Evaluation of the effectiveness of midnight serum cortisol in the diagnostic procedures for Cushing’s syndrome

Reimondo, Giuseppe; Allasino, Barbara; Bovio, Silvia; Paccotti, Piero; Angeli, Alberto; Terzolo, Massimo

doi:10.1530/eje.1.02042

Cited by 63 publications

(33 citation statements)

References 26 publications

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“…According to our data, a single MserC concentration of O243 nmol/l has a PPV of 98% in differentiating CD from PCS (NPV of 95%). This high diagnostic accuracy is in accordance with other studies which used almost similar patient groups (9,26). However, the impracticality and cost of admitting patients for MserC precludes the use of this test in the initial evaluation of patients with suspected hypercortisolism.…”

Section: Discussionsupporting

confidence: 89%

Differentiating between Cushing's disease and pseudo-Cushing's syndrome: comparison of four tests

Alwani

Jongbloed

Jong

et al. 2014

European Journal of Endocrinology

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Objective: To evaluate the diagnostic performance of four different tests in order to differentiate between Cushing's disease (CD) and pseudo-Cushing's syndrome (PCS). Methods: In this prospective study, a total of 73 patients with clinical features of hypercortisolism and insufficient suppression of serum cortisol after 1 mg overnight dexamethasone and/or an elevated excretion of cortisol in 24-h urine samples were included. The circadian rhythm of serum cortisol levels as well as midnight serum cortisol (MserC) levels were assessed in all 73 patients. Late-night salivary cortisol (LNSC) concentrations were obtained in 44 patients. The dexamethasone-CRH (Dex-CRH) test was performed in 54 patients. Results: Fifty-three patients were diagnosed with CD and subsequently treated. Twenty patients were classified as having PSC. Serum cortisol circadian rhythm: the diurnal rhythmicity of cortisol secretion was retained in PCS. A cortisol midnight:morning ratio of O0.67 is highly suggestive of CD (positive predictive value (PPV) 100% and negative predictive value (NPV) 73%). MserC concentration O243 nmol/l has a PPV of 98% in predicting true CD (NPV 95%). LNSC level O9.3 nmol/l predicted CD in 94% of patients (NPV 100%). Dex-CRH test: after 2 days of dexamethasone suppression, a CRH-stimulated cortisol level O87 nmol/l (TZ15 min) resulted in a PPV of 100% and an NPV of 90%. Conclusion: The Dex-CRH test as well as a single measurement of cortisol in serum or saliva at late (mid-) night demonstrated high diagnostic accuracy in differentiating PCS from true CD.

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Section: Discussionsupporting

confidence: 89%

Differentiating between Cushing's disease and pseudo-Cushing's syndrome: comparison of four tests

Alwani

Jongbloed

Jong

et al. 2014

European Journal of Endocrinology

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“…Conversely, the other parameters of cortisol secretion were not significantly associated with the presence or number of diabetes complications. In our opinion, these seemingly discordant results may be explainable considering that F24 is highly accurate for the diagnosis of hypercortisolism (5,15) and possibly better than UFC and F-Dex (33).…”

Section: Discussionmentioning

confidence: 84%

Cortisol Secretion in Patients With Type 2 Diabetes

et al. 2007

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OBJECTIVE -The presence of an enhanced cortisol secretion in patients with type 2 diabetes is debated. In type 2 diabetic subjects, cortisol secretion was found to be associated with the complications and metabolic control of diabetes. We evaluated cortisol secretion in 170 type 2 diabetic subjects and in 71 sex-, age-, and BMI-matched nondiabetic subjects. RESEARCH DESIGN AND METHODS-In all subjects, we evaluated ACTH at 8:00 A.M. in basal conditions and serum cortisol levels at 12:00 P.M. (F24) and at 9:00 A.M. after a 1-mg overnight dexamethasone suppression test and 24-h urinary free cortisol (UFC). In diabetic patients, we evaluated the presence of chronic complications (incipient nephropathy, asymptomatic neuropathy, background retinopathy, and silent macroangiopathy). Patients were subdivided according to the absence (group 1, n ϭ 53) or presence (group 2, n ϭ 117) of diabetes complications.RESULTS -In group 2, UFC (125.2 Ϯ 4.6 nmol/24 h) and F24 (120.6 Ϯ 4.1 nmol/l) were higher than in group 1 (109.2 Ϯ 6.8 nmol/24 h, P ϭ 0.057, and 99.7 Ϯ 6.1 nmol/l, P ϭ 0.005, respectively) and in nondiabetic patients (101.7 Ϯ 5.9 nmol/24 h, P ϭ 0.002, and 100.3 Ϯ 5.3 nmol/l, P ϭ 0.003, respectively). In diabetic patients, the number of complications was associated with F24 (R ϭ 0.345; P Ͻ 0.0001) and diabetes duration (R ϭ 0.39; P Ͻ 0.0001). Logistic regression analysis showed that the presence of diabetes complications was significantly associated with F24, sex, duration of diabetes, and glycated hemoglobin.CONCLUSIONS -In type 2 diabetic subjects, hypothalmic-pituitary-adrenal activity is enhanced in patients with diabetes complications and the degree of cortisol secretion is related to the presence and number of diabetes complications. Diabetes Care 30:83-88, 2007I n patients with type 2 diabetes, glucocorticoid secretion has been suggested to be a possible link between insulin resistance and the features of the metabolic syndrome (hypertension, obesity, coronary heart disease, hyperlipidemia, and type 2 diabetes) (1-4). In fact, while glucocorticoid excess (overt or subclinical) has been demonstrated to lead to diabetes or to worsen metabolic control (5-7), the relationship between cortisol levels, insulin resistance, and chronic complications in type 2 diabetic patients without hypercortisolism is still a matter of debate.In past years, the hypothalamicpituitary-adrenal (HPA) axis secretion in patients with type 2 diabetes has been extensively investigated (8 -14). In particular, some studies reported in these subjects an elevation of ACTH (10,12), basal (9 -11) and after dexamethasone test serum cortisol (13,14), and late-night salivary cortisol levels (15). In contrast, other previous studies (16 -17) did not show any alteration of pituitary-adrenal axis secretion. The presence of chronic complications of type 2 diabetes (i.e., macroangiopathy, retinopathy, and neuropathy) has been associated to with HPA axis activity (9,18 -23), and an association between the degree of severity of several clinical measures of d...

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“…This apparently surprising finding may be explained by the fact that autonomous cortisol secretion by an adrenal adenoma resists to dexamethasone suppression, whichever dose is used. Conversely, 1-mg dexamethasone is usually sufficient to suppress cortisol secretion by the non-adenomatous adrenal tissue that is driven by pituitary ACTH, while higher dexamethasone doses are not more effective (6,(26)(27)(28)(29)(30). As a matter of fact, the phenomenon of resistance to increasing doses of dexamethasone has been already observed in small groups of patients submitted to both tests (7,31,32).…”

Section: Discussionmentioning

confidence: 99%

Pros and cons of dexamethasone suppression test for screening of subclinical Cushing’s syndrome in patients with adrenal incidentalomas

Reimondo

Allasino

Bovio

et al. 2011

J Endocrinol Invest

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The results of dexamethasone suppression tests (DST) in the screening of subclinical hypercortisolism are not readily comparable. Aim of the present study was to review the effectiveness of the overnight 1-mg DST and 8-mg DST to look for functional autonomy of clinically inapparent adrenal adenomas.Sixty-eight consecutive patients with clinically inapparent adrenal adenomas were enrolled. All patients underwent 1-mg DST. The 8-mg DST was performed in the 11 patients who had post 1-mg DST cortisol >138 nmol/L and in 11 patients who had post 1-mg DST cortisol between 50 -138 nmol/L. The a priori probability to have autonomous cortisol secretion was defined by the presence of at least two alterations of the HPA axis among reduced ACTH concentrations, elevated UFC or elevated midnight serum cortisol. Cortisol levels > 138 nmol/L after the 1-mg DST increases the post-test probability of adrenal functional autonomy to 55%, whereas cortisol levels <50 nmol/L reduce the post-test probability to 8%. Cortisol levels recorded after the 8-mg DST were non-significantly lower than after the 1-mg DST and all the patients with cortisol >138 nmol/L after the 1 mg DST maintained cortisol above this cut-point.The 1-mg DST should be considered as the more effective test to detect autonomous cortisol secretion by a clinically inapparent adrenal adenoma when cortisol levels are >138 nmol/l, while cortisol levels < 50 nmol/L reduces remarkably the post-test probability of this event. The 8-mg DST seems to replicate by large the results of the 1-mg DST.4

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Evaluation of the effectiveness of midnight serum cortisol in the diagnostic procedures for Cushing’s syndrome

Cited by 63 publications

References 26 publications

Differentiating between Cushing's disease and pseudo-Cushing's syndrome: comparison of four tests

Differentiating between Cushing's disease and pseudo-Cushing's syndrome: comparison of four tests

Cortisol Secretion in Patients With Type 2 Diabetes

Pros and cons of dexamethasone suppression test for screening of subclinical Cushing’s syndrome in patients with adrenal incidentalomas

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