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Endocrinology and Metabolism (Seoul,... Jun 2024Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder.... (Review)
Review
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.
Topics: Humans; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Parathyroid Hormone; Renal Insufficiency, Chronic; Hyperparathyroidism, Secondary; Animals
PubMed: 38752265
DOI: 10.3803/EnM.2024.1978 -
Medicine Apr 2024To investigate the value of preoperative ultrasound combined with 99mTc-MIBI imaging for the diagnosis of ectopic intrathyroid parathyroid gland (ETPG) in patients with...
The value of ultrasound in combination with 99mTc-MIBI imaging department of ultrasound medicine, for the diagnosis of ectopic parathyroid glands in the thyroid gland in patients with secondary hyperparathyroidism.
To investigate the value of preoperative ultrasound combined with 99mTc-MIBI imaging for the diagnosis of ectopic intrathyroid parathyroid gland (ETPG) in patients with secondary hyperparathyroidism (SHPT). One hundred and eleven patients with SHPT who underwent total parathyroidectomy plus forearm transplantation from January 2015 to January 2022 in the Third Hospital of Hebei Medical University were selected. All patients underwent routine preoperative ultrasonography and 99mTc-MIBI imaging, and with pathological diagnosis as the gold standard, the clinical data of ETPG patients were selected, including clinical manifestations, laboratory tests, preoperative ultrasonography and 99mTc-MIBI imaging for localization and diagnosis, intraoperative exploration and postoperative pathology, and postoperative follow-up. To analyze the ultrasound manifestations of preoperative parathyroid hyperplasia and the results of 99mTc-MIBI imaging in patients with ETPG. Among 111 patients with SHPT, there were 5 patients with ETPG, 1 male and 4 females with a mean age of (45.00 ± 5.05) years, and 6 ectopic parathyroid glands were located in the thyroid gland. The incidence of ETPG was 4.5% (5/111), 4 were detected by ultrasound, 2 were not detected with a diagnostic accuracy of 66.7% (4/6), 3 were positive for 99mTc-MIBI imaging, 3 were negative with a diagnostic accuracy of 50.0% (3/6). Among them, one was not detected by ultrasound, but was positive for 99mTc-MIBI imaging, 2 with negative 99mTc-MIBI imaging, but all were detected by ultrasound, and one with negative 99mTc-MIBI imaging was detected by ultrasound but misdiagnosed as a thyroid nodule. A total of 5 ETPGs were detected by ultrasound combined with 99mTc-MIBI imaging, with a diagnostic accuracy of 83.3% (5/6). Patients' postoperative serum calcium and serum parathyroid hormone (PTH) levels were normalized or significantly decreased from preoperative levels. Ultrasound combined with 99mTc-MIBI imaging can achieve higher accuracy than either examination alone in the preoperative localization and diagnosis of ETPG in SHPT patients.
Topics: Humans; Male; Female; Hyperparathyroidism, Secondary; Technetium Tc 99m Sestamibi; Middle Aged; Parathyroid Glands; Ultrasonography; Adult; Choristoma; Thyroid Gland; Radiopharmaceuticals; Radionuclide Imaging; Parathyroidectomy
PubMed: 38669430
DOI: 10.1097/MD.0000000000037866 -
BMC Endocrine Disorders Apr 2024There has been a notable shift towards the diagnosis of less severe and asymptomatic primary hyperparathyroidism (PHPT) in developed countries. However, there is a...
BACKGROUND
There has been a notable shift towards the diagnosis of less severe and asymptomatic primary hyperparathyroidism (PHPT) in developed countries. However, there is a paucity of recent data from sub-Saharan Africa (SSA), and also, no reported data from SSA on the utility of intra-operative parathyroid hormone (IO-PTH) monitoring. In an earlier study from Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa (2003-2009), majority of patients (92.9%) had symptomatic disease. The aim of this study was to evaluate the clinical profile and management outcomes of patients presenting with PHPT at IALCH.
METHODS
A retrospective chart review of patients with PHPT attending the Endocrinology clinic at IALCH between July 2009 and December 2021. Clinical presentation, laboratory results, radiologic findings, surgical notes and histology were recorded.
RESULTS
Analysis included 110 patients (87% female) with PHPT. Median age at presentation was 57 (44; 67.5) years. Symptomatic disease was present in 62.7% (n:69); 20.9% (n:23) had a history of nephrolithiasis and 7.3% (n:8) presented with previous fragility fractures. Mean serum calcium was 2.87 ± 0.34 mmol/l; median serum-PTH was 23.3 (15.59; 45.38) pmol/l, alkaline phosphatase 117.5 (89; 145.5) U/l and 25-hydroxyvitamin-D 42.9 (33.26; 62.92) nmol/l. Sestamibi scan (n:106 patients) identified an adenoma in 83.02%. Parathyroidectomy was performed on 84 patients with a cure rate of 95.2%. Reasons for conservative management (n:26) included: no current surgical indication (n:7), refusal (n:5) or deferral of surgery (n:5), loss to follow-up (n:5) and assessed as high anaesthetic risk (n:4). IO-PTH measurements performed on 28 patients indicated surgical success in 100%, based on Miami criteria. Histology confirmed adenoma in 88.1%, hyperplasia in 7.1% and carcinoma in 4.8%. Post-operative hypocalcaemia developed in 30 patients (35.7%), of whom, 14 developed hungry bone syndrome (HBS). In multivariate analysis, significant risk factors associated with HBS included male sex (OR 7.01; 95% CI 1.28, 38.39; p 0.025) and elevated pre-operative PTH (OR 1.01; 95% CI 1.00, 1.02; p 0.008).
CONCLUSIONS
The proportion of asymptomatic PHPT has increased at this centre over the past decade but symptomatic disease remains the dominant presentation. Parathyroidectomy is curative in the majority of patients. IO-PTH monitoring is valuable in ensuring successful surgery.
Topics: Humans; Hyperparathyroidism, Primary; Female; Male; Middle Aged; Retrospective Studies; South Africa; Adult; Aged; Parathyroidectomy; Parathyroid Neoplasms; Parathyroid Hormone; Follow-Up Studies; Disease Management; Treatment Outcome; Prognosis; Calcium
PubMed: 38664758
DOI: 10.1186/s12902-024-01583-8 -
Cureus Mar 2024Primary hyperparathyroidism (PHPT) usually presents with symptoms of hypercalcemia which is due to excessive secretion of parathyroid hormone (PTH). Surgical removal of...
Primary hyperparathyroidism (PHPT) usually presents with symptoms of hypercalcemia which is due to excessive secretion of parathyroid hormone (PTH). Surgical removal of the secreting tumor either adenoma or hyperplasia remains the mainstay of treatment. Around 2% to 25% of the lesions are located in the mediastinum. We reviewed our institution's surgical treatment and approach to mediastinal parathyroid adenoma (MPA). We retrospectively reviewed the demography, comorbidities, clinical presentation, surgical approach, and outcome for patients in our institution who underwent surgery for MPA from September 2019 until August 2023. All patients with MPA who underwent surgery were included in the review. The surgical approaches used were both video-assisted thoracoscopic surgery (VATS) and median sternotomy. There were three patients with PHPT due to MPA who underwent surgery. Out of the three patients, two were female. The mean age was 48.6 years old, ranging from 16 to 66 years old. All of them presented with PHPT with a raised mean serum calcium level of 3.52 mmol/L (range: 2.84-4.38 mmol/L) and a mean PTH or intact PTH (iPTH) level of 274.6 pmol/L (range: 8.87-695 pmol/L). Ultrasound of the neck was performed for all the patients before further investigations were done to look for the ectopic parathyroid gland. Computed tomography (CT) of the thorax showed mediastinal parathyroid mass in all the patients with an average size of 2.4 x 2.1 x 2.3cm (range: 1.3-3.8cm), which showed uptake in 99mTc-hexakis-2-methoxyisobuthylisonitrile (Tc99m-MIBI) scintigraphy. VATS was performed for two cases and an upper partial sternotomy was performed for one patient. Postoperatively, iPTH and serum calcium levels were reduced significantly for all patients. There were no post-operative complications in our study. Comprehensive diagnostic imaging and surgical planning are important for the localization of MPA. In our review, all cases were promptly diagnosed and underwent surgery without complication.
PubMed: 38650780
DOI: 10.7759/cureus.56792 -
Cureus Mar 2024Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by mutations in the tumor suppressor gene and is characterized by parathyroid,...
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by mutations in the tumor suppressor gene and is characterized by parathyroid, pancreatic islet, and anterior pituitary tumors. Primary hyperparathyroidism is the most characteristic finding in MEN1, and intraoperative identification and accurate removal of the diseased parathyroid glands are vital since incomplete excision results in recurrence. This case report describes a 59-year-old woman who had pancreatic islet cell tumors and pituitary tumors and underwent selective transsphenoidal adenomectomy. Based on her medical history and examination, the diagnosis of primary hyperparathyroidism in MEN1 was made, and she underwent total parathyroidectomy with autotransplantation with SPY-Elite®️ Fluorescence Imaging (Stryker Corp., Kalamazoo, MI). Intraoperative identification of the parathyroid glands using autofluorescence with real-time intrinsic near-infrared (NIR) imaging made it easier to detect all of the parathyroid hyperplasia. After the surgery, she had hypoparathyroidism and continued with her oral calcium and vitamin D supplementation to maintain normal calcium levels during follow-up. Herein, we would like to advocate that the use of parathyroid gland autofluorescence with real-time intrinsic NIR imaging may be useful for identifying parathyroid tumors in patients with primary hyperparathyroidism in MEN1.
PubMed: 38586714
DOI: 10.7759/cureus.55706 -
Heliyon Mar 2024Brown tumors (osteitis fibrosa cystica) are rare pathognomonic signs that occur in patients with primary hyperparathyroidism (PHPT). Brown tumors can exist in multiple...
Brown tumors (osteitis fibrosa cystica) are rare pathognomonic signs that occur in patients with primary hyperparathyroidism (PHPT). Brown tumors can exist in multiple bones and can easily be misdiagnosed as a metastatic tumor or multiple myeloma. It is also localized in the forearm, humerus, and leg. The symptoms of hypercalcemia, pathologic fracture, and bodyweight loss may increase the diagnostic difficulty of brown tumors because multiple myeloma and bone metastasis also show the same symptoms. We studied a 68-year-old woman who had experienced unusual bodyweight loss in the past 6 months (56kg-40kg) and bone pain. She went to the hospital after a fall with a complaint of bone pain. An X-ray revealed a left bubbly-like cystic change and multiple fractures at the left ulna midshaft. Upon investigation, the level of intact parathyroid hormone was ascertained to be 1800 (normal: 10-60) pg/ml. Microscopically, the tumor demonstrated a benign bone lesion and was compatible with osteitis fibrosa cystica due to PHPT. The parathyroid scan (Tc-99 m sestamibi) indicated right parathyroid hyperplasia, which was later confirmed by a parathyroidectomy. She was diagnosed with osteitis fibrosa cystica associated with PHPT due to a parathyroid adenoma. PHPT can be presented with multiple fractures, bone pain, and bodyweight loss. Therefore, if a patient presents these symptoms, PHPT should be considered.
PubMed: 38524572
DOI: 10.1016/j.heliyon.2024.e28333 -
EBioMedicine Apr 2024To date, because of the difficulty in obtaining normal parathyroid gland samples in human or in animal models, our understanding of this last-discovered organ remains...
BACKGROUND
To date, because of the difficulty in obtaining normal parathyroid gland samples in human or in animal models, our understanding of this last-discovered organ remains limited.
METHODS
In the present study, we performed a single-cell transcriptome analysis of six normal parathyroid and eight parathyroid adenoma samples using 10 × Genomics platform.
FINDINGS
We have provided a detailed expression atlas of parathyroid endocrine cells. Interestingly, we found an exceptional high expression levels of CD4 and CD226 in parathyroid endocrine cells, which were even higher than those in lymphocytes. This unusual expression of lymphocyte markers in parathyroid endocrine cells was associated with the depletion of CD4 T cells in normal parathyroid glands. Moreover, CD4 and CD226 expression in endocrine cells was significantly decreased in parathyroid adenomas, which was associated with a significant increase in Treg counts. Finally, along the developmental trajectory, we discovered the loss of POMC, ART5, and CES1 expression as the earliest signature of parathyroid hyperplasia.
INTERPRETATION
We propose that the loss of CD4 and CD226 expression in parathyroid endocrine cells, coupled with an elevated number of Treg cells, could be linked to the pathogenesis of parathyroid adenoma. Our data also offer valuable information for understanding the noncanonical function of CD4 molecule.
FUNDING
This work was supported by the National Key R&D Program of China (2022YFA0806100), National Natural Science Foundation of China (82130025, 82270922, 31970636, 32211530422), Shandong Provincial Natural Science Foundation of China (ZR2020ZD14), Innovation Team of Jinan (2021GXRC048) and the Outstanding University Driven by Talents Program and Academic Promotion Program of Shandong First Medical University (2019LJ007).
Topics: Humans; Parathyroid Glands; Parathyroid Neoplasms; Down-Regulation; Carcinogenesis; Cell Transformation, Neoplastic; Hyperplasia; Lymphocytes
PubMed: 38471398
DOI: 10.1016/j.ebiom.2024.105053 -
Cureus Feb 2024Cure rates following parathyroidectomy for primary hyperparathyroidism are excellent, with well-documented low short-term recurrence rates of hypercalcaemia. Rates of...
BACKGROUND
Cure rates following parathyroidectomy for primary hyperparathyroidism are excellent, with well-documented low short-term recurrence rates of hypercalcaemia. Rates of long-term recurrence have been investigated to a lesser extent, but recent studies have reported higher than anticipated rates. This study sought to evaluate recurrence rates at more than four years post seemingly corrective surgery and depending on the findings, propose whether recommendations of annual calcium monitoring post-parathyroidectomy are appropriate based on the limited data available at the time of formulating guidelines.
METHODS
Fifty-two sequential parathyroidectomies for primary hyperparathyroidism from 2014-2016 from a single unit were retrospectively followed up with serum calcium levels. A hospital computer system was used to collect data on pre-operative, immediate post-operative and most recent follow-up calcium levels. Patients were excluded if there was no minimum of 48 months between the operation date and most recent calcium. Recurrence was defined as hypercalcaemia more than six months after eucalcaemia post-parathyroidectomy.
RESULTS
Of the 52 cases analysed, two were lost to long-term follow-up, two patients died during the follow-up period while 10 did not meet the inclusion criteria of at least 48 months follow-up. This resulted in a cohort of 38 patients (mean age 66.4 years, 78.9% female). The median follow-up of 73.17 months (range 48.77-95.47 months) demonstrated a hypercalcaemia recurrence of 5.26% (2/38 patients). These cases were due to misdiagnosed parathyroid hyperplasia as opposed to suspected adenoma. Therefore, the long-term cure rate was 94.74% (36/38 patients).
CONCLUSION
These findings support the high cure rates and low recurrence rates of the numerous short-term studies already performed despite a longer follow-up period. This is in contrast to recent series which have documented a higher recurrence in the long-term. This study would, therefore, suggests recommendations of annual calcium monitoring are excessive and that less frequent calcium monitoring is necessary in the first few years post-operation. However, the 5.26% recurrence rate in this study is not insignificant and follow-up is still paramount. Therefore, following the initial post-operative assessment, the authors propose a follow-up at the five-year mark and an annual continuation from this point forward due to the evidenced delayed recurrence of hypercalcaemia.
PubMed: 38449925
DOI: 10.7759/cureus.53591 -
Scandinavian Journal of Surgery : SJS :... Mar 2024Studies on the outcomes of parathyroid surgery are scarce. The aim was to report the outcomes and to study the association between pre- and peri-operative information...
BACKGROUND AND OBJECTIVE
Studies on the outcomes of parathyroid surgery are scarce. The aim was to report the outcomes and to study the association between pre- and peri-operative information with the outcomes of patients operated for primary hyperparathyroidism.
METHODS
This was a retrospective, descriptive study with unselected patients treated surgically for primary hyperparathyroidism from a catchment population of 704,500 in Finland. Data were acquired from the electronic hospital registers based on parathyroid surgery procedure codes between 1 January 2017 and 31 December 2018. Preoperative data, surgical data, preoperative and postoperative laboratory values, histopathological findings, and postoperative clinical data were recorded.
RESULTS
During the 2-year study period, 149 patients with primary hyperparathyroidism were treated surgically with a 97% remission rate. Surgical complications included postoperative bleeding in two patients (1%) and vocal cord paralysis in one patient (0.6%). No postoperative infections were reported. Three patients (2%) developed postoperative hypoparathyroidism necessitating the use of alfacalcidol more than 1 month after surgery. Ionized calcium measured 0-1 days after surgery was not statistically significantly associated with remission or postoperative hypoparathyroidism. Serum parathyroid hormone (PTH) assessed 0-1 days postoperatively was associated with persistent disease, but not with postoperative hypoparathyroidism. The histopathological diagnosis was adenoma or hyperplasia in 112 patients (75%), atypical adenoma in 28 patients (19%), and carcinoma in five patients (3%). Patients with parathyroid carcinoma had higher preoperative ionized calcium and PTH values than those with adenoma or hyperplasia.
CONCLUSIONS
Most patients who were operated due to primary hyperparathyroidism achieved normocalcemia after surgery, and the frequency of complications was low. Ionized calcium taken 0-1 days after surgery was not associated with remission of hyperparathyroidism or postoperative hypoparathyroidism. High postoperative serum PTH predicted persistent disease.
PubMed: 38433618
DOI: 10.1177/14574969241228409 -
Problemy Endokrinologii Feb 2024Hyperparathyroidism is a syndrome characterized by an excessive secretion of parathyroid hormone. Etiologically, hyperparathyroidism is subdivided into primary... (Review)
Review
Hyperparathyroidism is a syndrome characterized by an excessive secretion of parathyroid hormone. Etiologically, hyperparathyroidism is subdivided into primary hyperparathyroidism, which develops as a result of parathyroid adenoma, carcinoma or hyperplasia, and secondary hyperparathyroidism, which happens as a compensatory response to a hypocalcemia caused by condition outside the parathyroid glands. Turner syndrome may also be accompanied by mineral metabolism disorders of various etiology. An association of hyperparathyroidism and Turner syndrome is interesting because of multifactorial impact on bone mineral density, but only few cases of such coexistence have been previously described in the literature. This article describes two patients with Turner syndrome and hyperparathyroidism of different etiology. Hyperparathyroidism, normocalcemia, vitamin D deficiency, osteoporosis, parathyroid tumors were found in both cases. In one case a number of assays was performed to confirm the patient's normocalcemic primary hyperparathyroidism, and surgery was performed to achieve remission. In the second case, treatment of vitamin D deficiency resulted in normalization of serum concentration of parathormone, after which the patient was prescribed antiresorptive therapy. The pathogenetic association between Turner syndrome and hyperparathyroidism requires further investigation. Comprehensive approach to the diagnosis and treatment of mineral metabolism disorders are essential for patients with coexistence of these two diseases.
Topics: Humans; Turner Syndrome; Hyperparathyroidism, Primary; Hyperparathyroidism, Secondary; Parathyroid Hormone; Parathyroid Neoplasms; Triamcinolone; Minerals; Vitamin D Deficiency
PubMed: 38433542
DOI: 10.14341/probl13330