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Two Patients with Neuroglycopenia

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Two Patients with Neuroglycopenia A SELF-TEST IM BOARD REVIEW DAVID L. LONGWORTH, MD, JAMES K. STOLLER, MD, EDITORS OF CLINICAL RECOGNITION ANA MARIE DIZON, MD ROSSANA DANESE, MD BYRON J. HOOGWERF, MD Department of Endocrinology, Department of Endocrinology, Department of Endocrinology, and Cleveland Clinic. Cleveland Clinic. director, Internal Medicine Residency Program, Cleveland Clinic. Two patients with neuroglycopenia • CASE 1: A 47-YEAR-OLD MAN a low glucose level with a corresponding inap- WITH PERIODIC 'SILLINESS' propriately increased insulin concentration. When considering hypoglycemia as a 47-YEAR-OLD MAN was well until cause of "spells" or altered behavior, it is essen- 0approximately 2 years ago, when, tial to obtain a careful history of the precipi- according to his wife, he began to have tating and relieving factors. The physician episodes of "silliness," exhibiting unusual should ask about the onset and duration of behavior such as roaming around the house symptoms and their temporal relationship to naked with his underwear on his head. drugs, emotion, meals, and exercise. Often During these episodes, the patient experi- these details will have to be supplied by family ences diplopia, amnesia, and hallucinations. members or friends, because the patient may The patient claims that he has gained be amnesic about hypoglycemic events and approximately 40 lb within 1 year. unaware of any unusual pattern of behavior. The patient's wife states that the attacks usually occur at approximately 5:00 PM. The Autonomic and neuroglycopenic episodes are sometimes precipitated by work symptoms of hypoglycemia CNS or exercise and are relieved with food. There Hypoglycemia is associated with the release of is no family history of diabetes. The patient a number of counterregulatory hormones that symptoms takes no medications. Physical examination attempt to compensate for the low glucose usually reveals nothing remarkable; his mental status levels.1 The manifestations of hypoglycemia and neurological status are normal. can be physiologically divided into autonomic predominate and neuroglycopenic symptoms. in patients What test is needed? Autonomic symptoms result from simulta- neous sympathetic and parasympathetic activa- with What is the most appropriate diagnostic Itest at this point? tion of the hypothalamus; the most common are insulinomas diaphoresis, tremulousness, and palpitations. • A computed tomographic (CT) scan Neuroglycopenic symptoms, like those of the head in our patient, are the direct result of glucose • A CT scan of the abdomen deprivation of the central nervous system, • A glucose tolerance test resulting in impaired cognitive function.2'3 • A serum glucose measurement during Unlike adipose, muscle, or liver tissue, the an episode central nervous system needs a continuous • Angiography supply of glucose. In response to hypo- • Ultrasonography of the abdomen glycemia, the brain can increase its rate of glucose transport, but this compensatory This patient's symptoms suggest hypoglycemia, mechanism may be inadequate to maintain for which the most useful diagnostic test would adequate glucose concentrations in the brain be to measure the serum glucose level during an if the blood glucose level is extremely low. episode. Measuring the fasting glucose and Neuroglycopenic symptoms usually predomi- insulin levels would also be valuable, to look for nate in patients with insulinomas.'1.5 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 6 5 • NUMBER 2 FEBRUARY 1998 24 Downloaded from www.ccjm.org on September 27, 2021. For personal use only. All other uses require permission. Whipple's triad of symptoms for diagnosing insulinoma In 1933, Whipple6 proposed three criteria ("Whipple's triad") for diagnosing insulinoma: • Spontaneous symptoms of hypo- glycemia • Documented hypoglycemia during the symptoms • Immediate relief of symptoms by inges- tion of glucose Hyper insulin ism became another criteri- on after the immunoreactive radioimmunoas- say for insulin was developed in 1959. During episodes of hypoglycemia, plasma insulin lev- els higher than 6 |iU/mL and C-peptide levels higher than 0.2 nmol are consistent with hyperinsul inism.4-7 The classic insulin-to-glucose ratio should not be used with values measured during peri- ods of normoglycemia. (In this ratio, insulin FIGURE 1. Computed tomographic scan of the pancreas. A 2.5-3.0-cm isodense focal lobulation (arrow) extends values are expressed in (^U/mL and glucose anteriorly from the pancreatic body. values as mg/dL; ratios higher than 0.3 are abnormal.) The diagnosis of hypoglycemia with hyperinsulinism should be made clinically and biochemically before performing any imaging studies. The oral glucose tolerance test has been used to evaluate patients with symptoms consistent with reactive hypoglycemia (ie, autonomic symptoms in response to a meal); however, it is usually not helpful in diagnosing hyperinsulinemic hypoglycemia (characterized by neuroglycopenic symptoms when fasting). What is the best therapy for insulinoma? We obtained fasting glucose and insulin lev- els in this patient; his serum glucose level was 39 mg/dL (normal 65-110 mg/dL) and his insulin level was 31 j^U/mL (normal 4.0-24 jaU/mL). A CT scan (FIGURE 1) and an angiogram (FIGURE 2) showed findings consis- tent with a mass in the pancreas. 2 What is the best therapy for this patient? • Referral to a nutritionist FIGURE 2. Visceral arteriography. Injection of dye into • Diazoxide the celiac axis demonstrated a rounded hypervascular • Prednisone lesion (arrow) with an irregular contour in the region of • Propranolol the junction of the body and the tail of the pancreas. • Surgery CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 6 5 • NUMBER 2 FEBRUARY 1998 25 Downloaded from www.ccjm.org on September 27, 2021. For personal use only. All other uses require permission. NEUROGLYCOPENIA DIZON AND COLLEAGUES The only curative treatment for insulin-secret- • Send patient home and tell her ing islet-cell tumors is surgery. Such surgery not to worry should not be delayed, as prolonged and • Order a nutrition consult for diet control repeated hypoglycemic attacks may cause per- • Prescribe medical therapy with diazoxide manent cerebral damage.8 Before surgery, dietary adjustment with small frequent meals Any potentially debilitating condition needs can reduce symptoms in most cases. Medical to be confirmed before starting therapy; there- therapy with diazoxide (a nondiuretic ben- fore, fasting glucose and insulin levels should zothiadiazine derivative that inhibits insulin be obtained. Medical or surgical therapy is not release), somatostatin analogues, verapamil, appropriate at this point. If the patient is not and phenytoin has been used preoperatively in experiencing any symptoms during the exam- severe hypoglycemia and for patients with ination, it may be necessary to provoke hypo- nonresectable metastatic tumors.9 glycemia through an overnight fast with or The patient underwent subtotal distal without exercise. pancreatectomy and splenectomy. A mass The patient fasted for 24 hours as an out- measuring 3.5 X 3.5 X 3.0 cm was resected patient and experienced no hypoglycemic from the body of the pancreas. The patholog- symptoms. Fingerstick capillary glucose levels ic findings were consistent with an insulino- ranged from 53 to 76 mg/dL. ma. After surgery, the symptoms did not recur. A What is your next step? • CASE 2: A WOMAN WITH SYNCOPE • Admit for surgery A 40-year-old white woman with a history of • Admit for a 72-hour fast mitral valve prolapse was referred because of • Send the patient home and tell her syncope for which she had been hospitalized not to worry about it several times in the past 3 years. Extensive • Send her to a dietitian neurologic and cardiac evaluations had shown • Prescribe diazoxide The insulin-to- no clear cause of these events. Previous diag- glucose ratio noses included nonepileptic seizures and major Young, healthy women may have fasting depression. While the patient was in the hos- blood glucose values of less than 45 mg/dL is not helpful pital in October 1995, she had a fingerstick (2.5 mmol/L) without experiencing any 10 during normo- capillary glucose measurement of 41 mg/dL. A symptoms. Fasting values between 45 and CT scan of the abdomen showed some fullness 60 mg/dL (2.5-3.3 inmol/L) are not neces- glycemia in the pancreas. sarily pathologic and do not routinely need The patient complains of episodes of further evaluation if there are no accompa- tremulousness, diaphoresis, headaches, dizzi- nying symptoms or evidence of hyperin- ness, and palpitations when she misses meals. sulinism.10 Her weight is stable and her menses are nor- mal. Her father had diabetes and was "on How long a fast is necessary? pills"; her sister had a history of a brain tumor. If an overnight or 24-hour fast does not stim- The patient is thin and appears anxious; phys- ulate any symptoms, the next step is a 72-hour ical and neurologic examination reveals noth- fast—the most reliable test for evaluating ing remarkable. hypoglycemia caused by endogenous hyperin- sulinism due to an insulinoma. In a series of 51 What treatment is appropriate? patients with insulinomas reported by What is your next step? Service,7-10 35% developed Whipple's triad within 12 hours, 74% within 24 hours, and 92% within 48 hours. Approximately 2% of • Admit for surgery patients with insulinomas can fast for 72 or 96 • Obtain fasting glucose and insulin hours without developing Whipple's triad. determinations This patient's history of syncope associated
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