Black thyroid gland and tracheal cartilage
- 1 Division of Internal Medicine, Carle Foundation Hospital, Urbana, Illinois, USA
- 2 Pulmonary and Critical Care, Carle Illinois College of Medicine, Urbana, Illinois, USA
- 3 Otolaryngology, Carle Foundation Hospital, Urbana, Illinois, USA
- Correspondence to Dr Audrey Lam; audrey.lam@carle.com
Abstract
A woman in her 70s with a history of chronic minocycline use presented with complaints of a non-tender posterior neck mass. A thyroid gland ultrasound showed a highly suspicious right thyroid nodule. A total thyroidectomy revealed darkened discolouration of the thyroid gland and tracheal cartilage. The pathology report showed dark brown granules representing melanin. Chronic minocycline usage is known to cause pigmentation of nails, teeth, bones and the thyroid gland. Our case highlights the importance of recognising that long-term use of minocycline can cause discolouration of the thyroid and tracheal cartilage. Current case studies do not show any adverse health effects associated with black thyroid and tracheal cartilage. For patients who are to undergo neck surgery, physicians need to be aware of this side effect, and that further intervention, such as surgical resection, may not be required.
Background
Minocycline is a tetracycline derivative antibiotic commonly used to treat severe acne, rosacea and other inflammatory skin disorders. Pigmentation is a known side effect of minocycline use. It has been demonstrated that pigment is formed through the oxidation of minocycline by the enzyme thyroid peroxidase.1 This leads to discolouration of the skin, nails, teeth, bones, oral mucosa and the thyroid gland. It has been reported that a cumulative dose of greater than 100 g is thought to cause hyperpigmentation; although, skin and oral pigmentation caused by minocycline may occur regardless of the time or amount of drug administered.2
Black thyroid is a rare pigmentation change observed in patients taking chronic minocycline and rarely extends beyond the trachea. Our report demonstrates that it is important to recognise that black thyroid and black tracheal cartilage are associated with the long-term use of minocycline. There are no adverse effects related to black thyroid and black tracheal cartilage, and a surgical procedure is not required for the discoloured thyroid gland and tracheal cartilage in a patient with a history of long-term minocycline use.
Case presentation
A woman in her 70s presented with a complaint of a posterior neck mass. The patient had a history of chronic minocycline use, chronic sinusitis and hypothyroidism. The mass had been presented for the past year and had not changed in size. The mass was not tender. She denied any associated symptoms such as dysphagia, odynophagia, difficulty breathing, voice changes, fever, chills, night sweats or unintentional weight loss. The patient had a strong family history of cancer, including non-melanoma skin cancer, lymphoma and leukaemia. She did not have any personal history of cancer. She had been taking minocycline (100 mg/day) intermittently for 4 years for the treatment of acne vulgaris.
The patient’s temperature was 97.9°F, blood pressure 138/68 mm Hg, pulse 61 beats per minute, respiratory rate 18 breaths per minute and oxygen saturation 97% on room air. She was in no apparent distress. No stridor, stertor, accessory muscle use or drooling was appreciated. Her voice was intact with non-laboured respirations. Cranial nerves II–XII were grossly intact. The oral cavity showed no gross tonsillar hypertrophy, and no lesions were visualised. The trachea was midline, and no palpable thyroid nodules were appreciated. A mobile, posterior neck mass was located in the midline overlying the cervical spine. No cervical or supraclavicular lymphadenopathy. No rash or lesions on exposed skin.
Complete blood count showed a white blood cell count of 6.18 x 109/L, haemoglobin 13.0 g/L and platelet 272 x 109/L. A comprehensive metabolic panel showed a sodium of 134, calcium 9.1, alkaline phoshatase 67 and creatinine 0.9, thyroid stimulating hormone 2.47 and parathyroid hormone 97 (normal 9–77 pg/mL). An ultrasound of the neck showed a 1.4 cm hypoechoic area with a branch-like extension that was incompletely visualised.
Investigations
CT of the soft tissue neck with contrast revealed a 2.4 cm heterogenous partially calcified nodule within the right lobe of the thyroid. An ultrasound of the thyroid gland showed a highly suspicious right thyroid nodule (figure 1). Ultrasound-guided biopsy of the thyroid gland was suspicious for papillary thyroid carcinoma. The patient underwent a total thyroidectomy, which revealed darkened discolouration of the thyroid gland (figure 2A) and the tracheal cartilage (figure 2B). The final pathology of the surgical specimen demonstrated papillary thyroid carcinoma, encapsulated with focal capsular invasion, with no vascular invasion. There are dark brown granules present within the thyroid gland (figure 3).
Ultrasound of the thyroid revealed a 2.9 cm solid, hypoechoic, irregular right thyroid nodule, which is highly suspicious for malignancy.
(A) Gross image of the resected thyroid gland showing multiple darkened discolourations. (B) Gross image of the tracheal cartilage demonstrating darkened colouration similar to the thyroid gland.
A histological image of the thyroid gland with dark brown granules in the follicular epithelium.
Differential diagnosis
After further investigation of the patient’s medical history, it was found that the patient had long-term minocycline usage. Given the biopsy, showing melanin deposits seen in the pathological report and previously reported case report, this finding was likely from minocycline.
Treatment
The darkened discolouration of the thyroid gland and tracheal cartilage is secondary to a history of chronic minocycline use. Given the benign findings of the black tracheal cartilage, no further additional workup is required. However, a biopsy should be considered if the patient is at high risk or develops new symptoms.
Outcome and follow-up
The patient underwent total thyroidectomy for papillary thyroid carcinoma. She initially reported mild dysphagia and hoarseness following the intervention, which had improved at her most recent postoperative visit. The surgical neck incision healed well. She followed up with radiation oncology for possible radioactive iodine treatment following thyroidectomy. According to the American Thyroid Association, the patient was in a low-risk group for recurrence, and recommendations for adjuvant radioactive therapy are controversial in this group. Per guidelines, recommendations include surveillance with monitoring thyroglobulin level and follow-up imaging of the neck.
Although a definitive histological sample of the tracheal cartilage was not established, her history of long-term use of minocycline strongly suggested the diagnosis of minocycline-induced black thyroid and black tracheal cartilage.
Discussion
Black thyroid is a rare pigmentation change observed in patients taking chronic minocycline. It was discovered in laboratory animals in 1967 and the first human case of black thyroid was described in 1976. Since then, there have been more than 125 cases of black thyroid reported in the literature.3 Clinically, a black thyroid does not affect thyroid function, and only a few cases reported minocycline-induced hyperthyroidism. Black thyroid is often discovered during neck surgery or autopsy. On gross examination, it appears to have a coal-black appearance. Histologically, minocycline-included pigmentation presents as dark brown granules in the follicular epithelium and colloid, which is a melanin-like substance.4 When a black thyroid is incidentally discovered, the differentials should include cystic fibrosis, haemochromatosis, haemorrhage and melanin-producing medullary thyroid carcinoma. Some reports show a high rate of thyroid cancer (30%–65%) in those with black thyroids, such as papillary thyroid cancer; however, causation has not been established.5 It is recommended that if a black thyroid is incidentally found with a thyroid mass and a patient has a history of minocycline use, the surgeon should prompt a thyroid biopsy to rule out papillary thyroid cancer.6
The trachea is surrounded by approximately 14–16 hyaline cartilage rings. The hyaline cartilage has a pearly blueish-white tone. The presence of black pigmentation of the trachea can be seen with bronchoscopy.7 Hyperpigmentation of the airway can be seen with multiple aetiologies and is often benign such as congenital disease, inborn errors of metabolism and environmental exposures. It can also be seen with endobronchial metastases from malignant melanoma. Only one reported case found black thyroid, thyroid cartilage, cricoid cartilage and trachea during reconstructive surgery for hypopharyngeal squamous cell carcinoma.8 Postoperative histological findings confirmed black discolouration, with deposits of dark brown granules in the thyroid, trachea, thyroid cartilage and cricoid cartilage. The patient took 18 months of minocycline for the treatment of prurigo chronica multiformis. That case report demonstrated that chronic use of minocycline can extend from the thyroid to the surrounding structures such as thyroid cartilage, cricoid cartilage and the trachea.
Our case highlights the importance of recognising that black thyroid and black tracheal cartilage can be associated with the long-term use of minocycline and current case studies do not show any adverse health effects associated with a discoloured thyroid gland. For patients who are to undergo neck surgery, physicians need to be aware that minocycline can cause discolouration of the thyroid gland and tracheal cartilage, and that further intervention, such as surgical resection, may not be required.
Patient’s perspective
After I underwent a thyroidectomy for papillary thyroid cancer, the surgeon said that everything had gone well. This, of course, was a huge relief. However, the next day I was notified that the surgeon had mentioned that she saw an unusual black colouration on my thyroid and trachea and that she was sending photographs to a pulmonologist to see if anything further needed to be assessed. This was very concerning. We googled ‘black thyroid’ and discovered a number of articles in medical journals linking such black colouration to patients who had taken minocycline. Minocycline received US Food and Drug Administration approval in 1971. I knew that I had been prescribed some form of tetracycline for skin problems starting around that time and for a number of years afterwards, but the records from 50 years ago were no longer available to me. We shared this information with my surgeon along with links to several journal articles about this phenomenon. My surgeon’s staff then dug deep into my medical records and found that I had taken minocycline for at least 3 years, several decades ago. My surgeon shared this information and links to the articles, which included photographs, with the pulmonologist. Both physicians concluded that the black colouration on my thyroid and trachea was consistent with photos found in other medical journal articles that addressed abnormal colouration associated with minocycline use. When my surgeon shared the photos with me, we found them shocking. I’m very glad that there was evidence that this was not likely to be anything alarming. Later, someone reminded us that she had had a similar experience with short term minocycline use as a young adult. In her case, her lips and tongue turned bluish black. She stopped the medication immediately and the discolouration eventually went away. I am happy we know about this now in case any of my other organs turn up with this colouration. Now that I am not worried about it, I kind of enjoy sharing this story with my other physicians and medical professionals, most of whom have never heard of this phenomenon.
Learning points
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To recognise that black thyroid and black tracheal cartilage are associated with the long-term use of minocycline.
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No adverse effects related to black thyroid and black tracheal cartilage.
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Surgical procedure is not required for the discoloured thyroid gland and tracheal cartilage in a patient with a history of long-term minocycline use.
Ethics statements
Patient consent for publication
Footnotes
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Contributors AL wrote the case report with review from KC and BK. KC performed the thyroidectomy.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.
References
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