Journal of Postgraduate Medicine Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India ISSN: 0022-3859 EISSN: 0972-2823 Vol. 48, Num. 4, 2002, pp. 304-306

Journal of Postgraduate Medicine, Vol. 48, Issue 4, 2002 pp. 304-306

A Case With Diarrhoea, Hypotension, Wasting and Weight Loss

Chiam P, Tavintharan S, Poulose V, Fock KM

Department of Cardiology, National Heart Centre and Department of Medicine, Changi General Hospital, Singapore
Address for Correspondence: P. Chiam, Dept of Cardiology, National Heart Centre, Mistri Wing, 17 Third Hospital Avenue, Singapore - 168752 E-mail: Paul_Chiam@nhc.com.sg

Code Number: jp02101

A 67-yearold Chinese male was admitted for diarrhoea of 3 weeks, which was minimally bloody on one occasion and weight loss of 10 kg over 2 months. He was previously well and denied use of medications, recreational drugs or herbal preparations. He used to travel overseas frequently for social visits.

Clinical examination revealed wasting, blood pressure of 140/100 mmHg and temperature of 37.8⁰C. There was no buccal pigmentation, oral thrush, tremor or goitre. There was mild tenderness in the left iliac fossa. Neurological examination was unremarkable.

His haemoglobin was 12.8 g/dl (normocytic), leucocytes 6.8x 10³/ul, polymorphs 64%, lymphocytes 23.4%, eosinophils 2.6%. Serum sodium was 136 mmol/l, potassium 4.2 mmol/l, urea 4.6 mmol/l, random glucose 5.9 mmol/l, calcium 2.2 mmol/l (corrected). Thyroid function tests were normal. Chest radiograph (CXR) was unremarkable. Leucocytes were present in the stool. Blood and stool cultures did not yield any pathogens. A computed tomography of his abdomen was normal. He was treated empirically with intravenous ceftriaxone (2gm daily). A colonoscopy was considered in view of persistent diarrhoea.

What are the differential diagnoses for this patient based on clinical history and examination?

Differential diagnoses would include:
a) Gastrointestinal malignancy (especially colonic)
b) Inflammatory bowel disease
c) Gastrointestinal infections causing malabsorption, eg giardiasis
d) Other malabsorption syndromes, eg bacterial overgrowth, amyloidosis etc.
e) Thyrotoxicosis
f) Diabetes Mellitus with autonomic neuropathy

He became hypotensive on the evening of admission after a bout of loose stool and that was set right with fluid resuscitation. This was initially attributed to hypovolaemia and possibly `septic shock'. The colonoscopy was postponed because of presumed sepsis. However, over the next four to five days he continued to have recurrent daily hypotension with a systolic blood pressure of 80-90 mmHg. These episodes occurred in the night without associated tachycardia. Each time, he was treated for presumed sepsis, with fluid boluses.

What are the possible causes of persistent hypotension in this man?

Likely causes for persistent hypotension are:
a) Addisonian state
b) Autonomic neuropathy
c) Hypovolaemia secondary to diarrhoea
d) Septic shock

Due to the persistent hypotension in the night without tachycardia, we began to suspect adrenal insufficiency (AI).

Why does hypotension occur with relative bradycardia in AI?

Glucocorticoids potentiate the action of catecholamines. Hence AI leads to hypotension without tachycardia.

A short synacthen test was performed (using 250mg of synacthen) with the following results: 0 min (at 8am) cortisol 270 nmol/l, adrenocorticotrophic hormone (ACTH) 62.9 ng/l (9-52); 30 min cortisol 399 nmol/l; 60 min cortisol 424 nmol/l. This was consistent with adrenal insufficiency (AI). HIV serology by Western blot assay was subsequently positive.

What is the prevalence and pathophysiology of adrenal insufficiency (AI) in AIDS patients?

Clinically manifest AI in AIDS patients has been reported to range from less than 10% to 22%, although prevalence of adrenalitis ranges from 40% to 66%.^1,2,3 It is estimated that up to 90% of the adrenals needs to be affected before clinical manifestations.^1,2,3 The adrenalitis is probably not due to the HIV infection itself, but by secondary involvement of endocrine organs through opportunistic infections, metabolic disturbances or autoimmune process.^1,2,4

Why is it difficult to diagnose of AI in AIDS patients?

The manifestations of AI are usually non-specific and can be easily mistaken as due to AIDS itself. Common features of AI in AIDS patients are lethargy, wasting, vomiting, diarrhoea, fever and hypotension.^1,2 The characteristic skin pigmentation is less common.²

What factors can result in a falsely abnormal synacthen test in AIDS patients?

could account for the resolution of hypotension after hydrocortisone therapy.¹⁰ However, this is most commonly seen in patients with bacterial infections. In our patient, a detailed bacteriological workup was negative. Also, sepsis-associated hypotension does not usually occur in a nocturnal fashion. Another factor that is not seen commonly in septic shock is relative bradycardia.

Some drugs could result in relative AI. These include ketoconazole, fluconazole, opiates, rifampicin, phenytoin and megestrol acetate.^2,4,5,6

A central cause (e.g. pituitary disease) could also result in an abnormal synacthen test. However, this was unlikely in this patient as his serum ACTH was elevated.

Is there any difference in criteria used to diagnose AI in AIDS patients compared to the general population?

The diagnosis of AI is based on an inadequate rise in cortisol levels after a supraphysiologic dose of synacthen. Our patient met the criteria for adrenal insufficiency in AIDS patients using the one hour serum cortisol level < 496 nmol/l.^1,2,5 However, there is some controversy regarding the cut-off at which cortisol response is considered adequate.^2,6 Some authors found that certain patients with a post-stimulation cortisol value between 496 to 606 nmol/l had AI on further challenge with the insulin-induced hypoglycaemia test. Others suggest using only 1 mg of synacthen to increase the sensitivity of the test, allowing diagnosis of early partial AI.⁷ However, the risk of using a higher cut off would be inappropriate glucocorticoid therapy in AIDS patients without AI. Piedrola et al reported that a basal cortisol level at 0830 hours< 275 nmol/l was highly suggestive of AI in AIDS patients.² Our patient's 8 am cortisol level was 270 nmol/l. The corresponding level suggestive of AI in the general population is < 140 nmol/l.⁸ This difference may be because in some studies baseline cortisol levels were found to be significantly higher in AIDS patients compared to normal controls, most likely due to ongoing stress.^1,2,4,6,9

Intravenous hydrocortisone (100mg 6-hourly) replacement was initiated and that resulted in the correction of the hypotensive episodes.

What is the treatment of AI in AIDS patients?

Our patient responded well to intravenous hydrocortisone. Some patients may also require fludrocortisone.^4,9 Glucocorticoid should only be administered to AIDS patients with confirmed AI due to the risk of exacerbating underlying chronic opportunistic infections.

Could this patient's hypotension be secondary to "sepsis"?

Severe sepsis may be associated with relative AI and this could account for the resolution of hypotension after hydrocortisone therapy.10 However, this is most commonly seen in patients with bacterial infections. In our patient, a detailed bacteriological workup was negative. Also, sepsis-associated hypotension does not usually occur in a nocturnal fashion. Another factor that is not seen commonly in septic shock is relative bradycardia.

Over the next few days, he developed increasing dyspnoea. CXR revealed new bilateral infiltrates. Absolute CD4 and CD8 counts, done because of marked wasting and suspicious "contact" history, was 13 /ul and 725 /ul respectively. High resolution computed tomography of thorax showed bilateral symmetrical smooth thickening of interstitium consistent with interstitial lung disease.He was treated empirically for Pneumocystis carinii pneumonia (PCP) with intravenous cotrimoxazole (consisting of 200mg trimethoprim 8-hourly).

What are the causes of AI in AIDS patients?

Cytomegalovirus (CMV) is the commonest aetiological agent; others being Mycobacterium avium intracellulare, Mycobacterium tuberculosis, Cryptococcus, Toxoplasma gondii, Histoplasmosis, Pneumocystis carinii, Kaposi's sarcoma and non-Hodgkin's lymphoma.^2,3,4

We did not further investigate the cause of his AI (e.g. adrenal antibodies, cytomegalovirus antigen) as he was transferred to a specialist centre for AIDS patients where PCP was confirmed. However, he died nineteen days after the initial presentation.

What is the prognosis for AIDS patients with AI?

Prognosis in these patients is poor. All patients had CD4 cell count < 100/ul, and almost all patients had an opportunistic infection.^2,3,4 The mean survival ranged between few weeks to a few months.^2,3 However, despite the poor survival, treatment results in clinical improvement and a better quality of life.^3,4,9

Why is it important to recognise the association of AI in AIDS patients?

Prompt recognition of this association is imperative. These patients are at increased risk of infection which may precipitate an Addisonian crisis. This may be misdiagnosed as septic shock with treatment being misdirected. Early initiation of corticosteroid replacement will potentially improve the quality of life and reduce hospital stay, which is important for these ill patients in the remaining days of their lives.

References

1. Gonzalez-Gonzalez JG, Garza-Hernandez NE, Garza-Moran RA, Rivera-Morales IM, Montes-Villarreal J, Valenzuela-Rendon J, et al. Prevalence of abnormal adrenocortical function in human immunodeficiency virus infection by low-dose cosyntropin test. Int J STD AIDS 2001;12:804-10.
2. Piedrola G, Casado JL, Lopez E, Moreno A, Perez-Elias MJ, Garcia-Robles R. Clinical features of adrenal insufficiency in patients with acquired immunodeficiency syndrome. Clin Endocrinol 1996;45:97-101.
3. Baraia-Etxaburu AJ, Astigarraga AB, Elorza OR, Teira CR, Yoldi AA, Cisterna CR, et al. Primary adrenal failure and AIDS: report of 11 cases and review the literature. Rev Clin Esp 1998;198:74-9
4. Freda PU, Wardlaw SL, Brudney K, Goland RS. Primary adrenal insufficiency in patients with the acquired immunodeficiency syndrome: A report of five cases. J Clin Endocrinol Metab 1994;79:1540-5.
5. Casado JL, Piedrola G. Adrenal insufficiency in patients with AIDS: When to suspect it and how to diagnose it. AIDS Patient Care STDS 1997; 11: 339-43
6. Strauss K. Endocrine complications of the acquired immunodeficiency syndrome. Arch Intern Med 1991;151:1441-4
7. Wolff FH, Nhuch C, Cadore LP, Glitz CL, Lhullier F, Furlanetto TW. Low-dose adrenocorticotropin test in patients with the acquired immunodeficiency syndrome. Braz J Infect Dis 2001;5:53-9
8. Fitzgerald PA. Endocrinology In: Tierney LM, McPhee SJ, Papadakis MA, Editors. Current Medical Diagnosis and Treatment 38^th Edition. Appleton and Lange 1999. pp 1094-97
9. Cobbs R, Pepper GM, Torres JG, Gruenspan HL. Adrenocortical insufficiency with normal serum cortisol levels and hyporeninaemia in a patient with acquired immunodeficiency syndrome (AIDS). J Int Med 1991; 230: 179-81.
10. Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288: 862-71.

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