, thyroid enlargement is often asymmetric; the gland is stony hard and adherent to the neck structures, causing signs of compression and invasion, including dysphagia, dyspnea, pain, and hoarseness. Related conditions include retroperi toneal fibrosis, fibrosing mediastinitis, sclerosing cervicitis, subretinal fibrosis, and sclerosing cholangitis. Laboratory Findings In Hashimoto thyroiditis with clinically evident disease, there are usually increased circulating levels of antithy roid peroxidase (90%) or antithyroglobulin (40%) anti bodies. However, some patients with autoimmune thyroiditis have no detectable antithyroid antibodies. Antithyroid antibodies decline during pregnancy and are often undetectable in the third trimester. Because T4 is less active than T 3, the hyperthyroid ism seen in thyroiditis is usually less severe. Complications Hashimoto thyroiditis may lead to hypothyroidism or tran sient thyrotoxicosis. Hyperthyroidism may develop, either due to the emergence of Graves disease or due to the release of stored thyroid hormone, which is caused by inflammation. Pregnant women with Hashimoto thyroiditis have an increased risk of spontaneous miscarriage in the first trimester of pregnancy. Perimeno pausal women with high serum levels of antithyroperoxidase antibodies have a higher relative risk of depression, indepen dent of ambient thyroid hormone levels. In the suppurative forms of thyroiditis, any of the com plications of infection may occur. Subacute and chronic thyroiditis are complicated by the effects of pressure on the neck structures: dyspnea and, in Riedel struma, vocal cord palsy. Imaging Ultrasound in cases of Hashimoto thyroiditis typically shows a gland with characteristic diffuse heterogeneous density and hypoechogenicity. It helps distinguish thyroid itis from multinodular goiter or thyroid nodules that are suspicious for malignancy. Color-flow Doppler ultrasonography can help distinguish thyroiditis from Graves disease, since patients with Graves disease have a hypervascular thyroid gland, whereas in thyroiditis there is normal or reduced vascularity. Differential Diagnosis Thyroiditis must be considered in the differential diagnosis of all types of goiters, especially if enlargement is rapid. Thyroid autoantibody tests have been of help in the diagnosis of Hashimoto thyroiditis, but the tests are not specific (positive in patients with multinodular goi ters, malignancy [eg, thyroid carcinoma, lymphoma], and concurrent Graves disease). The subacute and suppurative forms of thyroiditis may resemble any infectious process in or near the neck structures. Chronic thyroiditis, especially if the enlargement is uneven and if there is pressure on sur rounding structures, may resemble thyroid carcinoma, and both disorders may be present in the same gland. Hashimoto Thyroiditis If hypothyroidism is present, levothyroxine should be given in the usual replacement doses (0. Suppressive doses of T4 tend to shrink the goiter an average of 30% over 6 months. If the goiter does not regress, lower replacement doses of leva thyroxine may be given. If the thyroid gland is only mini mally enlarged and the patient is euthyroid, regular observation is in order, since hypothyroidism may develop subsequently-often years later. Subacute Thyroiditis All treatment is empiric and must be continued for several weeks. Iodinated contrast agents cause a prompt fall in serum T3 levels and a dramatic improvement in thyrotoxic symptoms. Suppurative Thyroiditis Treatment is with antibiotics and with surgical drainage when fluctuation is marked. Immunocompromised indi viduals are particularly at risk and coccidioidomycosis thyroiditis has been reported. Riedel Struma the treatment of choice is tamoxifen, 20 mg orally twice daily, which must be continued for years. Tamoxifen can induce partial to complete remissions in most patients within 3-6 months. Short-term corticosteroid treatment may be added for partial alleviation of pain and compression symptoms. Surgical decompression usually fails to permanently alleviate compression symptoms; such surgery is difficult due to dense fibrous adhesions, making surgical complications more likely. Rituximab may be use ful for Riedel thyroiditis that is refractory to tamoxifen and corticosteroids. About 90% of palpable thyroid nodules are benign adenomas, colloid nodules, or cysts, but some are primary thyroid malignancies or (less frequently) metastatic malignancy. In recent years, an increased general use of scan ning has led to an increased rate of incidentally detecting nonpalpable thyroid nodules. The detection rate for thyroid nodules on ultrasound is about 30%; of these, 20% are larger than 1 em in diameter. Thyroid nodules 1 em or larger in diameter warrant follow-up and further testing for function and malignancy. An occasional nodule smaller than 1 em in diameter requires follow-up if it has high-risk char acteristics on ultrasound or if the patient is at high-risk for thyroid cancer due to prior head-neck radiation therapy dur ing childhood. Most patients with a thyroid nodule are euthyroid, but there is a high incidence of hypothyroidism or hyperthy roidism. Patients with multiple thyroid nodules have the same overall risk of thyroid cancer as patients with solitary nodules. The risk of a thyroid nodule being malignant is higher in males and among patients with a history of head neck radiation, total body radiation for bone marrow trans plantation, exposure to radioactive fallout as a child or teen, a family history of thyroid cancer or a thyroid cancer syn drome (eg, Cowden syndrome, multiple endocrine neopla sia type 2, familial polyposis, Carney syndrome), or a personal history of another malignancy. The risk of malig nancy is also higher if there is hoarseness or vocal fold paralysis, adherence to the trachea or strap muscles, cervical lymphadenopathy. The presence of Hashimoto thyroiditis does not reduce the risk of malignancy; a nodule of 1 em or larger in a gland with thyroiditis carries an 8% chance of malignancy. Prognosis Hashimoto thyroiditis is occasionally associated with other autoimmune disorders (celiac disease, diabetes mellitus, Addison disease, pernicious anemia, etc). In general, how ever, patients with Hashimoto thyroiditis have an excellent prognosis, since the condition either remains stable for years or progresses slowly to hypothyroidism, which is eas ily treated. Although 80% of women with postpartum thy roiditis subsequently recover normal thyroid function, permanent hypothyroidism eventually develops in about 50% within 7 years, more commonly in women who are multiparous or who have had a spontaneous abortion. In subacute thyroiditis, spontaneous remissions and exacer bations are common; the disease process may smolder for months. Papillary thyroid carcinoma carries a relatively good prognosis when it occurs in patients with Hashimoto thyroiditis. Clinical Findings Table 26-6 illustrates the approach to the evaluation of thyroid nodules based on the index of suspicion for malignancy. They may sometimes be detected only by having the patient swallow during careful inspection and palpation of the thyroid. A thyroid nodule or multinodular goiter can grow to become visible and of concern to the patient. Nodules that cause ipsilateral recurrent laryngeal nerve palsy are more likely to be malig nant. Retrosternal large multinodular goiters can cause dyspnea due to tracheal compression. Large substernal goiters may cause superior vena cava syndrome, mani fested by facial erythema and jugular vein distention that progress to cyanosis and facial edema when both arms are kept raised over the head. Depending on their cause, goiters and thyroid nodules may be associated with hypothyroidism (Hashimoto thy roiditis, endemic goiter) or hyperthyroidism (Graves dis ease, toxic nodular goiter, subacute thyroiditis, and thyroid cancer with metastases). However, thyroiditis frequently coexists with malignancy, so suspi cious nodules should always be biopsied. Imaging Neck ultrasonography should be performed to measure the size of a nodule and to determine its characteristics and whether a palpable nodule is part of a multinodular goiter. The following ultrasound characteristics of thyroid nod ules increase the likelihood of malignancy: irregular or indistinct margins, heterogenous nodule echogenicity, intranodular vascular images, microcalcifications, complex cyst, being taller than wider, or diameter over l em. Hyper functioning (hot) nodules are ordinarily benign (but may sometimes be malignant). For incidentally discovered thyroid nodules of borderline concern, follow-up thyroid ultrasound in 3-6 months may be helpful; growing lesions should be biopsied or resected. Treatment All thyroid nodules, including those that are benign, need to be monitored by regular periodic palpation and ultra sound about every 6 months initially. A toxic multi nodular goiter and hyperthyroidism may develop in patients who have had exposure to large amounts of iodine, either orally (eg, amiodarone) or intravenously (eg, radiographic contrast). Patients with toxic multinodular goiters may also be treated with methimazole, propranolol, or surgery. For multinodular goiters, the four largest nodules (1 em or larger in diameter) are usually biopsied to minimize the risk of missing a malignancy. The usual management is clinical follow-up with palpation or ultrasound at 6 - 1 8 month intervals. The usual management is either gene mutation analysis of the specimen or direct surgical lobectomy. The usual management is either gene mutation analysis of the specimen or direct thyroid lobectomy or near-total thyroidectomy. Another molecular approach is to assess for genetic abnormalities associated with thyroid cancer. Levothyroxine suppression therapy is not recommended for small benign thyroid nod ules. Thyroxine suppression therapy is more successful in iodine-deficient areas of the world. Thyroid nodule size increased in 29% of patients treated with levothyroxine versus 56% of patients not receiving levothyroxine. Leva thyroxine suppression also reduces the emergence of new nodules: 8% with levothyroxine and 29% without levothy roxine. Levothyroxine suppression therapy is not usually given to patients with coronary heart disease, since it increases the risk for angina and atrial fibrillation. Levothyroxine suppression needs to be carefully moni tored, since it carries a 1 7% risk of inducing hyperthyroid ism. Surgery may also be used to remove hyperfunctioning "hot" thyroid adenomas or toxic multinodular goiter causing hyperthyroidism. Percutaneous Ethanol I njection Percutaneous ethanol injection can shrink pure cysts; the success rate is 80%, although it must often be repeated. Percutaneous ethanol injection can also be used to shrink biopsy-proven benign nodules. While complications occur in about 9%, serious or permanent complications are rare. A meta-analytic review of the Bethesda System for Reporting Thyroid Cytopathology: has the rate of malig nancy in indeterminate lesions been underestimated Therapy with 1 3 1 I shrinks benign non toxic thyroid nodules by an average of 40% by 1 year and 59% by 2 years after 1 3 1 I therapy. Hypothy roidism is a risk and may occur years after 1 3 1 I therapy, so it is advisable to assess thyroid function every 3 months for the first year, every 6 months thereafter, and immediately for symptoms of hypothyroidism or hyperthyroidism. General Considerations the incidence of differentiated (papillary and follicular) thyroid carcinomas increases with age. Thyroid cancer mortality has been stable, account ing for about 1 500 deaths in the United States annually. In routine autopsy series, thyroid microcarcinoma (1 0 mm diameter or smaller) is found with the surprising frequency of 35%. However, larger thyroid cancers (palpable or greater than or equal to 1 em in diameter) are more malig nant and require treatment. Pure papillary (and mixed papillary-follicular) carcinoma comprises about 80% of all thyroid cancers. It usually presents as a single thyroid nod ule, but it can arise out of a multinodular goiter.

The focus of invasion usually involves the scar itself medicine hat alberta canada cheap requip 2mg with amex, and placenta previa is commonly associated with morbid adherence medications used for fibromyalgia discount 1 mg requip otc. Of serious concern for the field of obstetrics symptoms 6 week pregnancy order requip 0.25mg free shipping, the incidence of these syndromes has increased dramatically over the last 50 years commensurate with the increasing cesarean delivery rate symptoms 1 week after conception order online requip. After delivery of the infant medicine journal impact factor generic 0.5 mg requip visa, the morbidly adherent pla centa does not separate normally medications generic requip 0.25 mg amex, and the bleeding that results can be torrential. Rarely, inflamma tory carcinoma of the breast can be mistaken for puerperal mastitis. Unfortunately, strategies aimed at preventing mas titis in breastfeeding women have been unsuccessful. Mastitis frequently begins within 3 months after deliv ery and may start with an engorged breast and a sore or fissured nipple. Cellulitis is typically unilateral with the affected area of breast being red, tender, and warm. Treatment con sists of antibiotics effective against penicillin-resistant staphylococci (dicloxacillin 500 mg orally every 6 hours or a cephalosporin for 1 0 - 1 4 days) and regular emptying of the breast by nursing or by using a mechanical suction device. Although nursing of the infected breast is safe for the infant, local inflammation of the nipple may complicate latching. Failure to respond to usual antibiotics within 3 days may represent an organizing abscess or infection with a resistant organism. If an abscess is suspected, ultrasound of the breast can help confirm the diagnosis. Neonatal complications such as sepsis, pneumonia, intraventricular hemorrhage, and cerebral palsy are increased in the setting of chorioam nionitis. Intrapartum initiation of antibiotics, however, sig nificantly reduces neonatal morbidity. Foul smelling lochia may be present but is an insensitive marker of infection as many women without infection also experi ence an unpleasant odor. Likewise, some life-threatening infections such as necrotizing fasciitis are typically odor less. Cultures are typically not done because of the polymi crobial nature of the infection. Treatment Treatment is empiric with broad-spectrum antibiotics that will cover gram-positive and gram-negative organisms if still pregnant and gram-negative organisms and anaerobes if postpartum. A common regimen for chorioamnionitis is ampicillin, 2 g intravenously every 6 hours, and gentami cin, 2 mg/kg intravenous load then 1. Patients with metritis who do not respond in the first 24-48 hours may have enterococcus and require additional gram-positive cover age (such as ampicillin) to the regimen. General Considerations Pelvic infections are relatively common problems encoun tered during the peripartum period. Uterine infections diagnosed during pregnancy are referred to as chorioamni onitis-a generalized infection of all of the contents of the gravid uterus. Uterine infection after delivery is often called endometritis or endomyometritis, but the term "metritis" is probably most accurate to emphasize that the infection extends throughout the uterine tissue. These infections are polymicrobial and are most commonly attributed to uro genital pathogens. The single most important risk factor for puerperal infection is cesarean delivery, which increases the risk from 5- to 20-fold. Other recognized risk factors include prolonged labor, use of internal monitors, nullipar ity, multiple pelvic examinations, prolonged rupture of membranes, and lower genital tract infections. B ecause of these changes, the mean hemoglobin and hematocrit values are lower than in the nonpregnant state. Anemia in pregnancy is considered when the hemoglobin measurement is below 1 1 g/dL. By far, the most common causes are iron deficiency and acute blood loss anemia, the latter usually occurring in the peri partum period. In addition to its impact on maternal health, untoward preg nancy outcomes such as low birthweight and preterm delivery have been associated with second- and third trimester anemia. Most women with sickle cell disease will not require iron supplementation, but folate requirements can be appreciable due to red cell turnover from hemolysis. Other Anemias Although many of the inherited or acquired causes of ane mia are relatively rare in women of childbearing age, they can be encountered in pregnancy. The implications for the mother and her offspring vary widely depending on the etiology of anemia. For example, mild microcytic anemia may be caused by iron deficiency, but it could also repre sent anemia of chronic disease as a result of previously undiagnosed malignancy. As such, women who have ane mia caused by a disorder besides a nutritional deficiency are best managed in conjunction with a maternal fetal medicine specialist and a hematologist. Additionally, women who have an inherited form of anemia (hemoglo binopathies and thalassemia syndromes, for example) should be offered genetic counseling; prenatal diagnosis, if available, should be discussed if the parents wish to know whether the fetus is affected. Sickle cell disease in pregnancy: maternal com plications in a Medicaid-enrolled population. Maternal anemia in various trimesters and its effect on newborn weight and maturity: an observational study. I ron Deficiency Anemia the increased requirement for iron over the course of pregnancy is appreciable in order to support fetal growth and expansion of maternal blood volume. Dietary intake of iron is generally insufficient to meet this demand, and it is recommended that all pregnant women receive ab out 3 0 mg of elemental iron per day in the second and third trimesters. Oral iron therapy is commonly associated with gastrointestinal side effects, such as nausea and constipa tion, and these symptoms often contribute to noncompli ance. If supplementation is inadequate, however, anemia often becomes evident by the third trimester of pregnancy. Because iron deficiency is by far the most common cause of anemia in pregnancy, treatment is usually empiric and consists of 60- 1 00 mg of elemental iron per day and a diet containing iron-rich foods. Iron studies can confirm the diagnosis if necessary (see Chapter 1 3), and further evalu ation should be considered in patients who do not respond to oral iron. Intermittent iron supplementation (eg, every other day) has been associated with fewer side effects and may be reasonable for women who cannot tolerate daily therapy. Folic Acid Deficiency Anemia Megaloblastic anemia in pregnancy is almost always caused by folic acid deficiency, since vitamin B 2 deficiency is 1 extremely uncommon in the childbearing years. Folate deficiency is usually caused by inadequate dietary intake of fresh leafy vegetables, legumes, and animal proteins. The diagnosis is made by finding macrocytic red cells and hypersegmented neutrophils on a blood smear (see Chapter 1 3). However, blood smears in pregnancy may be difficult to interpret, since they frequently show iron defi ciency changes as well. With established folate deficiency, a supplemental dose of 1 mg/day and a diet with increased folic acid is generally sufficient to correct the anemia. Clinically, the diagnosis can be suspected after any of the following out comes: an episode of thrombosis, three or more unexplained consecutive spontaneous abortions prior to 10 weeks gesta tion, one or more unexplained deaths of a morphologically normal fetus after 1 0 weeks gestation, or a preterm delivery at less than 34 weeks due to preeclampsia or placental insuf ficiency. In addition to these clinical features, laboratory criteria include the identification of at least one of the fol lowing antiphospholipid antibodies: the lupus anticoagulant, anticardiolipin antibodies, or anti-beta-2-glycoprotein I antibodies. The lupus anticoagulant cannot be directly assayed, but it is tested for in several different phospholipid dependent clotting tests and is interpreted as either present or absent. Sickle Cell Anemia Women with sickle cell anemia are subj ect to serious com plications in pregnancy. The anemia becomes more severe, and acute pain crises often occur more frequently. There also continues to be an increased rate of maternal mortality, despite an increased recognition of the high-risk nature of these pregnancies. It is not clear whether continuation of therapy beyond the first trimester decreases the risk for stillbirth or placental dysfunction; however, treatment is typically continued through pregnancy and the early postpartum period for thromboprophylaxis. The use of corticosteroids and intravenous immunoglobulin is of unclear benefit in these patients, and neither treatment is recommended. It is essential to understand the gesta tional age-specific effects that pregnancy has on thyroid function tests, since these biochemical markers are required to make the diagnosis of thyroid dysfunction. Failure to recognize these physiologic alterations can result in mis classification or misdiagnosis. Women who have a history of a thyroid disorder or symptoms that suggest thyroid dysfunction should be screened with thyroid function tests. Screening asymptomatic pregnant women, however, is of unproven benefit and is not currently recommended. The condition in pregnancy has consistently been associated with an increase in complications such as spontaneous abortion, preterm birth, preeclampsia, placental abruption, and impaired neuropsychological development in the offspring. Many of the symptoms of hypothyroidism mimic those of normal pregnancy, making its clinical identifica tion difficult. Although some studies have found associations with untoward pregnancy out comes such as miscarriage, preterm birth, and preeclamp sia, others have failed to confirm these findings. There is currently no evidence, however, that identification and treatment of subclinical hypothyroidism will prevent any of these outcomes. Early observational studies also suggested that cognitive function was impaired in offspring of women with untreated subclinical hypothyroidism. Data from a more recent randomized, controlled trial, however, demon strated no improvement in cognitive function of 3-year-olds born to women screened and treated for subclinical hypo thyroidism. For these reasons, the American College of Obstetricians and Gynecologists and the American Associ ation of Clinical Endocrinologists recommend against uni versal screening for thyroid disease in pregnancy. Spontaneous abortion, preterm birth, pre eclampsia, and maternal heart failure occur with increased frequency with untreated thyrotoxicosis. Medical treatment of thyrotoxicosis is usually accom plished with the antithyroid drugs propylthiouracil or methimazole. Although teratogenicity has not been clearly established, in utero exposure to methimazole has been associated with aplasia cutis and choana! Propyl thiouracil is not believed to be teratogenic, but it has been associated with the rare complications of hepatotoxicity and agranulocytosis. Recommendations by the American Thyroid Association are to treat with propylthiouracil in the first trimester and convert to methimazole for the remainder of the pregnancy. Fetal hypothyroidism or hyperthyroidism is uncommon but can occur with maternal Graves disease, which is the most common cause of hyperthyroidism in pregnancy. Radioiodine ablation is absolutely contraindicated in pregnancy because it may destroy the fetal thyroid as well. Transient autoimmune thyroiditis can occur in the postpartum period and is evident within the first year after delivery. Over the next few months, there is a transition to a hypothyroid state, which may require treatment with levothyroxine. Spontaneous resolu tion to a euthyroid state within the first year is the expected course; however, some women remain hypothyroid beyond this time (see Chapter 26). Thus, both mild fasting hypoglycemia and postprandial hyper glycemia are physiologic. These metabolic changes are felt to be hormonally mediated with likely contributions from human placental lactogen, estrogen, and progesterone. Gestational Diabetes Mellitus Gestational diabetes mellitus is abnormal glucose tolerance in pregnancy and is generally believed to be an exaggeration of the pregnancy-induced physiologic changes in carbohy drate metabolism. Alternatively, pregnancy may unmask an underlying propensity for glucose intolerance, which will be evident in the nonpregnant state at some future time if not in the immediate postpartum period. Indeed, at least 50% of women with gestational diabetes are diagnosed with overt diabetes at some point in their lifetime. During the preg nancy, the principal concern in women identified to have gestational diabetes is excessive fetal growth, which can result in increased maternal and perinatal morbidity. Shoul der dystocia occurs more frequently in infants of diabetic mothers because of fetal overgrowth and increased fat deposition on the shoulders. Cesarean delivery and pre eclampsia are also significantly increased in women with diabetes, both gestational and overt. All asymptomatic pregnant women should undergo laboratory screening for gestational diabetes after 24 weeks gestation. The diagnostic thresholds for glucose tolerance tests in pregnancy are not universally agreed upon, and importantly, adverse pregnancy outcomes appear to occur along a continuum of glucose intolerance even if the diag nosis of gestational diabetes is not formally assigned. A two-stage testing strategy is recommended by the Ameri can College of Obstetricians and Gynecologists, starting with a 50-g screening test offered to all pregnant women at 24-28 weeks gestation. If this test is abnormal, the diagnos tic test is a 1 00-g oral glucose tolerance test (Table 1 9-4). Women in whom gestational diabetes is diagnosed should undergo nutrition counseling, and medications are typically initiated for those with persistent fasting hyper glycemia. Insulin has historically been considered the standard medication used to achieve glycemic control; however, oral medications appear to be equivalent in effi cacy, and either are appropriate first-line therapy. Insulin regimens commonly include multiple daily inj ections of a split dose mix of intermediate-acting and short-acting agents. Oral hypoglycemic agents, principally gly buride and metformin, have been evaluated in clinical tri als and appear to achieve similar degrees of glycemic control without increasing maternal or neonatal outcomes. Once therapy is initiated, blood glucose surveillance is important to assess for adequacy of glycemic control. Capillary blood glucose levels should be checked four times per day, once fasting and three times after meals. Intensive therapy with dietary modifications or insulin therapy, or both, has been demonstrated to decrease rates of macrosomia, shoulder dystocia, and preeclampsia. Because of the increased prevalence of overt diabetes in women identified to have gestational diabetes, they should be screened at 6 - 1 2 weeks postpartum with a fasting plasma glucose test or a 2-hour oral glucose tolerance test (75-g glucose load). Overt Diabetes Mellitus Overt diabetes is diabetes mellitus that antedates the preg nancy.

It commonly appears after pharyngitis or impetigo with onset 1 - 3 weeks after infection (average 7- 1 0 days) medicine vs nursing discount generic requip uk. These entities result in glomerular injury during active infection treatment zamrud discount requip 1mg with mastercard, and are better termed "infection-related glomerulonephri tis" rather than postinfectious glomerulonephritis medicine 101 discount requip american express. Urinary microscopy reveals red blood cells that are misshapen or dysmorphic from traversing a damaged glomerular filtration barrier symptoms torn meniscus purchase requip 0.5 mg otc. Biopsy-Kidney biopsy should be considered if there are no contraindications (eg medications similar to vyvanse cheap requip uk, bleeding disorders treatment juvenile rheumatoid arthritis order genuine requip, thrombo cytopenia, uncontrolled hypertension). Important mor phologic information is gleaned from light, electron, and immunofluorescent microscopy. Symptoms and Signs Disease presentation can vary widely across the nephritic spectrum from asymptomatic glomerular hematuria (espe cially in epidemic cases) to nephritic syndrome with hyper tension, oliguria, edema, and perhaps gross glomerular hematuria (smokey-colored urine). Treatment General measures for all include treatment of hypertension and of fluid overload if present. The inflam matory glomerular injury may require immunosuppressive agents (see specific diseases discussed below). Glomerular hematuria and subnephrotic pro teinuria are present; severe cases may demonstrate elevated serum creatinine and urinary red blood cell casts. Kidney biopsy shows a diffuse proliferative pattern of injury on light microscopy. Immunofluorescence demonstrates gran ular deposition of IgG and C3 in the mesangium and along the capillary basement membrane. When to Refer Any patient in whom a glomerulonephritis is suspected should be referred to a nephrologist. Treatment the underlying infection should be identified and treated appropriately; otherwise, treatment for postinfectious glo merulonephritis is supportive. Prognosis depends on the severity of the glomerular injury and age of the patient. Staphylococcus-related glomerulonephritis and poststreptococcal glomerulonephritis: why defining "post" is important in understanding and treating infection-related glomerulonephritis. Treatment the disease course of primary IgA nephropathy varies widely among patients; treatment approach needs to be tailored to risk for progression. Therapy should be titrated to reduce proteinuria to less than 1 g/day and to control blood pressure in the range of 1 25/75 mm Hg to 1 30/80 mm Hg. Azathioprine and mycophe nolate mofetil have also been used in patients at high risk for progression, but studies with these agents are small. General Considerations IgA nephropathy (Berger disease) is a primary renal dis ease of IgA deposition in the glomerular mesangium. The inciting cause is unknown but is likely due to deficient 0-linked glycosylation of IgA subclass 1 molecules. IgA nephropathy is the most common primary glo merular disease worldwide, particularly in Asia. It is most commonly seen in children and young adults, with males affected two to three times more commonly than females. Prognosis Approximately one-third of patients experience spontane ous clinical remission. The remaining patients have chronic microscopic hematuria and a stable serum creatinine. Clinical Findings An episode of gross hematuria is the most common pre senting symptom. Frequently, this is associated with a mucosal viral infection such as an upper respiratory infec tion. The urine becomes red or smokey-colored 1-2 days after illness onset-a so-called "synpharyngitic" presenta tion in contradistinction to the latent period seen in postinfectious glomerulonephritis. There are no serologic tests that aid in this diagnosis; serum IgA subclass 1 testing may be a possibility in the future. The typical pattern of injury seen on kidney biopsy is a focal glomerulonephritis 3. Henoch-Schonlein Purpura Henoch-Schonlein purpura is a systemic small-vessel leu kocytoclastic vasculitis associated with IgA subclass 1 deposition in vessel walls. It is most common in children and is often associated with an inciting infection, such as group A streptococcus or other exposure. Putative environmental exposures that may encite the initial response include S aureus and silica. Symptoms and Signs Symptoms of a systemic inflammatory disease, including fever, malaise, and weight loss may be present and usually precede initial presentation by several months. In addition to hematuria and proteinuria from glomerular inflamma tion, some patients exhibit purpura from dermal capillary involvement and mononeuritis multiplex from nerve arte riolar involvement. Ninety percent of patients with granu lomatosis with polyangiitis have upper (especially sinus) or lower respiratory tract symptoms with nodular lesions that can cavitate and bleed. Hemoptysis is a concerning sign and usually warrants hospitalization and aggressive immunosuppression. The renal lesions can be identical to those found in IgA nephropathy, and the underlying pathophysiology appears to be similar. Most patients with microscopic hematuria and minimal proteinuria recover fully over several weeks. Histologic clas sification of the lesions in children may also provide prog nostic information. To date, although several treatment regimens of various immunosuppressive agents have been clinically tested, none have been definitively proven to alter the course of severe Henoch-Schonlein purpura nephritis. Rituximab treatment and plasma exchange have been suc cessful for severe disease according to several case reports, but clinical trials are lacking. IgA vasculitis (Henoch-Shiinlein pur pura) in adults: diagnostic and therapeutic aspects. Renal biopsy demonstrates necrotizing lesions and crescents on light microscopy; immunofluorescence is negative for immune complex deposition. Induction therapy of high-dose corticosteroids (methylprednisolone, l -2 g/day intravenously for 3 days, followed by prednisone, 1 mg/kg orally for 1 month, with a slow taper over the next 6 months) and cytotoxic agents (cyclophosphamide, 0. Ritux imab has been shown to be noninferior to cyclophospha mide for induction and is also used in refractory or relapsing cases and as an alternative to azathioprine for maintenance of remission. Plasma exchange has been used in conjunction with induction therapy in particularly severe cases; however, its efficacy is controversial. However, with aggressive treatment, complete remission can be achieved in about 75% of patients. Treatment Treatment is a combination of plasma exchange therapy daily for up to 2 weeks to remove circulating antibodies, and administration of corticosteroids and cyclophospha mide to prevent formation of new antibodies and control the inflammatory response. Patients with oliguria and a serum creatinine greater than 6-7 mg/ dL, or who require dialysis upon presentation have a poor prognosis. The incidence peaks in the second and third decades of life dur ing which time males are predominantly affected and lung involvement is more common, and again in the sixth and seventh decades with less male sex predominance. Cryog lobuli n-Associated Glomerulonephritis Essential (mixed) cryoglobulinemia is a vasculitis associ ated with cold-precipitable immunoglobulins (cryoglobu lins). Other overt or occult infections (eg, viral, bacterial, and fungal) as well as some connective tissue diseases can also be causative. Patients exhibit purpuric and necrotizing skin lesions in dependent areas, arthralgias, fever, and hepatosplenomeg aly. Pulse corti costeroids, plasma exchange, rituximab and cytotoxic agents have been used when risk of exacerbating the underlying infection is resolved, or when no infection is present. A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis. Sym ptoms and Signs the onset of disease may be preceded by an upper respira tory tract infection; hemoptysis, dyspnea, and possible respiratory failure may ensue. Laboratory Findings Chest radiographs may demonstrate pulmonary infiltrates if pulmonary hemorrhage is present. The pathogenesis is likely a chronic antigenemia leading to classical complement pathway activation with immune complex deposition; however, it is now recognized that some cases may result from alternative complement path way dysregulation. Both types result in low circulating C3 complement; immune complex type I also has low C4. Treatment of idiopathic immune complex disease is controversial and controlled trial data are lacking. Treatment for the C3 glomerulopathies is in evolution as novel therapies to target the dysregulated alternative complement cascade are being explored; small, uncontrolled series suggest a possible benefit of eculizumab. Glomerular diseases dependent on complement activation, including atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, and C3 glomeru lopathy: core curriculum 20 1 5. Many patients have elevated serum transaminases and an elevated rheumatoid factor. Hypocomplementemia is very common, with C4 typically more reduced than C3; com plement levels and rheumatoid factor tend to be normal if there is a membranous pattern of injury. Renal function rarely improves unless viral suppres sion occurs, and renal function often worsens when therapy is stopped. Ribavirin may cause hemolysis in those with significant kidney impairment and is relatively contraindi cated in that population. Rituximab may be considered in addition to antiviral therapy, although controlled trials are lacking. Small, uncontrolled studies suggest an emerging role for sofosbuvir in the treatment of cryoglobulinemic vasculitis with or without kidney involvement. The pathogenesis may be dysregu lated cellular apoptosis resulting in autoantibodies against nucleosomes; antibody/nucleosome complexes then bind to components of the glomerulus to form immune com plex glomerular disease. Some experts recommend hydroxychloroquine treatment in all patients with lupus nephritis, regardless of histological class. Immu nosuppressive therapy for class V lupus nephritis is indi cated if superimposed proliferative lesions exist. All induction therapy includes corticosteroids (eg, methyl prednisolone 1 g intravenously daily for 3 days followed by prednisone, 1 mg/kg orally daily with subsequent taper over 6 - 1 2 months) in combination with either cyclophos phamide or mycophenolate mofetil. Data suggest that blacks and Hispanics respond more favorably to mycophe nolate mofetil rather than cyclophosphamide; in addition, mycophenolate mofetil has a more favorable side-effect profile than cyclophosphamide and should be favored when preservation of fertility is a consideration. Mycophe nolate mofetil induction is typically given at 2-3 g/day, then tapered to 1 -2 g/day for maintenance. Cyclophospha mide induction regimens vary but usually involve monthly intravenous pulse doses (500- 1 000 mg/m2) for 6 months. Induction is followed by daily oral mycophenolate mofetil or azathioprine maintenance therapy; mycophenolate mofetil may be superior to azathioprine maintenance and causes few adverse effects. Maintenance with calcineurin inhibitors may also be considered, but the relapse rate is high upon discontinuation of these agents. With stan dard therapy, remission rates with induction vary from 80% for partial remission to 50-60% for full remission; it may take more than 6 months to see these effects. Studies to assess safety and efficacy of newer biologic immunomodulatory drugs for lupus nephritis are ongoing. Lessons learned from the clinical trials of novel biologics and small molecules in lupus nephritis. General Considerations In American adults, the most common cause of nephrotic spectrum glomerular disease is diabetes mellitus. Any of these entities can present on the less severe end of the spec trum with a bland urinalysis and proteinuria, or with the most severe presentation of the nephrotic syndrome. Serum creatinine may or may not be abnormal at the time of presentation, depending on the severity, acuity and chronicity of the disease. Sym ptoms and Signs Patients with subnephrotic range proteinuria do not mani fest symptoms of the renal disease. In those with the nephrotic syndrome, peripheral edema is present and is most likely due to sodium retention and, at albumin levels less than 2 g/dL (20 g/L), arterial underfilling from low plasma oncotic pressure. Edema may present in dependent regions, such as the lower extremities, or it may become generalized and include periorbital edema. Dyspnea due to pulmonary edema, pleural effusions, and diaphragmatic compromise with ascites can occur. Kidney biopsy-Kidney biopsy is often performed in adults with new-onset idiopathic nephrotic syndrome if a primary renal disease that may require immunosuppres sive therapy is suspected. In the setting of long-standing diabetes mellitus type 1 or 2, proteinuric renal disease is rarely biopsied unless atypical features (such as significant glomerular hematuria or cellular casts) are also present, or if there is other reason to suspect an additional renal lesion. In those with proteinuria greater than 10 g/day, protein malnutrition may occur and daily protein intake should replace daily urinary protein losses. In both diabetic and nondiabetic patients, therapy that is aimed at reducing proteinuria may also reduce progres sion of renal disease. The urinary dipstick is a good screening test for proteinuria; however, it only detects albumin. The addition of sulfosalicylic acid to the urine causes total protein to precipitate, allowing for the possible discovery of paraproteins (and albumin). A spot urine protein to urine creatinine ratio gives a reasonable approxi mation of grams of protein excreted per day; a 24-hour urine sample for protein excretion is rarely needed. Microscopically, the urinary sediment has relatively few cellular elements or casts. However, if marked hyperlipid emia is present, urinary oval fat bodies may be seen. They appear as "grape clusters" under light microscopy and "Maltese crosses" under polarized light. Blood chemistries-The nephrotic syndrome results in hypoalbuminemia (less than 3 g/ dL [30 g/L]) and hypopro teinemia (less than 6 g/dL [60 g/L]). Hyperlipidemia occurs in over 50% of patients with early nephrotic syndrome, and becomes more frequent and worsens in degree as the sever ity of the nephrotic syndrome increases.

The ill effects of cigarettes treatment effect definition order requip discount, alcohol medicine used to induce labor requip 1mg with mastercard, and other recreational drugs on male fertility should be discussed symptoms mono cheap 2 mg requip with visa. Prescription medications that impair male potency and fac tors that may lead to scrotal hyperthermia medications that cause tinnitus generic requip 2mg free shipping, such as tight underwear or frequent use of saunas or hot tubs treatment borderline personality disorder requip 2mg, should be discussed medicine 5658 purchase requip with paypal. The gynecologic history should include the men strual pattern, the use and types of contraceptives, douch ing, libido, sex techniques, frequency and success of coitus, and correlation of intercourse with time of ovulation. Basic laboratory studies include complete blood count, urinalysis, cervical culture for Chlamydia, rubella antibody determination, and thy roid function tests. Couples should be advised that coitus resulting in concep tion occurs during the 6-day window around the day of ovulation. Ovulation predictor kits have in many cases replaced basal body temperatures for predicting ovulation, but temperature charting is a natural and inexpensive way to identify most fertile days. Basal body temperature charts cannot predict ovulation; they can only retrospectively confirm ovulation occurred. Men must abstain from sexual activ ity for at least 3 days before the semen is obtained. If the sperm count is abnormal, further evaluation includes physical examination of the male partner and a search for exposure to environmental and workplace toxins, alcohol or drug abuse. Gross deficiencies of sperm (number, motility, or appearance) require repeat analysis. A screening pelvic ultrasound and hysterosalpingogra phy to identify uterine cavity or tubal anomalies should be performed. Hysterosalpingography using an oil dye is performed within 3 days following the menstrual period if structural abnormalities are suspected. This radio graphic study will demonstrate uterine abnormalities (septa, polyps, submucous myomas) and tubal obstruction. Initial Testing During the initial interview, the clinician can present an overview of infertility and discuss a plan of study. Women who have had prior pelvic inflammation should receive doxycycline, 100 mg orally twice daily, begin ning immediately before and for 7 days after the radio graphic study. The number of antral follicles during the early follicular phase of the cycle can provide useful information about ovarian reserve and can confirm serum testing. In approximately 25% of women whose basic evaluation is normal, the first-line therapy is usually controlled ovarian hyperstimulation (usually clomiphene citrate) and intrauterine insemination. It acts as a selective estrogen receptor modulator, similar to tamoxifen and raloxifene, and binds to the estrogen receptor. After a normal menstrual period or induction of with drawal bleeding with progestin, 50 mg of clomiphene orally daily for 5 days, typically on days 3-7 of the cycle, should be given. If ovulation still does not occur, the course is repeated with 150 mg daily and then 200 mg daily for 5 days. Ovulation and appropriate timing of intercourse can be facilitated with the addition of chorionic gonadotropin, 1 0,000 units intramus cularly. The rate of ovulation following this treatment is 90% in the absence of other infertility factors. Twinning occurs in 5% of these patients, and three or more fetuses are found in rare instances (less than 0. Pregnancy is most likely to occur within the first three ovulatory cycles, and unlikely to occur after cycle six. In addition, several studies have suggested a two fold to threefold increased risk of ovarian cancer with the use of clomiphene for more than 1 year, so treatment with clomiphene is usually limited to a maximum of six cycles. There is a reduced risk of mul tiple pregnancy, a lack of antiestrogenic effects, and a reduced need for ultrasound monitoring. In women who have a history of estrogen dependent tumors, such as breast cancer, letrozole is preferred as the estrogen levels with this medication are much lower. Cabergoline is often used in patients who cannot tolerate the adverse effects of bromocriptine or in those who do not respond to bromocriptine. Medical Measures Fertility may be restored by treatment of endocrine abnor malities, particularly hypothyroidism or hyperthyroidism. Women who are anovulatory as a result of low body weight or exercise may become ovulatory when they gain weight or decrease their exercise levels. Surgical Measures Excision of ovarian tumors or ovarian foci of endometrio sis can improve fertility. Peritubal adhesions or endometriotic implants often can be treated via laparoscopy. In a male with a varicocele, sperm characteristics may be improved following surgical treatment. For men who have sperm production but obstructive azoospermia, trans-epidermal sperm aspiration or microsurgical epider mal sperm aspiration has been successful. Because of the complexities, laboratory tests, and expense associated with this treatment, these patients should be referred to an infertility specialist. Also, offer ing appropriately timed information about adoption is considered part of a complete infertility regimen. History and challenges surrounding ovarian stimulation in the treatment of infertility. Artificial I nsemi nation in Azoospermia If azoospermia is present, artificial insemination by a donor usually results in pregnancy, assuming female func tion is normal. Gamete intrafal lopian transfer and zygote intrafallopian transfer are rarely performed, although it may be an option in a few selected patients. All of the procedures involve ovarian stimulation to produce multiple oocytes, oocyte retrieval by transvaginal sonography-guided needle aspiration, and handling of the oocytes outside the body. The chance of a multiple gestation pregnancy (ie, twins, triplets) is increased in all assisted reproductive proce dures, increasing the risk of preterm delivery and other pregnancy complications. To minimize this risk, most infertility specialists recommend only transferring one embryo in appropriately selected patients with a favorable prognosis. In the event of a multiple gestation pregnancy, a couple may consider selective reduc tion to avoid the medical issues generally related to multi ple births. Studies esti mate that 40% of the 2 1 3 million pregnancies that occurred in 20 1 2 were unintended. Globally, 50% ended in abortion, 1 3 % ended in miscarriage, and 3 8 % resulted in an unplanned birth. It is important for primary care provid ers to educate their patients about the benefits of contra ception and to provide options that are appropriate and desirable for the patient. Efficacy and methods of use-Combined oral contra ceptives have a perfect use failure rate of 0. The pills can be initially started on the first day of the menstrual cycle, the first Sunday after the onset of the cycle or on any day of the cycle. If started on any day other than the first day of the cycle, a backup method should be used. If an active pill is missed at any time, and no intercourse occurred in the past 5 days, two pills should be taken immediately and a backup method should be used for 7 days. If intercourse occurred in the previous 5 days, emergency contraception should be used immediately, and the pills restarted the following day. Benefits of oral contraceptives-Noncontraceptive benefits of oral contraceptives include lighter menses, reducing the likelihood of anemia, and improvement of dysmenorrhea symptoms. The frequency of developing myomas is lower in patients who have taken oral contraceptives for longer than 4 years. Selection of an oral contraceptive-Any of the combi nation oral contraceptives containing 35 meg or less of ethinyl estradiol or 3 mg of estradiol valerate are suitable. Prognosis the prognosis for conception and normal pregnancy is good if minor (even multiple) disorders can be identified and treated; it is poor if the causes of infertility are severe, untreatable, or of prolonged duration (over 3 years). Couples with unexplained infertility who do not achieve pregnancy within 3 years may be offered ovulation induction or assisted reproductive technology. There is some variation in potency of the various progestins in the pills, but there are essentially no clinically significant differences for most women among the progestins in the low-dose pills. The available evi dence is insufficient to determine whether triphasic oral contraceptives differ from monophasic oral contraceptives in effectiveness, bleeding patterns or discontinuation rates. Therefore, monophasic pills are recommended as a first choice for women starting oral contraceptive use. Women who have acne or hirsutism may benefit from treatment with desogestrel, drospirenone, or norgestimate, since they are the least androgenic. A combination regimen with 84 active and 7 inert pills that results in only four menses per year is available. There is also a combination regimen that is taken continuously with no regular menses. Studies have not shown any signifi gestodene (not available in the United States), drosperi none, or desogestrel compared with women using oral contraceptives with levonorgestrel and norethindrone. Women in whom thrombophlebitis develops should stop using this method, as should those at increased risk for thrombophlebitis because of surgery, fracture, serious injury, hypercoagulable condition, or immobilization. Women should stop using contraceptives if such warning symptoms as severe headache, blurred or lost vision, or other transient neurologic disorders develop. The low-dose oral con traceptives commonly used in the United States are listed in Table 1 8-3. Drug interactions-Several medications interact with oral contraceptives to decrease their efficacy by causing induction of microsomal enzymes in the liver, or by other mechanisms. Some commonly prescribed medications in this category are phenytoin, phenobarbital (and other bar biturates), primidone, topiramate, carbamazepine, and rifampin and St. Women taking these medica tions should use another means of contraception for maxi mum safety. Antiretroviral medications, specifically ritonavir boosted protease inhibitors, may significantly decrease the efficacy of combined oral contraceptives, and the concomi tant use of oral contraceptives may increase the toxicity of these antiretroviral agents. Non-nucleoside reverse tran scriptase inhibitors have smaller effects on oral contracep tive efficacy, while nucleoside reverse transcriptase inhibitors appear to have no effect. Contraindications and adverse effects- O ral contra ceptives have been associated with many adverse effects; they are contraindicated in some situations and should be used with caution in others (Table 1 8-4). Cigarette smoking, obesity, hypertension, diabetes, or hypercholes terolemia increases the risk. Smokers over age 35 and women with other cardiovascular risk factors should use other methods of birth control. While the overall risk is very low (5-6 per 1 00,000 woman years compared to 50-300 per 1 00,000 pregnancies), sev eral studies have reported a twofold increased risk in women using oral contraceptives containing the progestins is no increased risk of breast can cer in women aged 35-64 who are current or former users of oral contraceptives. Women with a family history of breast cancer or women who started oral contraceptive use at a young age are not at increased risk. Combination oral contraceptives reduce the risk of endometrial carcinoma by 40% after 2 years of use and 60% after 4 or more years of use. The risk of ovarian cancer is reduced by 30% with pill use for less than 4 years, by 60% with use for 5- 1 1 years, and by 80% after 12 or more years. Rarely, oral contracep tives have been associated with the development of benign or malignant hepatic tumors; this may lead to rupture of the liver, hemorrhage, and death. Women in whom hyperten sion develops while using oral contraceptives should use other contraceptive methods. However, with regular blood pressure monitoring, nonsmoking women with well controlled mild hypertension may use oral contraceptives. If severe or frequent head aches develop while using this method, it should be discon tinued. While it is prefera ble to avoid the use of combination oral contraceptives during lactation, the effects on milk quality are small and are not associated with developmental abnormalities in infants. Combination oral contraceptives should be started no earlier than 6 weeks postpartum to allow for establish ment of lactation. Patients who had cholestatic jaundice during preg nancy may develop it while taking birth control pills. The minipill is begun on the first day of a menstrual cycle and then taken continuously for as long as contraception is desired. Advantages-The low dose of progestin and absence of estrogen make the minipill safe during lactation; it may increase the flow of milk. It is often tried by women who want minimal doses of hormones and by patients who are over age 35. Complications and contraindications Minipill users often have bleeding irregularities (eg, prolonged flow, spot ting, or amenorrhea); such patients may need regular pregnancy tests. Ectopic pregnancies are more frequent, and complaints of abdominal pain should be investigated with this in mind. Many of the absolute contraindications and relative contraindications listed in Table 1 8-4 apply to the minipill; however, the contraceptive benefit of the minipill may outweigh the risks for patients who smoke, who are over age 35, or who have such conditions as super ficial deep venous thrombosis or known thromboembolic disorders or diabetes with vascular disease. Minor side effects of combination oral contraceptives such as weight gain and mild headache may also occur with the minipill. It is important that obese women are not denied effective contraception as a result of concerns about complications or efficacy of oral contraceptives. Alterna tives, including progestin only injections, implants, or intrauterine devices, should be considered as first options instead of oral contraceptives. Minor side effects-Nausea and dizziness may occur in the first few months of pill use. Spotting or breakthrough bleeding between menstrual periods may occur, especially if a pill is skipped or taken late; this may be helped by switching to a pill of slightly greater potency (see section 3, above). A pregnancy test should be performed if pills have been skipped or if two or more expected men strual periods are missed. There has been extensive worldwide experience with this method over the past 3 decades. The medication is given as a deep intramuscular injection of 150 mg every 3 months and has a contraceptive efficacy of 99. Com mon side effects include irregular bleeding, amenorrhea, weight gain, and headache. It is associated with bone min eral loss that is usually reversible after discontinuation of the method.

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