Black Thyroid

TL;DR: Black thyroid is a benign condition characterized by the black discoloration of the thyroid gland that is typically associated with long-term minocycline therapy. It is typically asymptomatic and can be discovered incidentally during surgery or autopsy.

Abstract: Black discoloration of the thyroid gland was first reported as a side effect of minocycline, a long-acting tetracycline antibiotic, in laboratory animals in 1967.1 The first human case of black thyroid was subsequently described in 1976.2 During the following 4 decades, approximately 125 cases of black thyroid have been reported in the literature.3-5 Black thyroid is asymptomatic, so the discolored gland is typically discovered incidentally during surgery or upon autopsy.6 Notably, black thyroid cannot typically be diagnosed by fine-needle biopsy.3 On gross examination the gland has a coalblack appearance (figure 1, A), which is virtually pathognomonic for long-term minocycline therapy. However, other important causes of thyroid discoloration, such as cystic fibrosis and hereditary hemochromatosis, should be excluded.6.7 Histologically, coarse, dark-brown or black pigment granules are observed in the follicular epithelium and colloid (figure 1, B).8,9 The black, insoluble, nonfluorescent pigment is generated from minocycline by thyroid peroxidase through an oxidation reaction.2,10 Although minocycline is a competitive inhibitor of the enzyme, minocycline therapy is not associated with hypothyroidism, likely because of sufficient thyroid reserves.9-12 Despite the benign impact of minocycline on thyroid function, several studies have reported an association between black thyroid and thyroid cancer. For example, Kandil and colleagues reported finding thyroid cancer in 65% of patients with black thyroid.4 The cancer most frequently associated with black thyroid is papillary thyroid cancer (PTC), which has been observed in 30 to 39% of black thyroid cases. 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 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 eviFigure 1. A: Intraoperative photographs show black thyroid in 2 patients who received long-term minocycline therapy. The arrow marks the recurrent laryngeal nerve. B: Photomicrographs from pathology specimens of a black thyroid gland show dark-brown pigmentation within the follicular epithelium and colloid. A