[The role of calcium sensitive and vitamin D receptors in the pathogenesis of sporadic multiple parathyroid gland disease].

BACKGROUND: Sporadic multiple parathyroid gland disease is » cases of primary hyperparathyroidism (PHPT). However, a single tactic for diagnosing and operating volume in patients with this variant of PHPT has not yet been developed. One of the possible directions in the search for pathogenetically substantiated methods of diagnosis and treatment is the study of the molecular genetic features of the disease and associated clinical and laboratory factors. AIM: To study the features of the expression of calcium sensitive (CaSR) and vitamin D (VDR) receptors on the surface of parathyroid cells in primary hyperparathyroidism with solitary and multiple lesions of the parathyroid glands, as well as its changes under the influence of a decrease in the filtration function of the kidneys. MATERIALS AND METHODS: In a single center observational prospective study with retrospective data collection, there were patients who during 2019-2021. operated on for PHPT, secondary hyperparathyroidism (SHPT) and all cases of tertiary hyperparathyroidism (THPT) operated during 2014-2021. The expression of CaSR, VDR and its relationship with the main laboratory parameters, the clinical variant of hyperparathyroidism, and the morphological substrate were studied. RESULTS: The study included 69 patients: 19 with multiple and 25 with solitary PTG near PHPT, 15 with SHPT, 10 with THPT. A statistically significant decrease in the frequency of detection of normal expression of CaSR and VDR receptors occurs in any morphological variant of hyperparathyroidism and is observed in 93-60% of drugs. A decrease in the normal expression of CaSR in hyperplasia is detected statistically significantly less frequently than in adenoma (p≤0.01). The median expression intensity in adenoma was 2.5 (2:3), in hyperplasia 3.5 (3-4) (p≤0.01). The difference in the molecular mechanisms of the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma (PHPT with solitary adenoma) or hyperplasia (SHPT and PHPT with multiple PTG lesions) is realized in the frequency of maintaining normal CaSR expression in the PTG tissue. These mechanisms are implemented at the local level, their variability does not change under the influence of RRT. A common molecular genetic mechanism for the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma or hyperplasia has been found to reduce the frequency of maintaining normal VDR expression in PTG (up to 7-13%), p<0.01. This mechanism is implemented at the local level, its variability changes under the influence of RRT, reaching statistically significant differences in patients with THPT. CONCLUSION: The study demonstrates the features of changes in the expression of CaSR and VDR in PHPT with multiple lesions of the parathyroid glands. The relationship between the expression of these receptors and the clinical variant of hyperparathyroidism, the morphological substrate, the main laboratory parameters, and renal function was shown.

Misdiagnosed giant parathyroid cyst: differential diagnosis of a neck mass of the central region.

Parathyroid cysts (PCs) are rare benign lesions representing between the 0.08% and the 0.34% of the neck masses going on surgery. They should be considered in the differential diagnosis of neck masses, especially in the differential diagnosis of the cystic anterior neck masses.Approximately 300 cases of PC are reported within the international literature.The gold standard for diagnosis is the evidence of high-level intact parathyroid hormone in cystic fluid. It is important to diagnose PCs before surgery, not intraoperatively, in order to avoid unnecessary surgeries or superfluous excision of part of the thyroid gland and prevent the patient from iatrogenic hypothyroidism.A surgical approach is required in those patients with large-sized cysts, relapses despite needle aspirations or if it causes hyperparathyroidism.We describe a case report of a patient, initially misdiagnosed with a thyroid cyst swelling, who instead had a giant non-functioning PC, which produced dyspnoea or dysphagia.

Phosphate Metabolism and Pathophysiology in Parathyroid Disorders and Endocrine Tumors.

The advent of new insights into phosphate metabolism must urge the endocrinologist to rethink the pathophysiology of widespread disorders, such as primary hyperparathyroidism, and also of rarer endocrine metabolic bone diseases, such as hypoparathyroidism and tumor-induced hypophosphatemia. These rare diseases of mineral metabolism have been and will be a precious source of new information about phosphate and other minerals in the coming years. The parathyroid glands, the kidneys, and the intestine are the main organs affecting phosphate levels in the blood and urine. Parathyroid disorders, renal tubule defects, or phosphatonin-producing tumors might be unveiled from alterations of such a simple and inexpensive mineral as serum phosphate. This review will present all these disorders from a 'phosphate perspective'.

Selected Topics in the Pathology of the Thyroid and Parathyroid Glands in Children and Adolescents.

The goals of this chapter in keeping with the overall general themes of this special edition will be (1) to highlight aspects of development of the thyroid and parathyroid glands with particular focus on the role and contribution of the neural crest (or not) and how this may impact on the pathology that is seen, (2) to emphasize those lesions particularly more commonly arising in the pediatric population that actually generate specimens that the surgical pathologist would encounter, and (3) highlight more in depth specific lesions associated with heritable syndromes or specific gene mutations since the heritable syndromes tends to manifest in the pediatric age group. In this light, the other interesting areas of pediatric thyroid disease including medical thyroid diseases, congenital hypothyroidism, anatomic variants and aberrations of development that lead to structural anomalies will not be emphasized here.

Intraoperative near-infrared imaging of parathyroid glands: A comparison of first- and second-generation technologies.

BACKGROUND: Intraoperative near-infrared imaging (NIFI) of parathyroid glands (PG) by first-generation technology had limited image quality and depth penetration. Second-generation NIFI has recently been introduced. Our aim was to compare (1) capability to detect PG and (2) image quality between older and newer technologies. METHODS: Accurately detecting PG, as well as, quality of autofluorescence (AF) was compared between an older charge-coupled device (CCD) camera and a newer complementary metal-oxide semiconductor (CMOS). χ2 , t test, and analysis of variance were used for analysis. RESULTS: There were 300 patients who underwent parathyroidectomy (PTX) and/or thyroidectomy (THY) with NIFI, 200 with CCD, and 100 with CMOS. Although both NIFI technologies detected >94% of PG, CMOS was superior to CCD. Comparing AF quality, mean pixel intensity of PG compared with the background was higher with CMOS compared with CCD. When comparing PG detected by NIFI before visual identification by a surgeon, both CCD and CMOS had similar results (25% vs. 22%; p = .3). CONCLUSION: Both NIFI cameras were excellent at detecting PG. Second-generation NIFI (CMOS) displayed higher detection rates and AF intensity. Although surgeons identified majority of PG before NIFI detection, 25% of PG were identified with NIFI first, suggesting future advancements of this technology may expand its applications during parathyroid/thyroid operations.

Parathyroid cyst: differential diagnosis.

Parathyroid cysts are rare lesions of the cervical region and less frequently of the mediastinum. They occur mostly in women and are usually asymptomatic. They generally occur in the fourth and fifth decades of life and mainly are non-functioning. They commonly present as a neck mass that is found incidentally during surgery or in imaging test. Its importance lies in the difficulty in diagnosis, often confusing itself with thyroid pathology. The diagnosis is usually made intraoperatively, confirmed by histopathological examination.The aim of this paper is to report a case of parathyroid cyst that mimics a thyroid nodule.

Tissue-engineered parathyroid gland and its regulatory secretion of parathyroid hormone.

Parathyroid glands (PTGs) are important endocrine organs being mainly responsible for the secretion of parathyroid hormone (PTH) to regulate the balance of calcium (Ca) /phosphorus (P) ions in the body. Once PTGs get injured or removed, their resulting defect or loss of PTH secretion should disturb the level of Ca/P in blood, thus damaging other related organs (bone, kidney, etc.) and even causing death. Recently, tissue-engineered PTGs (TE-PTGs) have attracted lots of attention as a potential treatment for the related diseases of PTGs caused by hypoparathyroidism and hyperparathyroidism, including tetany, muscle cramp, nephrolithiasis, nephrocalcinosis, and osteoporosis. Although great progress has been made in the establishment of TE-PTGs with an effective strategy to integrate the key factors of cells and biomaterials, its regulatory secretion of PTH to mimic its natural rhythms in the body remains a huge challenge. This review comprehensively describes an overview of PTGs from physiology and pathology to cytobiology and tissue engineering. The state of the arts in TE-PTGs and the feasible strategies to regulate PTH secretion behaviors are highlighted to provide an important foundation for further investigation.

Hereditary Parathyroid Disease: Sometimes Pathologists Do Not Know What They Are Missing.

Parathyroid gland excision specimens are common and sometimes underestimated cases that many surgical pathologists encounter regularly. In the vast majority of cases, these will be spot diagnoses of sporadic primary parathyroid adenomas or, perhaps, hyperplasias commonly in the setting of renal failure. However, a small but significant number of parathyroid gland excisions may be due to heritable disease. In most cases, hereditary disease is suspected by the referring clinicians. Nevertheless, a subset of these are undetected which is significant, particularly in the setting of the multiple endocrine neoplasia (MEN), and the hyperparathyroidism jaw tumour (HPT-JT) syndromes. There have been recent advances in recognition of the morphological and immunohistochemical characteristics of these tumours and hyperplasias. While hereditary kindreds are over-represented at specialist referral centres, with awareness of the characteristic clinical and morphological features, the general surgical pathologist is frequently able to suggest the possibility of hereditary parathyroid disease. We therefore provide a succinct guide for pathologists to increase the recognition of hereditary parathyroid disease.

Rare PTH Gene Mutations Causing Parathyroid Disorders: A Review.

Since parathyroid hormone (PTH) was first isolated and its gene (PTH) was sequenced, only eight PTH mutations have been discovered. The C18R mutation in PTH, discovered in 1990, was the first to be reported. This autosomal dominant mutation induces endoplasmic reticulum stress and subsequent apoptosis in parathyroid cells. The next mutation, which was reported in 1992, is associated with exon skipping. The substitution of G with C in the first nucleotide of the second intron results in the exclusion of the second exon; since this exon includes the initiation codon, translation initiation is prevented. An S23P mutation and an S23X mutation at the same residue were reported in 1999 and 2012, respectively. Both mutations resulted in hypoparathyroidism. In 2008, a somatic R83X mutation was detected in a parathyroid adenoma tissue sample collected from a patient with hyperparathyroidism. In 2013, a heterozygous p.Met1_Asp6del mutation was incidentally discovered in a case-control study. Two years later, the R56C mutation was reported; this is the only reported hypoparathyroidism-causing mutation in the mature bioactive part of PTH. In 2017, another heterozygous mutation, M14K, was detected. The discovery of these eight mutations in the PTH gene has provided insights into its function and broadened our understanding of the molecular mechanisms underlying mutation progression. Further attempts to detect other such mutations will help elucidate the functions of PTH in a more sophisticated manner.

Paediatric and young adult manifestations and outcomes of multiple endocrine neoplasia type 1.

CONTEXT: Multiple endocrine neoplasia 1 (MEN 1) is an autosomal dominant disease presenting as hyperplasia and neoplasia of parathyroid, pituitary and enteropancreatic tissues. Over 90% of gene carriers develop phenotypic disease by age 30 years, potentially with onset of asymptomatic disease during childhood and adolescence. OBJECTIVE: To describe the paediatric and young adult manifestations of MEN 1. DESIGN: Descriptive retrospective study of 180 patients with a common MEN1 genotype. The paediatric and young adult (age <22 years) manifestations were determined using hospital records and disease surveillance data. RESULTS: Primary hyperparathyroidism (PHPT) was identified in 42 patients (mean age 17.2 ± 3.3 years). Parathyroidectomy was performed in 16 (38.1%; mean age 17.8 ± 3.2). Four patients experienced recurrent PHPT (25%), and six (37.5%) developed permanent hypoparathyroidism. Pituitary disease was identified in 13 patients. Prolactinoma was found in nine patients (mean age 16.6 ± 2.6 years) of whom four (44.4%) had macroprolactinoma. Two patients required surgical intervention; dopamine agonists showed efficacy in six patients. Two patients with Cushing's disease were successfully treated surgically. Three patients with nonfunctioning pituitary microadenoma managed conservatively. Pancreatic neuroendocrine neoplasms (pNENs) were diagnosed in 12 patients (mean age 17.0 ± 2.6 years): three patients with insulinoma successfully resected (two resected and one exhibiting perineural invasion) and nine patients with nonfunctioning adenomas (NFAs). CONCLUSION: Pituitary adenomas, PHPT and pNENs are encountered in the paediatric and young adult MEN 1 population. Successful outcomes are typically achieved using standard medical and surgical paradigms; however, parathyroidectomy was associated with a substantial complication rate.

MRI findings and utility of DWI in the evaluation of solid parathyroid lesions.

PURPOSE: To evaluate the MRI findings of solid parathyroid lesions and to elaborate on a possible improvement of MRI detection of parathyroid lesions by the use of additional DWI. MATERIALS AND METHODS: MRI and DWI properties of pathologically proven 20 solid parathyroid lesions were retrospectively reviewed. Mean ADC values (b50 + b400 + b800/3) of parathyroid lesions were compared with that of normal appearing thyroid parenchyma (TP), sternocleidomastoid muscle (SCM) and jugulodigastric lymph nodes (JDLN). RESULTS: Of lesions, 4 were parathyroid hyperplasia, 13 parathyroid adenoma and 3 parathyroid adenocarcinoma. All parathyroid lesions were very bright on fat-saturated T2W images. Parathyroid hyperplasia and adenoma were small sized, homogenous, well-defined and low on T1W, high on T2W and avidly enhancing. Parathyroid carcinoma was large sized, ill-defined and very heterogeneous on MRI including DWI. Means ADC values of parathyroid hyperplasia, adenoma, and adenocarcinoma, TP, SCM and JDLN were measured as 2.3 ± 0.14 × 10-3, 1.7 ± 0.45 × 10-3, 1.5 ± 1.48 × 10-3, 0.87 ± 0.40 × 10-3, 0.55 ± 0.21 × 10-3 and 0.96 ± 0.33 × 10-3 mm2/s, respectively. All parathyroid lesions had high diffusion properties comparing other soft tissue structures of head and neck region. By increasing strength (b value) of diffusion tensor on DWI, solid parathyroid lesions still kept their brightness comparing other soft tissue structures of head and neck region because of their high T2 properties. CONCLUSION: Solid parathyroid lesions had higher diffusion properties comparing other soft tissues structures of head and neck region. This feature makes them easily differentiate from nearby structures on fat-saturated T2W and DWI.

Prescription and Usage Pattern of Opioids after Thyroid and Parathyroid Surgery.

OBJECTIVE: We seek to characterize the prescribing patterns of opioids, opioid consumption, and pain severity after thyroid and parathyroid surgery. We also aim to determine if a relationship exists between preoperative medication use and postoperative pain or opioid consumption. STUDY DESIGN: Case series with chart review. SETTING: Academic university hospital. SUBJECTS AND METHODS: Medical records of 237 adult patients undergoing thyroid and parathyroid surgery were included. Clinicopathologic data were collected, including pain scores, preoperative medications, and inpatient pain medications. RESULTS: The mean maximum pain score was 5.74 and varied by surgery type (range, 0-10). Mean pain score decreased to 2.61 upon discharge (0-8) and to 0.51 at the first postoperative visit. Patients with a length of stay exceeding 1 day had significantly higher maximum pain scores than those with a length of stay of 0 or 1 day (8 vs 5.58, P < .001). Morphine milligram equivalents while in the hospital averaged 25.4 per day and were significantly influenced by preoperative opioid use (0-202). Acetaminophen/oxycodone was the most commonly prescribed opioid. The mean number of pills prescribed postoperatively was 43.1 (0-120). CONCLUSION: In our population, patients are discharged with opioid prescriptions that may be in excess of their requirements following thyroid and parathyroid surgery. Preoperative opioid use was associated with higher postoperative pain score and, on multivariate analysis, greater inpatient opioid consumption. Further investigation is warranted to ensure that we are prescribing opioids appropriately following thyroid and parathyroid surgery.

Postoperative Pain Control and Opioid Usage Patterns among Patients Undergoing Thyroidectomy and Parathyroidectomy.

OBJECTIVES: To examine opioid-prescribing patterns after endocrine surgery. To evaluate factors associated with postoperative pain and opioid use. STUDY DESIGN: Cross-sectional. SETTING: Academic university health system. SUBJECTS AND METHODS: The study sample included 209 patients who underwent total thyroidectomy, hemithyroidectomy, or parathyroidectomy by 4 surgeons between August 2015 and November 2017. Eighty-nine patients completed a phone survey about postoperative pain and opioid use. Prescription, demographic, and comorbidity data were collected retrospectively. Patient characteristics associated with opioid use, use of ≥10 opioid pills, and pain score were identified via chi-square, t test, analysis of variance, or Pearson correlation. Identified factors were further assessed with multivariable logistic and linear regression modeling. RESULTS: The median numbers of opioid pills prescribed were 20 for total thyroidectomy, 25 for hemithyroidectomy, and 20 for parathyroidectomy, and the median numbers of pills used were 1.5, 2, and 0, respectively. Of 1947 total prescribed pills, 19.7% were reported to be taken. The number of pills meeting the opioid needs of 80% of these patients was 10. In multivariable analyses, older age was associated with lower odds of opioid use (odds ratio, 0.97; 95% CI, 0.94-0.999; P = .04) and lower pain scores (Pearson correlation coefficient, -0.05; 95% CI, -0.10 to 0.001, P = .04). Charlson Comorbidity Index score >5 was associated with use of ≥10 pills (odds ratio, 6.62; 95% CI, 1.60-27.50; P = .01). CONCLUSION: Excess opioids are often prescribed for endocrine surgery. By using an ideal pill number and understanding predictors of postoperative pain, surgeons can more adequately treat pain and limit excess opioid prescriptions.

Parathyroid cysts: A review of 359 patients reported in the international literature.

BACKGROUND: Parathyroid cysts are lesions that represent 1-5% of neck masses. They are subdivided into two categories: functioning and non-functioning.The aim of the present review is to give a detailed account of all reported cases of parathyroid cysts in the literature and to analyze statistically the available data. METHODS: A bibliographic research was performed from 1905 until 2016. A database with the patients' characteristics was made and analyzed statistically. RESULTS: A total of 218 articles were found, reporting 359 cases of cysts. Mean age of patients was 49.24 y/o and the male/female ratio was 1:1.85. The most common locations were left thyroid lobe (113/358 patients, 31.6%), and superior mediastinum (69/358 patients, 19.3%), while the most common symptoms were neck mass (148/355 patients, 41.7%), compressive symptoms (73/355 patients, 206%) and hyperparathyroidism (62/355 patients, 17.5%). Non-functioning cysts were more frequent (220/357 patients, 61.6%). Regarding dimensions, mean diameter was 4.88 cm. Ultrasound and FNA are used for their diagnosis, while cystic fluid analysis may help the differential diagnosis. Recurrences were mentioned in 27/97 patients (27.8%) with available data. No deaths due to parathyroid cysts were mentioned in the literature. CONCLUSION: Parathyroid cysts should be taken into consideration in case of parathyroid dysfunction or asymptomatic neck mass. The surgeon's careful manipulations on the cyst are crucial for a definitive treatment.

Incidental Diagnosis of Parathyroid Lesions by Preoperative Use of Next-Generation Molecular Testing.

BACKGROUND: Parathyroid glands can mimic thyroid follicular lesions on fine-needle aspiration (FNA) cytology and can lead to unnecessary or incorrect surgery. Newer molecular panel tests using next-generation sequencing (NGS) include analysis of cell type-specific gene expression profiles such as parathyroid. The study aim is to determine the frequency and clinical implications of parathyroid tissue identification by molecular testing in cytologically indeterminate "thyroid" lesions. METHODS: Molecular analysis of indeterminate thyroid FNA specimens is obtained routinely and relies on amplification-based NGS inclusive of PTH-specific expression profiles. For this study, we retrospectively examined the clinical data and management of patients with molecular results positive for PTH expression from May 2014 until May 2016. RESULTS: Among 4765 consecutive patients with indeterminate cytology for a presumed thyroid nodule, NGS instead indicated a parathyroid lesion in 20 patients (0.42%). The clinical data of 15 patients were available, and the subsequent clinical management was altered in 93% (14/15 patients), including five (33%) eucalcemic patients who could avoid unnecessary surgery. Primary hyperparathyroidism was not suspected in seven patients until the molecular analysis results, and primary hyperparathyroidism was diagnosed in one (14%). During parathyroid exploration, most patients (6/8, 75%) required concurrent thyroidectomy or lobectomy, but thyroid preservation was still possible in two patients. A parathyroid gland was histologically confirmed in 89%. CONCLUSIONS: In 0.42% of patients with indeterminate cytology results, next-generation molecular results will indicate the presence of a parathyroid lesion. When this occurs, it is accurate and can robustly impact clinical management (93%).

Multiple Myeloma Presenting as Massive Amyloid Deposition in a Parathyroid Gland Associated with Amyloid Goiter: A Medullary Thyroid Carcinoma Mimic on Intra-operative Frozen Section.

Clinical examples of amyloid deposition in parathyroid glands are exceedingly rare and usually present as an incidental finding in a patient with amyloid goiter. Here, we present the first histologically documented case of parathyroid amyloid deposition that presented as a mass. The patient did not have hyperparathyroidism. The parathyroid gland was submitted for intra-operative frozen section and concern for medullary thyroid carcinoma was raised. An important histologic clue arguing against medullary thyroid carcinoma was the evenly dispersed nature of the amyloid. Histologic perinuclear clearing and parathyroid hormone immunohistochemistry confirmed parathyroid origin on permanent sections. The patient was also found to have associated amyloid goiter. Mass spectrometry of the amyloid showed it to be composed of kappa light chains. On further work-up, the patient was diagnosed with multiple myeloma. Awareness of parathyroid amyloid deposition is important as it is a histologic mimic of medullary thyroid carcinoma, especially on frozen section. Amyloid typing with evaluation for multiple myeloma in any patient with kappa or lambda light chain restriction is also important.

The diagnostic value of shear wave elastography for parathyroid lesions and comparison with cervical lymph nodes.

AIMS: The aim of this study was to prospectively assess the feasibility of the Virtual Touch tissue imaging quantification (VTIQ) method of shear wave elastography (SWE) for the discrimination of parathyroid lesions and to compare the lesions' stiffness with that of cervical lymph nodes. MATERIALS AND METHODS: SWE using VTIQ was performed on 66 patients with 87 histopathologically proven parathyroid lesions (54 parathyroid adenomas and 33 parathyroid hyperplasia) and 29 patients with 31 inflammatory cervical lymph nodes. The mean SWVs of the lesions were compared and receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic performance. RESULTS: The mean SWV of parathyroid adenomas (2.16±0.33 m/s) differed significantly from those of parathyroid hyperplasia and lymph nodes (1.75±0.28 m/s and 1.86±0.37 m/s respectively, p<0.001). Selecting a cutoff value of 1.92 m/s for diagnosing adenoma led to 80% sensitivity and 82% specificity (area under the curve [AUC]: 0.832 [95% confidence interval (CI): 0.742-0.921], p< 0.001). CONCLUSIONS: The VTIQ method of SWE can contribute to the differentiation of parathyroid adenoma from parathyroid hyperplasia and cervical lymphnodes.

Unusual presentations of enlarged parathyroid cysts: two case reports.

INTRODUCTION: Parathyroid cysts are infrequently encountered and have a variable presentation pattern depending on their size, location and secreting character. PATIENTS AND METHODS: We report two cases of parathyroid cysts characterized by their uncommon clinical presentation. RESULTS: In the first case the patient presented with a large cervical cystic mass without hypercalcemia, while in the second case, the patient experienced a hypercalcemic crisis associated with acute renal failure. The variable pattern of clinical manifestations is discussed. CONCLUSION: Parathyroid cysts are a rare entity. Surgical resection is the key to therapy when hyperparathyroidism or local compression are identified.