HYPERCALCEMIA–?FHH, HPTH, OR OTHER

QUESTION---Patient (64yo F) is followed for hypercalcemia of uncertain etiology, dating back to 2008.  When I saw her I took her off the hydrochlorothiazide.  Her calcium remains elevated and her parathyroid home concentration remains at the low end of normal at about 20. I think the differential dx is either: Malignancy, familial hypocalciuric hypercalcemia, primary hyperparathyroidism. I don't believe she has a malignancy given the fact that the hypercalcemia dates back 7 years, and is stable. Parathyroid hormone related peptide was low. I don't believe she has familial hypocalciuric hypercalcemia given the fact that the parathyroid hormone level is at the low end of normal. I thought (this is the question) that the [PTH] is high/normal in patients with FHH.  Her parents are deceased.  She has one sister but we do not know if her sister was ever hypercalcemic.

Labs:

DATE        Cr        calcium   TSH       PTH       VitD-25OH phos      albumin   Ca2+      PTHrp   1,25(OH)2D

02/03/15    1.10     H10.7                                                                          36 (nl)

01/13/15             H10.8                20.0                4.3

11/22/14    1.10     H10.2      0.506     20.9                4.1       4.3      H1.32      <2.0

07/23/14             H11.3                                    4.7

06/04/14    1.10     H11.2      0.659    L8.5       43

05/28/14    1.10     H11.2      0.381

06/12/13    1.00     H10.7      0.643

06/04/12    0.80     H10.2      0.696

06/15/11    0.90     H10.3      0.848

06/29/10    0.70     H10.4      0.699

05/12/09    0.80      9.9

06/04/08    1.00     H10.3

03/20/08    0.90     H10.7      0.39

DATE        U24 Calcium     Calcium         PTH 

07/30/14   113

11/22/14                   H10.2            20.9

01/13/15                   H10.8            20.0

02/03/15    90             H10.7                       4 glasses of milk

Calculated Fractional Excretion of Calcium = 0.010
Thus urine test is c/w FHH.
So, does the patient have FHH with a low [PTH]?
I am going to do a cinacalcet suppression test, as a way to assess if this is a PTH responsive hypercalcemia (but I am well aware this is not a validated test.)  Hayward Zwerling, M.D.

RESPONSE-- Your question has been referred to me by Dr. DeGroot. I am pleased to respond.Long-standing, well documented hypercalcemia essentially rules out malignancy, as you point out.FHH is highly unlikely for the facts that she is 61 years old, there is no family history, and the PTH is where it is. FHH virtually always surfaces by the age of 30 and the PTH is invariably in the upper range of normal or frankly elevated. The urinary cal/cr ratio of 0.01 could be compatible with PHPT as well as FHH. PHPT. This is the most likely diagnosis. Why the PTH is as low as it is, I don't know but we see it. Is she taking biotin? Biotin has been shown to interfere with the PTH assay and in patients with PHPT taking the biotin, the PTH can be low. (Waghray A et al. Endocr Practice 2013;19:451-455). As for the "cinacalcet supression test" it is not validated.
Assuming she has PHPT, you have not indicated whether she has any guidelines to recommend surgery. What is her BMD? Hx of kidney stones?  If she doesn't meet guidelines for surgery, then a conservative course might be best advised. John Bilezikian, MD