Hypophysitis and central nervous system involvement in association with Sjögren's syndrome along with hypoparathyroidism: a case report.

BACKGROUND: Patients with autoimmune diseases can develop multiple autoimmune diseases over a long period of time, and the presence of more than one autoimmune disease in a single patient is defined as polyautoimmunity. Polyautoimmunity may be clinical evidence that autoimmune diseases share similar immunological mechanisms. CASE PRESENTATION: We report a 30-year-old woman with a unique combination of autoimmune diseases predominantly affecting the central nervous system, with hypoparathyroidism, hypophysitis, medulla involvement, and pons and temporal lobe involvement associated with primary Sjögren's syndrome (pSS), occurring independently over a long period. The patient who had a history of muscle cramps and one seizure incident, presented with vomiting and blurred vision. She was diagnosed with hypophysitis and hypoparathyroidism with calcifications in the basal ganglia and cerebellum. She recovered after four months of corticosteroid treatment for hypophysitis and was started on treatment for hypoparathyroidism. Eight months later, she developed vomiting, hiccups, vertigo, and ataxia with a focal lesion in the medulla. She recovered with immunosuppressive treatment for 2 years. Fifty-eight months after the onset of hypophysitis, she developed diplopia and dry mouth and eyes. MRI showed infiltrative lesions in the left pons and left temporal lobe. Based on positive anti-Sjögren's syndrome-related antigen A antibodies and low unstimulated whole salivary flow rate, pSS was diagnosed. She received corticosteroids and continued mycophenolate mofetil treatment with recovery of neurological symptoms. CONCLUSION: This case highlights the need for long-term follow-up to detect autoimmune disease processes involving various organs.

Hypoparathyroidism after total thyroidectomy: reactive to symptoms supplementation.

INTRODUCTION: After total thyroidectomy (TT), postoperative hypoparathyroidism (PH) is the most frequent complication. Yet, management strategies for PH remain disputed. The aim of this study was to evaluate outcomes of a reactive supplementation in case of symptomatic PH. Additionally, risk factors for symptomatic PH and readmission due to PH were analyzed. MATERIALS AND METHODS: All consecutive patients who underwent TT or completion from 2017 to 2022 were considered for inclusion. During this period, a reactive to symptom vitamin-calcium supplementation was used. The primary outcome was the occurrence of severe PH after discharge resulting in readmission. RESULTS: Overall, 307 patients were included, of which 98 patients (31.9%) developed symptomatic PH including 43 patients before discharge. Independent risk factors for developing symptomatic PH were age (p = 0.010) and postoperative day 1 (POD1) PTH level (p < 0.001). Overall, 264 patients (86%) did not present PH before discharge and were discharged home. Among them, 55 patients (20.8%) experienced symptomatic PH, requiring readmission in 18 patients. The overall readmission rate owing to symptomatic PH requiring intravenous supplementation despite oral vitamin-calcium supplementation was 6.8% (n = 18). Independent risk factors for symptomatic PH-related readmission were age (p = 0.007) and POD1 PTH level (p < 0.001). Adequate cut-off values for predicting readmission were POD1 albumin-adjusted calcium = 2.1 mmol/l (Sensibility = 0.95, Specificity = 0.30) and POD1 PTH = 11.5 pg/ml (Sensibility = 0.90, Specificity = 0.71). CONCLUSION: Supplementing only symptomatic patients was safe and efficient. This attitude does not alter on morbidity, mortality or readmission rate which is in line with current literature.

Corticosteroid rhythms in hypoparathyroid patients.

OBJECTIVE: Previous studies indicate a possible bidirectional stimulatory relationship between parathyroid hormone (PTH) and adrenocortical hormones, but the pattern of adrenocortical secretion in hypoparathyroidism is unknown. We aimed to characterize the adrenocortical secretion in patients with postsurgical hypoparathyroidism, and whether continuous subcutaneous PTH (1-34) infusion alters secretion patterns. DESIGN: Crossover interventional study. METHODS: We recruited 10 patients with postsurgical hypoparathyroidism with very low PTH levels on stable treatment with active vitamin D and calcium. Cortisol, cortisone, and aldosterone levels were measured in microdialysate from subcutaneous tissue over 24 h, before and during continuous subcutaneous PTH (1-34) infusion. Cortisol was also assayed in serum, saliva, and urine, and aldosterone and ACTH in serum and plasma, respectively. Ten patients with primary hyperparathyroidism and 10 healthy volunteers matched for sex and age served as controls. RESULTS: Hypoparathyroid patients displayed both ultradian and circadian rhythmicity for tissue cortisol, cortisone, and aldosterone. Tissue aldosterone and cortisone levels were significantly lower in hypoparathyroid patients than in healthy controls, with no difference in tissue cortisol, but a higher cortisol to cortisone ratio. Treatment with PTH (1-34) increased tissue levels of aldosterone, cortisol, and cortisone and reduced the ratio of cortisol to cortisone. CONCLUSION: Adrenocortical hormone levels are reduced in postsurgical hypoparathyroidism, and partly restored by short-term continuous subcutaneous PTH (1-34) therapy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02986607.

Measuring treatment impacts on symptoms in adults with hypoparathyroidism: findings from the PaTHway trial.

BACKGROUND: Hypoparathyroidism is a rare endocrine disease frequently associated with serious physical and cognitive symptoms. This study's purpose was to understand the impacts of the phase 3 PaTHway clinical trial treatment, TransCon PTH, on patients' overall, physical, and cognitive hypoparathyroidism signs/symptoms and what patients consider meaningful improvement. METHODS: Individual telephone exit interviews were conducted with patients who recently completed the PaTHway trial blinded period. Using a semi-structured interview guide, interviews focused on trial treatment impact on hypoparathyroidism symptoms following the symptom list in the Hypoparathyroidism Patient Experience Scale-Symptom (HPES-Symptom). Meaningful changes in hypoparathyroidism symptoms were assessed with the Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) measures. Interviewees were probed on the meaningfulness of reported changes in symptoms from prior to starting trial treatment to the past 2 weeks/current time. Interviews were audiotaped and transcribed. Transcripts were coded for emerging concepts and themes/subthemes covered in the interview guide based on an adapted grounded theory approach. RESULTS: Nineteen adults with hypoparathyroidism participated in interviews in the United States (n = 13, 68.4%) and Canada (n = 6, 31.6%). Marked improvements in physical and cognitive symptoms were described among trial treatment group respondents. The majority of participants who reported experiencing hypoparathyroidism physical symptoms pre-trial indicated symptom improvement with treatment, including muscle twitching (100%, n = 15), low energy (92.9%, n = 13), feeling tired (92.3%, n = 12), muscle weakness (92.9%, n = 13), tingling without numbness (84.6%, n = 11), trouble sleeping (92.3%, n = 12), muscle cramping (92.3%, n = 12), tingling with numbness (92.3%, n = 12), muscle spasms (100%, n = 12), and pain (90.9%, n = 10). Most participants who reported experiencing cognitive symptoms pre-trial reported symptom improvement with treatment, including difficulty finding the right words (86.7%, n = 13), difficulty concentrating (93.3%, n = 14), trouble remembering (92.9%, n = 13), trouble thinking clearly (85.7%, n = 12), and difficulty understanding information (83.3%, n = 10). Those in the placebo group reported limited or no improvement. The vast majority of participants affirmed that the improvements they experienced in symptom frequency on the PGIS/PGIC and HPES-Symptom were meaningful. CONCLUSIONS: Findings indicate that TransCon PTH treatment improved participants' physical and cognitive hypoparathyroidism symptoms in meaningful ways, while reducing the daily burden associated with conventional therapy. TRIAL REGISTRATION: NCT04701203 Registered: 06 January 2021. https://clinicaltrials.gov/study/NCT04701203?term=NCT04701203&rank=1 .

The role of parathyroid autotransplantation for hypoparathyroidism following total thyroidectomy with bilateral central neck dissection.

Background: Hypoparathyroidism is the most common complication for patients who undergo total thyroidectomy (TT) with bilateral central lymph node dissection (BCLND). The objective of this retrospective study was to investigate the relationship between parathyroid autotransplantation (PA) and postoperative hypoparathyroidism. Materials and Methods: Four hundred and sixty-five patients with papillary thyroid carcinoma (PTC) who underwent TT with BCLND (including prophylactic and therapeutic BCLND) by the same surgeon were enrolled in this retrospective study. They were divided into five groups based on the number of PAs. Group 0 was defined as no PA, while Group 1, 2, 3, and 4 were considered as 1, 2, 3, and 4 PAs during TT with BCLND, respectively. Results: Transient and permanent hypoparathyroidism occurred in 83 (17.8%) and 2 (0.4%) patients who underwent TT and BCLND, respectively. The incidence of transient hypoparathyroidism increased gradually with an increase in the number of PAs. Compared with the previous group, Groups 2 and 3 had significantly more cases of transient hypoparathyroidism (p=0.03 and p=0.04, respectively). All cases of permanent hypoparathyroidism occurred in the patients without PA. Compared with Group 0, there were more removed central lymph nodes (RCLNs) in patients with one PA. Furthermore, Group 2 had more metastatic central lymph nodes(MCLNs) and RCLNs than Group 1.The number of PAs was the only identified risk factor for transient hypoparathyroidism after the multivariate logistic regression analysis. The median parathyroid hormone level recovered to the normal range within 1 month after surgery. Conclusion: With an increasing number of PAs, the possibility of transient hypoparathyroidism also increases in patients with PTC who undergo TT and BCLND. Considering the rapid recovery of transient hypoparathyroidism in 1 month, two PAs during TT and BCLND could be a good choice, leading to an increase in the central lymph node yield and no permanent hypoparathyroidism. However, this conclusion should be validated in future multicenter prospective studies.

Feasibility of remote-access and minimally invasive video-assisted approaches in lateral neck dissection for papillary thyroid carcinoma: A systematic review and network meta-analysis.

BACKGROUND: This study was conducted to evaluate the feasibility and surgical outcomes of minimally invasive video-assisted thyroidectomy (MIVAT) and three remote-access approaches, namely the robotic bilateral axillo-breast approach (BABA-R), endoscopic breast-chest approach (BCA-E), and robotic gasless transaxillary approach (GTAA-R) in lateral neck dissection for papillary thyroid carcinoma, compared with conventional transcervical approach (CTA). METHODS: The literature search was conducted in the PubMed, EMBASE, and Cochrane Library databases, covering the period January 2000 to February 2024. A systematic review and network meta-analysis were performed to compare surgical feasibility, safety, and oncologic outcomes between approaches. RESULTS: Fourteen articles on lateral neck dissection in patients with papillary thyroid carcinoma were included after systematic screening. The number of removed and metastatic lateral lymph nodes, the extent of lateral neck dissection, the rate of transient recurrent laryngeal nerve palsy and hypoparathyroidism, serum-stimulated thyroglobulin levels, and recurrence were not significantly different between the MIVAT and three remote-access approaches. Additionally, these were comparable to those of the CTA. However, the MIVAT and remote-access approaches took a longer operative time but provided superior cosmetic outcomes compared to the CTA. CONCLUSION: Lateral neck dissection using the MIVAT and three remote-access approaches was feasible and comparable to CTA in the number of lymph nodes removed, complications, stimulated thyroglobulin level, and recurrence. The MIVAT and remote-access approaches lasted longer but provided significantly superior cosmetic outcomes compared to the CTA.

Parathyroid Gland Generation from Pluripotent Stem Cells.

Patients with permanent hypoparathyroidism require lifelong treatment. Current replacement therapies sometimes have adverse effects (e.g., hypercalciuria and chronic kidney disease). Generating parathyroid glands (PTGs) from the patient's own induced pluripotent stem cells (PSCs), with transplantation of these PTGs, would be an effective treatment option. Multiple methods for generating PTGs from PSCs have been reported. One major trend is in vitro differentiation of PSCs into PTGs. Another is in vivo generation of PSC-derived PTGs by injecting PSCs into PTG-deficient embryos. This review discusses current achievements and challenges in present and future PTG regenerative medicine.

Long-term kidney outcomes in patients with permanent hypoparathyroidism after total thyroidectomy for benign disease: A population-based study.

BACKGROUND: Permanent hypoparathyroidism is a significant complication after total thyroidectomy. This study aimed to evaluate the long-term impact of postoperative permanent hypoparathyroidism on kidney outcomes. METHODS: Data of patients undergoing total thyroidectomy from 1999 to 2014 were retrieved. The estimated glomerular filtration rate was determined from serum creatinine results. Permanent hypoparathyroidism was defined as requiring oral calcium and vitamin D supplements postoperatively for at least 6 months. The primary outcome was a sustained decline in the estimated glomerular filtration rate from baseline by ≥50%. Secondary outcomes were end-stage kidney disease (a composite of sustained estimated glomerular filtration rate <15 mL/min/1.73 m2, need for dialysis, and kidney transplantation) and rate of estimated glomerular filtration rate decline. Patients with and without permanent hypoparathyroidism were compared. Multivariable Cox regression analysis was performed to identify independent risk factors for sustained estimated glomerular filtration rate decline by ≥50%. RESULTS: In total, 3,245 patients were eligible for analysis; 418 patients (12.9%) had permanent hypoparathyroidism. Upon median follow-up of 11.6 years, more patients with permanent hypoparathyroidism had a sustained decline in estimated glomerular filtration rate from baseline by ≥50% compared to those without (15.6% vs 6.9%, P < .001). Similar findings were obtained on Kaplan-Meier analysis (P < .001). Permanent hypoparathyroidism was an independent risk factor for sustained estimated glomerular filtration rate decline by ≥50% (adjusted hazard ratio 2.77, P < .001). Other risk factors included age, preoperative estimated glomerular filtration rate <60 mL/min/1.73m2, and diabetes mellitus. Patients with permanent hypoparathyroidism had a more rapid estimated glomerular filtration rate decline (-1.60 vs -0.70 mL/min/1.73 m2/year, difference -0.91 mL/min/1.73m2/year, P < .001). CONCLUSION: Patients with postsurgical permanent hypoparathyroidism were at greater risk of renal impairment. Further research is warranted to improve the identification and preservation of parathyroid glands during thyroidectomy to minimize patient morbidity.

From seizures to cognitive dysfunction: A case report of Fahr syndrome in an Afghan patient.

RATIONALE: Fahr syndrome is a rare, degenerative neurological condition characterized by bilateral idiopathic calcification of the periventricular region, especially the basal ganglia. This condition is often misdiagnosed as other neurological or psychiatric disorders due to its rarity and overlapping symptoms. PATIENT CONCERNS: A 34-year-old man had been experiencing seizures and cognitive dysfunction for few years, which were further compounded by slurred speech and motor difficulties as acute conditions. DIAGNOSIS: After investigations, severe hypocalcemia, and hypoparathyroidism were detected and his brain computed tomography showed extensive bilateral calcifications in basal ganglia, thalamus, dentate nuclei, and some parts of subcortical white matter, suggestive of Fahr syndrome. Although, the patient was initially misdiagnosed due to a lack of information and the rarity of this disease. INTERVENTION: The patient was treated with intravenous calcium gluconate, vitamin D3, l-ornithine l-aspartate syrup, and levetiracetam, replacing carbamazepine. OUTCOME: His symptoms, including slurred speech, muscle pain, and stiffness improved, serum calcium normalized, and he was discharged with medications for memory deficit and depression. LESSONS: This case underscores the importance of raising awareness among physicians, especially in areas with limited medical resources, about the significance of prompt diagnosis and appropriate symptomatic treatment in enhancing patient prognosis and quality of life.

Iatrogenic Hypoparathyroidism Development After Thyroidectomy: A Retrospective Cohort Study.

BACKGROUND: Iatrogenic hypoparathyroidism is a common cause of postthyroidectomy hypocalcaemia. It has varying incidence rates after neck surgery in Saudi Arabia, ranging from 0.07% to 65.30%. Hypoparathyroidism can manifest with a spectrum of symptoms, ranging from mild to severe and life-threatening. This study aimed to assess the rate and predictors of iatrogenic hypoparathyroidism after thyroid surgery and its natural course. METHODS: This retrospective cohort study used a data collection form to extract patient information from the electronic healthcare system (Best-Care) for patients treated from 2017 to 2022. Patients' demographics, surgical specifics and biochemical profiles were recorded for subsequent analysis. RESULTS: Among the 343 patients who underwent thyroidectomy, 130 (37.9%) developed hypoparathyroidism, primarily within the first day after surgery. Calcium or vitamin D supplementation before surgery did not significantly influence hypoparathyroidism development. Notably, extensive combined lymph node dissection was significantly associated with postoperative hypoparathyroidism development (p = 0.0004). More patients who underwent central and lateral lymph node dissection (n = 19, 79.17%) developed hypoparathyroidism than patients who underwent central (n = 18, 40.91%) or lateral (n = 8, 38.10%) dissection alone. Permanent hypoparathyroidism was observed in 40 patients (11.66%). CONCLUSION: This study revealed a high incidence of iatrogenic hypoparathyroidism and high rates of permanent hypoparathyroidism. Further research is warranted to better comprehend the risk factors and optimise management strategies for iatrogenic hypoparathyroidism. Overall, our findings emphasise the need for vigilant monitoring and effective management of patients undergoing thyroidectomy and the significance of postoperative replacement therapies.

Mechanistic Insights into Tanshinone IIA in the Amelioration of Post-Thyroidectomy Hypoparathyroidism.

BACKGROUND: Thyroidectomy causes impaired blood supply to the parathyroid glands, which leads to hypoparathyroidism. Tanshinone IIA (Tan IIA) is helpful in blood activation and cardiovascular protection. Therefore, the efficacy of Tan IIA in improving hypoparathyroidism was explored in this study. METHODS: New Zealand white rabbits were utilized to establish a unilateral parathyroid gland ischemia injury model. The model was created by selectively ligating the main blood supply vessel of one parathyroid gland, and the rabbits were then divided into three groups receiving 1, 5, and 10 mg/kg of Tan IIA. Serum calcium and parathyroid hormone (PTH) levels were measured using specialized assay kits. Immunohistochemistry was used to assess the microvessel density (MVD) in parathyroid glands. Western blotting (WB) was used to analyze protein expression related to the PI3K/AKT signaling pathway and the pathway-associated HIF-1α and VEGF. Moreover, MMP-2 and MMP-9 involved in angiogenesis were detected by WB. RESULTS: Tan IIA treatment effectively restored serum calcium and PTH levels in a dose-dependent manner. Notably, MVD in the parathyroid glands increased significantly, especially at higher doses. The Tan IIA treatment also elevated the p-PI3K/PI3K and p-AKT/AKT ratios, indicating that the PI3K/AKT pathway was reactivated. Moreover, Tan IIA significantly restored the decreased expression levels of VEGF and HIF-1α caused by parathyroid surgery. Additionally, Tan IIA increased MMP-2 and MMP-9 levels. CONCLUSION: Tan IIA activates the PI3K/AKT pathway, promotes angiogenesis by modulating VEGF, HIF-1α, MMP-2, and MMP-9, thereby further enhancing MVD within the parathyroid glands. This study demonstrates that Tan IIA improved post-thyroidectomy hypoparathyroidism.

Impact of autofluorescence-guided surgery of parathyroid glands during total thyroidectomy in experienced surgeons: A randomized clinical trial.

INTRODUCTION: Post-surgical hypoparathyroidism often occurs after total thyroidectomy (TT). The aim of this study is to investigate whether the use of near-infrared autofluorescence (NIRAF) of parathyroid glands (PGs) can aid experienced surgeons in identifying more PGs during surgery, potentially reducing unintended resection, and assessing its impact on post-surgical hypoparathyroidism. MATERIALS AND METHODS: All patients undergoing at least a TT by two experienced surgeons, between 2020 and 2021, were enrolled and randomized into two cohorts: NIRAF group (NG) and CONTROL group (CG). Transient hypoparathyroidism was defined by serum concentration of PTH<12 ng/mL at the 1st post-operative day and permanent by the need of calcium-active vitamin D treatment >6 months from the surgery with still undetectable PTH or <12 ng/m. RESULTS: Among 236 patients (111 in NG, 125 in CG), the number of PGs identified was higher in NG (93.9%, 417/444) compared to CG (81.4%, 407/500) (p < 0.001), with a mean of 3.76 ± 0.44 PGs per patient in NG and 3.25 ± 0.79 in CG. The number of unintendedly resected PGs was 14 in NG and 42 in CG (p < 0.0001). Transient hypoparathyroidism was observed in 18 patients (16.2%) in NG and 40 patients (32.0%) in CG (p = 0.004). Permanent hypoparathyroidism affected 1 patient in NG and 7 patients in CG (p = 0.06). The mean operative time was longer in NG (104.3 ± 32.08 min) compared to CG (85.5 ± 40.62 min) (p < 0.001). CONCLUSIONS: NIRAF enhances the identification of PGs, preventing their inadvertent resection and reducing the overall incidence of post-surgical hypoparathyroidism.

Evaluation of Hypocalcemia Following Total Laryngectomy With and Without Thyroidectomy.

OBJECTIVE: Hypoparathyroidism and associated hypocalcemia are well-established complications following laryngectomy. This study further characterizes the rates of hypocalcemia in patients undergoing total laryngectomy (TL) with and without thyroidectomy and hemithyroidectomy. STUDY DESIGN: Retrospective cohort study. SETTING: TriNetX. METHODS: We queried TriNetX, a deidentified patient database, to identify patients who underwent TL with and without thyroidectomy and hemithyroidectomy. Rates of hypocalcemia, low parathyroid hormone (PTH), calcium, and calcitriol supplementation were compared between groups with multivariable repeated measures logistic regression. RESULTS: We identified 870 patients in the TL without thyroidectomy cohort, 158 patients in the hemithyroidectomy cohort, and 123 in the total thyroidectomy cohort. Rates of hypocalcemia differed between patients receiving total thyroidectomy versus TL alone for 0 to 1 month (odds ratio [OR]: 2.88 [1.95-4.26]) 1 to 6 months (OR: 5.08 [2.29-11.3]), and 6 to 12 months (OR: 2.63 [1.003-6.88]) postoperatively, with adjustment for age at laryngectomy, race, ethnicity, and gender. Results were similar among those who received calcium supplementation. The rate of low PTH levels differed in these groups for 0 to 1 month (OR: 5.13 [3.10-8.51]), 1 to 6 months (OR: 3.47 [1.46-8.22]), and 6 to 12 months (OR: 3.63 [1.40-9.38]) following surgery. Rates of postoperative calcium supplementation were increased for patients receiving total thyroidectomy versus TL for 1 to 6 months (OR: 2.44 [1.62-3.68]), and 6 to 12 months following surgery (OR: 1.79 [1.18-2.72]). CONCLUSION: Patients undergoing TL with total thyroidectomy have a higher risk of postoperative hypocalcemia compared to patients receiving TL alone. Risk of parathyroid injury in these patients may warrant further emphasis on PTH measurement after surgery and a multidisciplinary approach to management.

New insights into renal calcium-sensing receptor activation.

PURPOSE OF REVIEW: Activation of the calcium-sensing receptor (CASR) in the parathyroid gland suppresses the release of parathyroid hormone (PTH). Furthermore, activation of the renal CASR directly increases the urinary excretion of calcium, by inhibiting transepithelial calcium transport in the nephron. Gain-of-function mutations in the CASR gene lead to autosomal dominant hypocalcemia 1 (ADH1), with inappropriately low PTH levels and hypocalcemia, indicative of excessive activation of the parathyroid CASR. However, hypercalciuria is not always observed. The reason why the manifestation of hypercalciuria is not uniform among ADH1 patients is not well understood. RECENT FINDINGS: Direct activation of the CASR in the kidney has been cumbersome to study, and an indirect measure to effectively estimate the degree of CASR activation following chronic hypercalcemia or genetic gain-of-function CASR activation has been lacking. Studies have shown that expression of the pore-blocking claudin-14 is strongly stimulated by the CASR in a dose-dependent manner. This stimulatory effect is abolished after renal Casr ablation in hypercalcemic mice, suggesting that claudin-14 abundance may gauge renal CASR activation. Using this marker has led to unexpected discoveries regarding renal CASR activation. SUMMARY: These new studies have informed on renal CASR activation thresholds and the downstream CASR-regulated calcium transport mechanisms.

Hypoparathyroidism update.

PURPOSE OF REVIEW: Since the release of the 2022 Second International Workshop Evaluation and Management of Hypoparathyroidism Summary Statement and Guidelines, updates and advances are now available in the cause, complications, and treatment of adult chronic hypoparathyroidism (hypoPTH). This review aims to highlight these new findings and implications to patient care. RECENT FINDINGS: Postsurgical hypoparathyroidism remains the most common cause, immune-related hypoparathyroidism from checkpoint inhibitors is an emerging autoimmune cause. In a large retrospective cohort study of thyroidectomies, incident fracture was lower, particularly in the vertebra, in the hypoPTH cohort, compared with postthyroidectomy control group. Hypercalciuria increases risk for renal calculi in hypoPTH independent of disease duration and treatment dose. Quality of life is impaired in hypoPTH patients on conventional therapy, improvement was noted post-PTH replacement. TranCon PTH phase 3 RCT reported eucalcemia with reduced renal calcium excretion, normalization of bone turn-over markers, stable BMD and improved quality of life. SUMMARY: HypoPTH is a chronic disease associated with significant morbidity and poor Quality of Life. Awareness of treatment targets and follow-up investigations can alleviate patient anxiety regarding over-treatment and under-treatment. Progress in long-acting PTH replacement strategies might provide accessible, feasible alternatives to conventional therapy in brittle hypoPTH patients.

Autofluorescence-Guided Total Thyroidectomy in Low-Volume, Nonparathyroid Institutions.

Importance: Hypoparathyroidism following thyroid surgery is a serious complication that occurs frequently when surgery is performed by low-volume thyroid surgeons without experience in parathyroid surgery. Objective: To evaluate the occurrence of hypoparathyroidism following total thyroidectomy after the introduction of autofluorescence in low-volume, nonparathyroid institutions. Design, Setting, and Participants: This prospective, multicenter cohort study, with a follow-up period of up to 1 year, was conducted in Denmark at 2 low-volume nonparathyroid institutions between January 2021 and November 2023. All adult patients referred for total thyroidectomy were assessed for eligibility (n = 90). Only patients with no history of thyroid surgery were considered (n = 89). Patients who only underwent lobectomy (n = 6) or declined to participate (n = 5) were excluded. All included patients completed follow-up. The prospective cohort was compared with a historical cohort of successive patients undergoing primary total thyroidectomy from 2016 to 2020 (before autofluorescence was available). Intervention: Included patients underwent autofluorescence-guided total thyroidectomy. Main outcomes and Measures: Rate of hypoparathyroidism. Immediate hypoparathyroidism was defined as the need for active vitamin D postoperatively, whereas permanent hypoparathyroidism was considered when there still was a need for active vitamin D 1 year after surgery. Results: Seventy-eight patients underwent autofluorescence-guided surgery (mean [SD] age, 55.6 [13.1] years; 67 [86%] female) and were compared with 89 patients in the historical cohort (mean [SD] age, 49.7 [12.8] years; 78 [88%] female). The rate of immediate hypoparathyroidism decreased from 37% (95% CI, 27%-48%) to 19% (95% CI, 11%-30%) after the introduction of autofluorescence (P = .02). Permanent hypoparathyroidism rates decreased from 32% (95% CI, 22%-42%) to 6% (95% CI, 2%-14%) (P < .001), reaching 0% at the end of the study. More parathyroid glands were identified with autofluorescence (75% [95% CI, 70%-80%] vs 61% [95% CI, 56%-66%]) (P < .001) and less parathyroid glands were inadvertently excised (4% [95% CI, 1%-11%] vs 21% [95% CI, 13%-31%]) (P = .001). Conclusions and Relevance: In this cohort study of autofluorescence-guided thyroid surgery in low-volume, nonparathyroid institutions, the use of autofluorescence was associated with a significant decrease in both immediate and permanent hypoparathyroidism. When autofluorescence was used, hypoparathyroidism rates were comparable with those of high-volume surgeons who also perform parathyroid surgery.

Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial.

INTRODUCTION: Individuals with chronic hypoparathyroidism managed with conventional therapy (active vitamin D and calcium) have an increased risk for renal dysfunction versus age- and sex-matched controls. Treatments that replace the physiologic effects of parathyroid hormone (PTH) while reducing the need for conventional therapy may help prevent a decline in renal function in this population. This post hoc analysis examined the impact of palopegteriparatide treatment on renal function in adults with chronic hypoparathyroidism. METHODS: PaTHway is a phase 3 trial of palopegteriparatide in adults with chronic hypoparathyroidism that included a randomized, double-blind, placebo-controlled 26-week period followed by an ongoing 156-week open-label extension (OLE) period. Changes in renal function over 52 weeks (26 weeks blinded + 26 weeks OLE) were assessed using estimated glomerular filtration rate (eGFR). A subgroup analysis was performed with participants stratified by baseline eGFR < 60 or ≥ 60 mL/min/1.73 m2. RESULTS: At week 52, over 95% (78/82) of participants remained enrolled in the OLE and of those, 86% maintained normocalcemia and 95% achieved independence from conventional therapy (no active vitamin D and ≤ 600 mg/day of calcium), with none requiring active vitamin D. Treatment with palopegteriparatide over 52 weeks resulted in a mean (SD) increase in eGFR of 9.3 (11.7) mL/min/1.73 m2 from baseline (P < 0.0001) and 43% of participants had an increase ≥ 10 mL/min/1.73 m2. In participants with baseline eGFR < 60 mL/min/1.73 m2, 52 weeks of treatment with palopegteriparatide resulted in a mean (SD) increase of 11.5 (11.3) mL/min/1.73 m2 (P < 0.001). One case of nephrolithiasis was reported for a participant in the placebo group during blinded treatment; none were reported through week 52 with palopegteriparatide. CONCLUSION: In this post hoc analysis of the PaTHway trial, palopegteriparatide treatment was associated with significantly improved eGFR at week 52 in addition to previously reported maintenance and normalization of serum and urine biochemistries. Further investigation of palopegteriparatide for the preservation of renal function in hypoparathyroidism is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT04701203.

Chronic hypoparathyroidism is caused by inadequate parathyroid hormone (PTH) levels. Hypoparathyroidism is managed with conventional therapy (active vitamin D and calcium), but over time the disease itself and conventional therapy can increase the risk of medical complications including kidney problems. This study looked at how a new treatment for chronic hypoparathyroidism, palopegteriparatide (approved in the European Union under the brand name YORVIPATH^®), affects kidney function in adults in the PaTHway clinical trial. Participants were randomly assigned to receive palopegteriparatide or a placebo injection once daily along with conventional therapy. For both groups, clinicians used a protocol to eliminate conventional therapy while maintaining normal blood calcium levels. After 26 weeks, participants on placebo switched to palopegteriparatide. Ninety-five percent of participants were still enrolled in the PaTHway trial after 52 weeks. Of those, 86% had normal blood calcium levels and 95% did not need conventional therapy (not taking vitamin D and not taking therapeutic doses of calcium [> 600 mg/day]). After 52 weeks of treatment with palopegteriparatide, significant improvements were seen in a measure of kidney function called estimated glomerular filtration rate (eGFR). Improvements in eGFR from the beginning of the trial to week 52 were considered clinically meaningful for over 57% of participants. In participants with impaired kidney function at the beginning of the trial, eGFR improvements were even greater, and 74% of participants had a clinically meaningful improvement. These results suggest that palopegteriparatide treatment may be beneficial for kidney function in adults with chronic hypoparathyroidism, especially those with impaired kidney function.