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. Author manuscript; available in PMC: 2020 Sep 18.
Published in final edited form as: Horm Res Paediatr. 2019 Sep 18;92(4):276–283. doi: 10.1159/000502843

Case Series Minocycline Associated Thyroiditis

Kate Millington 1,*, Alexandra Charrow 2, Jessica Smith 1
PMCID: PMC7078063  NIHMSID: NIHMS1048629  PMID: 31533103

Abstract

Introduction:

Minocycline, a member of the tetracycline class of antibiotics, has been associated with benign thyroid pigmentation, but reports of thyroid dysfunction are sparse.

Methods:

Cases were selected via an inquiry of the electronic medical record for patients with thyroid dysfunction and the use of a tetracycline antibiotic. Non-autoimmune thyroiditis was defined as an abnormally low or suppressed thyroid stimulating hormone (TSH < 0.3 uIU/mL) and elevated free thyroxine or total thyroxine, and undetectable anti-thyroid antibodies.

Results:

Nine cases of thyroiditis without autoimmunity were identified out of 423 reviewed patients. Cases of thyroiditis occurred in adolescents ages 14 – 17 years who had been taking minocycline for six months to 4 years. In all cases, minocycline was prescribed for the treatment of acne. Four of the 9 received treatment for thyrotoxicosis with a beta-blocker (3 cases) and/or anti-thyroid drug (2 cases). Thyroiditis was symptomatic in all but one individual, who presented with painless goiter. All thyroiditis was transient and resolved after a median of 4.5 months (range 2 – 5 months). In one case, thyroiditis was followed by transient hypothyroidism.

Discussion:

Minocycline is known to cause thyroid abnormalities, although it has not been definitively linked to thyroid dysfunction. Here we report nine cases of non-autoimmune thyroiditis in adolescents receiving minocycline for acne. We recommend that minocycline exposure be considered in the differential diagnosis for thyroiditis and that patients receiving minocycline be counseled regarding the risk of thyroid dysfunction.

Keywords: thyroiditis, minocycline, tetracycline, acne

Introduction:

Minocycline, a tetracycline antibiotic, is commonly prescribed for acne vulgaris (acne) in adolescents and adults. Minocycline has several well-documented adverse effects including an association with autoimmunity, in particular, autoimmune hepatitis, drug-induced lupus, and vasculitis.[1] With long-term use it also has a propensity to deposit pigment (both iron and hemosiderin) throughout bone, skin, and soft tissue.[2] Pigmentation of the thyroid gland, ‘black thyroid’, has been noted on autopsy and postoperative pathology in patients receiving minocycline.[2–4] Early reports of black thyroid did not describe any disturbance in thyroid function,[3,5–7] however; two later cases reported an association with hypothyroidism. [8] There have been reports of thyroiditis associated with minocycline treatment in adults, although they have been in association with severe autoimmune conditions and/or with evidence of thyroid autoimmunity.[9,10] There has only been one prior report of the development of thyroiditis in patients receiving minocycline in the absence of underlying thyroid autoimmunity.[11] We report an additional nine cases of minocycline associated non-autoimmune thyroiditis.

Methods:

The Boston Children’s Hospital Electronic Medical Record was queried using the ICD-9 or ICD-10 code for thyroid disorder and tetracycline antibiotic. Results were limited to those who presented to the outpatient endocrine clinic between January 1, 2000 and July 1, 2018. Patients with thyroid cancer, congenital hypothyroidism, thyroid nodules, Trisomy 21, or type 1 diabetes mellitus were excluded. Additionally, patients who were taking medications known to affect thyroid function such as lithium salts, amiodarone, anti-seizure drugs or who had evidence of thyroid autoimmunity as reflected by the presence of thyroperoxidase (TPO) or thyroglobulin (Tg) antibodies were excluded. Patients were included if they had a thyrotropin stimulating hormone (TSH), thyroxine (T4), or free thyroxine (Free T4) level outside of the reference range at any time. Medical record abstraction was performed for subjects to confirm that they met inclusion criteria and to document symptoms, tetracycline antibiotic use, and laboratory findings. As this was a retrospective chart review, written informed consent from subjects was not required and was not acquired.

Results:

Four hundred and twenty-three patients were reviewed, of whom 23 met inclusion criteria. Of these, ten patients had evidence of subclinical hyperthyroidism defined as suppressed TSH <0.3 uIU/mL, normal free T4, and total triiodothyronine (T3). Three had subclinical hypothyroidism (TSH > 5.7 uIU/mL, normal free T4 and total T3), and one had primary hypothyroidism. Nine patients had thyroiditis, and their cases are summarized as follows (Table 1).

Table 1.

Summary of cases of minocycline associated thyroiditis.

Age Sex Minocycline
treatment
length/dose		 Indication
for
minocycline		 Ab Symptoms
and signs		 Evidence of Thyroiditis Treatment Time to
euthyroidism
1 17 yr M 11 months / 200 mg/day Acne neg Tachycardia, palpitations, myalgias, insomnia TSH 0.005 (nl 0.7–5.7 mcIU/mL) Free T4 5.21 (nl 0.8–1.9 ng/dL) Total T3 420 (nl 80–210 ng/dL) Radioiodine uptake scan 2% Propranolol 3 months
2 16 yr M 4 years / 200 mg/day Acne neg Weight loss, fatigue, palpitations, diarrhea TSH 0.005 (nl 0.36–3.7 mcIU/mL) Free T4 2.13 (nl 0.76–1.46 ng/dL) None 5 months
3 15 yr F Unknown Acne neg Mood labiality, tremors, hypertension, hyperreflexia, goiter TSH 0.005 (nl 0.7–5.7 mcIU/mL) Total T4 11.3 (nl 5.2 – 10.7 mcg/dL) Total T3 189 (nl 86–153 ng/dL) None 4 months
4 16 yr M 15 months / 100 mg/day Acne neg Weight loss, palpitations TSH 0.006 (nl 0.37–5.22 mcIU/mL) Free T4 1.91 (nl 0.7–1.9 ng/dL) Propranolol 3 months
5 17 yr F 12 months / 200 mg/day Acne neg Secondary amenorrhea TSH 0.019 (nl 0.7–5.7 mcIU/mL) Total T4 12.5 (nl 4.7 – 12.4 mcg/dL) THBR1.22 (nl 0.77– 1.16) None 2 months
6 17 yr F 6 months / 100 mg/day Acne neg Fatigue TSH 0.006 (nl 0.7–5.7 mcIU/mL) Free T4 2.34 (nl 0.8–1.9 ng/dL) Total T3 194 (nl 80–210 ng/dL) None 5 months
7 15 yr F 8 months / 100 mg/day Acne neg Weight loss, fatigue TSH 0.020 (nl 0.27–4.2 mcIU/mL) Total T4 15.6 (nl 4.6 – 12.0 mcg/dL) Methimazole 5 months
8 14 yr F 8 months / unknown Acne neg Anxiety, weight loss, sleep difficulties TSH 0.013 (nl 0.7–5.7 mcIU/mL) Free T4 4.82 (nl 0.8–1.9 ng/dL) Total T3 223 (nl 80–210 ng/dL) Radioiodine uptake scan 3% Methimazole, Atenolol 5 months
9 16 yr F Unknown / 150 mg/day Acne neg None TSH 0.030 (nl 0.34–5.6 mcIU/mL) Total T4 14.4 (nl 5.0 – 12.2 mcg/dL) Free T4 3.19 (nl 0.54–1.64 na/dL) None 5 months
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yr = year, M = male, F = female, Ab = anti-Tg and anti-TPO antibodies, neg = negative, TSH = thyroid stimulating hormone, T4 = thyroxine, nl = normal

Case 1

A 17-year-old male developed tachycardia, palpitations, myalgias, insomnia, and restlessness approximately 11 months after starting oral minocycline 200 mg daily for the treatment of acne. There was no family history of thyroid dysfunction, and the patient was not taking other medications. On examination, the thyroid was normal in size and texture, and without evidence of nodularity. Serum TSH concentration was < 0.005 uIU/mL (reference range, 0.7 – 5.7 uIU/mL), Free T4 was elevated at 5.21 ng/dL (reference range, 0.8 – 1.9 ng/dL) and total T3 was elevated at 420 ng/dL (reference range, 80 – 210 ng/dL). Anti-thyroperoxidase (anti-TPO), anti-thyroglobulin (anti-Tg), and thyrotropin receptor antibodies (TRAbs) were undetectable. Thyrotropin stimulating immunoglobulins (TSI) were likewise negative. Scintigraphy with I-123 demonstrated low uptake (4% at 4 hours and 2% at 24 hours) consistent with acute thyroiditis. The patient was treated with beta-blockade for symptomatic tachycardia. Upon discontinuation of minocycline, the patient’s symptoms resolved in one month; restoration of euthyroidism occurred by three months.

Case 2

A 16-year-old male presented with weight loss, fatigue, palpitations, and diarrhea while receiving oral minocycline 200 mg daily for four years for acne. There was no family history of thyroid dysfunction. His thyroid was of normal size, texture, and without evidence of nodularity. TSH was suppressed at < 0.005 uIU/mL (reference range, 0.358 – 3.74 uIU/mL) and Free T4 was elevated at 2.13 ng/dL (reference range, 0.76 – 1.46 ng/dL). Anti-TPO, anti-Tg, and TRAbs antibodies were undetectable. After minocycline was discontinued thyrotoxicosis improved in one week, with total T4 9.2 mcg/dL (reference range, 4.7 – 12.4 mcg/dL), thyroid hormone binding ratio (THBR) of 1.11 (reference range, 0.88 – 1.08), and T3 132 ng/dL (reference range, 80 – 210 ng/dL). TSH remained suppressed for two months after which time the patient experienced transient subclinical hypothyroidism, TSH 10.43 uIU/mL (reference range, 0.27 – 4.2 uIU/mL) and Free T4 0.92 ng/dL (reference range, 0.9 – 1.7 ng/dL). Euthyroidism was restored five months after discontinuation of minocycline.

Case 3

A 15-year-old female was found to be hypertensive, tremulous, and hyperreflexic during evaluation for mood lability. She had been taking oral minocycline for acne for an unknown duration as well as sertraline for depression and albuterol for asthma. The thyroid was palpated at 1.5 times (20–25 grams) the normal size without evidence of a focal nodule. There was a history of hypothyroidism in the patient’s mother. Serum TSH concentration was < 0.005 uIU/mL (reference range, 0.7 – 5.7 uIU/mL). T4 and T3 were both elevated at 11.3 mcg/dL (reference range, 5.2 – 10.7 mcg/dL) and 189 ng/dL (reference range, 86 – 153 ng/dL) respectively. Anti-TPO, anti-Tg, TRAbs, and TSI antibodies were not detectable. Upon discontinuation of the minocycline, the thyrotoxicosis resolved, and euthyroidism was restored by four months.

Case 4

Approximately 15 months after starting treatment with oral minocycline 100 mg daily for acne, a 16-year-old male experienced palpitations and weight loss. His thyroid was normal in size and texture without appreciable nodules. Upon evaluation, his serum TSH was suppressed to 0.006 uIU/mL (reference range, 0.370 – 5.22 uIU/mL) and Free T4 was mildly elevated at 1.91 ng/dL (reference range, 0.7 – 1.9 ng/dL). Anti-TPO, anti-Tg, TRAbs, and TSI were negative. He was treated symptomatically with beta-blockade for heart palpitations. The thyrotoxicosis resolved in three months after the discontinuation of minocycline.

Case 5

A 17-year-old female presented with biochemical evidence of thyrotoxicosis during an evaluation for secondary amenorrhea. She had begun treatment with oral minocycline 200 mg daily for acne one year earlier. Her thyroid was smooth, not enlarged, and without nodularity. TSH was suppressed to 0.019 uIU/mL (reference range, 0.7 – 5.7 uIU/mL). T4 was elevated at 12.5 mcg/dL (reference range, 4.7 – 12.4 mcg/dL) with THBR 1.22 (0.77 – 1.16). Anti-TPO, anti-Tg, TRAbs, and TSI were negative. Thyrotoxicosis resolved within two months of discontinuation of minocycline treatment. The patient was started on oral contraceptive medication and experienced regular menses.

Case 6

A 17-year-old female presented for evaluation of fatigue at which time she was found to have a suppressed TSH at 0.006 uIU/mL (reference range, 0.7 – 5.7 uIU/mL) and elevated Free T4 of 2.34 ng/dL (reference range, 0.80 – 1.9). On exam, her thyroid was normal in size, texture, and without nodules. The T3 was normal, 194 ng/dL (reference range, 80 – 210 ng/dL). Six months prior, she was started on oral minocycline 100 mg daily for acne. Anti-TPO, anti-Tg, and TRAbs were negative. Thyrotoxicosis resolved five months after the discontinuation of minocycline.

Case 7

A 15-year-old female presented with weight loss and fatigue eight months after initiating oral minocycline 100 mg daily for acne. There was a family history of hypothyroidism in the patient’s mother and maternal grandmother. Her thyroid was smooth in texture, not enlarged, and without nodularity. TSH was suppressed at 0.020 uIU/mL (reference range, 0.27 – 4.2 uIU/mL) and T4 was elevated at 15.6 mcg/dL (reference range, 4.6 – 12.0 mcg/dL). Anti-TPO, anti-Tg, TRAbs, and TSI were negative. Minocycline was discontinued, and anti-thyroid drug (methimazole) treatment was started at 10 mg three times daily. After five months, the patient’s symptoms improved, and methimazole was discontinued. The result of follow – up thyroid function testing was within normal limits. Fifteen months later she developed subclinical hypothyroidism, which spontaneously resolved after two years.

Case 8

A 14-year-old female presented with thyrotoxicosis after evaluation for anxiety, weight loss, and insomnia. Eight months prior, she had begun treatment with oral minocycline for acne. There was no family history of thyroid disease. Her thyroid was smooth, not enlarged, and without palpable nodules. TSH was suppressed 0.013 uIU/mL (reference range, 0.7 – 5.7 uIU/mL). Free T4 and Total T3 were elevated at 4.82 ng/dL (reference range, 0.8 – 1.9 ng/dL) and 223 ng/dL (reference range, 80 – 210 ng/dL) respectively. Anti-TPO, anti-Tg, and TRAbs were negative. The patient was treated with the anti-thyroid drug (methimazole) 10 mg twice daily and beta-blockade for one month. Scintigraphy with I-123 was performed ten days after the discontinuation of methimazole and demonstrated low uptake (3% at 4 hours and 1% at 24 hours) consistent with thyroiditis. Her thyrotoxic symptoms improved within one month, and the restoration of euthyroidism was documented five months later.

Case 9

A 16-year-old female presented with biochemical evidence of thyrotoxicosis during an evaluation for possible goiter. She was taking oral minocycline 150 mg daily for acne for an unknown duration. There was no family history of thyroid dysfunction. On examination, her thyroid was smooth, not enlarged, and had no nodules. TSH was suppressed 0.03 uIU/mL (reference range, 0.34 – 5.6 uIU/mL), T4 was elevated at 14.4 mcg/dL (reference range, 5.0 – 12.2 mcg/dL) and Free T4 3.19 ng/dL (reference range, 0.54 – 1.64 ng/dL). Anti-TPO and anti-Tg were negative. Minocycline was discontinued. After two months Free T4 had improved to 0.96 ng/dL (reference range, 0.8 – 1.9 ng/dL), although TSH remained < 0.01 uIU/mL (reference range 0.7 – 5.7 uIU/mL) for five months.

Discussion:

We report here nine cases of thyroiditis in adolescents receiving minocycline for the treatment of acne. Non-autoimmune thyroiditis associated with tetracycline use has been reported, and this is the largest series to date.[11]

Tetracycline antibiotics were discovered in the early 1940s, and the first in the class, aureomycin, was approved by the United States Food and Drug Administration (FDA) for clinical use in December 1948. Following the publication of the tetracycline class molecular structure in 1952, synthetic modifications of the core molecule produced compounds with increased stability and efficacy including doxycycline (FDA approved in 1967), and minocycline (FDA approved in 1971).[12,13] Tetracyclines exert their bacteriostatic effect by binding to a highly conserved site within the 30S ribosomal subunit, interfering with transfer-RNA docking, and thus preventing protein translation.[14] Oral tetracyclines, chiefly doxycycline and minocycline, are routinely used in the treatment of acne for their anti-bacterial as well as anti-inflammatory properties. Minocycline is the only FDA approved antibiotic for the treatment of moderate to severe inflammatory acne and is considered first-line therapy in combination with a topical retinoid.[15,16]

Minocycline has the greatest lipid solubility of drugs in the tetracycline class, leading to a greater ability to penetrate tissues and a more variable half-life. After prolonged use, the half-life of minocycline can vary from 12 to 23 hours due to the release of drug by bodily lipids.[17,18] In one study of patients with minocycline-induced drug rash with eosinophilia and systemic symptoms (DRESS), 6 of the 8 patients had detectable serum levels of minocycline up to 17 months after cessation of the drug. [19]

Pigmentation of multiple tissues, including skin, tooth, and bone is a well-known adverse effect of tetracyclines, minocycline in particular.[2] Pigmentation of the thyroid, so-called ‘black thyroid’, was first reported in humans in 1976 after several reports of this phenomenon in animals.[3,20] Electron microscopic analysis of the pigment revealed its presence both in colloid and within lysosomal structures in follicular epithelial cells.[3,7] In animal studies, thyroid pigmentation by minocycline was prevented by co-administration of propylthiouracil or thyroid hormone supplements. Both decrease endogenous thyroid hormone production and lead to the hypothesis that the pigmentation was linked to the synthesis of thyroid hormone.[20] This observation was further supported by studies in rats showing that minocycline administration leads to goiter, increased radioactive iodine uptake by the thyroid, and decreased thyroid hormone synthesis. [21] Taurog et al. demonstrated that incubation of minocycline with thyroperoxidase (TPO) resulted in the oxidation of minocycline and/or its metabolites and the formation of black pigment. In vitro studies with minocycline demonstrated it to be a potent inhibitor of TPO guided iodination and of coupling of monoiodotyrosine and diiodotyrosine to form thyroid hormone.[22,23] In addition to inhibition of TPO by minocycline, other proposed mechanisms of pigment deposition include (1) binding of minocycline degradation products with lipofuscin, a normally occurring intracytoplasmic pigment associated with aging, (2) acceleration and accentuation of lipofuscin development, (3) accumulation of oxidized metabolites of minocycline, and (4) lysosome dysfunction given the presence of pigment in lysosomal type structures. [7,8,24,25]

‘Black thyroid’ has been noted in patients after a wide range of tetracycline exposure as well as those in whom the drug was discontinued. Pigment deposition may occur early in the treatment course and represents a permanent alteration in the thyroid.[4,26] The relatively common finding of ‘black thyroid’ and the potential for thyroid dysregulation has led many authors to call for routine monitoring of thyroid function in patients taking tetracyclines.

Drug-associated thyrotoxicosis has been reported in patients receiving amiodarone, lithium, interferon alpha, interleukin–2, tyrosine kinase inhibitors, and checkpoint inhibitor immunotherapy. Mechanisms of drug-associated thyrotoxicosis include delivery of an increased iodine load, as is the case in amiodarone-associated thyroiditis, release of preformed thyroid hormone through direct destruction of thyroid follicular cells, and via induction of thyroid autoimmunity. [25,27–32]

To our knowledge, there have been six cases reported in the literature of thyrotoxicosis associated with minocycline treatment (Table 2). Three of these cases were reported by Pollock et al. in 2016, all of whom were otherwise healthy adolescents receiving minocycline for the treatment of acne.[11] An additional case reported by Benjamin and Calikoglu was found in a 16-year-old male receiving minocycline for acne. This was confounded by the presence of a lupus-like syndrome, arthritis of the ankles, and positive markers of autoimmunity. After discontinuing minocycline, the patient’s thyroid dysfunction and arthritis resolved, and laboratory tests normalized.[33] Tacon et al. reported a case of a 31-year-old female who presented with antibody-negative thyroiditis and right-sided nodule. Upon fine needle aspiration, cytology was suspicious for papillary thyroid carcinoma. The patient proceeded to total thyroidectomy, which revealed a ‘black thyroid’ with histologic evidence of drug-induced thyroiditis similar to that observed with amiodarone exposure.[34] Thyroiditis was noted in association with several cases of DRESS associated with minocycline, although systemic symptoms including fever and rash were also observed in these cases.[9,10]

Table 2.

Summary of cases of minocycline associated non-autoimmune thyroiditis reported in the literature.

Ref Age Sex Minocycline
treatment
length/dose		 Indication
for
minocycline		 Ab Symptoms and
signs		 Evidence of Thyroiditis Treatment Time to
euthyroidism
11 16 yr F Unknown / 200 mg/day Acne neg Fatigue, headaches, weakness, diplopia TSH 0.013 (nl 0.5–5.5 mcIU/mL) Free T4 2.4 (nl 0.9–1.7 ng/dL) Total T3 253 (nl 80–160 ng/dL) Radioiodine uptake scan 2.9% None Unknown
11 16 yr M 23 months / 200 mg/day Acne neg Fatigue, headaches, heat intolerance, weight loss, insomnia, palpitations, diarrhea TSH <0.03 (nl 0.36–4.57 mcIU/mL) Free T4 7.57 (nl 0.75–1.54 ng/dL) Radioiodine uptake scan 0.3% Methimazole Propranolol Unknown
11 16 yr M 9 months / 200 mg/day Acne neg Fatigue, heat intolerance TSH 0.01 (nl 0.36–4.20 mcIU/mL) Free T4 3.26 (nl 0.7–1.45 ng/dL) Radioiodine uptake scan 0.5% Methimazole Propranolol Persistent hypothyroidism
33 16 yr M 18 months / 100 mg/day Unknown neg Tachycardia, tremulousness, goiter TSH < 0.05 (nl 0.370–6.0 mcIU/mL) Total T4 15 (nl 4.5–12 mcg/dL) Total T3 2.8 (nl 1.0–1.7 ng/mL) Methimazole Atenolol 4 months
34 31 yr F 18 months / 100 mg/day Acne neg Palpable nodule TSH 0.011 (nl 0.36–3.5 (μIU/L) Free T4 2.4 (nl 0.82–1.96 ng/dL) None 2 months
10 38 yr F 3 weeks/ unknown Acne neg Fever, rash, eosinophilia TSH 0.02 mcIU/mL Free T4 3.7 ng/dL Normal ranges not given Prednisone Unknown
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yr = year, M = male, F = female, Ab = anti-Tg and anti-TPO antibodies, neg = negative, TSH = thyroid stimulating hormone, T4 = thyroxine, nl = normal

In this case series, we report nine additional cases of thyroiditis following minocycline treatment for acne, which is the largest reportable series to date. Similar to previous cases, these patients developed thyroiditis after a wide range of minocycline exposure. In all cases, thyroiditis resolved by five months after its discontinuation except for one case in which transient hypothyroidism developed.

The concentration of minocycline and/or its metabolites in the thyroid have been demonstrated by the observation of ‘black thyroid’ in patients taking minocycline, and the histologic effect on the thyroid appears similar to that induced by amiodarone exposure.[34] Although further studies are needed to completely elucidate the mechanism of minocycline-induced thyroiditis, we propose that minocycline concentrates in the thyroid follicular cells where it and/or its metabolites are oxidized by TPO leading to cytotoxic damage and release of preformed thyroid hormone. This appears to be a self-limiting process that resolves after discontinuation of the drug. Treatment with anti-thyroid medications which inhibit thyroid hormone formation may not be warranted, and in the two reported cases, methimazole failed to hasten resolution of thyroiditis. Similar to other known mechanisms of drug-induced thyroiditis, minocycline induced thyroiditis is not dependent on the presence or development of thyroid autoimmunity. Minocycline causes non-autoimmune thyroiditis and may do so more frequently than previously appreciated. Exposure to minocycline should be considered in the differential of a patient presenting with thyroiditis. If discovered, minocycline associated thyroiditis should be treated similar to other forms of drug induced thyroiditis, with discontinuation of minocycline, symptomatic management with beta-blockade if indicated, and laboratory monitoring of thyroid function.

Our report is limited by its retrospective nature and single study site. Follow up information was limited, especially as most patients had a resolution of their symptoms and did not return for further evaluation. Although we have noted an association between minocycline use and the development of thyroiditis, we cannot establish causality in this observational study. Further prospective studies are needed to determine the incidence of thyroiditis in patients taking minocycline as well as investigate a potential mechanism.

Given the propensity of minocycline to cause other autoimmune syndromes, it is possible that it affects thyroid function via an underlying immune mechanism. However, in the absence of other symptoms, it is difficult to isolate the minocycline effect from auto-immune thyroiditis unrelated to drug exposure. Further controlled prospective studies are needed to address the development of autoimmune thyroiditis in patients taking minocycline.

Nearly all adolescents are affected by some degree of acne, and in up to 20% their acne is moderate or severe.[35] Oral minocycline is first-line therapy for moderate to severe acne and represents up to half of all oral antibiotics prescribed for this indication.[16,36] Estimates of adverse events with minocycline use are as high as 72 per million prescriptions, compared to 13 per million prescriptions for doxycycline, another commonly prescribed tetracycline. Many of the adverse events associated with minocycline are a mild gastrointestinal and vestibular disturbance, however, there are reports of fatal reactions including DRESS and hepatitis.[37,38] Minocycline is known to concentrate in the thyroid leading to ‘black thyroid’, which was thought to be a benign finding. However, we have observed that minocycline can also lead to non-autoimmune thyroiditis in adolescents at any time during the treatment course. Although there is not enough evidence to recommend routine monitoring of thyroid function, we do suggest that a history of minocycline exposure be elicited in any patient presenting with thyrotoxicosis while taking minocycline.

Conclusion:

Long known to cause thyroid pigmentation, it is hypothesized that minocycline can also lead to non-autoimmune thyroiditis. Acne is a common condition in adolescents for which minocycline is utilized. Clinicians prescribing minocycline should be aware of its potential to cause thyroiditis and should counsel patients regarding the symptoms of thyrotoxicosis. Patients presenting with thyroiditis should also be queried about the history of minocycline use. Further studies are needed to determine the cause and frequency of minocycline-induced thyroiditis.

Established Facts:

  • Several medications are known to cause non-autoimmune thyroiditis.

  • Minocycline causes thyroid pigmentation, “black thyroid”, which is thought to be a benign occurrence.

Novel Insights:

  • Minocycline is associated with non-autoimmune thyroiditis.

  • Clinicians prescribing minocycline should monitor patients for symptoms of thyroid dysfunction.

Acknowledgments

Funding Sources: KM was supported by NIH Grant T32-DK007699.

Footnotes

Statement of Ethics: The study was approved by the local ethics committee, the Institutional Review Board of Boston Children’s Hospital.

Disclosure Statement: The authors have no conflicts of interest to declare.

†

Pediatric Endocrine Society (PES) member

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