Resurgence of parathyroidectomy: evidence and outcomes.

PURPOSE OF REVIEW: Parathyroidectomy (PTx) is the definitive therapy for refractory secondary hyperparathyroidism (SHPT). The drastic effects of PTx on biochemical parameters of SHPT increases the possibility that this intervention will lead to a reduction in the adverse outcomes related to uncontrolled SHPT. RECENT FINDINGS: The effect of PTx on mortality and cardiovascular outcomes among dialysis patients with severe SHPT have been evaluated in many observational studies from different regions of the world, including Asia, Europe, North America, and South America. In all but one small study, there was a significant association of PTx with lower all-cause mortality. In addition, in all studies, there was a trend in favor of PTx for cardiovascular morbidity and mortality. The effect of PTx on fractures has been evaluated in only one epidemiological study from the United States, which demonstrated a significant association of PTx and lower hip and combined fractures. SUMMARY: Although randomized evidence is lacking, these highly consistent results may suggest a strong beneficial effect of PTx on long-term clinical outcomes and eliminate the potential concern of low parathyroid hormone after PTx.

FAM111A mutations result in hypoparathyroidism and impaired skeletal development.

Kenny-Caffey syndrome (KCS) and the similar but more severe osteocraniostenosis (OCS) are genetic conditions characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. We studied five individuals with KCS and five with OCS and found that all of them had heterozygous mutations in FAM111A. One mutation was identified in four unrelated individuals with KCS, and another one was identified in two unrelated individuals with OCS; all occurred de novo. Thus, OCS and KCS are allelic disorders of different severity. FAM111A codes for a 611 amino acid protein with homology to trypsin-like peptidases. Although FAM111A has been found to bind to the large T-antigen of SV40 and restrict viral replication, its native function is unknown. Molecular modeling of FAM111A shows that residues affected by KCS and OCS mutations do not map close to the active site but are clustered on a segment of the protein and are at, or close to, its outer surface, suggesting that the pathogenesis involves the interaction with as yet unidentified partner proteins rather than impaired catalysis. FAM111A appears to be crucial to a pathway that governs parathyroid hormone production, calcium homeostasis, and skeletal development and growth.

Associations between the levels of sclerostin, phosphate, and fibroblast growth factor-23 and treatment with vitamin D in hemodialysis patients with low intact PTH level.

UNLABELLED: Serum sclerostin levels could be closely associated with serum phosphate and fibroblast growth factor-23 levels in hemodialysis patients with low intact parathyroid hormone (PTH) levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low PTH levels without any vitamin D treatment. INTRODUCTION: Intact parathyroid hormone (iPTH) is involved in the interaction between sclerostin and phosphate/fibroblast growth factor-23 (FGF23) in animal models. However, their relationship in patients on hemodialysis (HD) is unclear. METHODS: Data of 102 HD patients were collected regarding clinical and laboratory parameters and mineral bone disorder medications. The patients were divided into subgroups according to the iPTH level (A, <70 pg/mL; B, 70-150 pg/mL; C, 150-300 pg/mL; and D, ≥ 300 pg/mL). RESULTS: The sclerostin level was significantly and positively correlated with phosphate and log of FGF23 levels in subgroups A, B, and combined A and B. Multiple linear regression analysis in the combined A and B subgroup revealed that male sex (t = 3.24, P = 0.01; 95% confidence interval [CI] 11.78 to 50.43) and phosphate level (t = 2.13, P = 0.04; 95% CI, 1.08 to 36.91) were independent factors for serum sclerostin level. The log of serum FGF23 level (t = 1.90, P = 0.06, 95% CI -1.85 to 63.50) appeared to be an important factor for serum sclerostin level. The frequency of patients using vitamin D treatment was not significantly different among subgroups A (93.1%), B (88.0%), C (85.2%), and D (90.5%). CONCLUSION: Serum sclerostin levels were associated with serum phosphate and FGF23 levels in patients with low iPTH levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low iPTH levels without vitamin D treatment.

The PTH-Vitamin D-FGF23 axis.

Fibroblast growth factor 23 (FGF23) has emerged as an important regulator of phosphate and vitamin D homeostasis. It is important to understand how FGF23 interacts with vitamin D and parathyroid hormone (PTH) in a FGF23-Vitamin D-PTH axis to regulate mineral homeostasis. In this review, we discuss the genomic structure, and transcriptional, translational, and posttranslational regulation of FGF23. We describe its interaction with PTH and vitamin D, disorders of altered FGF23 states, and emerging therapies for diseases of FGF23 based upon these findings. This discussion helps redefine the role of PTH and vitamin D in relation to a complex bone-kidney-parathyroid loop, and points to areas within this complicated field in need of further clarification and research.

Oral administration of soluble guanylate cyclase agonists to rats results in osteoclastic bone resorption and remodeling with new bone formation in the appendicular and axial skeleton.

Orally administered small molecule agonists of soluble guanylate cyclase (sGC) induced increased numbers of osteoclasts, multifocal bone resorption, increased porosity, and new bone formation in the appendicular and axial skeleton of Sprague-Dawley rats. Similar histopathological bone changes were observed in both young (7- to 9-week-old) and aged (42- to 46-week-old) rats when dosed by oral gavage with 3 different heme-dependent sGC agonist (sGCa) compounds or 1 structurally distinct heme-independent sGCa compound. In a 7-day time course study in 7- to 9-week-old rats, bone changes were observed as early as 2 to 3 days following once daily compound administration. Bone changes were mostly reversed following a 14-day recovery period, with complete reversal after 35 days. The mechanism responsible for the bone changes was investigated in the thyroparathyroidectomized rat model that creates a low state of bone modeling and remodeling due to deprivation of thyroid hormone, calcitonin (CT), and parathyroid hormone (PTH). The sGCa compounds tested increased both bone resorption and formation, thereby increasing bone remodeling independent of calciotropic hormones PTH and CT. Based on these studies, we conclude that the bone changes in rats were likely caused by increased sGC activity.

Measuring vitamin D levels: surrogates are insufficient.

AIMS: With the increasing evidence of adverse consequences because of low vitamin D levels on health demand for vitamin D, screening is increasing. The objective of the study was to assess whether parathyroid hormone (PTH) levels/bone profile is sufficient to identify patients with vitamin D insufficiency or deficiency, or whether vitamin D should be measured directly. METHODOLOGY: A total of 1560 serum specimens, with requests for 25-hydroxyvitamin D (25-OH vitamin D), calcium, phosphate, alkaline phosphatase (ALP), creatinine and PTH on the same sample were analysed at Salford Royal Hospital from November 2010 to November 2012. RESULTS: The prevalence of total vitamin D insufficiency or deficiency (defined as total 25-OH vitamin D < 50 nmol/l) was 62.9% (981/1560) overall, with males having higher proportions (67.2 vs. 59.3 per cent; χ(2) = 8.78, p = 0.003). There was no overall trend in mean serum adjusted calcium across categories of 25-OH vitamin D status but mean serum phosphate was significantly lower (F = 6.53, p < 0.0001) in patients with a 25-OH vitamin D level < 50 nmol/l. However in patients with vitamin D deficiency, a significant proportion had PTH, calcium, phosphate and alkaline phosphatase levels within the laboratory normal range. Even at a 25-OH vitamin D < 10 nmol/l, 71.6% had a normal PTH, 89.8% had normal serum calcium levels, 84.9% had normal phosphate levels and 81.6% had normal serum ALP. CONCLUSIONS: Therefore, despite the costs associated with the measurement of vitamin D, our findings show that no surrogate is adequate for screening for vitamin D deficiency.

Bilateral Truncal Ligation of the Inferior Thyroid Artery during Bilateral Subtotal Thyroidectomy Causes a Decrease in Parathormone without Clinically Manifest Hypoparathyroidism: A Randomized Clinical Trial.

BACKGROUND: Bilateral truncal ligation (BTL) of the inferior thyroid artery (ITA) is frequently used during subtotal thyroidectomy to reduce the risk of post-operative bleeding as well as to reduce the blood loss intra-operatively. However, its effect on parathyroid function has not been evaluated in relation to age, residual and resected thyroid volume. METHODS: A total of 83 patients were randomized to receive non-BTL or BTL. After bilateral resection, the residual thyroid tissue on each side was measured by intra-operative ultrasonography. Laboratory and clinical examinations were performed the day before operation, intra-operatively and on post-operative days 2 and 5. The primary outcome measure was the difference in intact parathormone (PTHi) on post-operative day 5. Secondary outcomes were laboratory-diagnosed hypocalcaemia or hypoparathyroidism and clinically manifest hypoparathyroidism, respectively. RESULTS: PTHi on post-operative day 5 was significantly lower in the BTL group (29.4 vs. 34.7 ng/l in the non-BTL group, p = 0.033), especially in 61- to 80-year-old patients (0 vs. -7.91 ng/l, p = 0.029). The biggest decline in PTHi was found in the BTL group (-14.067 ng/l PTH, p = 0.018) with a residual thyroid volume of 0.5-1.9 ml. There were two cases of asymptomatic hypoparathyroidism in each group (5.1 vs. 4.8%, respectively, p = 1.000). The only case of clinically manifest hypoparathyroidism was in a BTL group patient aged 64 years (2.4%, p = 1.000). CONCLUSION: BTL of the ITA during subtotal thyroidectomy causes a larger decrease in PTH but does not lead to a significantly higher rate of clinically manifest hypoparathyroidism. BTL of the ITA, age >61 years, and a very small thyroid remnant (<2 ml) may be risk factors for post-operative hypoparathyroidism.

Extracellular calcium-sensing receptor/PTH knockout mice colons have increased Wnt/ß-catenin signaling, reduced non-canonical Wnt signaling, and increased susceptibility to azoxymethane-induced aberrant crypt foci.

Epidemiological evidence suggests increased dietary calcium and dairy products reduce the onset of colon cancer. To understand a role of the colonic extracellular calcium-sensing receptor (CaSR) in calcium-mediated chemoprevention of colon cancer, we induced formation of aberrant crypt foci (ACF) caused by azoxymethane (AOM) injection in 'rescued' CaSR-/PTH- (C-/P-) double knockout colons compared with colons from control CaSR+/PTH+ (C+/P+) mice. C-/P- colonic epithelia had increased Wnt/ß-catenin signaling as evidenced by 3-8-fold increases in Wnt3a, CyclinD1, and MMP-7 proteins compared with C+/P+ colonic epithelia. The C-/P- colonic epithelia had reduced Wnt5a and Ror2, and a three-fold increase in TNFR1 compared with C+/P+ epithelia. The C-/P- colons and small intestine had extensive neutrophil infiltration with myeloperoxidase (MPO) levels 18-fold higher then C+/P+ small intestine and colon. Saline-injected C-/P- colons had the same number of ACF/cm(2) as C+/P+ colons, which were injected with AOM. However, there were eight times more ACF/cm(2) in the C-/P- injected with AOM compared with C+/P+ colons, which received AOM. Together our results suggest both inflammation and Wnt/ß-catenin signaling are increased in the epithelia of 'rescued' CaSR/PTH double knockout colons, and the capacity for non-canonical Wnt signaling through Wnt5a/Ror2 engagement is reduced. The loss of the colonic CaSR increased the number of ACF/cm(2) in response to AOM injection, suggesting colonic CaSR may mediate the chemoprotective effect of increased dietary calcium against colorectal cancer observed in humans.

Vitamin D deficiency and insufficiency after pediatric liver transplantation.

Vitamin D deficiency and insufficiency are increasingly recognized in the general population, including healthy children. There is also an increasing emphasis on the importance of vitamin D status following pediatric liver transplantation and specifically its relationship to metabolic bone disease and growth retardation. Vitamin D insufficiency has also been associated with multiple immunological and metabolic disorders in adults. To our knowledge, this has not been systematically evaluated in children undergoing liver transplantation to date. Between October 2004 and August 2008, serum 25-(OH)-vitamin D levels were measured in 199 children who had undergone liver transplantation at Birmingham Children's Hospital. Potential factors contributing to vitamin D levels were evaluated. Additionally, we evaluated a possible relationship between vitamin D levels and immunological phenomena and metabolic complications. Median 25-(OH)-vitamin D level was 19.5 ng/mL (range: 4.4-71.4 ng/mL). A total of 105 children (53%) had insufficient vitamin D levels and 28 children (14%) showed vitamin D deficiency. The only factors found to be associated with vitamin D deficiency were season of sample, ethnicity, and PTH levels. Vitamin D deficiency was more prevalent during the first year after transplantation. We did not find a significant relationship between vitamin D levels and graft function or any other immunological and metabolic complications. Vitamin D insufficiency and deficiency are common in children after liver transplantation, especially in winter and spring and in non-white patients. Initial post-transplant period and high PTH are significantly associated with vitamin D deficiency. Vitamin D status should be monitored following pediatric liver transplantation and vitamin D supplementation provided as required.

CASR gene activating mutations in two families with autosomal dominant hypocalcemia.

BACKGROUND: Autosomal dominant hypocalcemia (ADH) is an endocrine disorder caused by activating mutations of the calcium-sensing receptor (CASR) gene which plays a major role in maintaining calcium homeostasis. Biochemical features of ADH are hypocalcemia and hypercalciuria with inappropriately low levels of parathyroid hormone (PTH). We report on two four-generation families affected by ADH. AIM: To identify mutations of CASR gene in subjects affected by familial idiopathic hypoparathyroidism. To perform functional assays of identified CASR variants by transient transfection on HEK293 cells. RESULTS: We identified two CASR variants (Q681R and P221L): the Q681R variant was novel while the P221L had been previously published. Functional assays on the Q681R variant showed that it did not alter the whole expression nor the correct plasmamembrane localization, but enhanced the signaling function, increasing the sensitivity of the receptor as compared to the WT. CONCLUSIONS: We report two activating CASR mutations in two families affected by ADH and the functional assays performed on the novel variant Q681R. Our work enlarged the spectrum of mutations of the CASR and contributed to a better elucidation of the protein function.

Intraoperative serum parathyroid hormone level is an indicator of hypocalcaemia in total thyroidectomy patients.

Postoperative hypocalcaemia is the most frequent and common complication after total thyroidectomy. It is necessary to diagnose or to predict hypocalcaemia immediately after total thyroidectomy for minimizing complications. A prospective observational study was carried out in the Department of Clinical Pathology in collaboration with Department of Microbiology & Immunology, Department of Surgery, Department of Otolaryngology, Bangabandhu Sheikh Mujib Medical University (BSMMU) and Department of Otolaryngology, Dhaka Medical College & Hospital (DMC&H), Dhaka, during the period of September 2010 to August 2011 to evaluate intraoperative (20 minutes after total thyroidectomy) parathyroid hormone (PTH) measurement as a predictor of post thyroidectomy hypocalcaemia. Total 65 patients were enrolled in this study those came for total thyroidectomy. Postoperative hypocalcaemia developed in 25 cases. Intraoperative PTH was assessed and significant correlation was found between intraoperative PTH level and development of hypocalcaemia. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value of intraoperative serum PTH for prediction of post total thyroidectomy hypocalcaemia were 84.0%, 85.0%, 84.6%, 77.8%, and 89.5% respectively. Because of the high sensitivity, specificity and accuracy of intraoperative serum PTH of this study, the early prediction of hypocalcaemia could be made by single assay of intraoperative serum PTH level at 20 minutes after total thyroidectomy.

22q11.2 deletion presenting with severe hypocalcaemia, seizure and basal ganglia calcification in an adult man.

We report a 40-year-old man who was found to have profound hypocalcaemia and hypoparathyroidism when investigated for multiple, generalized, tonic/clonic seizures and a chest infection. Computed tomography scan of the brain revealed extensive symmetric bilateral calcification within the cerebellum, thalamus and basal ganglia. Molecular cytogenetic testing by fluorescent in situ hybridization using the commercial Vysis LSI DiGeorge/VCFS dual colour probe set showed a deletion of 22q11.2. The extraordinary feature of this case is the adult presentation of hypocalcaemia, hypoparathyroidism and basal ganglia calcification due to 22q11.2 deletion.

Parathyroid hormone deficiency after total thyroidectomy: incidence and time.

BACKGROUND: Parathyroid hormone (PTH) deficiency or hypoparathyroidism after total thyroidectomy is not an uncommon postoperative complication. Patients who have PTH deficiency will develop profound hypocalcemia if not properly treated with oral calcium supplementation and activated vitamin D (1,25-dihydroxycholecalciferol or calcitriol). However, there is little published on the long-term outcomes of these patients. The aim of this study was to determine the incidence of PTH deficiency and the time course to resolution after total thyroidectomy. METHODS: We identified 271 consecutive patients who underwent total thyroidectomy from January 2006 to December 2008. All patients had serum PTH levels tested 4 h after surgery and the morning after surgery. Patients were diagnosed with PTH deficiency if their serum PTH was <10 pg/mL. The outcomes of patients with PTH deficiency (group 1) were then compared with patients who did not have PTH deficiency (group 2). Patients in group 1 were evaluated for parathyroid function by measuring serum PTH levels as well as documenting usage of supplemental calcium and 1,25-dihydroxycholecalciferol. RESULTS: Of the 271 patients, 33 (12%) were found to have PTH deficiency. In comparing PTH deficient patients (group 1) with patients in group 2, there were no differences in age, gender, thyroid pathology, the incidence of thyroiditis, or other factors that would predict hypoparathyroidism. Twenty-four patients (73%) had recovery of their PTH levels to > or =10 pg/mL at their 1 wk follow-up appointment, while 9 (27%) patients still had PTH levels <10 pg/mL. With long term follow-up, 27 (82%) patients had recovered with a PTH level of > or = 10 pg/mL, while 6 (18%) patients had a serum PTH level <10 pg/mL. However, three of the 33 patients in group 1 (9%) required long-term 1,25-dihydroxycholecalciferol, but only two of these patients had undetectable PTH levels. Thus, the overall rate of hypocalemia requiring 1,25-dihydroxycholecalciferol was <1% (two of 271 total patients). CONCLUSIONS: We concluded that approximately 12% (33 of 271) of patients undergoing total thyroidectomy will develop PTH deficiency. Of the PTH deficient patients, 73% will return to normal parathyroid function within 1 wk of surgery. Furthermore, 82% of these PTH deficient patients will return to normal parathyroid function with long-term follow-up. Less than 1% (two of 271) of patients undergoing total thyroidectomy will require 1,25-dihydroxycholecalciferol for long-term hypocalcemia.

Parathormone decline levels are better markers of symptomatic hypocalcemia following total thyroidectomy than parathormone alone.

Background: We aimed to assess the predictive value of the absolute and relative intact parathormone (iPTH) decline levels as reliable markers of postoperative hypocalcemia. Materials & methods: iPTH levels were measured 4 h after surgery and the following morning after surgery (postoperative day 1). iPTH, absolute iPTH decline (ΔPTH) and relative iPTH decline (ΔPTH%) were calculated and correlated with symptomatic hypocalcemia. Results: Of the 95 patients, 20% of patients (n = 19) developed symptomatic hypocalcemia. The ΔPTH (U = 206; p < 0.001) and ΔPTH% (U = 127; p < 0.001) were significantly higher in patients with symptomatic hypocalcemia. A ΔPTH% of 20% (sensitivity of 84%; specificity of 91%); and an absolute iPTH decline of 3.75 pg/ml (sensitivity of 74%; specificity of 87%) were highly predictive of symptomatic hypocalcemia. Conclusion: Postoperative ΔPTH and ΔPTH% have the potential to be predictors of symptomatic hypocalcemia following thyroidectomy and could facilitate a safe early discharge.

The full-length calcium-sensing receptor dampens the calcemic response to 1alpha,25(OH)2 vitamin D3 in vivo independently of parathyroid hormone.

1Alpha,25(OH)(2) vitamin D(3) [1,25(OH)(2)D(3)] increases serum Ca(2+) concentration in vivo, an action counteracted by activation of the Ca(2+)-sensing receptor (CaSR), which decreases parathyroid hormone (PTH) secretion and increases renal Ca(2+) excretion. Relatively little is known of the role the CaSR plays in this response through its potentially direct actions in kidney, gut, and bone independently of PTH. We report PTH-independent roles of the CaSR in modulating the response to exogenous 1,25(OH)(2)D(3) in mice with targeted disruption of both the CaSR and PTH genes (C(-)P(-)) compared with that in mice with disruption of the PTH gene alone (C(+)P(-)) or wild-type mice (C(+)P(+)). After intraperitoneal injection of 0.5 ng/g body wt 1,25(OH)(2)D(3), peak calcemic responses were observed at 24 h in all three genotypes in association with 1) a greater increase in serum Ca(2+) in C(-)P(-) mice than in the other genotypes on a Ca(2+)-replete diet that was attenuated by a Ca(2+)-deficient diet and pamidronate, 2) increased urinary Ca(2+)-to-creatinine ratios (UCa/Cr) in the C(+)P(-) and C(+)P(+) mice but a lowered ratio in the C(-)P(-) mice on a Ca(2+)-replete diet, and 3) no increase in calcitonin (CT) secretion in the C(+)P(+) and C(+)P(-) mice and a small increase in the C(-)P(-) mice. PTH deficiency had the anticipated effects on the expression of key genes involved in Ca(2+) transport at baseline in the duodenum and kidney, and injection of 1,25(OH)(2)D(3) increased gene expression 8 h later. However, the changes in the genes evaluated did not fully explain the differences in serum Ca(2+) seen among the genotypes. In conclusion, mice lacking the full-length CaSR have increased sensitivity to the calcemic action of 1,25(OH)(2)D(3) in the setting of PTH deficiency. This is principally from enhanced 1,25(OH)(2)D(3)-mediated gut Ca(2+) absorption and decreased renal Ca(2+) excretion, without any differences in bone-related release of Ca(2+) or CT secretion among the three genotypes that could explain the differences in their calcemic responses.

Skeletal and hormonal effects of magnesium deficiency.

Magnesium (Mg) is the second most abundant intracellular cation where it plays an important role in enzyme function and trans-membrane ion transport. Mg deficiency has been associated with a number of clinical disorders including osteoporosis. Osteoporosis is common problem accounting for 2 million fractures per year in the United States at a cost of over $17 billion dollars. The average dietary Mg intake in women is 68% of the RDA, indicating that a large proportion of our population has substantial dietary Mg deficits. The objective of this paper is to review the evidence for Mg deficiency-induced osteoporosis and potential reasons why this occurs, including a cumulative review of work in our laboratories and well as a review of other published studies linking Mg deficiency to osteoporosis. Epidemiological studies have linked dietary Mg deficiency to osteoporosis. As diets deficient in Mg are also deficient in other nutrients that may affect bone, studies have been carried out with select dietary Mg depletion in animal models. Severe Mg deficiency in the rat (Mg at <0.0002% of total diet; normal = 0.05%) causes impaired bone growth, osteopenia and skeletal fragility. This degree of Mg deficiency probably does not commonly exist in the human population. We have therefore induced dietary Mg deprivation in the rat at 10%, 25% and 50% of recommended nutrient requirement. We observed bone loss, decrease in osteoblasts, and an increase in osteoclasts by histomorphometry. Such reduced Mg intake levels are present in our population. We also investigated potential mechanisms for bone loss in Mg deficiency. Studies in humans and and our rat model demonstrated low serum parathyroid hormone (PTH) and 1,25(OH)(2)-vitamin D levels, which may contribute to reduced bone formation. It is known that cytokines can increase osteoclastic bone resorption. Mg deficiency in the rat and/or mouse results in increased skeletal substance P, which in turn stimulates production of cytokines. With the use of immunohistocytochemistry, we found that Mg deficiency resulted in an increase in substance P, TNFalpha and IL1beta. Additional studies assessing the relative presence of receptor activator of nuclear factor kB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG), found a decrease in OPG and an increase in RANKL favoring an increase in bone resorption. These data support the notion at dietary Mg intake at levels not uncommon in humans may perturb bone and mineral metabolism and be a risk factor for osteoporosis.

[Chronic kidney disease (CKD) and bone. Impact of diabetes mellitus on the development of CKD-MBD].

Chronic kidney disease-mineral and bone disorder (CKD-MBD) develops as renal function deteriorates. The presence of diabetes mellitus as comorbidity modulates the severity of CKD-MBD. The prevalence of vascular calcification, which becomes higher in diabetic CKD patients than in non-CKD counterparts, increases cardiovascular mortality in diabetic patients. The main factor which causes vascular calcification in diabetic CKD patients is poor glycemic control, in contrast to hyperphosphatemia in non-diabetic CKD patients. Diabetes directly impairs osetoblasts to decrease bone mass, suppresses bone turnover to impair bone quality by impairing secretion of parathyroid hormone and increase AGE-modification of bone collagen. Therefore, therapeutic regimens for CKD-MBD should be considered specifically for diabetic CKD patients since the mode of its development differs between diabetic and non-diabetic CKD patients.

Executive summary of the SEORL CCC-SEEN consensus statement on post-thyroidectomy hypoparathyroidism. / Resumen ejecutivo del documento de consenso SEORL CCC-SEEN sobre hipoparatiroidismo postiroidectomía.

Hypoparathyroidism is the most common complication after total or completion thyroidectomy. It is defined as the presence of hypocalcemia accompanied by low or inappropriately normal parathyroid hormone (PTH) levels. Acute hypocalcemia is a potential lethal complication. Hypocalcemia treatment is based on endovenous or oral calcium supplements as well as oral calcitriol, depending on the severity of the symptoms. The risk of clinical hypocalcemia after bilateral thyroidectomy is considered very low if postoperative intact PTH decrease less than 80% with respect to preoperative levels. These patients could be discharged home without treatment, although this threshold may vary between institutions, and we recommend close surveillance in cases with increased risk (Graves disease, large goiters, reinterventions or evidence of parathyroid gland removal). Long-term treatment objectives are to control the symptoms and to keep serum calcium levels at the lower limit of the normal range, while preserving the calcium phosphate product and avoiding hypercalciuria.

Causes and differential diagnosis of hypocalcemia--recommendation proposed by expert panel supported by ministry of health, labour and welfare, Japan.

Serum calcium (Ca) level is maintained within a narrow range mainly by actions of parathyroid hormone (PTH) and 1,25-dihydroxyvitmain D [1,25(OH)(2)D]. While it is not rare to encounter hypocalcemia in clinical practice, there is currently no practical guideline for the differential diagnosis of hypocalcemia. We therefore propose flowcharts for the differential diagnosis of hypocalcemia and hypoparathyroidism, especially PTH-deficient hypoparathyroidism in which many genetic or other causes have been identified recently. Hypocalcemia can be divided into two categories, hypocalcemia with low serum phosphate level, and one with normal to elevated serum phosphate level. Deficient actions of 1,25(OH)(2)D, loss of Ca into urine, and deposition of Ca in bone or soft tissues are main causes of hypocalcemia with low to low normal serum phosphate level. Hypocalcemia with high normal to high serum phosphate level includes chronic renal failure and hypoparathyroidism. Hypoparathyroidism is subdivided into PTH-deficient hypoparathyroidism and pseudohypoparathyroidism. Recent investigations identified several causes of PTH-deficient hypoparathyroidism, including genetic abnormalities and parathyroid autoantibodies, which should be differentiated from idiopathic hypoparathyroidism. Physical and laboratory findings, the time of the onset of diseases and accompanying illness can be clues for identifying causes of PTH-deficient hypoparathyroidism.