What is the experience of our patients with transient hypoparathyroidism after total thyroidectomy?

BACKGROUND: We sought to better understand the experience of patients with transient hypoparathyroidism using patient interviews and quality of life surveys. METHODS: This is a prospective analysis of 62 patients after total thyroidectomy at a high-volume institution. Semistructured patient interviews and quality of life surveys were conducted preoperatively and postoperatively at 2 weeks, 6 weeks, 6 months, and 1 year and compared based on postoperative parathyroid hormone levels. RESULTS: Postoperative parathyroid hormone levels were <10 pg/mL in 32% of patients (n = 20), 10 to 20 pg/mL in 19% (n = 12), and >20 pg/mL in 48% (n = 30). Hypocalcemic symptoms at 2 weeks were reported in 28 of 55 patients (51%), but patients felt "well prepared" and reported it "wasn't a big deal." If symptoms persisted at 6 weeks, they became more bothersome. At 6 months and 1 year, patients reported calcium supplementation prevented most symptoms and did not interfere with daily activities. Quality of life as measured by the European Organization for Research and Treatment of Cancer and the 12-Item Short Form Survey demonstrated a slight improvement at 1 year postoperatively regardless of parathyroid hormone level. CONCLUSION: Early postoperative transient hypoparathyroidism is common but when appropriately managed did not have a substantial negative impact on the overall quality of life.

Severe chronic kidney disease environment reduced calcium-sensing receptor expression in parathyroid glands of adenine-induced rats even without high phosphorus diet.

BACKGROUND: Chronic kidney disease (CKD) disrupts mineral homeostasis and its main underlying cause is secondary hyperparathyroidism (SHPT). We previously reported that calcium-sensing receptor (CaSR) mRNA and protein expression in parathyroid glands (PTGs) significantly decreased in a CKD rat model induced by a 5/6 nephrectomy that were fed a high phosphorus diet. However, there was a significant difference in the severity of CKD between high phosphorus and adequate phosphorus diet groups. Thus, it was unclear whether CKD environment or the high phosphorus diet influenced CaSR expression, and the underlying mechanism remains largely unknown. METHODS: CKD was induced in rats with 0.75% adenine-containing diet. CKD and control rats were maintained for 5 days and 2 weeks on diets with 0.7% or 1.3% phosphorus. For gene expression analysis, quantitative real-time polymerase chain reaction was performed with TaqMan probes. Protein expression was analyzed by immunohistochemistry. RESULTS: PTG CaSR expression significantly decreased in the presence of a severe CKD environment, even without the high phosphate load. Ki67 expressing cells in PTGs were significantly higher only in the CKD rats fed a high phosphorus diet. Furthermore, among the many genes that could affect CaSR expression, only vitamin D receptor (VDR) and glial cells missing 2 (Gcm2) showed significant changes. Moreover, Gcm2 was significantly reduced at an early stage without significant changes in serum calcium, phosphorus and 1,25(OH)2 vitamin D, and there was no significant reduction in CaSR and VDR expressions. Then, significantly elevated Ki67-positive cell numbers were also only observed in the early CKD PTGs with high-phosphorus diets. CONCLUSIONS: Our data suggest that the cause of the decreased PTG CaSR expression is the reduction in VDR and Gcm2 expression; Gcm2 may play a role in the onset and progression of SHPT.

Protective Effects of Ligustroflavone, an Active Compound from Ligustrum lucidum, on Diabetes-Induced Osteoporosis in Mice: A Potential Candidate as Calcium-Sensing Receptor Antagonist.

Ligustroflavone is one major compound contained in active fraction from Fructus Ligustri Lucidi (the fruit of Ligustrum lucidum), which could regulate parathyroid hormone (PTH) levels and improve calcium balance by acting on calcium-sensing receptors (CaSR). This study aimed to explore the potency of ligustroflavone as a CaSR antagonist and its protective effects against diabetic osteoporosis in mice. LF interacted well with the allosteric site of CaSR shown by molecular docking analysis, increased PTH release of primary parathyroid gland cells and suppressed extracellular calcium influx in HEK-293 cells. The serum level of PTH attained peak value at 2 h and maintained high during the period of 1 h and 3 h than that before treatment in mice after a single dose of LF. Treatment of diabetic mice with LF inhibited the decrease in calcium level of serum and bone and the enhancement in urinary calcium excretion as well as elevated circulating PTH levels. Trabecular bone mineral density and micro-architecture were markedly improved in diabetic mice upon to LF treatment for 8 weeks. LF reduced CaSR mRNA and protein expression in the kidneys of diabetic mice. Taken together, ligustroflavone could transiently increase PTH level and regulate calcium metabolism as well as prevent osteoporosis in diabetic mice, suggesting that ligustroflavone might be an effective antagonist on CaSR.

Sevelamer hydrochloride suppresses proliferation of parathyroid cells during the early phase of chronic renal failure in rats.

AIM: We examined the effects of sevelamer on parathyroid cell proliferation and secondary hyperparathyroidism in rats following induction of early-phase of chronic renal failure (CRF) by unilateral ureteral obstruction (UUO). METHODS: For 5 days, rats in the control group received normal food, rats in the sevelamer group (SH) received control food plus 5% sevelamer, and rats in the low protein group (LP) received low protein food. Five rats of each group were killed at baseline (day 0). All other rats were given UUO, and five rats per group were killed on days 3, 7, 14, and 28 after UUO. Changes in body weight, serum phosphorus, calcium, intact-parathyroid hormone (i-PTH), creatinine (SCr), creatinine clearance rate (CCR), blood urea nitrogen (BUN), and 24-h urinary phosphorus were determined. Parathyroid tissues were removed for histological examination of proliferating cell nuclear antigen-positive (PCNA+) cells. RESULTS: Measurement of body weight, BUN, and SCr in the controls indicated successful establishment of this model of early-phase CRF. The controls also had remarkable proliferation of PCNA+ cells beginning on day 3, but this did not occur in the SH or LP groups. After 28 days, serum phosphorus had decreased more in the SH and LP groups than in the control group, and phosphorus excretion was much greater in the control group than in the SH and LP groups. The three groups had similar increases in serum i-PTH. CONCLUSION: Sevelamer rapidly lowered the serum phosphorus and inhibited the proliferation of PCNA+ cells in this experimental model of early-phase CRF.

The Emerging Role of Nutritional Vitamin D in Secondary Hyperparathyroidism in CKD.

In chronic kidney disease (CKD), hyperphosphatemia induces fibroblast growth factor-23 (FGF-23) expression that disturbs renal 1,25-dihydroxy vitamin D (1,25D) synthesis; thereby increasing parathyroid hormone (PTH) production. FGF-23 acts on the parathyroid gland (PTG) to increase 1α-hydroxylase activity and results in increase intra-gland 1,25D production that attenuates PTH secretion efficiently if sufficient 25D are available. Interesting, calcimimetics can further increase PTG 1α-hydroxylase activity that emphasizes the demand for nutritional vitamin D (NVD) under high PTH status. In addition, the changes in hydroxylase enzyme activity highlight the greater parathyroid 25-hydroxyvitmain D (25D) requirement in secondary hyperparathyroidism (SHPT); the higher proportion of oxyphil cells as hyperplastic parathyroid progression; lower cytosolic vitamin D binding protein (DBP) content in the oxyphil cell; and calcitriol promote vitamin D degradation are all possible reasons supports nutritional vitamin D (NVD; e.g., Cholecalciferol) supplement is crucial in SHPT. Clinically, NVD can effectively restore serum 25D concentration and prevent the further increase in PTH level. Therefore, NVD might have the benefit of alleviating the development of SHPT in early CKD and further lowering PTH in moderate to severe SHPT in dialysis patients.

Predictors of graft function after parathyroid autotransplantation during thyroid surgery.

BACKGROUND: The purpose of this study was to identify predictors associated with graft function after parathyroid autotransplantation during thyroid surgery. METHODS: One hundred fifty patients who underwent thyroid surgery with parathyroid autotransplantation were enrolled prospectively. During surgery, the misresected or devascularized parathyroid gland was autografted in the brachioradialis muscle of the forearm. Parathyroid hormone (PTH) levels in both arms were measured regularly after surgery. Patient age, sex, extent of surgery, and postoperative serum calcium levels were recorded. RESULTS: Graft function was documented in 115 patients (76.7%). Univariate analysis revealed that graft function had a significant association with lower serum calcium level 1 day after surgery. The cutoff point was 2.11 mmol/L, which was confirmed by a receiver-operating characteristic (ROC) curve. CONCLUSION: Low serum calcium levels in the early postoperative period may stimulate a functional recovery in an autografted parathyroid gland. Therefore, a moderate calcium supplement strategy was recommended for patients who underwent parathyroid autotransplantation during the early stage after total thyroidectomy.

Associations Between Change in Total and Free 25-Hydroxyvitamin D With 24,25-Dihydroxyvitamin D and Parathyroid Hormone.

Context: The physiologic role of free 25-hydroxyvitamin D [25(OH)D] in humans is unclear. Objective: To assess whether rise in total vs free 25(OH)D is associated with change in downstream biomarkers of 25(OH)D entry into target cells in kidney and parathyroid: 24,25-dihyroxyvitamin D [24,25(OH)2D] and PTH, respectively. Design: 16-week randomized controlled trial. Intervention: 60 µg (2400 IU)/d of D3 or 20 µg/d of 25(OH)D3. Setting: Academic medical center. Participants: 35 adults age ≥18 years with 25(OH)D levels < 20 ng/mL. Main Outcome Measures: 24,25(OH)2D, 1,25-dihyroxyvitamin D [1,25(OH)2D] and PTH. Results: At baseline, participants [D3 and 25(OH)D3 groups combined] were 35.1 ± 10.6 years. Mean total 25(OH)D, free 25(OH)D, 24,25(OH)2D, and PTH were 16.6 ng/mL, 4.6 pg/mL, 1.3 ng/mL, and 37.2 pg/mL, respectively. From 0 to 4 weeks, rise in only free 25(OH)D was associated with a concurrent 24,25(OH)2D increase [P = 0.03, adjusted for change in 1,25(OH)2D and supplementation regimen] and PTH decrease (P = 0.01, adjusted for change in calcium and supplementation regimen). Between 4 and 8 weeks, and again from 8 to 16 weeks, rises in free and total 25(OH)D were associated with 24,25(OH)2D increase; in contrast, rise in neither total nor free 25(OH)D was associated with PTH decrease during these time periods. Conclusions: Early rise in free 25(OH)D during treatment of vitamin D deficiency was more strongly associated with changes in biomarkers of 25(OH)D entry into target kidney and parathyroid cells, suggesting a physiologic role of free 25(OH)D in humans.

Transcription factor MafB may play an important role in secondary hyperparathyroidism.

The transcription factor MafB is essential for development of the parathyroid glands, the expression of which persists after morphogenesis and in adult parathyroid glands. However, the function of MafB in adult parathyroid tissue is unclear. To investigate this, we induced chronic kidney disease (CKD) in wild-type and MafB heterozygote (MafB+/-) mice by feeding them an adenine-supplemented diet, leading to secondary hyperparathyroidism. The elevated serum creatinine and blood urea nitrogen levels in heterozygous and wild-type mice fed the adenine-supplemented diet were similar. Interestingly, secondary hyperparathyroidism, characterized by serum parathyroid hormone elevation and enlargement of parathyroid glands, was suppressed in MafB+/- mice fed the adenine-supplemented diet compared to similarly fed wild-type littermates. Quantitative RT-PCR and immunohistochemical analyses showed that the increased expression of parathyroid hormone and cyclin D2 in mice with CKD was suppressed in the parathyroid glands of heterozygous CKD mice. A reporter assay indicated that MafB directly regulated parathyroid hormone and cyclin D2 expression. To exclude an effect of a developmental anomaly in MafB+/- mice, we analyzed MafB tamoxifen-induced global knockout mice. Hypocalcemia-stimulated parathyroid hormone secretion was significantly impaired in MafB knockout mice. RNA-sequencing analysis indicated PTH, Gata3 and Gcm2 depletion in the parathyroid glands of MafB knockout mice. Thus, MafB appears to play an important role in secondary hyperparathyroidism by regulation of parathyroid hormone and cyclin D2 expression. Hence, MafB may represent a new therapeutic target in secondary hyperparathyroidism.

Pilot study of parathyroid glands in adult and pediatric subjects exposed to ionizing radiation after the ChNPP accident, methodology of parathyroid diagnostic ultrasound. / PILOTNE DOSLIDZhENNIa STANU PRYShchYTOPODIBNYKh ZALOZ OSIB, OPROMINENYKh VNASLIDOK AVARIÏ NA ChAES DOROSLOGO TA DYTIaChOGO VIKU, METODOLOGIIa ÏKh UL'TRAZVUKOVOGO DOSLIDZhENNIa.

OBJECTIVE: Estimation of the parathyroid hyperplasia prevalence after the ChNPP accident in adults exposed to ion izing radiation and their descendants using the diagnostic ultrasound and its methodology elaboration. MATERIALS AND METHODS: The pilot prospective study of the prevalence of parathyroid hyperplasia among the Chornobyl Nuclear Power Plant (ChNPP) accident adult survivors (n=686) and their descendants (54 children) was performed using diagnostic ultrasound examination of thyroid and parathyroids. Among the study subjects there were 339 ChNPP accident clean up workers (ACUW), 32 persons were evacuated from the 30 km exclusion zone and 224 ones were included to the control group. Diagnostic ultrasound of thyroid and parathyroids was performed according to the standard method. Additionally, in children with parathyroid hyperplasia an additional assay of 25 hydroxyvitamin D levels in serum was performed. In calculating the statistical significance, its level p < 0.05 was considered statistically significant. RESULTS: Parathyroids are a few small but critically important endocrine glands that synthesize parathyroid hormone, regulating mainly phosphoric calcium metabolism. Insufficient (hypoparathyroidism) or excessive (hyperparathy roidism) function of parathyroids is harmful to the patients affecting the state of nervous and cardiovascular sys tem. Parathyroidss can accumulate isotopes of cesium, strontium and radioactive iodine. The available data testify to an increased incidence of clinically significant hyperplasia of parthyroids (more than 9 mm in adults and more than 5 mm in children) among persons exposed toionizng radiation as a result of the accident at the ChNPP (28.64%) and their descendants (23.8-70.6%). First of all are concerned those adults who live in contaminated areas in comparison with the control group (24.15% in not irradiated). Evacuees from the 30 km exclusion zone being the category of people who were exposed to the absorbed iodine isotopes in the first days of the Chernobyl accident are the another risk group. These data demonstrate sensitivity of parathyroidss to the impact of incorpo rated isotopes (iodine, cesium and strontium), which in the long term exposure create conditions for structural and functional changes in regulation of phosphorous calcium metabolism being the basis for a significant prevalence of osteopenia and osteoporosis in irradiated individuals and their descendants. A number of further studies are required to clarify the findings and to disclose the hormonal mechanisms of radiation effects on parathyroids. CONCLUSIONS: Parathyroid glands are radiosensitive and susceptible to effects of strontium, cesium and iodine iso topes, which cause parathyroid irradiation and subsequent structural and functional changes, being a prerequisite for development of osteopenia and osteoporosis in the ChNPP accident survivors and their descendants. High inci dence of parathyroid hypertrophy is found in the inhabitants of the radiation contaminated territories (long term irradiation by cesium isotopes), as well as in evacuated from the 30 km exclusion zone (irradiation by iodine iso topes in the early days of the accident).

Effect of the water fraction isolated from Fructus Ligustri Lucidi extract on bone metabolism via antagonizing a calcium-sensing receptor in experimental type 1 diabetic rats.

Our previous studies have demonstrated that the extract of Fructus Ligustri Lucidi (FLL) can maintain in vivo calcium homeostasis in aged and ovariectomized rats. This study was designed to elucidate the action of water fraction isolated from the FLL extract on bone metabolism and a calcium-sensing receptor (CaSR) in parathyroid glands and kidneys of diabetic rats. The streptozotocin-induced diabetic rats were treated with vehicle, FLL extract, and the water fraction (WF) isolated from the FLL extract for 4 weeks. Treatment with WF dramatically increased the serum levels of both calcium and parathyroid hormone and reduced urinary calcium excretion in diabetic rats as well as improved the pathological changes of trabecular bone as shown by the increased BA/TA, BMD/BV, and BV/TV. The mRNA expression of the calcium-binding protein 9k and protein expression of a vitamin D receptor (VDR) and plasma membrane Ca-ATPase in duodenum were significantly increased in diabetic rats after treatment with WF, which reduced the expression of CaSR in parathyroid gland and kidney as well as inhibited the up-regulation of VDR and 25-hydroxyvitamin D-24 hydroxylase expressions in the kidney of diabetic rats. This study reveals that the water fraction may be an active component of the FLL extract that exerts beneficial effects on improving bone metabolism via regulating vitamin D metabolism in kidney and vitamin D-dependent calcium transporters in duodenum as well as modulating the expression of CaSR in the parathyroid gland and kidneys.

Postsurgical Hypoparathyroidism: A Systematic Review.

This article reviews epidemiology, risk factors and treatment modalities of postsurgical hypoparathyroidism (PHypo). PHypo occurs after total thyroidectomy due to injury of parathyroid glands and/or their blood supply or after parathyroidectomy. PHypo results in hypocalcemia because parathyroid hormone (PTH) secretion is impaired and cannot mobilize calcium from bone, reabsorb calcium from the distal nephron and stimulate renal 1α-hydroxylase activity. It usually appears in the first days after surgery and it can be symptomatic or asymptomatic. Risk factors are low level of intraoperative PTH and presence of parathyroid gland in the pathological specimen. Patients usually present with paresthesia, cramps or tetany, but the disorder may also manifest acutely with seizures, bronchospasm, laryngospasm or cardiac rhythm disturbances. Standard treatment is vitamin D analogues and calcium supplementation.

Parathyroid Allotransplant With a New Technique: A Prospective Clinical Trial.

OBJECTIVES: Parathyroid allotransplant is a valuable alternative in treating permanent hypoparathyroidism. However, it is a difficult process that requires several trained staff and advanced laboratory equipment, which makes the costs high. Here, we identify a new parathyroid allotransplant technique. MATERIALS AND METHODS: After obtaining informed consent from patients, parathyroid cell suspensions obtained from 4 donors who had undergone a subtotal parathyroidectomy owing to chronic renal failure were transplanted in 10 patients with permanent hypoparathyroidism after short-term cell cultivation. Prednisolone were used as immunosuppressant for the first 10 days and discontinued thereafter. RESULTS: Allograft function was observed in 7 patients (70%) at a mean follow-up of 12 months. Daily oral calcium and vitamin D supplementations discontinued totally in 7 patients. No major or minor complication was observed. CONCLUSIONS: Our technique is simple, fast, and has a low cost, with a 70% success rate at a mean follow-up of 12 months. It requires few staff, minimal equipment, and short-term immunosuppressant use for maintenance. The technical developments of parathyroid allotransplant, as mentioned in this study, may be important in treating permanent hypoparathyroidism.

Fluoride Modulates Parathyroid Hormone Secretion in vivo and in vitro.

The study objective was to investigate the effects of fluoride on intact parathyroid hormone (iPTH) secretion. Thyro-parathyroid complexes (TPC) from C3H (n = 18) and B6 (n = 18) mice were cultured in Ca²âº-optimized medium. TPC were treated with 0, 250, or 500 µM NaF for 24 h and secreted iPTH assayed by ELISA. C3H (n = 78) and B6 (n = 78) mice were gavaged once with distilled or fluoride (0.001 mg [F⁻]/g of body weight) water. At serial time points (0.5-96 h) serum iPTH, fluoride, total calcium, phosphorus, and magnesium levels were determined. Expression of genes involved in mineral regulation via the bone-parathyroid-kidney (BPK) axis, such as parathyroid hormone (Pth), calcium-sensing receptor (Casr), vitamin D receptor (Vdr), parathyroid hormone-like hormone (Pthlh), fibroblast growth factor 23 (Fgf23), α-Klotho (αKlotho), fibroblast growth factor receptor 1c (Fgf1rc), tumor necrosis factor 11 (Tnfs11), parathyroid hormone receptor 1 (Pth1r), solute carrier family 34 member 1 (Slc34a1), solute carrier 9 member 3 regulator 1 (Slc9a3r1), chloride channel 5 (Clcn5), and PDZ domain-containing 1 (Pdzk1), was determined in TPC, humeri, and kidneys at 24 h. An in vitro decrease in iPTH was seen in C3H and B6 TPC at 500 µM (p < 0.001). In vivo levels of serum fluoride peaked at 0.5 h in both C3H (p = 0.002) and B6 (p = 0.01). In C3H, iPTH decreased at 24 h (p < 0.0001), returning to baseline at 48 h. In B6, iPTH increased at 12 h (p < 0.001), returning to baseline at 24 h. Serum total calcium, phosphorus, and magnesium levels did not change significantly. Pth, Casr,αKlotho,Fgf1rc,Vdr, and Pthlh were significantly upregulated in C3H TPC compared to B6. In conclusion, the effects of fluoride on TPC in vitro were equivalent between the 2 mouse strains. However, fluoride demonstrated an early strain-dependent effect on iPTH secretion in vivo. Both strains demonstrated differences in the expression of genes involved in the BPK axis, suggesting a possible role in the physiologic handling of fluoride.

The vitamin D, ionised calcium and parathyroid hormone axis of cerebral capillary function: therapeutic considerations for vascular-based neurodegenerative disorders.

Blood-brain barrier dysfunction characterised by brain parenchymal extravasation of plasma proteins may contribute to risk of neurodegenerative disorders, however the mechanisms for increased capillary permeability are not understood. Increasing evidence suggests vitamin D confers central nervous system benefits and there is increasing demand for vitamin D supplementation. Vitamin D may influence the CNS via modulation of capillary function, however such effects may be indirect as it has a central role in maintaining calcium homeostasis, in concert with calcium regulatory hormones. This study utilised an integrated approach and investigated the effects of vitamin D supplementation, parathyroid tissue ablation (PTX), or exogenous infusion of parathyroid hormone (PTH) on cerebral capillary integrity. Parenchymal extravasation of immunoglobulin G (IgG) was used as a marker of cerebral capillary permeability. In C57BL/6J mice and Sprague Dawley rats, dietary vitamin D was associated with exaggerated abundance of IgG within cerebral cortex (CTX) and hippocampal formation (HPF). Vitamin D was also associated with increased plasma ionised calcium (iCa) and decreased PTH. A response to dose was suggested and parenchymal effects persisted for up to 24 weeks. Ablation of parathyroid glands increased CTX- and HPF-IgG abundance concomitant with a reduction in plasma iCa. With the provision of PTH, iCa levels increased, however the PTH treated animals did not show increased cerebral permeability. Vitamin D supplemented groups and rats with PTH-tissue ablation showed modestly increased parenchymal abundance of glial-fibrillary acidic protein (GFAP), a marker of astroglial activation. PTH infusion attenuated GFAP abundance. The findings suggest that vitamin D can compromise capillary integrity via a mechanism that is independent of calcium homeostasis. The effects of exogenous vitamin D supplementation on capillary function and in the context of prevention of vascular neurodegenerative conditions should be considered in the context of synergistic effects with calcium modulating hormones.

Risk Factors of Parathyroid Dysfunction in Elderly Patients with Chronic Kidney Disease Undergoing Hemodialysis.

BACKGROUND: Aberrant mineral metabolism and bone diseases, which are commonly seen in chronic kidney disease (CKD), have been considered to be the important causes of morbidity and decreased quality of life. OBJECTIVES: We aimed to investigate the characteristics of calcium-phosphorus metabolism abnormalities and parathyroid dysfunction in elderly patients with chronic kidney disease undergoing hemodialysis. MATERIAL AND METHODS: A total of 336 patients undergoing maintenance hemodialysis were divided into two age groups: elderly (≥ 65 years) and non-elderly (< 65 years). Before dialysis, fasting blood samples were initially collected, then hemoglobin (Hb), serum creatinine (Scr), blood urea nitrogen (BUN), calcium, phosphorus, intact parathyroid hormone (iPTH), high-sensitivity C-reactive protein (HsCRP) and albumin (Alb) were measured. Serums BUN, ultrafiltration volume, dialysis duration and body weight were measured after dialysis. Finally, well-established formulas were used to obtain the serum albumin corrected calcium (Ac-Ca) and urea removal index (Kt/V). RESULTS: Elderly patients accounted for 52.7% of our patients; essential hypertension accounted for 35.6% of the cause for chronic renal failure, followed by chronic glomerulonephritis (21.5%) and diabetes mellitus (19.8%) in the elderly group; while in the non-elderly group, 43.4% of the chronic renal failure was due to chronic glomerulonephritis, followed by diabetes mellitus (23.9%) and essential hypertension (12.6%). Significant differences were found in the dialysis duration, blood pressure, concentrations of serum BUN, Scr, P, iPTH, Alb, standard-protein nitrogen present rate (nPNA) and Hs-CRP between the 2 groups. The multiple logistic regression analysis showed that age, plasma phosphorus, albumin and nPNA were independent risk factors for secondary hyperparathyroidism in patients undergoing maintenance hemodialysis. CONCLUSIONS: We conclude that most elderly patients undergoing hemodialysis experience hyperparathyroidism. The risk factors may include age and malnutrition but need further investigation.

Novel, selective vitamin D analog suppresses parathyroid hormone in uremic animals and postmenopausal women.

BACKGROUND: The use of 1α-hydroxylated vitamin D therapy to control secondary hyperparathyroidism in renal failure patients has been a success story, culminating with the demonstration of increased life expectancy in patients treated with these compounds. However, hypercalcemic episodes have been a recurrent problem with these therapies and have resulted in the added use of calcium mimetics. Clearly there is good reason to search for improved vitamin D therapy. In our inventory of vitamin D compounds, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD) surfaced as a potential candidate. This was based on its preferential localization in the parathyroid gland and a clear suppression of serum parathyroid hormone (PTH) levels without a change in serum calcium in a clinical trial in postmenopausal women. METHODS: 2MD has now been tested in the rat 5/6-nephrectomy model of renal failure, and in postmenopausal women to determine if it can suppress serum PTH at doses that do not elevate serum calcium and serum phosphorus concentrations. RESULTS: Daily oral treatment of uremic rats on 2.5 ng/bw/day of 2MD dramatically suppressed PTH without a change in serum calcium or serum phosphorus. Further, PTH was suppressed in postmenopausal women after only 3 daily oral doses of 2MD that continued for 4 weeks with no change in serum calcium or serum phosphorus. CONCLUSION: These results coupled with a pharmacokinetic half-life of ~24 h suggest that 2MD given either daily or at the time of dialysis may be a superior therapy for secondary hyperparathyroidism in chronic renal failure patients.

Recovery of parathyroid hormone secretion and function in postoperative hypoparathyroidism: a case series.

CONTEXT: Transient and permanent postoperative hypoparathyroidism are recognized complications of neck surgery. Postoperative hypoparathyroidism is usually considered permanent when it persists for 6 months; in rare cases, recovery of hypoparathyroidism through 1 year has been described. Recovery of hypoparathyroidism years after diagnosis has not previously been reported. OBJECTIVE: We report four patients being treated with PTH(1-84) in a research protocol who recovered from postoperative hypoparathyroidism many years after onset. METHODS: Recovery from hypoparathyroidism was established by: 1) serum calcium and PTH levels within the normal range off PTH(1-84) treatment for at least 1 week; 2) requirement for daily calcium supplementation reduced to ≤1 g; and 3) no supplemental active vitamin D therapy. RESULTS: Hypoparathyroidism developed in three subjects after repeated neck surgery for primary hyperparathyroidism and in one subject after total thyroidectomy for Graves' disease. Parathyroid tissue autotransplant was performed in two of the four subjects. Two had undetectable PTH levels at study entry, whereas the other two subjects had detectable, although low, PTH levels. Hypoparathyroidism had been present for at least 8 years, and in one case for 16 years. The recovery of parathyroid function followed treatment with PTH(1-84) for 36 to 63 months. CONCLUSIONS: Although it remains relatively rare, this report documents recovery of long-term postoperative hypoparathyroidism many years after the initial diagnosis. A potential role for exogenous PTH is intriguing with several plausible mechanisms.

Genistein affects parathyroid gland and NaPi 2a cotransporter in an animal model of the andropause.

This study aimed to examine the effects of genistein on the structural and functional changes in parathyroid glands (PTG) and sodium phosphate cotransporter 2a (NaPi 2a) in orchidectomized rats. Sixteen-month-old Wistar rats were divided into sham-operated (SO), orchidectomized (Orx) and genistein-treated orchidectomized (Orx+G) groups. Genistein (30 mg/kg/day) was administered subcutaneously for 3 weeks, while the controls received vehicle alone. PTG was analyzed histomorphometrically, while the expressions of NaPi 2a mRNA/protein levels from kidneys were determined by real time PCR and Western blots. Serum and urine parameters were determined biochemically. The PTG volume in Orx rats was increased by 30% (p<0.05), compared to the SO group. Orx+G treatment increased the PTG volume by 35% and 75% (p<0.05) respectively, comparing to Orx and SO animals. Orchidectomy led to increment of serum PTH by 27% (p<0.05) compared to the SO group, Orx+G decreased it by 18% (p<0.05) comparing to Orx animals. NaPi 2a expression in Orx animals was reduced in regards to its abundance in SO animals, although it was increased in Orx+G group compared to the Orx. Phosphorus urine content of Orx animals was raised by 12% (p<0.05) compared to that for the SO group, while Orx+G induced a 17% reduction (p<0.05) in regards to Orx animals. Our study shows that Orx increases PTG volume and serum PTH level, while protein expression of NaPi 2a is reduced. Application of genistein attenuates the orchidectomy-induced changes in serum PTH level, stimulates the expression of NaPi 2a and reduces urinary Pi excretion, implying potential beneficial effects on andropausal symptoms.

Inhibition of parathyroid hormone secretion by caffeine in human parathyroid cells.

CONTEXT AND OBJECTIVE: Caffeine is a highly consumed psychoactive substance present in our daily drinks. Independent studies have reported associations between caffeine consumption, low bone mineral density, and urinary calcium loss, as well as impaired bone development in vitro and in vivo. Calcium (Ca(2+)), vitamin D, and PTH are critical regulators of bone remodeling. A possible association between caffeine and parathyroid gland function has been suggested in the literature. DESIGN, SETTING, AND PATIENTS: Effects of caffeine on PTH secretion and Ca(2+) levels were determined by batch incubation and Fura-2, respectively, in pathological parathyroid cells. Protein expressions were studied by Western blot and immunohistochemistry in normal and parathyroid adenoma tissues. Alterations in gene expressions of adenosine receptor A1 (ADORA1) and A2 (ADORA2A) and PTH were quantified by PCR; intracellular cAMP levels and protein kinase A activity were analyzed by an antibody-based assay. RESULTS: We studied physiological concentrations of caffeine ranging from 1 to 50 µm and found that 50 µm caffeine caused a significant decrease of PTH secretion and PTH gene expression. This decrease occurred in parallel with a decrease of the intracellular cAMP level, protein kinase A activity, and ADORA1 gene expression, indicating a possible causal relationship. The intracellular level of Ca(2+) was unaffected even by high concentrations of caffeine. Protein expressions demonstrated two main targets for caffeine-ADORA1 and ADORA2A. CONCLUSION: A physiological high dose of caffeine inhibits PTH secretion in human parathyroid cells, possibly due to a decrease of the intracellular level of cAMP. The observation demonstrates a functional link between caffeine and parathyroid cell function.

Low molecular weight iron dextran increases fibroblast growth factor-23 concentration, together with parathyroid hormone decrease in hemodialyzed patients.

Fibroblast growth factor (FGF)-23 inhibits PTH production. Elevated FGF-23 and parathyroid hormone (PTH) levels are characteristic of hemodialyzed patients. Iron polymaltose was shown to increase FGF-23 concentration. The effect of intravenous low molecular weight iron dextran (LMID) on these hormones and bone metabolism has not been studied in hemodialysis (HD). Twelve HD patients were prospectively followed up for 3 weeks after a single infusion of LMID. Calcium, phosphate, FGF-23, PTH, degradation products of C-terminal telopeptides of type I collagen (CTX) and procollagen I N-terminal propeptide (PINP) were measured prior to, and at week 1 and week 3 after the LMID administration. FGF-23 increased significantly from 453.4 (68.6-3971.5) pg/mL at baseline to 971.8 (779.5-3361.4) pg/mL (P = 0.001) at week 1 and started to decrease toward the initial value at week 3. The changes were accompanied by a significant decline in PTH from 367.6 (21.4-1487.4) pg/mL at baseline to 315.7 (16.4-1339.8) pg/mL (P = 0.018) at week 1 and subsequently began to increase toward the initial values. Phosphate, calcium, CTX and PINP did not change over the study course. LMID causes an increase in FGF-23 concentration together with a decrease in PTH. Our study highlights a pathophysiological element, which may connect suppression of parathyroid glands with intravenous iron supplementation.