Sporadic Hyperparathyroidism Research Articles

Analysis of Bone Phenotype Differences in MEN1-Related and Sporadic Primary Hyperparathyroidism Using 3D-DXA.

Background: The rarity and variability of MEN1-related primary hyperparathyroidism (mPHPT) has led to contradictory data regarding the bone phenotype in this patient population. Methods: A single-center retrospective study was conducted among young age- and sex-matched patients with mPHPT and sporadic hyperparathyroidism (sPHPT). The main parameters of calcium-phosphorus metabolism, bone remodeling markers, and bone mineral density (BMD) measurements were obtained during the active phase of hyperparathyroidism before parathyroidectomy (PTE) and 1 year after. Trabecular Bone Score (TBS) and 3D-DXA analysis of the proximal femur were used to evaluate the differences in bone architecture disruption between groups. Results: Patients with mPHPT had significant lower preoperative BMD compared to sPHPT at lumbar spine-LS (p = 0.002); femur neck-FN (p = 0.001); and total hip-TH (p = 0.002). 3D-DXA analysis showed the prevalence of cortical rather than trabecular bone damage in mPHPT compared to sPHPT: cortical thickness (p < 0.001); cortical surface BMD (p = 0.001); cortical volumetric BMD (p = 0.007); and trabecular volumetric BMD (p = 0.029). One year after, PTE DXA and 3D-DXA parameters were similar between groups, while 3D-visualisation showed more extensive regeneration in cortical sBMD and cortical thickness in mPHPT. Conclusions: mPHPT is associated with lower preoperative BMD values with predominant architecture disruption in the cortical bone. The absence of differences in DXA and 3D-DXA parameters 1 year after PTE between mPHPT/sPHPT combined with significantly lower BMD in mPHPT at the initial stage may indicate faster bone recovery after surgery in mPHPT than in sPHPT.

Molecular Genetic Aspects of Sporadic Multiglandular Primary Hyperparathyroidism.

Multiglandular primary hyperparathyroidism (MGD) represents a rare form of primary hyperparathyroidism (PHPT). MGD is associated with hereditary PHPT, but the sporadic MGD is more common and affects a similar patient profile as single gland parathyroid disease (SGD). The distinction between SGD and MGD is of great clinical importance, especially for the strategy of parathyroidectomy. Based on the limited knowledge available, MGD is likely to be a genetically heterogeneous disease resulting from the interaction of germline and somatic DNA mutations together with epigenetic alterations. Furthermore, these events may combine and occur independently in parathyroid tumors within the same individual with MGD. Gene expression profiling has shown that SGD and MGD may represent distinct entities in parathyroid tumorigenesis. We are waiting for studies to analyze exactly which genes are different in SGD and MGD in order to identify potential biomarkers that can distinguish between the two forms of the disease.

SAT181 Clinical Profile And Treatment Outcomes Of Patients With Sporadic And Multiple Endocrine Neoplasia Syndrome-related Primary Hyperparathyroidism

Abstract Disclosure: U.E. Mathew: None. V.P. Jyotsna: None. A.S. Upadhyay: None. A. Goyal: None. D. Kandaswamy: None. C. Bal: None. A. Sharma: None. C.K. Sharma: None. S. Aggarwal: None. N. Tandon: None. Primary hyperparathyroidism (PHPT) is the most frequent endocrine disorder in MEN-1. The MEN-1 related PHPT (MPHPT) differs from sporadic (SPHPT) in many aspects. The distinction between them is very important at the point of diagnosis as it enables planning on treatment and subsequent surveillance for other endocrine tumours. Objective: The aim of study was to compare the clinical, biochemical, radiological features and surgical outcome in patients with MPHPT versus SPHPT and to identify the predictors of MEN-1 among apparently sporadic hyperparathyroidism. Design: Ambispective cross-sectional study from 2015-2021. Participants: 251 subjects with SPHPT and 23 subjects with MPHPT. Setting: The endocrine clinic of All India Institute of Medical Sciences, New Delhi, India. Results: The classical symptoms of hyperparathyroidism (80.5% vs 47.8%, p&amp;lt;0.001), mean serum calcium (12.7 vs 11.8 mg/dl, p=0.01) and alkaline phosphatase (ALP) levels (p=0.03) were significantly seen higher in SPHPT than MPHPT. MEN-1 patients showed low bone mineral density (BMD) at lumbar spine (-1.52±1.44 vs -2.6±1.25, p=0.001) and femoral neck (1.13±1.37 vs-1.81±1.01, p=0.002) and higher prevalence of complicated nephrolithiasis (34.5 % vs 56.5%, p=0.03) for the age. BMD at their lumbar spine showed an inverse correlation with serum PTH (r=-0.51, p=0.01). Whereas the typical radiological features of hyperparathyroidism and severe skeletal manifestations including brown tumours and fractures were observed less in MEN-1 (44.8% vs 21.7% vs, p=0.02). The overall remission rate was 98.6% in SPHPT and 90% in MPHPT on long term follow up.Despite milder biochemical features, the frequency of hungry bone syndrome was not different from SPHPT (11.6% vs 15.8%, p=0.32). The transient and permanent hypoparathyroidism were more common in MPHPT group (24.4% vs 50%, p=0.01: 0.4% vs 15%, p=0.002).The factors strongly predictive of MEN-1 in multivariate analysis were ALP within the normal range (OR 4.2(95% CI 1.1-16.9), p=0.038), lower lumbar spine BMD (OR 0.47 (95% CI (0.28-0.76), p=0.003) and hyperplastic parathyroid gland on histopathology (OR 37.1(95% CI (9.9-138.6), p&amp;lt;0.001). The multivariate predictive model showed an excellent discrimination between two classes with area under curve in ROC was 0.91. Conclusions: MEN-1 associated PHPT have severe bone and renal involvement despite milder biochemical features, even in Indian settings, where there is a higher frequency of severe symptomatic sporadic hyperparathyroidism. MEN-1 should be suspected when, a discordant finding of severe degree of bone demineralisation at lumbar spine and in normal range of ALP, has observed among apparently SPHPT. Our model can assist in deciding on screening for MEN-1 as the family history and multiglandular involvement may be absent at the presentation, and delay in development of other endocrine tumours. Presentation: Saturday, June 17, 2023

Late-onset hypocalcemia seizure: An interesting presentation of sporadic maternal primary hyperparathyroidism with hypovitaminosis D

Abstract The cardinal manifestation of primary hyperparathyroidism is secondary to hypercalcemia and high bone turnover disease due to sustained elevation of parathyroid hormone. A high index of suspicion for maternal primary hyperparathyroidism should be kept in the setting of neonatal hypocalcemia. Delayed presentation of hypocalcemic seizure secondary to maternal primary hyperparathyroidism is infrequent. Herein, we report a case of a 2-month-old infant who presented with late-onset (&gt;72 h) hypocalcemic seizure, biochemically mimicking pseudohypoparathyroidism, which eventually led to the diagnosis of maternal hyperparathyroidism with vitamin D deficiency.

Clinical profile and treatment outcomes among patients with sporadic and multiple endocrine neoplasia syndrome-related primary hyperparathyroidism.

Accurate demarcation between multiple endocrine neoplasia, type 1 (MEN1)- related primary hyperparathyroidism (MPHPT) and sporadic PHPT (SPHPT) is important to plan the management of primary parathyroid disease and surveillance for other endocrine and nonendocrine tumours. The objective of this study is to compare the clinical, biochemical and radiological features and surgical outcomes in patients with MPHPT versus SPHPT and to identify the predictors of MEN1 syndrome in PHPT. This was an ambispective observationalstudy involving 251 patients with SPHPT and 23 patients with MPHPT evaluated at the endocrine clinic of All India Institute of Medical Sciences, New Delhi, India between January 2015 and December 2021. The prevalence of MEN1 syndrome among patients with PHPT was 8.2% and a genetic mutation was identified by Sanger sequencing in 26.1% of patients with MPHPT. Patients with MPHPT were younger (p < .001), had lower mean serum calcium (p = .01) and alkaline phosphatase (ALP; p = .03) levels and lower bone mineral density (BMD) Z score at lumbar spine (p < .001) and femoral neck (p = .007). The prevalence of renal stones (p = .03) and their complications (p = .006) was significantly higher in MPHPT group. On multivariable analysis, factors predictive of MPHPT were hyperplasia on histopathology [OR 40.1, p < .001], ALP levels within reference range [OR 5.6, p = .02] and lumbar spine BMD [OR 0.39 per unit increase in Z score, p < .001]. Patients with MPHPT have more severe, frequent and early onset of bone and renal involvement despite milder biochemical features. A normal serum ALP, low BMD for age and gender at lumbar spine and histopathology evidence of hyperplasia are predictive factors for MEN1 syndrome in PHPT.

Clinical characteristics of sporadic and MEN1-associated primary hyperparathyroidism in young patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Comparison of Parathyroid Autofluorescence Signals in Different Types of Hyperparathyroidism.

There are scant data in the literature regarding whether parathyroid autofluorescence (AF) signal patterns vary based on the etiology of hyperparathyroidism. The aim of this study was to compare AF signals of parathyroid glands across different etiologies of hyperparathyroidism. As a prospective institutional review board-approved study between 2016 and 2019, AF intensities and heterogeneity indexes (HIs) of parathyroid glands in patients who underwent parathyroidectomy using AF were calculated and compared using Chi-square, Kruskal Wallis, Mann Whitney U, and logistic regression tests. Of the total of 183 patients, 127 patients had sporadic classic primary hyperparathyroidism, 30 patients had sporadic normohormonal primary hyperparathyroidism, 10 patients had sporadic normocalcemic primary hyperparathyroidism, 12 patients had tertiary hyperparathyroidism, and 4 patients had familial primary hyperparathyroidism related to multiple endocrine neoplasia (MEN) 2A. There were no statistical differences in AF signals of abnormal parathyroid glands in classic, normohormonal or normocalcemic sporadic hyperparathyroidism. Parathyroid glands in patients with tertiary hyperparathyroidism were similar in intensity, but more homogenous compared to those in sporadic primary hyperparathyroidism. The pattern of AF exhibited by abnormal parathyroid glands was similar across different spectrums of primary hyperparathyroidism, in accordance with observations in the literature. However, parathyroid glands in tertiary hyperparathyroidism were more homogeneous, despite exhibiting a similar intensity of AF compared to those in sporadic primary hyperparathyroidism. These differences should be kept in mind when using the AF pattern as an adjunct to visual assessment in parathyroid exploration.

Oral health aspects in sporadic and familial primary hyperparathyroidism.

BackgroundPrimary hyperparathyroidism (pHPT) is the third most common endocrinopathy, affecting 1-3% of postmenopausal women, with a total incidence of 21.6 cases per 100,000 people in the adult population. This study aimed to analyze the oral health and related aspects of individuals with pHPT. Material and MethodsA cross-sectional observational study was carried out on 51 patients diagnosed with pHPT associated with multiple endocrine neoplasia type 1 (MEN-1) (G1) or sporadic pHPT (G2). The oral aspects investigated were periodontal parameters, salivary flow, presence of dental caries, number of restored or missing teeth, and presence of tori. The biochemical parameters were collected in periods close to the dental evaluation. ResultsIn G1, 29 individuals (19 females) aged 40.24±13.06 years were included; in G2, 22 individuals (21 females) aged 64.09±10.01 years were included. Grade 2 mobility (p=0.031), mean probing depth (p<0.001), loss of clinical insertion level (p<0.001), gingival bleeding (p=0.009), and presence of palatine tori (p=0.007) were higher in G1. A higher mean of tooth loss (17.90±13.42; p=0.031), teeth with active and/or inactive caries (p<0.001), and visual change in enamel/enamel breakdown (p<0.001) were also observed in G1. Most patients were 50 years old or younger, with a higher prevalence of older individuals in G2 (p<0.001). G1 showed low socioeconomic status and G2 medium-high status (p<0.001). ConclusionsDespite the greater number of younger individuals, higher tooth loss and periodontal changes were observed in G1 patients. Differences in the degree of severity of pHPTor socioeconomic status alone could not explain these findings. Key words:Oral health, Primary hyperparathyroidism, Multiple endocrine neoplasia type 1, osteopenia, osteoporosis.

Surgical results and the location of pathological glands in the treatment of primary sporadic hyperparathyroidism with negative preoperative 99mTc-sestamibi scintigraphy

IntroductionThe primary hyperparathyroidism is a frequent disease whom the surgery is the only curative treatment. The preoperative location imaging techniques could help in the surgical management. Our objective was to analyze surgical results regarding the cure rate, etiology and location of the glands responsible for the primary hyperparathyroidism in patients with negative preoperative 99mTc-sestamibi scintigraphy. MethodsObservational study in patients with the diagnosis of primary sporadic hyperparathyroidism with negative 99mTc-sestamibi scintigraphy, operated consecutively in an endocrine surgery unit for 18 years. The cure rate, the intraoperatory PTH, the etiology and the pathological glands location were analyzed. ResultsIn the study were included 120 patients. After surgery 95% of patients (n = 114) presented cure criteria of hyperparathyroidism. 14.1% presented a multigland disease. 69% of the adenomas presented a typical perithyroid location, founding a percentage of 23.9% of ectopic adenomas in cervical location and a 7.1% in mediastinum. ConclusionsThe absence of uptake in the 99mTc-sestamibi scintigraphy should not condition the surgical indication. The success with experienced surgeons is similar to patients with positive results. The surgical indication must be established by clinical and biochemistry criteria.

Is necessary long-term follow-up of all patients with primary sporadic hyperparathyroidism undergoing parathyroidectomy?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

An update on parathyroid carcinoma

Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.

Resultados quirúrgicos y localización de las glándulas patológicas en el tratamiento del hiperparatiroidismo primario esporádico con gammagrafía 99mTc-sestamibi negativa

IntroductionThe primary hyperparathyroidism is a frequent disease whom the surgery is the only curative treatment. The preoperative location imaging techniques could help in the surgical management. Our objective was to analyze surgical results regarding the cure rate, etiology and location of the glands responsible for the primary hyperparathyroidism in patients with negative preoperative 99mTc-sestamibi scintigraphy. MethodsObservational study in patients with the diagnosis of primary sporadic hyperparathyroidism with negative 99mTc-sestamibi scintigraphy, operated consecutively in an Endocrine Surgery Unit for 18 years. The cure rate, the intraoperatory parathyroid hormone (PTH), the etiology and the pathological glands location were analyzed. ResultsIn the study were included 120 patients. After surgery 95% of patients (n = 114) presented cure criteria of hyperparathyroidism. The 14.1% presented a multigland disease; 69% of the adenomas presented a typical perithyroid location, founding a percentage of 23.9% of ectopic adenomas in cervical location and a 7.1% in mediastinum. ConclusionsThe absence of uptake in the 99mTc-sestamibi scintigraphy should not condition the surgical indication. The success with experienced surgeons is similar to patients with positive results. The surgical indication must be established by clinical and biochemistry criteria.

Mediastinal Videothoracoscopic Parathyroidectomy for Primary Sporadic Hyperparathyroidism—a Case Series Analysis

Primary hyperparathyroidism is one of the commonest endocrine diseases requiring surgical parathyroidectomy for its cure. Surgical excision through conventional open neck approach and sternotomy/thoracotomy for mediastinal parathyroid adenomas not accessible through neck is the treatment of choice. In this context, we evaluated the feasibility and safety of a thoracoscopic technique for mediastinal parathyroidectomy. This is a case series analysis conducted at a tertiary care endocrine surgery department, between May 2016 and August 2019. We employed a novel thoracoscopic route for parathyroidectomy in biochemically diagnosed sporadic primary hyperparathyroidism and radiologically localized mediastinal parathyroid tumours. All the clinical, investigative, operative, pathological and postoperative data were collected from our prospectively filled database. Statistical analysis was performed with SPSS 20.0 version. Under general anaesthesia, access to chest was obtained with 3 ports (three 10 mm triangulated port sites through 3rd, 4th and 5th intercostal spaces) insufflated with 6 mmHg CO2 (carbothorax) for working space. Mediastinal pleura was opened overlying the adenoma, internal mammary vein was clipped and meticulous dissection was performed to devascularise the lesion, without breaching its capsule. Excised specimen was delivered through one of the ports after placing it in custom-made endobag. Out of the 67 hyperparathyroidism cases operated during the study period, 6 (9%) were operated by this technique. Mean operative time was 142.5 SD 14.5 min (105–170). The postoperative course was uneventful with no mortality, persistent hypercalcemia or recurrent laryngeal nerve palsy. Cure and diagnosis were confirmed by > 50% fall in intraoperative serum parathyroid hormone levels and histopathology (all were benign solitary adenomas). Through this study, we propose that our thoracoscopic mediastinal parathyroidectomy is a feasibly safe approach for primary sporadic hyperparathyroidism.

Discussion on: Increasing trend of bilateral neck exploration in primary hyperparathyroidism

DR. CHRISTOPHER R. McHENRY (Cleveland, Ohio): Your results document the excellent outcomes of an experienced high volume endocrine surgeon with a 2.8% rate of persistent disease and a 1.1% rate of recurrent disease for patients with sporadic hyperparathyroidism undergoing initial parathyroidectomy. The authors report an increase in the rate of bilateral neck exploration from 30% in 2010 to 50% in 2017, and an increase in the detection of multiglandular from 22% in 2010 to 41% in 2017.

Impaired geometry, volumetric density, and microstructure of cortical and trabecular bone assessed by HR-pQCT in both sporadic and MEN1-related primary hyperparathyroidism

High-resolution peripheral quantitative CT is a novel imaging technique used to separately assess trabecular and cortical bone status of the radius and tibia in vivo. Using HR-pQCT, we aimed to evaluate bone features of primary hyperparathyroidism patients in a Chinese population and reveal similarities and differences in bone features in multiple endocrine neoplasia type 1-related PHPT and sporadic PHPT patients in the Chinese population. A case-control study was designed. In 58 PHPT patients and 58 sex- and age-matched healthy controls, the distal radius and tibia were scanned using HR-pQCT. Areal bone mineral density (aBMD) was also determined in PHPT patients using dual-energy X-ray absorptiometry (DXA). In comparison with controls, PHPT patients were observed to exhibit reduced volumetric BMD at the cortical and trabecular compartments, thinner cortices, and more widely spaced trabeculae. Significant differences were still observed when comparing data of female and male patients with age-matched controls separately. MHPT patients (n= 11) were found to have lower aBMD Z-scores in the lumbar spine, trochanteric region, and total hip compared with sporadic PHPT patients (n= 47), while no differences were observed in HR-pQCT indices between the two groups. In multiple linear regression models, no significant correlations were identified between PTH and HR-pQCT indices. However, height was found to positively correlate with HR-pQCT-derived trabecular indices at both the radius and tibia. PHPT affects geometry, volumetric density, and microstructure in both the cortical and trabecular bones in both male and female Chinese patients. MHPT patients were observed to have reduced aBMD as determined by DXA in the lumbar spine and hip in comparison with sporadic PHPT patients. However, HR-pQCT indices were not observed to differ.

Intraoperative Autofluorescence Parathyroid Identification in Patients With Multiple Endocrine Neoplasia Type 1

Intrinsic near-infrared (NIR) autofluorescence of the parathyroid gland enables intraoperative gland identification without the need for contrast agent injection. However, whether real-time autofluorescence imaging is useful in patients with multiple endocrine neoplasia type 1 (MEN1) and primary hyperparathyroidism is unknown. To compare quantified intraoperative parathyroid autofluorescence imaging results for patients with MEN1-associated vs those with non-MEN1 sporadic primary hyperparathyroidism. A retrospective analysis of prospectively collected data on a cohort of 71 consecutive patients undergoing surgery for primary hyperparathyroidism by 2 experienced endocrine surgeons between June 1, 2017, and July 31, 2018, was conducted. Intraoperative imaging was performed with a handheld NIR autofluorescence device and images were captured for analysis. Post hoc blinded imaging analysis was conducted with Image J software to quantify representative areas of greatest autofluorescence from the parathyroid, thyroid, and adjacent soft tissue. Primary end points were parathyroid autofluorescence and background thyroid and soft tissue autofluorescence, reported as median values with interquartile ranges. Rates of false-negative (lack of significant parathyroid gland autofluorescence compared with background autofluorescence, defined as parathyroid autofluorescence-background autofluorescence ratio <1.10) and false-positive autofluorescence (aberrant autofluorescence of nonparathyroid tissue confirmed by pathologic testing) were analyzed. Of the 71 consecutive patients with primary hyperparathyroidism who underwent parathyroidectomy during the study period, 6 patients had genetically or clinically diagnosed MEN1 and 65 had sporadic non-MEN1 hyperparathyroidism. Most patients were women (MEN1: 4 [67%]; non-MEN1: 51 [78%]). Median (interquartile range) age was 49.0 (38.0-53.8) years in the MEN1 cohort and 61.0 (54.0-67.0) years in the non-MEN1 cohort. No clinically significant differences in serum preoperative parathyroid hormone level or parathyroid gland size or weight on pathologic examination were observed between the 2 cohorts. The median absolute value of in situ parathyroid autofluorescence was significantly lower in the MEN1 cohort than the non-MEN1 cohort (54.4 vs 74.3; Hedges g = -1.03; 95% CI, -1.89 to -0.17), as was the ratio of parathyroid to background autofluorescence (1.08 vs 1.59; g = -1.59; 95% CI, -2.23 to -0.96). Three patients (50%) with MEN1 had false-negative nonfluorescent parathyroid adenomas vs 6 patients (9%) without MEN1. Nonparathyroid fibroadipose tissue of patients with MEN1 exhibited greater background autofluorescence, leading to high false-positive rates (5 of 6 patients [83%]) vs only 3 of 65 (5%) false-positive autofluorescence nonparathyroid specimens among patients without MEN1. Intraoperative identification of parathyroid glands using their autofluorescence by real-time NIR imaging appears to have utility in patients with primary hyperparathyroidism. In this initial cohort of patients with MEN1, decreased parathyroid autofluorescence and increased background autofluorescence of nonparathyroid tissue may be associated with high rates of false-negative and false-positive fluorescence, potentially limiting the utility of this adjunct in this specific subset of patients.

Prospective Evaluation of the Utility of Intraoperative Parathyroid Monitoring during Intended Bilateral Neck Exploration for Primary Sporadic Hyperparathyroidism

Chotai, Pranit N. MD; Kiernan, Colleen M. MD, MPH; Solorzano, Carmen C. MD, FACS Author Information

Multiple endocrine neoplasia type 1: clinical correlates of MEN1 gene methylation

Multiple endocrine neoplasia type 1 (MEN 1) has marked severity variation between individuals with the same mutation. To investigate any relationship between promoter methylation and clinical features, blood and tissue samples were collected from 16 members of the Tasman 1 MEN 1 kindred carrying a common splice site mutation and 7 patients with sporadic MEN 1. Methylation at 39 CpGs in the MEN1 promoter were assessed in formalin fixed, paraffin embedded parathyroid tissue. Clinical disease severity markers included age at first parathyroid operation, parathyroid hormone level and corrected serum calcium levels. Six patients with sporadic hyperparathyroidism were used for comparison. Minimal methylation was observed in all patients across CpG sites 1-23. In contrast, hypermethylation was observed at CpG sites 24-31 in MEN 1 patients, a pattern not observed in patients with non-MEN 1 parathyroid disease. Mean methylation at sites 24-31 was significantly correlated with age at first parathyroid operation (r= 0.652, p= 0.041). A permutation test, utilising the mean correlation coefficient (r= -0.401) revealed a possible association between relative PHPT severity and methylation score for each significant CpG site (p < 0.103). This novel study reveals evidence supporting a possible association between altered MEN1 promoter methylation and clinical severity of disease.

Applicability of transoral endoscopic parathyroidectomy through vestibular route for primary sporadic hyperparathyroidism: A South Indian experience.

Introduction:Primary hyperparathyroidism is one of the most common endocrine disorders requiring surgical parathyroidectomy for its definitive treatment. Surgical exploration is traditionally performed through conventional open neck approach. A wide range of minimal access and minimally invasive endoscopic techniques (gas less and with gas) have been attempted in the past two decades. In this context, we evaluated the feasibility and safety of an innovative transoral endoscopic parathyroidectomy (EP) technique, which represents a paradigm shift in transluminal endocrine surgery.Materials and Methods:This is a prospective study conducted at a tertiary care Endocrine Surgery Department in South India between May 2016 and August 2017. We employed a novel transoral, lower vestibular route for EP. All the clinical, investigative, operative, pathological and post-operative data were collected from our prospectively filled database. Statistical analysis was performed with SPSS 20.0 version.Operative Technique:Under inhalational general anaesthesia, access to the neck was obtained with 3 ports (central frenulotomy and two lateral port sites), dissected in subplatysmal plane and insufflated with 6 mm Hg CO2 for working space. Rest of surgical steps is similar to conventional open parathyroidectomy.Results:Out of the 38 hyperparathyroidism cases operated during the study, 12 (32%) were operated by this technique. Mean operative time was 112 ± 15 min (95–160). The post-operative course was uneventful with no major morbidity, hypocalcemia or recurrent laryngeal nerve palsy. Cure and diagnosis were confirmed by >50% fall in intraoperative parathyroid hormone levels and histopathology (all were benign solitary adenomas).Conclusions:Through this study, we opine that this novel transoral vestibular route parathyroidectomy is a feasibly applicable approach for primary sporadic hyperparathyroidism, especially with solitary benign adenomas.

MEN1 mutations and potentially MEN1-targeting miRNAs are responsible for menin deficiency in sporadic and MEN1 syndrome-associated primary hyperparathyroidism.

Inherited, germline mutations of menin-coding MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), while somatic MEN1 mutations are the sole main driver mutations in sporadic primary hyperparathyroidism (PHPT), suggesting that menin deficiency has a central role in the pathogenesis of PHPT. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to investigate both the role of MEN1 mutations and potentially MEN1-targeting miRNAs as the underlying cause of menin deficiency in MEN1-associated and sporadic PHPT tissues. Fifty six PHPT tissues, including 16 MEN1-associated tissues, were evaluated. Diagnosis of MEN1 syndrome was based on identification of germline MEN1 mutations. In silico target prediction was used to identify miRNAs potentially targeting MEN1. Menin expression was determined by immunohistochemistry while expression of miRNAs was analyzed by quantitative real-time PCR. Sporadic PHPT tissues were subjected to somatic MEN1 mutation analysis as well. Lack of nuclear menin was identified in all MEN1-associated and in 28% of sporadic PHPT tissues. Somatic MEN1 mutations were found in 25% of sporadic PHPTs. The sensitivity and specificity of menin immunohistochemistry to detect a MEN1 mutation were 86 and 87%, respectively. Expression levels of hsa-miR-24 and hsa-miR-28 were higher in sporadic compared to MEN1-associated PHPT tissues; however, no difference in miRNA levels occurred between menin-positive and menin-negative PHPT tissues. Menin deficiency is the consequence of a MEN1 mutation in most menin-negative PHPT tissues. Elevated expression of hsa-miR-24 and hsa-miR-28 mark the first epigenetic changes observed between sporadic and MEN1-associated PHPT.