Dalal S. Ali

Background: Postsurgical hypoparathyroidism (HypoPT) accounts for ∼75% of all HypoPT cases. It is recognized that this condition is largely preventable. Several studies have identified risk factors increasing the risk of developing postsurgical HypoPT, including patient-related factors, surgical factors, and, in some studies, presurgical factors. This narrative review highlights evidence-based guidelines for postsurgical HypoPT and provides strategies for its prevention, diagnosis, and management. Methods: We searched PubMed, Embase, Google Scholar, and the Cochrane Library from inception through December 2025. We included studies that examined the definition, diagnosis, prevalence, risk factors, management, long-term complications, and treatment outcomes of postsurgical HypoPT. Results: This review outlines strategies for identifying individuals at risk of developing postsurgical HypoPT, with the goal of minimizing these risks and using evidence-based approaches to accurately diagnose and effectively manage these patients. Historically, management of postsurgical HypoPT beyond the first 72 hours relied on calcium supplements with active vitamin D, which remains the first-line therapy in current practice. Parathyroid hormone (PTH) replacement has emerged as an option for individuals who do not respond to conventional therapy. More recently, a long-acting PTH molecule, palopegteriparatide, has been approved by the Food and Drug Administration for the management of HypoPT. This molecule has a 60-hour half-life and has demonstrated the ability to maintain normal serum calcium levels, lower urine calcium, lower serum phosphorus, and reduce the need for calcium and active vitamin D supplements. It has also demonstrated a positive impact on quality of life. Post hoc data from the phase 3 trial comparing palopegteriparatide with placebo demonstrated improvements in renal function with palopegteriparatide and cessation of conventional therapy in patients with HypoPT. Conclusions: Postsurgical HypoPT remains a significant complication of thyroid surgery; however, its risk can be mitigated by careful preoperative assessment and surgical technique. While conventional therapy continues to be the mainstay of treatment, the advent of PTH replacement therapies offers promising alternatives for patients with refractory HypoPT.

Primary hyperparathyroidism during pregnancy is rare but can lead to severe complications especially if the diagnosis is delayed. Herein, we present the case of a pregnant woman in her 30s (32 weeks’ gestation) with severe hypercalcaemia, skeletal brown tumours and pathological fractures. Initial management with fluids, calcitonin and cinacalcet was inadequate in controlling the hypercalcaemia. She required urgent parathyroidectomy, and this was completed successfully at 33 weeks’ gestation. A large single adenoma was removed, which was benign on histology. Postoperative complications included hungry bone syndrome and transient neonatal hypoparathyroidism, which resolved within 3 months.

Background: Chronic hypoparathyroidism (HypoPT) is a rare endocrine condition, having variable etiology, characterized by low parathyroid hormone levels, leading to reduced calcium levels and increased phosphorus values in the blood. Bone health is an important clinical aspect to be considered in patients with HypoPT, whose skeleton is exposed both to the HypoPT-induced alteration of bone mass and microarchitecture, and to the natural occurrence and progression of bone mass loss due to menopause and ageing. Aim: Investigating bone status in a cohort of Italian HypoPT patients from the HypoparaNET database. Methods: In this cross-sectional study, we retrospectively analyzed bone status in 162 adult, and 11 children and adolescent HypoPT cases, based to their sex, age, HypoPT etiology, urinary excretion of calcium and phosphate, and serum level of 25(OH)-vitamin D. Results: Overall prevalence of osteoporosis in adult HypoPT patients was found to be slightly lower to that of the general population (17.3% vs 18.3%), increasing with ageing and being more frequent in postmenopausal women. Data from our HypoPT cohort confirmed that ageing and female sex are independent risk factors for osteoporosis, even among individuals with HypoPT. Discussion: Results from this study suggest the importance of a regular follow-up of bone health in HypoPT, especially in postmenopausal women and young patients with a genetic form of HypoPT. Conclusions: Medical therapies aim at restoring a balanced bone turnover and preventing bone tissue loss could be indicated in HypoPT cases with reduced bone mass to grant a better bone health at any age.

Purpose: An international working group (IWG) consisting of experts in X-linked hypophosphatemia (XLH) developed global guidelines providing a comprehensive, evidence-based approach to XLH diagnosis, management, and monitoring. Methods: The IWG, consisting of 43 members as well as methodologists and a patient partner, conducted 2 systematic reviews (SRs) and narrative reviews to address key areas. The SRs addressed the impact of burosumab compared to conventional therapy (phosphate and active vitamin D) or no therapy on patient-important outcomes in adults. They also evaluated conventional therapy compared to no therapy. GRADE methodology was applied to evaluate the certainty of evidence. Non-GRADED recommendations were made in the presence of insufficient evidence to conduct SRs. These guidelines have been reviewed and endorsed by several medical and patient societies and organizations. Results: The diagnosis of XLH is based on integrating clinical evaluation, laboratory findings confirming renal phosphate wasting (following exclusion of conditions mimicking XLH), and skeletal imaging. Fibroblast growth factor 23 measurement and DNA analysis are of value in the diagnosis, if available. Pathogenic or likely pathogenic variants in the PHEX gene are confirmatory but not necessary for the diagnosis. Management requires a multidisciplinary team knowledgeable and experienced in XLH. Effective medical therapy with burosumab can improve fracture and pseudofracture healing. Main Conclusion: In adults with XLH and fractures or pseudofractures, burosumab is recommended over no therapy (strong recommendation, GRADEd). Additionally, burosumab is suggested as the preferred treatment compared to conventional therapy (conditional recommendation, GRADEd) in the absence of fractures or pseudofractures. If burosumab is not available, symptomatic adults should be treated with conventional therapy (Non-GRADEd recommendation).

The guideline panel, comprising international experts in X-linked hypophosphatemia (XLH), patient partners from the XLH patient population, and guideline methodologists, held 18 teleconferences between January 2023 and July 2024 to develop comprehensive guidelines for the diagnosis and management of XLH in children and adults. For a subset of our questions, we utilized the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, assessed the certainty of evidence and formulated GRADEd recommendations. For these questions, the panelists and methodologists collaboratively framed PICO (Population, Intervention, Control, and Outcomes) questions and conducted four systematic reviews assessing the impact of medical therapy—using either burosumab or phosphate and active vitamin D—on patient-important outcomes in the XLH population as well as the impact of medical intervention compared to no treatment. We assessed the risk of bias and transparently generated summary of findings tables using MAGICApp. The panel developed three GRADEd treatment recommendations for adults and two for children. Each GRADEd recommendation was linked to an underlying body of evidence, reflecting judgments on the certainty of evidence, recommendation strength, values, preferences, and considerations of costs, feasibility, acceptability, and equity. Due to the paucity of evidence, the panel developed very low-quality GRADEd recommendations on monitoring patients with XLH based on an expert clinical practice survey. Using a rigorous narrative literature review, the panel developed non-GRADEd recommendations including guidance for pregnant women, patients with dental complications, and other areas where evidence is limited. This article summarizes the methodology utilized for the development of both GRADEd and non-GRADEd recommendations for patients with XLH. Graphical abstract

This report provides recommendations for X-linked hypophosphatemia (XLH) monitoring based on current monitoring practices of experts in the management of XLH in children (<18 years) and adults. We surveyed 43 international experts in XLH to determine their monitoring practices for children and adults with XLH, including pregnant and lactating women. In the initial evaluation of children and adults with XLH, experts consistently obtain a family history of XLH or hypophosphatemia, a history of fractures and dental infections, and assess pain through age-appropriate clinical interviews or caregiver reports. They measure height, weight, and blood pressure and conduct DNA analysis of multiple genes associated with hypophosphatemia including the PHEX gene. For children follow-up, experts arrange follow-up every 3 to 6 months assessing height, weight, and blood pressure and examining for skeletal deformities. Laboratory tests in children include serum phosphorus, corrected total/ionized calcium, alkaline phosphatase, renal function, and PTH and spot morning urine for calcium, creatinine, and phosphorus. During adult follow-up, experts assess patients every 6 to 12 months, with a clinical examination focused on skeletal deformities and joint involvement. The laboratory profile is completed at least once a year. In the presence of bone pain, experts conduct X-rays both in children and adults to evaluate for fractures or joint damage. With respect to nephrocalcinosis, renal ultrasound is suggested on an annual basis or less frequently when monitoring children and adults with XLH. Experts conduct a dental assessment at baseline and then every 6 to 12 months for all patients with XLH. The findings of the survey inform practice for assessing new patients with XLH, monitoring existing patients, and identifying areas for future research. All recommendations based on these practices are weak with very low-quality evidence.