BRIEF COMMUNICATIONS
Hyperglycemia in anticholinesterase poisoning
DAVID MELLER,* MD; TAN FRASER, MD; MEIR KRYGER, MD, FRCP[C]
Organophosphate insecticides are
highly toxic to mammals.1 These
chemicals inactivate cholinesterase,
allowing accumulation of acetyl-
choline at cholinergic sites. Poison-
ing with these agents is thus equi-
valent to continuous stimulation of
cholinergic fibres in both the cen-
tral and the peripheral nervous sys-
tems. The major presenting features
of severe organophosphate poison-
ing are due to these effects and in-
clude skeletal muscle paralysis, cen-
tral nervous system dysfunction and
bradycardia. Nonketotic hypergly-
cemic coma with metabolic acidosis
may uncommonly occur, leading to
diagnostic confusion or delaying ap-
propriate management.
A woman and her son presented
simultaneously to our hospital with
coma, miosis, metabolic acidosis
and hyperglycemia; we will describe
their cases in detail. Two other
family members had an illness char-
acterized by nausea, vomiting, sa-
livation, diaphoresis and muscle
twitching. Subsequent findings led
to a probable diagnosis of mala-
thion poisoning.
Case reports
Case 1
A 39-year-old man was admitted
From the department of medicine,
University of Manitoba, and the
department of respiratory medicine,
St. Boniface General Hospital, Winnipeg
1Present address: P0 Box 1120,
Sparwood. BC VOB 2G0
Reprint requests to: Dr. Meir Kryger,
Director of respiratory medicine,
Department of respiratory medicine,
St. Boniface General Hospital, 409
Tache Ave., Winnipeg, Man. R2H 2A6
For prescribing information see page 763
to another hospital with generalized
muscle twitching, hyperreflexia,
profuse sweating and major seizures
leading to coma with nonreactive
pinpoint pupils. His rectal tempera-
ture was only 340C. His blood pres-
sure was 140/90 mm Hg and his
pulse rate 125 beats/mm. The cor-
neal reflexes and doll's eye move-
ments were intact. A right flexor
plantar reflex was elicited. In ar-
terial blood the carbon dioxide ten-
sion (Paco2) was 51 mm Hg, the
oxygen tension (Paol) 48 mm Hg
and the pH 7.25. The blood glucose
concentration was 29.0 mmol/l
(522 mg/dl). The serum electrolyte
concentrations were normal and ke-
tonuria was absent. The cerebro-
spinal fluid was free of cells; the
protein concentration was 0.53 g/l
and the glucose concentration 8.7
mmol/l (157 mg/dl). Therapy con-
sisted of oxygen supplementation,
mechanical ventilation and intra-
venous administration of fluids and
sodium bicarbonate.
The patient's level of conscious-
ness dramatically improved 31/2
hours after admission and the en-
dotracheal tube was removed. Ap-
proximately 15 hours after admis-
sion his rectal temperature was
370C. While he was breathing room
air the Paco2 was 31 mm Hg, the
Pao2 62 mm Hg and the arterial
blood pH 7.46. The blood glucose
concentration 18 hours after admis-
sion was 6.2 mmol/l (111 mg/dl).
Subsequently a 3-hour oral glucose
tolerance test and a 48-hour fast
with simultaneous glucose and in-
sulin measurements gave normal re-
sults. The patient was discharged
without a diagnosis.
The man was well for about 2
weeks, then a similar illness devel-
CMA JOURNAL/MARCH 15, 1981/VOL. 124 745
oped. After the onset of nausea,
respiratory distress and coma he
was admitted to a community hos-
pital. He quickly became apneic
and required endotracheal intuba-
tion and ventilatory support. Pin-
point pupils, generalized muscle
twitching and profuse sweating were
noted.
When transferred to our intensive
care unit he was unresponsive to
deep pain, sweating and pale. The
intra-arterial blood pressure was
50/30 mm Hg, the heart rate 70
beats/mm and the rectal tempera-
ture 320C. His pupils were pinpoint
and nonreactive. The corneal re-
flexes and doll's eye movements
were intact. Prominent eyelid fasci-
culations and excess salivation were
noted. The neck was supple. There
was generalized muscle twitching
accompanied by flaccidity of the
extremities. The reflexes were brisk
in all limbs and symmetric. Flexor
plantar reflexes were elicited.
The hemoglobin concentration
was 13 g/dl, the leukocyte count
10.8 x 1 0./l (more immature cells
were present than is normal) and
the platelet count 540 x l0./l. The
following concentrations were de-
termined: sodium 136 mmol/l, po-
tassium 3.2 mmol/l, total CO2 10
mmol/l, glucose 33.5 mmol/l (604
mg/dl), urea 6.8 mmol/l (urea ni-
trogen 19 mg/dl) and amylase 130
lU/I (normal less than 15 IU/l).
Arterial blood values corrected for
temperature were: Pacol 49 mm
Hg, PaQI 53 mm Hg and calcu-
lated bicarbonate concentration 14
mmol/l with a fractional oxygen
intake (F1o2) of 0.9; the pH was
7.03. The urine had a specific grav-
ity of 1.011 and contained 2% glu-
cose but no ketones. A drug screen
 revealed no salicylates, ethanol,
methanol, barbiturates, tricyclic an-
tidepressants or ethclorvynol in the
blood or urine. Michel's test for
pseu.Jocholinesterase activity in the
blood2 revealed no activity, sup-
porting the diagnosis of anticholin-
esterase poisoning.
Ventilatory support was prompt-
ly begun and the metabolic acidosis
treated with intravenous adminis-
tration of bicarbonate, which raised
the blood pH to 7.30. An infusion
of 5% albumin and dopamine did
not increase the blood pressure.
Naloxone, 0.4 mg given intraven-
ously, also had no effect. Atropine
given repeatedly in 0.6-mg incre-
ments resulted in a prompt increase
in heart rate and blood pressure.
After the report of no detectable
pseudocholinesterase activity 1 g of
pralidoxime, a cholinesterase reac-
tivator, was given. Within 2 hours
the patient's level of consciousness
and cardiovascular status drama-
tically improved. He became alert.
Eight hours after admission the
Paco2 was 32 mm Hg and the Pao2
166 mm Hg with an F1o2 of 0.4;
the arterial blood pH was 7.35. The
endotracheal tube was then re-
moved. An infusion of crystalline
insulin, 1 U/h, lowered the blood
glucose concentration to 5.8
mmol/l (104 mg/dl) in 7 hours.
On the day after admission, epi-
gastric pain and tenderness asso-
ciated with a serum amylase con-
centration of 360 lU/I were noted.
These abnormalities, along with de-
lusions of grandeur, subsided over
the next 5 days.
One month later the man was
asymptomatic and had normal pseu-
docholinesterase activity in the
blood.
Case 2
The 81-year-old mother of pa-
tient 1 was brought to hospital at
the same time as her son. After
complaining of nausea and exces-
sive oral secretions she had abruptly
become comatose. She required en-
dotracheal intubation and ventila-
tory support prior to transfer to
our intensive care unit. On arrival
she was aggressive. Her blood pres-
sure was 180/100 mm Hg, her
heart rate 48 beats/mm with a reg-
746 CMA JOURNAL/MARCH 15, 1981/VOL. 124
ular rhythm and her rectal tem-
perature 35 0C. Response to deep
pain, miosis and fluttering of the
eyelids were noted. The corneal re-
flexes and doll's eye movements
were intact, and deep tendon and
plantar reflexes were normal.
The hemoglobin concentration
was 15.0 g/dl and the leukocyte
count 19.2 x l0./l (more imma-
ture cells were present than is nor-
mal). The Pacol was 39 mm Hg
and the Pao2 50 mm Hg with an
F.o2 of 0.9; the arterial blood pH
was 7.32. The following serum con-
centrations were determined: so-
dium 128 mmol/l, potassium 3.0
mmol/l, chloride 94 mmol/l, total
CO. 16 mmol/l, glucose 25.5
mmol/l (460 mg/dl) and amylase
23.5 lU/i. The urine had a specific
gravity of 1.013 and contained 3%
protein and 2% glucose but no
ketones. The drug screen gave neg-
ative results.
After initiation of ventilatory
support, atropine was given intra-
venously; the heart rate immediately
increased to 98 beats/mm. A total
of 6.6 mg of atropine was admin-
istered over the ensuing 6 hours
to keep the heart rate over 90
beats/mm. Five units of crystalline
insulin administered subcutaneously
lowered the blood glucose concen-
tration to 5.6 mmol/l (101 mg/dl)
9 hours after admission. Once it
was found that there was no detect-
able pseudocholinesterase activity
1 g of pralidoxime was given. The
endotracheal tube was removed 23
hours after admission, when the
patient was alert.
When the patient's level of con-
sciousness had returned to normal,
questioning revealed that two other
family members had suffered from
nausea, diarrhea, excessive oral se-
cretions and hypothermia that spon-
taneously resolved. In addition, a
dog and a cat were found dead on
the family's home property; the ani-
mals' bodies were not available for
examination. Enquiries by public
health authorities uncovered the
fact that an adjacent farmer's field
had been sprayed with malathion
shortly before the family's symp-
toms began. Unfortunately, efforts
to detect malathion on vegetables
from the family garden following
rain in the area were unsuccessful.
Discussion
The anticholinesterase effects oi
organophosphate insecticides are
produced by the binding of the
phosphate groups of these chem-
icals to the enzyme that hydrolyzes
acetylcholine in the liver and serum
(pseudocholinesterase) and in nerv-
ous tissue and erythrocytes (true
cholinesterase). With the enzyme
inhibited, acetylcholine accumulates
at cholinergic sites. Acetylcholine
excess produces muscarinic (para-
sympathomimetic) effects, which in-
clude miosis, bradycardia, glandu-
lar hypersecretion, gastrointestinal
dysfunction and nicotinic effects,
which include seizures, muscular
twitching and respiratory muscle
paresis resulting from a depolarizing
blockade of the neuromuscular
junction ..
Our cases fulfil the diagnostic
criteria for organophosphate poi-
soning: (a) possible exposure; (b)
characteristic manifestations, in-
cluding muscle twitching and mi-
osis; (c) improvement following ad-
ministration of pralidoxime and
atropine, with increased tolerance
to atropine; and (d) reduction in
blood cholinesterase activity. How-
ever, the clinical presentation of
coma with pinpoint pupils had sug-
gested other diagnoses, including
pontine hemorrhage, opiate over-
dose and muscarine intoxication
from the ingestion of mushrooms.
The simultaneous presentation of
mother and son, the lack of re-
sponse to naloxone and the absence
of a history of ingestion of mush-
rooms, respectively, excluded these
diagnoses.
When a history of exposure to
insecticides is absent the hypergly-
cemia that can occur in severe or-
ganophosphate intoxication1 may
suggest an incorrect diagnosis. In
an African series of 105 patients,3
including 44 with depressed levels
of consciousness and 42 with mus-
cle fasciculations, hyperglycemia
was found in only 7% and glyco-
suria in 14%. Paradoxically, hypo-
glycemia* has also been reported,4
as has lowering of the blood glu-
cose level in an insulin-treated dia-
betic individual.5 The hypoglycemic
effect has been attributed to in-
creased insulin secretion secondary
 to direct or indirect effects of chol-
inergic stimulation. Of interest is
the accompanying hyperamylasemia
in both our patients. Dressel and
colleagues6 have presented clinical
and experimental evidence in dogs
for acute anticholinesterase-induced
pancreatitis secondary to functional
duct obstruction and stimulated ex-
ocrine secretion. Whether the hyper-
glycemia in severe organophosphate
poisoning is a manifestation of the
response to initial hypoglycemia or
the result of severe necrotizing pan-
creatitis is unclear. Likewise, the
origin of the hyperamylasemia is
uncertain.
Miliary tuberculosis presenting as adrenal failure
JOSEPH BRAIDY,* MD, FRCP[C]; CLAUDE POTHEL,t MD, FRCP [C]; SULEMAN AMRA,* MD, FRCP[C]
Miliary tuberculosis can mimic
many clinical disorders,1'2 and Ad-
dison's disease may be a late com-
plication of tuberculous infection.
The coexistence of miliary tubercu-
losis and Addison's disease has oc-
casionally been described.3 We re-
port a case in which subacute
adrenal failure was the first mani-
festation of miliary tuberculosis.
A tuberculous mycotic aneurysm
found at autopsy was thought to
have been the source of the tubercle
bacilli that eventually destroyed the
adrenals. Such an association has
not previously been described. The
various presentations of adrenal in-
volvement in tuberculosis are re-
viewed.
Case report
Clinical course
An 84-year-old man was ad-
mitted to hospital because of pro-
gressive deterioration of his mental
and physical status .over the past 6
months. Personality change and for-
From the departments of *medicine
and tpathology, Reddy Memorial
Hospital, Montreal
Reprint requests to: Dr. Joseph Braidy,
Montreal General Hospital, 1650 Cedar
Ave., Rm. 5578, Montreal, PQ H3J 1A4
748 CMA JOURNAL/MARCH 15, 1981/VOL. 124
The presence of nonketotic hy-
perglycemic coma with metabolic
acidosis should suggest, in addition
to diabetes mellitus, organophos-
phate intoxication, which character-
istically will be associated with
miosis and muscle fasciculations.
References
I. NAMBA T, NOLTE CT, JACKREL J,
GROB D: Poisoning due to organo-
phosphate insecticides: acute and
chronic manifestations. Am J Med
1971; 50: 475-492
2. MICHEL HO: Electrometric method
for determination of red cell and
plasma cholinesterase activity. J Lab
Cli,i Med 1949; 34: 1564-1568
getfulness had been noticed by his
family. He complained of afternoon
weakness, difficulty walking, uri-
nary urgency and incontinence, and
a weight loss of 9 kg. There was no
history of cough, dyspnea, fever,
night sweats, dizziness or headache.
He had been a clothing designer
and had still been interested in his
business before his illness. He had
had a cholecystectomy in 1975,
with prompt recovery. He had
stopped smoking cigars 10 years
before this admission.
He looked younger than his
stated age, although he appeared
chronically ill. He was afebrile. The
blood pressure was 100/60 mm Hg
and the pulse rate 70 beats/mm.
His teeth were preserved and the
fundi were normal. There was no
mucosal or skin hyperpigmentation.
The results of thoracic and abdom-
inal examination were normal. Neu-
rologic examination disclosed that
he was confused, that his answers
were inappropriate and that his
memory for recent events was poor.
The neck was supple and the
cranial nerve function normal.
There were no motor or sensory
abnormalities. Deep tendon reflexes
were absent in the legs, but the
plantar reflexes were normal. Bi-
lateral palmomental reflexes were
3. HAYES MM, VAN DER WESTHUIZEN
NG, GELFAND M: Organophosphate
poisoning in Rhodesia. A study of the
clinical features and management of
105 patients. S Air Med J 1978; 54:
230-234
4. HRUBAN Z, SCHULMAN 5, WARNER
NE, Du Bois KP, BUNNAG S. BUNNAG
SC: Hypoglycemia resulting from in-
secticide poisoning. JAMA 1963; 184:
590-593
5. SAMANTRY 5K: Organophosphorus
poisoning and remission of diabetes
(C). Med J Aust 1978; 1: 443
6. DRESSEL TD, GOODALE RL, ARNESON
MA, BORNER JW: Pancreatitis as a
complication of anticholinesterase in-
secticide intoxication. Ann Surg 1979;
189: 199-204
present; grasp and snout reflexes
were absent.
The hemoglobin concentration
was 12.7 g/dl and the leukocyte
count was 8.5 x 10./l (78% neu-
trophils, 13% lymphocytes and 9%
monocytes). The following serum
levels were determined: urea 20
mmol/l (urea nitrogen 56 mg/dl),
creatinine 239 ..tmol/l (2.7 mg/dl),
glucose 5.4 mmol/l (98 mg/dl), so-
dium 117 mmol/l, potassium 6.2
mmol/l, chloride 85 mmol/l and
carbon dioxide combining power 19
mmol/l. Urinalysis gave normal re-
sults. Chest roentgenograms were
first interpreted as showing intersti-
tial changes in the lower lobe of
the left lung (Fig. 1).
After the serum electrolyte values
were received blood was drawn for
measurement of the cortisol concen-
tration, and therapy for adrenal
failure was begun with a 0.9%
saline infusion, hydrocortisone and
fludrocortisone acetate. During the
next few days the patient's condi-
tion generally improved. On the
fourth day the following serum
levels were found: urea 10 mmol/l
(urea nitrogen 29 mg/dl), sodium
135 mmol/l, chloride 98 mmol/l
and CO2 combining power 22
mmol/l. The next day the cortisol
level in blood drawn before ther-