By Louis Kuritzky, MD
Combined Levothyroxine Plus Liothyronine Compared to Levothyroxine Alone in Primary Hypothyroidism
Prior to sophisticated development of drug therapy, thyroid hormone was administered as a derivative of animal thyroid glands, with varying amounts of T3 and T4. Currently, although solitary levothyroxine (T4) is the preparation provided to more than 90% of patients with hypothyroidism (hTHY), there has been some enthusiasm for use of combination products (T3 and T4) or T3 alone. However, it remains controversial whether T3 provides additional benefit over simply using T4 and anticipating adequate T3 derivation from that. A 1999 study had suggested that dual treatment enhanced cognitive function.
Clyde and colleagues randomized 46 stable hTHY patients to T4 alone vs T4 + T3. T3 was provided in a dose of 7.5 mg b.i.d. to replace 50 mg of T4 (ie, if a patient had been previously well controlled on 150 mg/d T4, they were switched to 100 mg T4 + 7.5 mg T3 b.i.d).
Both regimens provided appropriate suppression of TSH and adequate levels of T4 and T3, indicative of accurate therapeutic replacement. As might be anticipated, T3 supplementation resulted in higher serum T3, accompanied by compensatory reduced T4, although neither measurement exceeded boundaries of normal. No discernible benefit for symptoms, cognitive performance, or mood was demonstrated for dual treatment.
The accompanying editorial reflects upon 2 additional recently published trials with similar results. Though the idea of combination thyroid replacement is appealing for patients who report hypothyroid symptoms despite laboratory documentation of adequate replacement, these recent data questions the viability of such an approach, which also entails greater complexity and expense.
Clyde PW, et al. JAMA. 2003;290: 2952-2958.
Specific Site Involvement in Fixed Drug Eruption
Fixed drug eruption (FDE) is the recurrent presentation of cutaneous drug allergy manifest at the same local site. In the United States, the glans penis is one of the most common sites of FDE, often precipitated by tetracycline or trimethoprim-sulfamethoxazole (TMP-SMX).
This study provides details on 105 FDE patients seen in the Istanbul Medical Faculty Department of Dermatology Clinic 1996-2000. To confirm the FDE diagnosis and precipitating agent, oral provocation testing was performed. TMP-SMX and naproxen were the most common causes of FDE (63.8% and 23.8%, respectively). Less common causes were oxicams such as piroxicam [Feldene] (4.8%), acetaminophen (0.95%), and dimenhydrinate (0.95%).
The most commonly involved sites for FDE were the genital mucosa (50.5%), trunk (38.1%), lips (37.1%), and hands (32.4%). Drug-specific differences were noted, in that TMP-SMX most often produced genital FDE, whereas NSAIDs most commonly affected the lips. Site-specific associations between drugs and FDE may help clinicians confirm diagnostic hypotheses.
Ozkaya-Bayazit E. J Am Acad Derm. 2003;49:1003-1007.
Anticoagulation Therapy for Stroke Prevention in Patients with Atrial Fibrillation
There is little challenge to the credibility of anticoagulation for stroke prevention in atrial fibrillation (SPAF) as demonstrated in numerous large clinical trials. Nonetheless, clinicians may not apply the same sanguine approbation when considering the options in "real life" settings, perhaps wondering whether clinical trial results reflect a more pristine patient population and whether the risk benefit-ratio will be similar in their particular local setting.
The cohort study reported by Go and colleagues assessed nonvalvular atrial fibrillation patients (n = 11,526) from an integrated health care system in Northern California, which might more accurately represent nonacademic practice milieu. The effect of warfarin treatment was very salutary (compared to no antithrombotic therapy), providing a 64% reduction in odds of thromboembolism. Similarly, warfarin treatment was associated with reduced all-cause mortality (31%). Although the risk of intracranial hemorrhage in persons on warfarin was increased (hazard ratio =1.97), the absolute number of events was very small (0.46 per 100 person-years) and far out-weighed by the other beneficial effects, including stroke reductions of 61%.
Clinicians should be heartened that application of literature-proven interventions may yield similar positive effect in traditional ambulatory settings.
Go AS, et al. JAMA. 2003;290:2685-2692.
Dr. Kuritzky, Clinical Assistant Professor, University of Florida,, Gainesville, is Associate Editor of Internal Medicine Alert.
Combined Levothyroxine Plus Liothyronine Compared to Levothyroxine Alone in Primary Hypothyroidism; Specific Site Involvement in Fixed Drug Eruption; Anticoagulation Therapy for Stroke Prevention in Patients with Atrial Fibrillation
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