Myxoedema coma caused by immunotherapy-related thyroiditis and enteritis

Summary Thyroid dysfunction is among the most common immune-related adverse reactions associated with immune checkpoint inhibitors. It most commonly manifests as painless thyroiditis followed by permanent hypothyroidism. This usually causes mild toxicity that does not interfere with oncological treatment. In rare instances, however, a life-threatening form of decompensated hypothyroidism called myxoedema coma may develop. We present a case of myxoedema coma in a woman in her sixties who was treated with a combination of CTLA-4 and PD-1 immune checkpoint inhibitors; for stage four malignant melanoma. She became hypothyroid and required thyroxine replacement after an episode of painless thyroiditis. Six months after the initial diagnosis of malignant melanoma, she presented to the emergency department with abdominal pain, profuse diarrhoea, lethargy and confusion. She was drowsy, hypotensive with a BP of 60/40 mmHg, hyponatraemic and hypoglycaemic. Thyroid function tests (TFTs) indicated profound hypothyroidism with a TSH of 19 mIU/L, and undetectable fT3 and fT4, despite the patient being compliant with thyroxine. She was diagnosed with a myxoedema coma caused by immune-related enteritis and subsequent thyroxine malabsorption. The patient was treated with i.v. triiodothyronine (T3) and methylprednisolone in the ICU. While her clinical status improved with T3 replacement, her enteritis was refractory to steroid therapy. A thyroxine absorption test confirmed persistent malabsorption. Attempts to revert to oral thyroxine were unsuccessful. Unfortunately, the patient’s malignant melanoma progressed significantly and she passed away four months later. This is the first reported case of myxoedema coma that resulted from two distinct immune-related adverse reactions, namely painless thyroiditis and enterocolitis. Learning points Myxoedema coma, a severe form of decompensated hypothyroidism is a rare immunotherapy-related endocrinopathy. Myxedema coma should be treated with either i.v. triiodothyronine (T3) or i.v. thyroxine (T4). Intravenous glucocorticoids should be co-administered with thyroid hormone replacement to avoid precipitating an adrenal crisis. Thyroid function tests (TFTs) should be monitored closely in individuals with hypothyroidism and diarrhoea due to the risk of thyroxine malabsorption. A thyroxine absorption test can be used to confirm thyroxine malabsorption in individuals with persistent hypothyroidism.

A case of thyrotoxicosis-induced anemia in a patient with painless thyroiditis

Background There have been several reports of secondary anemia associated with Graves’ disease. There are no reports of secondary anemia resulting from thyrotoxicosis due to painless thyroiditis (silent thyroiditis). We report the case of a patient with pancreatic diabetes who developed anemia caused by thyrotoxicosis due to painless thyroiditis. Case presentation The patient was a 37-year-old man who visited the hospital complaining of fatigue, palpitations, and dyspnea. His hemoglobin was 110 g/l (reference range, 135–176), and mean corpuscular volume was 81.5 fl (81.7–101.6). His free thyroxine (FT4) was high, at 100.4 pmol/l (11.6–21.9); the free triiodothyronine (FT3) was high, at 27.49 pmol/l (3.53–6.14); TSH was low, at < 0.01 mIU/l (0.50–5.00); and TSH receptor antibody was negative. Soluble IL-2 receptor (sIL-2R) was high, at 1340 U/ml (122–496); C-reactive protein (CRP) was high, at 6900 μg/l (< 3000); and reticulocytes was high, at 108 109 /l (30–100). Serum iron (Fe) was 9.5 (9.1–35.5), ferritin was 389 μg/l (13–401), haptoglobin was 0.66 g/l (0.19–1.70. Propranolol was prescribed and followed up. Anemia completely disappeared by 12 weeks after disease onset. Thyroid hormones and sIL-2R had normalized by 16 weeks after onset. He developed mild hypothyroidism and was treated with L-thyroxine at 24 weeks. Conclusions This is the first case report of transient secondary anemia associated with thyrotoxicosis due to painless thyroiditis. The change in sIL-2R was also observed during the clinical course of thyrotoxicosis and anemia, suggesting the immune processes in thyroid gland and bone marrow.

A Case of Thyrotoxicosis-induced Anemia After the Onset of Painless Thyroiditis in a Patient With Pancreatic Diabetes Mellitus: Profile of Hemoglobin, Thyroid Hormones, Soluble IL-2 Receptor, LDL-C, HDL-C and Liver Function.

Background: There have been several reports of secondary anemia associated with Graves' disease. There are no reports of secondary anemia resulting from thyrotoxicosis due to painless thyroiditis (silent thyroiditis). We report the case of a patient with pancreatic diabetes who developed normocytic anemia caused by thyrotoxicosis due to painless thyroiditis.Case presentation: The patient was a 37-year-old man who visited the hospital complaining of fatigue, palpitations, and dyspnea. His hemoglobin was 110 g/l, and mean corpuscular volume was 81.5 fl. His free thyroxine (FT4) was high, at 1.004 pmol/l, the free triiodothyronine (FT3) was high, at 27.49 pmol/l, TSH was <0.01 mIU/l, and TSH receptor antibody was negative. Soluble IL-2 receptor (sIL-2R) was high, at 1,340 U/ml, low-density lipoprotein cholesterol (LDL-C) was 0.78 mmol/l, and high-density lipoprotein cholesterol (HDL-C) was 0.75 mmol/l. Propranolol was prescribed and followed up. Thyroid hormones, sIL-2R, LDL-C, and HDL-C had almost normalized by 8 weeks after onset. Anemia completely disappeared by 12 weeks after disease onset. Slight increases in liver enzyme levels and a decrease in serum albumin were observed, and recovered later than normalization of thyroid function and cholesterol levels. He developed mild hypothyroidism and was treated with L-thyroxine at 24 weeks.Conclusions: This is the first case report of transient secondary anemia associated with thyrotoxicosis due to painless thyroiditis. Changes in sIL-2R, HDL-C, LDL-C and liver function were also observed during the clinical course of thyrotoxicosis and anemia, suggesting the autoimmune processes in thyroid gland, bone marrow and liver.

Painless thyroiditis in a dupilumab-treated patient

Summary Dupilumab an inhibitor of the interleukin (IL)-4R-alpha subunit is used for the treatment of allergic diseases. The patient was a 49-year-old man who received dupilumab for the treatment of severe atopic dermatitis. He presented hyperthyroidism with elevated thyroglobulin and anti-thyroid antibody negativity at 4 months after the initiation of therapy. On scintigraphy, the thyroid radioiodine uptake was low. Ultrasonography showed a diffuse hypoechoic area in the thyroid gland. A pathological study revealed lymphocytic infiltration. The administration of dupilumab was continued because of his atopic dermatitis that showed an excellent response. The patient`s hyperthyroidism changed to hypothyroidism 3 weeks later. Six months later his thyroid function normalized without any treatment. We herein describe the case of a patient with atopic dermatitis who developed painless thyroiditis under treatment with dupilumab. To the best of our knowledge, this is the first report of this event in the literature. Learning points: Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has been shown to be effective in the treatment atopic dermatitis and asthma with eosinophilia. Painless thyroiditis is characterized by transient hyperthyroidism and hypothyroidism and recovery without anti-thyroid treatment. This is the first report of painless thyroiditis as an adverse effect of dupilumab, although conjunctivitis and nasopharyngitis are the main adverse effects of dupilumab.