Quick Consult: Symptoms: Multiple Episodes of Transient Altered Mental Status : Emergency Medicine News

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Symptoms: Multiple Episodes of Transient Altered Mental Status

Maurantonio, Michael MD

Emergency Medicine News 45(1):p 17-18, January 2023. | DOI: 10.1097/01.EEM.0000911924.36979.df
    FU1-15
    Figure:
    transient altered mental status, thyroid nodule, MRI, insulinoma
    FU2-15
    Figure

    A man in his 40s with hypogonadism on testosterone replacement therapy and a reportedly benign thyroid nodule presented to the emergency department via EMS with altered mental status. The patient's wife said the patient had had multiple similar episodes over the past few months, each lasting less than 10 minutes.

    He had sought ED care for a previous episode but left prior to evaluation because wait times were long and his symptoms had resolved within half an hour of arrival. The patient's wife said this episode had lasted longer, about 15 minutes, and was accompanied by incomprehensible speech and bizarre arm movements.

    The patient was found on the floor on the day of this presentation. His wife called EMS when he did not return to baseline. A glucose of 49 mg/dL was noted in the field, for which the patient received a bolus of glucose-containing fluids.

    No reliable trigger or family history of similar symptoms was identified for these episodes. The patient had not started any new medications nor adjusted his existing medications. He seemed to improve after the first ED visit after eating a candy bar from the vending machine in the waiting room.

    He was alert, oriented, and otherwise well-appearing. An extensive neurologic examination revealed no focal deficit. An examination of his skin was unremarkable, and his wife said he appeared to be at his baseline mental status.

    What is the diagnosis?

    Find the diagnosis and case discussion on next page.

    Diagnosis: Insulinoma

    This patient's altered mental status was likely caused by his hypoglycemia, which had not been detected during prior episodes. He was asked about a history of endocrine neoplasms given his medical history. Inquiring about these, specifically neoplasms involving the pituitary and parathyroid glands, is warranted when considering a diagnosis of insulinoma. (StatPearls [Internet]. July 24, 2022; http://bit.ly/3AdKxV8.)

    An insulinoma is a functional neuroendocrine tumor that secretes insulin with resultant fasting hypoglycemia. (StatPearls [Internet]. July 24, 2022; http://bit.ly/3AdKxV8.) This can present as an isolated entity, but it may also be a manifestation of multiple endocrine neoplasia (MEN1).

    It is not uncommon for patients to experience a delay in diagnosis because this condition is rare, with an incidence of one to three cases per million per year (Endotext [Internet]. Oct. 25, 2020; http://bit.ly/3fYyP9Q), and it requires high clinical suspicion to detect because one can misattribute the symptoms to other etiologies including psychiatric, neurologic, and cardiac conditions. (World J Gastroenterol. 2013;19[6]:829; http://bit.ly/3UvOQD7.)

    Patients can present with a variety of autonomic and neuroglycopenic symptoms, such as diaphoresis, tremor, palpitations, confusion, behavioral or personality change, and even seizure and coma. (World J Gastroenterol. 2013;19[6]:829; http://bit.ly/3UvOQD7.)

    The clinical syndrome is classically characterized by a set of criteria termed Whipple's triad, which consists of episodic hypoglycemia, CNS symptoms temporally related to episodes of hypoglycemia, and reversal of CNS symptoms by administering glucose. (BMJ Case Rep. 2010;2010:bcr08.2009.2158; http://bit.ly/3O4XOVO.) It dates back to the 1930s when it was proposed by Allen Whipple, MD, to help determine which patients with symptoms of hypoglycemia would benefit from pancreatic surgery because advanced imaging modalities and laboratory testing to determine the presence of an insulinoma were not yet available. (J Int Chir. 1938;3:237.) Arguably, these criteria are of limited utility in today's medical practice and more accurately describe a patient with symptomatic hypoglycemia from all causes.

    Unfortunately for the emergency physician, prehospital hypoglycemia is usually rapidly corrected at time of detection, often by EMS, and this can invalidate laboratory testing by the time the patient arrives at the emergency department, necessitating a supervised fasting period before collecting laboratory studies. (Future Oncol. 2010;6[2]:229; http://bit.ly/3Tsf3kF.) A 72-hour fasting period without symptoms essentially excludes a diagnosis of insulinoma.

    It is important when considering this diagnosis to investigate other causes of hypoglycemia, such as factitious disorder, accidental overdose involving oral hypoglycemic agents, the administration of exogenous insulin, noninsulinoma pancreatogenous hypoglycemia syndrome, and etiologies for which hypoglycemia is a secondary finding, such as complications of bariatric surgery or sepsis. One should also consider psychiatric, cardiac, and neurologic conditions in the differential for transient altered mental status. No specific physical exam maneuvers or findings (excluding external manifestations of ongoing hypoglycemia) suggest this diagnosis. (StatPearls [Internet]. July 24, 2022; http://bit.ly/3AdKxV8.)

    Laboratory testing during or after a 72-hour observed fast should include:

    • Serum insulin (equal to or greater than 3 U/mL)
    • Serum glucose (less than 55 mg/dL)
    • Serum proinsulin (equal to or greater than 5 pmol/L)
    • Serum c-peptide (equal to or greater than 0.6 ng/mL)
    • Serum beta-hydroxybutyrate (equal to or less than 2.7 mmol/L)
    • Sulfonylurea level (negative)

    CT imaging has a sensitivity of 30%-80% depending on tumor size. These lesions tend to be hyperattenuating on arterial phase imaging, and many hospitals have a CT pancreas protocol that can aid in detecting tumors as small as 6 mm. (J Clin Transl Endocrinol Case Rep. 2021;19:100075; http://bit.ly/3V9aYDx; Br J Radiol. 1998;71[841]:20.) MRI imaging of the pancreas with gadolinium contrast has a sensitivity up to 85%. (J Clin Transl Endocrinol Case Rep. 2021;19:100075; http://bit.ly/3V9aYDx; Br J Radiol. 2001;74[886]:968.)

    Endoscopic ultrasound is the preferred imaging modality if noninvasive imaging is negative, and it has the added benefit of allowing for tissue sampling at the time of imaging. (StatPearls [Internet]. July 24, 2022; http://bit.ly/3AdKxV8; Gastrointest Endosc. 2011;73[4]:691.)

    Immediate management in the emergency department involves correcting the hypoglycemia. Medical management, useful for patients awaiting surgical therapy or who are not surgical candidates, includes dietary modification to prevent prolonged fasting. Pharmacotherapy includes the initiation of somatostatin analogues such as octreotide or the benzothiadiazide derivative diazoxide.

    Ninety percent of cases will resolve after surgical resection, and this is the preferred management. (World J Gastroenterol. 2013;19[6]:829; http://bit.ly/3UvOQD7; Res Rep Endocr Disord. 2015;5:125.) Patients in whom symptomatic hypoglycemia is encountered as a manifestation of presumed insulinoma warrant admission for urgent endocrinology consultation, an observed fasting period, and imaging as indicated.

    This patient was admitted for continued monitoring, appropriate laboratory testing, and endocrinology consultation. He was discharged from the hospital the next day in stable condition with a presumptive diagnosis of insulinoma.

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    Dr. Maurantoniois a third-year emergency medicine resident in the Denver Health Residency in Emergency Medicine. Read past Quick Consult columns athttp://bit.ly/EMN-QuickConsult.

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