Take the New Interactive Medical Case!

Posted by Karen Buckley • April 9th, 2015

A 43-year-old man with a 6-week history of abdominal pain and diarrhea. The pain was initially epigastric and occurred after eating but then became more constant and diffuse.  The patient rated the pain at 7 on a scale of 0 to 10, with 10 being the most severe pain.  The diarrhea began gradually and was watery, occurred six or seven times daily (including when the patient fasted, at night), and was associated with urgency and tenesmus.

Test your diagnostic and therapeutic skills with this latest Interactive Medical Case, and earn CME credit or MOC points.

Interactive Medical Cases are online simulations based on a real patient’s experience of illness. You follow interactive steps through an evolving patient’s history, diagnosis, and management, from presentation to outcome. During the presentation of the case, you access videos, lab results and brief commentary that explain concepts important for diagnosis and treatment.

You may also wish to browse the list of 35 previous Interactive Medical Cases.

A Woman with Headache and Fever

Posted by Carla Rothaus • April 9th, 2015

In the latest Case Record of the Massachusetts General Hospital, a 28-year-old woman was seen in the emergency department of this hospital because of the acute onset of headache, fever, rash, and myalgias. On examination, she had petechiae on the chest, abdomen, and thighs and a purpuric lesion on the right shoulder.

Neisseria meningitidis is the second most common cause of bacterial meningitis in adults, and most cases occur sporadically.

Clinical Pearls

- What clinical and laboratory findings are often associated with bacterial meningitis?     

The following clinical findings are often associated with bacterial meningitis: mental-status changes, a CSF neutrophil count of greater than 1000 cells per cubic millimeter, visible organisms on Gram’s staining, hypoglycorrhachia (a low CSF glucose level), and an elevated CSF protein level. However, it is important to recognize that one or more clinical or laboratory signs or symptoms that are typical of meningitis — such as fever, nuchal rigidity, altered mental status, and a CSF white-cell count of greater than 1000 per cubic millimeter — may be absent in a substantial number of patients with this diagnosis, and the CSF glucose and protein levels may be normal.

- What microbiologic findings are characteristic of Neisseria meningitidis?

Gram-negative diplococci with a coffee-bean shape are characteristic of N. meningitidis.

Figure 3. Microbiologic Study.

Morning Report Questions

Q: Describe some of the features associated with meningococcal meningitis.

A: N. meningitidis is associated with a rapidly progressive, sometimes fulminant illness characterized by sepsis, petechial rash, purpura, and meningitis. Of adults with meningococcal meningitis, 49% seek medical attention less than 24 hours after the onset of symptoms and 64% have a rash, of whom the majority have petechiae and one fourth have purpura, ecchymoses, or both; impaired consciousness may be absent in 49% and Gram’s staining of CSF may be negative for organisms in 11%.

Q: What disorder has been associated with recurrent meningococcal meningitis?

A: A deficiency in one of the terminal complement components, with the exception of C9, has been associated with recurrent meningococcal meningitis. Although low-grade or transient meningococcal bacteremia can be overcome by opsonization and subsequent phagocytosis, higher-grade or persistent bacteremia requires the complement system for eradication. Vaccination is performed in an attempt to boost the early opsonophagocytic response. Ultimately, however, an intact and a sufficient response of the terminal complement components is crucial in overwhelming the defense mechanisms of this microorganism and in protecting against invasive disease. The risk of N. meningitides infection among persons with a terminal complement deficiency is 7000 to 10,000 times as high as the risk among persons without such a deficiency; furthermore, approximately 50% of persons with a terminal complement deficiency who have had N. meningitidis infection have recurrent infections. However, N. meningitidis infection is often milder and associated with lower mortality among persons with a terminal complement deficiency than it is among persons without such a deficiency.

Effects of Red-Cell Storage Duration on Patients Undergoing Cardiac Surgery

Posted by Chana Sacks • April 8th, 2015

“Age,” the great boxer Muhammad Ali famously said, “is whatever you think it is. You are as old as you think you are.”

The role that aging plays in vitality, strength, and wisdom has long been debated, but more recently the question of whether younger is better has been raised about red blood cells.  Currently, blood bank regulations allow for storage of red cells for up to 6 weeks before transfusion.   Some observational studies, including data published in the Journal, suggest this might be too long, finding an association between red cell units stored for more than 2 to 3 weeks and serious adverse events.

Given the confounding inherent in observational data, Steiner and colleagues designed a randomized controlled trial to more definitively explore this question.   Their findings, now published in the Journal, call the conclusions of these prior observational studies into question.

Investigators enrolled participants 12 years of age or older who were undergoing complex cardiac surgery and were deemed likely to undergo red blood cell transfusions.  For all intraoperative and postoperative transfusions, participants were randomized to either a shorter storage group (RBCs stored for 10 days or less) or a longer storage group (RBCs stored for 21 days or more).   The primary outcome was the change in the Multiple Organ Dysfunction Score (MODS), a measure from 0-24 that is sensitive to minor changes in clinical status and incorporates mortality, through day 7, death or discharge.

Fourteen hundred and eighty-one participants underwent randomization, with 1098 who ultimately received red cell transfusions included in the analysis. Participants had a median age in their early 70s, were about 40% male, and 90% white; there was no significant difference in baseline MODS between groups. The median storage time of RBCs was 7 days in the short storage group and 28 days in the longer storage group.

The results: there was no significant difference in the primary endpoint, with a mean change in MODS of 8.5 in the shorter storage group versus 8.7 in the longer storage group (p = 0.44).  There were no differences in either serious or non-serious adverse events except that hyperbilirubinemia was more common in the longer storage group, likely attributable to hemolysis in older red blood cells.  While statistically significant, the absolute change in total serum bilirubin was 1.5mg/dL in the longer storage group versus 0.8 in the shorter-term storage group — a difference that seems unlikely to be highly clinically significant.

NEJM Deputy Editor Dr. Dan Longo describes this trial as “an important study that demonstrates no clinical benefit to the preferential transfusion of younger red blood cells.” He cautions, however, against overstating this conclusion: given that the older blood group used red cells stored for a median of 4 weeks and current regulations allow storage up to 6, he notes, “This trial doesn’t address whether 5- or 6-week-old blood might be more harmful.”

With that caveat in mind, age as studied here doesn’t seem to make a difference. When we here at the Now@NEJM blog called Mr. Ali for comment about the fact that he had been right all along, he didn’t seem surprised: “It’s hard being humble,” he says, “when you’re as great as I am.”

See also: NEJM Quick Take video summary on this trial

NEJM Group Open Forum – Take part in the conversation!

Posted by Karen Buckley • April 7th, 2015

These active and engaging discussions are happening now on the NEJM Group Open Forum on Medstro.com. Read the questions and answers posted so far, like, share and comment to become a part of the conversation.

Women Transforming the Culture of Medicine: How do women physicians communicate with each other and with their male colleagues? Can the culture of medicine be improved by more inclusion of women in leadership roles? Part 4 of a 6 part discussion series featuring women physicians, brought to you by the NEJM CareerCenter, starts today on the NEJM Group Open Forum, and continues through April 16.

Extracting the Benefits of a Mentorship:  How do you find the right mentor? We’re talking to successful mentor/mentee pairs to see how they made it happen in part 3 of the NEJM CareerCenter discussion series featuring women physicians.  This discussion is ongoing through April 9.

Detecting Trisomies in a General Population: Ask the authors about a new study that confirms cell-free DNA (cfDNA) testing is superior to routine screening for detecting trisomies among pregnant women in a general prenatal screening population.  This discussion is ongoing through April 10.

Free registration is required. Social login is now available through Facebook, Twitter, Google, and LinkedIn.

Emergency Contraception

Posted by Carla Rothaus • April 3rd, 2015

Ulipristal and levonorgestrel pills are the most commonly used form of emergency contraception; ulipristal is slightly more effective, but levonorgestrel is available over the counter in the United States. The most effective approach is insertion of a copper IUD.  Read the new Clinical Practice review article on Emergency Contraception.

Unintended pregnancy is common; in 2008, the most recent year for which data are available, half the 6.8 million pregnancies reported in the United States were unintended.

Clinical Pearls

- Describe the oral emergency contraceptive pills that are available in the United States.

Oral emergency contraceptive pills are the most commonly used form of emergency contraception. Two regimens are currently marketed in the United States: ulipristal acetate (30 mg) and levonorgestrel (1.5 mg). In 39 clinical trials that included a combined total of more than 18,000 women, rates of pregnancy after use of one of these two regimens ranged from 0 to 6.5%. Interpretation of these numbers is problematic because the likelihood of pregnancy in the absence of emergency contraception was not directly assessed; estimates that were based on the days of the menstrual cycle on which the participants had sex suggest that use of each of these regimens reduces the risk of pregnancy after a single sex act by 40 to 90%. In the United States, products containing 1.5 mg of levonorgestrel in one tablet may legally be sold over the counter to women and men of all ages. Although the ulipristal regimen was recently approved for nonprescription sale in Europe, it still requires a prescription in the United States; consequently, use of this regimen in the United States is limited. Some but not all data suggest reduced efficacy of the levonorgestrel regimen in obese women.

- How should oral emergency contraceptives be used?

The levonorgestrel regimen is effective for at least 4 or 5 days after sex but may be more effective the sooner it is taken; data on the ulipristal regimen have not indicated a decrease in efficacy through 120 hours after sex. However, since both regimens work largely by delaying or inhibiting ovulation, and since women are usually unaware of whether ovulation is imminent, prompt use is prudent. Neither of these two oral emergency contraceptive regimens has any recognized contraindications.

Morning Report Questions

Q: How does the copper intrauterine device (IUD) compare with the oral regimens for emergency contraception?

A: The most effective form of emergency contraception is the copper IUD. A review of 42 studies showed that, of 7034 women who received IUDs up to 10 days after unprotected sex, only 0.09% subsequently became pregnant. Recent analyses suggest that the IUD is effective for emergency contraception throughout the menstrual cycle and can be inserted at any point if pregnancy is ruled out. A key advantage of the IUD over oral emergency contraceptive pills is that the IUD can provide ongoing contraception for at least 10 years. Almost all women can safely use an IUD for emergency contraception; the only recognized contraindications are pregnancy, cancer of the genital tract, uterine malformation preventing device placement, copper allergy, mucopurulent cervicitis, current pelvic inflammatory disease, and known current cervical infection with chlamydia or gonorrhea. These conditions can be reasonably ruled out on the basis of interview, examination, and, if indicated, pregnancy test; routine testing for cervical infection is not necessary.

Q: Are these forms of emergency contraception associated with serious complications?

A: No deaths or serious complications have been causally linked to either oral emergency contraception regimen. Previous studies over the past decades have not revealed adverse effects of levonorgestrel exposure during pregnancy on either the woman or the conceptus. Data on ulipristal exposure during pregnancy are limited, but combined data from postmarketing surveillance and clinical trials showed that among 232 pregnancies with a known outcome in which the woman and conceptus were exposed to ulipristal, no teratogenic effects were seen. The incidence of pelvic inflammatory disease after IUD insertion is less than 5% even when the device is inserted through an infected cervix; whether IUD insertion itself increases this incidence has not been definitively established. IUD insertion can be uncomfortable, and some women have vaginal bleeding and cramping after insertion. In the one published study of IUD insertion for emergency contraception, which was conducted in community clinics, the IUD insertion attempt was unsuccessful in 18% of women; this proportion is higher than that reported in clinical trials of IUD insertion for routine contraception.

Table 1. Situations in Which Emergency Contraception May Be Indicated in a Woman Using Routine Contraception.

Community-Acquired Pneumonia in Adults

Posted by Carla Rothaus • April 3rd, 2015

Antimicrobial choices for community-acquired pneumonia in hospitalized patients who do not require ICU-level care continue to be debated. In a new trial, empirical beta-lactam–based therapy with or without a macrolide was compared with fluoroquinolones as initial treatment.

The choice of empirical antibiotic treatment for patients with clinically suspected community-acquired pneumonia (CAP) who are admitted to non-intensive care unit (ICU) hospital wards is complicated by the limited availability of evidence. Postma et al. conducted a cluster-randomized crossover trial in the Netherlands to assess whether a strategy of preferred empirical treatment with beta-lactam monotherapy is noninferior to either preferred beta-lactam-macrolide combination therapy or preferred fluoroquinolone monotherapy, with regard to 90-day all-cause mortality among adults with clinically suspected CAP who are admitted to non-ICU wards.

Clinical Pearls

- What do current guidelines recommend for the empirical treatment of adult patients with suspected CAP who are admitted to non-intensive care unit wards?

For patients with clinically suspected CAP who are admitted to a non-intensive care unit ward, guidelines recommend either combination therapy with a beta-lactam plus a macrolide or plus ciprofloxacin or monotherapy with moxifloxacin or levofloxacin for empirical treatment.

- Is there evidence in support of these recommendations?

These guidelines have increased the use of macrolides and fluoroquinolones, although these antibiotic classes have been associated with increased development of resistance. The evidence in support of these recommendations is limited. The recommendation to  add a macrolide to a beta-lactam is based on observational studies, which are prone to confounding by indication. Although fluoroquinolones have been evaluated in randomized, controlled trials, their superiority over beta-lactam monotherapy has not been shown.

Morning Report Questions

Q: Is empirical treatment with beta-lactam monotherapy noninferior to beta-lactam-macrolide combination therapy or fluoroquinolone monotherapy with respect to 90-day all-cause mortality among this population?

A: In the trial by Postma et al., the absolute difference in the adjusted risk of death between the beta-lactam strategy and the beta-lactam-macrolide strategy was 1.9 percentage points (90% confidence interval [CI], −0.6 to 4.4) in favor of the beta-lactam strategy, and the absolute difference between the beta-lactam strategy and the fluoroquinolone strategy was −0.6 percentage points (90% CI, −2.8 to 1.9) in favor of the fluoroquinolone strategy. These confidence intervals do not include the prespecified margin of a 3-percentage-point higher 90-day mortality, thus demonstrating the noninferiority of the beta-lactam strategy to the beta-lactam-macrolide and fluoroquinolone strategies.

Figure 2. Noninferiority Plots.

Q: Is a strategy of empirical treatment with beta-lactam monotherapy associated with a higher rate of complications as compared with beta-lactam-macrolide combination therapy or fluoroquinolone monotherapy?

A: In the Postma study, there were no significant differences among the three strategies in the incidence of major or minor complications.

Initial Antibiotic Choice for Community Acquired Pneumonia

Posted by John Staples • April 2nd, 2015

The basic symptoms which occur in pneumonia … are as follows: acute fever, sticking pain in the side, short rapid breaths, serrated pulse and cough.

  – Maimonides (1138–1204 AD)

Antibiotic treatment of community-acquired pneumonia (CAP) is one of the most remarkable medical developments of the 20th century, yet the choice of initial antibiotics is not without controversy. Current guidelines advise coverage for atypical organisms, but some investigators have pointed to the low incidence of atypical pathogens, the risk of fostering antibiotic resistance, and the specter of increased cardiac events with macrolides. What’s a clinician to do?

In an effort to shed light on this dilemma, Drs. D.F. Postma and C.H. van Werkhoven (University Medical Center, The Netherlands) and colleagues report on the results of the CAP-START study in this week’s NEJM. Seven Dutch hospitals were randomly assigned to treat patients admitted to non-ICU wards with CAP according to one of three antibiotic strategies: Beta-lactam monotherapy (such as ceftriaxone alone), beta-lactam/macrolide combination therapy (such as ceftriaxone plus azithromycin), or fluoroquinolone monotherapy (such as levofloxacin alone). Physicians could deviate from the strategy at their discretion. Hospitals crossed over to a different strategy every four months until trial completion, at which time a total of 2,283 patients had been recruited.

The investigators found that beta-lactam monotherapy was non-inferior to the other strategies, with similar crude 90-day mortality rates for all three groups (9%, 11%, and 9%, respectively). Median hospital length of stay was 6 days for all strategies.

“The non-inferiority of beta-lactam monotherapy for CAP is intriguing and should be considered in light of the risk of side effects (albeit small but not inconsequential) and the increasing burden of antimicrobial resistance,” says infectious disease specialist and NEJM Deputy Editor Dr. Lindsey Baden. “But readers should note that deviations from the recommended strategy for medical reasons occurred in about 25% of patients – suggesting there’s still a need for clinical judgment based on local and clinical factors.”

Unlike the pre-antibiotic era (when Sir William Osler called pneumonia “the Captain of the Men of Death”), modern medicine has a panoply of effective antibiotics from which to choose when a patient is admitted with CAP. What is the take-home message from CAP-START? Perhaps beta-lactam monotherapy is an adequate first volley to fire at the Captain.

Detecting Trisomy

Posted by Rena Xu • April 1st, 2015

A simple prenatal blood test made national headlines last year after a study published in NEJM reported its superiority to standard prenatal screening. The test, called cell-free fetal DNA (cfDNA), identified common trisomies (21, 18, and 13) by detecting fragments of fetal DNA in maternal blood. Screening could be done early in a pregnancy and at no risk to the fetus.

While cfDNA was already recognized as a more effective screen for “high-risk” pregnancies, experts had cautioned that it was not recommended for everyone. Last year’s study, which enrolled relatively low-risk women, suggested it might in fact be a better screen across the board. This week, NEJM reports findings from a second and larger multicenter study confirming that cfDNA is superior to routine screening for detecting trisomies among pregnant women in general.

In this study, over 15,000 pregnant women who were between 10 and 14 weeks’ gestation underwent cfDNA testing in addition to standard screening. Participants were informed of the standard screening results but kept blinded to the cfDNA results. Birth outcomes were then determined based on diagnostic genetic testing or newborn exam.

Among pregnancies with an interpretable cfDNA result, there were thirty-eight cases of trisomy 21. The cfDNA assay identified all of them – it was 100% sensitive — whereas standard screening only identified thirty out of the thirty-eight cases, for a sensitivity of 79%. Additionally, the rate of false positives was nearly a hundred times lower with cfDNA: there were only nine false-positive cases, versus 854 with standard screening. All told, the positive predictive value of cfDNA was nearly 81%, whereas for standard screening it was 3.4%.

It should be noted that among three percent of women in the study, a cfDNA result could not be obtained. This was attributed to a low amount of fetal DNA in the maternal blood, or in some cases, to assay variance or failure. Among these 488 women without a cfDNA result, 13 aneuploidies were ultimately found — a higher than average rate, compared to the overall study population. Had these women been included in the study as “not detected” by cfDNA, the calculated effectiveness of the assay would have been lower.

The authors write, “While these data support use of cfDNA screening in women regardless of age or risk status, further cost utility studies are warranted.” Among women who get a negative result with standard screening, nearly 1900 cfDNA tests would need to be done to find a single case of trisomy 21; the costs associated with this would be considerable. On the other hand, reducing the number of false positive results could reduce the need for invasive testing and avoid the associated financial as well as emotional and physical costs.

NEJM associate editor and chief of obstetrics at Massachusetts General Hospital, Dr. Michael Greene states, “Although still a screen and not a definitive diagnostic test, the major advantages of cfDNA screening compared to the prior standard are the increased reassurance that a negative screen really does mean that the fetus is normal and the reduced number of false positives sparing many women invasive diagnostic testing of normal fetuses.”

Ask the authors about this study in the NEJM Group Open Forum on Medstro.com (free registration required).

 

Sciatica

Posted by Carla Rothaus • March 27th, 2015

Pain that extends from the buttock down the course of the sciatic nerve is common. Nearly 85% of cases are associated with a disk disorder. The causes, assessment, and management of sciatica are discussed in a new review article.

The mundane malady sciatica has been known to physicians since antiquity. It is defined as pain that radiates from the buttock downward along the course of the sciatic nerve.

Clinical Pearls

- What is the most common cause of sciatica?

Although sciatica has several causes, Mixter and Barr extended previous observations to establish in 1934 that the principal source is compression of a lumbar nerve root by disk material that has ruptured through its surrounding annulus. Neuroradiologic studies affirm that 85% of cases of sciatica are associated with disk disorder. The fourth and fifth lumbar nerve roots and the first two sacral nerve roots join in the lumbosacral plexus to form the peroneal and tibial nerves that leave the pelvis in an ensheathed single trunk as the sciatic nerve, the largest nerve in the body.

Disturbances anywhere along its course can give rise to sciatica, but the most common areas are at the sites of disk rupture and osteoarthritic change — at the L4-L5 and L5-S1 levels and, less frequently, the L3-L4 level — where there is generally compression of the root below the corresponding disk.

Table 1. Causes of Sciatica and of Conditions Simulating Sciatica.

Figure 1. Origin and Course of the Sciatic Nerve and the Main Sites of Damage.

- How do leg-raising tests help establish the cause of sciatica?

Many clinical tests have been devised to determine whether sciatic pain is caused by disk compression of a spinal nerve root; most of the tests are variations of the straight-leg-raising test. In a patient in the supine position, raising the leg with the knee extended stretches the nerve root over the protruded disk and results in a nocifensive response of muscle contraction. A positive sign consists of reproduction or marked worsening of the patient’s initial pain and firm resistance to further elevation of the leg. A diagnosis of disk compression is likely if pain radiates from the buttock to below the knee when the angle of the leg is between 30 and 70 degrees. Sensitivity of the test for disk herniation is approximately 90%, but specificity is low. Many persons without spinal abnormalities have hamstring and gluteal tightness with discomfort elicited by straight-leg raising, but the pain is more diffuse than in sciatica and the leg can be lifted higher if the maneuver is performed slowly. Increased pain on dorsiflexion of the foot or large toe increases sensitivity. The crossed straight-leg-raising test (Fajersztajn’s test) for sciatic pain involves raising the unaffected leg; this test is 90% specific for disk herniation on the contralateral side but is insensitive.

Figure 2. Straight-Leg-Raising Test.

Morning Report Questions

Q: How effective is conservative treatment?

A: The most common initial treatment is pain control by means of medication and physical therapy. Activity is usually self-limited in proportion to the degree of discomfort, and although rest is often recommended, it is not better than movement in patients who are able to remain active. Nonsteroidal antiinflammatory medications may provide short-term relief for low back and sciatic pain; however, it is difficult to determine their effect on sciatica, and many patients report little relief. Orally or systemically administered glucocorticoids have been used to ameliorate sciatica, but it is difficult to interpret their effect. Guidelines recommend restrictions on the use of opioids. Antiepileptic drugs, antidepressant agents (e.g., tricyclic agents), muscle relaxants, and pain medications that enhance the activity of gamma-aminobutyric acid have been used but with little supporting data. The benefits of physical therapy and various exercise regimens are difficult to determine, and the superiority of any one program has not been established, although most appear to be safe. Spinal manipulation for sciatica is widely used and has been studied with an assortment of designs and comparators; therefore, reviews of existing trials, most considered of low or moderate quality, draw limited conclusions.

Epidural injections of glucocorticoids are frequently administered for low back pain and related conditions. Trials have suggested an associated short-term decrease in leg pain but no decrease in the need for subsequent surgery.

Q: How does surgery compare to conservative treatment of sciatica caused by disk disease?

A: Most trials comparing surgical treatment and conservative treatment of sciatica due to lumbar disk disease favor surgery, because it results in earlier relief of pain. A review of major trials with adequate data for analysis concluded that there was conflicting evidence on long-term benefit but that surgery relieved pain more rapidly and to a greater degree than did conservative therapy. North

American Spine Society guidelines state that diskectomy provides more effective and more rapid symptom relief than do other treatments for symptoms that warrant surgery, although less severe symptoms can be managed conservatively. Complications of surgery are infrequent but include dural tears with leakage of cerebrospinal fluid, as well as damage to the root or cauda equina.

A Girl with Graves’ Disease

Posted by Carla Rothaus • March 27th, 2015

In the latest Case Record of the Massachusetts General Hospital, a 15-year-old girl with Graves’ disease was admitted to the hospital because of psychotic symptoms — including depression, hallucination, and suicidal thoughts — that began approximately 2 months after treatment with methimazole had been initiated.

Before a diagnosis of primary mood disorder can be made, organic causes of the symptoms must be ruled out.

Clinical Pearls

- What kind of psychiatric symptoms are associated with Graves’ disease?

The majority of patients with Graves’ disease report some degree of psychiatric symptoms, including irritability, anxiety, anger, or sadness, which may precede other manifestations of the illness by weeks to months. While these psychiatric symptoms usually do not reach the level of impairment necessary to make a psychiatric diagnosis, a substantial minority of patients have symptoms of sufficient severity to warrant psychiatric diagnosis. In a study involving recently diagnosed, untreated adults with Graves’ disease, 45% met criteria for an anxiety disorder and 30% met criteria for major depressive disorder.

- What are some considerations when treating Graves’ disease with associated psychiatric symptoms?

Treatment of the underlying condition is sufficient to address most psychiatric disorders secondary to hyperthyroidism. However, a more assertive approach should be considered when a patient’s psychiatric symptoms are severe, concerns about the patient’s safety emerge, or treatment of the underlying condition alone does not lead to rapid improvement in the patient’s mental state. Psychiatric medications with the potential to exacerbate known physiological complications of hyperthyroidism should be used with caution or avoided altogether. For instance, low potency antipsychotics have the potential to worsen tachycardia and medications with significant risk of QTc prolongation, such as ziprasidone, may put a patient with hyperthyroidism at particularly high risk of arrhythmia.

Morning Report Questions

Q: How is Graves’ disease in children treated?

A: Antithyroid medication is typically the first line of therapy for pediatric patients. The use of methimazole is preferred to propylthiouracil; the latter has recently been given a black-box warning in pediatrics by the U.S. Food and Drug Administration due to the unacceptably high risk of liver failure in children. Antithyroid medications act by inhibiting oxidization and organification of iodide. Normalization of thyroid hormone levels takes about 8 to 12 weeks. More definitive therapy is required as second-line therapy if there is no remission within a few years. Radioactive iodine and surgical thyroidectomy are both safe and effective in this age group.

Q: What are some of the risks of total thyroidectomy for Graves’ disease?

A: Total thyroidectomy can be done safely by an experienced surgeon.

Ultrasonography may be used to assess the size of the gland, the extent of inflammatory changes, and the presence of nodules. Computed tomographic scanning and fiberoptic laryngoscopy are not necessary. Unilateral recurrent laryngeal nerve (RLN) injury occurs in 1 to 2% of the cases, and can result in a paralyzed vocal cord on the side of the injury and permanent hoarseness, a whispery voice, and sometimes aspiration. Bilateral nerve injury, though very rare, can result in immobility of both vocal cords and the need for a tracheostomy. Temporary RLN palsies due to stretching or bruising can occur in up to 5% of patients, but the nerves often recover within 6 months. Minor voice change, including difficulty with projection and reaching the highest pitches, can be seen in some patients, especially if the external branch of the superior laryngeal nerve is injured. Permanent hypoparathyroidism occurs in 2% of patients. Temporary hypoparathyroidism occurs in up to 20% of patients and is more common in children, women, and patients with Graves’ disease. Neck hematoma can occur in approximately 1 of 300 patients who undergo total thyroidectomy and always requires reoperation; high vascularity in

Graves’ disease may contribute to a slightly higher risk.