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Current Opinion in Nephrology and... Jul 2024Activation of the calcium-sensing receptor (CASR) in the parathyroid gland suppresses the release of parathyroid hormone (PTH). Furthermore, activation of the renal CASR... (Review)
Review
PURPOSE OF REVIEW
Activation of the calcium-sensing receptor (CASR) in the parathyroid gland suppresses the release of parathyroid hormone (PTH). Furthermore, activation of the renal CASR directly increases the urinary excretion of calcium, by inhibiting transepithelial calcium transport in the nephron. Gain-of-function mutations in the CASR gene lead to autosomal dominant hypocalcemia 1 (ADH1), with inappropriately low PTH levels and hypocalcemia, indicative of excessive activation of the parathyroid CASR. However, hypercalciuria is not always observed. The reason why the manifestation of hypercalciuria is not uniform among ADH1 patients is not well understood.
RECENT FINDINGS
Direct activation of the CASR in the kidney has been cumbersome to study, and an indirect measure to effectively estimate the degree of CASR activation following chronic hypercalcemia or genetic gain-of-function CASR activation has been lacking. Studies have shown that expression of the pore-blocking claudin-14 is strongly stimulated by the CASR in a dose-dependent manner. This stimulatory effect is abolished after renal Casr ablation in hypercalcemic mice, suggesting that claudin-14 abundance may gauge renal CASR activation. Using this marker has led to unexpected discoveries regarding renal CASR activation.
SUMMARY
These new studies have informed on renal CASR activation thresholds and the downstream CASR-regulated calcium transport mechanisms.
Topics: Receptors, Calcium-Sensing; Humans; Animals; Kidney; Hypercalciuria; Calcium; Hypercalcemia; Claudins; Hypocalcemia; Hypoparathyroidism
PubMed: 38690798
DOI: 10.1097/MNH.0000000000000998 -
Radiography (London, England : 1995) May 2024Dual phase technetium-99mTc-methoxy isobutyl isonitrile (MIBI) single-photon emission computed tomography with computed tomography (SPECT/CT) may be the most accurate...
INTRODUCTION
Dual phase technetium-99mTc-methoxy isobutyl isonitrile (MIBI) single-photon emission computed tomography with computed tomography (SPECT/CT) may be the most accurate conventional imaging approach for localization of enlarged parathyroid gland (EPG). The imaging is based on the radiopharmaceutical (RP) retention in EPG compared to washout from normal thyroid and normal parathyroid glands. This study aimed to estimate and optimize the contribution of computed tomography (CT) scan and scan range to effective dose (ED) in dual-phase MIBI SPECT/CT parathyroid scintigraphy.
METHODS
The study included seventy-four patients; thirty-seven with reduced and thirty-seven with extended CT scan range. The ED caused by the CT scan was calculated using Dose Length Product (DLP) data and estimated using the Imaging Performance Assessment of CT scanners (ImPACT) calculator.
RESULTS
For all patients, the contribution of CT to the ED in a combined SPECT/CT examination was 2.62 ± 0.29 mSv (48%). The contribution of CT to the total ED was 1.8 ± 0.18 mSv (33%) when using reduced and 3.44 ± 0.23 mSv (64%) when using extended scan range. The DLP and ED were statistically significantly different between the reduced and extended CT scan range (p < 0.001) in the first and second phases. The individual organ dose was reduced from 8% to 94%.
CONCLUSION
The hybrid SPECT/CT improves the interpretation of nuclear medicine images and also increases the radiation dose to the patient. An adequately defined CT scan range on SPECT/CT imaging, can significantly reduce a patient's ED.
IMPLICATIONS FOR PRACTICE
The research findings showed that knowledge of anatomy, pathology and technology can provide optimising diagnostic procedures and reduce patient ED after SPECT/CT scans.
Topics: Humans; Male; Female; Middle Aged; Single Photon Emission Computed Tomography Computed Tomography; Radiopharmaceuticals; Radiation Exposure; Technetium Tc 99m Sestamibi; Aged; Radiation Dosage; Adult; Parathyroid Glands; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 38688163
DOI: 10.1016/j.radi.2024.04.013 -
International Journal of Molecular... Apr 2024Transient receptor potential canonical sub-family channel 3 (TRPC3) is considered to play a critical role in calcium homeostasis. However, there are no established...
Transient receptor potential canonical sub-family channel 3 (TRPC3) is considered to play a critical role in calcium homeostasis. However, there are no established findings in this respect with regard to TRPC6. Although the parathyroid gland is a crucial organ in calcium household regulation, little is known about the protein distribution of TRPC channels-especially TRPC3 and TRPC6-in this organ. Our aim was therefore to investigate the protein expression profile of TRPC3 and TRPC6 in healthy and diseased human parathyroid glands. Surgery samples from patients with healthy parathyroid glands and from patients suffering from primary hyperparathyroidism (pHPT) were investigated by immunohistochemistry using knockout-validated antibodies against TRPC3 and TRPC6. A software-based analysis similar to an H-score was performed. For the first time, to our knowledge, TRPC3 and TRPC6 protein expression is described here in the parathyroid glands. It is found in both chief and oxyphilic cells. Furthermore, the TRPC3 staining score in diseased tissue (pHPT) was statistically significantly lower than that in healthy tissue. In conclusion, TRPC3 and TRPC6 proteins are expressed in the human parathyroid gland. Furthermore, there is strong evidence indicating that TRPC3 plays a role in pHPT and subsequently in parathyroid hormone secretion regulation. These findings ultimately require further research in order to not only confirm our results but also to further investigate the relevance of these channels and, in particular, that of TRPC3 in the aforementioned physiological functions and pathophysiological conditions.
Topics: Humans; TRPC Cation Channels; Hyperparathyroidism, Primary; Parathyroid Glands; Female; Male; TRPC6 Cation Channel; Down-Regulation; Middle Aged; Aged; Adult; Immunohistochemistry; Parathyroid Hormone
PubMed: 38673977
DOI: 10.3390/ijms25084392 -
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 -
JACS Au Apr 2024The kidney, parathyroid gland, and choroid plexus express the aging-related transmembrane protein α-Klotho, a coreceptor of the fibroblast growth factor 23 (FGF23)...
The kidney, parathyroid gland, and choroid plexus express the aging-related transmembrane protein α-Klotho, a coreceptor of the fibroblast growth factor 23 (FGF23) receptor complex. Reduced α-Klotho levels are correlated with chronic kidney disease and other age-related diseases, wherein they are released from membranes into circulation. Klotho's potential physiological action as a hormone is of current scientific interest. Part of the challenges associated with advancing these studies, however, has been the long-standing difficulty in detecting soluble α-Klotho in biofluids. Here, we describe the discovery of peptides that recognize α-Klotho with high affinity and selectivity by applying in-solution size-exclusion-based affinity selection-mass spectrometry (AS-MS). After two rounds of AS-MS and subsequent N-terminal modifications, the peptides improved their binding affinity to α-Klotho by approximately 2300-fold compared to the reported starting peptide Pep-10, previously designed based on the C-terminal region of FGF23. The lead peptide binders were shown to enrich α-Klotho from cell lysates and to label α-Klotho in kidney cells. Our results further support the utility of in-solution, label-free AS-MS protocols to discover peptide-based binders to target proteins of interest with high affinity and selectivity, resulting in functional probes for biological studies.
PubMed: 38665650
DOI: 10.1021/jacsau.3c00650 -
Frontiers in Endocrinology 202424-Hydroxylase, encoded by the gene, is a crucial enzyme involved in the catabolism of vitamin D. Loss-of-function mutations in result in PTH-independent... (Review)
Review
INTRODUCTION
24-Hydroxylase, encoded by the gene, is a crucial enzyme involved in the catabolism of vitamin D. Loss-of-function mutations in result in PTH-independent hypercalcaemia with high levels of 1,25(OH)D. The variety of clinical manifestations depends on age, and underlying genetic predisposition mutations can lead to fatal infantile hypercalcaemia among neonates, whereas adult symptoms are usually mild.
AIM OF THE STUDY
We report a rare case of an adult with primary hyperparathyroidism and loss-of-function mutations in the gene and a review of similar cases.
CASE PRESENTATION
We report the case of a 58-year-old woman diagnosed initially with primary hyperparathyroidism. Preoperatively, the suspected mass adjoining the upper pole of the left lobe of the thyroid gland was found via ultrasonography and confirmed by 99mTc scintigraphy and biopsy as the parathyroid gland. The patient underwent parathyroidectomy (a histopathology report revealed parathyroid adenoma), which led to normocalcaemia. After 10 months, vitamin D supplementation was introduced due to deficiency, and the calcium level remained within the reference range. Two years later, biochemical tests showed recurrence of hypercalcaemia with suppressed parathyroid hormone levels and elevated 1,25(OH)D concentrations. Further investigation excluded the most common causes of PTH-independent hypercalcaemia, such as granulomatous disease, malignancy, and vitamin D intoxication. Subsequently, vitamin D metabolites were measured using LC-MS/MS, which revealed high levels of 25(OH)D, low levels of 24,25(OH)D and elevated 25(OH)D/24,25(OH)D ratios, suggesting a defect in vitamin D catabolism. Molecular analysis of the gene using the NGS technique revealed two pathogenic variants: p.(Arg396Trp) and p.(Glu143del) (rs114368325 and rs777676129, respectively).
CONCLUSIONS
The diagnostic process for hypercalcaemia becomes complicated when multiple causes of hypercalcaemia coexist. The measurement of vitamin D metabolites using LC-MS/MS may help to identify carriers of mutations. Subsequent molecular testing may contribute to establishing the exact frequency of pathogenic variants of the gene and introducing personalized treatment.
Topics: Humans; Hypercalcemia; Female; Middle Aged; Vitamin D3 24-Hydroxylase; Parathyroid Neoplasms; Adenoma; Mutation; Parathyroidectomy
PubMed: 38665259
DOI: 10.3389/fendo.2024.1355916 -
Journal of the American Veterinary... Apr 2024To describe a novel presentation of paraneoplastic hypercalcemia caused by a canine salivary carcinoma.
OBJECTIVE
To describe a novel presentation of paraneoplastic hypercalcemia caused by a canine salivary carcinoma.
ANIMAL
A 6-year-old intact male Husky with hypercalcemia and a spontaneous salivary carcinoma, stage III.
CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES
The dog presented with polyuria, polydipsia, and hypercalcemia. Physical examination revealed a 37 X 43-mm firm mass in the ventrolateral aspect of the right-hand side of the neck, caudal to the temporomandibular joint. Incisional biopsy was suspicious of metastatic carcinoma to the mandibular lymph node. A full-body CT scan found a large, heterogenous, contrast-enhancing mass on the right ventrolateral neck that appeared to be originating from either the mandibular lymph node or right mandibular salivary gland. Parathyroid hormone-related protein was considered within normal reference intervals, and both parathyroid glands appeared ultrasonographically normal.
TREATMENT AND OUTCOME
The patient was treated with a marginal surgical excision of the mass, without immediate complications. Histopathology confirmed the presence of a salivary carcinoma with narrow margins of excision and invasion of the mandibular lymph node. Twenty-four hours after surgery, ionized calcium returned to normal reference values and clinical signs completely resolved.
CLINICAL RELEVANCE
Hypercalcemia is an urgent pathology with important systemic implications requiring prompt diagnosis and intervention. In this case report, we identify the first salivary carcinoma associated with a paraneoplastic hypercalcemia, including this pathology as a new differential diagnosis. The hypercalcemia resolved with marginal surgical excision, but interestingly the parathyroid hormone-related protein was not overexpressed, meaning that this neoplasia could mediate hypercalcemia by another pathophysiological mechanism.
PubMed: 38663442
DOI: 10.2460/javma.24.01.0058 -
Journal of Pediatric Endocrinology &... Jun 2024The most common cause of primary hyperparathyroidism (PPH) in children is a parathyroid adenoma. Among this population, PPH exhibits higher levels of morbidity, severity...
OBJECTIVES
The most common cause of primary hyperparathyroidism (PPH) in children is a parathyroid adenoma. Among this population, PPH exhibits higher levels of morbidity, severity and target organ involvement compared to adults. When there is suspicion of PPH, cervical ultrasound and Tc-sestamibi SPECT/CT are the imaging test traditionally indicated. Among adults, the use of [F]fluorocholine PET/CT has shown a higher sensitivity than ultrasound and [Tc]sestamibi SPECT/CT, leading to an expanding adoption in recent years. However, its role in paediatrics has not been clearly defined yet.
CASE PRESENTATION
The patient is an adolescent female aged 13 years presented with lithiasis. The analytical study revealed elevated PTH, hipovitaminosis D, hypercalcaemia and hypophosphataemia. Due to the suspicion of PPH, cervical ultrasound and Tc-sestamibi SPECT/C were performed, failing to identify hyperfunctioning parathyroid glands. We proceeded to carry out a [F]fluorocholine PET/CT where a hypermetabolic nodular image was identified, compatible with a hyperfunctioning parathyroid adenoma. The patient underwent surgery, resulting in the normalisation of PTH levels. Pathological anatomy confirmed the presence of a parathyroid adenoma.
CONCLUSIONS
In cases where conventional imaging tests yield negative results or discrepancies, we suggest the possibility of the use of [F]fluorocholine PET/CT for the detection of hyperfunctioning parathyroid adenomas.
Topics: Humans; Female; Adolescent; Hyperparathyroidism, Primary; Choline; Positron Emission Tomography Computed Tomography; Parathyroid Neoplasms; Radiopharmaceuticals; Prognosis; Adenoma; Fluorine Radioisotopes
PubMed: 38661069
DOI: 10.1515/jpem-2023-0556 -
Tropical Doctor Jul 2024Can a smart phone application be reliably used for laryngoscopy? This thesis was tested for peri-operative evaluation of vocal cords in patients undergoing thyroid and...
Can a smart phone application be reliably used for laryngoscopy? This thesis was tested for peri-operative evaluation of vocal cords in patients undergoing thyroid and parathyroid surgery.
Topics: Humans; Laryngoscopy; Pilot Projects; Vocal Cords; Smartphone; Thyroid Gland; Thyroidectomy; Male; Female; Middle Aged; Adult
PubMed: 38654398
DOI: 10.1177/00494755241246823 -
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