Oxyphilic (Hürthle Cell) Adenoma Arising in a Black Thyroid Gland

Dm, Faddis; Pj, Daroca; Et, Krementz

doi:10.1097/00007611-199008000-00031

Cited by 7 publications

(6 citation statements)

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“…The resulting prolonged growth stimulus to thyroid follicular cells is thought to provide selective pressure for transformation (34). The reports of human thyroid cancer associated with MN therapy are consistent with this hypothesis (8)(9)(10)(11).…”

Section: Discussionsupporting

confidence: 64%

“…Anti-thyroid effects observed in rodents include goiter and inhibition of thyroid hormone synthesis (7). MN use has also been associated with induction of thyroid cancer in humans (8)(9)(10)(11). In a previous study (12), we described a causative role for thyroid peroxidase (TPO), the key enzyme in thyroid hormone synthesis, in formation of the MN-derived black pigment in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Mechanism for the Anti-Thyroid Action of Minocycline

Doerge

Divi

Deck

et al. 1997

Chem. Res. Toxicol.

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Administration of minocycline (MN), a tetracycline antibiotic, produces a black pigment in the thyroids of humans and several species of experimental animals and antithyroid effects in rodents. We have previously shown that these effects appear to be related to interactions of MN with thyroid peroxidase (TPO), the key enzyme in thyroid hormone synthesis. In the present study, the mechanisms for inhibition of TPO-catalyzed iodination and coupling reactions by MN were investigated. MN was stable in the presence of TPO and H2O2, but adding iodide or a phenolic cosubstrate caused rapid conversion to several products. TPO-dependent product formation, characterized by on-line LC-APCI/MS and 1H-NMR, involved oxidative elimination to form the corresponding benzoquinone with subsequent dehydrogenation at the aliphatic 4-(dimethylamino) group. Addition of thiol-containing polymers (bovine serum albumin or thiol-agarose chromatographic beads) had a minimal effect on MN oxidation by TPO, but substantially reduced product formation and produced concomitant losses in free thiols. Covalent bonding through a thioether linkage of a reactive intermediate, the benzoquinone iminium ion, was inferred from these findings. Iodide- and phenolic cosubstrate-dependent oxidation of tetracycline to demethylated and dehydrogenated products was also observed, although at a slower rate than MN. The products and kinetics observed with MN were consistent with oxidation of MN by either the enzymatic iodinating species formed by reaction of TPO compound I with iodide or phenoxyl radicals/cations generated by TPO-mediated oxidation of a phenolic cosubstrate. The proposed reaction mechanism is consistent with alternate substrate inhibition of TPO-catalyzed iodination of tyrosyl residues in thyroglobulin (Tg) by MN, as previously reported. Furthermore, the observed phenoxyl radical-mediated oxidation of MN is consistent with its previously reported potent inhibition of the coupling of hormonogenic iodotyrosine residues in Tg in the reaction that forms thyroid hormones. The proposed reaction mechanism also implicates a reactive benzoquinone iminium ion intermediate that could be important in toxicity of MN.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Mechanism for the Anti-Thyroid Action of Minocycline

Doerge

Divi

Deck

et al. 1997

Chem. Res. Toxicol.

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“…Similarly, other reports have shown black thyroid in association with follicular carcinoma, Hürthle cell adenoma, and nodular hyperplasia. 5,6,12 Our series, to the contrary, reveals no neoplasms during a maximum follow-up period of 20 years.…”

Section: Discussioncontrasting

confidence: 61%

Black thyroid: A collaborative series

Hecht

Wenig

Sessions

1999

Otolaryngol.--head neck surg.

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“…4,7,13,14 Other histologic types of cancer have been observed in patients with black thyroid, including oncocytic (Hürthle cell) carcinoma and follicular carcinoma, although these tumors remain less common than PTC. 4,5,15,16 Despite an apparent elevation in the incidence of thyroid cancer among patients with black thyroid, PTC found in patients with black thyroid does not appear to be more aggressive than PTC in patients without black thyroid. 4 Furthermore, there is no current evi- dence implicating minocycline as a potential human carcinogen, 17 suggesting that the drug may not directly contribute to malignant transformation in patients with black thyroid.…”

Section: Black Thyroid Thyroid and Parathyroid Clinicmentioning

confidence: 98%

“…It is notable that in cases of black thyroid with PTC there is decreased pigmentation of malignant cells compared to the surrounding tissue (figure 2). 4,7,13,14 Other histologic types of cancer have been observed in patients with black thyroid, including oncocytic (Hürthle cell) carcinoma and follicular carcinoma, although these tumors remain less common than PTC 4,5,15,16…”

mentioning

confidence: 99%