“Normal Suppression” to Dexamethasone in Cushing's Disease: An Expression of Decreased Metabolic Clearance for Dexamethasone

F, J; Meikle, A.W.; Check, J H; Cohen, Sidney

doi:10.1210/jcem-47-3-667

Cited by 39 publications

(10 citation statements)

References 16 publications

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“…Glucocorticoids with greater potency and more sustained action than hydrocortisone are widely available; these produce greater suppression of endogenous steroids and ACTH secretion (4,7,(13)(14)(15)(16). However, their long term value is not yet established, and their relative potency in humans is still uncertain due to indirect determinations of dose equivalence (17,18).…”

mentioning

confidence: 99%

Steroid Replacement in Addison's Disease and in Subjects Adrenalectomized for Cushing's Disease: Comparison of Various Glucocorticoids*

Khalid

Burke

Hurley

et al. 1982

The Journal of Clinical Endocrinology & Metabolism

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mentioning

confidence: 99%

Steroid Replacement in Addison's Disease and in Subjects Adrenalectomized for Cushing's Disease: Comparison of Various Glucocorticoids*

Khalid

Burke

Hurley

et al. 1982

The Journal of Clinical Endocrinology & Metabolism

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“…We used low doses of dexamethasone, with the hypothesis that this could limit the duration of the pharmacological stimulus and might reveal whether there is a specific time of altered sensitivity of the HHAA during the night. Results of measurement of dexamethasone would have been useful, because of the individual variation in its clearance: normal suppression in a case of Cushing's disease has been attributed to a decreased clearance of dexamethasone (Caro et al 1978). Unfortunately, the concentration of dexamethasone in plasma at 8 a.m. was lower than the limit of detection by HPLC.…”

Section: Resultsmentioning

confidence: 99%

Influence of the time of administration of dexamethasone 0.25 MG on cortisol secretion in normal humans

Schulz¹,

Costa²,

Widmer³

et al. 1986

Psychopharmacology

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Single low doses (0.25 mg) of dexamethasone were given at 11 p.m., 2, 5 and 8 a.m. on separate days to five normal subjects. The concentrations of cortisol in plasma on the next day were significantly decreased compared to results after placebo administration, and cortisol suppression was maximal after dexamethasone had been given at 8 a.m. Our findings suggests that the postulated phase-advance of circadian rhythms is not a major cause of cortisol non-suppression in depressives given dexamethasone.The utility of the dexamethasone suppression test (DST) in psychiatry has been the subject of numerous studies. Generally, 1 mg dexamethasone was given at 11 p.m. to patients and cortisol concentrations in plasma during the next day were compared to those measured in matched normal controls. Through such protocols, the known overproduction of cortisol during major depressive episodes (Doig et al. 1966;Conroy et al. 1968;Fullerton et al. 1968) has been confirmed in subgroups of patients.Circadian rhythms of cortisol sercretion might be abnormal, i.e. phase-advanced by a few hours, during major depressive episodes (Jarrett et al. 1983;Sachar et al. 1973), though other authors did not confirm this observation (Claustat et al. 1984). If there exists a phase-advance of cortisol rhythms in depressives, then one could conclude that administering dexamethasone at 11 p.m. to depressives would correspond to giving the drug between 1 and 3 a.m. to normal subjects. We therefore studied the influence on cortisol secretion of the time of dexamethasone administration in normal subjects, to establish whether chronobiological changes in the sensitivity of the hypothalamic-pituitaryadrenal axis (HHAA) might lead to a false positive nonsuppression. Materials and methodsSeven normal subjects of 25-38 years of age participated. The study was conducted in May and June. A pilot study in two subjects revealed complete suppression after 1 mg dexamethasone (Millicortene R, Ciba) given at 2 or 5 a.m.Offprint requests to: P. Schulz (with the exception of the 8 a.m. samples drawn after the 5 a.m. administration). Partial suppression was obtained after 0.25 mg given at 11 p.m. or 3 a.m. to the same two subjects. Therefore, 0.25 mg dexamethasone was administered orally to the other five subjects, at 11 p.m., 2 a.m., 5 a.m. and 8 a.m., using a cross-over latin square design. An identical placebo was administered once at 11 p.m. Each drug or placebo administration was separated by at least 5 days. According to Yerevanian et al. (1985), weekly administration of dexamethasone to normal subjects does not lead to false positive non-suppression. Venous blood samples were drawn through an indwelling catheter (BectonDickinson), using no heparin, every 2 h from 8 a.m. to 8 p.m. after dexamethasone and plasma was stored at -20 ° C pending analysis. The concentration of cortisol in plasma was measured using a commercial kit (Bio-M6rieux) based on the competition for transcortin. There was an excellent concordance between cortisolaemia measured with this assay a...

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“…However, some cases were reported to be normally suppressed with dexamethasone in doses even less than those required to inhibit secretion in Cushing's disease (Caro et al, 1978, King et al, 1983. On the other hand, Hiramatsu et al(1983) and Carey et al(1980) reported the cases in which plasma cortisol was not suppressed with high doses of dexamethasone.…”

Section: Discussionmentioning

confidence: 99%

“…However, plasma cortisol was not suppressed with 0.25mg of dexamethasone. Caro et al (1978) and King et al(1983) reported that patients with Cushing's disease whose plasma cortisol was normally suppressed with a low dose of dexamethasone showed decreased clearance of dexamethasone. The plasma dexamethasone level of our patients was not measured but, even if the plasma cortisol levels were suppressed with 0.5mg of dexamethasone, UFC levels were not suppressed with this dose.…”

Section: Patientsmentioning

confidence: 99%

The Changes in Plasma Cortisol and Urinary Free Cortisol by an Overnight Dexamethasone Suppression Test in Patients with Cushing's Disease.

Odagiri¹,

Demura²,

Demura³

et al. 1988

Endocrinol Japon

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“Normal Suppression” to Dexamethasone in Cushing's Disease: An Expression of Decreased Metabolic Clearance for Dexamethasone

Cited by 39 publications

References 16 publications

Steroid Replacement in Addison's Disease and in Subjects Adrenalectomized for Cushing's Disease: Comparison of Various Glucocorticoids*

Steroid Replacement in Addison's Disease and in Subjects Adrenalectomized for Cushing's Disease: Comparison of Various Glucocorticoids*

Influence of the time of administration of dexamethasone 0.25 MG on cortisol secretion in normal humans

The Changes in Plasma Cortisol and Urinary Free Cortisol by an Overnight Dexamethasone Suppression Test in Patients with Cushing's Disease.

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