Table 11.
Chronologic and technical evolution of the post-dexamethasone suppression interpretation threshold for Cushing disease diagnosis (low dose) and localization (high dose) in dogs.
| Ref. | Sample medium | Cortisol assay | Dexamethasone suppression tests† | Cushing population | Compared population | IT | Source of the IT | Se (%) | Sp (%) |
|---|---|---|---|---|---|---|---|---|---|
| 32 | Plasma (not specified) | FMM (non-immune) | LDDST (0.01 mg/kg IV) | 22 PDH | 24 healthy kennel dogs | 140 nmol/L (5.1 μg/dL) | 32 | 100‡ | — |
| • 8 h post-dex range normal dogs: 15–130 nmol/L | |||||||||
| • 8 h post-dex range PDH: 150–520 nmol/L | |||||||||
| 33 | Plasma (not specified) | RIA | LDDST (0.01 mg/kg IV) | 8 AT | 21 healthy kennel dogs | Not provided | 33 | 100‡ | — |
| Deducible IT from provided data: 41–65 nmol/L (1.5–2.4 μg/dL) | |||||||||
| • 8 h post-dex range normal dogs: 0–40 nmol/L | |||||||||
| • 8 h post-dex range AT: 66–290 nmol/L | |||||||||
| 11 | Plasma (heparinized) | CBPM (non-immune radioassay) | LDDST (0.01 mg/kg IV) | 26 PDH, 7 AT, 31 HAC (unknown location) | 22 control dogs | 38.6 nmol/L (1.4 µg/kg) | 11 | 92 HAC | — |
| (Post 8 h only) | • 8 h post-dex normal dogs: mean + 3SD = 37.8 nmol/L (1.37 µg/dL) | 96 PDH | |||||||
| 100 AT | |||||||||
| 10 | Plasma (heparinized) | CBPM (non-immune radioassay) | HDDST (0.1 mg/kg IV) | 10 PDH, 3AT | 20 control dogs | 8 h >50% baseline | 10 | 92§ | — |
| (Post 8 h only) | • 8 h post-dex all normal dogs <50% baseline | ||||||||
| • better than 8 h > (mean + 3SD) of healthy dogs: 27.6 nmol/L (1 µg/dL) | |||||||||
| 12 | Plasma (heparinized) | CBPM (non-immune radioassay) | LDDST (0.01 mg/kg IV) | 15 PDH, 6 AT | None | 38.6 nmol/L (1.4 μg/dL) | Quoted study11 | 100 | — |
| 7 | Plasma (EDTA) | RIA | LDDST (0.01 mg/kg IV) | None | 33 NAI 14 clinically normal dogs | 37 nmol/L (1.34 μg/dL) | 7 | — | 52 |
| • 8 h post-dex normal dogs: mean + 2SD = 37 nmol/L | |||||||||
| 13 | Plasma (heparinized) | CBPM (non-immune radioassay) | LDDST (0.01 mg/kg IV) | 14 PDH, 3 AT | None | 38.6 nmol/L (1.4 μg/dL) | Quoted study11 | 94 | — |
| 44 | Plasma (not specified) | RIA | LDDST (0.01 mg/kg IV) | 129 HAC | 37 HAC-S | 40 nmol/L (1.45 μg/dL) | No source | 85 | 73 |
| 30 | Plasma (heparinized) | Enzyme immunoassay | LDDST (0.01 mg/kg dexamethasone phosphate IV) | 14 PDH, 4 AT | 5 healthy control dogs | 38.6 nmol/L (1.4 μg/dL) | Quoted study10¦ | 100 | 100 |
| LDDST (0.015 mg/kg dexamethasone polyethylene glycol IV) | 14 PDH, 4 AT | 5 healthy control dogs | 38.6 nmol/L (1.4 μg/dL) | Quoted study10¦ | 89 HAC | 100 | |||
| 86 PDH | |||||||||
| 100 AT | |||||||||
| 43 | Plasma (heparinized) | CBPM (non-immune radioassay) | LDDST (0.01 mg/kg IV) | 28 AT, 26 PDH | 22 healthy dogs | 38.6 nmol/L (1.4 μg/dL) | Quoted study10¦ | 98 HAC | — |
| 100 AT | |||||||||
| 96 PDH | |||||||||
| 26 | Plasma (not specified) | Enzyme immunoassay | LDDST (0.01 mg/kg IV) | 33 PDH | None | 38.6 nmol/L (1.4 nmol/L) | Quoted study11 | 97 | — |
| 24 | Serum | RIA | LDDST (0.015 mg/kg IV) | 20 PDH | 59 NAI | About 30 nmol/L# (~1.1 μg/dL#) | No source | 100 | 44 |
| 16 | Plasma (heparinized) | Enzyme immunoassay | LDDST (0.01 mg/kg IV) | 181 PDH, 35 AT | None | For HAC diagnosis: 38.6 nmol/L (1.4 nmol/L) | For HAC diagnosis: quoted study11 | 61§ | 100§ |
| Post 4 h and 8 h | For HAC localization: 4 h >1.4 μg/dL | For HAC localization: article itself | |||||||
| Or 4 h or 8 h >50% baseline | |||||||||
| HDDST (0.1 mg/kg IV) | 181 PDH, 35 AT | 35 AT | 4 h or 8 h: >1.4 μg/dL or >50% baseline | 16 | 75§ | 95§ | |||
| Post 4 h and 8 h | |||||||||
| 49 | Plasma (not specified) | Assay not specified | LDDST (0.01 mg/kg IV) | 28 HAC | 10 NAI | 41.4 nmol/L (1.5 μg/dL) | IT established by the endocrine diagnostic laboratory at the teaching hospital (unpublished data) | 96 | 70 |
| 4 | Plasma (heparinized) | CLIA: Immulite 1000 and 2000 (Siemens) | LDDST (0.015 mg/kg IV) | 59 HAC | 64 NAI | 4 h or 8 h >27.6 nmol/L (1 μg/dL) | No source | 96.6 | 67.2 |
| Post 4 h and 8 h | |||||||||
| 36 | Serum | CLIA: Elecsys/Cobas (Roche) | LDDST (0.01 mg/kg IV) | LDDST only for selection of HAC cases, not part of the investigation (focused on the best ACTH threshold) | 8 h >30.3 nmol/L (1.1 μg/dL) | IT based on the laboratory’s RI for these tests and previous reports | — | — | |
Dash (—) = Se or Sp not provided; ACTH = adrenocorticotropic hormone; AT = dogs with adrenal tumor responsible for hyperadrenocorticism; CBPM = competitive binding protein method; CLIA = chemiluminescent immunoassay; Dex = dexamethasone; F = intact females; FMM = fluorometric method of Mattingly; HAC = dogs with hyperadrenocorticism; HAC-S = dogs suspected of hyperadrenocorticism confirmed to not have hyperadrenocorticism; HDDST = High dose dexamethasone suppression test; IT = interpretation threshold; LDDST = Low dose dexamethasone suppression test; M = intact males; NAI = dogs with non-adrenal illness; NM = neutered males; PDH = dogs with pituitary-dependent hyperadrenocorticism; RI = reference interval; RIA = radioimmunoassay; ROC = receiver operating characteristic; Se = sensitivity; SF = spayed females; Sp = specificity.
Articles in which the ACTH stimulation test is also investigated.
When hours are not specified, it is a suppression 8 h post-dexamethasone injection. It does not necessarily mean that no previous time points (3 and/or 4 h) have not been performed in the studies, but we do not report them. When we chose to report the additional time point at 4 h, it is associated with an important conclusion in the studies.
The sensitivity of the LDDST for HAC was not stated in the article, but could be computed from the provided data, and is also stated as such by later reviews.
Those Se and Sp are not for the diagnosis of HAC; they are for the localization of HAC as PDH, provided that HAC has already been diagnosed. In this context, a “positive” dog is a dog that suppresses cortisol after dexamethasone injection (LDDST or HDDST), whereas a “negative” dog does not suppress. Thus, imperfect sensitivity (presence of false positives) corresponds with PDH, which do not suppress, and imperfect specificity (presence of false negatives) corresponds with AT, which suppress.
Those studies are wrongly referencing the Feldman’s study on HDDST10 to support their choice of IT for the LDDST. They intended to reference another study.11 The mistake is not rare, as both studies from Feldman were published in 1983 and in the same journal.
No IT was provided in the text; a figure contained a shaded area picturing the “reference range values,” from which the threshold could be only roughly inferred.