Search Results (22)

Background/Objectives: Despite its increasing incidence in older patients, parathyroidectomy for primary hyperparathyroidism (PHPT) is frequently deferred owing to risks and age-related comorbidities and the limited evidence of age-specific surgical safety and biochemical outcomes. We evaluate age-related differences in clinical characteristics, perioperative outcomes, postoperative complications, and biochemical responses, including bone turnover markers, after parathyroidectomy for PHPT. Methods: We retrospectively enrolled 596 patients who underwent parathyroidectomy between 2009 and 2022, stratified into three age groups: <65, 65–74, and ≥75 years (Group A, n = 401; Group B, n = 141; and Group C, n = 54, respectively). Demographics, comorbidities, operative details, complications, pathology, and biochemical parameters were compared between the groups. Results: Older patients exhibited a higher prevalence of hypertension, cardiovascular disease, diabetes, osteoporosis, and chronic kidney disease (all p < 0.01), whereas multiple endocrine neoplasias were more frequent in younger patients (p = 0.002). Younger patients had a longer operation time (p = 0.006). There were no significant intergroup differences in postoperative hospital stay and complication rates, including transient hypoparathyroidism, hungry bone syndrome, and recurrent laryngeal nerve injury. Pathologic diagnoses were comparable, with single adenoma being most common (81.0–86.2%). The postoperative calcium and parathyroid hormone levels normalized in all groups. Younger patients had higher baseline bone turnover markers and demonstrated greater absolute reductions postoperatively (p = 0.030 and p = 0.042, respectively); however, improvements were observed in all age groups. Conclusions: When appropriately selected, parathyroidectomy is safe and effective in all age groups, including older patients with comorbidities. Considering its evident biochemical and skeletal benefits, age should not preclude surgical intervention for PHPT. Full article

Parathyroid gland disorders, including secondary hyperparathyroidism, have emerged as significant endocrine complications in people living with HIV (PLWHIV). This narrative review synthesises recent evidence on the prevalence, mechanisms, and clinical implications of parathyroid dysfunction in PLWHIV. HIV infection, combined antiretroviral therapy (cART), and immune activation contribute to parathyroid dysfunction, with cART regimens, particularly Tenofovir Disoproxil Fumarate (TDF), exacerbating these disturbances by altering the calcium and parathyroid hormone (PTH) dynamics. Studies show that PTH levels in PLWHIV on TDF were significantly elevated compared to those on non-TDF-based cART regimens. Histopathological studies highlight a higher prevalence of parathyroid hyperplasia in PLWHIV, often linked to chronic deficiencies in calcium, magnesium, and vitamin D, as well as immune dysregulation. The dysfunction observed ranges from inappropriate elevation of PTH levels to hypoparathyroidism, leading to rapid bone density loss and an increased fracture risk. Despite the fact that HIV is a condition associated with high malignancy, parathyroid malignancy is a very rare issue. Despite the growing recognition of these complications, routine screening for PTH and bone health remains inadequate in standard clinical HIV care. This review advocates for incorporating routine monitoring of serum PTH, calcium, phosphate, and vitamin D levels, especially in those on TDF-based cART. Early detection of subclinical parathyroid dysfunction can prevent complications such as secondary hyperparathyroidism and neuromuscular symptoms. Clinicians should be aware of atypical biochemical presentations, such as elevated PTH with normal calcium, which may indicate cART-induced dysregulation, improving patient management and outcomes. Full article

Autoimmune polyendocrine syndrome type 1 (APS-1, APECED) is a rare monogenic disorder caused by biallelic AIRE mutations and is classically associated with chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency. Apart from the autoimmune manifestations, APS-1 is associated with an increased risk of squamous cell carcinoma (SCC), particularly in the oral cavity and esophagus. However, the evidence is patchy and has not yet been systematically reviewed. We conducted a scoping review according to the PRISMA-ScR guidelines. Pub-Med, Scopus, and Web of Science were searched using the terms APS-1/APECED and malignancy until July 2025. Eligible studies reported on APS-1 patients with histologically confirmed head, neck or esophageal cancer. Clinical, pathological, genetic and outcome data were summarized narratively. Nine publications described 19 APS-1 patients with 26 tumors. The mean age at cancer diagnosis was 35 years, with a latency period of ~24 years from the onset of APS-1. Tumors occurred most frequently in the oral cavity (65%), followed by the lip (19%) and esophagus (15%). In 96% of cases, the tumors were SCC. The grade of the tumor varied, and almost half of the cases were diagnosed at an advanced stage. As far as reported, the usual risk factors were not particularly pronounced; many patients did not smoke or drink alcohol. The main treatment consisted of surgery, often in combination with radiotherapy or chemoradiotherapy, alongside long-term antifungal therapy. Despite the multimodal treatment, outcomes were poor: the overall survival rate was ~50%, with recurrence occurring in 38% of cases and a second primary tumor in 26%. A further 14 cases were reported from another Italian cohort, which together with the national cohort dana suggest a risk of approximately ~10% with APS-1; however, the true lifetime risk remains uncertain. Head and neck malignancies in APS-1 occur early, often without classic risk factors, and have a high recurrence and mortality rate. Lifelong surveillance, antifungal stewardship and increased clinical awareness, ideally as part of multidisciplinary treatment pathways, are critical to improving outcomes in this rare but high-risk population. Full article

Background/Objectives: Patients with chronic hypoparathyroidism are at increased risk of kidney complications. Also, chronic kidney disease is associated with increased cardiovascular risk. The aim was to analyze the factors that influence kidney function, including cardiovascular diseases (CVD), in a cohort of patients with chronic hypoparathyroidism. Methods: This was a retrospective longitudinal study that included 100 patients with chronic hypoparathyroidism. Results: The estimated glomerular filtration rate (eGFR) was associated with the duration of disease (p = 0.014). During follow-up, a significant decrease in eGFR was observed over time (p < 0.001), and changes in the eGFR were associated with the duration of disease (p < 0.001). We found that the eGFR was lower in patients with urolithiasis (p = 0.003), hypertension (p < 0.001), type 2 diabetes (p = 0.031) and dyslipidemia (p < 0.001). In total, 14% of patients had a chronic kidney disease (CKD), and these patients had a longer duration of disease (p < 0.001). The percentage of patients with urolithiasis (p = 0.003), nephrocalcinosis (p = 0.008), hypertension (p = 0.005), type 2 diabetes (p < 0.001), dyslipidemia (p < 0.001), coronary heart disease (p = 0.008), and arrhythmia (p < 0.001) was higher in patients with CKD. Logistic regression models showed that disease duration was associated with CKD (OR = 1.11; 95% CI [1.03–1.22]; p = 0.008). We used ROC curves to assess the usefulness of disease duration as a marker of CKD, and the AUC was 0.850 (95% CI 0.763–0.937, p < 0.001). A duration of disease > 15.5 years had a sensitivity of 85.7% and a specificity of 71.9% for a diagnosis of CKD. Conclusions: The duration of disease appears to be a predictor of the presence of renal dysfunction in patients with chronic hypoparathyroidism. In addition, the coexistence of CVD factors could result in greater renal damage. Full article

Background: Thyroidectomy constitutes an important portion of endocrine surgery procedures and is associated with various complications such as bleeding, recurrent laryngeal nerve injury, and postoperative hypoparathyroidsm. Effective parathyroid preservation during thyroid surgery is crucial for patient well-being, with current strategies heavily reliant on surgeon experience. Among various methods, Indocyanine Green Angiography (ICGA) offers a promising method for intraoperative assessment of parathyroid gland perfusion. Methods: In a retrospective study, patients undergoing bilateral thyroidectomy from January 2021 to January 2023 were analyzed, excluding those with previous thyroidectomy, parathyroid disease, or chronic kidney disease. The study compared a control group (n = 175) with an ICGA group (n = 120), using propensity score matching for statistical analysis. Matched cohorts included 120 patients in each group. The primary outcome of this study was identified as temporary postoperative hypoparathyroidism, with secondary outcomes including the rate of parathyroid reimplantation and the incidence of permanent postoperative hypoparathyroidism. Results: The ICGA group showed significantly more parathyroid autotransplantations (p < 0.01). While not statistically significant, the control group had a higher incidence of temporary postoperative hypoparathyroidism (p < 0.09). Rates of hypocalcemia on postoperative day 1 and permanent hypocalcemia were similar. Subgroup analysis indicated more postoperative day 1 hypoparathyroidism in the control group during central neck dissections (p < 0.049). Conclusions: Intraoperative ICGA use correlated with higher parathyroid autotransplantation and suggested reduced postoperative hypoparathyroidism. Changes in fluorescence intensity following a second ICG injection may provide an objective method to assess parathyroid perfusion. Further large-scale studies are needed to fully understand ICGA’s impact on parathyroid preservation. Full article

Objective: Familial isolated hypoparathyroidism is a rare genetic disorder due to no or low production of the parathyroid hormone, disturbing calcium and phosphate regulation. The resulting hypocalcemia may lead to dental abnormalities, such as enamel hypoplasia. The aim of this paper was to describe the full-mouth rehabilitation of a 15-year-old girl with chronic hypocalcemia due to a rare congenital hypoparathyroidism. Clinical considerations: In this patient, in the young adult dentition, conservative care was preferred. Onlays or stainless-steel crowns were performed on the posterior teeth, and direct or indirect (overlays and veneerlays) were performed on the maxillary premolars, canines, and incisors, using a digital wax-up. The mandibular incisors were bleached. The treatment clearly improved the patient’s oral quality of life, with fewer sensitivities, better chewing, and aesthetic satisfaction. The difficulties were the regular monitoring and the limited compliance of the patient. Conclusion: Despite no clinical feedback in the literature, generalized hypomineralized/hypoplastic teeth due to hypoparathyroidism in a young patient can be treated as amelogenesis imperfecta (generalized enamel defects) with a conservative approach for medium-term satisfactory results. Highlights: This study provides new insights into the management of enamel hypoplasia caused by familial isolated hypoparathyroidism, helping to improve patient outcomes in similar cases. Full article

Hypocalcemia is a common occurrence in pediatric patients, attributed to various causes and presenting with diverse clinical manifestations. A prompt evaluation is necessary to determine its underlying cause, whether it presents acutely or chronically, and to tailor treatment based on its severity. Among the potential causes of chronic hypocalcemia, primary hypoparathyroidism stands out. The case of a seven-year-old male patient with hypocalcemia reported in this article serves as an illustration, wherein targeted next-generation sequencing revealed a homozygous p.R257X mutation in the AIRE gene, indicative of autoimmune polyendocrine syndrome type 1 (APS-1). It poses challenges due to its multisystemic nature and involvement of specific autoantibodies, often leading to underdiagnosis, owing to its rarity, varied manifestations, and incomplete penetrance. A comprehensive review of the APS-1 literature was conducted to provide insights into the clinical manifestations, genetic spectrum, potential immunological mechanisms, and current medical strategies. Additionally, the recognition of AIRE gene mutations is crucial for facilitating genetic diagnosis, prognosis, and potential treatment strategies for APS-1. The management of such cases involves individualized approaches to treatment, regular monitoring, medication adjustments, and the early identification of associated conditions. Full article

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), or polyglandular autoimmune syndrome type 1 (PAS-1/APS-1), is a rare autosomal recessive disorder linked to mutations in the autoimmune regulator (AIRE) gene. This review provides a detailed analysis of cutaneous manifestations in APECED, focusing on chronic mucocutaneous candidiasis (CMC), alopecia areata (AA), and vitiligo. The classic triad of hypoparathyroidism, adrenal insufficiency, and CMC serves as a diagnostic cornerstone. However, the varied clinical spectrum of APECED, particularly its cutaneous presentations, poses a diagnostic challenge. CMC, often an early sign, varies in prevalence across populations, including Finnish (100%), Irish (100%), Saudi Arabian (80%), Italian (60–74.7%), North American (51–86%), and Croatian (57.1%) populations. Similarly, AA prevalence varies in different populations. Vitiligo also exhibits variable prevalence across regions. The review synthesizes the current knowledge arising from a narrative analysis of 14 significant human studies published in English up to October 2023. Moreover, this paper underscores the importance of early detection and monitoring, emphasizing cutaneous manifestations as key diagnostic indicators. Ongoing research and clinical vigilance are crucial for unraveling the complexities of this rare autoimmune syndrome and enhancing patient care. Full article

Vitamin D is essential for life—its sufficiency improves metabolism, hormonal release, immune functions, and maintaining health. Vitamin D deficiency increases the vulnerability and severity of type 2 diabetes, metabolic syndrome, cancer, obesity, and infections. The active enzyme that generates vitamin D [calcitriol: 1,25(OH)₂D], CYP27B1 (1α-hydoxylase), and its receptors (VDRs) are distributed ubiquitously in cells. Once calcitriol binds with VDRs, the complexes are translocated to the nucleus and interact with responsive elements, up- or down-regulating the expression of over 1200 genes and modulating metabolic and physiological functions. Administration of vitamin D₃ or correct metabolites at proper doses and frequency for longer periods would achieve the intended benefits. While various tissues have different thresholds for 25(OH)D concentrations, levels above 50 ng/mL are necessary to mitigate conditions such as infections/sepsis, cancer, and reduce premature deaths. Cholecalciferol (D₃) (not its metabolites) should be used to correct vitamin D deficiency and raise serum 25(OH)D to the target concentration. In contrast, calcifediol [25(OH)D] raises serum 25(OH)D concentrations rapidly and is the agent of choice in emergencies such as infections, for those who are in ICUs, and for insufficient hepatic 25-hydroxylase (CYP2R1) activity. In contrast, calcitriol is necessary to maintain serum-ionized calcium concentration in persons with advanced renal failure and hypoparathyroidism. Calcitriol is, however, ineffective in most other conditions, including infections, and as vitamin D replacement therapy. Considering the high costs and higher incidence of adverse effects due to narrow therapeutic margins (ED50), 1α-vitamin D analogs, such as 1α-(OH)D and 1,25(OH)₂D, should not be used for other conditions. Calcifediol analogs cost 20 times more than D₃—thus, they are not indicated as a routine vitamin D supplement for hypovitaminosis D, osteoporosis, or renal failure. Healthcare workers should resist accepting inappropriate promotions, such as calcifediol for chronic renal failure and calcitriol for osteoporosis or infections—there is no physiological rationale for doing so. Maintaining the population’s vitamin D sufficiency (above 40 ng/mL) with vitamin D₃ supplements and/or daily sun exposure is the most cost-effective way to reduce chronic diseases and sepsis, overcome viral epidemics and pandemics, and reduce healthcare costs. Furthermore, vitamin D sufficiency improves overall health (hence reducing absenteeism), reduces the severity of chronic diseases such as metabolic and cardiovascular diseases and cancer, decreases all-cause mortality, and minimizes infection-related complications such as sepsis and COVID-19-related hospitalizations and deaths. Properly using vitamin D is the most cost-effective way to reduce chronic illnesses and healthcare costs: thus, it should be a part of routine clinical care. Full article

Only a few studies evaluating the metabolism of vitamin D in patients with hypoparathyroidism (HypoPT) have been performed thus far, and, in particular, they mainly investigated the process of vitamin D activation (specifically, 1α-hydroxylation). This study, therefore, aimed to evaluate the extended spectrum of vitamin D metabolites in patients with HypoPT compared to healthy individuals. We examined 38 adult patients with chronic HypoPT in comparison to 38 healthy adults. The assessment included biochemical parameters (total calcium, albumin, phosphorus, creatinine, and magnesium), parathyroid hormone (PTH), and vitamin D metabolites (25(OH)D₃, 25(OH)D₂, 1,25(OH)₂D₃, 3-epi-25(OH)D₃, and 24,25(OH)₂D₃) in serum. Our data show that an adequate level of 25(OH)D₃ (median 35.3 (29.6; 42.0) ng/mL) is achieved with standard doses of cholecalciferol (median 2000 (2000; 2500) IU per day) in HypoPT patients. They also presented with supraphysiological levels of 1,25(OH)₂D₃ (median 71 (47; 96) vs. 40 (34; 59) pg/mL, p < 0.001) and the increased production of inactive metabolite (median 24,25(OH)₂D₃ 3.8 (3.0; 5.1) vs. 1.9 (1.3; 2.7) ng/mL, p < 0.001; median 25(OH)D₃/24,25(OH)₂D₃ ratio 8.9 (7.6; 11.1) vs. 13.5 (11.1; 17.0), p < 0.001) as compared to the control group. This might be a consequence of the therapy received (treatment with activated vitamin D) and the pathophysiology of the disease (lack of PTH). The abnormality of vitamin D metabolism does not seem to interfere with the achievement of hypoparathyroidism compensation. Full article

This review highlights oral anomalies with major clinical impact in Addison disease (AD), including dental health and dermatologic features, through a dual perspective: pigmentation issues and AD comorbidities with oral manifestations. Affecting 92% of AD patients, cutaneomucosal hyperpigmentation is synchronous with or precedes general manifestations by up to a decade, underlying melanocytic infiltration of the basal epidermal layer; melanophages in the superficial dermis; and, rarely, acanthosis, perivascular lymphocytic infiltrate, and hyperkeratosis. Intraoral pigmentation might be the only sign of AD; thus, early recognition is mandatory, and biopsy is helpful in selected cases. The buccal area is the most affected location; other sites are palatine arches, lips, gums, and tongue. Pigmented oral lesions are patchy or diffuse; mostly asymptomatic; and occasionally accompanied by pain, itchiness, and burn-like lesions. Pigmented lingual patches are isolated or multiple, located on dorsal and lateral areas; fungiform pigmented papillae are also reported in AD individuals. Dermoscopy examination is particularly indicated for fungal etiology; yet, it is not routinely performed. AD’s comorbidity burden includes the cluster of autoimmune polyglandular syndrome (APS) type 1 underlying AIRE gene malfunction. Chronic cutaneomucosal candidiasis (CMC), including oral CMC, represents the first sign of APS1 in 70–80% of cases, displaying autoantibodies against interleukin (IL)-17A, IL-17F ± IL-22, and probably a high mucosal concentration of interferon (IFN)-γ. CMC is prone to systemic candidiasis, representing a procarcinogenic status due to Th17 cell anomalies. In APS1, the first cause of mortality is infections (24%), followed by oral and esophageal cancers (15%). Autoimmune hypoparathyroidism (HyP) is the earliest endocrine element in APS1; a combination of CMC by the age of 5 years and dental enamel hypoplasia (the most frequent dental complication of pediatric HyP) by the age of 15 is an indication for HyP assessment. Children with HyP might experience short dental roots, enamel opacities, hypodontia, and eruption dysfunctions. Copresence of APS-related type 1 diabetes mellitus (DM) enhances the risk of CMC, as well as periodontal disease (PD). Anemia-related mucosal pallor is related to DM, hypothyroidism, hypogonadism, corresponding gastroenterological diseases (Crohn’s disease also presents oral ulceration (OU), mucogingivitis, and a 2–3 times higher risk of PD; Biermer anemia might cause hyperpigmentation by itself), and rheumatologic diseases (lupus induces OU, honeycomb plaques, keratotic plaques, angular cheilitis, buccal petechial lesions, and PD). In more than half of the patients, associated vitiligo involves depigmentation of oral mucosa at different levels (palatal, gingival, alveolar, buccal mucosa, and lips). Celiac disease may manifest xerostomia, dry lips, OU, sialadenitis, recurrent aphthous stomatitis and dental enamel defects in children, a higher prevalence of caries and dentin sensitivity, and gingival bleeding. Oral pigmented lesions might provide a useful index of suspicion for AD in apparently healthy individuals, and thus an adrenocorticotropic hormone (ACTH) stimulation is useful. The spectrum of autoimmune AD comorbidities massively complicates the overall picture of oral manifestations. Full article

Beta-thalassemia (BTH), a recessively inherited haemoglobin (Hb) disorder, causes iron overload (IO), extra-medullary haematopoiesis and bone marrow expansion with major clinical impact. The main objective of this review is to address endocrine components (including aspects of reproductive health as fertility potential and pregnancy outcome) in major beta-thalassemia patients, a complex panel known as thalassemic endocrine disease (TED). We included English, full-text articles based on PubMed research (January 2017–June 2022). TED includes hypogonadism (hypoGn), anomalies of GH/IGF1 axes with growth retardation, hypothyroidism (hypoT), hypoparathyroidism (hypoPT), glucose profile anomalies, adrenal insufficiency, reduced bone mineral density (BMD), and deterioration of microarchitecture with increased fracture risk (FR). The prevalence of each ED varies with population, criteria of definition, etc. At least one out of every three to four children below the age of 12 y have one ED. ED correlates with ferritin and poor compliance to therapy, but not all studies agree. Up to 86% of the adult population is affected by an ED. Age is a positive linear predictor for ED. Low IGF1 is found in 95% of the population with GH deficiency (GHD), but also in 93.6% of persons without GHD. HypoT is mostly pituitary-related; it is not clinically manifested in the majority of cases, hence the importance of TSH/FT4 screening. HypoT is found at any age, with the prevalence varying between 8.3% and 30%. Non-compliance to chelation increases the risk of hypoT, yet not all studies confirmed the correlation with chelation history (reversible hypoT under chelation is reported). The pitfalls of TSH interpretation due to hypophyseal IO should be taken into consideration. HypoPT prevalence varies from 6.66% (below the age of 12) to a maximum of 40% (depending on the study). Serum ferritin might act as a stimulator of FGF23. Associated hypocalcaemia transitions from asymptomatic to severe manifestations. HypoPT is mostly found in association with growth retardation and hypoGn. TED-associated adrenal dysfunction is typically mild; an index of suspicion should be considered due to potential life-threatening complications. Periodic check-up by ACTH stimulation test is advised. Adrenal insufficiency/hypocortisolism status is the rarest ED (but some reported a prevalence of up to one third of patients). Significantly, many studies did not routinely perform a dynamic test. Atypical EM sites might be found in adrenals, mimicking an incidentaloma. Between 7.5–10% of children with major BTH have DM; screening starts by the age of 10, and ferritin correlated with glycaemia. Larger studies found DM in up to 34%of cases. Many studies do not take into consideration IGF, IGT, or do not routinely include OGTT. Glucose anomalies are time dependent. Emerging new markers represent promising alternatives, such as insulin secretion-sensitivity index-2. The pitfalls of glucose profile interpretation include the levels of HbA1c and the particular risk of gestational DM. Thalassemia bone disease (TBD) is related to hypoGn-related osteoporosis, renal function anomalies, DM, GHD, malnutrition, chronic hypoxia-induced calcium malabsorption, and transplant-associated protocols. Low BMD was identified in both paediatric and adult population; the prevalence of osteoporosis/TBD in major BTH patients varies; the highest rate is 40–72% depending on age, studied parameters, DXA evaluation and corrections, and screening thoracic–lumbar spine X-ray. Lower TBS and abnormal dynamics of bone turnover markers are reported. The largest cohorts on transfusion-dependent BTH identified the prevalence of hypoGn to be between 44.5% and 82%. Ferritin positively correlates with pubertal delay, and negatively with pituitary volume. Some authors appreciate hypoGn as the most frequent ED below the age of 15. Long-term untreated hypoGn induces a high cardiovascular risk and increased FR. Hormonal replacement therapy is necessary in addition to specific BTH therapy. Infertility underlines TED-related hormonal elements (primary and secondary hypoGn) and IO-induced gonadal toxicity. Males with BTH are at risk of infertility due to germ cell loss. IO induces an excessive amount of free radicals which impair the quality of sperm, iron being a local catalyser of ROS. Adequate chelation might improve fertility issues. Due to the advances in current therapies, the reproductive health of females with major BTH is improving; a low level of statistical significance reflects the pregnancy status in major BTH (limited data on spontaneous pregnancies and growing evidence of the induction of ovulation/assisted reproductive techniques). Pregnancy outcome also depends on TED approach, including factors such as DM control, adequate replacement of hypoT and hypoPT, and vitamin D supplementation for bone health. Asymptomatic TED elements such as subclinical hypothyroidism or IFG/IGT might become overt during pregnancy. Endocrine glands are particularly sensitive to iron deposits, hence TED includes a complicated puzzle of EDs which massively impacts on the overall picture, including the quality of life in major BTH. The BTH prognostic has registered progress in the last decades due to modern therapy, but the medical and social burden remains elevated. Genetic counselling represents a major step in approaching TH individuals, including as part of the pre-conception assessment. A multidisciplinary surveillance team is mandatory. Full article

Burn injury serves as an example of a condition with a robust systemic inflammatory response. The elevation of circulating interleukins (IL)-1β and -6 in children and adolescents with severe burn injury upregulates the parathyroid calcium-sensing receptor (CaSR), resulting in hypocalcemic hypoparathyroidism accompanied by urinary calcium wasting. This effect protects the body from the hypercalcemia that results from bone resorption, liberating calcium into the circulation. Extracellular calcium can exacerbate and prolong the inflammatory response by stimulating mononuclear cell chemokine production as well as the NLRP3 inflammasome of the innate immune system, resulting in increased IL-1 production by monocytes and macrophages. Interestingly, the CaSR upregulation in response to inflammatory cytokines disappears with age, potentially trapping calcium from bone resorption in the circulation, allowing it to contribute to increased inflammation and possibly increased calcium deposition in small arteries, such as the coronaries, as conditions with increased chronic inflammation, such as spinal cord injury, osteoarthritis, and rheumatoid arthritis have an incidence of cardiovascular disease and coronary artery calcium deposition significantly higher than the unaffected age-matched population. Full article

Background: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare monogenetic autosomal recessive disorder caused by a mutation in the autoimmune regulator (AIRE) gene characterized by complex phenotypic characteristics discovered over years of follow-up. Methods: 7 patients were recruited in this case series in a period of the last 37 years from Southern Croatia. All patients were screened for AIRE R257X mutations. Results: This study group had a mean current age of 25.3 years (age range from 5.4 to 40.2 years), while the mean age at the onset of the disease was 6.5 years (age range from 0.7 to 9.2 years) and with a mean follow-up period of 17.8 years. The overall prevalence of APECED syndrome is estimated to be 1 in 75,000. The most common initial manifestation of the disease was onychodystrophy, while the first major component of APECED syndrome was chronic mucocutaneous candidiasis. Conclusions: APECED is a ‘‘multi-faced’’ disease based on the very unpredictable and inconsistent onset of major components. Furthermore, based on our results, we suggest that onychodystrophy could be included as a warning sign of APECED syndrome. Full article

Surgical treatment for autoimmune thyroid disease is theoretically risky due to its chronic inflammatory status. This study aimed to investigate the correlation between preoperative serum migration inhibitory factor (MIF) levels and the difficulty of thyroidectomy in patients with autoimmune thyroiditis. Forty-four patients (average age: 54 years) were prospectively recruited: 30 with autoimmune thyroiditis and 14 with nodular goiter. Preoperative serum samples were collected to measure MIF levels. The difficulty of thyroidectomy was evaluated using a 20-point thyroidectomy difficulty scale (TDS) scoring system. The potential correlations between MIF levels and clinicopathological features as well as postoperative complications were analyzed. Preoperative serum thyroid-stimulating hormone (TSH), TSH receptor antibody, thyroid peroxidase antibodies levels, TDS score, and serum MIF levels were significantly higher in the autoimmune thyroiditis group than those in the goiter group. MIF levels were significantly associated with postoperative transient recurrent laryngeal nerve injury and hypoparathyroidism. MIF levels were positively correlated with TDS score, operation time, and blood loss in the autoimmune thyroiditis group. Increased preoperative serum MIF levels are associated with higher TDS scores, operation time, blood loss, and postoperative complications. Preoperative serum MIF level may be a useful predictor of difficult thyroidectomy and help surgeons provide better preoperative management. Full article