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Tomomi Nakao First Department of Internal Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan

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Ken Takeshima First Department of Internal Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan

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Hiroyuki Ariyasu First Department of Internal Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan

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Chiaki Kurimoto First Department of Internal Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan

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Shinsuke Uraki First Department of Internal Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan

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Shuhei Morita First Department of Internal Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan

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Yasushi Furukawa First Department of Internal Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan

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Hiroshi Iwakura First Department of Internal Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan

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Takashi Akamizu First Department of Internal Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan

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Summary

Thyroid storm (TS) is a life-threatening condition that may suffer thyrotoxic patients. Therapeutic plasma exchange (TPE) is a rescue approach for TS with acute hepatic failure, but it should be initiated with careful considerations. We present a 55-year-old male patient with untreated Graves’ disease who developed TS. Severe hyperthyroidism and refractory atrial fibrillation with congestive heart failure aggregated to multiple organ failure. The patient was recovered by intensive multimodal therapy, but we had difficulty in introducing TPE treatment considering the risk of exacerbation of congestive heart failure due to plasma volume overload. In addition, serum total bilirubin level was not elevated in the early phase to the level of indication for TPE. The clinical course of this patient instructed delayed elevation of bilirubin until the level of indication for TPE in some patients and also demonstrated the risk of exacerbation of congestive heart failure by TPE.

Learning points:

  • Our patient with thyroid storm could be diagnosed and treated promptly using Japan Thyroid Association guidelines for thyroid storm.

  • Delayed elevation of serum bilirubin levels could make the decision of introducing therapeutic plasma exchange difficult in cases of thyroid storm with acute hepatic failure.

  • The risk of worsening congestive heart failure should be considered carefully when performing therapeutic plasma exchange.

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Fumiaki Kawano Departments of Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Tadato Yonekawa Neurology, Respirology, Endocrinology and Metabolism, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Hideki Yamaguchi Neurology, Respirology, Endocrinology and Metabolism, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Nobuhiro Shibata Clinical Oncology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Kousei Tashiro Departments of Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Makoto Ikenoue Departments of Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Shun Munakata Departments of Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Kazuhiro Higuchi Departments of Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Hiroyuki Tanaka Diagnostic Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Yuichiro Sato Diagnostic Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Ayumu Hosokawa Clinical Oncology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Shinsuke Takeno Departments of Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Kunihide Nakamura Departments of Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Atsushi Nanashima Departments of Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

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Summary

A 54-year-old woman was referred to our hospital with a cervical tumor. CT revealed a cervical tumor extending to the upper mediastinum, tracheal deviation and tumor infiltration in the cervical vessels. She was followed-up because no diagnosis of malignancy was made by cytology. However, 2 months later, a CT scan showed enlargement of the tumor and tracheal stenosis, and a surgical biopsy was performed and she was diagnosed with anaplastic thyroid cancer (ATC). The tracheal tube with tracheal stenosis could not be removed due to the rapid growth of the tumor, necessitating management by mechanical ventilation. Due to the difficulty of surgical resection, she was treated with lenvatinib. A lenvatinib solution was made and administered via a nasogastric tube. After lenvatinib treatment, the tumor volume decreased and the tracheal stenosis improved. The tracheal tube was removed and oral intake became possible. She was discharged and received ambulatory lenvatinib therapy. The tumor was significantly reduced in size, but gradually grew and was exposed through the cervical wound 6 months later. Esophageal perforation occurred 10 months after the start of treatment. Lenvatinib was re-administered via a nasogastric tube. Eleven months later, the patient died of massive bleeding from the exposed cervical tumor. Patients with advanced ATC may require management with mechanical ventilation for airway stenosis or with a nasogastric tube for esophageal stenosis and perforation. We experienced a case in which lenvatinib was safely administered via a nasogastric tube while performing mechanical ventilation.

Learning points:

  • An anaplastic thyroid cancer patient under mechanical ventilator management was treated with lenvatinib via a nasogastric tube.

  • The lenvatinib solution can easily be prepared and administered via a nasogastric tube.

  • The lenvatinib solution was effective for a patient with difficulty in oral intake.

  • Lenvatinib could also improve the prognosis of an anaplastic thyroid cancer patient with severe airway and esophageal trouble.

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Dured Dardari Diabetology Department, Centre Hopitalier Sud Francilien, Corbeil-Essonnes, France
Sorbonne Université, Paris, France

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Alfred Penfornis Diabetology Department, Centre Hopitalier Sud Francilien, Corbeil-Essonnes, France
Paris-Sud Medical School, Paris-Saclay University, Orsay, France

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Agnes Hartemann Diabetology Department, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France
Sorbonne Université, Paris, France

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Summary

We report the onset of acute Charcot neuroarthropathy during pregnancy in two patients with type 1 diabetes using retrospective review of case notes. We describe for the first time the onset of acute Charcot neuroarthropathy during pregnancy in two patients with type 1 diabetes. Pregnancy may promote the onset and worsening of a number of diabetic complications. A link between pregnancy and the onset of acute Charcot neuroarthropathy is demonstrated for the first time in this report.

Learning points:

  • Patients with already diagnosed sensitive neuropathy can develop an active phase of Charcot neuroarthropathy during pregnancy.

  • The rapid correction of hyperglycaemia may induce an active phase of Charcot neuroarthropathy during pregnancy.

Open access
Mauro Boronat Section of Endocrinology and Nutrition, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de Gran Canaria, Spain
Research Institute in Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain

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Summary

Isolated, adult-onset central hypothyroidism is very rare, and its diagnosis can be challenging. A 42-year-old patient was referred for evaluation of a 2.8 cm thyroid nodule. She referred symptoms that could be attributed to hypothyroidism and thyroid tests showed low TSH and normal-low levels of free T4. However, evaluation of the remaining pituitary hormones and pituitary MRI were normal, yet a radionuclide scanning revealed that the thyroid nodule was ‘hot’ and the tracer uptake in the remaining thyroid tissue was suppressed. Interpretation of these studies led to a misdiagnosis of subclinical hyperthyroidism and the patient was treated with radioiodine. Soon after treatment, she developed a frank hypothyroidism without appropriate elevation of TSH and the diagnosis of central hypothyroidism was made a posteriori. Long term follow-up revealed a progressive pituitary failure, with subsequent deficiency of ACTH and GH. This case should alert to the possibility of overlooking central hypothyroidism in patients simultaneously bearing primary thyroid diseases able to cause subclinical hyperthyroidism.

Learning points:

  • Although rarely, acquired central hypothyroidism can occur in the absence of other pituitary hormone deficiencies.

  • In these cases, diagnosis is challenging, as symptoms are unspecific and usually mild, and laboratory findings are variable, including low, normal or even slightly elevated TSH levels, along with low or low-normal concentrations of free T4.

  • In cases with low TSH levels, the coexistence of otherwise common disorders able to cause primary thyroid hyperfunction, such as autonomous nodular disease, may lead to a misdiagnosis of subclinical hyperthyroidism.

Open access
Mawson Wang Department of Endocrinology and Diabetes, Blacktown Hospital, Sydney, Australia
Blacktown Clinical School, School of Medicine, Western Sydney University, Sydney, Australia

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Benjamin Jonker Department of Neurosurgery, St. Vincent’s Hospital, Sydney, Australia

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Louise Killen Department of Pathology, St. Vincent’s Hospital, Sydney, Australia

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Yvonne Bogum NSW Health Pathology East, Prince of Wales Hospital, Sydney, Australia

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Ann McCormack Department of Endocrinology, St. Vincent’s Hospital, Sydney, Australia
Garvan Institute of Medical Research, Sydney, Australia
St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, Australia

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Ramy H Bishay Department of Endocrinology and Diabetes, Blacktown Hospital, Sydney, Australia
Blacktown Clinical School, School of Medicine, Western Sydney University, Sydney, Australia

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Summary

Cushing’s disease is a rare disorder characterised by excessive cortisol production as a consequence of a corticotroph pituitary tumour. While the primary treatment is surgical resection, post-operative radiation therapy may be used in cases of ongoing inadequate hormonal control or residual or progressive structural disease. Despite improved outcomes, radiotherapy for pituitary tumours is associated with hypopituitarism, visual deficits and, rarely, secondary malignancies. We describe an unusual case of a 67-year-old female with presumed Cushing’s disease diagnosed at the age of 37, treated with transsphenoidal resection of a pituitary tumour with post-operative external beam radiotherapy (EBRT), ketoconazole for steroidogenesis inhibition, and finally bilateral adrenalectomy for refractory disease. She presented 30 years after her treatment with a witnessed generalised tonic-clonic seizure. Radiological investigations confirmed an extracranial mass infiltrating through the temporal bone and into brain parenchyma. Due to recurrent generalised seizures, the patient was intubated and commenced on dexamethasone and anti-epileptic therapy. Resection of the tumour revealed a high-grade osteoblastic osteosarcoma. Unfortunately, the patient deteriorated in intensive care and suffered a fatal cardiac arrest following a likely aspiration event. We describe the risk factors, prevalence and treatment of radiation-induced osteosarcoma, an exceedingly rare and late complication of pituitary irradiation. To our knowledge, this is the longest reported latency period between pituitary irradiation and the development of an osteosarcoma of the skull.

Learning points:

  • Cushing’s disease is treated with transsphenoidal resection as first-line therapy, with radiotherapy used in cases of incomplete resection, disease recurrence or persistent hypercortisolism.

  • The most common long-term adverse outcome of pituitary tumour irradiation is hypopituitarism occurring in 30–60% of patients at 10 years, and less commonly, vision loss and oculomotor nerve palsies, radiation-induced brain tumours and sarcomas.

  • Currently proposed characteristics of radiation-induced osteosarcomas include: the finding of a different histological type to the primary tumour, has developed within or adjacent to the path of the radiation beam, and a latency period of at least 3 years.

  • Treatment of osteosarcoma of the skull include complete surgical excision, followed by systemic chemotherapy and/or radiotherapy.

  • Overall prognosis in radiation-induced sarcoma of bone is poor.

  • Newer techniques such as stereotactic radiosurgery may reduce the incidence of radiation-induced malignancies.

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Ravikumar Ravindran Section of Endocrinology, YYF Hospital, Ystrad Fawr Way, Caerphilly, UK

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Justyna Witczak Section of Endocrinology, YYF Hospital, Ystrad Fawr Way, Caerphilly, UK

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Suhani Bahl Section of Endocrinology, YYF Hospital, Ystrad Fawr Way, Caerphilly, UK

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Lakdasa D K E Premawardhana Section of Endocrinology, YYF Hospital, Ystrad Fawr Way, Caerphilly, UK
Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff, UK

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Mohamed Adlan Section of Endocrinology, YYF Hospital, Ystrad Fawr Way, Caerphilly, UK

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Summary

A 53-year-old man who used growth hormone (GH), anabolic steroids and testosterone (T) for over 20 years presented with severe constipation and hypercalcaemia. He had benign prostatic hyperplasia and renal stones but no significant family history. Investigations showed – (1) corrected calcium (reference range) 3.66 mmol/L (2.2–2.6), phosphate 1.39 mmol/L (0.80–1.50), and PTH 2 pmol/L (1.6–7.2); (2) urea 21.9 mmol/L (2.5–7.8), creatinine 319 mmol/L (58–110), eGFR 18 mL/min (>90), and urine analysis (protein 4+, glucose 4+, red cells 2+); (3) creatine kinase 7952 U/L (40–320), positive anti Jo-1, and Ro-52 antibodies; (4) vitamin D 46 nmol/L (30–50), vitamin D3 29 pmol/L (55–139), vitamin A 4.65 mmol/L (1.10–2.60), and normal protein electrophoresis; (5) normal CT thorax, abdomen and pelvis and MRI of muscles showed ‘inflammation’, myositis and calcification; (6) biopsy of thigh muscles showed active myositis, chronic myopathic changes and mineral deposition and of the kidneys showed positive CD3 and CD45, focal segmental glomerulosclerosis and hypercalcaemic tubular changes; and (7) echocardiography showed left ventricular hypertrophy (likely medications and myositis contributing), aortic stenosis and an ejection fraction of 44%, and MRI confirmed these with possible right coronary artery disease. Hypercalcaemia was possibly multifactorial – (1) calcium release following myositis, rhabdomyolysis and acute kidney injury; (2) possible primary hyperparathyroidism (a low but detectable PTH); and (3) hypervitaminosis A. He was hydrated and given pamidronate, mycophenolate and prednisolone. Following initial biochemical and clinical improvement, he had multiple subsequent admissions for hypercalcaemia and renal deterioration. He continued taking GH and T despite counselling but died suddenly of a myocardial infarction.

Learning points:

  • The differential diagnosis of hypercalcaemia is sometimes a challenge.

  • Diagnosis may require multidisciplinary expertise and multiple and invasive investigations.

  • There may be several disparate causes for hypercalcaemia, although one usually predominates.

  • Maintaining ‘body image’ even with the use of harmful drugs may be an overpowering emotion despite counselling about their dangers.

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Anna Luiza Galeazzi Rech Kantonsspital Sankt Gallen, Klinik für Allgemeine Innere Medizin/Hausarztmedizin, Sankt Gallen, Switzerland

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Yvon Stüve Kantonsspital Sankt Gallen, Klinik für Allgemeine Innere Medizin/Hausarztmedizin, Sankt Gallen, Switzerland

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Andreas Toepfer Kantonsspital Sankt Gallen, Klinik für Orthopädische Chirurgie und Traumatologie des Bewegungsapparts, Sankt Gallen, Switzerland

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Katrin E Schimke Kantonsspital Sankt Gallen, Klinik für Allgemeine Innere Medizin/Hausarztmedizin, Sankt Gallen, Switzerland

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Summary

Acute Charcot neuropathic osteoarthropathy (CN) is a clinical entity which can easily go unrecognized in its acute early stages due to lack of awareness and unspecific presentation. However, missing early diagnosis can lead to severe complications. We present the case of a 72-year-old male patient who went through the natural course of the disease unnoticed before the very eyes of his physicians leading to a tragic end. We aim to raise awareness for this rare diabetic complication, emphasizing the necessity of early diagnosis and adequate, interdisciplinary treatment.

Learning points:

  • Clinical signs and symptoms of acute Charcot neuropathic osteoarthropathy (CN).

  • Red flags.

  • Importance of early diagnosis and correct treatment.

  • Diagnostic challenges of acute CN.

  • Awareness of high morbidity and mortality.

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Daramjav Narantsatsral Division of Endocrinology and Metabolism, Department of Internal Medicine

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Takagi Junko Division of Endocrinology and Metabolism, Department of Internal Medicine

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Iwayama Hideyuki Department of Pediatrics, Aichi Medical University School of Medicine, Nagakute, Japan

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Inukai Daisuke Department of Otolaryngology, Aichi Medical University School of Medicine, Nagakute, Japan

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Takama Hiroyuki Department of Dermatology, Aichi Medical University School of Medicine, Nagakute, Japan

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Nomura Yuka Division of Endocrinology and Metabolism, Department of Internal Medicine

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Hirase Syo Division of Endocrinology and Metabolism, Department of Internal Medicine

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Morita Hiroyuki Division of Endocrinology and Metabolism, Department of Internal Medicine

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Otake Kazuo Division of Endocrinology and Metabolism, Department of Internal Medicine

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Ogawa Tetsuya Department of Otolaryngology, Aichi Medical University School of Medicine, Nagakute, Japan

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Takami Akiyoshi Department of Hematology, Aichi Medical University School of Medicine, Nagakute, Japan

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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.

Open access
Raku Son Department of Nephrology, St. Luke’s International Hospital, Tokyo, Japan

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Masahiko Nagahama Department of Nephrology, St. Luke’s International Hospital, Tokyo, Japan

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Fumiaki Tanemoto Department of Nephrology, St. Luke’s International Hospital, Tokyo, Japan

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Yugo Ito Department of Nephrology, St. Luke’s International Hospital, Tokyo, Japan

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Fumika Taki Department of Nephrology, St. Luke’s International Hospital, Tokyo, Japan

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Ryosuke Tsugitomi Department of Pulmonary Medicine, Thoracic Center, St. Luke’s International Hospital, Tokyo, Japan

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Masaaki Nakayama Department of Nephrology, St. Luke’s International Hospital, Tokyo, Japan

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Summary

The etiology of hyponatremia is assessed based on urine osmolality and sodium. We herein describe a 35-year-old Asian man with pulmonary tuberculosis and perforated duodenal ulcer who presented with hyponatremia with hourly fluctuating urine osmolality ranging from 100 to 600 mosmol/kg, which resembled urine osmolality observed in typical polydipsia and SIADH simultaneously. Further review revealed correlation of body temperature and urine osmolality. Since fever is a known non-osmotic stimulus of ADH secretion, we theorized that hyponatremia in this patient was due to transient ADH secretion due to fever. In our case, empiric exogenous glucocorticoid suppressed transient non-osmotic ADH secretion and urine osmolality showed highly variable concentrations. Transient ADH secretion-related hyponatremia may be underrecognized due to occasional empiric glucocorticoid administration in patients with critical illnesses. Repeatedly monitoring of urine chemistries and interpretation of urine chemistries with careful review of non-osmotic stimuli of ADH including fever is crucial in recognition of this etiology.

Learning points:

  • Hourly fluctuations in urine osmolality can be observed in patients with fever, which is a non-osmotic stimulant of ADH secretion.

  • Repeated monitoring of urine chemistries aids in the diagnosis of the etiology underlying hyponatremia, including fever, in patients with transient ADH secretion.

  • Glucocorticoid administration suppresses ADH secretion and improves hyponatremia even in the absence of adrenal insufficiency; the etiology of hyponatremia should be determined carefully in these patients.

Open access
Frank Gao Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne, Australia

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Stephen Hall Department of Medicine, Monash University and Cabrini Health, Melbourne, Australia

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Leon A Bach Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne, Australia
Department of Medicine (Alfred), Monash University, Melbourne, Australia

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Summary

Sodium/glucose co-transporter 2 (SGLT2) inhibitors are novel oral hypoglycaemic agents that are increasingly used in the management of type 2 diabetes mellitus (T2DM). They are now recommended as second-line pharmacotherapy (in conjunction with metformin) in patients with type 2 diabetes and established atherosclerotic heart disease, heart failure or chronic kidney disease due to their favourable effects on cardiovascular and renal outcomes. We report a case of a 69-year-old man who developed muscle pain, weakness and wasting after commencing the SGLT2 inhibitor empagliflozin. This persisted for 1 year before he underwent resistance testing, which confirmed muscle weakness. His symptoms resolved within weeks of ceasing empagliflozin, with improvement in muscle strength on clinical assessment and resistance testing and reversal of MRI changes. No other cause of myopathy was identified clinically, on biochemical assessment or imaging, suggesting that empagliflozin was the cause of his myopathy.

Learning points:

  • Empagliflozin, a commonly used SGLT2 inhibitor, was associated with myopathy.

  • A high degree of suspicion is required to diagnose drug-induced myopathy, with a temporal relationship between starting the medication and symptom onset being the main indicator.

  • Recognition of drug-induced myopathy is essential, as discontinuation of the offending drug typically improves symptoms.

Open access