QUESTION: I have a 30 year old female pt with high calcitriol. What does this mean? I am having a hard time finding its relevance although 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 we see cortisol shoot up with anticipation this much? Initial complaints are hair loss, possible lean PCOS but she is on BCP and has likely celiac (tests were not conclusive), zonulin has been elevated in the past and we are awaiting further tests. 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 is normal, metals also normal. Hormone panels normal except for copper and SHBG , 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. We are working on the gut but they are freaking out and I need some perspective.
ANSWER: Good question. 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).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 there are no other signs of cancer, then no, you should not 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 Calcium 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) Calcium is the only way to keep the pulsatile PTH release from causing this.
Visit: Enzymatic studies on the key enzymes of vitamin D metabolism for supporting paper.