Calcium Citrate Versus Calcium Carbonate in the Management of Chronic Hypoparathyroidism: A Randomized, Double-Blind, Crossover Clinical Trial

In hypoparathyroidism (HypoPT), calcium supplementation is virtually always required, although the disease is likely to be associated with an increased risk of nephrolithiasis. The use of calcium citrate (Ca-Cit) theoretically could have a positive impact on the nephrolithiasis risk because citrate salts are used to reduce this risk. Our objective was to evaluate the potential therapeutic advantage of Ca-Cit in comparison with calcium carbonate (CaCO3) in HypoPT, on nephrolithiasis risk factors, as well as to their ability to maintain desirable serum calcium levels. We also evaluated these preparations on quality of life (QOL). This randomized, double-blind, crossover trial recruited 24 adults with postsurgical chronic hypoparathyroidism at Campus Bio-Medico University of Rome. Participants were randomized 1:1 to Ca-Cit or CaCO3 for 1 month and then crossed over to the other treatment for another month. The primary outcomes were changes in albumin-adjusted serum calcium and in ion activity product of calcium oxalate levels (AP[CaOx] index). Secondary efficacy outcomes included changes in SF-36 survey score, fatigue score, constipation, and adverse events. No difference in terms of AP(CaOx) index was observed between the two groups. However, Ca-Cit was associated with a significant reduction in the oxalate/creatinine ratio compared with CaCO3 (-2.46 mmol/mol [SD 11.93] versus 7.42 mmol/mol [SD 17.63], p = 0.029). Serum calcium and phosphorus concentration was not different between the two calcium preparations. Ca-Cit was associated with less constipation (p = 0.047). No difference was found in QOL scores. Although Ca-Cit did not modify the AP(CaOx) index when compared with CaCO3, it was associated with a reduction in urinary oxalate excretion that could have a potential beneficial effect on nephrolithiasis risk. These results are likely to have clinical implications in HypoPT, particularly those who do not tolerate CaCO3 and those affected by nephrolithiasis. A longer-term experience is needed to confirm these findings. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) Position Statement : clinical Management of Vitamin D Deficiency in Adults

Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice

PTH(1-34) for Surgical Hypoparathyroidism: A Prospective, Open-Label Investigation of Efficacy and Quality of Life

CONTEXT: Conventional therapy for hypoparathyroidism consists of calcium and calcitriol, but sometimes normal serum calcium cannot be maintained, and/or this approach might lead to nephrocalcinosis, nephrolithiasis, or renal insufficiency. OBJECTIVE: The objective of the study was to investigate the effects of 6 months of PTH(1-34) treatment in adult subjects with postoperative hypoparathyroidism and to evaluate quality-of-life changes. DESIGN: This was a 2-year prospective, open-label study. At baseline and after 6 months of PTH(1-34) treatment, calcium and vitamin D supplementation requirements, serum calcium, phosphate, creatinine, alkaline phosphatase, uric acid, and 24-hour urinary calcium excretion were evaluated. Quality of life was evaluated by the Rand 36-Item Short Form Health Survey covering eight domains of physical and mental health. SETTING: This was an Italian multicentric study. PARTICIPANTS: Participants included 42 subjects with surgical hypoparathyroidism (90% females, age range 34-77 y). INTERVENTION: The intervention included a twice-daily PTH(1-34) 20 μg sc injection. RESULTS: The mean serum calcium levels significantly increased from baseline to 15 days (7.6 ± 0.6 vs 9.1 ± 0.9 mg/dL, P < .001) and remained stable until the end of the observational period, despite a significant reduction in calcium and vitamin D supplementation. Phosphate levels gradually decreased from baseline to the sixth month (P = .005 for the trend), whereas the alkaline phosphatase increased (P < .001). Data from the Rand 36-Item Short Form Health Survey showed a significant improvement in the mean scores of all eight domains (P < .001). CONCLUSION: This is the largest study that demonstrates the effectiveness of PTH(1-34) in the treatment of adult patients with postsurgical hypoparathyroidism, and it shows that PTH(1-34) may improve the mental and physical health in hypoparathyroid subjects

Papillary Thyroid Microcarcinoma: Differences between Lesions in Incidental and Nonincidental Settings—Considerations on These Clinical Entities and Personal Experience

Papillary thyroid microcarcinoma (PTMC) represents 35–40% of all papillary cancers; it is defined as a nodule ≤ 10 mm at the time of histological diagnosis. The clinical significance of PTMC is still controversial, and it may be discovered in two settings: incidental PTMC (iPTMC), in which it is identified postoperatively upon histological examination of thyroid specimens following thyroid surgery for benign disease, and nonincidental PTMC (niPTMC), in which it is diagnosed before surgery. While iPTMC appears to be related to mild behavior and favorable clinical outcomes, niPTMC may exhibit markers of aggressiveness. We retrospectively review our experience, selecting 54 PTMCs: 28 classified as niPTMC (52%) and 26 classified as iPTMC (48%). Patients with niPTMC showed significant differences, such as younger age at diagnosis (p p p p = 0.035). Other differences found in the niPTMC subgroup included a higher preoperative serum TSH level, higher hospital morbidity and a greater need for postoperative iodine ablation therapy (p p = 0.331) after a mean follow-up (FU) of 87 months, with one nodal recurrence among niPTMCs. The differences between iPTMC and niPTMC were consistent: patients operated on for total thyroidectomy and showing iPTMC can be considered healed after surgery, and follow-up should be designed to properly calibrate hormonal supplementation; conversely, niPTMC may sometimes exhibit aggressive behavior, and so the FU regimen should be closer and aimed at early detection of cancer recurrence

Cardiovascular Autonomic Neuropathy as a New Complication of Postsurgical Chronic Hypoparathyroidism

ABSTRACT   Postsurgical hypoparathyroidism (hypoPT) increases fatigue and seems to affect the risk of mortality. Cardiovascular autonomic neuropathy (CAN) is an impairment of the cardiovascular autonomic system, a cause of increased mortality, and associated with increased fatigability. The aim of this study is to evaluate CAN in hypoPT and its relationship with hypocalcemia, PTH levels, and hyperphosphatemia. This is a cross-sectional study comparing 51 postsurgical hypoPT patients treated with calcium and calcitriol and 43 control subjects without any PTH/calcium/phosphate disorders who underwent thyroidectomy. CAN was assessed by heart rate (HR) response to deep breathing, HR response to the lying-to-standing test, HR response to the Valsalva maneuver, and blood pressure response to standing. Participants were considered to have "early CAN" if they had one abnormal result in the HR tests and "definite CAN" with two or more abnormal results. The prevalence of CAN was 23% in the control group and 78% in the hypoPT group (OR 11.48; 95% CI, 4.48 to 32.17). Patients with hypoPT and serum calcium (sCa) ≥8.5 mg/dL had a prevalence of early CAN of 72.4% and the prevalence was 86.4% in those with sCa &lt;8.5 mg/dL. Definite CAN was found in 2.3% of the control group, 24.1% of the hypoPT group without hypocalcemia, and 59.1% of the hypoPT group with hypocalcemia. In the hypoPT group, the OR for definite CAN in the patients with hypocalcemia compared to the patients with normocalcemia was 4.54 (95% CI, 1.36 to 15.11). The association between low sCa and definite CAN was confirmed after adjustment for confounders with OR 13.62 (95% CI, 2.12 to 149.84). No association was found between definite CAN and PTH levels or high phosphate levels. HypoPT is associated with CAN and hypocalcemia seems to affect its severity. Larger and prospective studies are needed to confirm our findings. © 2018 American Society for Bone and Mineral Research

Preoperative Transcatheter Arterial Embolization and En-Bloc Resection for Giant Non-Functioning Left Adrenocortical Carcinoma: A Case Report

Objective: To demonstrate efficacy and relative safety of compartment surgery in a case of large sized adrenocortical carcinoma (ACC), whenever associated with preoperative transcatheter arterial embolization (TAE) and adjuvant treatment with mitotane. Introduction: ACC is a rare illness; non-functioning lesions account for 40-55% of patients, may reach a large size, and show a clear attitude to infiltrate neighbouring organs. Case Report: Middle aged male visited for a huge left abdominal mass; contrast CT scan showed origin from the left adrenal lodge and possible extension of the tumor to surrounding structures. Preoperative adrenal work-up confirmed non-functioning nature of the adrenal mass. In order to allow a safe compartment excision and to decrease blood loss, preoperative angiography and TAE was performed. Patient underwent en-bloc resection of the mass, together with nephrectomy and distal splenopancreasectomy. No postoperative transfusions were required. Patient received adjuvant therapy with mitotane for 36 months since surgery, without any sign of tumor recurrence. Conclusion: An aggressive surgical approach seems justified also in locally advanced and infiltrating ACC; compartment resection is mandatory in order to obtain adequate resection margins. Preoperative TAE decreases intraoperative blood loss and need for transfusions. Adjuvant treatment with mitotane may contribute to reach remarkable disease-free survival