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The Substance project is considering a change, which if implemented, will affect the mapping of LOINC terms.
The suggested change is to deprecate the instances of Free X (substance) and replace them with X (substance). E.g 259355006 | Free testosterone (substance) | will be deprecated and replaced by 43688007 | Testosterone (substance) |

The modelling of Testosterone has changed to reflect the change:

January 2018 release:



July 2018 release:


Currently the mapping of the LOINC Parts to SNOMED CT is as following (based on confirmation with RII). The changes in substance hierarchy will have an effect on mapping of the LOINC parts, specifically Testosterone and Testosterone total:


PartNum

Part Type

PartName

Concept ID

FSN

Correlation

LP18811-7

COMPONENT

Testosterone.free

259355006

Free testosterone (substance)

Exact

LP29116-8

COMPONENT

Testosterone.bound

720374004

Testosterone bound to sex hormone-binding globulin (SHBG) (substance)

Exact

LP15881-3

COMPONENT

Testosterone.free+weakly bound

710118001

Bioavailable testosterone (substance)

Exact

LP19233-3

COMPONENT

Testosterone.weakly bound

720355007

Testosterone bound to albumin (substance)

Exact

LP14045-6

COMPONENT

Testosterone

43688007

Testosterone (substance)

Snomed CT broader

LP32165-0

DIVISORS

Testosterone.total

43688007

Testosterone (substance)

Snomed CT broader


From LOINC website: Testosterone is an androgenic steroid and is the primary male sex hormone. Approximately half of circulating testosterone is tightly bound to a protein called sex hormone binding globulin (SHBG) and is biologically inactive. Another fraction is weakly bound to other proteins, such as albumin, and the remainder is unbound, or "free". Weakly bound and free testosterone together represent bioavailable testosterone. Both total and free testosterone levels decrease with age. Low testosterone is associated with many other conditions, including osteoporosis, Alzheimer’s disease, obesity, diabetes and ischemic heart disease.

Example LOINC terms:





 Other examples:

PartNumPartTypeNamePartNameConceptIdFSN
LP18655-8COMPONENTEstradiol.free259349001Free estradiol (substance)
LP32049-6DIVISORSEstradiol.total126172005Estradiol (substance)
LP32015-7DIVISORSCarnitine.free (C0)709152004Free carnitine (substance)
LP32016-5DIVISORSCarnitine.total59888006Carnitine (substance)


PartNumPartTypeNamePartNamePrimary_ConceptIdPrimary_FSN
LP29075-6COMPONENTInsulin.free706937006Free insulin (substance)
LP31777-3COMPONENTInsulin.bound706973004Bound insulin (substance)
LP14676-8COMPONENTInsulin67866001Insulin (substance)
LP70329-5DIVISORSInsulin67866001Insulin (substance)


PartNumPartTypeNamePartNameConceptIdFSN
LP15448-1COMPONENTBilirubin79706000Bilirubin (substance)
LP15447-3COMPONENTBilirubin.albumin bound73828001Bilirubin-albumin complex (substance)
LP15446-5COMPONENTBilirubin.glucuronidated259498006Bilirubin glucuronide (substance)
LP15445-7COMPONENTBilirubin.glucuronidated+Bilirubin.albumin bound54462003Direct reacting bilirubin (substance)
LP15449-9COMPONENTBilirubin.non-glucuronidated37852002Indirect reacting bilirubin (substance)
LP31996-9DIVISORSBilirubin.total79706000Bilirubin (substance)

 

From LOINC website: "Bilirubin is an orange-yellow pigment produced by the normal breakdown of heme, a component of the hemoglobin found in red blood cells. It is processed by the liver and excreted in bile. Conditions that cause red blood cell breakdown or interfere with liver or bile processing can cause elevated levels of bilirubin. Bilirubin exists in many forms. Non-glucuronidated bilirubin (also called unconjugated or indirect) is the breakdown product of heme and is not water-soluble. Hemolytic anemias, which cause increased red blood cell breakdown, are one cause of elevated non-glucuronidated bilirubin. Glucuronidated bilirubin (also called conjugated) is a water-soluble form of bilirubin that is made in the liver by the addition of sugar molecules to non-glucuronidated bilirubin. Conditions that affect liver function (such as hepatitis, cirrhosis and liver tumors) or physically block the bile ducts (such as gallstones) can cause elevated levels of glucuronidated bilirubin. A third form of bilirubin is that which is bound to albumin, and it is also known as delta bilirubin because it was originally identified based on the unexpected difference between the total bilirubin level and the level of glucuronidated plus non-glucuronidated bilirubin in some patient samples. Prior to the discovery of albumin-bound bilirubin, the term "direct" bilirubin was used as a synonym for glucuronidated bilirubin, but direct bilirubin is actually glucuronidated PLUS albumin-bound bilirubin."

Contributors (2)

2 Comments

  1. During the E2O discussion this AM, the team expressed concern that the use case for "Bound X substance" was not clear or important.  Questions were raised when the proposed changes to the substance model would be implemented?

  2. Hi James R. Campbell

    I am afraid I don't understand the question fully. Is the concern that "Bound X substance" concepts are not required? Or is the concern related to their modelling?

    As for implementation of the changes, the existing concepts were remodelled in 2018 as per existing guidelines:

    As discussed earlier via email, the existing guidelines are the result of discussing the initial proposal by the Substance project as noted above (i.e. to deprecate the instances of Free X (substance) and replace them with X (substance)) with the Observable project group back in June and July 2018. The Observable project group didn't agree with this proposal. The group recommendation, as noted in the minutes of the 2018-07-16 call (https://confluence.ihtsdotools.org/display/OBSERVABLE/2018-07-16+-+OBSERVABLE+Meeting [confluence.ihtsdotools.org]), was as follows:

    • The current plan is to represent the base substance, the bound and the free substance as three siblings with a "substance X and derivatives" common subsumer.
    • This would support the Observables use cases of allowing querying for substances without regard for "bound-ness", and to distinguish between bound, free, and total.
    • Three patterns for Observables would be:
      • Free X Observable === Observable & component = Free X
      • Bound X Observable === Observable & component = Bound X (or X bound to Y)
      • Total X Observable === Observable & component X (base substance concept)

    The recommendation was to support measurement of bioavailable/bioactive and total substances. 

    Is the E2O project recommending a change in the above guidelines?

    Thanks,

    Farzaneh

    CC: Suzanne Santamaria