Case Report: Severe Hypocalcemic Episodes Due to Autoimmune Enteropathy.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare monogenic disorder, associated with endocrine deficiencies and non-endocrine involvement. Gastrointestinal (GI) manifestations appear in approximately 25% of patients and are the presenting symptom in about 10% of them. Limited awareness among pediatricians of autoimmune enteropathy (AIE) caused by destruction of the gut endocrine cells in APECED patients delays diagnosis and appropriate therapy. We describe an 18-year-old female presenting at the age of 6.10 years with hypoparathyroidism, oral candidiasis and vitiligo. The clinical diagnosis of APECED was confirmed by sequencing the autoimmune regulator-encoding (AIRE) gene. Several characteristics of the disease-Hashimoto's thyroiditis, Addison's disease, diabetes mellitus type 1 and primary ovarian insufficiency-developed over the years. She had recurrent episodes of severe intractable hypocalcemia. Extensive GI investigations for possible malabsorption, including laboratory analyses, imaging and endoscopy with biopsies were unremarkable. Revision of the biopsies and chromogranin A (CgA) immunostaining demonstrated complete loss of enteroendocrine cells in the duodenum and small intestine, confirming the diagnosis of AIE. Management of hypocalcemia was challenging. Only intravenous calcitriol maintained calcium in the normal range. Between hypocalcemic episodes, the proband maintained normal calcium levels, suggesting a fluctuating disease course. Repeated intestinal biopsy revealed positive intestinal CgA immunostaining. The attribution of severe hypocalcemic episodes to AIE emphasizes the need for increased awareness of this unique presentation of APECED. The fluctuating disease course and repeated intestinal biopsy showing positive CgA immunostaining support a reversible effect of GI involvement. CgA immunostaining is indicated in patients with APECED for whom all other investigations have failed to reveal an explanation for the malabsorption.

Hypocalcemia is associated with adverse clinical course in patients with upper gastrointestinal bleeding.

Acute non-variceal upper gastrointestinal bleeding (NV-UGIB) is associated with significant morbidity and mortality. Early and efficient risk stratification can facilitate management and improve outcomes. We aimed to determine whether the level of ionized calcium (Ca++), an essential co-factor in the coagulation cascade, is associated with the severity of bleeding and the need for advanced interventions among these patients. This was a retrospective single-center cohort study of all patients admitted due to NV-UGIB. The primary outcome was transfusion of ≥ 2 packed red blood cells, arterial embolization, or emergency surgery. Secondary outcomes included (1) transfusion of ≥ 2 packed red blood cells, (2) arterial embolization, or emergency surgery, and (3) all-cause in-hospital mortality. Multivariable logistic regression was performed to determine whether Ca++ was an independent predictor of these adverse outcomes. 1345 patients were included. Hypocalcemia was recorded in 604 (44.9%) patients. The rates of primary adverse outcome were significantly higher in the hypocalcemic group, 14.4% vs. 5.1%, p < 0.001. Secondary outcomes-multiple transfusions, need for angiography or surgery, and mortality were also increased (9.9% vs. 2.3%, p < 0.001, 5.3% vs. 2.8%, p = 0.03, and 33.3% vs. 24.7%, p < 0.001, respectively). Hypocalcemia was an independent predictor of primary and all the secondary outcomes, except mortality. Hypocalcemia in high-risk hospitalized patients with NV-UGIB is common and independently associated with adverse outcomes. Ca++ monitoring in this population may facilitate the rapid identification of high-risk patients. Trials are needed to assess whether correction of hypocalcemia will lead to improved outcomes.

Preoperative Vitamin D Supplementation in Patients With Vitamin D Deficiency Undergoing Total Thyroidectomy.

BACKGROUND: Transient hypocalcemia due to parathyroid gland or vessel manipulation is a common complication following thyroidectomy. Considering the role of 25-hydroxyvitamin D (25(OH)D) in calcium hemostasis, this study aimed to evaluate the effect of preoperative vitamin D supplementation on hypocalcemia incidence in thyroidectomy patients. METHODS: In this randomized clinical trial, 100 patients scheduled for total thyroidectomy and suffering from preoperative moderate or severe vitamin D deficiency were enrolled. Patients were randomly allocated to either study or control groups using the sealed envelope method. Patients in the study group received vitamin D3 50,000-unit pearl weekly for 4 weeks prior to the operation. The control group received placebo. Total and ionized serum calcium levels were checked before surgery, the day after surgery, and 2 weeks postoperatively. RESULTS: No significant difference was observed in terms of demographic data. During serial total calcium checks (5 episodes), total calcium levels changed significantly in patients who had received vitamin D supplements compared to the control group (P = 0.043). Symptomatic hypocalcemia incidence was significantly lower in patients supplemented with 25-hydroxyvitamin D (25(OH)D) (P = 0.04). Also, the requirement for intravenous calcium administration in order to treat the hypocalcemia symptoms was significantly lower in the study in comparison to the control group (P = 0.03). CONCLUSIONS: Vitamin D supplementation in patients with vitamin D deficiency might lead to a lower incidence of early-onset symptomatic hypocalcemia; hence, requiring less calcium supplementation for the management of hypocalcemia.

Hungry bone syndrome after parathyroidectomy in end-stage renal disease patients: review of an alkaline phosphatase-based treatment protocol.

AIM: Hyperparathyroidism in chronic kidney disease-mineral and bone disorder is associated with significant morbidity and mortality. Parathyroidectomy is widely carried out as treatment despite complications such as hypocalcaemia post-surgery. Our centre has been using an ALP-based protocol to replace calcium postoperatively to prevent hypocalcaemia. We aim to describe and audit our calcium replacement protocol post-parathyroidectomy METHODS: We, retrospectively, analyse 167 end-stage kidney disease patients who had parathyroidectomy with auto-implantation in Singapore General Hospital between January 2008 and December 2013. Their calcium replacement postoperatively was initiated upon patient arrival back in ward on the same day of surgery based on their pre-op ALP prior to occurrence of hypocalcaemia. Patient demographics, surgical and laboratory parameters were reviewed from medical records. Changes in calcium postoperatively were reported to look for incidence of calcium derangement. RESULTS: Mean calcium levels between pre-operation day and post-operation day 7 ranged from 2.31 to 2.70 mmol/L. Decline in serum calcium was common in all patients prior to starting calcium replacement. Eighteen patients (10.9%) experienced hypocalcaemia immediately post-operation prior to commencement of IV calcium replacement. Patients with immediate post-operation hypocalcaemia had lower pre-operation calcium but higher pre-operation alkaline phosphatase (ALP) and pre-operation intact parathyroid hormone. Hypercalcaemia is common likely from aggressive IV calcium replacement using the protocol. The average length of stay for patients prior to calcium stabilization and discharge was 9 days. CONCLUSION: Implementation of an ALP-based prophylactic calcium replacement protocol with daily serum calcium monitoring can ameliorate severe hypocalcaemia post-parathyroidectomy.

Hypocalcemic cardiomyopathy: a rare presenting manifestation of hypoparathyroidism.

Hypoparathyroidism patients present with features of hypocalcemia like carpopedal spasm, numbness and paresthesias but hypocalcemic cardiomyopathy leading to congestive heart failure (CHF) is a rare presentation. We present here a case of 55-year-old Asian man who was a known case of dilated cardiomyopathy for 6 months, presented with the chief complaints of shortness of breath on exertion and decreased urine output. On general physical examination, features suggestive of CHF were seen. Chvostek and Trousseau's sign was positive. The patient had a history of cataract surgery of both eyes 15 years ago. Further investigations revealed hypocalcemia. Echo showed severe global hypokinesia of left ventricle with left ventricle ejection fraction 15%. This CHF was refractory to conventional treatment, though, with calcium supplementation, the patient improved symptomatically. On follow-up after 3 months, an improvement was seen in the echocardiographic parameters with ejection fraction improving to 25%.

Comparison of hypocalcemia rates between LigaSure and clamp-and-tie hemostatic technique in total thyroidectomies.

BACKGROUND: Postoperative hypocalcemia (PH) is a serious complication after total thyroidectomy. This study aimed to compare PH rates between LigaSure Small Jaw (LSJ) and clamp-and-tie hemostatic technique in patients undergoing total thyroidectomy. METHODS: Four hundred twenty patients were divided into two groups: group L (210 patients) performed with LSJ and group C (210 patients) with clamp-and-tie technique. Serum ionized calcium (iCa) was measured before and 12, 24, 48, 72 hours after surgery. PH was defined as iCa lower than 4.2 mg/dL in at least two measurements. RESULTS: There was no significant difference between groups in sex, age, extent of surgery, pathology, and the strategy of intraoperative management of parathyroid glands (PG). The PH rate was significantly lower in group L compared to group C (22.9% vs 32.4%, P = .03). CONCLUSIONS: Compared to clamp-and-tie technique, LigaSure is superior to decrease PH rate after total thyroidectomy.

Impaired residual renal function predicts denosumab-induced serum calcium decrement as well as increment of bone mineral density in non-severe renal insufficiency.

Denosumab treatment of osteoporotic patients, except those with severe renal insufficiency, reduced cCa levels. Low baseline cCa, low estimated glomerular filtration rate, and high bone turnover increased the risk of lower cCa, while increasing bone mineral density. Pretreatment with antiresorptive agents was beneficial in reducing the risk of hypocalcemia. INTRODUCTION: Although denosumab-induced hypocalcemia has been frequently observed in patients with chronic kidney disease (CKD) stages 4-5D being treated with denosumab for osteoporosis, few studies have assessed the risk factors for serum-corrected calcium (cCa) reductions in patients with non-severe renal insufficiency. This study assessed the risk factors for reduced cCa concentration following denosumab administration and analyzed factors predictive of changes in bone mineral density (BMD). METHODS: Seventy-seven osteoporotic patients, not including those with CKD stages 4-5D, were treated with 60 mg denosumab once every 6 months. Biochemical parameters and BMD were analyzed from prior to the initial dose until 1 month after the second dose. RESULTS: Following the first administration of denosumab, cCa levels decreased, reaching a minimum on day 7. Multiple linear regression analyses showed that baseline cCa, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, tartrate-resistant acid phosphatase-5b (TRACP-5b), and bone alkaline phosphatase (BAP) or pretreatment with antiresorptive agents were significant factors independently associated with the absolute reduction in cCa from baseline to day 7 (ΔcCa0-7 days). ΔcCa0-7 days after the second dose of denosumab was significantly lower than that after the first dose. After 6 months of denosumab treatment, both LS-BMD and FN-BMD significantly increased from baseline. LS-BMD and FN-BMD correlated significantly with baseline TRACP-5b or BAP and eGFR, respectively. CONCLUSIONS: Both low eGFR and high bone turnover were independent risk factors for denosumab-induced cCa decrement, and for increases in BMD. Pretreatment with antiresorptive agents may reduce the risk of hypocalcemia.

The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases.

The Ca2+-sensing receptor (CaSR) is a dimeric family C G protein-coupled receptor that is expressed in calcitropic tissues such as the parathyroid glands and the kidneys and signals via G proteins and ß-arrestin. The CaSR has a pivotal role in bone and mineral metabolism, as it regulates parathyroid hormone secretion, urinary Ca2+ excretion, skeletal development and lactation. The importance of the CaSR for these calcitropic processes is highlighted by loss-of-function and gain-of-function CaSR mutations that cause familial hypocalciuric hypercalcaemia and autosomal dominant hypocalcaemia, respectively, and also by the fact that alterations in parathyroid CaSR expression contribute to the pathogenesis of primary and secondary hyperparathyroidism. Moreover, the CaSR is an established therapeutic target for hyperparathyroid disorders. The CaSR is also expressed in organs not involved in Ca2+ homeostasis: it has noncalcitropic roles in lung and neuronal development, vascular tone, gastrointestinal nutrient sensing, wound healing and secretion of insulin and enteroendocrine hormones. Furthermore, the abnormal expression or function of the CaSR is implicated in cardiovascular and neurological diseases, as well as in asthma, and the CaSR is reported to protect against colorectal cancer and neuroblastoma but increase the malignant potential of prostate and breast cancers.

Outpatient versus inpatient thyroidectomy: A systematic review and meta-analysis.

BACKGROUND: Outpatient thyroidectomy has gained popularity due to improved resource utilization. METHODS: We conducted a systematic review and meta-analysis using MEDLINE, EMBASE, CINAHL, Web of Science, and the Cochrane library. We included all studies examining the outcomes of outpatient thyroidectomy as compared with those of inpatient thyroidectomy. Risk of bias was assessed using the Newcastle-Ottawa scale. Postoperative complications (hematoma, hypocalcemia, and recurrent laryngeal nerve injury) and readmission/reintervention rates were compared. RESULTS: After screening 1665 records, 10 nonrandomized observational studies were included. There were fewer complication rates in the outpatient group than the inpatient group (relative risk [RR] 0.56; 95% confidence interval [CI] 0.37-0.83). There was no difference in readmission/reintervention rates (RR 0.60; 95% CI 0.33-1.09). CONCLUSION: The results suggest outpatient thyroidectomy may be as safe as inpatient thyroidectomy in appropriately selected patients. The results are limited by high risk of bias. Well-designed prospective studies are necessary to further assess the safety of outpatient thyroidectomy.

Carpal spasm in a girl as initial presentation of celiac disease: a case report.

BACKGROUND: Celiac disease is an immune-mediated disorder elicited by ingestion of gluten in genetically susceptible persons. This disorder is characterized by specific histological changes of the small intestine mucosa resulting in malabsorption. This case was written up as it was an unusual and dramatic presentation of celiac disease. CASE PRESENTATION: We report the case of a 3-year-old Albanian girl who presented at our clinic with carpal spasms and hand paresthesia. A physical examination at admission revealed a relatively good general condition and body weight of 10.5 kg (10 percentile). Carpal spasms and paresthesias of her extremities were present. Neuromuscular irritability was demonstrated by positive Chvostek and Trousseau signs. Blood tests showed severe hypocalcemia with a total serum calcium of 1.2 mmol/L (normal range 2.12 to 2.55 mmol/L), ionized calcium of 0.87 (normal range 1.11 to 1.30 mmol/L), and 24-hour urine calcium excretion of 9.16 mmol (normal range female <6.2 mmol/day). Among other tests, screening for celiac disease was performed: antigliadin immunoglobulin A, anti-tissue transglutaminase, and anti-endomysial immunoglobulin A antibodies were positive. A duodenal biopsy revealed lymphocyte infiltration, crypt hyperplasia, and villous atrophy compatible with celiac disease grade IIIb according to the Marsh classification. Following the diagnosis of celiac disease, human leukocyte antigen typing was performed, giving a definite diagnosis of celiac disease. She was started on a gluten-free diet. Due to failure to follow a gluten-free diet, episodes of carpal spasms appeared again. Unfortunately, at the age of 7 years she presents with delayed psychophysical development. CONCLUSIONS: Although hypocalcemia is a common finding in celiac disease, hypocalcemic carpal spasm is a rare initial manifestation of the disease. Therefore, the possibility of celiac disease should be considered in patients with repeated carpal spasms that seem unduly difficult to treat. This should be evaluated even in the absence of gastrointestinal symptoms since hypocalcemia and its manifestation may present as initial symptoms of celiac disease even in young children.

Morbidity of central compartment clearance: Comparison of lesser versus complete clearance in patients with thyroid cancer.

BACKGROUND: Extent of central compartment neck dissection (CCND) in thyroid cancers has been a debate because of associated morbidity. There have been attempts to reduce the extent of surgery in an attempt to decrease morbidity. PATIENTS AND METHODS: We analyzed the morbidity of CCND from our prospectively maintained surgical morbidity database. CCND was divided into bilateral complete clearance (BCC) and less than complete clearance (LCC). LCC was performed for clinicoradiologically node negative patients. Rates of hypocalcemia and recurrent laryngeal nerve (RLN) palsy rates were compared for LCC versus BCC. We also classified procedures performed in the central neck according to the extent of dissection. RESULTS: Of 153 evaluable patients, BCC was performed in 43.8% and LCC in 56.2%. Rate of postoperative hypocalcemia was 40.2% in BCC group versus 17.4% in LCC group. We had an overall RLN palsy rate of 7.4%. There was no significant difference in RLN palsy rates between the groups. CONCLUSION: Lesser extent of dissection in central compartment reduces postoperative hypocalcemia but has no influence on RLN palsy rates.

Preoperative vitamin D level as predictor of post-thyroidectomy hypocalcemia in patients sustaining transient parathyroid injury.

BACKGROUND: Several studies have sought to identify predictors of postoperative hypocalcemia after total thyroidectomy; however, there have been conflicting results regarding the impact of preoperative vitamin D deficiency. METHODS: The medical records of patients undergoing total thyroidectomy were retrospectively reviewed. The number of parathyroid glands identified or reimplanted at the time of surgery was used as a marker of transient parathyroid gland damage. RESULTS: Sixty-seven patients were included in the study. Vitamin D deficiency was a significant predictor of hypocalcemia in patients in whom ≥3 parathyroid glands were identified, but not in patients in whom 0-2 parathyroid glands were identified intraoperatively (odds ratio [OR] 5.8; P = .036). CONCLUSION: Vitamin D deficiency is a significant predictor of postoperative hypocalcemia in patients in whom ≥3 parathyroid glands are identified intraoperatively, but not in patients who sustain minimal transient damage to the parathyroid glands.

MicroRNAs in parathyroid physiopathology.

Parathyroid glands regulate calcium homeostasis through synthesis and secretion of parathormone (PTH). They sense the extracellular calcium concentration through the G-protein coupled calcium sensing receptor (CASR) and release PTH in order to preserve calcium concentration in the physiological range. Tumors of the parathyroid glands are common endocrine neoplasia associated with primary or secondary/tertiary hyperparathyroidisms. Small non-coding RNAs are regulators of gene expression able to modulate hormone synthesis, hormone release and endocrine cell proliferation. In this scenario, microRNA (miRNA) expression profiles have been investigated in parathyroid tumors, while miRNAs are involved in hypocalcemia and uremia-induced PTH release from normal parathyroid cells. Here we reviewed data about the role of miRNAs in the regulation of: 1) PTH synthesis and secretion; 2) CASR expression; 3) parathyroid cell tumorigenesis. Though studies about miRNAs in parathyroid gland pathophysiology are limited, they contribute in elucidating regulatory pathways involved in PTH release and parathyroid cell tumorigenesis.

Risk stratification for outpatient parathyroidectomy and predictors of postoperative complications.

INTRODUCTION: The mainstay of treatment for primary hyperparathyroidism is surgery. Hypocalcemia after parathyroidectomy is common and poses a significant challenge, leading to increased patient morbidity and health care costs. While several groups have found predictor factors for hypocalcemia, none have created a risk stratification model. Here, we recognize important factors and optimal cut-off values that can allow risk stratification of patients. METHODS: A single-institution retrospective chart review of 339 patients that underwent parathyroidectomy from 2009 to 2012 was conducted. Pre-operative, intra-operative, and post-operative data were collected. A non-routine outcome was defined as post-operative admission, outpatient hypocalcemia-related complication, or inpatient hypocalcemia-related complication. The preoperative or intraoperative factors of patients that experienced a non-routine outcome were compared to those that did not. Optimal cut-off values were determined for preoperative and intraoperative factors and a risk stratification method was created. RESULTS: A total of 39 patients experienced a non-routine outcome including 24 postoperative admissions, 2 inpatient hypocalcemia-related complications, and 17 outpatient hypocalcemia-related complications. Patients with a non-routine outcome displayed a trend toward preoperative hypercalcemia (calcium >11.0mg/dL) than not (p=0.0543). The median preoperative parathyroid hormone (PTH) level was significantly higher among patients with a non-routine outcome (p=0.0037). Furthermore, the median percent decrease in PTH at 20min intraoperatively among patients with a non-routine outcome was significantly higher compared to those that did not (p=0.0421). The optimal cut-off value for preoperative PTH was 129pg/mL and for median percent decrease in intraoperative PTH at 20min was 90.7% for predicting a non-routine outcome. A risk stratification model was created based on these data. CONCLUSION: Our analysis reveals that patients with larger intraoperative decrease in PTH levels (greater than 90.7% drop at 20min), higher preoperative hypercalcemia (greater than 11mg/dL), and higher preoperative PTH levels (greater than 129pg/mL) are more likely to experience a non-routine outcome during outpatient parathyroidectomy. Patients can be risk stratified based on this criteria.

Parathyroid responsiveness during hypocalcemia after total parathyroidectomy and autotransplantation in patients with renal hyperparathyroidism. / Responsividade paratireoideana à hipocalcemia após paratireoidectomia total com autoimplante em portadores de hiperparatireoidismo associado à doença renal crônica.

INTRODUCTION: Hyperparathyroidism is a frequent complication of chronic kidney disease (CKD). Total parathyroidectomy (PTX) with parathyroid tissue autotransplantation (AT) is a treatment option in those individuals that do not respond to clinical management. OBJECTIVE: To evaluate grafted parathyroid tissue response during induced hypocalcemia among CKD patients who underwent total PTX with AT. METHODS: Eighteen patients with renal hyperparathyroidism were submitted to total PTX with parathyroid AT selected by stereomicroscopy between April and October 2008. Eleven (eight with successful kidney transplantation, 2 in peritoneal dialysis and 1 in hemodialysis) were clinically stable and eligible for testing. Hypocalcemia was induced using sodium bicarbonate infusion in 5 healthy controls and in patients 6-12 months after surgery. RESULTS: Among controls, hypocalcemia elicited a major rise in intact PTH (iPTH) levels 4 minutes after bicarbonate infusion. In patients, a significant decrease in ionized calcium concentration was observed [from 1.17 ± 0.12 to 1.09 ± 0.11 mean (± SE) mmol/L] in the 4th minute (p < 0.001) illustrating the nadir point. In the 10thminute, ionized calcium did not show a statistical increase compared to the 4th minute (p = 0.451). The iPTH levels ranged from 34.8 ± 18.6 to 34.1 ± 18.8 pg/mL (similar values between base line and 4thminute p = 0.087) and did not change in the 10th minute (33.3 ± 19,6 pg/ mL p = 0.693). CONCLUSION: Among CKD patients tested 6-12 months after surgery, grafted parathyroid tissue revealed a blunted secretory capacity during bicarbonate induced hypocalcemia with no changes in iPTH levels.

Denosumab-associated hypocalcaemia: incidence, severity and patient characteristics in a tertiary hospital setting.

PURPOSE: Denosumab-associated hypocalcaemia (DAH) has been reported in patients with osteoporosis or metastatic bone disease and is associated with stages 4 and 5 chronic kidney disease (CKD, estimated glomerular filtration rate <30 mL/min/1.73m2 ). Other risk factors for hypocalcaemia have not been fully elucidated. We aimed to investigate the incidence of hypocalcaemia amongst patients receiving denosumab and to identify clinical features associated with this adverse event. METHODS: Retrospective cohort study between June 2013 and June 2014 of patients administered denosumab (60/120 mg) at a tertiary hospital in Melbourne, Australia, to identify the incidence of an albumin-adjusted serum calcium concentration <2.10 mmol/L or ionized calcium <1.13 mmol/L within 6 months of treatment. Univariable and multivariable logistic regression analyses were performed to identify clinical features associated with DAH. RESULTS: One hundred and fifty-five patients were administered denosumab (100 osteoporosis, 55 bone metastases). Twenty-two patients (14% [95%CI 9.1-20.7]) developed hypocalcaemia: 55% were men, and 55% had osteoporosis. Eighty-six per cent had a 25-hydroxyvitamin D concentration >50 nmol/L, and 91% were on calcium/colecalciferol supplementation. Stages 4 and 5 CKD (adjusted odd ratio [aOR] 4.71, 95%CI 1.61-13.79, p = 0.005) and male sex (aOR 4.30, 95%CI 1.69-10.96, p = 0.002) were associated with DAH. No patients were documented as having hypocalcaemic symptoms. One patient received intravenous calcium gluconate treatment. CONCLUSIONS: The incidence of denosumab-associated hypocalcaemia was 14% (95%CI 9.1-20.7) within 6 months of treatment despite widespread use of appropriate calcium/colecalciferol supplementation. Stages 4 and 5 CKD and male sex were associated with subsequent hypocalcaemia. Copyright © 2016 John Wiley & Sons, Ltd.

Responsividade paratireoideana à hipocalcemia após paratireoidectomia total com autoimplante em portadores de hiperparatireoidismo associado à doença renal crônica / Parathyroid responsiveness during hypocalcemia after total parathyroidectomy and autotransplantation in patients with renal hyperparathyroidism

Resumo Introdução: O hiperparatireoidismo é uma complicação frequente da doença renal crônica (DRC). A paratireoidectomia (PTX) total com autotransplante (AT) de tecido paratireoideano é uma opção terapêutica para os indivíduos que não respondem ao manejo clínico. Objetivo: Avaliar a resposta do tecido paratireoideano enxertado durante hipocalcemia induzida em pacientes portadores de DRC submetidos à PTX total com AT. Métodos: Dezoito pacientes portadores de hiperparatiroidismo associado à DRC foram submetidos à PTX total com AT de tecido paratireoideano selecionado por estereomicroscopia entre Abril e Outubro de 2008 em nosso serviço. Onze indivíduos (oito com transplante renal funcionante, 2 em diálise peritoneal e 1 em hemodiálise) apresentavam boa condição clínica e foram elegíveis para o teste. Induziu-se hipocalcemia por infusão de bicarbonato de sódio em 5 controles normais e nos pacientes 6-12 meses após a PTX. Resultados: A hipocalcemia determinou um aumento importante dos níveis de PTH intacto (iPTH) no grupo controle 4 minutos após a infusão de bicarbonato. Nos pacientes, houve uma redução significativa do cálcio ionizado [de 1,17 ± 0,12 para 1,09 ± 0,11 (media ± EP) mmol/L] no 4º minuto (p < 0,001) ilustrando o nadir do teste. No 10º minuto não houve elevação do cálcio ionizado comparado ao 4º minuto (p = 0,451). Os níveis de iPTH foram de 34,8 ± 18,6 para 34,1 ± 18,8 pg/mL (valor basal semelhante ao 4º minuto p = 0,087) e se mantiveram no 10º minuto (33,3 ± 19,6 pg/mL p = 0,693). Conclusão: Em pacientes portadores de DRC testados 6-12 meses depois da cirurgia, o enxerto de tecido paratireoideano revelou incapacidade de resposta à hipocalcemia induzida por bicarbonato sem mudança dos níveis de iPTH.

Abstract Introduction: Hyperparathyroidism is a frequent complication of chronic kidney disease (CKD). Total parathyroidectomy (PTX) with parathyroid tissue autotransplantation (AT) is a treatment option in those individuals that do not respond to clinical management. Objective: To evaluate grafted parathyroid tissue response during induced hypocalcemia among CKD patients who underwent total PTX with AT. Methods: Eighteen patients with renal hyperparathyroidism were submitted to total PTX with parathyroid AT selected by stereomicroscopy between April and October 2008. Eleven (eight with successful kidney transplantation, 2 in peritoneal dialysis and 1 in hemodialysis) were clinically stable and eligible for testing. Hypocalcemia was induced using sodium bicarbonate infusion in 5 healthy controls and in patients 6-12 months after surgery. Results: Among controls, hypocalcemia elicited a major rise in intact PTH (iPTH) levels 4 minutes after bicarbonate infusion. In patients, a significant decrease in ionized calcium concentration was observed [from 1.17 ± 0.12 to 1.09 ± 0.11 mean (± SE) mmol/L] in the 4th minute (p < 0.001) illustrating the nadir point. In the 10thminute, ionized calcium did not show a statistical increase compared to the 4th minute (p = 0.451). The iPTH levels ranged from 34.8 ± 18.6 to 34.1 ± 18.8 pg/mL (similar values between base line and 4thminute p = 0.087) and did not change in the 10th minute (33.3 ± 19,6 pg/ mL p = 0.693). Conclusion: Among CKD patients tested 6-12 months after surgery, grafted parathyroid tissue revealed a blunted secretory capacity during bicarbonate induced hypocalcemia with no changes in iPTH levels.

Is calcitonin an active hormone in the onset and prevention of hypocalcemia in dairy cattle?

The objective of this study was to assess the potential importance of calcitonin (CALC) in the onset of subclinical hypocalcemia (experiment 1) and in the physiological mechanisms underlying the prevention of bovine hypocalcemia under metabolic acidosis (experiments 2 and 3). In experiment 1, 15 Holstein cows naturally incurring subclinical hypocalcemia during the first 5d postpartum were classified as low subclinical hypocalcemia (LSH) when blood Ca concentrations were between 7.5 and 8.5mg/dL, or as high subclinical hypocalcemia (HSH) when blood Ca concentrations were between 6.0 and 7.6 mg/dL. Blood samples were taken daily from d -5 to 5 relative to parturition to determine concentrations of parathyroid hormone (PTH), CALC, and 1,25(OH)2D3. In experiment 2, 24 Holstein bulls (497 ± 69 kg of body weight and 342 ± 10.5d of age) were assigned to 2 treatments (metabolic acidosis or control). Metabolic acidosis was induced by an oral administration of ammonium chloride (2.5 mEq/d) during 10 d, and animals were slaughtered thereafter. Blood samples were collected before slaughter to determine CALC, PTH, 1,25(OH)2D3, and samples of urine, kidney, parathyroid, and thyroid glands were obtained immediately after slaughter to determine expression of several genes in these tissues. Last, in experiment 3, we tested the activity of CALC under metabolic acidosis in vitro using breast cancer cell (T47D) cultures. Although PTH tended to be greater in HSH than in LSH, the levels of 1,25(OH)2D3 were lower in HSH cows (experiment 1). Blood CALC concentration was not affected by the severity of subclinical hypocalcemia, but it was influenced by days from calving (experiment 1). The expression of PTH receptor (PTHR) in the kidney was increased under metabolic acidosis (experiment 2). Furthermore, the activity of CALC was impaired under acidic blood pH (experiment 3). In conclusion, the CALC rise in HSH cows after calving impaired the recovery of blood Ca concentrations because the PTHR response was not sufficient to activate 1,25(OH)2D3 and compensate for the CALC effect. Metabolic acidosis prevents hypocalcemia because the expression of PTHR is upregulated in the kidney, resulting in an increased PTH activity and a subsequent increase in 1,25(OH)2D3 serum concentrations. Moreover, an impairment of CALC activity at low pH enhances the hypercalcemic role of PTH.

Post-thyroidectomy complications. The role of the device: bipolar vs ultrasonic device: Collection of data from 1,846 consecutive patients undergoing thyroidectomy.

BACKGROUND: Specific complications after thyroid surgery, such as recurrent laryngeal nerve injury (RLN) or hypoparathyroidism, are feared because they may give rise to a lifelong disability for the patient. The aim of this study was to evaluate the possible association between the types of device used (bipolar vs ultrasound-based harmonic scalpel defined Harmonic Focus) and major postoperative complications. METHODS: During a 1-year period, between October 2010 and October 2011, Italian Endocrine Surgery Units affiliated with the Italian Endocrine Surgery Units Association collected data on all consecutive patients older than 18 years who had undergone primary total thyroidectomy, near total thyroidectomy, and completion thyroidectomy. The data were included in a dataset, listing demographic variables, details on the surgical procedure, and 2 major complications of the thyroid surgery: postoperative RLN palsy/hypomobility and hypocalcemia. RESULTS: Our population comprised 1,846 subjects (78.6% women, median age 52 years). Six hundred four (32.7%) subjects underwent thyroidectomy by bipolar forceps and 1,242 (67.3%) by ultrasonic device. The risk of hypocalcemia in subjects undergoing thyroidectomy by ultrasonic device was similar to those undergoing thyroidectomy by bipolar after adjusting for sex, type of thyroidectomy, and central lymphadenectomy (odds ratio .94, 95% confidence interval .76 to 1.17). Subjects who underwent thyroidectomy by ultrasonic device had a lower risk of RLN paralysis compared with those undergoing thyroidectomy by bipolar forceps also after adjusting for central lymphadenectomy (odds ratio .39, 95% confidence interval .2 to .7). CONCLUSION: This multicenter study acknowledges the value of the ultrasonic device as a protective factor only for RLN palsy, confirming nodal dissection as a risk factor for postoperative hypocalcemia and vocal folds disorders.