Hypoinsulinemic hypoglycemia as a presenting feature of systemic lupus erythematosus

Mahmoud, Sarah A.; Soliman, Mohammed A.; El-Ebiary, Ahmad A.

doi:10.1016/j.medcle.2020.05.054

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Mahmoud, Mohammed A. Soliman, Ahmad A. El-Ebiary" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Sarah A." "apellidos" => "Mahmoud" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Mohammed A." "apellidos" => "Soliman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:4 [ "nombre" => "Ahmad A." "apellidos" => "El-Ebiary" "email" => array:1 [ 0 => "a.ebiary@med.tanta.edu.eg" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Faculty of Medicine, Tanta University, Tanta, Egypt" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "NMC Specialty Hospital, Al Nahda, Dubai, United Arab Emirates" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hipoglucemia hipoinsulinémica como manifestación inicial de un lupus eritematoso sistémico" ] ] "textoCompleto" => "Systemic lupus erythematosus (SLE) is associated with type B insulin resistance syndrome in some patients. Most cases present with high insulin levels. However, few cases may suffer hypoglycemia with low insulin blood levels. We present an atypical case of autoimmune hypoglycemia that was associated with a newly diagnosed SLE on presentation.Case presentationA 33-year-old woman presented to the emergency department with loss of consciousness. The patient was found hypoglycemic (25mg/dl), so dextrose 25% was administered immediately, and she regained her full consciousness. The patient reported recurrent attacks of sweating, dizziness and palpitation during fasting over the past year that were attributed to low blood glucose (fasting hypoglycemia). She had no history of chronic diseases, operations or drug administration.The physical examination was unremarkable except for mild hypertension, mild bilateral lower limb edema, and a hyperpigmented skin rash on the cheeks and forehead.Magnetic resonance imaging of the brain was found normal. On doing the 72-hour fasting test, serum insulin and C-peptide samples were withdrawn at a random blood glucose concentration of 35mg/dl after 13h of fasting. Morning serum cortisol and adrenocorticotropic hormone, thyroid functions, routine laboratory investigations, and analysis for anti-insulin antibodies were requested.She had an erythrocyte sedimentation rate above 100 in the first hour; leukopenia (leukocytic count=2000/mm3); serum creatinine of 1.4mg/dl; and positive urine analysis for proteins (++). Anti-nuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), C3, C4, and 24-hour urinary protein were ordered, and the results were positive with high titer of ANA (1/300), positive anti-dsDNA, and low C3 and C4. The 24-h urinary protein level was 984mg and a renal biopsy was indicated. The fasting insulin and C-peptide levels were very low (1.16μIU/ml and 0.56ng/ml, respectively). Normal thyroid functions (thyroid stimulating hormone=1.13) and normal morning serum cortisol (28mcg/dl) levels were detected.The possibility of autoimmune hypoglycemia was investigated despite a negative anti-insulin antibody test. The possibility of a paramalignant condition with insulin-like growth factor 2 secretion was also investigated by performing computed tomography scanning of the chest and abdomen with contrast, and they were found normal except for mild hepatomegaly and bilateral minimal pleural effusion. Serum levels of tumor-markers (CA 19-9 and CEA) were normal. Lupus anticoagulant and anticardiolipin IgG and IgM were negative. The renal biopsy showed diffuse proliferative glomerulonephritis. Consequently, pulse steroid and cyclophosphamide 500mg were administered. Our patient showed improvement in the form of reduced proteinuria (400mg/24h), decreased serum creatinine (1mg/dl) and sustained normal blood glucose concentration (90–130mg/dl) after discharge from hospital for 4 months.This is an atypical case of autoimmune hypoglycemia that was associated with a newly diagnosed SLE on presentation. The causes of hypoglycemia in adults are various, including an overdose with drugs (such as insulin or insulin secretagogue), excess alcohol intake, critical illnesses (hepatic, renal or cardiac failure, sepsis), cortisol deficiency, hypothyroidism, non-islet cell tumor, insulinoma, autoimmune hypoglycemia, and endogenous insulin secretagogue.<a class="elsevierStyleCrossRefs" href="#bib0030">1,2</a>These causes were considered in the differential diagnosis of our patient. The positive findings revealed by the diagnostic work-up indicated a diagnosis of lupus activity and nephritis. Consequently, we postulated that hypoglycemia was the result of an autoimmune condition.In our patient, anti-insulin-antibody test was negative. Analysis of anti-insulin-receptor antibodies was not available, but the patient was suspected – mainly through exclusion of other potential etiologies – to suffer from an atypical form of type B insulin resistance.The occurrence of hypoglycemia in type B insulin resistance is unusual as the majority of patients suffer from hyperglycemia. However, anti-receptor antibodies were demonstrated to exert insulin-like bioactivity in vitro, thus they may mimic the action of insulin.<a class="elsevierStyleCrossRef" href="#bib0040">3</a>Affected individuals often have a history of other autoimmune disorders. Our patient fulfilled six out of 11 criteria for the classification of SLE determined by the American College of Rheumatology and the European League Against Rheumatism, including serositis (pleural effusion), hematologic disorder (leucopenia), renal affection (proteinuria and nephritis), immunologic disorder (high anti-ds antibodies, low C3), and high titer of ANA.Glucocorticoid therapy has been reported to improve both hypoglycemia and the activity of SLE. The beneficial effects of glucocorticoids in such cases may be exerted either by inhibiting antibody production or by blocking the post-receptor cellular responses after binding of the antibody to the receptors. Our patient, as well as the similar reported cases,<a class="elsevierStyleCrossRefs" href="#bib0040">3–5</a> showed improvement after administration of steroid therapy.FundingThis study received no funding from any funding source.Conflict of interestThe authors declare that they have no conflict of interest." 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