Novel Glial Cells Missing-2 (GCM2) variants in parathyroid disorders.

OBJECTIVE: The aim of this study was to analyze variants of the gene glial cells missing-2 (GCM2), encoding a parathyroid cell-specific transcription factor, in familial hypoparathyroidism and in familial isolated hyperparathyroidism (FIHP) without and with parathyroid carcinoma. DESIGN: We characterized 2 families with hypoparathyroidism and 19 with FIHP in which we examined the mechanism of action of GCM2 variants. METHODS: Leukocyte DNA of hypoparathyroid individuals was Sanger sequenced for CASR, PTH, GNA11 and GCM2 mutations. DNA of hyperparathyroid individuals underwent MEN1, CDKN1B, CDC73, CASR, RET and GCM2 sequencing. The actions of identified GCM2 variants were evaluated by in vitro functional analyses. RESULTS: A novel homozygous p.R67C GCM2 mutation which failed to stimulate transcriptional activity in a luciferase assay was identified in affected members of two hypoparathyroid families. Oligonucleotide pull-down assay and in silico structural modeling indicated that this mutant had lost the ability to bind the consensus GCM recognition sequence of DNA. Two novel (p.I383M and p.T386S) and one previously reported (p.Y394S) heterozygous GCM2 variants that lie within a C-terminal conserved inhibitory domain were identified in three affected individuals of the hyperparathyroid families. One family member, heterozygous for p.I138M, had parathyroid carcinoma (PC), and a heterozygous p.V382M variant was found in another patient affected by sporadic PC. These variants exerted significantly enhanced in vitrotranscriptional activity, including increased stimulation of the PTH promoter. CONCLUSIONS: We provide evidence that two novel GCM2 R67C inactivating mutations with an inability to bind DNA are causative of hypoparathyroidism. Additionally, we provide evidence that two novel GCM2 variants increased transactivation of the PTH promoter in vitro and are associated with FIHP. Furthermore, our studies suggest that activating GCM2 variants may contribute to facilitating more aggressive parathyroid disease.

Renal complications and quality of life in postsurgical hypoparathyroidism: a case-control study.

PURPOSE: Conventional therapy (calcium and activated vitamin D) does not restore calcium homeostasis in patients with chronic hypoparathyroidism (HypoPT) and is associated with renal complications and reduced quality of life (QoL). The aim of this study was to evaluate in a case-control, cross-sectional study, the rate of renal complications and QoL in two sex- and age-matched cohort of patients with differentiated thyroid cancer with (n = 89) and without (n = 89) chronic post-operative HypoPT (PoHypoPT) and their relationship with the biochemical control of the disease. METHODS: Serum and urinary parameters, renal ultrasound and QoL were assessed by SF-36 and WHO-5 questionnaires. RESULTS: Forty-three (48.3%) PoHypoPT patients reported symptoms of hypocalcemia. Twenty-six (29.2%) patients were at target for all 6 parameters, 46 (51.6%) for 5. The most frequently unmet targets were gender-specific 24-h urinary calcium (44.9%) and serum calcium (37.1%). Serum phosphate, magnesium and 25(OH)D were in the normal range in > 90% of patients. Renal calcifications were found in 26 (29.2%) patients, with no correlation with 24-h urinary calcium. eGFR did not differ between patients and controls. Conversely, patients had a significant higher rate of renal calcifications and a lower SF-36, but not WHO-5, scores. SF-36 scores did not differ between PoHypoPT patients who were, or not, hypocalcemic. CONCLUSIONS: Our study shows that the rate of renal calcifications was higher in patients with PoHypoPT than in those without. This finding, together with the reduced QoL and the presence of hypocalcemic symptoms in about half patients, underscores that the treatment of chronic HypoPT with conventional therapy is suboptimal.

Discovery of a Long-Acting Parathyroid Hormone 1-34 Analogue to Treat Hypoparathyroidism.

Hypoparathyroidism (HP) is a rare disease with clinical manifestations of hypocalcemia and hyperphosphatemia, resulting from deficient or absent parathyroid hormone (PTH) secretion. Conventional treatment for patients with HP involves extensive calcium and vitamin D supplementation. In 2015, PTH1-84 was approved by the United States Food and Drug Administration as an adjunct for HP patients who cannot be well-controlled on conventional treatment. However, PTH1-84 therapy requires a daily injection, leading to poor patient compliance. The purpose of this study was to develop a long-acting PTH1-34 analogue by increasing its affinity to albumin. Three PTH1-34 variants were generated by substituting two of the three lysine (Lys) residues with arginine, reserving a single Lys as the modification site in each sequence. A series of side chains, containing fatty acid, deoxycholic acid, or biotin groups, were synthesized to modify these PTH1-34 variants by using a solid-liquid phase synthesis approach. In vitro bioactivity and albumin affinity tests were used to screen these new PTH1-34 analogues. Finally, Lys27-AAPC was selected from 69 synthesized analogues as a candidate therapeutic compound because it retained potency and exhibited a high albumin-binding capacity. In pharmacodynamic experiments, Lys27-AAPC demonstrated enhanced and prolonged efficacy in serum calcium elevating relative to PTH1-84. Moreover, a lyophilized powder for injection containing Lys27-AAPC was developed for further testing and represented a potential long-acting HP treatment.

Near-Infrared Autofluorescence Imaging May Reduce Temporary Hypoparathyroidism in Patients Undergoing Total Thyroidectomy and Central Neck Dissection.

Background: Near-infrared autofluorescence (NIRAF) imaging is known to reduce the incidence of post-thyroidectomy hypocalcemia. However, there are no studies on how much NIRAF imaging affects the serum parathyroid hormone (PTH) level after surgery. We investigated the changes of the serum PTH level and ionized calcium (iCa.) in patients undergoing total thyroidectomy with central neck dissection (CND). Materials and Methods: This retrospective study with historical control enrolled 542 patients who underwent total thyroidectomy with CND. Patients were divided into two groups: the NIRAF group (261 patients) and the control group (281 patients). PTH and iCa. levels were measured at the hospital stay, 1, 3, and 6 months after surgery. In addition, the number of identified parathyroid glands (PGs), autotransplanted PGs, and the inadvertent resection rate of PGs was evaluated. Results: The incidence of postoperative hypoparathyroidism (PTH <15 pg/mL) was significantly lower in the NIRAF group during the hospitalization (88 patients: 33.7% vs. 131 patients: 46.6%; p = 0.002) and at 1 month postoperatively (23 patients: 8.8% vs. 53 patients: 18.9%; p = 0.001). There was no difference in the permanent hypoparathyroidism rate (6 months after surgery) between the NIRAF group and the control group (4.2% vs. 4.6%; p = 0.816). There was no difference in the incidence of hypocalcemia (iCa. <1.09 mmol/L) (during hospitalization: 6.5% vs. 10.0%; 1 month: 2.3% vs. 2.5%; 3 months: 0.8% vs. 0.7%; 6 months after surgery: 1.1% vs. 1.1%) between the two groups. The number of inadvertently resected PGs was significantly lower in the NIRAF group (18:6.9% vs. 36:12.8%; p = 0.021). Conclusions: These results suggest that NIRAF imaging may reduce temporary hypoparathyroidism and the risk of inadvertent resection of PGs in patients undergoing total thyroidectomy with CND.

Basal Ganglia Calcification Is Associated With Local and Systemic Metabolic Mechanisms in Adult Hypoparathyroidism.

CONTEXT: Hypoparathyroidism is characterized by low serum calcium, increased serum phosphorus, and inappropriately low or decreased serum parathyroid hormone, which may be associated with soft tissue calcification in the basal ganglia of the brain. OBJECTIVE: To assess the prevalence and factors involved in the pathophysiology of basal ganglia calcification (BGC) in the brain in chronic hypoparathyroidism and to evaluate proposed pathophysiologic mechanisms. DESIGN: Case-control study with retrospective review of medical records over 20 years. SETTING: Single academic medical center. PATIENTS: 142 patients with chronic hypoparathyroidism and computed tomography (CT) head scans followed between January 1, 2000 and July 9, 2020, and 426 age- and sex-matched controls with CT head scans over the same interval. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Demographic, biochemical, and CT head imaging findings, with semiquantitative assessment of volumetric BGC. RESULTS: The study found that 25.4% of 142 patients followed for a median of 17 years after diagnosis of chronic hypoparathyroidism had BGC, which developed at a younger age than in controls. BGC was 5.1-fold more common in nonsurgical patients and less common in postsurgical patients. Low serum calcium and low calcium/phosphate ratio correlated with BGC. Neither serum phosphorus nor calcium × phosphate product predicted BGC. Lower serum calcium was associated with greater volume of BGC. The extent of BGC varied widely, with nonsurgical patients generally having a greater volume and distribution of calcification. CONCLUSIONS: BGC is associated with low serum calcium and low serum calcium/phosphate ratio, which may be related to severity of the disease, its etiology, or duration of treatment.

Impaired Immune Function in Patients With Chronic Postsurgical Hypoparathyroidism: Results of the EMPATHY Study.

CONTEXT: Despite the pivotal role of calcium signaling in immune response, little is known about immune function in patients affected by hypoparathyroidism. OBJECTIVE: This work aimed to evaluate immune function in hypoparathyroidism. METHODS: The Evaluation of iMmune function in Postsurgical and AuToimmune HYpoparathyroidism (NCT04059380) is a case-control, cross-sectional study set in an Italian referral center. Participants included 20 patients with postsurgical hypoparathyroidism (12 females) and 20 age- and sex-matched controls. Main outcome measures included calcium metabolism assessment, peripheral blood mononuclear cells (PBMC) profiling via flow cytometry, parathyroid hormone receptor 1 (PTHr1) expression analysis using immunofluorescence and PrimeFlow RNA assay, gene expression analysis via real-time polymerase chain reaction, cytokine measurement, and evaluation of infectious disease frequency and severity. RESULTS: Immune cell profiling revealed decreased monocytes, regulatory, naive, and total CD4+ T lymphocytes, which correlated with total calcium, ionized calcium, and PTH levels, in patients with hypoparathyroidism. Patients with hypoparathyroidism had a higher CD3-CD56+ natural killer (NK) cell count, which inversely correlated with calcium, PTH, and vitamin D levels. Furthermore, they exhibited decreased tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor gene expression and decreased circulating TNF levels. Gene expression and immunofluorescence analysis confirmed PTHr1 expression in all PBMC lineages; however, the percentage of cells expressing PTHr1 was lower, whereas the intensity of PTHr1 expression in monocytes, total T lymphocytes, CD8+CD4+ and CD4+ T lymphocytes, and total NK cells was higher in patients with hypoparathyroidism. CONCLUSIONS: This study describes for the first time the immune alterations in patients with hypoparathyroidism receiving conventional therapies, supporting the immunoregulatory role of PTH and proposing an explanation for the increased susceptibility to infections observed in epidemiological studies.

[Clinical value of intact parathyroid hormone levels on the first day after total thyroidectomy on prediction for permanent hypoparathyroidism].

Objective: To examine the value serum calcium and intact parathyroid hormone (iPTH) levels measured on the first day after total thyroidectomy on prediction for permanent hypoparathyroidism. Methods: Totally 546 patients with thyroid cancer and benign thyroid lesions who underwent total thyroidectomy at Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University from February 2008 to December 2018 were analyzed retrospectively. There were 158 males and 388 females aging (50.9±13.2) years (range: 19.0 to 79.2 years). Serum calcium and iPTH levels were collected before surgery, on the first day and 6 months after surgery. Logistic regression was used to analyze the correlation between each data and the occurrence of permanent hypoparathyroidism after surgery.The area under the receiver operating characteristic curve was used to evaluate the predictive power of iPTH for postoperative occurrence of permanent hypoparathyroidism. Results: Among the 546 cases of total thyroidectomy, 22 cases of permanent hypoparathyroidism occurred, with an incidence of 4.0% (22/546). Multivariate analysis showed that iPTH levels on the first day after total thyroidectomy (OR=2.932, 95%CI: 1.129 to 7.616, P=0.027) and serum calcium levels (OR=2.584, 95%CI: 1.017 to 6.567, P=0.046) were independent prognosis factors for postoperative permanent hypoparathyroidism. When the threshold value of iPTH at 24 hours after total thyroidectomy was 5.51 ng/L, the AUC was 0.956 (95%CI: 0.936 to 0.972, P=0.000), sensitivity was 100%, specificity was 85.1%, positive predictive value was 22%, negative predictive value was 100%. When the threshold value of serum calcium at 24 hours after total thyroidectomy was 1.93 mmol/L, the AUC was 0.733 (95%CI: 0.694 to 0.770, P=0.000), sensitivity was 63.6%, specificity was 78.1%, positive predictive value of 10.8% and negative predictive value of 98.1%. Conclusions: Serum iPTH and calcium levels on the first day after total thyroidectomy were related to the occurrence of permanent hypoparathyroidism postoperatively. The predictive value of iPTH level is higher than that of serum calcium level.

Characteristics of hypoparathyroidism in Colombia: data from a single center in the city of Medellín.

OBJECTIVE: Hypoparathyroidism is a rare condition, whose most common etiology is complications of neck surgery. The aim of the study was to identify the clinical and biochemical profile of the patients with diagnosis of hypoparathyroidism, including the frequency of symptoms, clinical signs, long-term complications and disease control. Additionally, the study sought to know what the medication profile was, and the doses required by the patients. SUBJECTS AND METHOD: A retrospective cohort study was conducted wherein all patients with ICD-10 codes associated with hypoparathyroidism between 2011 and 2018 at the Hospital Universitario San Vicente Fundación were included. We investigated the etiology of the disease; biochemical profile including lowest serum calcium, highest serum phosphorus, 25OHD levels, calciuria and calcium/phosphorus product; medication doses, disease control, and presence of complications, especially renal and neurologic complications were also evaluated. RESULTS: The cohort included 108 patients (99 women/9 men) with a mean age of 51.6 ± 15.6 years. The main etiology was postoperative (93.5%), the dose of elemental calcium received was relatively low (mean 1,164 mg/day), and in only 9.2% of cases more than 2,500 mg/day of elemental calcium was necessary. We were able to evaluate the follow-up in 89 patients, and found that only 57.3% met the criteria for controlled disease. CONCLUSION: The clinical profile of patients with hypoparathyroidism in our cohort is similar to that described in other international studies, with predominantly postoperative etiology. With standard therapy, only adequate control is achieved in a little more than half of patients. Arch Endocrinol Metab. 2020;64(3):282-9.

Measurement of serum intact parathyroid hormone concentration 1 day after total thyroidectomy to assess risk of permanent hypoparathyroidism.

OBJECTIVE: This study was performed to assess the clinical value of measuring the intact parathyroid hormone (iPTH) concentration 1 day after total thyroidectomy to estimate the occurrence of permanent hypoparathyroidism (pHPP). METHODS: Data of 546 patients who underwent total thyroidectomy from February 2008 to December 2018 were retrospectively analyzed. Calcium and iPTH concentrations were collected preoperatively and at 1 day and 6 months postoperatively. Logistic regression was used to analyze the correlation between clinical indexes and postoperative pHPP. RESULTS: Of the 546 patients, 22 (4.03%) developed pHPP. Multivariate analysis showed that the iPTH and serum calcium concentrations measured 1 day after surgery were independent predictors of the risk of pHPP. An iPTH concentration of 5.51 pg/mL measured 1 day postoperatively was used as the cut-off value, and the area under the curve was 0.956. The risk of pHPP was identified with a sensitivity of 100%, specificity of 85.1%, positive predictive value of 22%, and negative predictive value of 100%. CONCLUSIONS: The iPTH concentration measured 1 day after total thyroidectomy is closely related to the occurrence of pHPP postoperatively and is an independent predictive risk factor. The postoperative iPTH concentration can be helpful in identifying patients at risk for developing pHPP.

Autosomal dominant hypocalcaemia: identification of two novel variants of CASR gene.

Autosomal dominant hypocalcaemia is a rare aetiology of hypocalcaemia, caused by gain-of-function mutations of the calcium-sensing receptor (CASR) gene. We present two cases of two asymptomatic women (50-year-old-case 1 and 25-year-old-case 2), referred to our endocrinology department for investigation of hypocalcaemia, hyperphosphatemia and inappropriately low parathormone. Both patients had relatives with the same laboratorial findings. At diagnosis, both patients presented basal ganglia calcifications. Genetic analysis was performed, identifying two novel heterozygous CASR variants: c.2269G>A (p.Glu757Lys) and c.2086C>G (p.Leu696Val), respectively, for case 1 and case 2. Affected individuals started oral calcium and vitamin D analogues, aiming to a low-normal calcium level. They remain under observation and are asymptomatic.

Characteristics of hypoparathyroidism in Colombia: data from a single center in the city of Medellín

ABSTRACT Objective Hypoparathyroidism is a rare condition, whose most common etiology is complications of neck surgery. The aim of the study was to identify the clinical and biochemical profile of the patients with diagnosis of hypoparathyroidism, including the frequency of symptoms, clinical signs, long-term complications and disease control. Additionally, the study sought to know what the medication profile was, and the doses required by the patients. Subjects and method A retrospective cohort study was conducted wherein all patients with ICD-10 codes associated with hypoparathyroidism between 2011 and 2018 at the Hospital Universitario San Vicente Fundación were included. We investigated the etiology of the disease; biochemical profile including lowest serum calcium, highest serum phosphorus, 25OHD levels, calciuria and calcium/phosphorus product; medication doses, disease control, and presence of complications, especially renal and neurologic complications were also evaluated. Results The cohort included 108 patients (99 women/9 men) with a mean age of 51.6 ± 15.6 years. The main etiology was postoperative (93.5%), the dose of elemental calcium received was relatively low (mean 1,164 mg/day), and in only 9.2% of cases more than 2,500 mg/day of elemental calcium was necessary. We were able to evaluate the follow-up in 89 patients, and found that only 57.3% met the criteria for controlled disease. Conclusion The clinical profile of patients with hypoparathyroidism in our cohort is similar to that described in other international studies, with predominantly postoperative etiology. With standard therapy, only adequate control is achieved in a little more than half of patients. Arch Endocrinol Metab. 2020;64(3):282-9

Postoperative Hypoparathyroidism After Total Thyroidectomy in Children.

BACKGROUND: Postoperative hypocalcemia because of hypoparathyroidism is the most common complication of total thyroidectomy in children. We hypothesized that most children with postoperative hypocalcemia would be eucalcemic by 12 mo and sought to define risk factors for permanent hypoparathyroidism. METHODS: We retrospectively reviewed children who underwent total thyroidectomy at a single children's hospital from 2012 to 2019. Patients with prior neck surgery were excluded. Indication for operation, final pathologic diagnosis, and postoperative serum calcium up to 12 mo were recorded. Permanent hypoparathyroidism was defined as supplemental calcium requirement beyond 1 y postoperatively. RESULTS: Sixty-eight patients underwent total thyroidectomy. Graves' disease was the most common benign indication for surgery (38 patients). Twenty-six patients (38%) had cancer on final pathology. Central lymph node dissection (CLND) was performed in 12 cancer patients. Twenty-eight patients (41%) had postoperative hypocalcemia. Eight patients (12%) had hypocalcemia at 6 mo. Risk factors for hypoparathyroidism at 6 mo were a cancer diagnosis (odds ratio [OR] 6.7; P = 0.02), CLND (OR 12.6; P < 0.01), and parathyroid tissue in the surgical specimen on pathologic analysis (OR 19.5; P < 0.01). Only two patients (3%) developed permanent hypoparathyroidism, both of whom had thyroidectomy for cancer and underwent CLND. CONCLUSIONS: Children with thyroid cancer are at high risk for postoperative hypocalcemia after total thyroidectomy. The risk is further increased by CLND, which should be performed selectively. A majority of patients with hypoparathyroidism at 6 mo postoperatively regain normal parathyroid function by 1 y. Permanent hypoparathyroidism in children after total thyroidectomy at a pediatric endocrine surgery center is rare.

A Rapid Intraoperative Parathyroid Hormone Assay Based on the Immune Colloidal Gold Technique for Parathyroid Identification in Thyroid Surgery.

Objective: A novel immunochromatographic test strip method was developed to detect tissue parathyroid hormone (PTH) using the immune colloidal gold technique (ICGT). The accuracy and application value of this method for intraoperative parathyroid identification were evaluated. Methods: Serum samples were collected to measure PTH by both ICGT and electrochemiluminescence immunoassay (ECLIA). Patients who underwent unilateral and total thyroidectomy were enrolled to evaluate the feasibility and clinical efficacy of rapid intraoperative identification of parathyroid glands via PTH determination using ICGT. Two sample preparation methods, fine needle aspiration (FNA) and tissue block homogenate (TBH), were used for PTH-ICGT analysis. Results: Bablok analysis showed a linear relationship between the serum PTH measurements obtained by ICGT and ECLIA. Non-parathyroid tissues had much lower PTH concentrations (14.8 ± 2.1 pg/ml, n = 97) detected by ICGT, compared to the parathyroid gland tissues (955.3 ± 16.1 pg/ml, n = 79; P < 0.0001), With biopsy results as the standard, ICGT showed higher diagnosis rates as compared with direct visual inspection, for identifying both parathyroid glands (97.4 vs. 78.2%) and non-parathyroid tissues (100 vs. 68.9%). The cut-off values for parathyroid identification by FNA and TBH methods were 63.99 and 136.30 pg/ml, respectively. The detection time was 2 min by TBH method for in vitro tissue detection and 6 min by FNA method for in situ tissue detection, both of which were faster than traditional intraoperative cryopathological examination (usually >30 min). Intraoperative application of ICGT method was associated with higher postoperative serum calcium and blood PTH levels at 1 and 3 months as well as a lower incidence of postoperative transient hypocalcemia, as compared with direct visual inspection. Conclusion: PTH-ICGT assay shows high potential as a rapid, novel alternative for intraoperative parathyroid identification.

The most reliable time point for intact parathyroid hormone measurement to predict hypoparathyroidism after total thyroidectomy with central neck dissection to treat papillary thyroid carcinoma: a prospective cohort study.

PURPOSE: We assessed the optimal time for intact parathyroid hormone (iPTH) measurement for early detection of post-total thyroidectomy (TT) hypocalcemia in patients with papillary thyroid carcinoma (PTC). METHODS: In this single-center prospective cohort study, 143 patients who underwent TT with central neck dissection with or without lateral neck dissection for PTC were included. Biochemical profiles including iPTH, corrected total calcium, and ionized calcium within 24 h after surgery were analyzed. RESULTS: The 4-h postoperative iPTH was the most reliable predictor of post-TT transient or permanent hypoparathyroidism (cutoff for hypocalcemia was 3.75 pg/mL, AUC = 0.885, P < 0.001, sensitivity 81.6%, specificity 86.0%; cutoff for permanent hypocalcemia was 2.48 pg/mL, AUC = 0.819, P < 0.001, sensitivity 100%, specificity 57.8% calculated using ROC curves). CONCLUSIONS: The 4-h postoperative iPTH can most accurately predict hypoparathyroidism after TT with central neck dissection to treat PTC and facilitate the early discharge of low-risk postoperative hypoparathyroidism patients and decrease unnecessary overnight observation and calcium supplementation.

Post-thyroidectomy Hypocalcemia - Risk Factors and Management.

The complications of thyroidectomy vary from hypocalcemia and recurrent laryngeal nerve lesions to injury of vocal folds, local hematoma, cysts, granuloma. Post-operative hypocalcemia has an incidence of 1.2-40%. Permanent hyoparathyroidism is registered in 3% of cases. This is a brief narrative review focusing on the levels of calcium after performing a thyroidectomy and the need of calcium supplements under these circumstances. This complication, even it seems rather harmless at first, in fact it represents an important contributor to hospitalization delay and, especially for severe forms, to poor quality of life, including the risk of life threatening episodes. Devascularisation of parathyroid glands in addition to injury or dissection causes hypoparathyroidism. Hypocalcemia risk differs with sex (females have a higher risk), lymph node dissection (it increases the risk), it differs with type of thyroidectomy (larger dissections have a higher risk; also the intervention for recurrent goitre and second intervention for post-operatory bleeding increase the risk of hypocalcemia; while Basedow disease is probably at higher risk than multinodular goitre among benign conditions) and the duration of procedure. Pre-operatory low calcium, parathormon (PTH), 25-hydroxivitamin D increases the risk. The calcium drop rate matters as well: a decrease of 1 mg/dL calcium over 12 hours after surgery is independently correlated with the risk of symptomatic hypocalcemia. Early post-operatory PTH and calcium are best predictors for the need of oral calcium supplements. Routine post-operatory calcium and vitamin D supplementation statistically significant decreases the risk of developing transitory hypocalcemia and acute complications compare to calcium alone supplements or no supplements. In cases of hypoparathyroidism calcitriol is preferred.

Postoperative Hypoparathyroidism in Patients After Total Thyroidectomy - Experience of a Tertiary Center in Romania.

Background: Post-surgical hypoparathyroidism (PoSH) is a common long-term complication after thyroid surgery. The reported median (range) incidence rates of temporary and permanent PoSH was 27% (19 - 38%) and 1% (0 - 3%) respectively. Material and Methods: We retrospectively analyzed the files of 552 patients who underwent thyroidectomy in our surgery department between 2015- 2017 with the aim to assess the prevalence of PoSH and to identify patient and disease related factors associated with postoperative hypocalcemia. Results: 171 (30.97%) patients developed PoSH, 88.37% transient, 11.63% permanent. The median (IQR) duration of postoperative hypocalcemia was 60 (67.5) days. Preoperative biological parameters were similar in PoSH and the control group, except median (IQR) serum magnesium level that was significantly higher in PoSH group [2.04 (0.17) vs. 1.89 (0.28) mg/dl, p=0.005]. In the subgroup of patients with thyroid carcinoma the surgery duration was longer in PoSH patients compared to the control group [135 (60) vs. 110 (43) minutes, p=0.020]. In patients with PoSH, median post-operative serum calcium was significantly higher in patients with reported difficult surgery [8.2 (0.2) vs. 7.9 (0.6) mg/dl, p=0.043] and the mean serum calcium decrease was higher in patients with cervical neck dissection and lymphadenectomy (1.94 +-0.59 vs. 1.68 +-0.56 mg/dl, p=0.033). Conclusions: Our data show a high prevalence of PoSH that is likely to increase given the rising number of thyroid surgeries being performed. Further research is needed in order to better define this condition, to establish appropriate treatment and preventive measures.

Possible role of low magnesium levels in the onset of postoperative hypoparathyroidism following thyroidectomy.

BACKGROUND: A positive correlation between calcium and magnesium serum levels is well known and depends upon various factors. This study aims at verifying the existence of this association in a retrospective series of patients who underwent thyroid surgery. METHODS: Two hundred and eighty-five consecutive patients (202 female, 83 male, mean age 57 years) who underwent at least total thyroidectomy (TT) and had a complete clinical and biochemical pre- and postoperative evaluation were included in the study. Patients were evaluated with regard to: sex, age, indications for surgery, operative time, number of accidentally removed parathyroids, extent and time of surgery, thyroiditis, final histology, pre- and postoperative levels of calcium, magnesium, vitamin D, and creatinine, presence of symptoms of hypocalcemia. Statistical analysis was performed using the R software. RESULTS: In the postoperative period, biochemical hypocalcemia (<8.5 mg/dL) was observed in 126 patients (44%) and severe hypocalcemia (<7.5 mg/dL, a level indicating the need for longer hospitalization) was seen in 40 (14%). When analyzing patients with and without postoperative hypocalcemia, the factors affecting postoperative biochemical hypocalcemia were: older age (P=0.019), longer operative time (P=0.039), and a highly significant correlation between postoperative calcium and magnesium levels (r=0.432; P<0.001). CONCLUSIONS: The only factor among the ones we analyzed in this retrospective study that would appear to be linked to the onset of clinically relevant hypocalcemia is low magnesium levels in the postoperative period. A prospective randomized study with a group of patients undergoing magnesium replacement in the postoperative period can clarify the possible role of magnesium repletion on hypocalcemia.

Update on hypoparathyroidism.

PURPOSE OF REVIEW: Hypoparathyroidism is a rare endocrine disorder characterized by low or insufficient parathyroid hormone (PTH) concentrations leading to hypocalcemia, hyperphosphatemia, and markedly reduced bone turnover. Despite being a rare disease, hypoparathyroidism has a profound impact on affected patients. RECENT FINDINGS: Recent epidemiologic surveys demonstrate a prevalence of between 5.3 and 40/100 000, confirming the orphan status of this disease. There is a female predominance, and anterior neck surgery is the most common etiology. Recent studies have better elucidated the chronic manifestations of the disease, impacting quality of life and multiple organ systems including the renal, cardiovascular, and skeletal systems. There are now data on longer term use of parathyroid hormone (PTH) and PTH analogs. SUMMARY: This review focuses on recent contributions to the literature on the prevalence and epidemiology of the disease, risk of chronic manifestations, and treatment with PTH(1-34) and rhPTH(1-84). Further research is needed to determine the pathophysiology of complications in hypoparathyroidism and whether interventions can decrease future risk of these complications. In addition, further data are needed with regards to more physiologic dosing regimens and long-term treatment with PTH and PTH analogs.

Serum levels of intact parathyroid hormone on the first day after total thyroidectomy as predictor of permanent hypoparathyroidism. / Uso del valor de la hormona paratiroidea intacta en el primer día postoperatorio tras tiroidectomía total como predictor de hipoparatiroidismo permanente.

BACKGROUND: Permanent hypoparathyroidism is the most common long-term complication after total thyroidectomy, causing significant morbidity and requiring long-term replacement therapy. Our study objective was to assess whether intact parathyroid hormone (iPTH) levels on the first day after total thyroidectomy are a good predictor of permanent hypoparathyroidism. PATIENTS AND METHODS: A retrospective observational study of all patients undergoing total thyroidectomy between January 2009 and December 2014. iPTH and calcium levels were measured the first day after surgery. Patients were followed up for at least one year after surgery. RESULTS: The study group consisted of 481 patients with a mean age of 53±14 years, 82% of them females. The most common reason for thyroidectomy was multinodular goiter (75%), followed by papillary thyroid cancer (15%). Transient hypocalcemia was the most common early complication after total thyroidectomy (49%), and permanent hypoparathyroidism was the most common long-term complication (6%). ROC curve analysis showed that iPTH level on the first postoperative day was a good predictor of permanent hypoparathyroidism (area under the curve 0.87; 95% CI: 0.84-0.91). Cut-off iPTH levels of 5pg/mL had 95% sensitivity, 77% specificity, 21.6% positive predictive value, and 99.6% negative predictive value. CONCLUSIONS: iPTH level on the first day after total thyroidectomy is a useful predictor of permanent hypoparathyroidism because of its high negative predictive value. Serum iPTH levels >5pg/mL virtually exclude presence of permanent hypoparathyroidism.