Naoto Azuma, Naoaki Hashimoto, Aki Nishioka and Hajime Sano

A 72-year-old-woman with polymyositis was admitted for Pseudomonas aeruginosa pneumonia in April 2008. Myositis had been stable on oral prednisolone only (10 mg/day). After the administration of antibiotics (doripenem), pneumonia improved promptly. Although subsequently she was treated with oral minocycline (MINO) intermittently for 13 months (total dosage; approximately 20000 mg) for refractory bronchitis, pneumonia frequently relapsed and she died of the pneumonia exacerbation in August 2009. The autopsy finding revealed a coal-black coloration of the thyroid parenchyma (Picture 1). Microscopic examination demonstrated prominent dark brown to black pigments that demonstrated finely positive in lipofuscin stain in the follicular cells (Picture 2). MINO-induced black thyroid (MIBT) has been considered a rare and harmless phenomenon since the first human case report in 1976 (1). Since then, over 60 cases have been published, but only four reports have described the cytopathological features (2). Miller et al (3) described the following four mechanisms of the accumulation of pigment: 1) the combination of degradation products of MINO and lipofuscin products; 2) oxidative changes in degradation products of MINO; 3) altered tyrosine metabolism, secondary to the inhibition of thyroid peroxidase (TPO) by MINO; 4) a disruption in lysosomal transport, which changes in staining characteristics of MIBT follicular epithelial cells for ubiquitin, vimentin and cytoplasmic thyroglobulin suggests. Taurog et al (4) demonstrated that the pigment might represent products of MINO oxidation by TPO, and MINO could inhibit thyroid function competitive inhibition of TPO, in vitro. Although the presence of hyperplasia, adenoma, or papillary and follicular carcinoma in MIBT specimens has been reported, no carcinogenic role has been ascribed to MINO (2). However, the etiology has not been elucidated and the clinical significance is also unclear (2, 3). In the present case, euthyroidism had been persistent and there was no evidence of the cause of the pigmentation.


References

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2. Hall AH, Bean SM. Minocycline-induced black thyroid. Diagn Cytopathol 2009 [Epub ahead of print].
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4. Taurog A, Dorris ML, Doerge DR. Minocycline and the thyroid: antithyroid effects of the drug, and the role of thyroid peroxidase in minocycline-induced black pigmentation of the gland. Thyroid 6: 211-219, 1996.