Sudden Death in Addison's Disease - Healthcare Bulletin

ENDOCRINE DISEASES | CASE STUDY
Sudden Death in Addison’s Disease:
Lead Poisoning-like Gum Appearance
Boonsak Hanterdsith, M.D. Division of Forensic Medicine, Lamphun Hospital,
& Pongsak Mahanupab, M.D. Department of Pathology, Faculty of Medicine, Chiang Mai University, Thailand
Received: 1/5/2011, Reviewed 20/5/2011, Accepted 6/6/2011
Key words: Sudden death, Addison’s disease, Lead poisoning-like gum appearance, Autopsy
DOI: 10.5083/ejcm.20424884.32
ABSTRACT
Fatal Addison’s disease is rarely found in forensic cases. We report the sudden and unexplained death
of a 51-year-old woman on arrival at the emergency room. Previous clinical history revealed frequent
hypotension, hyponatremia and persistent hyperpigmented skin consistent with Addison’s disease.
However, the diagnosis could only be made during autopsy. The adrenal gland was completely
absent. Postmortem blood cortisol was very low (0.86 µg/dL). The thyroid gland showed Hashimoto
thyroiditis. The probable cause of Addison’s disease in this case was autoimmune adrenalitis.
INTRODUCTION
Chronic adrenocortical insufficiency is an uncommon
disorder resulting from progressive destruction
of the adrenal cortex (1) . Clinical features
include progressive anaemia, bronze skin pigmentation,
severe weakness, hypotension, nausea, vomiting,
anorexia, weight loss and hypoglycemia (1-4) .
Hyponatremia is observed in about 80% of acute
cases whereas less than half present with hyperkalemia
(5) . These clinical features were first reported as
Addison’s disease in “On the Constitutional and Local
Effects of Disease of the Supra-renal Capsules” in
the London Medical Gazette, 1849 by Thomas Addison
(2) .
Nowadays autoimmune disease is the most common
cause of Addison’s disease in western countries
(2, 4, 6) . The remaining causes are tuberculosis,
adrenomyeloneuropathy, systemic fungal infection,
AIDS, metastatic carcinoma and isolated glucocorticoid
deficiency (2, 4) . The prognosis is excellent (7) ,
but mortality rate was more than 2-fold higher
compared with the normal population in a 14 year
period (8) . We report a fatal case of autoimmune
Addison’s disease that was diagnosed only during
autopsy.
CASE REPORT
A 51-year-old woman was found unconsciousness
at home. Her relative called the Emergency
Medical Service (EMS) for help. EMS personnel
transported her to the emergency room of the
provincial hospital. The patient was found apnoeic
and pulseless.
Initial cardiac rhythm showed asystole. Fingertip
dextrose-strip examination showed 20 mg
of glucose. Cardiopulmonary resuscitation was
performed for an hour but she could not be resuscitated.
Death was pronounced at 12.00 AM
on 2 November 2009. The cause of death could
not be explored by external examinations. Her
relative informed the doctor that the patient
had suffered from toothache for 2 days before
her death.
According to her medical history, she had had
chronic anemia with intermittent significant
hyponatremia (serum sodium = 125 mmol/dl)
since 12 February 2007. Causes of anemia were
iron deficiency (serum iron = 84 microgram per
dl; total iron binding capacity = 321 microgram
per dl; serum saturated transferrin = 26 percent)
and primary hypothyroid disease. The thyroid
function test was recorded in the OPD card on
17 October 2007 as follows: TSH level was 21.04
(normal range is 0.2-3.2 microIU/ml), T3 was
0.813 (normal range is 0.8-2.1 ng/ml). Complete
blood count showed anemia (Hb 7.6-9.1) in all of
her follow-up visits.
Her hyperpigmented skin was mentioned in the
OPD card two times in 2007; however, there was
no further investigation. She sometimes complained
about malaise. Her blood pressure was
intermittent, rising and falling between 90/60
and 120/80 mmHg (frequent hypotension). The
body weight was stable at 40-42 kg for 1.5 year.
Main treatments were oral iron tablets, folic and
vitamin B complex supplement for treatment of
iron deficiency anemia. The last follow-up visit
was on 3 July 2008.
CORRESPONDENCE
Boonsak Hanterdsith
Division of Forensic Medicine,
Lamphun Hospital,
Lamphun, 51000.
Tel. +66-0-8678-12869
+66-0-5356-9100
ext. 1998-9
Fax: +66-0-5356-9191
E-mail: trapezius60@yahoo.com
FINANCIAL SUPPORT:
No fund or financial support
ISSN 2042-4884
38 EUROPEAN JOURNAL OF CARDIOVASCULAR MEDICINE VOL I ISSUE III

SUDDEN DEATH IN ADDISON’S DISEASE: LEAD POISONING-LIKE GUM APPEARANCE
The autopsy was performed on 3 November 2009 (21 hours after
the pronounced death). The body was of a middle aged, poor nourished
female, 153 cm in length with short black hair. Axillary and
pubic hair was completely absent. Her skin looked generally dark
especially on the palmar creases, all joint areas, and lips. The upper
gum showed bluish-black patches, which looked like a lead line in
lead poisoning (Figure 1).
Figure 1: Hyperpigmentation of the gum mimicking the
lead line in lead poisoning
The toxicological analysis was negative. Lead in the blood sample
was negative. Postmortem blood cortisol was 0.86 µg/dL (range
5-25 AM, 2.5-12.5 PM).
Unfortunately, anti-adrenal and anti-thyroid antibodies could not
be analysed in Thailand. Brain, thyroid gland, heart, lung and kidney
tissues were submitted for microscopic examination: The cardiac
muscles showed hypertrophy with a small focal area of fibrosis.
Some focal haemorrhages were present in the subepicardium and
the myocardium. There were random contraction band necroses.
The thyroid gland showed Hashimoto thyroditis. There was pulmonary
oedema with some focal hemorrhages in the lungs. The brain
tissue was unremarkable.
DISCUSSION
Fatal Addison’s disease is rarely found in forensic practice, especially
in Northern Thailand. Sudden death from Addison’s disease
has been reported (9-12) but mostly in Caucasians. Several studies
showed that Addison’s disease could only be diagnosed during autopsy
(9-12) . The most specific sign of primary adrenal insufficiency
is hyperpigmentation of the skin and mucosal surfaces which is due
to the high plasma corticotrophin concentrations that occur as a result
of a decrease of cortisol feedback (4) . Malaise, hyperpigmented
skin, hypotension and hyponatremia in our case were clues for diagnosis
of chronic primary adrenal insufficiency. However, the dark
line on the gum may be mistaken as the lead line in lead poisoning.
Eur J Cardiovasc Med © Healthcare Bulletin 2011
There was no wound or injection mark on the skin. The internal examination
showed no evidence of vital organs injury. The brain had
no pathological lesion. The pituitary fossa had no abnormal mass.
The thyroid gland was normal shape and weighed 15 g. The airways
showed no edema or foreign body obstruction. Both lungs showed
mild edema with left upper lung consolidation. There was no pulmonary
thromboembolism. The right and the left lung weighed
370 g and 470 g, respectively. There were some petechiae on the
anterior external surface of the heart. The left anterior descending
coronary artery showed 10% stenosis. The right main coronary artery
was widely patent. The left ventricular free wall thickness was
12 mm. Neither valvular abnormality nor congenital anomaly was
observed. The heart weighed 290 g and had a normal shape.
There was no evidence of peritonitis. The liver, spleen, small bowel,
large bowel and pancreas had no significant gross pathologic abnormality.
Both kidneys showed a diffuse micronodular surface.
No evidence of acute pyelonephritis was detected. The adrenal
gland was searched for in the suprarenal areas and in other areas
including chest wall, but could not be identified grossly. There was
no fibrosis at the suprarenal areas. The retroperitoneal region had
no blood collection. The pelvic organs showed no significant gross
lesion. There were 10 millilitres of light green mucous-mixed liquid
in the stomach. The mucosa of the stomach showed generalised
gastritis. The femoral blood, heart blood and gastric contents were
submitted for toxicological analysis at the Regional Medical Science
Center, Chiang Mai province.
Corticotropin stimulation is the most commonly used test for the
diagnosis of primary adrenal insufficiency (4) , but it cannot be performed
postmortem. However, a very low level of plasma cortisol (3
or less µg/dL) confirmed adrenal insufficiency (4) . A previous study
showed that serum cortisol remains constant during the early postmortem
period (13) . This supports that the very low level of postmortem
blood cortisol is due to severe adrenal insufficiency in this
case. The absence of the adrenal gland in our case may be caused
by severe atrophy.
However, the detection of blood cortisol indicates some remaining
cortisol secreting tissue. Autoimmune adrenalitis is the main cause
of Addison’s disease and may occur alone or as a component of
type I or II autoimmune polyglandular syndrome (2, 4, 6) . The Hashimoto
thyroiditis of this case indicated that the autoimmune disease
was the probable cause of adrenocortical insufficiency.
Autoantibodies against 21-hydroxylase, one of the enzymes in
steroid biosynthesis inside the adrenal glands, can be found in approximately
80% of the Addisonian persons. These autoantibodies
thus clearly correlate with the disease (14) and are useful for its diagnosis.
Approximately 21% of persons positive for adrenal cortex
autoantibodies (ACA) developed overt Addison’s disease within
5.2 years, while negative ACA persons maintained normal adrenal
function during the observation period (15) . ACA is also an additional
marker to predict Addison’s disease. In conclusion, clinicians
should not overlook hyperpigmentation of the skin combined with
other significant clinical signs and basic laboratory tests for the correct
diagnose of adrenal insufficiency which is potentially fatal if
not recognised and promptly treated.
EUROPEAN JOURNAL OF CARDIOVASCULAR MEDICINE
VOL I ISSUE III
39

HEALTHCARE BULLETIN | ENDOCRINE DISEASES
Figure 2: Photomicrograph of the thyroid gland tissue of
the deceased (X 20 magnification): The thyroid parenchyma
contains a dense lymphocytic infiltration with germinal centers
(Hashimoto thyroiditis).
Eur J Cardiovasc Med © Healthcare Bulletin 2011
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