EVALUATION OF HYPOGLYCEMIA

& Insulin Autoimmune Syndrome (Hirata disease)

Andrew Maclennan, MD April 23, 2010 Morning
Report
SYMPTOMS OF HYPOGLYCEMIA
Neuroglycopenic symptoms
Cognitive impairment, behavioral changes,
psychomotor abnormalities, coma, death
Neurogenic symptoms
Tremors, palpitations, anxiety/arousal,
sweating, hunger, paresthesias
WHO TO EVALUATE?
Whipples Triad:
Symptoms consistent with hypoglycemia
Allen Oldfather
Whipple

A low plasma glucose - measured with a

precise method (not a glucometer)
Relief of symptoms after glucose level
normal
DIAGNOSTIC APPROACH
Fast (overnight or post-prandial)
72 hr fast if initial fast is negative
End fast when
glucose 45 mg/dL
Pt has signs/sx of hypoglycemia
72 hours have elapsed
glucose <55 mg/dL if Whipple's triad documented previously
Check Q6 hrs, more frequently when glucose < 60 mg/dL
plasma glucose, insulin, C-peptide, proinsulin, BHOB, and oral
hypoglycemic agents
At end of fast
IV glucagon and measure glucose 10, 20, and 30 minutes later
Feed patient
WHAT TO MEASURE?
In symptomatic patients with hypoglycemia
Insulin > 3 microU/mL is excess insulin; consistent w/ insulinoma
Caution! Glucose < 50 mg/dL in some normal subjects & >50 mg/dL in some patients
with insulinoma.
Proinsulin > 5 pmol/L consistent w/ insulinoma
Beta-hydroxybutyrate - Insulin is antiketogenic
BHOB levels lower in insulinoma patients than in normal subjects.
C-peptide - distinguishes endogenous from exogenous hyperinsulinemia
Sulfonylurea and meglitinide screen
Glucose response to glucagon
Insulin is antiglycogenolytic and hyperinsulinemia permits retention of glycogen
within the liver.
In insulin-mediated hypoglycemia, response to glucagon is release of glucose
Normal patients have virtually exhausted hepatic glycogen stores after 72hrs and
cant respond as vigorously.
(Insulin & insulin receptor antibodies)
LOCALIZING STUDIES
Radiologic studiesCT, MRI,
transabdominal US can detect most insulinomas
Arterial calcium stimulationto distinguish
between insulinoma and a diffuse process (islet
cell hypertrophy/nesidioblastosis).
Inject calcium gluconate into gastroduodenal, splenic
and superior mesenteric artery
Sample hepatic vein for insulin
Increased insulin secretion localizes area of
hyperfunctioning islets.
TREATMENT OF HYPERINSULINEMIC HYPOGLYCEMIC
STATES

Insulinoma surgical resection of

tumor
Nesidioblastosis partial or subtotal
pancreatectomy
Antibodies to insulin receptors
immunosuppressants (poor response)
Antibodies to insulin
glucocorticoids (good response)
INSULIN AUTOIMMUNE SYNDROME
CLINICAL MANIFESTATIONS
Episodes of hyperinsulinemic
hypoglycemia
Often post-prandial, after exercise
Paradoxic hyperglycemia
May occur after meal or oral glucose
challenge
EPIDEMIOLOGY
Extremely uncommon in West (58 case reports in non-
Asian populations)
3rd leading cause of hypoglycemia in Japan
No sex preference
Age > 40yrs
Associated with rheumatologic disease
SLE, RA,
May see positive ANA, anti DSDNA, RF
Association with medications
Captopril, penicillamine, hydralazine, procainamide, INH,
penicillin G
Meds with sulfhydryl group (especially methimazole)
PATHOPHYSIOLOGY

1. Insulin secreted after meal bound by

antibodies (IgG)
2. Hyperglycemia persists causing more
insulin secretion (results in high A1C
over time)
3. As hyperglycemia abates, insulin-
bound to antibodies is released, with
inappropriately high insulin levels
4. Hypoglycemia results.
LABORATORY AND CLINICAL
FINDINGS
Autoimmune Forms of Hypoglycemia.
Lupsa, Beatrice; Chong, Angeline; Cochran,
Elaine; MSN, CRNP; Soos, Maria; Semple,
Robert; MB, PhD; Gorden, Phillip

Medicine. 88(3):141-153, May 2009.

DOI: 10.1097/MD.0b013e3181a5b42e
REFERENCES
Lupsa BC et al, Autoimmune Forms of Hypoglycemia.
Medicine, vol 88(3):141-153; May 2009.
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