Misleading Normal 25-hydroxy vit-D [25(OH)D] Levels During Vit-D deficiency Due to Estrogen-Induced Increase In Vit-D Binding Protein

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 234-256-Bone & Calcium Metabolism: Clinical Trials & Case Series
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-237
Rachanon Murathanun*1 and Baha M Arafah2
1University Hospitals Case Med Ctr, Cleveland, OH, 2Case Western Reserve Univ, Cleveland, OH
Introduction: Circulating 25(OH)D is bound to vit-D binding protein (DBP) with the free fraction being less than 0.1%; thus, serum 25(OH)D levels can be altered by DBP concentrations. Measurements of free vit-D and DBP are not yet clinically available. Earlier reports suggested that 25(OH)D levels were higher in estrogen-treated women. We postulate that 25(OH)D levels are higher than expected in women receiving oral estrogen therapy and that 25(OH)D levels would be less elevated if estrogen administration is shifted to transdermal. Here in, we report a case of an estrogen-treated woman with vit-D deficiency who had falsely normal 25(OH)D. 

Clinical Case: A 76 year-old female with stage 3 CKD, chronic pancreatitis and vit-D deficiency, was evaluated for high plasma PTH levels. Her medications included ergocalciferol 50,000 IU weekly, oral conjugated estrogen 0.625 mg daily and pancrelipase. Physical examination was unremarkable. Lab data revealed Ca: 9.1 mg/dL, albumin: 4.3 g/dL, Cr: 1.44 mg/dL, GFR: 35 L/min/1.73 m2, PTH: 452 pg/mL (nl 14-72), 25(OH)D: 29 ng/mL and 1,25(OH)D: 23 pg/mL (nl 15-75). The diagnoses of increased DBP, secondary hyperparathyroidism caused by CKD and vit-D deficiency (due to malabsorption) were made. Though not directly measured, it was suspected that her DBP was elevated due to oral estrogen therapy while the bioavailable 25(OH)D was low.  As a surrogate of DBP, SHBG and CBG were measured, and were both elevated (79 nmol/L and 69 mg/L, respectively). Ergocalciferol was increased to 50,000 IU 4 times a week, which resulted in lowering PTH level to near 150 pg/mL and also an increase in 25(OH)D level to 91 ng/mL. On the latter regimen, both PTH and 25(OH)D had remained relatively unaltered for 5 months until estrogen administration route was changed from oral to transdermal. With that change, serum levels of SHBG and CBG normalized; and despite being maintained on the same dose of ergocalciferol, plasma PTH decreased to 77 pg/mL while 25(OH)D level was unchanged with stable serum calcium, phosphorus, creatinine and GFR. 

Summary and conclusions: Circulating DBP level is increased by oral estrogen. 25(OH)D level in individuals taking estrogen may appear normal, even in those with true vit-D deficiency. Since measurements of DBP and free 25(OH)D are not currently available, clinical judgment on vit-D replacement therapy should be primarily based on other lab values, such as PTH, Ca, with close monitoring of the trend of 25(OH)D levels.

Nothing to Disclose: RM, BMA

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm