Deletion of the vitamin D receptor specifically in the parathyroid demonstrates a limited role for the receptor in parathyroid physiology

2009 ◽  
Vol 297 (5) ◽  
pp. F1192-F1198 ◽  
Author(s):  
Tomer Meir ◽  
Ronen Levi ◽  
Liesbet Lieben ◽  
Steven Libutti ◽  
Geert Carmeliet ◽  
...  

1,25(OH)2D3 decreases parathyroid hormone (PTH) gene transcription through the vitamin D receptor (VDR). Total body VDR−/− mice have high PTH levels, hypocalcemia, hypophosphatemia, and bone malformations. To investigate PTH regulation by the VDR specifically in the parathyroid, we generated parathyroid-specific VDR knockout mice ( PT-VDR−/−). In both strains, there was a decrease in parathyroid calcium receptor (CaR) levels. The number of proliferating parathyroid cells was increased in the VDR−/− mice but not in the PT-VDR−/− mice. Serum PTH levels were moderately but significantly increased in the PT-VDR−/− mice with normal serum calcium levels. The sensitivity of the parathyroid glands of the PT-VDR−/− mice to calcium was intact as measured by serum PTH levels after changes in serum calcium. This indicates that the reduced CaR in the PT-VDR−/− mice enables a physiologic response to serum calcium. Serum C-terminal collagen crosslinks, a marker of bone resorption, were increased in the PT-VDR−/− mice with no change in the bone formation marker, serum osteocalcin, consistent with a resorptive effect due to the increased serum PTH levels in the PT-VDR−/− mice. Therefore, deletion of the VDR specifically in the parathyroid decreases parathyroid CaR expression and only moderately increases basal PTH levels, suggesting that the VDR has a limited role in parathyroid physiology.

PEDIATRICS ◽  
1959 ◽  
Vol 24 (2) ◽  
pp. 258-269
Author(s):  
David W. Smith ◽  
Robert M. Blizzard ◽  
Harold E. Harrison

A case of idiopathic hypercalcemia present from early infancy and diagnosed at 5 years of age is reported in which the serum assay of vitamin D indicated elevated levels. After discontinuation of supplemental vitamin D and a diet low in calcium the concentrations of calcium and vitamin D in the serum gradually returned to normal over a period of 18 months. Roentgenograms of the bones showed evidence of demineralization rather than increased density as reported in other cases of "idiopathic" hypercalcemia. During a subsequent 2-year follow-up the patient has maintained a normal serum calcium. The etiology is discussed with particular reference to the role of vitamin D in this case


1982 ◽  
Vol 79 (15) ◽  
pp. 4791-4794 ◽  
Author(s):  
G. E. Lester ◽  
C. J. VanderWiel ◽  
T. K. Gray ◽  
R. V. Talmage

2014 ◽  
Vol 58 (5) ◽  
pp. 583-586 ◽  
Author(s):  
Larissa Pimentel ◽  
Sirley Portela ◽  
Alyne Loureiro ◽  
Francisco Bandeira

Normocalcemic primary hyperparathyroidism (NPHPT) is a condition characterized by elevation of the parathyroid hormone (PTH) in the presence of normal serum calcium and the absence of secondary causes. The case described illustrates the long-term follow-up of a postmenopausal woman with NPHPT patient who progressed with multiple adenomas. This case reports a 77-year-old female who has chronic generalized pain and osteoporosis. Her initial serum PTH was 105 pg/mL, with total serum calcium of 9.6 mg/dL, albumin 4.79 g/dL, phosphorus 2.8 mg/dL, and 25OHD after supplementation was 34.6 ng/mL. The bone densitometry (BMD) results were as follows: lumbar spine: T-score -3.0, femoral neck: T-score -2.6 and distal radius: -4.2. Other causes of secondary hyperparathyroidism were ruled out and cervical ultrasound and Tc-99-Sestamibi scan were negative. She used oral alendronate and three infusions of zoledronic acid for treatment of osteoporosis. In the 10th year of follow-up, after successive negative cervical imaging, ultrasound showed a nodule suggestive of an enlarged right inferior parathyroid gland. PTH levels in fluid which was obtained during fine-needle aspiration (FNA) were over 5,000 pg/mL and a Sestamibi scan was negative. The patient underwent parathyroidectomy, and a histological examination confirmed parathyroid adenoma. Post-operatively serum PTH remained elevated in the presence of normal serum calcium levels. A follow-up cervical ultrasound showed a new solid nodule suggestive of an enlarged right superior parathyroid gland. PTH levels in the aspiration fluid were remarkably high. A second parathyroidectomy was performed, with the excision of a histologically confirmed parathyroid adenoma. In conclusion, this is an unusual presentation of NPHPT and highlights the long-term complications.


1986 ◽  
Vol 251 (2) ◽  
pp. E234-E240 ◽  
Author(s):  
M. E. Holtrop ◽  
K. A. Cox ◽  
D. L. Carnes ◽  
M. F. Holick

In the present study, we have evaluated the role of calcium and phosphorus concentrations in serum on the mineralization of bone in the absence of vitamin D. This was accomplished by feeding mother rats and subsequently their pups vitamin D-deficient diets varying in calcium, phosphorus, and lactose content. After 5-7 wk on these diets, serum concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-hydroxyvitamin D [1,25(OH)2D] were undetectable. Rats fed a vitamin D-deficient diet containing 0.44% calcium and 0.3% phosphorus showed a serum calcium of 4.9-5.9 mg/dl and a serum phosphorus of 7.3-8.2 mg/dl; rickets (wide epiphysial plates) had developed as well as osteomalacia (wide osteoid seams). Rats maintained on a vitamin D-deficient diet containing 3% calcium and 0.65% phosphorus had normal serum calcium, low serum phosphorus, and severe rickets, but osteomalacia was not seen. Rats fed a diet containing 20% lactose, 4% calcium, and 1% phosphorus showed normal serum calcium, somewhat low serum phosphorus, normal serum PTH, normal width of the epiphysial plate, normal volume density of trabecular bone, and normal volume density of osteoid seams. These data confirm the findings of others, using a different experimental model, that serum calcium and phosphorus concentrations are the determining factors in mineralization defects and not the absence of 25(OH)D or 1,25(OH)2D. In these rats thyroparathyroidectomy is well tolerated, which makes for an ideal model for the study of the effects of calcium-regulating hormones on bone histology, cytology, and biochemistry.


1967 ◽  
Vol 22 (1) ◽  
pp. 325-326 ◽  
Author(s):  
Reed M. Stringham ◽  
Carlos A. Bonilla ◽  
Ivan M. Lytle

Author(s):  
Aron Chakera ◽  
William G. Herrington ◽  
Christopher A. O’Callaghant

The extracellular calcium ion concentration is tightly regulated through the actions of parathyroid hormone (PTH) and vitamin D (1,25-dihydroxyvitamin D) on bone, kidney, and intestines. Abnormalities in these homeostatic mechanisms may lead to increased or decreased serum calcium concentrations, resulting in hypercalcaemia or hypocalcaemia, respectively. Hypercalcaemic disorders may be further divided into those associated with a high/high-normal serum PTH level, and those associated with a low serum PTH concentration. Hypocalcaemia occurs when abnormalities in the physiological regulation of PTH and vitamin D results in calcium levels lower than the desired normal range. Failure of release of calcium from bone, and increased binding of calcium in the circulation, are other factors causing hypocalcaemia. This chapter discusses hypercalcaemia and hypocalcaemia, exploring definitions of the diseases, their etiologies, typical and uncommon symptoms, demographics, natural history, complications, diagnostic approaches, other diagnoses that should be considered, prognosis, and treatment.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Maimoona Bahlol ◽  
Alan Scott Sacerdote ◽  
Gul Bahtiyar

Abstract •Our patient is a 63-year-old African American female with medical history significant for hypertension, class 1 obesity, osteoarthritis of knees who initially presented to the adult ambulatory clinic on 9/19/2013 with complaints of body aches and bone pain. Labs were remarkable for a serum calcium level of 9.8 mg/dl, serum phosphorous of 4.7 mg/dl, and serum parathyroid hormone level of 166 pg/ml (15-65 pg/ml), normal GFR and serum vitamin 25-OH D of 62. A DEXA scan was performed which showed mild osteopenia wof 1.0 (0.8-1.8), serum 1,25 - OH vitamin D of <8 pg/ml, normal alpha and beta carotene level, negative endomysial antibodies and normal magnesium level. A diagnosis of secondary hyperparathyroidism with unclear etiology was made. Same treatment was continued and a follow up in 3 months with repeat labs was advised. Repeat PTH went up to 281pg/ml but serum calcium and phosphate remained normal. Based on normal serum 25 OH vitamin D and low 1, 25 OH vitamin D, patient was started on calcitriol 0.25 mg daily. On next follow up in 3 months PTH decreased to 203pg/ml and 1, 25 OH vitamin D level normalized (35pg/ml). MEN was excluded with normal serum free metanephrine and gastrin levels. On subsequent visits DEXA scan normalized and PTH further trended downward to 101.7 pg/ml. Patient was discharged from endocrine clinic back to the PCP. • •Patient continued to follow up in adult medicine clinic but calcitriol fall off of patient’s medication list likely due to an error. Patient was off of calcitriol for 6 months but continue to take calcium vitamin D.PTH trended up to 186pg/ml and then to 350pg/ml. A referral to endocrinology was made again and a parathyroid sestamibi scan was obtained which did not reveal any abnormal uptake. Serum calcium, phosphate, magnesium and vitamin OH 25 vitamin D remained normal. •Patient was started back on calcitriol 0.5 mg daily and PTH again started to trend downward. The last PTH was down to 82 on March 20th 2019 with normal serum calcium, phosphate, magnesium and eGFR. The final diagnosis was secondary hyperparathyroidism due to decrease 1 alpha hydroxylase activityith a T score of −1.5 at left forearm. A diagnosis of primary hyperparathyroidism was made by the PCP and patient was started on calcium vitamin D and Fosamax and was referred to endocrinology for further evaluation. • •Further testing in the endocrine clinic revealed 24-hour urine calcium of 49 mg (100-300) and urine creatinine. This case report concludes that low 1-alpha hydroxylase activity should be considered as a cause of secondary hyperparathyroidism in a patient with normal GFR and 25-OH vitamin D level


BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Reshi Suthakaran ◽  
Imeshi Indigahawela ◽  
Krinal Mori ◽  
Kiat Lim ◽  
Ahmad Aly

Abstract Introduction Uncertain nutritional outcomes following common metabolic surgical techniques are concerning given the long-term potential for postoperative metabolic bone disease. This study aims to investigate the variations in serum calcium, vitamin D, and parathyroid hormone (PTH) levels following Roux-en-Y Gastric bypass (RYBP) and Sleeve Gastrectomy (SG). Methods A retrospective analysis of 370 patients who underwent metabolic surgery at a single-centre group practice in Melbourne, Australia, over 2 years. Results Patients underwent SG (n = 281) or RYGP (n = 89), with 75% and 87% of the cohort being female, respectively. Postoperative mean serum calcium levels and median serum vitamin D levels improved significantly by 24 months within both cohorts. Serum PTH levels within the RYBP group were significantly higher than the SG group across all time points. PTH levels significantly fell from 5.7 (IQR 4.2–7.4) to 5.00 (4.1–6.5) pmol/L by 24 months following SG. However, PTH levels following RYBP remained stable at 24 months, from 6.1 (IQR 4.7–8.7) to 6.4 (4.9–8.1) pmol/L. Furthermore, we failed to notice a significant improvement in PTH levels following RYBP among those with higher PTH levels preoperatively. Conclusion Higher PTH levels following RYBP, compared to SG, may imply we are undertreating patients who are inherently subjected to a greater degree of malabsorption and underlying nutritional deficiencies. This finding calls for a tailored supplementation protocol, particularly for those with high preoperative PTH levels undergoing RYBP, to prevent deficiencies.


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