Category: Adrenal Disorders
Objective : In endocrinology, clinical decisions are mainly made based on the hormonal levels. Laboratory interference is a drawback in hormonal testing, and clinicians should have a high index of suspicion when faced with biochemical results discordant with the patient's clinical manifestations. We present a case of a patient with similar scenario.
Methods : A 20 y-old female with history of common variable immunodeficiency, asthma, hypothyroidism presented to our office for second opinion with concern for Cushing's disease. She reported 55 lbs weight gain in one year. Her medications are levothyroxine 50 mcg daily and human immune globulin (IG) biweekly subcutaneous injections. She denied any recent exogenous steroid and reported regular menses. She had tried various diets without success. She had initially seen an outside endocrinologist and had extensive work up including midnight salivary cortisol, 24-hour urine free cortisol, overnight dexamethasone suppression test, ACTH levels. All were within normal limits except for an ACTH level of 327 (normal range 7.2-63 pg/ml). She had repeat blood work 3 months later and had normal cortisol levels (urine and saliva) but ACTH level was reported to be 270.5. She had a pituitary MRI which showed a hypointense 4X3X4mm cyst in the pituitary. She was then recommended petrosal sinus venous sampling and presented to us for second opinion. Her physical exam was unremarkable, had no cushingoid features. Because of the discrepancy between the biochemical results and the clinical picture, laboratory interference was high on our differential especially with her being on IgG injections. Patient’s blood sample was collected and processed in our laboratory. As a first step, all the antibodies/immunoglobulins were isolated from the serum and ACTH levels were remeasured with an immunoassay method.
Results : ACTH level in our laboratory was reported as normal - 53 ng/mL [ref: 9 - 46pg/ml]. To further validate the results same sample (without immunoglobulins) was sent to outside lab and ACTH levels were reported to be in normal range (39.6 [ ref:7.2-63.3pg/ml]).
Discussion : Interference in immunoassays is a serious but underestimated problem. Analytic interference can result in erroneous values that can lead to costly investigations, misdiagnosis, and unnecessary treatments. Several cases were described in literature about IG interference with TSH, LH, FSH assays but ours is the first case to report about ACTH interference and IG injections.
Conclusion : Our case reiterates that clinicians should have a high index of suspicion about the interference when the clinical picture is inconsistent with biochemical results.
Deepika Nandiraju– Fellow in training, Thomas Jefferson University hospital, Philadelphia, Pennsylvania
Serge Jabbour– Professor of Medicine, Director - Division of Endocrinology, Thomas Jefferson University Hospital, philadelphia, Pennsylvania
Douglas Stickle– Professor, Pathology, Jefferson University Hospital, Philadelphia, Pennsylvania
Fellow in training
Thomas Jefferson University hospital
second year Fellow in training
Professor of Medicine, Director - Division of Endocrinology
Thomas Jefferson University Hospital
Jabbour is Professor of Medicine and Director of the Division of Endocrinology, Diabetes, and Metabolic Diseases in the Department of Medicine at Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia, Pennsylvania. He is also Director of the Jefferson Diabetes Center.
Dr Jabbour completed his training in Endocrinology, Diabetes, and Metabolic Diseases at Thomas Jefferson University in Philadelphia.