Misinterpretation of serum cortisol in a patient with hyponatraemia
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《英国医生杂志》
1 Department of Medicine, Bristol Royal Infirmary, Bristol BS2 8HW
Correspondence to: J C Smith, Department of Diabetes and Endocrinology, Bristol Royal Infirmary, Bristol BS2 8HW jamie.smith@virgin.net
Introduction
When adrenal insufficiency presents acutely in its classic form, characteristic clinical and biochemical findings usually lead to a prompt diagnosis. However, in more atypical insidious presentations, such as in the present case, the diagnosis can initially be overlooked when predominant symptoms such as nausea and vomiting are attributed to localised gastrointestinal pathology rather than being recognised as a manifestation of adrenal insufficiency.
Although hyponatraemia is a common electrolyte disturbance in elderly people, its clinical evaluation and investigation are often incomplete.2 3 For example, in one retrospective study from a UK teaching hospital involving 47 cases of severe hyponatraemia, adrenal insufficiency was excluded in only one case.2 The present case shows the importance of a careful evaluation of hyponatraemia in elderly people. The syndrome of inappropriate antidiuretic hormone secretion should be regarded as a diagnosis of exclusion and cannot be said to occur in the presence of other underlying conditions that may be responsible for hyponatraemia. It is difficult to suggest a threshold of hyponatraemia below which adrenal insufficiency should be formally excluded. Rather, adrenal insufficiency should be considered in any hyponatraemic patient in whom an alternative precipitating cause for hyponatraemia is not apparent.
Although measurement of random serum cortisol can a useful screening test to exclude adrenal insufficiency,4 careful interpretation of the result with regard to the patient's clinical status is required. A morning (8-9 am) cortisol concentration of > 500 nmol/l effectively rules out the possibility of adrenal insufficiency in most cases, whereas a concentration of < 100 nmol/l (especially in a stressed individual) is highly suggestive of the diagnosis.4 For acutely ill patients with major trauma or severe sepsis, a safe cut off is unknown, but cortisol concentrations of > 700 nmol/l probably rule out adrenal insufficiency.5 With values falling below this level, diagnostic doubt remains and dynamic testing is required. Thus, in the present case a cortisol concentration of 163 nmol/l did not exclude adrenal insufficiency. Furthermore, this level of cortisol should have been regarded as below normal in the presence of an acute illness (pneumonia), during which activation of the hypothalamic-pituitary-adrenal axis would be expected.
The short corticotrophin test is safe and simple to perform, and interpretation of the results is straightforward.4 There should therefore be a low threshold for performing this investigation in unexplained hyponatraemia. A blunted response to a 250 μg dose in association with elevated plasma adrenocorticotrophic hormone is diagnostic of primary adrenal insufficiency. When adrenal insufficiency is suspected in acutely ill patients, administration of corticosteroids should not be delayed pending results of diagnostic tests. In such patients, hydrocortisone should be given immediately after blood samples are drawn for cortisol and adrenocorticotrophic hormone. The combination of a low serum cortisol (< 100 nmol/l) and elevated plasma adrenocorticotrophic hormone (> 100 ng/l) is diagnostic in these circumstances.1
Autoimmune adrenalitis resulting in slow destruction of the gland is responsible for most cases of Addison's disease in Westernised populations.1 However, adrenal infections with a variety of organisms—including tuberculosis, fungal infections such as histoplasmosis, and opportunistic bacterial infections associated with immunodeficiency states—may lead to Addison's disease.1 In the present case the absence of adrenal autoantibodies together with the radiological finding of adrenal calcification might indicate previous exposure to tuberculosis. The finding of small atrophic adrenal glands is indicative of previous infection, whereas in active disease adrenal enlargement is almost universal.6
The possibility of hypoadrenalism must be considered in unexplained hyponatraemia, and cortisol measurements should be interpreted carefully
Contributors: JCS drafted and revised the manuscript. HS helped with managing the patient and performed the relevant literature searches. RJMC helped with drafting and revising the manuscript. RJMC is the guarantor.
Competing interests: None declared.
References
Oelkers W. Current concepts: adrenal insufficiency. N Engl J Med 1996;335: 1206-12.
Crook MA, Velauthar U, Moran L, Griffiths W. Review of investigation and management of severe hyponatraemia in a hospital population. Ann Clin Biochem 1999;36: 158-62.
Saeed BO, Beaumont D, Handley GH, Weaver JU. Severe hyponatraemia: investigation and management in a district general hospital. J Clin Pathol 2002;55: 893-6.
Grinspoon SK, Biller BM. Laboratory assessment of adrenal insufficiency. J Clin Endocrinol Metab 1994;79: 923-31.
Vermes I, Beishuizen A, Hampsink RM, Haanen C. Dissociation of plasma adrenocorticotropin and cortisol levels in critically ill patients: possible role of endothelin and atrial natiuretic peptide. J Clin Endocrinol Metab 1995;80: 1238-42.
Vita JA, Silverberg SJ, Goland RS, Austin JH, Knowlton AI. Clinical clues to the cause of Addison's disease. Am J Med 1985;78: 461-6.(Jamie C Smith, specialist)
Correspondence to: J C Smith, Department of Diabetes and Endocrinology, Bristol Royal Infirmary, Bristol BS2 8HW jamie.smith@virgin.net
Introduction
When adrenal insufficiency presents acutely in its classic form, characteristic clinical and biochemical findings usually lead to a prompt diagnosis. However, in more atypical insidious presentations, such as in the present case, the diagnosis can initially be overlooked when predominant symptoms such as nausea and vomiting are attributed to localised gastrointestinal pathology rather than being recognised as a manifestation of adrenal insufficiency.
Although hyponatraemia is a common electrolyte disturbance in elderly people, its clinical evaluation and investigation are often incomplete.2 3 For example, in one retrospective study from a UK teaching hospital involving 47 cases of severe hyponatraemia, adrenal insufficiency was excluded in only one case.2 The present case shows the importance of a careful evaluation of hyponatraemia in elderly people. The syndrome of inappropriate antidiuretic hormone secretion should be regarded as a diagnosis of exclusion and cannot be said to occur in the presence of other underlying conditions that may be responsible for hyponatraemia. It is difficult to suggest a threshold of hyponatraemia below which adrenal insufficiency should be formally excluded. Rather, adrenal insufficiency should be considered in any hyponatraemic patient in whom an alternative precipitating cause for hyponatraemia is not apparent.
Although measurement of random serum cortisol can a useful screening test to exclude adrenal insufficiency,4 careful interpretation of the result with regard to the patient's clinical status is required. A morning (8-9 am) cortisol concentration of > 500 nmol/l effectively rules out the possibility of adrenal insufficiency in most cases, whereas a concentration of < 100 nmol/l (especially in a stressed individual) is highly suggestive of the diagnosis.4 For acutely ill patients with major trauma or severe sepsis, a safe cut off is unknown, but cortisol concentrations of > 700 nmol/l probably rule out adrenal insufficiency.5 With values falling below this level, diagnostic doubt remains and dynamic testing is required. Thus, in the present case a cortisol concentration of 163 nmol/l did not exclude adrenal insufficiency. Furthermore, this level of cortisol should have been regarded as below normal in the presence of an acute illness (pneumonia), during which activation of the hypothalamic-pituitary-adrenal axis would be expected.
The short corticotrophin test is safe and simple to perform, and interpretation of the results is straightforward.4 There should therefore be a low threshold for performing this investigation in unexplained hyponatraemia. A blunted response to a 250 μg dose in association with elevated plasma adrenocorticotrophic hormone is diagnostic of primary adrenal insufficiency. When adrenal insufficiency is suspected in acutely ill patients, administration of corticosteroids should not be delayed pending results of diagnostic tests. In such patients, hydrocortisone should be given immediately after blood samples are drawn for cortisol and adrenocorticotrophic hormone. The combination of a low serum cortisol (< 100 nmol/l) and elevated plasma adrenocorticotrophic hormone (> 100 ng/l) is diagnostic in these circumstances.1
Autoimmune adrenalitis resulting in slow destruction of the gland is responsible for most cases of Addison's disease in Westernised populations.1 However, adrenal infections with a variety of organisms—including tuberculosis, fungal infections such as histoplasmosis, and opportunistic bacterial infections associated with immunodeficiency states—may lead to Addison's disease.1 In the present case the absence of adrenal autoantibodies together with the radiological finding of adrenal calcification might indicate previous exposure to tuberculosis. The finding of small atrophic adrenal glands is indicative of previous infection, whereas in active disease adrenal enlargement is almost universal.6
The possibility of hypoadrenalism must be considered in unexplained hyponatraemia, and cortisol measurements should be interpreted carefully
Contributors: JCS drafted and revised the manuscript. HS helped with managing the patient and performed the relevant literature searches. RJMC helped with drafting and revising the manuscript. RJMC is the guarantor.
Competing interests: None declared.
References
Oelkers W. Current concepts: adrenal insufficiency. N Engl J Med 1996;335: 1206-12.
Crook MA, Velauthar U, Moran L, Griffiths W. Review of investigation and management of severe hyponatraemia in a hospital population. Ann Clin Biochem 1999;36: 158-62.
Saeed BO, Beaumont D, Handley GH, Weaver JU. Severe hyponatraemia: investigation and management in a district general hospital. J Clin Pathol 2002;55: 893-6.
Grinspoon SK, Biller BM. Laboratory assessment of adrenal insufficiency. J Clin Endocrinol Metab 1994;79: 923-31.
Vermes I, Beishuizen A, Hampsink RM, Haanen C. Dissociation of plasma adrenocorticotropin and cortisol levels in critically ill patients: possible role of endothelin and atrial natiuretic peptide. J Clin Endocrinol Metab 1995;80: 1238-42.
Vita JA, Silverberg SJ, Goland RS, Austin JH, Knowlton AI. Clinical clues to the cause of Addison's disease. Am J Med 1985;78: 461-6.(Jamie C Smith, specialist)