By Louis Kuritzky, MD
Urinary Tetrahydroaldosterone as a Screen for Primary Aldosteronism
It has recently been suggested that a substantial minority of persons with hypertension—as many as 1 out of 7 or 8—suffer overlooked primary hyperaldosteronism (PHA) as an etiology. Although unprovoked hypokalemia, when present, is a useful stimulus to direct investigation toward PHA as a cause, the inconsistency of this finding, coupled with the frequency of other equally rational explanations for hypokalemia present in hypertensive patients (eg, diuretic therapy), conspire to obscure the diagnosis.
A variety of biochemical diagnostic tests have been used to establish the diagnosis of PHA, including plasma rennin-to-aldosterone ratio, plasma aldosterone concentration, 24-hour urinary aldosterone-18-glucouronide, and free aldosterone. Abdelhamid and colleagues sought to prospectively compare the measurement of 24-hour urinary tetrahydroaldosterone (THA), a primary hepatic metabolite of aldosterone, with other commonly used diagnostic measures in a population (n = 1976) of hypertensives, compared to controls.
The diagnostic test with the best sensitivity (96%) and specificity (95%) for PHA was THA, which compared very favorably with plasma aldosterone (89% and 90%), 24-hour urinary free aldosterone (87% and 91%), plasma aldosterone-to-renin ratio (85% and 85%), and even the combination of the latter 2 tests (82% and 85%). Based upon these data, Abdelhamid et al suggest that THA is the appropriate initial best diagnostic test; in the uncommon scenario of a false-negative THA, measuring urinary free aldosterone and aldosterone-18-glucuronide would discover essentially all of the other PHA cases.
Abdelhamid S, et al. Am J Hypertens. 2003;16:522-530.
Finasteride and Prostate Cancer
It is apparent that androgenic hormones, in particular dihydrotestosterone (DHT), are participants in the generation of prostate cancer (PCA). Since 5-alpha-reductase inhibitors (5ARI) like finasteride (Proscar) and dutasteride (Avodart) are well demonstrated to reduce levels of DHT and have a favorable effect on the progression of BPH, the idea that such agents might also favorably affect development of PCA has been conceptually appealing for several years.
In the Prostate Cancer Prevention Trial, men aged 55 years or older (n = 18,882) with normal digital rectal examination (DRE) and serum PSA (< 3.0 ng/mL) were randomly assigned to either 5ARI (finasteride) or placebo and followed for 7 years. Men underwent prostate biopsy if an abnormal DRE or PSA elevation (> 4.0 ng/mL) occurred during follow-up. For men who were receiving 5ARI, the PSA was appropriately adjusted (measured PSA multiplied by 2.3) due to the well-known PSA-reducing effect of 5ARI treatment.
PCA was found in 18.4% of the 5ARI group, as opposed to 24.4% of the placebo group, indicating a statistically significant 25% reduction in prevalence. PCA with high Gleason scores (ie, highly aggressive) were seen significantly more frequently in the 5ARI than placebo group (37% vs 22%), but overall there was a net reduction in all PCA.
Erectile dysfunction, reduced ejaculate volume, loss of libido, and gynecomastia were more frequent in the 5ARI group; BPH and related symptoms, urinary retention, need for invasive prostate procedures, and UTI were more frequent in the placebo group. Finasteride has been demonstrated to prevent or delay the onset of PCA; for men who seek clinician’s advice on such treatment, it will be important to acknowledge the slight increase of aggressive PCA tumor incidence and other potential adverse effects that need to be weighed in the risk benefit analysis.
Thompson IM, et al. N Engl J Med. 2003;349:215-224.
Impermeable Bed Covers in Patients with Allergic Rhinitis
Sufferers of allergic rhinitis (ALR) are often sensitive to a variety of allergens, of which house-dust mites are a commonplace troublemaker. The 2 most common offending house-dust antigens, Dermatophagoides pteronyssinus and D farinae, are readily measured in samples of dust from floors and fabric. Although numerous environmental control measures have been advocated for patients with dust and mold allergy, their efficacy in producing symptom reduction is only scantily supported.
This trial included patients with ALR (n = 279) who were randomly assigned to impermeable bedding covers (which reduce house-dust mite populations) vs standard coverings (placebo). Outcomes measured included concentrations of house-dust mite antigens, as well as clinical symptoms, over 12 months’ observation.
Despite reductions in concentration of house-dust mite antigen, no clinical ly meaningful improvements in ALR symptom scores were seen. Because substantial amounts of time, energy, and economic resources are spent upon environmental manipulation for persons with allergy, these negative outcomes should stimulate reappraisal of the role of tools like impermeable mattress covers in the management of AR.
Terreehorst I, et al. N Engl J Med. 2003;349:237-246.
Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.