. References 1 Hirata Y Ishizu H Ouchi N Motomura S Abe M Hara Y Wakasugi H Takahashi I Sakano H Tanaka M 1970 Insulin autoimmunity in a case of spontaneous hypoglycemia . Journal of the Japan Diabetes Society 13
Pooja Sahni, Nitin Trivedi, and Abdulkadir Omer
M Horsey, P Hogan, and T Oliver
-Malefora A 2015 Autoimmune mechanisms in pernicious anaemia & thyroid disease . Autoimmunity Reviews 14 763 – 768 . ( doi:10.1016/j.autrev.2015.04.011 ) 8 Andrès E Loukili NH Noel E Kaltenbach G Abdelgheni MB Perrin AE
Florence Gunawan, Elizabeth George, and Adam Roberts
Immune checkpoint inhibitors are the mainstay of treatment for advanced melanoma, and their use is being increasingly implicated in the development of autoimmune endocrinopathies. We present a case of a 52-year-old man with metastatic melanoma on combination nivolumab and ipilumimab therapy who developed concurrent hypophysitis, type 1 diabetes mellitus (T1DM) and diabetes insipidus. He presented prior to third cycle of combination treatment with a headache, myalgias and fatigue. Biochemistry and MRI pituitary confirmed anterior pituitary dysfunction with a TSH: 0.02 mU/L (0.5–5.5 mU/L), fT4: 5.2 pmol/L (11–22 pmol/L), fT3: 4.0 pmol/L (3.2–6.4 pmol/L), cortisol (12:00 h): <9 nmol/L (74–286 nmol/L), FSH: 0.7 IU/L (1.5–9.7 IU/L), LH: <0.1 IU/L (1.8–9.2 IU/L), PRL: 1 mIU/L (90–400 mIU/L), SHBG: 34 nmol/L (19–764 nmol/L) and total testosterone: <0.4 nmol/L (9.9–27.8 nmol/L). High-dose dexamethasone (8 mg) was administered followed by hydrocortisone, thyroxine and topical testosterone replacement. Two weeks post administration of the third cycle, he became unwell with lethargy, weight loss and nocturia. Central diabetes insipidus was diagnosed on the basis of symptoms and sodium of 149 mmol/L (135–145 mmol/L). Desmopressin nasal spray was instituted with symptom resolution and normalization of serum sodium. Three weeks later, he presented again polyuric and polydipsic. His capillary glucose was 20.8 mmol/L (ketones of 2.4 mmol), low C-peptide 0.05 nmol/L (0.4–1.5 nmol/L) and HbA1c of 7.7%. T1DM was suspected, and he was commenced on an insulin infusion with rapid symptom resolution. Insulin antibodies glutamic acid decarboxylase (GAD), insulin antibody-2 (IA-2) and zinc transporter-8 (ZnT8) were negative. A follow-up MRI pituitary revealed findings consistent with recovering autoimmune hypophysitis. Immunotherapy was discontinued based on the extent of these autoimmune endocrinopathies.
- The most effective regime for treatment of metastatic melanoma is combination immunotherapy with nivolumab and ipilumimab, and this therapy is associated with a high incidence of autoimmune endocrinopathies.
- Given the high prevalence of immune-related adverse events, the threshold for functional testing should be low.
- Traditional antibody testing may not be reliable to identify early-onset endocrinopathy.
- Routine screening pathways have yet to be adequately validated through clinical trials.
Clarissa Ern Hui Fang, Mohammed Faraz Rafey, Aine Cunningham, Sean F Dinneen, and Francis M Finucane
cell autoimmunity, presence of hyperosmolarity, excess adiposity, strong family history, probable hepatic steatosis, acanthosis and excellent response to metformin and lifestyle modification, we diagnosed risperidone-induced KPD. (We thought that
Cliona Small, Aoife M Egan, El Muntasir Elhadi, Michael W O’Reilly, Aine Cunningham, and Francis M Finucane
) ( 3 , 4 ), though some do ( 5 , 6 ). Heterogeneity exists in the approach to diagnosing KPD. Some authorities emphasise adiposity and ethnicity ( 7 ), whereas others consider beta-cell function and markers of beta-cell autoimmunity in assessing the
Wann Jia Loh, Kesavan Sittampalam, Suan Cheng Tan, and Manju Chandran
be undertaken with regard to autoimmunity as a possible underlying mechanism in the development of this fascinating disease. Case presentation A 55-year-old Chinese man presented to the hospital with fatigue, knee joint pains and
-intolerance subsequent to the development of autoimmune diseases (1) . Graves' disease is recognised as a disease that involves both Th2-mediated autoantibodies and Th1-stimulated Tc cytokines (2) . The pathophysiological role of Treg in thyroid autoimmunity remains
Christine Yu, Inder J Chopra, and Edward Ha
second trigger or exacerbating factor may have been the large iodine load from the CT angiogram, inducing a Jod Basedow effect in the setting of ipilimumab-induced autoimmunity. This phenomenon, also known as iodine-induced hyperthyroidism, occurs when
Elena Carrillo, Amparo Lomas, Pedro J Pinés, and Cristina Lamas
. Investigation A complete biochemistry ( Table 1 ) showed hypomagnesemia, hypertransaminasemia and renal failure (serum creatinine of 2.7 mg/dL, descending to 2.1 mg/dL with intravenous fluid therapy). The study of pancreatic autoimmunity was negative and C
Chih-Ting Su and Yi-Chun Lin
Insulin antibodies (IA) associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA) found in insulin autoimmune syndrome (IAS), which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%), high insulin concentration (111.9 IU/mL) and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly.
- Insulin autoimmune syndrome (IAS) or IAS-like situation should be one of the differential diagnosis in patients with hyperinsulinemic hypoglycemia.
- Although less reported, insulin antibodies (IA) caused by exogenous insulin analog should be considered as the cause of hypoglycemia.
- Patients with suspected insulin autoimmune syndrome (IAS) should be screened for drugs related to autoimmunity to endogenous insulin.