Transcript Evaluation of hypoglycemia

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?

Whipple’s Triad:
 Symptoms
consistent with hypoglycemia
 A low plasma glucose - measured with a precise
method (not a glucometer)
 Relief of symptoms after glucose level normal
Allen Oldfather Whipple
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



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




Caution! Glucose < 50 mg/dL in some normal subjects & >50 mg/dL in some
patients with insulinoma.
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 can’t respond as vigorously.
(Insulin & insulin receptor antibodies)
LOCALIZING STUDIES
Radiologic studies — CT, MRI, transabdominal US
can detect most insulinomas
 Arterial calcium stimulation — to 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 nonAsian populations)




No sex preference
Age > 40yrs
Associated with rheumatologic disease



3rd leading cause of hypoglycemia in Japan
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.
2.
3.
4.
Insulin secreted after meal bound by
antibodies (IgG)
Hyperglycemia persists causing more insulin
secretion (results in high A1C over time)
As hyperglycemia abates, insulin-bound to
antibodies is released, with inappropriately
high insulin levels
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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