Rectal thionamide administration in the setting of thyroid storm: a case report and review of the literature

Thyroid storm is a clinical diagnosis characterized by life-threatening multisystemic organ involvement in the setting of uncontrolled hyperthyroidism. Current estimates suggest a mortality rate of up to 30%. Treatment often consists of the administration of thionamide medications, iodine solution(s), corticosteroids, and beta-blockers; in extreme circumstances, both plasmapheresis and thyroidectomy are subsequent therapeutic options. Thionamides are typically administered orally, with the intent of preventing further thyroid hormone synthesis; however, in the literature, there are instances whereby oral access cannot be obtained, and alternative routes of administration are required. We present a case of a patient who presented with a thyroid storm due to lack of adherence to methimazole. During admission, he was found to have significant abdominal pain and ultimately a duodenal perforation requiring strict nil-per-os (NPO) status, due to which he was unable to receive oral thionamides. Due to the lack of availability of intravenous formulations of thionamides in the United States, this patient was treated with an enema compound of propylthiouracil for a total of five per rectum (PR) doses. He would later develop hepatocellular injury, requiring discontinuation and eventual transition to oral methimazole. The literature pertaining to alternative-route thionamide administration is scant, and therefore this case report and literature review is written to provide an up-to-date review and further educate all levels of clinicians about this infrequent (but emergent) situation.

Learning points

• Thyroid storm is a clinical diagnosis for which urgent recognition is required to prevent untoward mortality.
• Treatment for thyroid storm requires prompt administration of thionamides, iodine, corticosteroids, and beta-blockers. In extreme circumstances, treatment considerations include plasmapheresis and thyroidectomy.
• Infrequently, patients with a thyroid storm may not be able to tolerate oral medications, for which alternative routes of access are required.
• Currently, available alternatives include intravenous methimazole (in Europe and Japan), as well as both enema and suppository preparations of propylthiouracil and methimazole.

Background

First described in 1926 by Lahey as ‘the crisis of exophthalmic goiter’, thyroid storm (alternatively referred to as a thyrotoxic crisis) is a life-threatening, multisystemic manifestation of hyperthyroidism (1). Systemic involvement includes (but is not limited to) gastrointestinal, cardiovascular, and central nervous system complications. It is estimated that around 1–2% of hospital admissions for thyrotoxicosis are due to a thyroid storm (2). Diagnosis is clinical, with the Burch-Wartofsky scoring system assisting in severity; it should be noted, however, that even with early recognition, the mortality rate can be as high as 30%, with the most common cause of death being multi-organ failure. In the study by Furukawa et al. (3), however, their registry study noted a reduction in the mortality rate to 5.5% (compared to 10.9% from other nationwide assessments). A multitude of precipitating factors are responsible for a thyroid storm, which is frequently superimposed in the setting of medication non-compliance (4, 5).

Prompt treatment is necessary for this endocrine emergency. Management is multifactorial and includes the prevention of thyroid hormone production (thionamides, which include propylthiouracil and methimazole), followed by the subsequent prevention of stored thyroid hormone release (via administration of iodine-containing solutions), and blocking the peripheral effects of thyroid hormone (controlled with the administration of a beta-blocker and glucocorticoid). Recent guidelines additionally favor the administration of cholestyramine to enhance the clearance of thyroid hormones by preventing entero-reabsorption. Should the aforementioned interventions be unsuccessful or contraindicated, succeeding treatments include emergent thyroidectomy and/or plasmapheresis (6). Albeit less commonly encountered, instances arise whereby oral access is prevented, and therefore thionamide administration must be administered through alternative routes. While methimazole exists as an intravenous medication, this is not available in the United States; therefore, alternative options include rectal administration of either propylthiouracil or methimazole (7).

We report a case of a thyroid storm in a patient with non-compliance to methimazole, presenting with an acute abdomen with a perforated duodenal ulcer. Oral access was contraindicated, and therefore management included compounding rectal propylthiouracil. Furthermore, we analyze the existing literature pertaining to non-oral thionamide administration.

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Maxim John Levy Barnett, Carlo Casipit, Sri Ram Teja Sathi, and Ana Del Carmen Rivadeneira Rodriguez, Rectal thionamide administration in the setting of thyroid storm: a case report and review of the literature in Endocrinology, Diabetes & Metabolism Case Reports, DOI: https://doi.org/10.1530/EDM-24-0067, Volume/Issue: Volume 2024: Issue 3, Article Type: Research Article, Online Publication Date: 04 Sep 2024

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