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To understand the etiology of metabolic disorders, including obesity and type II diabetes, it is essential to gain better insight into how stored and available energy sources are monitored by the central nervous system. In particular, a comprehension of the fine cellular interplay and intracellular mechanisms that enable appropriate hypothalamic and consequent endocrine and behavioral responses to both circulating hormonal and nutrient signals remains elusive. Recent data, including those from our laboratories, raised the notion that reactive oxygen species (ROS) generation is not merely a by-product of substrate oxidation, but it plays a crucial role in modulating cellular responses involved in the regulation of energy metabolism. These review summarizes the published recent data on the effect of ROS levels in the regulation of neuronal function, including that of hypothalamic melanocortin neurons, pro-opiomelanocortin and neuropeptide Y-/agouti related peptide-neurons, in the modulation of food intake.

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Autophagy plays a crucial role in the maintenance of cellular nutrient balance and the function of organelles such as mitochondria or the endoplasmic reticulum, which are important in intracellular metabolism, insulin release, and insulin sensitivity. In the insulin-producing pancreatic β-cells, autophagy is important in the maintenance of β-cell mass, structure, and function. Mice with deficiencies in β-cell-specific autophagy show reduced β-cell mass and defects in insulin secretion that lead to hypoinsulinemia and hyperglycemia but not diabetes. However, these mice developed diabetes when bred with ob/ob mice, suggesting that autophagy-deficient β-cells have defects in dealing with the increased metabolic stress imposed by obesity. These results also imply that autophagy deficiency in β-cells could be a factor in the progression from obesity to diabetes. Another important function of autophagy is in hypothalamic neurons for the central control of energy expenditure, appetite, and body weight. In addition, mice with autophagy deficiencies in the target tissues of insulin have yielded diverse phenotypes. Taken together, these results suggest that autophagy is important in the control of whole body energy and nutrient homeostasis, and its dysregulation could play a role in the development of metabolic disorders and diabetes.

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The majority of the vitamin D in our body is produced by cutaneous synthesis in response to sunlight. As more and more people live in cities and spend the bulk of their time indoors, it can be difficult to get sufficient sun exposure for adequate cutaneous production of vitamin D. Therefore, vitamin D insufficiency has become a very common health problem worldwide. The Korea National Health and Nutrition Examination Survey IV 2008 showed that the prevalence of vitamin D insufficiency, defined as a serum 25-hydroxyvitamin D [25(OH)D] level below 50 nmol/L, was 47.3% in males and 64.5% in females. Only 13.2% of males and 6.7% of females had a serum 25(OH)D level of greater than 75 nmol/L. In Korea, vitamin D insufficiency was more prevalent in young adults than in elderly people, likely due to the indoor lifestyle of younger people. Compared with the United States and Canada, Korea has a lower mean 25(OH)D level and a higher prevalence of vitamin D insufficiency. To improve the vitamin D status of the Korean population, more aggressive policies on food fortification and vitamin D supplementation are needed.

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Cancer metastases to the thyroid or adrenal gland are uncommon. Furthermore, cases showing long-term survival after surgical resection of those metastatic tumors are rare. We report a case of pulmonary artery intimal sarcoma with metastases to the thyroid and adrenal glands sequentially that was successfully treated with sequential metastasectomies. A 62-year-old woman presented with a 4-week history of dyspnea on exertion and facial edema in November 1999. Echocardiography and chest computed tomography (CT) revealed an embolism-like mass in the pulmonary trunk. Pulmonary artery endarterectomy with pulmonary valve replacement was performed, and histopathology revealed pulmonary artery intimal sarcoma. A thyroid nodule was found by chest CT in November 2001 (2 years after initial surgery). During follow-up, this lesion showed no change, but we decided to obtain fine needle aspiration cytology (FNAC) in August 2004 (4.7 years after initial surgery). FNAC revealed atypical spindle cells suggestive of metastatic intimal sarcoma. She underwent total thyroidectomy. During follow-up, a right adrenal gland mass was detected by chest CT in March 2006 (6.3 years after initial surgery), and adrenalectomy was done, which also revealed metastatic sarcoma. She has been followed up without any evidence of recurrent disease until May 2012 (12.5 years after initial surgery).

Citations

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• Reoperation of Pulmonary Artery Intimal Sarcoma for Recurrence After Pulmonary Artery Replacement
  Kentaro Miyazaki, Isao Matsumoto, Satoshi Nishikawa, Takashi Wada, Tetsuya Takayama, Daisuke Saito, Shuhei Yoshida, Kenji Iino, Hirofumi Takemura
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• Intimal sarcoma of the pulmonary artery with multiple lung metastases: Long-term survival case
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• Clinical Characteristics and Treatment Outcomes of Primary Pulmonary Artery Sarcoma in Korea
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• Presentation and management of pulmonary artery sarcoma
  Han Hsi Wong, Ioannis Gounaris, Ann McCormack, Marius Berman, Dochka Davidson, Gail Horan, Joanna Pepke-Zaba, David Jenkins, Helena M Earl, Helen M Hatcher
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• Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
  Won-Young Lee
  Endocrinology and Metabolism.2014; 29(3): 251.     CrossRef

Acute suppurative thyroiditis (AST) is a rare condition, as the thyroid gland is relatively resistant to infection. Thyroid function tests are usually normal in AST. A few cases of AST associated with thyrotoxicosis have been reported in adults. We report a case of AST that was associated with thyrotoxicosis in a 70-year-old woman. We diagnosed AST with thyroid ultrasonography and fine needle aspiration of pus. The patient improved after surgical intervention and had no anatomical abnormality. Fine needle aspiration is the best method for the difficult task of differentiating malignancy and subacute thyroiditis from AST with thyrotoxicosis. Earlier diagnosis and proper treatment for AST might improve the outcome.

Citations

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• Ultrasonographic Findings of Thyroid Parenchymal Disease
  Sung-Woo Kim
  Clinical Ultrasound.2024; 9(1): 25.     CrossRef
• Acute suppurative thyroiditis with Graves disease – A very rare association
  Inês Damásio, Joana Maciel, Maria Manuel Costa, Luisa Raimundo
  Archives of Endocrinology and Metabolism.2023;[Epub]     CrossRef
• Thyrotoxicosis as a rare presentation in acute suppurative thyroiditis: a case report
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• Infection of Thyroid Cyst Occurring 1 Month after Fine-Needle Aspiration in an Immunocompetent Patient
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  International Journal of Thyroidology.2018; 11(2): 182.     CrossRef
• Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
  Won-Young Lee
  Endocrinology and Metabolism.2014; 29(3): 251.     CrossRef

We report here the cases of two females with Graves' disease who developed insulin autoimmune syndrome after treatment with methimazole. The patients exhibited a sudden altered mental state after treatment with methimazole for approximately 4 weeks. Patients had hypoglycemia with serum glucose below 70 mg/dL, and laboratory findings showed both high levels of serum insulin and high titers of insulin autoantibodies. The two women had never been exposed to insulin or oral antidiabetic agents, and there was no evidence of insulinoma in imaging studies. After glucose loading, serum glucose, and total insulin levels increased abnormally. One of the patient was found to have HLA-DRB1*0406, which is known to be strongly associated with methimazole-induced insulin autoimmune syndrome. After discontinuation of methimazole, hypoglycemic events disappeared within 1 month. Insulin autoantibody titer and insulin levels decreased within 5 months and there was no further development of hypoglycemic events. We present these cases with a review of the relevant literature.

Citations

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• A Case of Methimazole-Induced Insulin Autoimmune Syndrome and Literature Review
  东昕 王
  Advances in Clinical Medicine.2024; 14(10): 19.     CrossRef
• HLA Alleles Associate with Insulin Autoimmune Syndrome
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• Methimazole-Induced Insulin Autoimmune Syndrome in a Korean Patient with Graves’ Disease Treated with Propylthiouracil: a Case Report and Literature Review
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  International Journal of Thyroidology.2024; 17(2): 295.     CrossRef
• Insulin Autoimmune Syndrome: A Systematic Review
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  International Journal of Endocrinology.2023; 2023: 1.     CrossRef
• Safety of Antithyroid Drugs in Avoiding Hyperglycemia or Hypoglycemia in Patients With Graves’ Disease and Type 2 Diabetes Mellitus: A Literature Review
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  Cureus.2023;[Epub]     CrossRef
• Case report: hypoglycemia secondary to methimazole-induced insulin autoimmune syndrome in young Taiwanese woman with Graves’ disease
  Hsuan-Yu Wu, I-Hua Chen, Mei-Yueh Lee
  Medicine.2022; 101(25): e29337.     CrossRef
• Analysis of the clinical characteristics of insulin autoimmune syndrome induced by methimazole
  Linli Sun, Weijin Fang, Dan Yi, Wei Sun, Chunjiang Wang
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• Preoperative plasmapheresis experience in Graves’ disease patients with anti-thyroid drug-induced hepatotoxicity
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• Glycemic variation in uncontrolled Graves’ disease patients with normal glucose metabolism: Assessment by continuous glucose monitoring
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  David Church, Luís Cardoso, Richard G Kay, Claire L Williams, Bernard Freudenthal, Catriona Clarke, Julie Harris, Myuri Moorthy, Efthmia Karra, Fiona M Gribble, Frank Reimann, Keith Burling, Alistair J K Williams, Alia Munir, T Hugh Jones, Dagmar Führer,
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• MANAGEMENT OF ENDOCRINE DISEASE: Pathogenesis and management of hypoglycemia
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  Endocrinology and Metabolism.2014; 29(3): 251.     CrossRef

Radioactive iodine (RAI) therapy has been used as a treatment option for Graves' disease, and it has been widely accepted to be safe. On the other hand, some evidence suggests that RAI therapy is possibly associated with a small increased risk of thyroid cancer. Herein, we report a rare case of anaplastic thyroid carcinoma (ATC) associated with Graves' disease, following RAI treatment. A 42-year-old woman had been diagnosed with Graves' disease and although she was treated with an antithyroid drug, she remained in a hyperthyroid state, which led to two RAI treatments. More than 10 years later, the patient revisited our clinic due to hoarseness, dysphagia, and dyspnea, which had lasted for 2 months. Neck computed tomography suggested thyroid carcinoma and a lymph node biopsy showed metastatic papillary carcinoma. The patient underwent total thyroidectomy and was finally diagnosed as having an ATC. It is not clear if the occurrence of ATC reported here was influenced by the RAI therapy or alternatively, it may only represent the delayed recognition of a rare change in the natural history of Graves' disease. Nevertheless, this report is worthwhile since it presents a very rare case of ATC that occurred eleven years after the RAI therapy for Graves' disease.

Citations

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• V600E BRAF-mutated anaplastic thyroid carcinoma after radioactive iodine for Graves’ disease: a case report and a review of the literature
  Marta Villanova, Luigi di Filippo, Filippo Maria Bolamperti, Carlo Rodella, Laura Castellino, Raffaele Giubbini
  Clinical and Translational Imaging.2024; 12(5): 467.     CrossRef
• Evaluation of ultrasonographical and cytological features of thyroid nodules in patients treated with radioactive iodine for hyperthyroidism
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• Papillary thyroid carcinoma in cervical lymph nodes with vanished thyroid gland after ablation of Graves’ disease by radioactive iodine
  O Hamdy, S Raafat, GA Saleh, K Atallah, Mahmoud M Saleh, AM Shebl, MA Hegazy
  The Annals of The Royal College of Surgeons of England.2019; 101(5): e122.     CrossRef
• Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
  Won-Young Lee
  Endocrinology and Metabolism.2014; 29(3): 251.     CrossRef

We report the case of a 36-year-old woman who presented with headache, fever, and amenorrhea. Laboratory analysis revealed hypopituitarism and autoimmune thyroiditis, while a cerebrospinal fluid study suggested concurrent aseptic meningitis. A magnetic resonance image (MRI) scan revealed a 1.0×0.9 cm cystic mass enlarging the sella turcica. Surgical resection via an endoscopic transsphenoidal route was performed. The histological finding of the excised tissue revealed foamy histiocytes with vacuolated cytoplasm, supporting the diagnosis of xanthomatous hypophysitis. Although a residual soft lesion was observed on the MRI image postoperatively, the patient's headache and fever improved. Ten months after surgery, the patient complained of visual impairment and headache, and the residual mass had enlarged into the suprasellar area. High dose (500 mg intravenous) methylprednisolone was administered for 3 days. During the methylprednisolone pulse therapy, the patient's visual acuity and headache improved. A follow-up MRI taken after methylprednisolone therapy showed a marked mass reduction. Our case supports an autoimmune pathophysiology for xanthomatous hypophysitis and suggests that high dose glucocorticoid therapy as a treatment option.

Citations

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• Xanthomatous hypophysitis causing hypogonadotropic hypogonadism resulting in delayed presentation of slipped capital femoral epiphysis
  Kirit Singh, Avinash Kumar Kanodia, Peter Ross, Antonia Torgersen, Jamie Maclean, Graham Leese, Kismet Hossain-Ibrahim
  British Journal of Neurosurgery.2022; 36(2): 286.     CrossRef
• Full recovery from chronic headache and hypopituitarism caused by lymphocytic hypophysitis: A case report
  Mao-Guang Yang, Han-Qing Cai, Si-Si Wang, Lin Liu, Chun-Mei Wang
  World Journal of Clinical Cases.2022; 10(3): 1041.     CrossRef
• Xanthomatous Hypophysitis Secondary to a Ruptured Rathke’s Cleft Cyst: A Case Report
  Emre Gezer, Burak Çabuk, Büşra Yaprak Bayrak, Zeynep Cantürk, Berrin Çetinarslan, Alev Selek, Mehmet Sözen, Damla Köksalan, Savaş Ceylan
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• Successful immunomodulatory treatment for recurrent xanthogranulomatous hypophysitis in an adolescent: illustrative case
  Sarah DeCou, Pablo F. Recinos, Richard A. Prayson, Christopher Karakasis, Anzar Haider, Neha Patel
  Journal of Neurosurgery: Case Lessons.2022;[Epub]     CrossRef
• Xanthogranulomatous hypophysitis: A rare presentation in a young female patient
  Mohammad Ali Yaghoubi, Samira Zabihyan, Amin Saeidinia, Masoumeh Gharib, Ramin Ghiyasi Moghaddam
  Clinical Case Reports.2022;[Epub]     CrossRef
• Xanthomatous Hypophysitis Presenting in an Adolescent Girl: A Long-Term Follow-Up of a Rare Case and Review of the Literature
  Jeanne Sze Lyn Wong, Azraai Bahari Nasruddin, Nalini M. Selveindran, Kartikasalwah Abd Latif, Fauziah Kassim, Sukanya Banerjee Nair, Janet Y.H. Hong
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• Xanthomatous Hypophysitis: A Case Report and Comprehensive Literature Review
  Jianyu Zhu, Zhicheng Wang, Wenze Wang, Jinghua Fan, Yi Zhang, Xiaoxu Li, Jie Liu, Shenzhong Jiang, Kan Deng, Lian Duan, Yong Yao, Huijuan Zhu
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• Recurring Primary Xanthomatous Hypophysitis Behaving Like Pituitary Adenoma: Additional Case and Literature Review
  Mansour Mathkour, Tyler Zeoli, Cassidy Werner, Tyler Scullen, Juanita Garces, Joseph Keen, Marcus Ware
  World Neurosurgery.2020; 138: 27.     CrossRef
• Imaging findings in hypophysitis: a review
  Ferdinando Caranci, Giuseppe Leone, Andrea Ponsiglione, Massimo Muto, Fabio Tortora, Mario Muto, Sossio Cirillo, Luca Brunese, Alfonso Cerase
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• Hypophysitis in the era of immune checkpoint inhibitors and immunoglobulin G4-related disease
  Leen Wehbeh, Sama Alreddawi, Roberto Salvatori
  Expert Review of Endocrinology & Metabolism.2019; 14(3): 167.     CrossRef
• Xanthomatous Hypophysitis Is Associated with Ruptured Rathke’s Cleft Cyst
  Kai Duan, Sylvia L. Asa, Daniel Winer, Zadeh Gelareh, Fred Gentili, Ozgur Mete
  Endocrine Pathology.2017; 28(1): 83.     CrossRef
• Xanthomatous Hypophysitis Presenting with Diabetes Insipidus Completely Cured Through Transsphenoidal Surgery: Case Report and Literature Review
  Wei Lin, Lu Gao, Xiaopeng Guo, Wenze Wang, Bing Xing
  World Neurosurgery.2017; 104: 1051.e7.     CrossRef
• Review of xanthomatous lesions of the sella
  B.K. Kleinschmidt‐DeMasters, Kevin O. Lillehei, Todd C. Hankinson
  Brain Pathology.2017; 27(3): 377.     CrossRef
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  Bishoy Hanna, Yan M. Li, Timothy Beutler, Parul Goyal, Walter A. Hall
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• Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
  Won-Young Lee
  Endocrinology and Metabolism.2014; 29(3): 251.     CrossRef

Atypical antipsychotics have replaced conventional antipsychotics in the treatment of schizophrenia because they have less of a propensity to cause undesirable neurologic adverse events including extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome (NMS). However, atypical antipsychotics have been known to result in various metabolic complications such as impaired glucose tolerance, diabetes and even diabetic ketoacidosis (DKA). In addition, a number of NMS cases have been reported in patients treated with atypical antipsychotics, although the absolute incidence of neurologic side effects is currently significantly low. Here, we report a patient who simultaneously developed DKA, acute renal failure and NMS with rhabdomyolysis after olanzapine treatment. Olanzapine-induced metabolic complications and NMS were dramatically improved with cessation of the olanzapine treatment and initiation of supportive management including fluid therapy, hemodialysis, and intensive glycemic control using insulin. At short-term follow-up, insulin secretion was markedly recovered as evidenced by a restoration of serum C-peptide level, and the patient no longer required any hypoglycemic medications. Despite the dramatic increase in the use of atypical antipsychotics treatment, individualized treatments along with careful monitoring may be prudent for high risk or vulnerable patients in order to avoid the development of metabolic side effects.

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  Francesco Piacenza, Suet Kee Ong, Patrick O’Brien, Maurice Clancy
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  Won-Young Lee
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