Curbside Consults

VOL 115 / NO 4 / APRIL 2004 / POSTGRADUATE MEDICINE

Are hypertension and bypass linked?

Q: Is there a connection between hypertension and coronary artery bypass surgery? In this case, the patient had a history of hypertension but was receiving no medical therapy at the time of his bypass. Six weeks after surgery, he presented with a blood pressure of 170/120 mm Hg. Would a beta-blocker be the treatment of choice for this patient?

Cardiologist, Illinois

A: There is no connection between hypertension and coronary artery bypass surgery. Recent-onset severe hypertension warrants evaluation for secondary hypertension. In the case you mention, careful history taking and a physical examination should be followed by routine laboratory tests, including measurement of the patient's serum potassium. A serum potassium level below 3.5 mEq/L suggests primary aldosteronism. This suspicion should be confirmed by measurement of plasma aldosterone and renin. In primary aldosteronism, the ratio of aldosterone to renin is more than 20.

The patient should also be evaluated for renovascular hypertension by giving a renogram using the angiotensin-converting enzyme (ACE) inhibitor captopril (Capoten) or enalapril (Vasotec). If the findings are unremarkable, the patient should next be evaluated for pheochromocytoma by measurement of plasma catecholamines and the diagnosis confirmed with a 24-hour measurement of urinary catecholamines and metabolites.

Patients who have coronary artery disease often have atherosclerosis in other arteries, including the renal artery. It is possible that during bypass surgery, the renal artery or one of its branches was blocked. The blockage may have triggered the renin-angiotensin-aldosterone system, causing hypertension.

If no cause for secondary hypertension is detected, the patient will probably require two or three medications to control his hypertension. The combination of a diuretic and an ACE inhibitor would be most beneficial. If this combination is insufficient, a beta-blocker should be added. If maximum doses of these drugs are insufficient, a calcium channel blocker (eg, amlodipine [Norvasc], diltiazem hydrochloride) can be added. Verapamil hydrochloride should not be used with a beta-blocker because the combination can cause severe bradycardia or even heart block.

Mahendr S. Kochar, MD
Professor, Department of Medicine and Department of Pharmacology and Toxicology
Medical College of Wisconsin
Milwaukee

A combination of T₃ and T₄ for hypothyroidism?

Q: I have heard that some patients with hypothyroidism do better taking a combination of triiodothyronine (T₃) and thyroxine (T₄) than T₄ replacement alone. If so, is a serum assay for free T₃ valuable in determining which patients will improve with the combination? What are the appropriate agents and doses to supply T₃ and T₄?

Primary care physician, Texas

A: Under normal circumstances, the thyroid gland primarily secretes T₄ as well as smaller amounts of T₃. T₄ is converted to T₃, the active molecule, by deiodination in peripheral tissues. T₃ is the predominantly active hormone moiety and has an affinity for the thyroid hormone receptor that is 10 times that of T₄. In general, however, the preferred treatment for primary hypothyroidism is replacement of T₄. T₄ has a long half-life (7 days), which allows for once-daily dosing and little fluctuation in serum concentration during the day. Patients treated with T₃ or preparations containing T₃ can have wide fluctuations in their serum T₃ concentration because of the rapid gastrointestinal absorption and shorter half-life of T₃.

The issue of whether to treat patients with T₄ alone or with a combination of T₃ and T₄ was addressed in a study by Bunevicius and colleagues (1). In that study, patients receiving a combination of T₃ and T₄ had slightly better mood, sense of physical well-being, and cognitive function than those receiving T₄ alone. Thyrotropin (TSH) concentrations and lipid levels were similar in both groups. However, the study was small, and many endocrinologists do not support its conclusions. A small post hoc analysis suggested that most of the improvement occurred in patients who had surgical treatment or radioablation of the thyroid and had no residual functional thyroid tissue.

A more recent small, randomized, double-blind, placebo-controlled study by Clyde and associates (2) showed no evidence of benefit in patients treated with combination therapy compared with T₄ alone. A study by Saravanan and associates (3) found that between 9% and 13% of patients with hypothyroidism who were taking T₄ replacement and had "normal" TSH concentrations had a decreased sense of psychologic well-being compared with patients who did not have hypothyroidism. However, it is becoming evident that for many patients, the accepted normal range of TSH may be too wide and that some patients feel better when their TSH concentration is in the lower end of the range (<2 microIU/mL). If after adjusting a T₄ dose to achieve such a TSH concentration the patient still does not feel perfectly well, a trial of a combination of T₃ and T₄ is reasonable. However, it is unlikely that this combination would benefit patients with autoimmune hypothyroidism.

Unfortunately, T₃ concentration is not helpful in identifying which patients might benefit from combination therapy. In the previously mentioned studies, 12.5 to 15 micrograms of T₃ was substituted for 50 micrograms of T₄. T₃ is available by itself (liothyronine sodium [Cytomel]) or in combination with T₄ (liotrix [Thyrolar]) in a ratio of 75 micrograms of T₄ to 18.75 micrograms of T₃. TSH concentration (determined 4 to 6 weeks after a dose adjustment) remains the final arbiter in assessing the adequacy of replacement.

Yehia Y. Mishriki, MD
Professor of Clinical Medicine
Pennsylvania State University
College of Medicine
Hershey

References

1. Bunevicius R, Kazanavicius G, Zalinkevicius R, et al. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med 1999;340(6):424-9
2. Clyde PW, Harari AE, Getka EJ, et al. Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. JAMA 2003;290(22):2952-8
3. Saravanan P, Chau WF, Roberts N, et al. Psychological well-being in patients on "adequate" doses of 1-thyroxine: results of a large, controlled community-based questionnaire study. Clin Endocrinol 2002;57(5):577-85

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