QUESTION: I have a 30 year old female pt with high calcitirol. What does this mean?? I am having a hard time finding its relevance. Though maybe I read something about low calcium in the diet or intestines??? Her calcitriol is 149.3, range is 10-75. She has low normal vitamin D levels (36, range 30-100) . Low PTH (12, range 15-65). Calcium, ionized serum is 5.0, range 4.5-5.6, serum calcium on CMP is 9.5, range 8.7-10.2. Her blood cortisol is also high, 38.2, range 2.3-19.4. We did a salivary diurnal 2 months ago that looked quite good. She gets very, very worked up before blood work however and feels that this is why her cortisol is up. But would you expect to see cortisol shoot up with anticipation this much? Initial complaints are hair loss, possibly lean PCOS but she is on BCP and has likely celiac (tests were not conclusive but long standing sleepiness, nightmares, thrashing and yelling in her sleep, energy better, canker sores gone, etc…) zonulin has been elevated in the past and we are awaiting further tests. Any thoughts on the calcitriol???
ANSWER: Recall that after 25-OH-D3 is formed the kidneys convert it to its active metabolites via either 24 hydroxylase (to 24,25-OH-D3) or 1-a-hydroxylase (to 1,25-OH-D3). The “24” step is blocked by PTH rises as the 24,25 side causes bone uptake of Ca++ (and if one is putting out increased PTH it is due to Ca++ dropping in serum through the day – so the bone uptake is blocked). The 1,25 side supports Ca++ moving into plasma from GI, Ki and Bone and is triggered by the blockade of the 24 side plus PTH. so yes, if normal 25 and High 1,25 then a likely cause is chronic PTH release due to Ca++ corrections. (i.e. imbalance in the homeostatic 24,25 / 1,25 balance).
QUESTION: but in looking at the post it seems like I would have expected to see high PTH. And this is not the case, it is low. ANA’s , CCP Ab, RF, thyroid anti-bodies have been negative. Lyme and co-infections neg, so much testing has been done before they came to me. Not only conventional but functional as well. Sed rate and CRP normal, CBC usually will show a high percentage of lymphs but overall number nml. Metals also normal, hormone panels normal except for copper and SHBG , I assumed from the pill. Do I need to be worried about cancer?? How can I further evaluate why this is happening? I guess same question for AI ( i know we may never find AI). We are working on the gut but they (pt and her mom) are freaking out and Mom can only see cancer online and I need some perspective.
ANSWER: Good question. You’ll almost never catch a high PTH even with this type of difference in 25 and 1,25 forms. Why? Cause it is so pulsitile. Unless you did a 24 hour urine PTH it almost never would show unless they had parathyroid disease. It is a functional problem mostly. If no other signs of cancer then no you shouldn’t have that too high on the list. Most likely and common is poor Ca nutrition, Ionization, Absorption or a combo of the three. Also the helpers to Ca absorption (D, Mg, Boron etc) may be amiss. Also CYP-SNP status is all the rage in Vit D metabolism [1 alpha-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24) ] – so there can be “those” reasons for alterations too. Generally if no SNP issues or AI/Cancer, then the availability of, digestion and absorption of (with co-factors) Ca is the only way to keep the pulsatile PTH release from causing this.
So – Re VDR and Vit D metabolism – gene stuff first then metabolism Q&A follows.
Official Symbol: VDR
Official Full Name: vitamin D (1,25- dihydroxyvitamin D3) receptorprovided by HGNC Also known as NR1I1; PPP1R163
Summary: This gene encodes the nuclear hormone receptor for vitamin D3. This receptor also functions as a receptor for the secondary bile acid lithocholic acid. The receptor belongs to the family of trans-acting transcriptional regulatory factors and shows sequence similarity to the steroid and thyroid hormone receptors. Downstream targets of this nuclear hormone receptor are principally involved in mineral metabolism though the receptor regulates a variety of other metabolic pathways, such as those involved in the immune response and cancer. Mutations in this gene are associated with type II vitamin D-resistant rickets. A single nucleotide polymorphism in the initiation codon results in an alternate translation start site three codons downstream. Alternative splicing results in multiple transcript variants encoding different proteins. [provided by RefSeq, Feb 2011]
See also: http://www.ncbi.nlm.nih.gov/gene/7421
And: PMID: 11686044
