Calcium and PTH-rp

[TheMightyAngus]

Edit: Title of this thread should be Phosphorous and PTH-rp

Question for the Step 1 hot shots: why is the phosphorous level normal in a squamous cell carcinoma secreting ectopic PTH-related peptide, but low in the case of a parathyroid adenoma?

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[lankysudanese]

the PTH receptor in the cells of the proximal convoluted tubules must only recognize PTH and not PTH-rp (i.e. PTH-rp differs from PTH by not being capable of binding the PTH receptor in the PCT), and thus squamous carcinoma can not cause hypophosphatemia but hyperparathyroidism/parathyroid adenoma do.

just my postulation...but i'm sure the real heavy-hitters have the answer

 

[medhacker]

Question for the Step 1 hot shots: why is the phosphorous level normal in a squamous cell carcinoma secreting ectopic PTH-related peptide, but low in the case of a parathyroid adenoma?

1) In the case of PTH-related peptide, the released calcium would feedback inhibit PTH release from the parathyroid, leaving PTH-related peptide to regulate phosphorous resorption at the proximal tubule and thus levels could be normal (wild guess...)

2) In the case of parathyroid adenoma, the abnormal tissue does not exhibit feedback inhibition by calcium and thus levels of PTH are high and as a consequence phosphorous reabsorption at the proximal tubule is kept at a low.

 

[lankysudanese]

the PTH receptor in the cells of the proximal convoluted tubules must only recognize PTH and not PTH-rp (i.e. PTH-rp differs from PTH by not being capable of binding the PTH receptor in the PCT), and thus squamous carcinoma can not cause hypophosphatemia but hyperparathyroidism/parathyroid adenoma do.

just my postulation...but i'm sure the real heavy-hitters have the answer

I take this back...just found out that PTH and PTH-rp both bind to the PTH receptor in the PCT (type I PTH receptor). medhacker's explanation makes a lot of sense.

 

[werd]

i feel like the premise of the question is off... that is, i thought that PTH-rp caused about the same effects as standard PTH, phos included. this study supports that notion: http://joe.endocrinology-journals.org/cgi/content/abstract/120/1/45. I think PTH-rp has mostly the same effects, but people focus on the calcium bc it's what gets patients into trouble first.

 

[TheMightyAngus]

i feel like the premise of the question is off... that is, i thought that PTH-rp caused about the same effects as standard PTH, phos included. this study supports that notion: http://joe.endocrinology-journals.org/cgi/content/abstract/120/1/45. I think PTH-rp has mostly the same effects, but people focus on the calcium bc it's what gets patients into trouble first.

Nope, premise is correct. This was the teaching point to a question from USMLERx, but the authors didn't explain the mechanism.

Just read in Harrison's that the PTH2 receptors bind PTH but not PTHrp...but these receptors are mostly in the brain/pancreas not kidney.

 

[werd]

hm, interesting... this explanation is apparently debatable, as the reference i sited showed that PTH-rp increases phos excretion by the kidney. since this is a step 1 thread... i thought i'd say that this, while an interesting discussion, isn't in my experience (ie my test) the sort of thing that's asked on the usmle; it's just too poorly understood/characterized and too minute. cheers.

 

[osli]

I like medhacker's theory.

 

[mm3781]

Diet could be a factor as well. Low dietary phosphate results in conservation of phosphate even in the face of high levels of either PTH or PTHrP, and normal or high dietary phosphate intake results in normal response to PTH or PTHrP and results in phosphaturia. Perhaps the decreased dietary intake in lung cancer patients results in enough of a dietary phosphate deficiency to override the effects of PTHrP, or perhaps I am way wrong.