Black thyroid

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 coal-black 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

Figure 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.

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

Figure 2.

Papillary thyroid cancer (arrow) is seen in the context of black thyroid. Note the pink color of the tumor compared to the dark staining in the rest of the gland.

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 evidence implicating minocycline as a potential human carcinogen,¹⁷ suggesting that the drug may not directly contribute to malignant transformation in patients with black thyroid. Instead, the correlation between thyroid cancer and black thyroid may result from the observation that black thyroid is usually discovered incidentally in patients undergoing thyroidectomy for other reasons. Therefore, these patients may be more likely than the general population to harbor a thyroid neoplasm.

Because of the relative paucity of data, the clinical implications for black thyroid remain unclear. Although black thyroid is strongly correlated with minocycline therapy, the proportion of patients who develop black thyroid after receiving minocycline is not known. Despite several case reports of PTC occurring in the context of black thyroid, there are no current recommendations that patients treated with minocycline therapy undergo additional screening for PTC.

For black thyroid that is discovered incidentally during surgery, Kandil and colleagues recommend thorough pathologic examination of a biopsy specimen for PTC.⁴ Discovery of PTC necessitates removal of the gland; however, there are currently no recommendations that patients with black thyroid but without evidence of thyroid cancer on pathology undergo prophylactic thyroidectomy.⁶ Other recommendations include the careful monitoring of patients receiving minocycline for thyroid enlargement, and discontinuing the drug if discoloration develops in any part of the body.^7,18

In conclusion, black thyroid is a striking finding in patients who have received long-term minocycline therapy, although the clinical significance of this finding remains unclear. Further research is needed to establish whether a true link exists between black thyroid and thyroid cancer and to direct management of incidentally discovered black thyroid.