Atypical Thyrotoxicosis Relapse after Carbimazole Discontinuation: A Case Report with Pharmacological View

authors: Sharique Ahmad, Saeeda Wasim, Mohammed Tariq Salman, Mohammed Aqwam Siddiqui,
Nahid Shabnam, Pragya Khanna

A 15-year-old girl who presented with pyrexia of unknown origin of 3 month’s duration was evaluated and examined. She had two palpable axillary lymph nodes associated with mild hepatosplenomegaly and leukopenia (white blood cell count - 1700/cmm). Later was assessed for systemic infection, hematological malignancies and autoimmune disorders. All investigations showed no cause pertaining leukopenia and fever. There was moderate sized goiter in midline of neck with past history of hyperthyroidism associated with tachycardia, tremors, weight loss and thyroid hormone profi le suggesting hyperthyroidism, which prompted to think about thyrotoxicosis associated autoimmunity leading to lymphadenopathy, hepatosplenomegaly and leukopenia. Patient improved rapidly in 3 days after initiation of anti-thyroid drug. 

Atypical Thyrotoxicosis Relapse after Carbimazole Discontinuation

Single daily poly-pill for HIV

In a prospective, randomized trial, a single daily tablet containing efavirenz, emtricitabine, and tenofovir (Atripla; Bristol Myers Squibb & Gilead Sciences LLC) maintained viral suppression in HIV-1 infected patients as well as the standard multiple-pill regimen.

The report of the study, published in the Journal of the Acquired Immune Deficiency Syndrome, notes that at baseline, all 300 participants were on stable antiretroviral therapy (ART) regimens, with viral loads of less than 200 copies/mL for at least 3 months. Their mean CD4 count was 540 cells/�L, and 96% of subjects had HIV-1 RNA <50>

On randomization, 203 were assigned to the Atripla regimen while 97 remained on their baseline regimen. The entire 48-week study was completed by 266 patients.

In the intent-to-treat analysis, it was found that at 48 weeks, the primary endpoint -- HIV-1 RNA below 200 copies/mL -- had been achieved by 89% of the patients in the single-tablet group versus 88% of those on unmodified antiretroviral regimens, "indicating noninferiority" of the newer approach.

Similarly, there was no significant difference between groups in maintenance of viral load below 50 copies/mL and no significant changes in CD4 cell counts within or between the two arms of the study.

Discontinuation rates were similar between the groups, but more patients in the single-tablet group discontinued due to adverse events, "most commonly for nervous system symptoms," according to the investigators.

Three patients in the single-tablet group and one in the control group had virologic failure.

"In summary," the researchers conclude, "patients who were stable and virologically suppressed while receiving a wide array of non-nucleoside reverse transcriptase inhibitor- and protease inhibitor-based antiretroviral regimens and had their treatment simplified to a single-tablet regimen of efavirenz, emtricitabine, and tenofovir maintained high rates of virologic suppression compared to those who continued their regimen unmodified."

Source: J Acquir Immune Defic Syndr 2009;51:163-174.

ACE Inhibitors or ARBs in Hypertension and/or Chronic Kidney Disease?

A pair of articles in the January 1, 2008 Annals of Internal Medicine brings together the existing literature to address issues that have persisted since the introduction of angiotensin-receptor blockers (ARBs): namely, when and how these drugs might be advantageous in conditions long served by angiotensin-converting enzyme (ACE) inhibitors.

A meticulous survey of studies found that the two drug classes are about equally safe and effective at managing high blood pressure and have similar effects on other risk factors and clinical outcomes in patients with essential hypertension. It also confirmed that ARBs are less likely to cause coughing, but suggested that the side effect might be less common with ACE inhibitors than randomized trials indicate.

In the setting of chronic kidney disease (CKD), concludes the other study, which is a meta-analysis, ACE inhibitor and ARB monotherapy are similarly effective at reducing proteinuria, but a combination of the two angiotensin-2-suppressing drugs works better than either agent individually. But a blanket recommendation to combine them would be premature, according to the authors, because there is little evidence that the combination would improve clinical outcomes over monotherapy, and the safety of such combination therapy is largely undefined.

Study Highlights

• Essential hypertension
  
  • Included were studies that directly compared ACE inhibitors and ARBs of any design (RCTs, controlled trials, nonrandomized trials, cohort and case control studies) lasting at least 12 weeks and enrolling at least 20 patients, which provided direct comparison of ACE inhibitors and ARBs.
  • Outcomes examined were blood pressure control, adherence, quality of life, intermediate outcomes, and harms.
  • Of 61 studies analyzed, 47 were RCTs, 9 were retrospective cohort studies, 1 cross-sectional, 1 case control cohort, and 1 nonrandomized trial.
  • Rates of use as monotherapy were similar for the 2 classes of drugs.
  • ACE inhibitors and ARBs had similar efficacy for blood pressure control, with no significant differences in benefits or harms (strength of evidence: high).
  • Quality-of-life measures and adherence were similar for ACE inhibitors and ARBs.
  • There were no consistent differential effects seen for death and cardiovascular events.
  • Both classes of medication had similar effects on lipid levels, left ventricular mass, and risk for dysglycemia or renal dysfunction.
  • Adverse effects of headache and dizziness were similar for the 2 classes.
  • Cough as an adverse effect was 3 times more common with ACE inhibitors, with overall rates much higher in randomized trials (9.9% vs 3.2%) vs cohort-based studies (1.7% vs 0.6%).
  • The number needed to treat to cause 1 case of chronic cough for ACE inhibitors was 15.
  • The average duration of follow-up exceeded 6 months in only one third of the head-to-head studies, and there was a lack of long-term studies.
  • There was a lack of adequate studies reporting adverse effect profile of both medication classes.
• Chronic renal disease
  
  • Included were RCTs of short-term (1 to 4 months) and longer-term (5 to 12 months) studies involving a total of 6181 patients with microalbuminuria and proteinuria of diabetic origin and other causes and reported changes in proteinuria during follow-up.
  • Trials were at least 4 weeks in duration with parallel group or crossover designs.
  • Excluded were studies of patients who had renal transplantation and those with less than 10 participants.
  • Of 49 RCTs, 12 compared ARBs with placebo, 9 with calcium-channel blockers, 23 with ACE inhibitors, and 16 with the combination of ACE inhibitors and ARBs.
  • 23 trials compared combination ARBs and ACE inhibitors with an ACE inhibitor alone.
  • Monotherapy with ACE inhibitors or ARBs reduced proteinuria to a similar degree but less than combination therapy.
  • Mean reduction in proteinuria with combination vs ARB monotherapy in 5- to 12-month studies was 0.75 vs 0.82 (ratio of means) with ACE inhibitors.
  • Monotherapy with ARBs reduced proteinuria vs placebo, with a ratio of means of 0.57 in 1 to 4 months and 0.69 in 5 to 12 months.
  • Results were similar for ACE inhibitors and ARBs vs calcium-channel blockers.
  • 92% of studies lacked quantitative data on adverse drug reactions.
  • In the absence of safety data on long-term combination therapy with ACE inhibitors and ARBs, therapy should be limited to those with stage 3 or 4 disease with close monitoring of potassium levels.
  • The editorialist concluded that monotherapy with ACE inhibitors or ARBs was sufficient treatment for early-stage renal disease with relatively low albumin exertion, and combination therapy was effective for patients with heavier proteinuria when monotherapy failed to decrease 24-hour urinary protein excretion to less than 0.5 g.

Summary

• ACE inhibitors and ARBs are equivalent in efficacy for the treatment of essential hypertension, and ACE inhibitors are associated with a 3 times higher rate of chronic cough.
• ACE inhibitors and ARBs are similar in efficacy for the treatment of proteinuria of chronic renal disease, with the combination being more effective than monotherapy with either drug, but long-term adverse effects are not well documented.

Sources:

Sources

1. Matchar DB, McCrory DC, Orlando LA, et al. Systematic review: Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension. Ann Intern Med. 2008;148:16-29.
2. Kunz R, Friedrich C, Wolbers M, Mann JFE. Meta-analysis: Effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med. 2008;148:30-48.
3. Steve Stiles, Désirée Lie. ACE Inhibitors or ARBs in Hypertension? In Chronic Kidney Disease? Medscape Medical News, Medscape Internal Medicine. January 17, 2008; Reviewed and Renewed: February 13, 2009
   
   

Rimonibant banned in Europe

The European Medicines Agency (EMEA) has banned the new antiobesity drug rimonabant in European Union. EMEA has suspended the marketing authorisation as the benefits no longer outweigh the risks of psychiatric adverse effects.