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Biomedical subjects

Leonard Wartofsky

Publications and source records attributed to Leonard Wartofsky.

14 recordsLinked to original sources

Myxedema coma.

Myxedema coma is the term given to the most severe presentation of profound hypothyroidism and is often fatal in spite of therapy. Decompensation of the hypothyroid patient into a coma may be precipitated by a number of drugs, systemic illnesses (eg, pneumonia), and other causes. It typically presents in older women in the winter months and is associated with signs of hypothyroidism, hypothermia, hyponatremia, hypercarbia, and hypoxemia. Treatment must be initiated promptly in an intensive care unit setting. Although thyroid hormone therapy is critical to survival, it remains uncertain whether it should be administered as thyroxine, triiodothyronine, or both. Adjunctive measures, such as ventilation, warming, fluids, antibiotics, pressors, and corticosteroids, may be essential for survival.

Aged↗

Overt and 'subclinical' hypothyroidism in women.

UNLABELLED: Thyroid disease in general, and hypothyroidism in particular, are very common in women. In the USA, the most common cause of primary thyroid deficiency is on an autoimmune basis due to lymphocytic (Hashimoto) thyroiditis. Because there are thyroid hormone receptors in virtually every tissue of the body, the manifestations of hypothyroidism are varied, but problems with abnormal menses, conception, fertility, and pregnancy can be especially troubling in young women. The single most important diagnostic test is measurement of serum thyrotropin (TSH). The overwhelming majority of patients with hypothyroidism are treated with a single daily dose of synthetic levothyroxine with the goal of therapy being restoration of a normal metabolic state with return of the TSH level down to the range of 0.5 to 1.5 mlU/L. "Subclinical" hypothyroidism refers to those patients with early or mild thyroid hypofunction manifested as slight elevations of thyrotropin (approximately 4-10 mlU/L) although serum thyroxine (T4) and triiodothyronine (T3) levels are within their reference ranges. The entity is somewhat controversial in regard to its consequences if left untreated, and whether or not we should be screening patients, at least susceptible populations, for the condition. Reports indicate an association between subclinical hypothyroidism and poor outcomes of pregnancy, as well as dyslipidemias, atherogenesis, and increased mortality in the long term. We believe these consequences are sufficiently compelling to warrant screening and treatment with levothyroxine when found to halt progression to overt hypothyroidism, and improve symptoms, pregnancy outcomes, lipid abnormalities, and cardiovascular function. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that hypothyroidism is a common disease in women, has many protean manifestations, and can be successfully diagnosed and treated; explain that the condition of subclinical hypothyroidism can be diagnosed and if treated can prevent many untoward complications; and state that there should be heightened awareness of the disease so that proper screening tests can be performed.

Female↗

Optimal thyrotropin level: normal ranges and reference intervals are not equivalent.

This paper marshals arguments in support of a narrower, optimal or true normal range for thyrotropin (TSH) of 0.4 to 2.5 mIU/L, based on clinical results and recent information on the relatively stable and narrow range of values in patients without thyroid disease. The terminology used for TSH results is clarified in an attempt to help physicians interpret, explain, and respond to TSH test results for their patients.

Circadian Rhythm↗

The evidence for a narrower thyrotropin reference range is compelling.

Debate and controversy currently surround the recommendations of a recent consensus conference that considered issues related to the management of early, mild, or so-called subclinical hypothyroidism and hyperthyroidism. Intimately related to the controversy is the definition of the normal reference range for TSH. It has become clear that previously accepted reference ranges are no longer valid as a result of both the development of more highly sensitive TSH assays and the appreciation that reference populations previously considered normal were contaminated with individuals with various degrees of thyroid dysfunction that served to increase mean TSH levels for the group. Recent laboratory guidelines from the National Academy of Clinical Biochemistry indicate that more than 95% of normal individuals have TSH levels below 2.5 mU/liter. The remainder with higher values are outliers, most of whom are likely to have underlying Hashimoto thyroiditis or other causes of elevated TSH. Importantly, data indicating that African-Americans with very low incidence of Hashimoto thyroiditis have a mean TSH level of 1.18 mU/liter strongly suggest that this value is the true normal mean for a normal population. Recognition and establishment of a more precise and true normal range for TSH have important implications for both screening and treatment of thyroid disease in general and subclinical thyroid disease in particular.

Humans↗

Perioperative management of patients with hypothyroidism.

Hypothyroidism is a common disorder affecting the cardiovascular, respiratory, hematopoietic, and renal organ systems--each of which is particularly germane in the management of the surgical patient. In general, treatment of recognized hypothyroidism is recommended before any surgical procedure whenever possible and euthyroidism should be documented by measurement of serum TSH as part of the preoperative evaluation. Such a strategy is likely to result in better surgical outcomes with improved morbidity and mortality. One exception to treating first with thyroid hormone is the patient with angina or coronary artery disease requiring bypass grafting, angioplasty or stenting. In this setting, preoperative thyroid hormone therapy could tax the ischemic myocardium. The coronary blood flow should be addressed first, and thyroid hormone therapy initiated afterwards. The authors have emphasized the need for caution in the interpretation of low serum thyroid hormones in sick or surgical patients because of the importance of distinguishing between hypothyroidism and the "euthyroid sick syndrome." There is no clear evidence at this point to support thyroid hormone replacement in the latter patients, and it may be potentially harmful. Rather, we hold that T3 treatment of various surgical and other patients with nonthyroidal illness should be deferred until proof of its therapeutic efficacy is demonstrated.

Cardiovascular Diseases↗

Management of low-risk well-differentiated thyroid cancer based only on thyroglobulin measurement after recombinant human thyrotropin.

A multicenter study was undertaken to ascertain prevalence and significance of recombinant human thyrotropin (rhTSH)-stimulated increases in thyroglobulin (Tg) levels in thyroid cancer patients classified to be at low risk for recurrence. Patients were eligible for enrollment if they had undergone near-total or total thyroidectomy and remnant ablation between 1-10 years prior to enrollment and had received thyroxine suppression therapy (THST) with a TSH level of < 0.5 mU/L and Tg level less than or equal to 5 ng/mL within the prior year. Patients with anti-Tg antibodies, distant metastases, or other evidence of residual disease were excluded. Four hundred eighty-six patients were entered into the study, and 300 were considered eligible and comprise the study population. TSH, Tg, and anti-Tg antibody levels were obtained at baseline, followed by intramuscular injection of 0.9 mg of rhTSH on days 1 and 2 and measurement of Tg on day 5. After rhTSH, 53 patients (18%) had elevations in Tg of at least 2 ng/mL, including 33 patients (11%) with increases from baseline of equal to or greater than 5 ng/mL. Patients with an initial advanced stage of disease were more likely to display elevations in Tg after rhTSH. One third of those with stage III disease displayed elevations in Tg of 2 ng/mL or more. Patients within 5 years of thyroidectomy were as likely to display elevations in rhTSH-stimulated Tg as those 5-10 years from surgery. In conclusion, these data suggest rhTSH-stimulated Tg testing without scan may be a useful tool in the follow-up of patients with low-risk thyroid cancer, and may serve to identify patients previously thought free of disease on the basis of undetectable Tg levels while undergoing THST. A strategy is presented for incorporation of this approach into the management of patients with low-risk well-differentiated thyroid cancer.

Adult↗

Dosimetrically determined doses of radioiodine for the treatment of metastatic thyroid carcinoma.

In the absence of definitive studies relating radioiodine dose to outcomes, selection of a dose of radioiodine to treat metastatic thyroid carcinoma is problematic, and several approaches have been used. These include empiric fixed doses and doses used on dosimetric approaches specific for each patient. This paper is a review of the rationale and technique for dosimetrically-determined doses of radioiodine for the treatment of metastatic thyroid carcinoma. This review (1) discusses the alternatives for selection of a dose, (2) discusses the two major approaches for determining radioiodine doses dosimetrically, (3) briefly reviews several modifications of these approaches, (4) reviews the literature regarding the results, (5) discusses the side effects of these different approaches, and (6) concludes with recommendations for patient management and future research. This review does not address use of dosimetrically-determined doses of radioiodine for the initial ablation of thyroid tissue postoperatively.

Carcinoma↗

Levothyroxine: therapeutic use and regulatory issues related to bioequivalence.

Levothyroxine is the overwhelming choice of clinicians for the treatment of hypothyroidism and for the suppression of goitre and thyroid nodules in selected cases. The monitoring of serum levels of thyroid stimulating hormone is necessary for appropriate dosage adjustment of levothyroxine. Levothyroxine has a narrow therapeutic index: both underdosage (subclinical hypothyroidism) and excessive dosage (subclinical hyperthyroidism) are associated with adverse symptoms and pathophysiological effects and are to be avoided. The consequent necessity for careful titration of doses has had an impact on the issue of switchability, or bioequivalence, of the various marketed levothyroxine products. In this article, the basis for concern about currently accepted standards of the FDA for pharmacological bioequivalence are examined in the context of levothyroxine. The history and status of the recent request by the FDA for a new drug application for all levothyroxine products, and its impact on the market leader Synthroid, is also discussed.

Biological Availability↗