Silicon-Rhodamine Functionalized Evocalcet Probes Potently and Selectively Label Calcium Sensing Receptors In Vitro, In Vivo, and Ex Vivo.

The calcium sensing receptor (CaSR) is a ubiquitously expressed G-protein coupled receptor (GPCR) that regulates extracellular calcium signals via the parathyroid glands. CaSR has recently also been implicated in noncalcitropic pathophysiologies like asthma, gut inflammation, and cancer. To date, molecular tools that enable the bioimaging of CaSR in tissues are lacking. Based on in silico analyses of available structure-activity relationship data on CaSR ligands, we designed and prepared silicon-rhodamine (SiR) conjugates of the clinically approved drug evocalcet. The new probes EvoSiR4 and EvoSiR6, with differing linker lengths at the evocalcet carboxyl end, both showed a 6-fold and 3-fold increase in potency toward CaSR (EC50 < 45 nM) compared to evocalcet and the evocalcet-linker conjugate, respectively, in an FLIPR-based cellular functional assay. The specificity of the EvoSiR probes toward CaSR binding and the impact of albumin was evaluated in live cell experiments. Both probes showed strong albumin binding, which facilitated the clearance of nonspecific binding interactions. Accordingly, in zebrafish embryos, EvoSiR4 specifically labeled the high CaSR expressing neuromasts of the lateral line in vivo. EvoSiR4 was also assessed in human parathyroid tissues ex vivo, showing a specific absolute CaSR-associated fluorescence compared to that of parathyroid autofluorescence. In summary, functionalization of evocalcet by SiR led to the preparation of potent and specific fluorescent CaSR probes. EvoSiR4 is a versatile small-molecular probe that can be employed in CaSR-related biomedical analyses where antibodies are not applicable.

Syndromic MEN1 parathyroid adenomas consist of both subclonal nodules and clonally independent tumors.

Primary hyperparathyroidism with parathyroid tumors is a typical manifestation of Multiple Endocrine Neoplasia Type 1 (MEN1) and is historically termed "primary hyperplasia". Whether these tumors represent a multi-glandular clonal disease or hyperplasia has not been robustly proven so far. Loss of Menin protein expression is associated with inactivation of both alleles and a good surrogate for a MEN1 gene mutation. The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene is mutated in MEN4 and encodes for protein p27 whose expression is poorly studied in the syndromic MEN1 setting.Here, we analyzed histomorphology and protein expression of Menin and p27 in parathyroid adenomas of 25 patients of two independent, well-characterized MEN1 cohorts. The pattern of loss of heterozygosity (LOH) was assessed by fluorescence in situ hybridization (FISH) in one MEN1-associated parathyroid adenoma. Further, next-generation sequencing (NGS) was performed on eleven nodules of four MEN1 patients.Morphologically, the majority of MEN1 adenomas consisted of multiple distinct nodules, in which Menin expression was mostly lost and p27 protein expression reduced. FISH analysis revealed that most nodules exhibited MEN1 loss, with or without the loss of centromere 11. NGS demonstrated both subclonal evolution and the existence of clonally unrelated tumors.Syndromic MEN1 parathyroid adenomas therefore consist of multiple clones with subclones, which supports the current concept of the novel WHO classification of parathyroid tumors (2022). p27 expression was lost in a large fraction of MEN1 parathyroids and must therefore be used with caution in suggesting MEN4.

Is COVID-19 perceived as a threat to equal career opportunities amongst Swiss medical students? A cross-sectional survey study from Bern and Geneva.

Introduction: Students frequently rely on part-time jobs to earn a living wage. We sought to evaluate the sociodemographic status of Swiss medical students and their perception regarding equal career opportunities in view of impaired part-time job opportunities under the COVID-19 pandemic. Methods: We conducted an anonymous online survey among Swiss medical students from Bern and Geneva over a period of 4 months between December 2020 and April 2021. We evaluated sociodemographic data, current living situation, part-time job occupation as well as other sources of income to fund living expenses, and, by means of a five-point Likert scale (1=strongly disagree and 5=strongly agree), whether COVID-19 was perceived as impeding equal career opportunities. Results: Of 968 participants, corresponding to around 13.8% of all medical students in Switzerland, 81.3% had part-time jobs. Amongst the employed, 54.8% worked to afford living expenses and 28.9% reported a negative financial impact due to reduced part-time jobs under the pandemic. The loss of part-time jobs was perceived to make medical studies a privilege for students with higher socioeconomic status (4.11±1.0), whose opportunity to study is independent of a regular income. A governmental backup plan was considered crucial to support affected students (4.22±0.91). Discussion: COVID-19 and its sequelae are perceived as a threat for Swiss medical students and lead to a disadvantage for those with lower socioeconomic status. Nationwide measures should be established to foster equal career opportunities.

Multiple endocrine neoplasia type 4: a new member of the MEN family.

Objective: Multiple endocrine neoplasia type 4 (MEN4) is caused by a CDKN1B germline mutation first described in 2006. Its estimated prevalence is less than one per million. The aim of this study was to define the disease characteristics. Methods: A systematic review was performed according to the PRISMA 2020 criteria. A literature search from January 2006 to August 2022 was done using MEDLINE® and Web of ScienceTM. Results: Forty-eight symptomatic patients fulfilled the pre-defined eligibility criteria. Twenty-eight different CDKN1B variants, mostly missense (21/48, 44%) and frameshift mutations (17/48, 35%), were reported. The majority of patients were women (36/48, 75%). Men became symptomatic at a median age of 32.5 years (range 10-68, mean 33.7 ± 23), whereas the same event was recorded for women at a median age of 49.5 years (range 5-76, mean 44.8 ± 19.9) (P = 0.25). The most frequently affected endocrine organ was the parathyroid gland (36/48, 75%; uniglandular disease 31/36, 86%), followed by the pituitary gland (21/48, 44%; hormone-secreting 16/21, 76%), the endocrine pancreas (7/48, 15%), and the thyroid gland (4/48, 8%). Tumors of the adrenal glands and thymus were found in three and two patients, respectively. The presenting first endocrine pathology concerned the parathyroid (27/48, 56%) and the pituitary gland (11/48, 23%). There were one (27/48, 56%), two (13/48, 27%), three (3/48, 6%), or four (5/48, 10%) syn- or metachronously affected endocrine organs in a single patient, respectively. Conclusion: MEN4 is an extremely rare disease, which most frequently affects women around 50 years of age. Primary hyperparathyroidism as a uniglandular disease is the leading pathology.

Treatment for gastrointestinal and pancreatic neuroendocrine tumours: a network meta-analysis.

BACKGROUND: Several available therapies for neuroendocrine tumours (NETs) have demonstrated efficacy in randomised controlled trials. However, translation of these results into improved care faces several challenges, as a direct comparison of the most pertinent therapies is incomplete. OBJECTIVES: To evaluate the safety and efficacy of therapies for NETs, to guide clinical decision-making, and to provide estimates of relative efficiency of the different treatment options (including placebo) and rank the treatments according to their efficiency based on a network meta-analysis. SEARCH METHODS: We identified studies through systematic searches of the following bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); and Embase from January 1947 to December 2020. In addition, we checked trial registries for ongoing or unpublished eligible trials and manually searched for abstracts from scientific and clinical meetings. SELECTION CRITERIA: We evaluated randomised controlled trials (RCTs) comparing two or more therapies in people with NETs (primarily gastrointestinal and pancreatic). DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data to a pre-designed data extraction form. Multi-arm studies were included in the network meta-analysis using the R-package netmeta. We separately analysed two different outcomes (disease control and progression-free survival) and two types of NET (gastrointestinal and pancreatic NET) in four network meta-analyses. A frequentist approach was used to compare the efficacy of therapies. MAIN RESULTS: We identified 55 studies in 90 records in the qualitative analysis, reporting 39 primary RCTs and 16 subgroup analyses. We included 22 RCTs, with 4299 participants, that reported disease control and/or progression-free survival in the network meta-analysis. Precision-of-treatment estimates and estimated heterogeneity were limited, although the risk of bias was predominantly low. The network meta-analysis of progression-free survival found nine therapies for pancreatic NETs: everolimus (hazard ratio [HR], 0.36 [95% CI, 0.28 to 0.46]), interferon plus somatostatin analogue (HR, 0.34 [95% CI, 0.14 to 0.80]), everolimus plus somatostatin analogue (HR, 0.38 [95% CI, 0.26 to 0.57]), bevacizumab plus somatostatin analogue (HR, 0.36 [95% CI, 0.15 to 0.89]), interferon (HR, 0.41 [95% CI, 0.18 to 0.94]), sunitinib (HR, 0.42 [95% CI, 0.26 to 0.67]), everolimus plus bevacizumab plus somatostatin analogue (HR, 0.48 [95% CI, 0.28 to 0.83]), surufatinib (HR, 0.49 [95% CI, 0.32 to 0.76]), and somatostatin analogue (HR, 0.51 [95% CI, 0.34 to 0.77]); and six therapies for gastrointestinal NETs: 177-Lu-DOTATATE plus somatostatin analogue (HR, 0.07 [95% CI, 0.02 to 0.26]), everolimus plus somatostatin analogue (HR, 0.12 [95%CI, 0.03 to 0.54]), bevacizumab plus somatostatin analogue (HR, 0.18 [95% CI, 0.04 to 0.94]), interferon plus somatostatin analogue (HR, 0.23 [95% CI, 0.06 to 0.93]), surufatinib (HR, 0.33 [95%CI, 0.12 to 0.88]), and somatostatin analogue (HR, 0.34 [95% CI, 0.16 to 0.76]), with higher efficacy than placebo. Besides everolimus for pancreatic NETs, the results suggested an overall superiority of combination therapies, including somatostatin analogues. The results indicate that NET therapies have a broad range of risk for adverse events and effects on quality of life, but these were reported inconsistently. Evidence from this network meta-analysis (and underlying RCTs) does not support any particular therapy (or combinations of therapies) with respect to patient-centred outcomes (e.g. overall survival and quality of life). AUTHORS' CONCLUSIONS: The findings from this study suggest that a range of efficient therapies with different safety profiles is available for people with NETs.

[Smarter Medicine: From the Diagnosis to the Intervention in General and Visceral Surgery]. / Smarter Medicine in der Viszeralchirurgie.

Smarter Medicine: From the Diagnosis to the Intervention in General and Visceral Surgery Abstract. More is not always a plus. With this slogan, in smarter medicine it is a principle to make a decision together. In general surgery diagnostic or therapeutic interventions have the potential to harm the patient. The admission to the emergency room of a young patient with abdominal pain does not necessarily require a computed tomography. A potential acute appendicitis without typical clinical and laboratory findings could potentially be unmasked by watchful waiting, or even a nonessential operation could be avoided. Possibly, acute cholecystitis or some forms of hollow organ perforation could be treated solely with antibiotics. Is it feasible to treat an acute severe diverticulitis with antibiotics only? In addition, if a colon resection is necessary, could a direct anastomosis be made, and a second operation be avoided? Are there thyroid nodules that do not need removal? The management of diseases in the surgical domain are evaluated with evidence-based medicine in the focus of smarter medicine and newly reconsidered.

Case Report: Modified Thoracoscopic-Assisted Cervical Resection for Retrosternal Goiter.

Introduction: The treatment of choice for retrosternal goiters (RSG) is surgical resection to relieve symptoms and rule out malignancy. Although the majority of RSG can be removed by a cervical approach only, an extracervical approach (e.g., sternotomy, thoracotomy or thoracoscopy) may be required. Herein, we describe a refined thoracoscopic-assisted cervical two-team RSG resection without thoracoscopic mediastinal dissection. Technique: A 57-year-old man presented with a large RSG with posterior mediastinal extension (PME) and extensive peritumoral vascularization. Due to its extension below the aortic arch and its small connection with the right thyroid lobe, a combined cervical and thoracoscopic approach was intended. The endocrine surgery unit performed the cervical mobilization of the right thyroid lobe, while the thoracic surgery unit gently pushed the mediastinal tumor through the thoracic inlet without performing mediastinal dissection. This allowed a safe visualization of the inserting vessels by the endocrine surgery team at the neck, followed by a stepwise division of the vessels and resection of the retrosternal nodule through the cervical access. Comment: The described approach is indicated for RSG with posterior mediastinal extension, anteroposterior dimension smaller than the thoracic inlet and inaccessibility from a cervical approach only. This minimally invasive approach is associated with a faster recovery, decreased morbidity and postoperative pain, shorter hospital stay and better cosmetic results.

[From thyroid nodules to thyroid cancer]. / Vom Schilddrüsenknoten zum Schilddrüsenkarzinom.

From thyroid nodules to thyroid cancer Abstract. The prevalence of thyroid nodules is around 1 % per life year, whereas 5 % of the nodules are malignant. Primary diagnostics consist of examination of TSH and cervical ultrasound. Depending on the findings, additional laboratory investigations, a scintigraphy or a biopsy are indicated. In case of thyroid cancer, the primary treatment is usually surgery. There are at least nine different clinical guidelines worldwide to provide a standardized perioperative management, whereas the guidelines of the German Association of Endocrine Surgeons (CAEK) and the American Thyroid Association (ATA) are most frequently used in the German speaking part of Europe. Individual therapy concepts are determined at the interdisciplinary endocrinological tumour boards. The indication for postoperative radioiodine treatment or thyroid hormone supplementation in TSH suppression dose in case of differentiated (papillary or follicular) thyroid cancer is evaluated according to the American Thyroid Association (ATA) risk stratification.

Accreditation of endocrine surgery units.

BACKGROUND/PURPOSE: A key measure to maintain and improve the quality of healthcare is the formal accreditation of provider units. The European Society of Endocrine Surgeons (ESES) therefore proposes a system of accreditation for endocrine surgical centers in Europe to supplement existing measures that promote high standards in the practice in endocrine surgery. METHODS: A working group analyzed the current healthcare situation in the field of endocrine surgery in Europe. Two surveys were distributed to ESES members to acquire information about the structure, staffing, caseload, specifications, and technology available to endocrine surgery units. Further data were sought on tracer diagnoses for quality standards, training provision, and research activity. Existing accreditation models related to endocrine surgery were included in the analysis. RESULTS: The analysis of existing accreditation models, available evidence, and survey results suggests that a majority of ESES members aspire to a two-level model (termed competence and reference centers), sub-divided into those providing neck endocrine surgery and those providing endocrine surgery. Criteria for minimum caseload, number and certification of staff, unit structure, on-site collaborating disciplines, research activities, and training capacity for competence center accreditation are proposed. Lastly, quality indicators for distinct tracer diagnoses are defined. CONCLUSIONS: Differing healthcare structures, existing accreditation models, training models, and varied case volumes across Europe are barriers to the conception and implementation of a pan-European accreditation model. However, there is consensus on accepted standards required for accrediting an ESES competence center. These will serve as a basis for first-stage accreditation of endocrine surgery units.

Association of Surgical Volume and Quality Management in Thyroid Surgery: A Two-Nation Multicenter Study.

BACKGROUND: High-volume caseload in thyroid surgery is associated with lower postoperative complication rates resulting to better outcomes. The aim of the present study was to investigate the correlation of the departments' annual number of thyroid surgeries on the adherence to consensus guidelines and on the implementation of measures for quality assurance. METHODS: In 2016, we sent an anonymous electronic survey with questions related to the perioperative management in thyroid surgery to all directors of departments in operative medicine in Switzerland and Austria. We compared the pre- and postoperative management with the summarized recommendations of the four most frequently used consensus guidelines. Analogously, we analyzed the implementation of six measures for quality assurance related to thyroid surgery for each participating department. Using logistic regression analysis, we evaluated the correlation of number of guidelines respected and number of measures for quality assurance with the departments' annual number of surgeries performed. Furthermore, we evaluated the number of departments providing thyroid cancer surgery and their experience in neck dissection. RESULTS: The management corresponded in 64.0% to the summarized recommendations. Adherence to the summarized recommendations and implementation of measures for quality assurance were significantly more likely with increasing numbers of surgeries performed (p = 0.049 and p < 0.001). Ninety-two departments provided thyroid cancer surgery, whereas 12/92 (13.0%) were not able to perform central and/or lateral neck dissection. CONCLUSION: Consensus guidelines are insufficiently implemented within thyroid surgery, and quality management is associated with surgical volume.

Intertumor heterogeneity in 60 pancreatic neuroendocrine tumors associated with multiple endocrine neoplasia type 1.

BACKGROUND: Patients with multiple endocrine neoplasia type 1 (MEN-1) develop multiple pancreatic neuroendocrine neoplasias (PNENs). Size at diagnosis and growth during follow-up are crucial parameters. According to the WHO 2017, grading is another important parameter. The impact of grading compared to size (WHO 2000) on the clinical course needs to be evaluated. METHODS: Sixty PNENs of six patients with MEN-1 were retrospectively evaluated. RESULTS: Fifty-one tumors with a diameter of < 20 mm were graded as G1. Two of 9 tumors with diameters of ≥20 mm were graded as G2. Tumor size of ≥20 mm correlated significantly with higher proliferation (p = 0.000617). Lymph node metastases were documented in two patients with a total of 19 tumors. In one patient, all 13 tumors (diameter: 0.4 to 100 mm) were classified as G1. However, metastases were documented in 9/29 lymph nodes. In the other patient, 5 tumors (3.5 to 20 mm) were classified as G1. The sixth tumor (30 mm) was classified as G2 (Ki-67: 8%). Metastases were revealed in 2/20 lymph nodes. CONCLUSIONS: Tumor size of ≥20 mm seems to correlate with more aggressive MEN-1 related pancreatic disease, regardless of individual proliferation. Tumors ≥20 mm and tumors graded as G2 should be treated surgically regardless of their size.

Therapeutic Options for Neuroendocrine Tumors: A Systematic Review and Network Meta-analysis.

IMPORTANCE: Multiple therapies are currently available for patients with neuroendocrine tumors (NETs), yet many therapies have not been compared head-to-head within randomized clinical trials (RCTs). OBJECTIVE: To assess the relative safety and efficacy of therapies for NETs. DATA SOURCES: PubMed, Embase, the Cochrane Central Register of Controlled Trials, trial registries, meeting abstracts, and reference lists from January 1, 1947, to March 2, 2018, were searched. Key search terms included neuroendocrine tumors, gastrointestinal neoplasms, therapy, and randomized controlled trial. STUDY SELECTION: Randomized clinical trials comparing 2 or more therapies in patients with NETs (primarily gastrointestinal and pancreatic) were evaluated. Thirty RCTs met the selection criteria. DATA EXTRACTION AND SYNTHESIS: Pairs of independent reviewers screened studies, extracted data, and assessed the risk of bias. A network meta-analysis with a frequentist approach was used to compare the efficacy of therapies; the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. MAIN OUTCOMES AND MEASURES: Disease control, progression-free survival, overall survival, adverse events, and quality of life. RESULTS: The systematic review identified 30 relevant RCTs comprising 3895 patients (48.4% women) assigned to 22 different therapies for NETs. These therapies showed a broad range of risk for serious and nonserious adverse events. The network meta-analyses included 16 RCTs with predominantly a low risk of bias; nevertheless, precision-of-treatment estimates and estimated heterogeneity were limited. The network meta-analysis found 7 therapies for pancreatic NETs: everolimus (hazard ratio [HR], 0.35 [95% CI, 0.28-0.45]), everolimus plus somatostatin analogue (HR, 0.35 [95% CI, 0.25-0.51]), everolimus plus bevacizumab plus somatostatin analogue (HR, 0.44 [95% CI, 0.26-0.75]), interferon (HR, 0.37 [95% CI, 0.16-0.83]), interferon plus somatostatin analogue (HR, 0.31 [95% CI, 0.13-0.71]), somatostatin analogue (HR, 0.46 [95% CI, 0.33-0.66]), and sunitinib (HR, 0.42 [95% CI, 0.26-0.67]), and 5 therapies for gastrointestinal NETs: bevacizumab plus somatostatin analogue (HR, 0.22 [95% CI, 0.05-0.99]), everolimus plus somatostatin analogue (HR, 0.31 [95% CI, 0.11-0.90]), interferon plus somatostatin analogue (HR, 0.27 [95% CI, 0.07-0.96]), Lu 177-dotatate plus somatostatin analogue (HR, 0.08 [95% CI, 0.03-0.26], and somatostatin analogues (HR, 0.40 [95% CI, 0.21-0.78]) with higher efficacy than placebo and suggests an overall superiority of combination therapies. CONCLUSIONS AND RELEVANCE: The findings from this study suggest that a range of efficient therapies with different safety profiles is available for patients with NETs.

Neuroendocrine Liver Metastasis-a Specific Set of Markers to Detect Primary Tumor Sites.

The diagnosis of neuroendocrine neoplasia (NEN) is often made at an advanced stage of disease, including hepatic metastasis. At this point, the primary may still be unknown and sometimes cannot even be detected by functional imaging, especially in very small tumors of the pancreas (pan) and small intestinal (si) entities. The site of the primary may be based on biopsy specimens of the liver applying a specific set of markers. Specimens of liver metastases from 87 patients with NENs were studied. In retrospect, 50 patients had si and 37 pan NENs. Tissue samples were evaluated by immunohistochemistry. The markers applied were insulin gene enhancer protein Islet-1 (ISL-1), homeobox protein CDX-2 (CDX2), thyroid transcription factor 1 (TTF-1), and serotonin. Positive stains for CDX2 were documented in 43 (86%) and for serotonin in 45 (90%) of 50 siNENs. Three panNENs were positive for CDX2 and one for serotonin, respectively. ISL-1 was negative throughout in siNENs and also negative in 8 of 50 panNENs (21.6%). TTF-1 was negative in more than 90% of the specimens of either entity. Immunohistochemical markers in liver metastasis can lead the way to the site of the primary NEN. They should always be used in combined clusters.

Electronic Voting to Improve Morbidity and Mortality Conferences.

BACKGROUND: It is of major importance in clinical surgery to identify potential patterns and specific causes of complications. Therefore, morbidity and mortality meetings (M&M) are widely used to discuss and evaluate deviations from expected outcomes in order to improve surgical practice. Moreover, M&M represent an important tool for continuous medical education. In this study, we introduced an electronic voting system to assess whether anonymity during M&M could limit potential biases due to hierarchical structures or opinion leaders. METHODS: This study was conducted in the surgical department of a European tertiary care center. During the study period, electronic voting was applied in 412 M&M cases and compared with a baseline of 330 conventional M&M entries. In this interrupted time series, the educational quality and participant satisfaction of the M&M were assessed using surveys before and after the introduction of electronic voting. The surveys were refined using principle component analysis. In addition, the classification of the cause of the complication was recorded. RESULTS: The introduction of electronic voting led to a significant increase in perceived educational quality from 2.63 to 3.36 (p < 0.01), and the overall participant satisfaction increased from 2.6 ± 0.9 to 3.7 ± 1.2 (p < 0.01) on a five-point Likert scale. The frequency of voting shifted from "patient's disease" (before 42.9, after 27.6%, p = 0.04) to "misadventure" (before 1.1, after 16.0%, p < 0.01). The voting frequencies for the causes attributed to "management" and "technical" remained constant. CONCLUSIONS: An electronic voting system in M&M meetings increases perceived educational quality and participant satisfaction.

The impact of vitamin D status on hungry bone syndrome after surgery for primary hyperparathyroidism.

OBJECTIVE: Prolonged hypocalcemia but normal intact parathyroid hormone (iPTH) levels after surgery for primary hyperparathyroidism (PHPT) are referred to as 'hungry bone syndrome' (HBS). The aim was to evaluate preoperative risk factors for HBS with a focus on the impact of 25-hydroxyvitamin D (25(OH)D) deficiency. DESIGN: Patients having undergone initial successful surgery for sporadic PHPT within 6 years were considered for retrospective analysis. METHODS: A total of 385 patients were evaluated, of whom 33 (8.6%) developed HBS influencing negatively the postoperative bone metabolism. All patients underwent biochemical evaluations two days before parathyroid surgery and were followed biochemically on a daily basis in the first postoperative week and thereafter at 8 weeks and 6 months. CONCLUSIONS: No relationship was established between preoperative 25(OH)D deficiency and HBS. The only significant risk factor for HBS in multivariable analysis was high levels of preoperative iPTH. As HBS therefore cannot be predicted preoperatively, we recommend a consistent postoperative calcium and vitamin D supplementation to improve the bone metabolism.

Primary hyperparathyroidism: Dynamic postoperative metabolic changes.

OBJECTIVE: Little is known about the natural changes in parathyroid function after successful parathyroid surgery for primary hyperparathyroidism. The association of intact parathyroid hormone (iPTH) and calcium (Ca) with "temporary hypoparathyroidism" and "hungry bone syndrome" (HBS) was evaluated. DESIGN: Potential risk factors for temporary hypoparathyroidism and HBS were evaluated by taking blood samples before surgery, intra-operatively, at postoperative day (POD) 1, at POD 5 to 7, in postoperative week (POW) 8 and in postoperative month (POM) 6. PATIENTS: Of 425 patients, 43 (10.1%) had temporary hypoparathyroidism and 36 (8.5%) had HBS. MEASUREMENTS: The discriminative ability of iPTH and Ca on POD 1 for temporary hypoparathyroidism and HBS. RESULTS: Intact parathyroid hormone (IPTH) on POD 1 showed the highest discriminative ability for temporary hypoparathyroidism (C-index = 0.952), but not for HBS. IPTH was helpful in diagnosing HBS between POD 5 and 7 (C-index = 0.708). Extending the model by including Ca resulted in little improvement of the discriminative ability for temporary hypoparathyroidism (C-index = 0.964) and a decreased discriminative ability for HBS (C-index = 0.705). Normal parathyroid metabolism was documented in 139 (32.7%) patients on POD 1 and in 423 (99.5%) 6 months postoperatively, while 2 (0.5%) patients had persistent hyperparathyroidism, one diagnosed between POD 5 and 7 and another at POW 8. No patients suffered from permanent hypoparathyroidism. CONCLUSIONS: The necessity for Ca and vitamin D3 substitution cannot be predicted with certainty before POD 5 to 7 without serial laboratory measurements. Based on the results, a routine 8-week course of Ca and vitamin D3 treatment seems reasonable and its necessity should be evaluated in a follow-up study.

Factors influencing pre-operative urinary calcium excretion in primary hyperparathyroidism.

OBJECTIVE: Normal or elevated 24-hour urinary calcium (Ca) excretion is a diagnostic marker in primary hyperparathyroidism (PHPT). It is used to distinguish familial hypocalciuric hypercalcaemia (FHH) from PHPT by calculating the Ca/creatinine clearance ratio (CCCR). The variance of CCCR in patients with PHPT is considerable. The aim of this study was to analyse the parameters affecting CCCR in patients with PHPT. DESIGN: The data were collected prospectively. Patients with sporadic PHPT undergoing successful surgery were included in a retrospective analysis. PATIENTS: The analysis covered 381 patients with pre-operative workup 2 days before removal of a solitary parathyroid adenoma. MEASUREMENTS: The impact of serum Ca and 25-hydroxyvitamin D3 (25-OH D3) on CCCR. RESULTS: The coefficient of determination (R2 ) in the multivariable model for CCCR consisting of age, Ca, 25-OH D3, 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3), testosterone (separately for males and females), intact parathyroid hormone (iPTH) and osteocalcin was 25.8%. The only significant parameters in the multivariable analysis were 1,25-(OH)2 D3 and osteocalcin with a drop in R2 of 15.4% (P<.001) and 2.4% (P=.006), respectively. Bone mineral densities at the lumbar spine, distal radius and left femoral neck were not associated with CCCR (r=-.08, r=-.10 and r=-0.09). CONCLUSIONS: In multivariable analysis, 1,25-(OH)2 D3 and osteocalcin were the only factors correlating with CCCR. Vitamin D3 replacement may therefore impair the diagnostic value of CCCR and increase the importance of close monitoring of urinary Ca excretion during treatment.