INTRODUCTION

Chronic adrenocortical insufficiency is an uncom-mon disorder resulting from progressive destruc-tion of the adrenal cortex (1). Clinical features include progressive anaemia, bronze skin pigmen-tation, severe weakness, hypotension, nausea, vom-iting, anorexia, weight loss and hypoglycemia(1-4). Hyponatremia is observed in about 80% of acute cases whereas less than half present with hyperka-lemia(5). These clinical features were first reported as Addison’s disease in “On the Constitutional and Lo-cal Effects of Disease of the Supra-renal Capsules” in the London Medical Gazette, 1849 by Thomas Ad-dison (2).

Nowadays autoimmune disease is the most com-mon cause of Addison’s disease in western coun-tries (2, 4, 6). The remaining causes are tuberculosis, adrenomyeloneuropathy, systemic fungal infection, AIDS, metastatic carcinoma and isolated glucocor-ticoid 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 unconscious-ness 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 ap-noeic and pulseless.

CORRESPONDENCE

Boonsak Hanterdsith

Division of Forensic Medicine, Lamphun Hospital, Lamphun, 51000.

Tel. +66-0-8678-12869+66-0-5356-9100 ext. 1998-9 Fax: +66-0-5356-9191E-mail: trapezius60@yahoo.com

FINANCIAL SUPPORT:

No fund or financial support

ISSN 2042-4884

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.

Sudden Death in Addison’s Disease: Lead Poisoning-like Gum Appearance

ENDOCRINE DISEASES | CASE STUDY

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, AutopsyDOI: 10.5083/ejcm.20424884.32

Initial cardiac rhythm showed asystole. Finger-tip dextrose-strip examination showed 20 mg of glucose. Cardiopulmonary resuscitation was performed for an hour but she could not be re-suscitated. 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 com-plained 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.

38 EUROPEAN JOURNAL OF CARDIOVASCULAR MEDICINE VOL I ISSUE III

39EUROPEAN JOURNAL OF CARDIOVASCULAR MEDICINE VOL I ISSUE III

The autopsy was performed on 3 November 2009 (21 hours after the pronounced death). The body was of a middle aged, poor nour-ished 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).

There was no wound or injection mark on the skin. The internal ex-amination 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 pul-monary 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 ar-tery 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 ab-normality. 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.

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 kid-ney tissues were submitted for microscopic examination: The car-diac 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 pulmo-nary oedema with some focal hemorrhages in the lungs. The brain tissue was unremarkable.

DISCUSSION

Fatal Addison’s disease is rarely found in forensic practice, espe-cially 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 au-topsy(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 re-sult of a decrease of cortisol feedback(4). Malaise, hyperpigmented skin, hypotension and hyponatremia in our case were clues for di-agnosis of chronic primary adrenal insufficiency. However, the dark line on the gum may be mistaken as the lead line in lead poisoning.

Corticotropin stimulation is the most commonly used test for the diagnosis of primary adrenal insufficiency (4), but it cannot be per-formed 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 post-mortem period (13). This supports that the very low level of post-mortem 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 Hashi-moto 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 ap-proximately 80% of the Addisonian persons. These autoantibodies thus clearly correlate with the disease (14) and are useful for its di-agnosis. 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 addi-tional 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 cor-rect diagnose of adrenal insufficiency which is potentially fatal if not recognised and promptly treated.

SUDDEN DEATH IN ADDISON’S DISEASE: LEAD POISONING-LIKE GUM APPEARANCE

Figure 1: Hyperpigmentation of the gum mimicking the lead line in lead poisoning

Eur J Cardiovasc Med © Healthcare Bulletin 2011

HEALTHCARE BULLETIN | ENDOCRINE DISEASES

40 EUROPEAN JOURNAL OF CARDIOVASCULAR MEDICINE VOL I ISSUE III

Maitra A. The endocrine system. In: Kumar V, Abbas AK, Fausto N, Mitchell RN, editors. Robbins basic Pathology. 8th ed. Philadelphia: W.B.Saunders Company, 2007: 793-5.

Addison’s disease [online]. 2010. Available at: http://www.whonamedit.com/doctor.cfm/68.html. Accessed April 5, 2010.

Williams GH, Dluhy RG. Disorders of the Adrenal cortex. In: Fauci AS, Braunwald E, Kasper DL, et al, editors. Harrison’s principles of internal medicine. 17th ed. USA: McGraw-Hill Companies, 2008:2262-4.

Olekers W. Adrenal insufficiency. N Eng J Med 1996;335:1206-12.

Arlt W. The approach to adult with newly diagnosed adrenal insufficiency. J Clin Endocrinol Metab 2009;94(4):1059-67.

Kong MF, Jeffcoate W. Eighty-six cases of Addison’s disease. Clin Encocrino 1995;43(1):130-1.

Erichsen MM, Lovas K, Fougner KJ, et al. Normal overall mortality rate in Addison’s disease, but young patients are at risk of premature death. EJE 2009;160:233-7.

1

2

3

4

5

6

7

REFERENCES

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).

Bergthorsdottir R, Zachrisson ML, Oden A, Johannsson G. Premature mortality in patients with Addison’s disease: A population-based study. JCEM 2006;91(12):4849-53.

Brosnan CM, Gowing NFC. Addison’s disease. BMJ 1996;312:1085-7.

Sabri AMA, Smith N, Busuttil. Sudden death due to auto-immune Addison’s disease in a 12-year-old girl. Int J Legal Med 1997;110:278-80.

Burke MP, Opeskin K. Adrenocortical insuffiency. Am J Forensic Med Pathol 1999;20(1):60-5.

Moallem M, Nader N, Auckley D. A 22-year-old woman with fever, jaw pain, and shock. CHEST 2007;132:1077-9.

Coe JI. Postmortem chemistry of blood, cerebrospinal fluid and vitreous humor. In Tedeschi CG, Eckert WC, Tedeschi LG, editors. Forensic medicine. Philadelphia: saunders Co., 1977:1030-60.

Myhre AG, Undlien DE, Lovas K, et al. Autoimmune adrenocortical failure in Norway autoantibodies and human leukocyte antigen class II associations related to clinical features. J Clin Endocrinol Metab 2002;87(2):618-23.

Betterle C, Volpato M, Smith BR, et al. Adrenal cortex and steroid 21-hydroxylase autoantibodies in adult patients with organ-specific autoimmune disease: Markers of low progression to clinical Addison’s disease. J Clin Endocrinol Metab 1997;82:932-8.

8

9

10

11

12

13

14

15

Eur J Cardiovasc Med © Healthcare Bulletin 2011