In 1998, Scantibodies developed the first specific 1-84 PTH assay (Gao et al. JBMR 2001). That development enabled us to discover that the 7-84 PTH was the “other PTH hormone”. Since that time there have been a number of new terms used. The purpose of this glossary is to provide definitions for those terms—some of which must be defined more clearly by function.
Intact PTH assay – the original 2nd generation PTH test which was later discovered not to be “intact”—but rather to measure both 1-84 PTH and 7-84 PTH as a sum result of the two hormones. This created cross-reactivity problems and led to the development of the first specific 1-84 PTH assay in 1998.
Whole PTHTM assay – Descriptive term for the 3rd generation PTH assay which measures only 1-84 PTH without the cross-reactivity problem with 7-84 PTH.
CAPTM – The original name given Scantibodies Whole PTH 3rd Generation assay; an anagram for Cyclase Activating PTH. This refers to the fact that the 1-84 PTH binds to the PTH/PTHrp receptor and operates through the pathway wherein adenylate cyclase is stimulated. The use of CAPTM is intended to distinguish the PTH measured as operating through the PTH/PTHrp receptor – adenylate cyclase pathway as opposed to CIPTM (anagram for Cyclase Inactive PTH) which binds to a separate C terminal receptor that does not activate adenylate cyclase.
7-84 PTH Hormone – The demonstration that the molecules of 7-84 PTH compose a second PTH hormone is the most important discovery in PTH-mediated calcium metabolism in the last three decades. There have been several names given to this hormone. They are as follows:
- Large C terminal fragments – This term emphasizes the fact that the method of determination (subtracting the CAPTM from the total PTH) detects all of the fragments that are probably like 7-84 PTH with inverse biological activity that MAY be present in the patient.
- PINTM – PTH Inhibitor – this refers to the fact that 7-84 PTH has an inverse biological action to that of the 1-84 PTH hormone. This term is not often used.
- CIPTM – “Cyclase INACTIVE PTH” (note that “I” does Not stand for “inhibiting”). This definition of CIP is subtle and important, because it refers to the fact that 7-84 PTH operates through a different receptor than does the 1-84 PTH. This separate receptor has a different intercellular biochemical pathway. In 1999, Scantibodies worked with Dr. Eduardo Slatopolsky on generating data for the KI paper. 7-84 PTH was studied for its ability to inhibit adenylate cyclase that was stimulated by 1-84 PTH. 1-84 PTH was shown to stimulate adenylate cyclase that was stimulated by 1-84 PTH. 1-84 was shown to stimulate adenylate cyclase in vitro, (measured by an increase in camp in bone cell culture supernatant). It was fully expected that when 7-84 PTH was added along with the 1-84 PTH that there would be a reduction in the camp, indicating an inhibition of the adenylate cyclase which would have indicated that the 7-84 PTH competed with the 1-84 PTH for the same receptor (PTH/PTHrp receptor). Following our expectations, we thought of calling 7-84 PTH “CIPTM” for Cyclase Inhibiting PTH. But, to our amazement, we could not demonstrate that 7-84 PTH had any effect on the PTH receptor linked to adenylate cyclase. Therefore, we realized that 7-84 PTH worked through a receptor that did not have adenylate cyclase as part of its pathway. Scantibodies salvaged the term “CIPTM” because the “I” also well describes the “inactive” non-function of 7-84 PTH in regard to inhibiting 1-84 PTH. This term is still very important for 7-84 PTH because it emphasizes that 7-84 PTH has its own PTH C-terminal receptor (yet to be cloned) with a pathway that does not involve adenylate cyclase.
- 7-84 PTH refers to the fact that the other PTH HPLC peak detected in humans co-migrates with synthetic 7-84 PTH. Moreover, Dr. D’Amour has three patients in which he has now sequenced by peptide analysis, 7-84 PTH from within the parathyroid gland. For this reason, we are moving away from saying “likely 7-84 PTH” or “probably 7-84 PTH”. Much work has been completed by Dr. Divietti and Dr. Malluche with 7-84 PTH, that further demonstrates its opposite biological activity compared to 1-84 PTH and the fact that it operates through a yet to be cloned C terminal receptor.
PTH AccuratioTM – 1-84 PTH/7-84 PTH ratio – is Scantibodies’ new trademark for the state-of-the-art panel available at Scantibodies Clinical Lab. It is composed of the CAP 1-84 Whole PTHTM Assay value, the Total PTHTM (intact PTH) value and the calculated value of CIPTM (7-84 PTH). From these values, the ratio is assembled, giving physicians a more accurate, non-invasive way to determine bone status in renal and osteodystrophy patients, as well as a better way to monitor PTH levels.
Total PTHTM – (tPTH) is Scantibodies improved version of the 2nd generation PTH test, which measures the sum of 1-84 PTH and 7-84 PTH. Total PTH values are more accurately determined with this newer test because of the highly specific antibody developed by Scantibodies for this measurement.
CAPTM (Whole PTH) Assay – is Scantibodies 1-84 Whole PTH assay newly developed with a highly sensitive and specific antibody to measure 1-84 PTH without the cross-reactivity to 7-84 PTH of the intact PTH assay. It is separate and distinct from the 2nd generation PTH assays, as well as the Bio-Intact PTH Assay, recently marketed by competitors. All 3rd generation PTH assays are NOT created equal.
