Citations

The isolated, perfused rat liver has been used to study the metabolic pathways of I131-labeled l-thyroxine (T4), l-3,5,3'-triiodothyronine (T3), their partially deiodinated derivatives, and d-thyroxine. l-Thyroxine was metabolized less rapidly than the l-thyronines with fewer iodine atoms. l-T4 accumulated in the liver more rapidly than l-3,3',5'T3 or l-3,3'T2 but less rapidly than l-3,5,3'T3 or d-T4. Conjugation with glucuronic acid proceeded in the liver most rapidly from 3,5,3'T3 and at much lower rates from d-T4, l-T4, l-3,3',5'T3, and l-3,3'-diiodothyronine (T2). Deiodination of l-3,3',5'T3 and l-3,3'T2 proceeded most rapidly.

Dogs with biliary fistulas metabolized triiodothyronine rapidly to inorganic iodide, as did normal dogs. The amount and distribution of I131 compounds in the urine were not greatly altered by withdrawal of the bile, which contained about one-fourth of the I131 administered. Dogs with biliary obstruction excreted more of compounds b, iodide and the conjugate than normal dogs. The absence of enterohepatic circulation of metabolic products of triiodothyronine usually excreted in the bile did not appreciably alter the products or rate of metabolism of triiodothyronine. Some of the same products of triiodothyronine appeared in both bile and urine but there was very little inorganic iodide in the bile and much more of the glucuronide and the water-soluble, column residual fraction.

The total amount of I131-containing compounds excreted in the urine of the dehepatized dog receiving either radioactive thyroxine or triiodothyronine is similar to that of the normal dog receiving similar injections. The important role of the liver in the deiodination of thyroxine and triiodothyronine is indicated by the failure of the liverless animal to convert these compounds to inorganic iodide as completely as does the normal dog. Only a small percentage of the I131 compounds excreted by the liverless dog appears as inorganic iodide. The most abundant iodine compound in the urine of the dehepatized dog is a conjugate of thyroxine when thyroxine is injected, and an unidentified compound, b, when triiodothyronine is injected.

Dogs excreted the same compounds in the urine after injections of radioactive thyroxine whether they were normal or had a biliary fistula or biliary obstruction. Dogs with biliary fistulas excreted more of the conjugate in the urine than did normal dogs. Dogs with biliary obstruction excreted the largest amounts of the conjugate and also showed increased levels of the conjugate in the blood. All the changes were minor, however, compared to those found after hepatectomy. No evidence was found for conversion of thyroxine to triiodothyronine or tetraiodothyroacetic acid, but the present studies would not exclude the possibility that these substances are rapidly transformed intermediates in the metabolism of thyroxine.

The initial description of Carney complex (CNC) in 1985 included myxomas, spotty skin pigmentation, and endocrine overactivity (of the adrenal, the pituitary, and the testis). In 1997, thyroid neoplasms were found in 3 patients with CNC and involvement of the gland in the syndrome was apparent. Herein, we describe the clinical, pathologic, and follow-up findings in 26 patients with CNC and a disorder of the thyroid gland. The patients were predominantly middle-aged women with an asymptomatic thyroid mass. Four patients had hyperthyroidism, which was caused by follicular hyperplasia in 2 patients and by toxic adenoma in 2 others. Pathologic findings included benign lesions (follicular hyperplasia, nodular hyperplasia, and follicular adenoma) in 16 patients and carcinomas (follicular or papillary) in 10 patients. The follicular carcinomas had unusual features, multifocality, bilaterality, and lymph node metastasis. The tumor was fatal in 3 of 4 patients with a tumor ≥3 cm in diameter. One patient had an unusual multifocal microscopic follicular hyperplasia. Detection and treatment of the thyroid neoplasms in patients with CNC requires long-term follow-up of patients with the syndrome.