Multiglandular Parathyroid Disease Research Articles

Pilot study of plasma miRNA signature panel for differentiating single vs multiglandular parathyroid disease.

The ability to differentiate sporadic primary hyperparathyroidism (sPHPT) caused by a single parathyroid adenoma (PTA) from multiglandular disease (MGD) pre-operatively, as well as definitely diagnose sPHPT in difficult patients, would enhance surgical decision making. Identify miRNA (miR) signatures for MGD, single- and double-PTA, as well as cell-free miRNA (cfmiR) in plasma samples from patients with single-PTAs to use as biomarkers. 47 patients with sPHPT (single-PTA n=32, double-PTA n=12, MGD n=9). Pre-operative plasma samples from 16 single-PTA and 29 normal healthy donors (NHD). All specimens were processed and analyzed for 2,083 miRs using HTG EdgeSeq miR whole transcriptome assay and normalized using DESeq2 to identify differentially expressed (DE) miRs. MiR classifiers were identified using Random Forest. ROC curves and AUC. MiR signatures distinguished normal parathyroid from MGD and PTA as well as MGD from PTA in tissue samples. Common miRs were found in the single-PTA and double-PTAs. Data integration identified a 27-miR signature in single-PTA tissue samples compared to the rest of the tissue samples. In plasma samples analysis, significant cfmiRs were DE in single-PTA patients compared to NHD. Of those, only 9 miRNAs/cfmiRs were found DE in both tissue and plasma samples from patients diagnosed with a single-PTA (AUC=76%). Twenty-seven miRs were consistently found DE in single-PTA tissue and plasma samples. Data integration showed a 9-cfmiR signature with potential clinical utility to pre-operatively diagnose sPHPT caused by a single-PTA, which could decrease more invasive parathyroid explorations.

Imaging Recommendations for Diagnosis and Management of Primary Parathyroid Pathologies: A Comprehensive Review.

Parathyroid pathologies are suspected based on the biochemical alterations and clinical manifestations, and the predominant roles of imaging in primary hyperparathyroidism are localisation of tumour within parathyroid glands, surgical planning, and to look for any ectopic parathyroid tissue in the setting of recurrent disease. This article provides a comprehensive review of embryology and anatomical variations of parathyroid glands and their clinical relevance, surgical anatomy of parathyroid glands, differentiation between multiglandular parathyroid disease, solitary adenoma, atypical parathyroid tumour, and parathyroid carcinoma. The roles, advantages and limitations of ultrasound, four-dimensional computed tomography (4DCT), radiolabelled technetium-99 (99mTc) sestamibi or dual tracer 99mTc pertechnetate and 99mTc-sestamibi with or without single photon emission computed tomography (SPECT) or SPECT/CT, dynamic enhanced magnetic resonance imaging (4DMRI), and fluoro-choline positron emission tomography (18F-FCH PET) or [11C] Methionine (11C -MET) PET in the management of parathyroid lesions have been extensively discussed in this article. The role of fluorodeoxyglucose PET (FDG-PET) has also been elucidated in this article. Management guidelines for parathyroid carcinoma proposed by the American Society of Clinical Oncology (ASCO) have also been described. An algorithm for management of parathyroid lesions has been provided at the end to serve as a quick reference guide for radiologists, clinicians and surgeons.

Cell cycle regulation in parathyroid adenomas and multiglandular parathyroid disease: Similarities, differences and heterogeneity

Cell cycle regulation in parathyroid adenomas and multiglandular parathyroid disease: Similarities, differences and heterogeneity

Primary hyperparathyroidism: predictors of sporadic multi-gland disease.

In this review, we discuss the definition, prevalence, and etiology of sporadic multiglandular disease (MGD), with an emphasis on its preoperative and intraoperative predictors. Primary hyperparathyroidism (PHPT) is the third-most common endocrine disorder, and multiglandular parathyroid disease (MGD) is a cause of PHPT. Hereditary MGD can be definitively diagnosed with detailed family history and genetic testing, whereas sporadic MGD presents a greater challenge in clinical practice, and parathyroidectomy for MGD is associated with a higher risk of surgical failure than single gland disease (SGD). Therefore, it is crucial to be able to predict the presence of sporadic MGD in a timely manner, either preoperatively or intraoperatively. Various predictive methods cannot accurately identify all cases of sporadic MGD, but they can greatly optimize the management of MGD diagnosis and treatment and optimize the cure rate. Future research will urge us to investigate more integrative predictive models as well as increase our understanding of MGD pathogenesis.

Primary Multiglandular Parathyroid Disease in the Setting of Pompe Disease.

Primary Multiglandular Parathyroid Disease in the Setting of Pompe Disease.

SAT249 Femur Lysis Calcium Crisis

Abstract Disclosure: G. Gupta: None. S. Idriss: None. N. Barua: None. J. Hodge: None. I. Jamal: None. Introduction: Primary hyperparathyroidism usually presents with symptoms of bone pain, fatigue, polyuria, constipation, and nephrolithiasis. Here we describe a 27-year-old female with a femoral neck fracture and found to have a parathyroid mass. Case: 27 y/o female with autism spectrum, presented to the ED for evaluation of a mechanical fall and was found to have a left femur and pubic ramus fracture. On arrival she was vitally stable, labs were significant for parathyroid hormone-related hypercalcemia corrected Ca 14.8 mg/dL, PTH 911 peaked to 2884 pg/mL, vit D level of 12.7 ng/mL, phosphorus of 2.3 mg/dL. Trauma workup revealed numerous osseous lytic lesions lower extremities. Review of system was negative except for localized pain at fracture site. Family history negative for hypercalcemia or hyperparathyroidism. She was managed with IV fluids, IV Zoledronic Acid 4 mg, SC calcitonin 240 units, and 50K IU D3. During hospitalization, she needed re-dozing with Zoledronic acid and Cinacalcet due to recurrence of significant hypercalcemia, warranting further imaging. CT neck showed mandibular and maxillary bone lesions raising suspicion of hyperparathyroidism jaw tumor syndrome (HPT-JT) vs brown tumors, 3.1 cm lobular mass inferior to the right thyroid lobe suspicious for large parathyroid adenoma vs carcinoma, and other multiple enlarged parathyroids. She underwent left femur cephalomedullary nailing and prophylactic nailing for the impending right femur fracture. Bone pathology showed fragmented bone, adipose, and skeletal muscle with fibrinous debris. She underwent subtotal parathyroidectomy (4-1/2 glands) and intraoperative PTH level declined from 1537 to 75 pg/mL 15 minutes after removal. Pathology showed tissue consistent with multi glandular parathyroid disease without evidence of malignancy. Postop her course was complicated with hungry bone syndrome requiring a few weeks on IV calcium. Discussion: Pathologic conditions in primary hyperparathyroidism include single adenomas (80-90% of the time), multiglandular hyperplasia multiple-gland (three or more glands) accounting for approximately 6%, and parathyroid carcinomas account for 1-2% of cases. Other conditions as with primary hyperparathyroidism include Familial hyperparathyroidism such as MEN 1 & 2A, Familial isolated hyperparathyroidism, and Familial HPT-JT syndrome, previously termed familial cystic parathyroid adenomatosis. Interestingly our pt had multiglandular hyperplasia which is a less common cause, she also demonstrated jaw lesions but didn’t fulfill the criteria for HPT-JT. Conclusion: Our patient had an unusual presentation of large bone fracture and multiple lytic lesions likely representing a brown tumor of the bone due to primary hyperparathyroidism. Most patients with lytic lesions have malignancy, however, endocrine pathologies should also be considered. Presentation: Saturday, June 17, 2023

Preoperative parathyroid localization. Relevance of MIBI SPECT-CT in adverse scenarios

PurposeSelective parathyroidectomy, the treatment of choice for primary hyperparathyroidism, requires precise preoperative localization. Our purpose was to compare the accuracy and concordance of pre-surgical MIBI parathyroid scintigraphy and ultrasonography, as well as to assess the relevance of hybrid acquisition (SPECT/CT) in compromised circumstances: low-weight or ectopic adenomas, coexisting thyroid disease and re-interventions. MethodsThe study included 223 patients with primary hyperparathyroidism operated in a single Surgical Unit from August 2016 to March 2021. Preoperative ultrasonography and double-phase MIBI were performed with early SPECT/CT acquisition. A minimally invasive surgical approach was initially attempted, except in patients with concomitant thyroid surgery or multiglandular parathyroid disease. ResultsSelective parathyroidectomy was accomplished in 179 patients (80.2%); cervicotomy and/or thoracoscopy in 44. Removal of the parathyroid lesion was achieved in 211 patients (94.6%), corresponding 204 (96.7%) to adenomas (37 ectopic). The cure rate was 94.2%. Preoperative MIBI SPECT/CT showed higher sensitivity and accuracy (84%; 80%) compared to ultrasound (72%; 71%), being more precise in defining the exact anatomical location (75.8% vs 68.7%). These differences reached statistical significance in ectopic glands. The existence of concomitant thyroid pathology did not decrease the sensitivity of SPECT/CT (84.2%). Mean parathyroid weight was 692.2mg (95%CI: 443.5-941) in MIBI-negative cases and 1145.9mg (95%CI: 983.6-1308.3) in MIBI-positive (p=0.001). Re-intervention was successful in the 8 patients with previous surgery. ConclusionMIBI SPECT/CT presents greater sensitivity, accuracy and anatomical precision than ultrasound for preoperative parathyroid localization, even in the case of ectopic glands or coexisting thyroid pathology. The weight of the pathological gland is a significantly limiting factor.

Advances and Updates in Parathyroid Pathology.

Hyperparathyroidism is a common endocrine disorder characterized by elevated levels of parathyroid hormone and hypercalcemia and is divided into 3 types: primary, secondary, and tertiary. Distinction between these types is accomplished by correlation of clinical, radiologic, and laboratory findings with pathologic features. Primary hyperparathyroidism occurs sporadically in 85% of cases with the remaining cases associated with multiple familial syndromes. The pathologic manifestations of primary hyperparathyroidism include parathyroid adenoma, parathyroid hyperplasia, and parathyroid carcinoma. Recent advances in the understanding of the pathogenesis of parathyroid disease has helped to refine the diagnosis and classification of parathyroid lesions. The identification of multiple clonal proliferations in traditional multiglandular parathyroid hyperplasia has led to the adoption by the World Health Organization (WHO) of the alternate term of primary hyperparathyroidism-related multiglandular parathyroid disease. Additional nomenclature changes include the adoption of the term atypical parathyroid tumor in lieu of atypical parathyroid adenoma to reflect the uncertain malignant potential of these neoplasms. Clinical and morphologic features characteristic of familial disease have been described that can help the practicing pathologist identify underlying familial disease and provide appropriate management. Use of ancillary immunohistochemistry and molecular studies can be helpful in classifying parathyroid neoplasms. Parafibromin has proven useful as a diagnostic and prognostic marker in atypical parathyroid tumors and parathyroid carcinomas. This review provides an update on the diagnosis and classification of parathyroid lesions considering the recent advances in the understanding of the molecular and clinical features of parathyroid disease and highlights the use of ancillary studies (immunohistochemical, and molecular) to refine the diagnosis of parathyroid lesions.

Multiglandular Parathyroid Disease.

Introduction: Multiglandular parathyroid disease (MGD) is an uncommon cause of primary hyperparathyroidism (pHPT) and has been reported in the literature in 8–33% of patients with pHPT. The aim of our study was to review the clinical characteristics and management of MGD and evaluation of surgical treatment failures. Methods: We performed a retrospective study of 163 patients with pHPT undergoing parathyroidectomy (PTX) at the Department of General and Endocrine Surgery between 1983 and 2018. All these patients were diagnosed with MGD. This group of patients was compared with a group of 856 patients with solitary disease operated for pHPT in the same period. Results: Among 163 patients—127 (79%) of them had two lesions, 28 (16%) had three, and 8 (5%) four. They were prevalently women over the age of 50. The diagnosis was based on PTH and ionized calcium studies and used sestamibi technetium-99m scintigraphy (MIBI) as well for us. Treatment was surgical. Conclusions: Parathyroidectomy (PTX) for multiglandular parathyroid disease (MGD) is associated with a higher operative risk of failure compared to solitary disease. Preoperative diagnosis and localization of the parathyroid glands is an extremely important element of treatment. Diagnosis is based on PTH and calcium levels. Ultrasonography (USG), MRI, and scintigraphy are very helpful in diagnosis. Mediastinal multiglandular parathyroid disease (MGD) is associated with increased surgical treatment failures. The treatment is surgical and consists of the removal of the masses or complete parathyroidectomy. Based on this study, we support the existence of multiple adenomas and advocate the removal of only macroscopically enlarged parathyroid glands in patients with primary hyperparathyroidism.

Preoperative parathyroid localization. Relevance of MIBI SPECT-CT in adverse scenarios

PurposeSelective parathyroidectomy, the treatment of choice for primary hyperparathyroidism, requires precise preoperative localization. Our purpose was to compare the accuracy and concordance of pre-surgical MIBI parathyroid scintigraphy and ultrasonography, as well as to assess the relevance of hybrid acquisition (SPECT/CT) in compromised circumstances: low-weight or ectopic adenomas, coexisting thyroid disease and re-interventions. MethodsThe study included 223 patients with primary hyperparathyroidism operated in a single Surgical Unit from August 2016 to March 2021. Preoperative ultrasonography and double-phase MIBI were performed with early SPECT/CT acquisition. A minimally invasive surgical approach was initially attempted, except in patients with concomitant thyroid surgery or multiglandular parathyroid disease. ResultsSelective parathyroidectomy was accomplished in 179 patients (80.2%); cervicotomy and/or thoracoscopy in 44. Removal of the parathyroid lesion was achieved in 211 patients (94.6%), corresponding 204 (96.7%) to adenomas (37 ectopic). The cure rate was 94.2%. Preoperative MIBI SPECT/CT showed higher sensitivity and accuracy (84%; 80%) compared to ultrasound (72%; 71%), being more precise in defining the exact anatomical location (75.8% vs 68.7%). These differences reached statistical significance in ectopic glands. The existence of concomitant thyroid pathology did not decrease the sensitivity of SPECT/CT (84.2%). Mean parathyroid weight was 692.2mg (95%CI: 443.5-941) in MIBI-negative cases and 1145.9mg (95%CI: 983.6-1308.3) in MIBI-positive (p=0.001). Re-intervention was successful in the 8 patients with previous surgery. ConclusionMIBI SPECT/CT presents greater sensitivity, accuracy and anatomical precision than ultrasound for preoperative parathyroid localization, even in the case of ectopic glands or coexisting thyroid pathology. The weight of the pathological gland is a significantly limiting factor.

Multiglandular Parathyroid Disease in Primary Hyperparathyroidism With Inconclusive Conventional Imaging.

Inconclusive preoperative imaging is a strong predictor of multiglandular parathyroid disease (MGD) in patients with primary hyperparathyroidism (PHPT). MGD was investigated in a cohort of 17 patients with PHPT (mean age 64.9 years, total calcium 2.75 mmol/l and parathyroid hormone (PTH) 113.3 ng/l) who underwent 18F-fluorocholine PET/CT (FCH) imaging before surgery. The initial MIBI SPECT scintigraphy (MIBI) and/or neck ultrasound were not conclusive or did not localize all pathological parathyroid glands, and PHPT persisted after surgery. Sporadic MGD was present in 4 of 17 patients with PHPT (24 %). In 3 of 4 patients with MGD, FCH correctly localized 6 pathological parathyroid glands and surgery was successful. Excised parathyroid glands were smaller (p <0.02) and often hyperplastic in MGD than in single gland disease. In two individuals with MGD, excision of a hyperplastic parathyroid gland led to a false positive decline in intraoperative PTH and/or postoperative serum calcium. Although in one patient it was associated with partial false negativity, parathyroid imaging with FCH seemed to be superior to neck ultrasound and/or MIBI scintigraphy in MGD.

Overview of the 2022 WHO Classification of Parathyroid Tumors.

The 2022 WHO classification reflects increases in the knowledge of the underlying pathogenesis of parathyroid disease. In addition to the classic characteristic features of parathyroid neoplasms, subtleties in histologic features which may indicate an underlying genetic abnormality reflect increased understanding of the clinical manifestations, histologic, and genetic correlation in parathyroid disease. The importance of underlying genetic aberrancies is emphasized due to their significance to the care of the patient. Traditionally, the term "parathyroid hyperplasia" has been applied to multiglandular parathyroid disease; however, the concept of hyperplasia is generally no longer supported in the context of primary hyperparathyroidism since affected glands are usually composed of multiple "clonal" neoplastic proliferations. In light of these findings and management implications for patient care, the 2022 WHO classification endorses primary hyperparathyroidism-related multiglandular parathyroid disease (multiglandular multiple parathyroid adenomas) as a germline susceptibility-driven multiglandular parathyroid neoplasia. From such a perspective, pathologists can provide additional value to genetic triaging by recognizing morphological and immunohistochemical harbingers of MEN1, CDKN1B, MAX, and CDC73-related manifestations. In the current WHO classification, the term "parathyroid hyperplasia" is now used primarily in the setting of secondary hyperplasia which is most often caused by chronic renal failure. In addition to expansion in the histological features, including those that may be suggestive of an underlying genetic abnormality, there are additional nomenclature changes in the 2022 WHO classification reflecting increased understanding of the underlying pathogenesis of parathyroid disease. The new classification no longer endorses the use of "atypical parathyroid adenoma". This entity is now being replaced with the term of "atypical parathyroid tumor" to reflect a parathyroid neoplasm of uncertain malignant potential. The differential diagnoses of atypical parathyroid tumor are discussed along with the details of worrisome clinical and laboratory findings, and also features that define atypical histological and immunohistochemical findings to qualify for this diagnosis. The histological definition of parathyroid carcinoma still requires one of the following findings: (i) angioinvasion (vascular invasion) characterized by tumor invading through a vessel wall and associated thrombus, or intravascular tumor cells admixed with thrombus, (ii) lymphatic invasion, (iii) perineural (intraneural) invasion, (iv) local malignant invasion into adjacent anatomic structures, or (v) histologically/cytologically documented metastatic disease. In parathyroid carcinomas, the documentation of mitotic activity (e.g., mitoses per 10mm2) and Ki67 labeling index is recommended. Furthermore, the importance of complete submission of parathyroidectomy specimens for microscopic examination, and the crucial role of multiple levels along with ancillary biomarkers have expanded the diagnostic workup of atypical parathyroid tumors and parathyroid carcinoma to ensure accurate characterization of parathyroid neoplasms. The concept of parafibromin deficiency has been expanded upon and term "parafibromin deficient parathyroid neoplasm" is applied to a parathyroid neoplasm showing complete absence of nuclear parafibromin immunoreactivity. Nucleolar loss is considered as abnormal finding that requires further molecular testing to confirm its biological significance. The 2022 WHO classification emphasizes the role of molecular immunohistochemistry in parathyroid disease. By adopting a question-answer framework, this review highlights advances in knowledge of histological features, ancillary studies, and associated genetic findings that increase the understanding of the underlying pathogenesis of parathyroid disease that are now reflected in the updated classification and new entities in the 2022 WHO classification.

GCM2 Variants in Familial and Multiglandular Primary Hyperparathyroidism.

Multiglandular and familial parathyroid disease constitute important fractions of primary hyperparathyroidism (PHPT). Germline missense variants of GCM2, a regulator of parathyroid development, were observed in familial isolated hyperparathyroidism and sporadic PHPT. However, as these previously reported GCM2 variants occur at relatively high frequencies in the population, understanding their potential clinical utility will require both additional penetrance data and functional evidence relevant to tumorigenicity. Determine the frequency of GCM2 variants of interest among patients with sporadic multigland or familial parathyroid disease and assess their penetrance. DNA-encoding PHPT-associated GCM2 germline variants were polymerase chain reaction-amplified and sequenced from 107 patients with either sporadic multigland or suspected/confirmed familial parathyroid tumors. GCM2 variants were observed in 9 of 107 cases (8.4%): Y282D in 4 patients (6.3%) with sporadic multigland disease; Y394S in 2 patients (11.1%) with familial PHPT and 3 (4.8%) with sporadic multigland disease. Compared with the general population, Y282D was enriched 5.9-fold in multigland disease, but its penetrance was very low (0.02%). Y394S was enriched 79-fold in sporadic multigland disease and 93-fold in familial PHPT, but its penetrance was low (1.33% and 1.04%, respectively). Observed in vitro-activating GCM2 variant alleles are significantly overrepresented in PHPT patients with multiglandular or familial disease compared to the general population, yet penetrance values are very low; that is, most individuals with these variants in the population have a very low risk of developing PHPT. The potential clinical utility of detecting these GCM2 variants requires further investigation, including assessing their possible role as pathogenic/low-penetrance alleles.

Parathyroid disorder and concomitant thyroid cancer in patients with multiple endocrine neoplasia type 1: A retrospective cohort study.

This study aimed to determine the rates and characteristics of parathyroid disorder and thyroid cancer in patients with multiple endocrine neoplasia type 1 vs sporadic primary hyperparathyroidism (SPHP) undergoing parathyroidectomy.Patients with multiple endocrine neoplasia type 1-associated primary hyperparathyroidism (MPHP) or SPHP who underwent initial or reoperative parathyroid exploration from 1999 to 2019 were identified via a clinical database. The data for MPHP patients (n = 15) were compared to those of a selected 2:1 age- and sex-matched SPHP cohort (n = 30) who all underwent thyroidectomy for concurrent thyroid nodules.Compared with that of the SPHP group, the parathyroid hormone level of the MPHP group was much higher (470.67 ± 490.74 pg/mL vs 217.77 ± 165.60 pg/mL, P = .001). Multiglandular parathyroid disease (6/15 [40%] vs 3/30 [10%], P = .026) and more hyperplasia (7/15 [46.7%] vs 5/30 [16.7%], P = .039) were found in the MPHP group, and more parathyroid lesions presented as a round shape (long/short meridian < 2) by ultrasound (16/20 [80%] vs 8/31 [25.8%], P < .001). Regarding thyroid nodules, there was no difference in the rate of histologic thyroid cancer, but more thyroid cancer was found in the last 5 years among the MPHP cases (5/9 [55.6%] vs 3/18 [16.7%], P = .052).Multiglandular parathyroid disease and hyperplasia were more frequent in the MPHP cohort than in the SPHP cohort, and the parathyroid lesions usually presented with a round shape on ultrasonography. More concurrent thyroid cancer was found in MPHP than SPHP patients over the previous 5 years.

An Unusual Presentation of Primary Hyperparathyroidism: Ectopic Parathyroid Gland and Multiglandular Disease

Primary hyperparathyroidism (PHPT) can be associated as a single parathyroid adenoma in approximately 85% of patients, the remaining 15% of them correspond to individuals with hyperplasia. The multiglandular parathyroid disease varies in range 7–33% and contribute a persistent PHPT. We report a case of primary hyperparathyroidism with an unusual presentation of ectopic mediastinal parathyroid. The case was of a 54-year-old female, who started her illness 3 years ago, with frequent headache, regular fatigue and muscle pain, denied losing weight. She was admitted to emergency room for a urinary infection. During the hospitalization showed bilateral nephrocalcinosis, hypercalcemic crisis. She has a background of total thyroidectomy and subtotal parathyroidectomy because a thyroid adenomatous hyperplasia and parathyroid hyperplasia with removal of a total of three parathyroid glands. She had very high PTH level. Laboratory: serum calcium: 16.8mg/dl; ionic calcium: 2.37 mmol/L; P: 1.9 (2.7–4.5g/dL); Hb: 9 g/dL; Platelets: 558 000 per microliter; Leukocytes 9 600 cells/mcL; Albumin: 4g/dl; TSH: 0.06 mU/L; fT4: 1.29 (L-T4 doses were 100 ug). Four months after parathyroid surgery, the intact PTH level dropped from 1602 ng/l to 550 (15–65 ng/L). Computed tomography and Tc-sestamibi scintigraphy - SPECT revealed a residual cervicothoracic mass in retroesophageal region (D1-D2) (Fig1 -2). The patient underwent a new surgery and the intact PTH dropped 39ng/L. Histopathology revealed characteristic features of a parathyroid adenomatous (10 gram weight) (Fig.3); additionally a retroesternal ectopic thyroid tissue. There was not reappearance of high blood calcium and parathormone levels more than 6 months after second surgery for PHPT. An unusual case of PHPT caused by a multiglandular disease parathyroid varies (four glands and a ectopic gland), reliable histopathologic adenomatous and hyperplastic parathyroid disease, and persistent primary hyperparathyroidism with very high serum intact PTH level.Reference: (1) Masi L. Primary Hyperparathyroidism. Brandi ML (ed): Parathyroid Disorders. Focusing on Unmet Needs. Front Horm Res. Basel, Karger, 2019, vol 51, pp 1–12. (2) Pecheva M, Mahendran K, Kadlec J, Lofthouse M1, Van Tornout F. Mediastinal giant parathyroid adenoma-a minimally invasive mediastinal surgical approach for an emergency presentation. Ann Cardiothorac Surg. 2016 Jan;5(1):70–3. (3) Cakmak H 1, Tokat AO, Karasu S, Özkan M. Adenoma paratiroideo mediastínico gigante. Tuberk Toraks. 2011; 59 (3): 263–5. (4)Thier M, Daudi S, Bergenfelz A, Almquist M. Predictors of multiglandular disease in primary hyperparathyroidism. Langenbecks Arch Surg. 2018;403(1):103–109.

Multiglandular Parathyroid Disease: the Results of Surgical Treatment

Background. Sporadic multiple gland disease in primary hyperparathyroidism occurs in 7 to 33 % of cases. The absence of specific risk factors, low sensitivity of imaging methods, and low efficiency of bilateral neck exploration and intraoperative monitoring of parathyroid hormone indicate the complexity of the diagnosis and treatment of this disease’s form. Aim of the research. To analyze the results of surgical treatment of multiple lesions of the parathyroid gland in primary and secondary hyperparathyroidism. Methods. There was retrospective study, which included 100 observations of surgical treatment for primary and secondary hyperparathyroidism in the thoracic department of Irkutsk Regional Clinical Hospital from May 2018 to September 2019. The main point was to identify the frequency of surgical treatment outcomes in patients with multiple parathyroid lesions. As part of the study, potential predictors of multiple gland disease in primary hyperparathyroidism were analyzed. Results. Multiple gland disease in primary hyperparathyroidism occurs in 29 % of cases and causes persistence of the disease (p ≤ 0.01). Signs of multiple gland disease in primary hyperparathyroidism include the level of ionized calcium, parathyroid hormone (p ≤ 0.05), creatinine level and glomerular filtration rate (p ≤ 0.01). A negative result of intraoperative monitoring correlates with persistence of primary hyperparathyroidism in multiple lesions (χ2, p ≤ 0.05). Selective parathyroidectomy is associated with persistence of hyperparathyroidism in multiple lesions (χ2, p ≤ 0.05), while total parathyroidectomy is associated with remission of the disease (χ2, p ≤ 0.05). We did not find a statistically significant relationship between the results of surgical treatment for morphology of the parathyroid glands (χ2, p &gt; 0.1). Conclusion. Multiple gland disease is the main cause of persistence of primary hyperparathyroidism. This form of the disease corresponds to lower levels of calcium, parathyroid hormone, and kidney function. Persistence factors have been established: removal of less than four parathyroid glands and a negative result of intraoperative monitoring of parathyroid hormone. Bilateral neck exploration does not reduce the incidence of disease persistence.

Multiglandular parathyroid disease in patients with primary hyperparathyroidism and inconclusive conventional imaging

Multiglandular parathyroid disease in patients with primary hyperparathyroidism and inconclusive conventional imaging

Effectiveness of Intraoperative Parathyroid Monitoring (ioPTH) in predicting a multiglandular or malignant parathyroid disease

AimThe main goal of our study was to confirm the usefulness of intra-operative parathyroid hormone (PTH) monitoring (ioPTH) when using minimally invasive techniques for treatment of sporadic Primary hyperparathyroidism (pHTP). Furthermore, we aimed to evaluate if ioPTH monitoring may help to predict the etiology of primary hyperparathyroidism, especially in malignant or multiglandular parathyroid disease. MethodsA retrospective review of 125 consecutive patients with pHPT who underwent parathyroidectomy between 2001 and 2016 at the Department of General Surgery was performed.For each patient, the specific preoperative work-up consisted of: high-resolution US of the neck by a skilled sonographer, sestamibi parathyroid scan, laryngoscopy, and serum measurement of PTH, serum calcium levels, and serum 25(OH)D levels. ResultsThe study included 125 consecutive patients who underwent surgery for pHPT. At the histological examination, we registered 113 patients with simple adenomatous pathology (90,4%), 5 atypical adenomas (4%), 3 cases of parathyroid carcinoma (2,4%),, , and 4 histological exams of different nature (3,2%). Overall, 6 cases (4,8%) of multiglandular disease were found. We reported 10 cases (8%) of recurrent/persistent hyperparathyroidism: 1/10 in a patient affected by atypical adenoma, 9/10 in patients with benign pathology. Regarding these 10 cases, in three (30%) patients, ioPTH wasn't dosed (only frozen section (FS) exam was taken), in 5 cases (50%) ioPTH dropped more than 50% compared to basal value (false negative results), and in 2 (20%) cases, ioPTH did not drop >50% from the first samples taken, the extemporary exam had confirmed the presence of adenoma and the probable second hyperfunctioning adenoma was not found. ConclusionsIoPTH determinations ensure operative success of surgical resection in almost all hyperfunctioning tissue; in particular it is very important during minimally invasive parathyroidectomy, as it allows avoiding bilateral neck exploration. The use of ioPTH monitoring offer increased sensitivity in detecting multiglandular disease and can minimize the need and risk associated with recurrent operations, and may facilitate cost-effective minimally invasive surgery. Moreover, intraoperative PTH monitoring could be a reliable marker to predict a malignant disease during parathyroidectomy, showing higher ioPTH baseline value and superior drop compared to benign disease.

Multiple endocrine neoplasia type 1 syndrome: single centre experience from western India.

Multiple endocrine neoplasia type 1 syndrome (MEN1) is a rare autosomal dominant familial cancer syndrome affecting multiple endocrine glands. Published literature on MEN1 from Indian subcontinent is scarce. We report here a case series of MEN1 patients (n=18) from 14 unrelated families. Retrospective study describing the clinical profile of MEN1 patients from endocrine unit of a tertiary care hospital from western India. Additionally clinical profile of primary hyperparathyroidism (PHPT) in MEN1 patients was compared with that of apparently sporadic PHPT cohort from our centre. Eighteen patients (10 males, 8 females) diagnosed as MEN1 were included. Mean age at diagnosis was 31.5±10.6years (range 17-54). Incidence of primary hyperparathyroidism (PHPT), pituitary adenoma (PA), and gastro-entero-pancreatic neuroendocrine tumor (GEP-NET) was 94.4, 72.2, and 72.2%, respectively. GEP-NET was the commonest presenting lesion (33.3%), followed by PA (27.7%), PHPT (16.6%), thymic carcinoid (5.5%), while 16.6% cases were identified on family screening. PHPT manifestations (clinical and biochemical) in MEN1 were less severe as compared to those of sporadic PHPT. Contrast enhanced computed tomography (CECT) and (68)Ga-DOTANOC PET/CT were equally sensitive (64.7 vs. 63.5%) in identifying multiglandular parathyroid disease. Non functioning tumors (NFT) were the most common GEP-NET, followed by insulinoma (5/13, two were metastatic). (68)Ga-DOTANOC PET/CT had higher sensitivity in detecting GEP-NET lesions than CECT (100 vs. 62.5%). The most common pituitary lesion was prolactinoma, and all were cabergoline responsive. Genetic analysis was available in 13 patients and 11 patients showed mutation in MEN1 gene. The clinical profile of MEN1 in Asian Indian patients is largely comparable to that reported in other cohorts. Peculiar findings of our cohort are predominance of GEP-NET as a presenting manifestation and relatively higher prevalence of insulinoma with higher occurrence of metastatic insulinoma. Clinical and biochemical profile of MEN1 associated PHPT is less severe than that of our sporadic PHPT.

A randomized, prospective trial of operative treatments for hyperparathyroidism in patients with multiple endocrine neoplasia type 1

Hyperparathyroidism (HPT) in multiple endocrine neoplasia (MEN) type 1 is associated with multiglandular parathyroid disease. Previous retrospective studies comparing subtotal parathyroidectomy (SP) and total parathyroidectomy with autotransplantation (TP/AT) have not established clearly better outcomes with either procedure. Patients were assigned randomly to either SP or TP/AT and data were collected prospectively. The rates of persistent HPT, recurrent HPT, and postoperative hypoparathyroidism were compared. The study cohort included 32 patients randomized to receive either SP or TP/AT (mean follow-up, 7.5 ± 5.7 years). The overall rate of recurrent HPT was 19% (6/32). Recurrent HPT occurred in 4 of 17 patients (24%) treated with SP and 2 of 15 patients (13%) treated with TP/AT (P = .66). Permanent hypoparathyroidism occurred in 3 of 32 patients (9%) overall. The rate of permanent hypoparathyroidism was 12% in the SP group (2/17) and 7% in the TP/AT group (1/15). A second operation was performed in 4 of 17 patients initially treated with SP (24%), compared with 1 of 15 patients undergoing TP/AT (7%; P = .34). This randomized trial of SP and TP/AT in patients with MEN 1 failed to show any difference in outcomes when comparing results of SP versus TP/AT. Both procedures are associated with acceptable results, but SP may have advantages in that is involves only 1 surgical incision and avoids an obligate period of transient postoperative hypoparathyroidism.