SMJ Current Issue


 
CLINICAL NOTES
 
Cushing’s syndrome. Case illustration and guidelines in management
 
  Abdelqawi A Al-Mansarit,  Marwane W Najjare,  Sattame S Lingawie
 
 
 
Saudi Medical Journal 2004; Vol.  (9): 1274-1276 doi: http://dx.doi.org/
 

 

The patient is a 43-year-old housewife, with a history of gaining weight over the last 19 years, in addition to type 2 diabetes mellitus (DM) and hypertension over the past 9 years. Blood glucose was increasingly uncontrolled, eventually requiring insulin treatment. Physical examination showed a depressed lady with truncal obesity (103 kg), supraclavicular fat padding and abdominal striae.P>

Low dose dexamethasone suppression test (LDDST) was positive for Cushing’s syndrome (CS) with a plasma cortisol of 31.4µg /dl (normal < 1.8 µg /dl). Baseline cortisol level was greater than 50 µg/dl and adrenocorticotropin hormone (ACTH) 44 pg/ml (both are high) indicating ACTH dependent Cushing’s disease (CD). For localization of ACTH production, high dose dexamethasone suppression test (HDDST) was carried out and cortisol level decreased to 6 µg/dl (more than 80% reduction) suggesting pituitary ACTH production. Magnetic resonance imaging (MRI) of the pituitary gland was non-conclusive as far as demonstrating pathology (Figure 1a & 1b). Inferior petrosal sinus sampling was thus, conducted to confirm the diagnosis of CD and try to lateralize the side of ACTH secretion. It was suggestive of a left-sided pituitary adenoma (Table 1). P>

The patient underwent sub-labial transsphenoidal pituitary surgery, where a left-sided adenoma was found and resected, with an uneventful postoperative course. Eight-am serum cortisol level on the 3rd postoperative day, was less than 1 µg/dl. A month after the surgery the patient’s mood was very good, and she had lost 6 kg with a fasting blood glucose of 120 mg/dl off insulin. The serum ACTH level was less than 10, indicating cure after holding prednisone for 2 days. P>

Management of Cushing’s Syndrome.B>I> Clinical suspicion is still the corner stone in detecting suspected cases of CS.1 The decision of further investigating the patient, depends on how high the suspicion is; especially that several disorders can raise the cortisol level, in addition to the possibility of having false negative results in episodic and intermittent CS variant. Endogenous CS is caused by excess glucocorticoids production due to increased ACTH secretion in 80-85% of the cases, or less frequently due to primary adrenal disease.1 Detailed history including intake of oral, inhaled, or topical steroids, and history of weight gain and associated diseases is an integral part of assessment, in addition to thorough physical examination looking for abdominal obesity, supraclavicular fat pad and purple striae.1 P>

Does the patient have CS?B>I> Overnight 1 mg dexamethasone is a simple inexpensive screening test, taking into consideration that the normal level was lowered from 5 µg/dl to 1.8 µg/dl. Lowering the normal value, increased the sensitivity, allowing detection of mild cases at the expense of specificity.2 Pseudo-Cushing’s, medical illness, or abnormalities in cortisol binding globulin (CBG) might test positive.2,3 Twenty-four-hour urinary cortisol is both a screening and confirmatory test. It measures free (unbound) cortisol, so it is not affected by CBG abnormalities.2 Up to 3 urine collections may be performed, as some patients have intermittent hypercortisolism state.1 Urine volume and kidney functions are major determinants, so urine creatinine should be requested in all collections. Late-night salivary cortisol is a useful test and correlates with free plasma cortisol. The test is conducted in limited centers, and the normal values are not standardized.3 Elevated midnight plasma cortisol (over 1.8 µg/dl) is a very sensitive test but lacks specificity, which can be as high as 100% if the value went up to 7.5 µg/dl.3 Low-dose dexamethasone suppression test is the classical test, with a sensitivity of 79% and specificity of 74% only. Both can be enhanced to more than 95%, if plasma cortisol was measured ins

 

From the Department of Endocrinology and Diabetes (Al-Mansari), and the Department of Neurosurgery (Najjar), Dr. Erfan and Bagedo Hospitals, Jeddah, Department of Radiology (Lingawi), King Abdel-Aziz University Hospital, Kingdom of Saudi Arabia.

Address correspondence and reprint requests to Dr. Marwan W. Najjar, Dr. Erfan and Bagedo Hospitals, King Fahd St. (Al Sitteen), PO Box 6519, Jeddah 21452, Kingdom of Saudi Arabia. Tel. +966 (2) 6820022 / 280. Fax. +966 (2) 6917747. E-mail: mwnajjar@yahoo.com

 

References

1. Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, et al. Diagnosis and Complications of Cushing’s Syndrome: A Consensus Statement. JCEM 2003; 88: 5593-5602. P>

2. Invitti C, Giraldi FP, de Martin M, Cavagnini F. Diagnosis and management of Cushing’s syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab 1999; 84: 440—448.P>

3. Findling JW, Raff H. Newer diagnostic techniques and problems in Cushing’s disease. Endocrinol Metab Clin North Am 1999; 28: 191—210.P>

4. Aron DC, Raff H, Findling JW. Effectiveness versus efficacy: the limited value in clinical practice of high dose dexamethasone suppression testing in the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab 1997; 82: 1780-1785.P>

5. Kaltas GA, Giannulis MG, Newell-Price JDC, et al. A critical analysis of the value of simultaneous inferior petrosal sinus sampling in Cushing’s disease and the occult ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 1999; 84: 487-492. P>

6. Etxabe J, Vazquez JA. Morbidity and mortality in Cushing’s disease: an epidemiological approach. Clin Endocrinol (Oxf) 1994; 40: 479—484. P>

7. Blevins Jr LS, Christy JH, Khajavi M, Tindall GT. Outcomes of therapy for Cushing’s disease due to adrenocorticotropin-secreting pituitary macroadenomas. J Clin Endocrinol Metab 1998; 83: 63—67.P>

8. Bochicchio D, Losa M, Buchfelder M. Factors influencing the immediate and late outcome of Cushing’s disease treated by transsphenoidal surgery: a retrospective study by the European Cushing’s Disease Survey Group. J Clin Endocrinol Metab 1995; 80: 3114—3120.P> FONT>DIR> DIR> FONT>



Saudi Medical Journal is copyright under the Berne Convention and the International Copyright Convention. All rights reserved. Saudi Medical Journal is an Open Access journal and articles published are distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC). Readers may copy, distribute, and display the work for non-commercial purposes with the proper citation of the original work. Electronic ISSN 1658-3175. Print ISSN 0379-5284.