Diagnosis and Treatment > Investigation > White blood cell differential count

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Ali A Zaied Divisions of Pulmonary and Critical Care Medicine, Mayo Clinic, Jacksonville, Florida, USA

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Halis K Akturk Divisions of Endocrinology, Mayo Clinic, Jacksonville, Florida, USA

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Richard W Joseph Divisions of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida, USA

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Augustine S Lee Divisions of Pulmonary and Critical Care Medicine, Mayo Clinic, Jacksonville, Florida, USA

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Summary

Nivolumab, a monoclonal antibody against programmed cell death-1 receptor, is increasingly used in advanced cancers. While nivolumab use enhances cancer therapy, it is associated with increased immune-related adverse events. We describe an elderly man who presented in ketoacidosis after receiving nivolumab for metastatic renal cell carcinoma. On presentation, he was hyperpneic and laboratory analyses showed hyperglycemia and anion-gapped metabolic acidosis consistent with diabetic ketoacidosis. No other precipitating factors, besides nivolumab, were identified. Pre-nivolumab blood glucose levels were normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. He was diagnosed with insulin-dependent autoimmune diabetes mellitus secondary to nivolumab. Although nivolumab was stopped, he continued to require multiple insulin injection therapy till his last follow-up 7 months after presentation. Clinicians need to be alerted to the development of diabetes mellitus and diabetic ketoacidosis in patients receiving nivolumab.

Learning points:

  • Diabetic ketoacidosis should be considered in the differential of patients presenting with metabolic acidosis following treatment with antibodies to programmed cell death-1 receptor (anti-PD-1).

  • Autoimmune islet cell damage is the presumed mechanism for how insulin requiring diabetes mellitus can develop de novo following administration of anti-PD-1.

  • Because anti-PD-1 works by the activation of T-cells and reduction of ‘self-tolerance’, other autoimmune disorders are likely to be increasingly recognized with increased use of these agents.

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Han Soo Park Department of Internal Medicine, Division of Endocrinology and Metabolism

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Su Kyoung Kwon Department of Internal Medicine, Division of Endocrinology and Metabolism

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Ye Na Kim Division of Nephrology, Kosin University College of Medicine, Busan, Republic of Korea

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Summary

Thyroid storm is a rare and potentially life-threatening medical emergency. We experienced a case of thyroid storm associated with sepsis caused by pneumonia, which had a catastrophic course including recurrent cardiac arrest and subsequent multiple organ failure (MOF). A 22-year-old female patient with a 10-year history of Graves’ disease was transferred to our emergency department (ED). She had a cardiac arrest at her home and a second cardiac arrest at the ED. Her heart recovered after 20 min of cardiac resuscitation. She was diagnosed with thyroid storm associated with hyperthyroidism complicated by pneumonia and sepsis. Although full conventional medical treatment was given, she had progressive MOF and hemodynamic instability consisting of hyperthermia, tachycardia and hypotension. Because of hepatic and renal failure with refractory hypotension, we reduced the patient’s dose of beta-blocker and antithyroid drug, and she was started on continuous veno-venous renal replacement therapy (CRRT) with intravenous albumin and plasma supplementation. Subsequently, her body temperature and pulse rate began to stabilize within 1 h, and her blood pressure reached 120/60 mmHg after 6 h. We discontinued antithyroid drug 3 days after admission because of aggravated hyperbilirubinemia. The patient exhibited progressive improvement in thyroid function even after cessation of antithyroid drug, and she successfully recovered from thyroid storm and MOF. This is the first case of thyroid storm successfully treated by CRRT in a patient considered unfit for antithyroid drug treatment.

Learning points:

  • The presenting manifestations of thyroid storm vary and can include cardiac arrest with multiorgan failure in rare cases.

  • In some patients with thyroid storm, especially those with severe complications, conventional medical treatment may be ineffective or inappropriate.

  • During thyroid storm, the initiation of CRRT can immediately lower body temperature and subsequently stabilize vital signs.

  • Early initiation of CRRT can be life-saving in patients with thyroid storm complicated by MOF, even when used in combination with suboptimal medical treatment.

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Marlene Tarvainen School of Medicine, University of Tampere, Tampere, Finland

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Satu Mäkelä School of Medicine, University of Tampere, Tampere, Finland
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland

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Jukka Mustonen School of Medicine, University of Tampere, Tampere, Finland
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland

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Pia Jaatinen School of Medicine, University of Tampere, Tampere, Finland
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Division of Internal Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland

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Summary

Puumala hantavirus (PUUV) infection causes nephropathia epidemica (NE), a relatively mild form of haemorrhagic fever with renal syndrome (HFRS). Hypophyseal haemorrhage and hypopituitarism have been described in case reports on patients with acute NE. Chronic hypopituitarism diagnosed months or years after the acute illness has also been reported, without any signs of a haemorrhagic aetiology. The mechanisms leading to the late-onset hormonal defects remain unknown. Here, we present a case of NE-associated autoimmune polyendocrinopathy and hypopituitarism presumably due to autoimmune hypophysitis. Thyroid peroxidase antibody seroconversion occurred between 6 and 12 months, and ovarian as well as glutamate decarboxylase antibodies were found 18 months after acute NE. Brain MRI revealed an atrophic adenohypophysis with a heterogeneous, low signal intensity compatible with a sequela of hypophysitis. The patient developed central (or mixed central and peripheral) hypothyroidism, hypogonadism and diabetes insipidus, all requiring hormonal replacement therapy. This case report suggests that late-onset hormonal defects after PUUV infection may develop by an autoimmune mechanism. This hypothesis needs to be confirmed by prospective studies with sufficient numbers of patients.

Learning points:

  • Pituitary haemorrhage resulting in hypopituitarism has been reported during acute HFRS caused by PUUV and other hantaviruses.

  • Central and peripheral hormone deficiencies developing months or years after HFRS have also been found, with an incidence higher than that in the general population. The pathogenesis of these late-onset hormonal defects remains unknown.

  • This case report suggests that the late-onset hypopituitarism and peripheral endocrine defects after HFRS could evolve via autoimmune mechanisms.

  • The sensitivity of current anti-pituitary antibody (APA) tests is low. A characteristic clinical course, together with typical brain MRI and endocrine findings may be sufficient for a non-invasive diagnosis of autoimmune hypophysitis, despite negative APAs.

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Ling Zhu Department of Endocrinology, Singapore General Hospital, Singapore

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Sueziani Binte Zainudin Department of Endocrinology, Singapore General Hospital, Singapore

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Manish Kaushik Department of Renal Medicine, Singapore General Hospital, Singapore

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Li Yan Khor Department of Pathology, Singapore General Hospital, Singapore

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Chiaw Ling Chng Department of Endocrinology, Singapore General Hospital, Singapore

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Summary

Type II amiodarone-induced thyrotoxicosis (AIT) is an uncommon cause of thyroid storm. Due to the rarity of the condition, little is known about the role of plasma exchange in the treatment of severe AIT. A 56-year-old male presented with thyroid storm 2months following cessation of amiodarone. Despite conventional treatment, his condition deteriorated. He underwent two cycles of plasma exchange, which successfully controlled the severe hyperthyroidism. The thyroid hormone levels continued to fall up to 10h following plasma exchange. He subsequently underwent emergency total thyroidectomy and the histology of thyroid gland confirmed type II AIT. Management of thyroid storm secondary to type II AIT can be challenging as patients may not respond to conventional treatments, and thyroid storm may be more harmful in AIT patients owing to the underlying cardiac disease. If used appropriately, plasma exchange can effectively reduce circulating hormones, to allow stabilisation of patients in preparation for emergency thyroidectomy.

Learning points

  • Type II AIT is an uncommon cause of thyroid storm and may not respond well to conventional thyroid storm treatment.

  • Prompt diagnosis and therapy are important, as patients may deteriorate rapidly.

  • Plasma exchange can be used as an effective bridging therapy to emergency thyroidectomy.

  • This case shows that in type II AIT, each cycle of plasma exchange can potentially lower free triiodothyronine levels for 10h.

  • Important factors to consider when planning plasma exchange as a treatment for thyroid storm include timing of each session, type of exchange fluid to be used and timing of surgery.

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Apostolos K A Karagiannis Department of Endocrinology, Diabetes and Metabolism, Korgialeneio Benakeio EES, Peripheral General Hospital Athens, Athens, Greece

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Fotini Dimitropoulou Department of Endocrinology, Diabetes and Metabolism, Korgialeneio Benakeio EES, Peripheral General Hospital Athens, Athens, Greece

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Athanasios Papatheodorou Department of Radiology, Korgialeneio Benakeio EES, Peripheral General Hospital Athens, Athens, Greece

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Stavroula Lyra Department of Radiology, Korgialeneio Benakeio EES, Peripheral General Hospital Athens, Athens, Greece

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Andreas Seretis Department of Neurosurgery, General Hospital of Athens ‘G. Gennimatas’, Athens, Greece

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Andromachi Vryonidou Department of Endocrinology, Diabetes and Metabolism, Korgialeneio Benakeio EES, Peripheral General Hospital Athens, Athens, Greece

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Summary

Pituitary abscess is a rare life-threating entity that is usually misdiagnosed as a pituitary tumor with a definite diagnosis only made postoperatively. Over the last several decades, advances in healthcare have led to a significant decrease in morbidity and mortality due to pituitary abscess. We report a case of a 34-year-old woman who was admitted to our department for investigation of a pituitary mass and with symptoms of pituitary dysfunction, headaches and impaired vision. During her admission, she developed meningitis-like symptoms and was treated with antibiotics. She eventually underwent transsphenoidal surgery for excision of the pituitary mass. A significant amount of pus was evident intraoperatively; however, no pathogen was isolated. Six months later, the patient was well and had full recovery of the anterior pituitary function. Her menses returned, and she was only on treatment with desmopressin for diabetes insipidus that developed postoperatively.

Learning points

  • Pituitary abscess is a rare disease and the reported clinical features vary mimicking other pituitary lesions.

  • The diagnosis of pituitary abscess is often very difficult to make and rarely included in the differential.

  • The histological findings of acute inflammatory infiltration confirm the diagnosis of pituitary abscess.

  • Medical and surgical treatment is usually recommended upon diagnosis of a pituitary abscess.

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Alessandro Mantovani Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Maddalena Trombetta Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Chiara Imbriaco Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Riccardo Rigolon Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Lucia Mingolla Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Federica Zamboni Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Francesca Dal Molin Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Dario Cioccoloni Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Viola Sanga Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Massimiliano Bruti Division of Plastic Surgery, Department of Surgery, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Enrico Brocco Regional Referral Center for the Treatment of Diabetic Foot, Policlinico Abano Terme, Padova, Italy

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Michela Conti Division of Infectious Disease, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Giorgio Ravenna Division of Neurosurgery, Department of Surgery, University and Azienda Ospedaliera Universitaria Integrataof Verona, Verona, Italy

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Fabrizia Perrone Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Vincenzo Stoico Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Enzo Bonora Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Summary

Vertebral osteomyelitis (or spondylodiscitis) is steadily increasing in Western countries and often results from hematogenous seeding, direct inoculation during spinal surgery, or contiguous spread from an infection in the adjacent soft tissue. We present the case of a 67-year-old white patient with type 2 diabetes who went to Hospital for high fever, back pain, and worsening of known infected ulcers in the left foot. Despite intravenous antibiotic treatment and surgical debridement of the foot infection, high fever and lower back pain continued. Bone biopsy and two consecutive blood cultures were positive for Staphylococcus aureus. A spinal magnetic resonance imaging (MRI) was performed, revealing serious osteomyelitis in L4 and L5 complicated by an epidural abscess. Contiguous or other distant focuses of infection were not identified. In this case, diabetic foot could be considered as a primary distant focus for vertebral osteomyelitis. Clinicians should consider vertebral osteomyelitis as a ‘possible’ diagnosis in patients with type 2 diabetes complicated by foot infection that is associated with fever and lower back pain.

Learning points

  • Vertebral osteomyelitis is increasing in Western countries, especially in patients with type 2 diabetes.

  • The primary focus of infection is the genitourinary tract followed by skin, soft tissue, endocarditis, bursitis, septic arthritis, and intravascular access.

  • Diabetic foot could be a rare primary focus of infection for vertebral osteomyelitis, and, however, vertebral osteomyelitis could be a serious, albeit rare, complication of diabetic foot.

  • Clinicians should keep in mind the many potential complications of diabetic foot ulcerations and consider vertebral osteomyelitis as a “possible” diagnosis in patients with type 2 diabetes and foot ulcers associated with nonspecific symptoms such as lower back pain.

  • Early diagnosis and correct management of vertebral osteomyelitis are crucial to improve clinical outcomes.

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Hiroto Minamino The First Department of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8509, Japan
Department of Diabetes and Endocrinology, Wakayama Red Cross Hospital, Wakayama, Japan

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Hidefumi Inaba The First Department of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8509, Japan

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Hiroyuki Ariyasu The First Department of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8509, Japan

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Hiroto Furuta The First Department of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8509, Japan

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Masahiro Nishi The First Department of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8509, Japan

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Takashi Yoshimasu Department of Dermatology, Wakayama Medical University, Wakayama, Japan

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Akinori Nishikawa Department of Hematology, Wakayama Medical University, Wakayama, Japan

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Masanori Nakanishi Department of Respiratory Medicine & Medical Oncology, Wakayama Medical University, Wakayama, Japan

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Shigeki Tsuchihashi Department of Otolaryngology, Wakayama Medical University, Wakayama, Japan

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Fumiyoshi Kojima Department of Human Pathology, Wakayama Medical University, Wakayama, Japan

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Shin-ichi Murata Department of Human Pathology, Wakayama Medical University, Wakayama, Japan

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Gen Inoue Department of Diabetes and Endocrinology, Wakayama Red Cross Hospital, Wakayama, Japan

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Takashi Akamizu The First Department of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8509, Japan

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Summary

A 73-year-old man with Hashimoto's thyroiditis (HT) suffered from purpura on the lower legs. He was diagnosed with IgG4-related disease (IgG4-RD) with serum IgG4 elevation and dacryo-sialadenitis confirmed histologically. Serum Th2 and Treg cytokines, interleukin 7 (IL7), IL8 and Th2 chemokine levels were elevated, while skewed Th1 balance was seen in fluorescence-activated cell sorting (FACS). Therefore, preferential Th1 balance in HT appeared to be followed by IgG4-RD characterized with Th2 and Treg polarization. The commencement of steroid therapy dramatically exacerbated clinical manifestations including IgG4-RD-associated HT. The measurement of cytokine and chemokine levels as well as FACS analysis in the development of IgG4-RD seemed to be beneficial. In conclusion, an innovative association of HT, IgG4-RD and vasculitis was observed. This report also offers novel diagnostic and therapeutic approaches for IgG4-RD.

Learning points

  • Recently, a subtype of HT has been considered to be a thyroid manifestation of IgG4-RD, although the etiology of IgG4-RD is not established yet.

  • Immunologically a close association between HT and vasculitis was reported.

  • Leukocytoclastic vasculitis is a rare skin presentation of IgG4-RD.

  • In the current case, during the course of HT, IgG4-RD and leukocytoclastic vasculitis occurred; thus, innate immunity and acquired immunity seem to be involved in the development of IgG4-RD.

  • The measurement of cytokine and chemokines appeared to be beneficial in the development of IgG4-RD.

  • Remarkably, effectiveness of steroid therapy for HT suggested presence of IgG4-RD-associated HT. Therefore, this report highlights the pathogenesis of IgG4-RD and proposes novel therapeutic mechanisms. Clinicians should pay attention to the development of IgG4-RD and vasculitis during long course of HT.

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Junji Kawashima Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

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Hideaki Naoe Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

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Yutaka Sasaki Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

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Eiichi Araki Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

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Summary

Anti-tumor necrosis factor (TNF)-α therapy is established as a new standard for the treatment of various autoimmune inflammatory diseases. We report the first case showing subacute thyroiditis-like symptoms with an amyloid goiter after anti-TNF-α therapy. A 56-year-old man with Crohn's disease presented with fever and a diffuse, tender goiter. To control the diarrhea, anti-TNF therapy (infliximab) was administered 4 weeks before the thyroid symptoms emerged. The patient reported a swollen neck with tenderness on the right side and fever 4 days after the second infliximab injection. An elevated serum C-reactive protein (CRP) and serum thyroid hormone level with suppressed serum thyrotropin were observed. The thyroid-stimulating antibody was not elevated. An ultrasonograph of the thyroid revealed an enlarged goiter with posterior echogenicity attenuation and a low echoic region that was tender. The thyroid uptake value on technetium-99m scintigraphy was near the lower limit of the normal range. The patient was initially diagnosed with thyrotoxicosis resulting from subacute thyroiditis. Administration of oral prednisolone improved the fever, thyroid pain, and thyroid function, but his thyroid remained swollen. The patient developed diarrhea after prednisolone withdrawal; therefore, adalimumab, another TNF inhibitor, was administered. After three injections, his abdominal symptoms were alleviated, but the thyroid pain and fever recurred. Elevated serum CRP levels in the absence of thyroid dysfunction were observed. The patient's symptoms resolved after prednisolone retreatment, but an elastic, firm goiter persisted. A fine-needle biopsy revealed amyloid deposition in the thyroid.

Learning points

  • Many cases with thyroid dysfunction accompanied by amyloid goiter have been reported.

  • There are cases that develop amyloid goiter with subacute thyroiditis-like symptoms after anti-TNF therapy.

  • When the thyroid remains swollen after improvement of thyrotoxicosis following treatment with prednisolone, it should be assessed to differentiate between an amyloid goiter and common subacute thyroiditis.

Open access