-
Cureus Oct 2023Background Parathyroid hormone (PTH) and Dickkopf-related protein 1 (DKK-1) have been mentioned together at the intersection of autoimmune rheumatologic diseases (ARDs)...
Background Parathyroid hormone (PTH) and Dickkopf-related protein 1 (DKK-1) have been mentioned together at the intersection of autoimmune rheumatologic diseases (ARDs) and osteoimmunology. However, few studies have evaluated the association between primary hyperparathyroidism (PHPT) and ARDs. Methodology This retrospective study included 225 PHPT patients and 386 patients with thyroid nodules as a control group. The electronic hospital records of all patients were screened going back nine years for the presence of ARDs. Patients who were diagnosed at least three months ago, had complete serologic tests, and were continuing with rheumatologic follow-up were included. Results The prevalence of ARDs in the PHPT group was 9.77% (22/225), while the prevalence of ARDs in the CG was 1.04% (4/386, p < 0.001). The prevalence of rheumatoid arthritis in the PHPT group was 4.4% (10/225), ankylosing spondylitis 3.1% (7/225), systemic lupus erythematosus 0.88% (2/225), Behçet's disease 0.88% (2/225), and mixed connective tissue disease 0.44% (1/225). Of the 22 patients with ARDs, 21 (95.45%) were diagnosed before they were diagnosed with PHPT, and the median time from diagnosis with ARD to the onset of PHPT was 36 months (interquartile range = 61.5). Logistic regression analysis showed a positive correlation between the duration of PHPT and ARDs (odds ratio (OR) = 1.06; 95% confidence interval (CI) = 1.02-1.09, p < 0.001) and a negative correlation between ARDs and calcium levels (OR = 0.26; 95% CI = 0.09-0.79, p = 0.018). Conclusions The prevalence of ARDs increased in PHPT patients and PHPT accompanying ARDs developed after rheumatologic disease. ARDs with PHPT are cases with a prolonged duration of PHPT and mildly elevated calcium, probably preceded by parathyroid hyperplasia. Therefore, the factors that cause ARDs may trigger a process that leads to mild PHPT.
PubMed: 37841984
DOI: 10.7759/cureus.46906 -
Clinical Nephrology. Case Studies 2023We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of...
PURPOSE
We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of this rare yet highly disabling condition.
OBSERVATIONS
We report two cases of ophthalmic calciphylaxis presenting as (1) anterior ischemic optic neuropathy (AION) and cilioretinal artery occlusion in a 76-year-old woman with pre-dialysis kidney failure, and (2) AION with contralateral central retinal artery occlusion (CRAO) in a 44-year-old man on hemodialysis.
CONCLUSION AND IMPORTANCE
These cases highlight the need for judicious clinical suspicion of calciphylaxis in patients with kidney failure, presenting with microvascular ischemic ophthalmic pathology such as AION or CRAO. Confirmation with temporal artery biopsy is essential to direct targeted individualized multi-disciplinary treatment of calciphylaxis and avoid unnecessary steroid exposure in cases masquerading as giant cell arteritis (GCA).
PubMed: 38169875
DOI: 10.5414/CNCS111088 -
Frontiers in Endocrinology 2023Until recently no major epidemiological research of primary hyperparathyroidism (PHPT) has been conducted in the Russian Federation, this led to the creation of the...
INTRODUCTION
Until recently no major epidemiological research of primary hyperparathyroidism (PHPT) has been conducted in the Russian Federation, this led to the creation of the Russian online registry. The objective of this study is to estimate the clinical and biochemical profile, classical and non-classical complications, surgical intervention and medical therapy of the patients with different forms of PHPT in the Russian Federation.
MATERIALS AND METHODS
The cross-sectional, observational, continuous study was conducted at the Endocrinology Research Centre (Moscow). The present study explored retrospective data from 6003 patients submitted to the Registry between 12.12.2016 and 25.10.2022 from 81 regions of the Russian Federation (http://pgpt.clin-reg.ru/).
RESULTS
The median age was 59 [60; 66] years with a female:male ratio of 11.7:1. Symptomatic PHPT was observed in 74.3% while asymptomatic form - only in 25.7% of cases. Bone pathology was the predominant clinical manifestation in 62.5% of cases (n=2293), mostly in combination with visceral complications 45.7% (n=1676). The majority of patients (63.3%) had combined visceral disorders including kidney damage in 51.8% and gastroduodenal erosions/ulcers in 32.3% of patients. Symptomatic patients were older (60 [53; 67] vs. 54 [45; 62] years, p<0.001) and had more severe biochemical alterations of calcium-phosphorus metabolism. Cardiovascular disease (СVD) was recorded in 48% of patients, among them the most frequent was arterial hypertension (up to 93.9%). A genetic test was conducted in 183 cases (suspicious for hereditary PHPT) revealing the mutations in , , genes in 107, 6 and 2 cases, respectively. Surgery was performed in 53.4% of patients with remission achievement in 87%, the relapse/persistence were recorded in 13% of cases. Histological examination revealed carcinoma in 4%, atypical adenoma in 2%, adenoma in 84% and hyperplasia in 11% of cases. Drug therapy was prescribed in 54.0% of cases, most often cholecalciferol.
CONCLUSION
The detection rate of PHPT has increased in the Russian Federation in recent years. This increase is associated with the start of online registration. However, the majority of patients remain symptomatic with significant alterations of phosphorus-calcium metabolism that indicates delayed diagnosis and requires further modifications of medical care.
Topics: Humans; Male; Female; Middle Aged; Calcium; Retrospective Studies; Hyperparathyroidism, Primary; Cross-Sectional Studies; Registries; Calcium, Dietary; Adenoma; Phosphorus
PubMed: 37465121
DOI: 10.3389/fendo.2023.1203437 -
Journal of Medical Case Reports Sep 2023There is some evidence supporting the idea that double parathyroid adenomas represent a different entity from multiglandular hyperplasia; however, the distinction among...
BACKGROUND
There is some evidence supporting the idea that double parathyroid adenomas represent a different entity from multiglandular hyperplasia; however, the distinction among them is not straightforward.
CASE PRESENTATION
We described a case of primary hyperparathyroidism (PHPT) with pronounced clinical manifestations, caused by a bilateral giant parathyroid adenoma. A 34-year-old Hispanic/Latino male was diagnosed with PHPT caused by two giant parathyroid adenomas. The preoperative tests were neck ultrasound and computed tomography scan (CT-scan), showing two masses in the territory of parathyroid glands, bilaterally distributed (right was 31 × 18 × 19 mm and the left was 38 × 15 × 14 mm); sestamibi scan was not available. Parathyroid hormone (PTH) was highly elevated. Multiple complications of PHPT were present, such as bone lytic lesions, renal and pancreatic calcifications, and cardiovascular disease, the latter of which is an overlooked complication of PHPT. Multiple endocrine neoplasia 1 and 2 (MEN 1/2) were ruled out by the absence of clinical, biochemical, and radiological findings in other endocrine glands. The patient underwent subtotal parathyroidectomy with an intraoperative histopathological study; both intraoperative and definitive histopathology results were consistent with parathyroid adenomas; afterward, adequate suppression of PTH was assured, and later on, the patient presented hungry bone syndrome (HBS).
CONCLUSIONS
The diagnosis of double parathyroid adenomas is difficult. Regarding the similarities between multiglandular hyperplasia and parathyroid adenomas, this case report contributes to the further distinction between these two clinical entities. This case report also represents, in particular, the challenge of difficult diagnosis in places with limited resources, such as developing countries.
Topics: Humans; Adult; Parathyroid Neoplasms; Hyperplasia; Hypocalcemia; Bone Diseases; Parathyroid Hormone
PubMed: 37653552
DOI: 10.1186/s13256-023-04102-w -
Medicine Jul 2023Hyperparathyroidism is caused by parathyroid tumors combined with gastroenteropancreatic tumors and pituitary tumors, which is common in patients with multiple endocrine... (Review)
Review
RATIONALE
Hyperparathyroidism is caused by parathyroid tumors combined with gastroenteropancreatic tumors and pituitary tumors, which is common in patients with multiple endocrine neoplasia 1 syndrome (MEN-1). As its main pathogenic factor involves genetic mutations, it can cause a variety of different clinical symptoms. However, cases with negative genetic testing results and multiple nonfunctional malignant neuroendocrine tumors (NETs) with metastasis are relatively rare.
PATIENT CONCERNS
A 33-year-old man was admitted to the hospital for hyperparathyroidism. Imaging examination revealed multiple nodules in the parathyroid gland, pancreas, thymus, and adrenal gland, and multiple metastases to the lung, liver, thoracolumbar, as well as mediastinal lymph nodes.
DIAGNOSES
After multidisciplinary consultation, this patient was diagnosed with MEN-1 syndrome with various original tumors and multiple systemic metastases.
INTERVENTIONS
The patient underwent parathyroid tumor resection and metastasis biopsy.
OUTCOMES
The patient received denosumab and sorafenib treatment.
LESSONS
As an autosomal dominant hereditary disease, MEN-1 patients present with parathyroid hyperplasia, pancreatic and intestinal tumors, pituitary tumors, and so on, which are caused by genetic mutations. These patients would have hyperparathyroidism, hypoglycemia, gastric ulcer, and gastrointestinal diseases. However, some patients with MEN-1 syndrome cannot be diagnosed by genetic testing and simultaneously present with multiple nonfunctional NETs with systemic metastasis. This increases the difficulty of diagnosis and the subsequent treatment.
Topics: Male; Humans; Adult; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pituitary Neoplasms; Multiple Endocrine Neoplasia; Hyperparathyroidism; Parathyroid Neoplasms; Pancreatic Neoplasms
PubMed: 37478229
DOI: 10.1097/MD.0000000000034350 -
JCEM Case Reports Jan 2024Parathyroid adenoma (PA) and parathyroid hyperplasia (PH) are common causes of primary hyperparathyroidism (PHPT), for which the only definitive treatment is surgery....
Parathyroid adenoma (PA) and parathyroid hyperplasia (PH) are common causes of primary hyperparathyroidism (PHPT), for which the only definitive treatment is surgery. Abnormalities in the parathyroid glands can be identified with various imaging modalities including ultrasound (US), sestamibi scan (MIBI), 4-dimensional computed tomography (4D-CT), and positron emission tomography/computed tomography (PET/CT). While it is not uncommon for parathyroid pathology to be undetected on imaging, this is more typical of low-volume hyperplasia and smaller-sized adenomas. We present the case of a 65-year-old man with PHPT who initially had a solitary parathyroid mass detected by US, but who was ultimately discovered to have massive PH with hyperplastic glands not visualized on US or MIBI. This atypical presentation may help guide providers in decisions on ordering and interpreting various imaging modalities for patients with PHPT. In this case, 4D-CT was the only modality in which large hyperplastic glands were identified, suggesting superior sensitivity. This case also highlights the importance of intraoperative parathyroid hormone testing to aid in diagnostic prediction.
PubMed: 38188905
DOI: 10.1210/jcemcr/luad173 -
Frontiers in Endocrinology 2023A germline mutation can be identified in up to 10% of patients with primary hyperparathyroidism (PHPT). In 2017, a high frequency of the [(NM_ 004752.4) c.1181A> C;...
CONTEXT
A germline mutation can be identified in up to 10% of patients with primary hyperparathyroidism (PHPT). In 2017, a high frequency of the [(NM_ 004752.4) c.1181A> C; p.Tyr394Ser; rs142287570] variant was reported in PHPT Ashkenazi Jews (AJ).
OBJECTIVE
To evaluate the presence of the p.Tyr394Ser variant in Israeli patients addressed for genetic evaluation to characterize their phenotype and clinical management.
METHOD
Patients with PHPT who underwent addressed for genetic screening for suspected familial hypocalciuric hypercalcemia (FHH), a family history of isolated hyperparathyroidism (FIHP), or failed parathyroidectomy with persistent PHPT were recruited. Those with normal initial selected gene sequencing or hyperparathyroid genetic panel completed the p.Tyr394Ser variant sequencing. The prevalence of this variant was evaluated using our local genomic database.
RESULTS
A total of 42 single individuals from unrelated kindreds were evaluated. A disease-causing mutation was found in 11 (26.1%) patients: 10 were diagnosed with FHH (eight and two mutations), and one patient had a CKN2B mutation. In 28 of the remaining patients, the p.Tyr394Ser variant was positive in three (10.7%), and all were AJ. Within AJ (15/28, 53.5%), the rate of the p.Tyr394Ser variant was 3/15 (20%), and of those, two had a history of familial isolated hyperparathyroidism. Multi-glandular parathyroid adenoma/hyperplasia was also observed in two of these patients. No clinical or laboratory findings could discriminate patients with the p.Tyr394Ser variant from those with FHH. Cinacalcet normalized the calcium levels in one patient. The prevalence of the p.Tyr394Ser variant in 15,407 tests in our local genomic database was 0.98%.
CONCLUSION
In contrast to previous observations, the p.Tyr394Ser variant-associated phenotype may be mild in AJ with FIHP, sometimes mimicking FHH. Because surgery may be curative, surgeons should be aware of the possibility of multiple gland diseases in these patients. The clinical spectrum and clinical utility of screening for this variant warrant further investigation.
Topics: Humans; Hyperparathyroidism, Primary; Israel; Parathyroid Hormone; Mutation; Nuclear Proteins; Transcription Factors
PubMed: 38130397
DOI: 10.3389/fendo.2023.1254156 -
Virchows Archiv : An International... May 2024Primary hyperparathyroidism with parathyroid tumors is a typical manifestation of Multiple Endocrine Neoplasia Type 1 (MEN1) and is historically termed "primary...
Primary hyperparathyroidism with parathyroid tumors is a typical manifestation of Multiple Endocrine Neoplasia Type 1 (MEN1) and is historically termed "primary hyperplasia". Whether these tumors represent a multi-glandular clonal disease or hyperplasia has not been robustly proven so far. Loss of Menin protein expression is associated with inactivation of both alleles and a good surrogate for a MEN1 gene mutation. The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene is mutated in MEN4 and encodes for protein p27 whose expression is poorly studied in the syndromic MEN1 setting.Here, we analyzed histomorphology and protein expression of Menin and p27 in parathyroid adenomas of 25 patients of two independent, well-characterized MEN1 cohorts. The pattern of loss of heterozygosity (LOH) was assessed by fluorescence in situ hybridization (FISH) in one MEN1-associated parathyroid adenoma. Further, next-generation sequencing (NGS) was performed on eleven nodules of four MEN1 patients.Morphologically, the majority of MEN1 adenomas consisted of multiple distinct nodules, in which Menin expression was mostly lost and p27 protein expression reduced. FISH analysis revealed that most nodules exhibited MEN1 loss, with or without the loss of centromere 11. NGS demonstrated both subclonal evolution and the existence of clonally unrelated tumors.Syndromic MEN1 parathyroid adenomas therefore consist of multiple clones with subclones, which supports the current concept of the novel WHO classification of parathyroid tumors (2022). p27 expression was lost in a large fraction of MEN1 parathyroids and must therefore be used with caution in suggesting MEN4.
Topics: Humans; Parathyroid Neoplasms; Multiple Endocrine Neoplasia Type 1; Male; Proto-Oncogene Proteins; Cyclin-Dependent Kinase Inhibitor p27; Middle Aged; Female; Adult; Adenoma; Aged; Loss of Heterozygosity; Hyperparathyroidism, Primary; Biomarkers, Tumor; Young Adult; High-Throughput Nucleotide Sequencing; In Situ Hybridization, Fluorescence
PubMed: 38244045
DOI: 10.1007/s00428-023-03730-3 -
The Lancet Regional Health. Europe Dec 2023Neck ultrasound (US) is a widely used and accessible operator-dependent technique that helps characterize thyroid nodules and pathologic parathyroid glands (PPGs)....
BACKGROUND
Neck ultrasound (US) is a widely used and accessible operator-dependent technique that helps characterize thyroid nodules and pathologic parathyroid glands (PPGs). However, thyroid nodules may sometimes be confused with PPGs. PARATH-US study aims at identifying US characteristics to differentiate PPGs from thyroid nodules, as there is no study, at present, which directly compares the US features of these two common neoplasms.
METHODS
PARATH-US is a single-center study that was conducted at a tertiary referral center, including consecutive lesions from patients undergoing neck US examination from 2016 to 2022.
FINDINGS
176 PPGs (158 patients: serum calcium levels 2.91 [IQR 2.74-3.05] mmol/L, PTH levels 173 [112-296] ng/L) were compared to 232 size- and volume-matched thyroid nodules (204 age- and sex-matched patients). The morphologic patterns, echoic content and vascular status were all different between PPGs and thyroid neoplasms (p < 0.01 for all comparisons). The combined parameters maximally discriminated PPGs from thyroid nodules (OR, 7.6; 95% CI: 3.4, 17.1, p < 0.0001). When applying risk stratification systems developed for thyroid malignancies, 58-63% of PPGs were classified as high-risk lesions. Parathyroid adenomas had larger sizes and volumes than hyperplasias (p = 0.013 and p = 0.029). Serum calcium and PTH levels were significantly correlated with PPG size and volume (p < 0.0001 for all comparisons).
INTERPRETATION
We demonstrate the presence of distinct US characteristics in PPGs, which help differentiate them from thyroid nodules. When mistaken for thyroid nodules, PPGs bear high-risk US features. When dealing with high-risk cervical lesions detected on US, a PPG should be suspected, and an assessment of calcium levels recommended to avoid unnecessary invasive procedures.
FUNDING
CYTO-TRAIN, C2022DOSRH053, funded by the French Regional Health Agency.
PubMed: 37915399
DOI: 10.1016/j.lanepe.2023.100751 -
JCI Insight Jan 2024The resting zone of the postnatal growth plate is organized by slow-cycling chondrocytes expressing parathyroid hormone-related protein (PTHrP), which include a subgroup...
The resting zone of the postnatal growth plate is organized by slow-cycling chondrocytes expressing parathyroid hormone-related protein (PTHrP), which include a subgroup of skeletal stem cells that contribute to the formation of columnar chondrocytes. The PTHrP-Indian hedgehog feedback regulation is essential for sustaining growth plate activities; however, molecular mechanisms regulating cell fates of PTHrP+ resting chondrocytes and their eventual transformation into osteoblasts remain largely undefined. Here, in a mouse model, we specifically activated Hedgehog signaling in PTHrP+ resting chondrocytes and traced the fate of their descendants using a tamoxifen-inducible Pthrp-creER line with patched-1-floxed and tdTomato reporter alleles. Hedgehog-activated PTHrP+ chondrocytes formed large, concentric, clonally expanded cell populations within the resting zone ("patched roses") and generated significantly wider columns of chondrocytes, resulting in hyperplasia of the growth plate. Interestingly, Hedgehog-activated PTHrP+ cell descendants migrated away from the growth plate and transformed into trabecular osteoblasts in the diaphyseal marrow space in the long term. Therefore, Hedgehog activation drives resting zone chondrocytes into transit-amplifying states as proliferating chondrocytes and eventually converts these cells into osteoblasts, unraveling a potentially novel Hedgehog-mediated mechanism that facilitates osteogenic cell fates of PTHrP+ skeletal stem cells.
Topics: Mice; Animals; Chondrocytes; Parathyroid Hormone-Related Protein; Growth Plate; Receptor, Parathyroid Hormone, Type 1; Hedgehog Proteins; Red Fluorescent Protein
PubMed: 38051593
DOI: 10.1172/jci.insight.165619