Table 9.
Chronologic and technical evolution of the urine cortisol:creatinine ratio interpretation threshold to exclude the differential of hyperadrenocorticism in dogs.
| Ref. | Cortisol assay | UCCR | Population with hyperadrenocorticism | Compared population | IT | Source of IT | Se (%) | Sp (%) |
|---|---|---|---|---|---|---|---|---|
| Stolp et al. 19 | FMM (non-immune) | Morning urine | 27 HAC | 28 adult healthy pet dogs | Not provided | 19 | 100‡ | -‡ |
| Deducible IT from provided data: 8–10 × 10−6 | ||||||||
| • UCCR range normal dogs: 1.2–6.9 × 10−6 | ||||||||
| • UCCR range HAC: 11–235 × 10−6 | ||||||||
| Rijnberk et al. 16 | RIA | Mean of 2 consecutive mornings | 93 HAC | 57 HAC-S | 10.10−6 | Quoted study 19 | 99 | 77§ |
| Feldman et al. 4 | RIA‡‡ | Morning urine | 40 HAC | 20 healthy dogs | 13.5 × 10−6¦ | 100 | 22# | |
| 23 PUPD non-HAC (including 11 DM) | • UCCR normal dogs: mean + 2SD = 13.5 × 10−6 | |||||||
| range 0.5–17.7 × 10−6 | ||||||||
| • UCCR PUPD non-HAC dogs: mean + 2SD = 61.4 × 10−6 | ||||||||
| range: 8.0–144 × 10−6 | ||||||||
| • UCCR HAC dogs: mean ± SD = 337.6 ± 72.0 × 10−6 | ||||||||
| range: 20–2,100 × 10−6 | ||||||||
| Smiley et al. 17 | RIA‡‡ | Morning urine | 25 HAC | 31 normal dogs | 30 × 10−6 | No source | 9 | Spnormal 97** |
| 21 HAC-S | Remark from provided data: | SpHAC-S 95** | ||||||
| 28 severe NAI | • UCCR normal dogs: mean + 2SD = 27.1 × 10−6 | |||||||
| range: 0.1–31.2 × 10−6 | SpNAI 21** | |||||||
| • UCCR HAC-S dogs: mean + 2SD = 30.3 × 10−6 | ||||||||
| range: 6.9–36.1 × 10−6 | ||||||||
| • UCCR NAI dogs: mean + 2SD = 30.1 × 10−6 | ||||||||
| range: 2.7–524 × 10−6 | ||||||||
| • UCCR HAC dogs: range: 21.3–432 × 10−6 | ||||||||
| Kaplan et al. 10 | RIA§§ | Morning urine | 20 HAC PDH | 59 NAI | About 20 × 10−6†† | 75 | 24 | |
| Jensen et al. 8 | ELISA§§ | Morning urine; 1 or mean of 2 consecutive mornings | 18 HAC | 20 dogs without HAC (no other selection criteria) | 60 × 10−6 | 8 | 100 | 85§ |
| Mean = 142.4 × 10−6 | Mean = 34.2 × 10−6 | • ROC curve optimal threshold: 62.5 × 10−6 | ||||||
| Zeugswetter et al. 20 | Immulite 1000 | Morning urine collected at home | 66 HAC | 50 healthy dogs | 30.81 × 10−6 | 20 | 97 | 65 |
| 87 HAC-S | • Upper limit of the RI on 50 healthy dogs of normal distribution as mean + 2SD | |||||||
| 26.5 × 10−6 | 100 | 54.2 | ||||||
| • ROC curve HAC vs. HAC-S optimal threshold for a test of exclusion | ||||||||
| 161.2 × 10−6 | 51.5 | 98.8 | ||||||
| • ROC curve HAC vs. HAC-S optimal threshold for a confirmatory test |
DM = diabetes mellitus; FMM = fluorometric method of Mattingly; HAC = dogs with hyperadrenocorticism; HAC-S = dogs suspected of hyperadrenocorticism confirmed to not have hyperadrenocorticism; IT = interpretation threshold; LDDST = low-dose dexamethasone suppression test; NAI = dogs with non-adrenal illness; PDH = dogs with pituitary-dependent hyperadrenocorticism; RI = reference interval; RIA = radioimmunoassay; Se = sensitivity; Sp = specificity; UCCR = urine cortisol:creatinine ratio.
The article also included investigation with a LDDST.
The article also included investigation with an adrenocorticotropic hormone stimulation test.
The sensitivity is not mentioned in the article but can be retrieved from the data. Here the threshold is low enough to allow a sensitivity of 100%. The specificity has never been quoted as “100%” from this article, even if this is what data support, as the comparison group is healthy and has an especially low range of urinary cortisol, not reflecting the situation in real life.
Surprising high specificity, mismatching with other studies, and not reflecting the performances of the UCCR when applied in a dog reasonably suspected of HAC.
Authors chose to define the IT as (mean + 2SD) of the healthy population (13.5 × 10−6). Yet, because the lower limit of the range for HAC dogs is substantially higher (20 × 10−6), they could have set up the IT at 19 × 10−6, which would likely have (slightly) improved the low specificity when compared to PUPD non-HAC dogs.
This is the specificity according to the chosen IT applied to the PUPD non-HAC dog population. The specificity within the healthy population is useless and not reported.
The IT has been chosen as (mean + 2SD) of the HAC-S or NAI populations, which may be better than based on the healthy population, when the sensitivity does not drop too much with this approach.
It is surprising to find a specificity that high in the HAC-S population, very close from the specificity in the normal population, and very far from the low specificity in the NAI population. Explanations may be that HAC-S suspicions were too readily applied, and also that NAI were severe. Yet, the reality of the specificity of UCCR for HAC is closer from what is observed in the NAI population.
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.
Article including some intrinsic validation of the cortisol assay in canine urine.
Article quoting a source for validation of the cortisol assay in canine urine.