scholarly journals Nivolumab-induced fulminant diabetic ketoacidosis followed by thyroiditis

Author(s):  
Ploutarchos Tzoulis ◽  
Richard W Corbett ◽  
Swarupini Ponnampalam ◽  
Elly Baker ◽  
Daniel Heaton ◽  
...  

Summary Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which acts as immune checkpoint inhibitor against the programmed cell death protein-1, for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as evidenced by venous glucose of 47 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95 and bicarbonate of 6.6 mmol/L. She has had no personal or family history of diabetes mellitus (DM), while random venous glucose, measured 1 week prior to hospitalisation, was 6.1 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12 kIU/L (0–5 kU/L), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab was recommenced without the development of other immune-mediated phenomena until 6 months later, when she developed hypothyroidism with TSH 18 U/L and low free T4. She remains insulin dependent and has required levothyroxine replacement, while she has maintained good radiological and clinical response to immunotherapy. This case is notable for the rapidity of onset and profound nature of DKA at presentation, which occurred two months following commencement of immunotherapy. Despite the association of nivolumab with immune-mediated endocrinopathies, only a very small number of patients developing type 1 DM has been reported to date. Patients should be closely monitored for hyperglycaemia and thyroid dysfunction prior to and periodically during immunotherapy. Learning points: Nivolumab can induce fulminant type 1 diabetes, resulting in DKA. Nivolumab is frequently associated with thyroid dysfunction, mostly hypothyroidism. Nivolumab-treated patients should be monitored regularly for hyperglycaemia and thyroid dysfunction. Clinicians should be aware and warn patients of potential signs and symptoms of severe hyperglycaemia.

2016 ◽  
Vol 53 (5) ◽  
pp. 853-856 ◽  
Author(s):  
Sung Hye Kong ◽  
Seo Young Lee ◽  
Ye Seul Yang ◽  
Tae Min Kim ◽  
Soo Heon Kwak

Vestnik ◽  
2021 ◽  
pp. 107-111
Author(s):  
С.И. Сабирова ◽  
С.Г. Надырова ◽  
А.Б. Жанзак ◽  
А.Е. Манасбаева ◽  
Ж.Ж. Нургалиева

Целью научной работы является изучение структуры заболеваний щитовидной железы у больных сахарным диабетом 1 типа. В данной статье мы ретроспективно проанализировали 972 историй болезни больных детей с СД 1 типа, находившихся на стационарном лечении в ДГКБ №2 г. Алматы (Казахстан) в период с 2014 по 2019 гг. Были изучены и оценены показатели физического развития, объективные данные (кожные покровы, ЧСС, АД, пальпация ЩЖ), лабораторно - уровней гормонов ТТГ, свТ4, свТ3, а/т к ТПО, а/т к ТГ в сыворотки крови, инструментально - УЗИ ЩЖ. Всего за 2014-2019 гг. через отделение эндокринологии ДГКБ №2 прошли 972 детей с диагнозом СД 1 типа. Большинство детей (382 человек, 79,9%) имели стаж болезни СД до 5 лет. 88 детей (18,5%) со стажем от 5 до 10 лет, 8 человек (1,7%) страдали СД более 10 лет. СД1 в основном был диагностирован в возрасте 7-12 лет (245-51,3%), меньше всего выявили СД 1 типа у детей до 3 лет (21 - 4,4%). Из общего количества пациентов с СД1 (972) было обследовано на функцию ЩЖ 478 детей (49,2%). Среди них было выявлено 319 детей с дисфункцией ЩЖ, что составляет 66,7%. Так, за 2014 год из 92 детей - 7 (7,6%), обследованных на функцию щитовидной железы, в результате чего было выявлено 6 (85,7%) детей с дисфункцией щитовидной железы. С каждым годом росло количество детей, которых направляли на обследование ЩЖ, так в сравнении с 2014 годом, когда из 92 детей - 7 (7,6%) были обследованы на функцию щитовидной железы, в 2019 году были обследованы уже 222 (92,1%) детей из 241. Симптомы как гиперфункции, так и гипофункции ЩЖ, особенно их субклинические варианты протекают под маской других заболевании и не сразу обнаруживаются, исходя из этого следует сразу обследовать на функцию ЩЖ при поступлении и в дальнейшим их наблюдать в динамике. В ходе исследования дисфункция щитовидной железы диагностирована у 319 (67,7%) пациентов, что должно привлечь внимание не только эндокринологов, но и врачей общей практики, педиатров и настроить их на прицельный поиск этой патологии и своевременную коррекцию гипотиреоза или другой патологии ЩЖ при его наличии The purpose of this research is to study the structure of thyroid diseases in patients with type 1 diabetes. In this article, we retrospectively analyzed 972 case histories of sick children with type 1 diabetes who were treated in the children's city clinical hospital No. 2 in Almaty (Kazakhstan) in the period from 2014 to 2019. Physical development indicators, objective data (skin, heart rate, blood pressure, thyroid palpation), laboratory levels of TSH, thyroxine, triiodothyronine, antibodies to thyroperoxidase, antibodies to thyroglobulin in blood serum, instrumental ultrasound examination of the thyroid gland were studied and evaluated. In total, in 2014-2019, 972 children with a diagnosis of type 1 diabetes mellitus passed through the endocrinology Department of the children's city clinical hospital No. 2.The majority of children (382 people, 79.9%) had a history of diabetes up to 5 years. 88 children (18.5%) with experience from 5 to 10 years, 8 people (1.7%) had diabetes for more than 10 years. Type 1 diabetes was mainly diagnosed at the age of 7-12 years (245-51. 3%), the least detected type 1 diabetes in children under 3 years (21 - 4.4%). Out of the total number of patients with type 1 diabetes (972), 478 children (49.2%) were examined for thyroid function. Among them, 319 children with thyroid dysfunction were identified, which is 66.7%. So, in 2014, out of 92 children, 7 (7.6%) were examined for thyroid function, as a result of which 6 (85.7%) children had thyroid dysfunction. Every year, the number of children referred for thyroid examination increased, so compared to 2014, when out of 92 children - 7 (7.6%) were examined for thyroid function, in 2019, 222 (92.1%) children out of 241 were examined. Symptoms of both hyperfunction and hypofunction of the thyroid gland, especially their subclinical variants, occur under the guise of other diseases and are not immediately detected, so you should immediately investigate the function of the thyroid gland at admission and further observe them in dynamics. During the study, thyroid dysfunction was diagnosed in 319 (67.7%) patients, which should attract the attention of not only endocrinologists, but also General practitioners, pediatricians and set them up for a targeted search for this pathology and timely correction of hypothyroidism or other thyroid pathology if it is present.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Peng ◽  
Jinna Yuan ◽  
Valentina Chiavaroli ◽  
Guanping Dong ◽  
Ke Huang ◽  
...  

BackgroundDiabetic ketoacidosis (DKA) is a potentially life-threatening complication of type 1 diabetes (T1D), and a leading cause of death in children aged <15 years with new-onset T1D.Aimsi) to assess the incidence of DKA in children and adolescents newly diagnosed with T1D over a 10-year period at a large regional center in China; and ii) to examine the clinical symptoms and demographic factors associated with DKA and its severity at diagnosis.MethodsWe carried out a retrospective audit of a regional center, encompassing all youth aged <16 years diagnosed with T1D in 2009–2018 at the Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China). DKA and its severity were classified according to ISPAD 2018 guidelines.Results681 children were diagnosed with T1D, 50.1% having DKA at presentation (36.0% mild, 30.0% moderate, and 33.9% severe DKA). The number of patients diagnosed with T1D progressively rose from approximately 39 cases/year in 2009–2010 to 95 cases/year in 2017–2018 (≈2.5-fold increase), rising primarily among children aged 5–9 years. DKA incidence was unchanged but variable (44.8% to 56.8%). At T1D diagnosis, 89% of patients reported polyuria and 91% polydipsia. Children presenting with DKA were more likely to report vomiting, abdominal pain, and particularly fatigue. DKA was most common among the youngest children, affecting 4 in 5 children aged <2 years (81.4%), in comparison to 53.3%, 42.7%, and 49.3% of patients aged 2–4, 5–9, and ≥10 years, respectively. Children with severe DKA were more likely to report vomiting, fatigue, and abdominal pain, but less likely to report polyuria, polydipsia, and polyphagia than those with mild/moderate DKA. Rates of severe DKA were highest in children aged <2 years (51.1%).ConclusionsThe number of children diagnosed with T1D at our regional center increased over the study period, but DKA rates were unchanged. With 9 of 10 children reporting polyuria and polydipsia prior to T1D diagnosis, increasing awareness of this condition in the community and among primary care physicians could lead to earlier diagnosis, and thus potentially reduce rates of DKA at presentation.


2020 ◽  
Vol 26 (3) ◽  
pp. 305-311
Author(s):  
Janaki D. Vakharia ◽  
Sungeeta Agrawal ◽  
Janine Molino ◽  
Lisa Swartz Topor

Objective: To determine the relationship between family history of diabetes mellitus (DM) and diabetic ketoacidosis (DKA) recurrence in youth with established type 1 diabetes mellitus (T1DM). Methods: We performed a retrospective chart review of patients with DKA admitted to a pediatric hospital between January, 2009, and December, 2014. We compared patients with recurrent (≥2 admissions) and nonrecurrent DKA (1 admission) and investigated patient level factors, including family history, that may be associated with DKA recurrence in pediatric patients with established T1DM. Results: Of the 131 subjects in the study, 51 (39%) subjects were in the recurrence group. Age ≥15 years old, public health insurance, and family history of T1DM or type 2 diabetes mellitus were associated with recurrent DKA admissions in both univariable and multivariable analyses. Family history was associated with DKA recurrence, with an incidence rate ratio of 1.5 (95% confidence interval = 1.0 to 2.3; P = .03). The association was not explained by type of familial diabetes, first degree relative status, or whether the family member lived in the household. Conclusion: Recognition that a positive family history of DM may be associated with a higher risk for DKA recurrence in patients with established T1DM may allow for targeted education and focus on a previously unidentified population at increased risk for DKA. Understanding the mechanism underlying the effect of family history of diabetes on the rates of DKA in patients with established T1DM may allow for improved identification and education of patients who may be at risk for DKA recurrence. Abbreviations: CI = confidence interval; DKA = diabetic ketoacidosis; EHR = electronic health record; IBD = inflammatory bowel disease; IRR = incidence rate ratio; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus


2017 ◽  
Vol 5 (19) ◽  
pp. 6
Author(s):  
Rocio Gavidia Quezada ◽  
Hawa Edriss

Diabetic ketoacidosis is a well-known acute complication in patients with both type 1 andtype 2 diabetes mellitus. Although mortality has decreased considerably, it remains an importantcause for admission to intensive care units. Medical management includes intravenous fluidtherapy, insulin, correction of electrolyte abnormalities, and addressing the precipitating factorwhich in most cases is infection or non-compliance with insulin therapy. Usually patients withdiabetic ketoacidosis are admitted to the intensive care unit for continuous infusion of insulin;however, the development of rapid acting insulin analogues has made it possible to treatmild to moderate diabetic ketoacidosis with subcutaneous insulin. Although studies usingsubcutaneous insulin include only a small number of patients, this approach seems as effectiveas intravenous insulin infusions in patients with mild to moderate diabetic ketoacidosis. Diabeticeducation and close follow-up for patients admitted for diabetic ketoacidosis remain essentialto avoid recurrence and readmissions.Keywords: Diabetic ketoacidosis, acute complication in diabetes, rapid acting insulinanalogues, subcutaneous insulin in diabetic ketoacidosis


Author(s):  
A Chinoy ◽  
N B Wright ◽  
M Bone ◽  
R Padidela

Summary Hypokalaemia at presentation of diabetic ketoacidosis is uncommon as insulin deficiency and metabolic acidosis shifts potassium extracellularly. However, hypokalaemia is a recognised complication of the management of diabetic ketoacidosis as insulin administration and correction of metabolic acidosis shifts potassium intracellularly. We describe the case of a 9-year-old girl with newly diagnosed type 1 diabetes mellitus presenting in diabetic ketoacidosis, with severe hypokalaemia at presentation due to severe and prolonged emesis. After commencing management for her diabetic ketoacidosis, her serum sodium and osmolality increased rapidly. However, despite maximal potassium concentrations running through peripheral access, and multiple intravenous potassium ‘corrections’, her hypokalaemia persisted. Seventy two hours after presentation, she became drowsy and confused, with imaging demonstrating central pontine myelinolysis – a rare entity seldom seen in diabetic ketoacidosis management in children despite rapid shifts in serum sodium and osmolality. We review the literature associating central pontine myelinolysis with hypokalaemia and hypothesise as to how the hypokalaemia may have contributed to the development of central pontine myelinolysis. We also recommend an approach to the management of a child in diabetic ketoacidosis with hypokalaemia at presentation. Learning points: Hypokalaemia is a recognised complication of treatment of paediatric diabetic ketoacidosis that should be aggressively managed to prevent acute complications. Central pontine myelinolysis is rare in children, and usually observed in the presence of rapid correction of hyponatraemia. However, there is observational evidence of an association between hypokalaemia and central pontine myelinolysis, potentially by priming the endothelial cell membrane to injury by lesser fluctuations in osmotic pressure. Consider central pontine myelinolysis as a complication of the management of paediatric diabetic ketoacidosis in the presence of relevant symptoms with profound hypokalaemia and/or fluctuations in serum sodium levels. We have suggested an approach to the management strategies of hypokalaemia in paediatric diabetic ketoacidosis which includes oral potassium supplements if tolerated, minimising the duration and the rate of insulin infusion and increasing the concentration of potassium intravenously (via central line if necessary).


Author(s):  
A Majid ◽  
B J Wheeler

Summary In clinical practice, seizures independent of hypoglycemia are observed in patients with type 1 diabetes mellitus (T1DM) more frequently than expected by chance, suggesting a link. However, seizures during management of diabetic ketoacidosis (DKA) have generally been considered a bad prognostic factor, and usually associated with well-known biochemical or neurological complications. We present the case of a 17-year-old girl with known T1DM managed for severe DKA complicated by hypocapnic seizure. We review the literature on this rare occurrence as well as outline other possible differentials to consider when faced with the alarming combination of DKA and seizure. Learning points: Seizures during DKA treatment require immediate management as well as evaluation to determine their underlying cause. Their etiology is varied, but a lowered seizure threshold, electrolyte disturbances and serious neurological complications of DKA such as cerebral edema must all be considered. Sudden severe hypocapnia may represent a rare contributor to seizure during the treatment of DKA.


2019 ◽  
Vol 12 (8) ◽  
pp. e229568 ◽  
Author(s):  
Hafez Mohammad Ammar Abdullah ◽  
Radowan Elnair ◽  
Uzma Ikhtiar Khan ◽  
Muhammad Omar ◽  
Oscar L Morey-Vargas

Nivolumab is a programmed cell death receptor (PD-1) inhibitor that is increasingly used for various malignancies, both as a first line agent and as salvage therapy. Being a PD-1/PD-1 ligand checkpoint inhibitor, it is known to cause autoimmune inflammation of various organs and has been associated with thyroiditis, insulitis, colitis, hepatitis and encephalitis to name a few. There are increasing reports of nivolumab leading to acute onset fulminant type 1 diabetes and diabetic ketoacidosis (DKA). We present a case of a 68-year-old man who developed DKA after 2 doses of nivolumab for metastatic melanoma. He was found to have type 1 diabetes, but no diabetes related antibodies were positive. He recovered from diabetes and continues to use insulin 1 year after his diagnosis. This case and associated review illustrates the importance of educating and monitoring patients who start nivolumab therapy regarding this potentially life threatening complication.


Author(s):  
Semine Özdemir Dilek ◽  
Fatih Gürbüz ◽  
İhsan Turan ◽  
Can Celiloğlu ◽  
Bilgin Yüksel

Abstract Objectives The COVID-19 pandemic is a global health problem with high morbidity and mortality. This study aimed to investigate patients who were diagnosed with type 1 diabetes during the pandemic and evaluate the effect of the pandemic on the clinical findings of these patients by comparing them with findings from a year prior. Methods Patients diagnosed with type 1 diabetes mellitus between 2019 and 2021 were separated into two groups: Patients diagnosed prepandemic and those diagnosed during the pandemic. Results The number of newly diagnosed diabetes cases increased from 46 in the prepandemic period to 74 in the pandemic period. The number of cases diagnosed with diabetic ketoacidosis (DKA) in the clinic increased from 58.7 to 91.9%. We found that moderate and severe DKA rates from 18.5 and 14.8% to 23.5 and 22.1%, respectively. Besides, the average HbA1c was higher, while the average bicarbonate was lower in cases diagnosed during the pandemic period compared to the prepandemic period (p=0.048 and p<0.001, respectively). We found that celiac autoantibody positivity antibodies to glutamic acid decarboxylase (anti GAD) positivity, and islet cell antibodies (ICA), ICA and anti GAD positivity coexistence were higher (p=0.045, p=0.008, and p=0.007, respectively) among the patients diagnosed during the pandemic. Conclusions We observed an increase in the number of patients newly diagnosed with type 1 diabetes mellitus, an increase in autoantibody positivity, and higher rates and severity of DKA during the COVID-19 pandemic period compared to the prepandemic period.


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