NAME: GRAJO, Rianette M. INSTRUCTOR: Mrs.

Coloma

DATE :____________________

CASE STUDY IN ENDOCRINOLOGY

CASE BACKGROUND:

The deceased was 22 years old male. He was found unconscious in his room and shifted to
the hospital with primary sign and symptoms of alcoholic intoxication, increased pulse and respiratory
rate absence of reflexes. Symptomatic and supportive treatment was given after 2 days he developed
acute nephritis, bronchopneumonia and hypertension and passed away after three days. This revealed
that the cause of death is not only the alcohol but there must be some other agent ignorantly or
intentionally taken with the alcohol. Because alcohol does not give such type of sign and symptoms. As it
is known that it is a common hazard of drunker to take poison by mistaking it for alcohol. In the condition
the person died, it may be denatured spirit or any other similar liquid, which might have taken by the
deceased in effect of alcohol. Looking back to the history of the deceased it was known that the deceased
was transferred few days back from Leh to Bhopal. Leh is a cold place, where defence personals use
antifreeze to protect them from cold, as it does not get absorbed at all through the skin. Inhalation also
does not result in clinical toxicity because of its low vapour pressure. Therefore ingestion is the main route
of toxicity. Basing on these lines the investigation was started.

QUESTIONS TO CONSIDER:

1. What is your diagnosis?

Ethylene glycol poisoning. Ethylene Glycol chemically occupies a position between ethyl
alcohol and glycerol. It is a colorless, odorless, clear, nonvolatile, bittersweet but pleasant taste.
Its minimum lethal dose is 100 ml for a 150-pond man. It is miscible with water and ethanol. It is
reported to be taken accidentally in lieu of alcohol or also as a substitute of alcohol. Fatalities
have been reported in many cases. On ingestion, it chiefly causes cerebral damage. Fatal period
is 3 days. Half life is 3-5 hours. Antidote is pure ethyl alcohol, as ethylene glycol is metabolized by
alcohol dehydrogenase enzyme in absence of ethyl alcohol and metabolizes to glyceraldehydes
and subsequently to lactic acid and oxalic acid, calcium oxalate crystals are deposited in the
kidney. Thus ethylene glycol itself is probably non-toxic; its toxic effects are due to its metabolites.
Ethylene glycol is used as antifreeze, coolant, industrial solvent and in electrolytic condensers.

2. What criteria did you base your diagnosis?

The diagnosis of ethylene glycol toxicity is made using historical, clinical, and laboratory factors.
It should be suspected in any individual who appears inebriated but does not have an ethanol
 odor. Several laboratory abnormalities are indicative of ethylene glycol intoxication. Patients with
significant toxicity typically have an elevated anion gap metabolic acidosis and an elevated osmol
gap. Calcium oxalate crystals in the urine are generally a late finding, appearing 4 to 8 hours after
the ingestion. These are only found in approximately 50% of patients on admission, but this
increases during the hospital course. Two forms of oxalate crystals may be found. The
monohydrate form is an elongated crystal that may be confused with hippurate or urate crystals.
The dihydrate form occurs at higher oxalate concentrations and is octahedral-shaped, appearing
as pyramids. Fluorescein is a green fluorescent dye that is added to antifreeze products in the
United States to assist in leak detection. This can be detected in the urine early after ethylene
glycol ingestion, but is usually cleared within 4 hours of the ingestion.12 Testing for urinary
fluorescence is a simple, rapid test that can easily be performed in the emergency department or
a clinic setting. To detect fluorescein, the urine is poured through white filter paper or a white
paper towel and the paper is then is examined for fluorescence with a Wood’s lamp. A control
sample with water is recommended.

Plastic urine containers are not recommended because many of these have some
degree of fluorescence. The results must be interpreted with caution. False positive results can
be obtained if the urine is placed in certain plastic containers. A negative test does not rule out
ethylene glycol toxicity because the fluorescein is usually cleared within 4 hours and the ethylene
glycol will persist. The anion gap represents the presence of unmeasured anions in the blood.
Normally, the anion gap is between 12 and 16 mmol/L for most hospitals. Early in the course of
ethylene glycol toxicity, there may be a low or minimal anion gap. This is because insufficient
amounts of ethylene glycol have been metabolized to the organic acids responsible for the anion
gap. When there has been a coingestion of ethanol, the appearance of an anion gap is delayed.

3. Discuss the disease of the patient.

Ethylene glycol is rapidly absorbed after oral administration, with peak levels occurring 1
to 4 hours after ingestion. It is highly water soluble with a low volume of distribution (0.5–0.8
L/kg).5 It is metabolized by cytosolic enzymes in the liver. The metabolism occurs in a sequential
process, as shown in Figure 1. The first step involves oxidation of one of the alcohol moieties
forming glycoaldehyde. This step is catalyzed by the enzyme alcohol dehydrogenase (AD). This
step is inhibited by ethanol because AD has a much greater affinity for ethanol than it does for
ethylene glycol. It is also the site of action of the drug fomepizole. The elimination half-life of
ethylene glycol is typically approximately 3 hours, but may be up to 8 hours.6–8 Ethanol at a
concentration of 100 mg/dL increases the elimination half-life to approximately 17 to 18 hours.6
Fomepizole increases the half-life to approximately 20 hours.

The toxicity of ethylene glycol is primarily a result of its metabolic by-products and not
the parent compound. Glycolic acid, glyoxylic acid, and oxalic acid all contribute to the metabolic
acidosis. The rate-limiting step in the metabolism of ethylene glycol is the conversion of glycolic
acid to glyoxylic acid.5 This results in an accumulation of glycolic acid in the blood. Furthermore,
because the numerous metabolic steps require the conversion of nicotine adenine dinucleotide
to its reduced form reduced nicotine adenine dinucleotide, the increased reduced nicotine
 adenine dinucleotide to nicotine adenine dinucleotide ratio favors the conversion of pyruvate to
lactate, resulting in a lactic acidosis.

The primary toxic effects of ethylene glycol are metabolic derangements and renal toxicity. An
anion gap metabolic acidosis is the main metabolic effect. The renal toxicity results in an acute
tubular necrosis with deposition of calcium oxalate crystals in the tubular lumen. Hypocalcemia
may occur, presumably as a result of the formation of calcium oxalate crystals. Ethylene glycol is
also a direct irritant on the gastric mucosa, resulting in focal hemorrhages in severe toxicity.
Ethylene glycol is a central nervous system (CNS) depressant and may cause cerebral edema.
Myocardial depression can occur from calcium oxalate crystals depositing in the myocardium, but
it is more likely a result of the metabolic derangements.

4. What other tests would you recommend for confirmation?

Osmolality is a measure of the number of dissolved solutes in the serum. The osmolality gap is
the difference between the measured and calculated serum osmolality. Serum osmolality can be
measured by freezing point depression or vapor point osmometry, with freezing point depression
being the more accurate and preferred method. The difference between the measured osmolality
and the calculated osmolarity is usually 10 to 15 mOsm/kg water. Anything larger than this
suggests the presence of uncharged solutes. Low molecular weight alcohols and ketones
(methanol, ethanol, acetone, isopropanol, and ethylene glycol), if present, will elevate the osmol
gap. At low concentrations of ethylene glycol, the osmol gap may still remain in the normal range.

5. What treatment would you recommend the patient?

Gastric lavage, enemas, administration of Alkalis and fluids, sodium bicarbonate (i.v.) for
acidosis, short acting barbiturates for convulsions, oxygen, artificial respiration, maintain body
heat, fluid and electrolyte balance. Treat for kidney damage - Haemodialysis. Block the
metabolism of ethylene glycol by administering ethanol, which has a high affinity for alcohol
dehydrogenase (100 times more than that of ethylene glycol). A serum ethanol level of 100 mg/dl
is essential to achieve this object. The dose is the same as that for methanol poisoning i.e. 1g per
kg of 20-30 percent alcohol and maintenance dose is 130 mg/kg per hour.

BIBLIOGRAPHY:

http://medind.nic.in/jbc/t04/i1/jbct04i1p33.pdf

https://watermark.silverchair.com/milmed.169.8.660.pdf?token=AQECAHi208BE49Ooan9kkhW
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