Intratracheal parathyroid gland: an unexpected diagnosis.

Ectopic or supernumerary parathyroid tissue has been generally described in the literature in cases found during workup for parathyroid adenoma. We present two unique cases of intratracheal parathyroid gland, a rare occurrence that has not yet been described in the literature. In both cases, the masses were found incidentally and showed no clinical or laboratory evidence of hyperparathyroidism. In both cases, surveillance was chosen as the method of treatment. We present this case series to increase awareness of this potential diagnosis.

Preoperative F-18 fluorocholine PET/CT for the detection of hyperfunctioning parathyroid glands in patients with secondary or tertiary hyperparathyroidism: comparison with Tc-99m sestamibi scan and neck ultrasound.

OBJECTIVES: Currently, neck ultrasound is the preferred preoperative imaging in patients with secondary/tertiary hyperparathyroidism, and the use of Tc-99m sestamibi scan is limited in these patients. We conducted this study to compare the diagnostic utilities of F-18 fluorocholine PET/CT, Tc-99m sestamibi scintigraphy, and neck ultrasound for localizing hyperfunctioning parathyroid glands in secondary/tertiary hyperparathyroidism. METHODS: We prospectively enrolled 30 dialysis patients with a diagnosis of secondary/tertiary hyperparathyroidism; of these, 27 participants underwent all three imaging modalities, including dual-phase F-18 fluorocholine PET/CT (PET acquired 5 and 60 min after tracer injection), dual-phase Tc-99 m sestamibi SPECT/CT, and neck ultrasound. All patients underwent parathyroidectomy after imaging. We compared the lesion-based sensitivity, specificity, and accuracy of the three image tools using histopathology as the reference. RESULTS: A total of 27 patients (107 lesions) underwent all three imaging modalities and entered the final analysis. The lesion-based sensitivities of F-18 fluorocholine PET/CT, Tc-99m sestamibi, and ultrasound were 86%, 55%, and 62%, respectively (both p < 0.001, when comparing F-18 fluorocholine PET/CT to Tc-99 m sestamibi scan and to ultrasound). F-18 fluorocholine PET/CT, Tc-99m sestamibi, and ultrasound had similar specificities of 93%, 80%, and 87%, respectively. The accuracy of F-18 fluorocholine PET/CT (87%) was significantly higher than that of Tc-99m sestamibi (59%) and ultrasound (65%) (both p < 0.001). F-18 fluorocholine PET/CT identified more hyperplastic glands than ultrasound in 52% (14/27) patients. The sensitivity of F-18 fluorocholine PET/CT reached 95% for hyperplastic parathyroid masses as low as 200 mg. CONCLUSIONS: F-18 fluorocholine PET/CT shows superior accuracy over the conventional imaging modalities in patients with secondary or tertiary hyperparathyroidism. The combination of F-18 fluorocholine PET/CT and neck ultrasound may enable better surgical planning in these patients. REGISTRATION IDENTIFICATION NUMBER: NCT04316845.

Measurement of the AST to LD Ratio in Parathyroid Tissue Suspension Can Precisely Differentiate a Hyperfunctioning Parathyroid.

BACKGROUND: Frozen section of excised tissue is used to confirm removal of the etiology of primary hyperparathyroidism in the current era of intraoperative parathyroid hormone measurement and provides safeguards for surgeons. We recently reported that the aspartate aminotransferase (AST)/lactate dehydrogenase (LD) ratio in tissue suspension can accurately distinguish normal parathyroid tissue from other tissues. Therefore, we hypothesized that this ratio may also be applied to distinguish hyperfunctioning parathyroid tissue (HPT) from other tissues. METHODS: We prospectively analyzed 22 patients who underwent parathyroidectomy for primary hyperparathyroidism (benign, 21; malignant, 1) from July 2018 to October 2019. In total, 27 specimens were examined. Approximately 1 mm3 of minced HPT as confirmed by frozen sections was suspended in 1 mL of normal saline and AST and LD levels were measured. The AST/LD ratios of other tissues (normal parathyroid tissue, thyroid gland, adipose tissue, and others; n = 94) were obtained from our previous report. RESULTS: The AST/LD ratio of benign HPT was consistently higher than that of other tissues (P < 0.001). The optimal cut-off value was 0.36 according to the receiver operating characteristic curve, with 100% sensitivity and specificity. The AST/LD ratio in malignant HPT was also markedly lower than that in benign HPT. CONCLUSION: This method might be a new adjunct for intraoperative differentiation of HPT with an accuracy and turnaround time comparable with those of frozen sections, minimal cost, and no need for dedicated pathological staff. Additionally, this method might increase the treatment success rate in settings with limited medical resources.

A Functional Parathyroid Cyst from the Hemorrhagic Degeneration of a Parathyroid Adenoma.

A 77-year-old man with a history of hypertension, prostate hyperplasia, and urolithiasis was admitted for acute kidney injury caused by hypercalcemia. Neck ultrasonography showed a large cyst adjacent to the right lower thyroid lobe. Although a 99mtechnetium sestamibi scan was negative, an extremely high intracystic intact parathyroid hormone level suggested that the cyst had a parathyroid origin and that a functional parathyroid cyst was present. Immunohistochemical staining for the calcium-sensing receptor (CaSR) after right lower parathyroidectomy revealed CaSR-positive cells lining the cyst, indicating that the functional parathyroid cyst had originated from the hemorrhagic degeneration of a parathyroid adenoma.

Ultrasonography of Extrathyroidal Diseases Mimicking Intrinsic Thyroid Lesions.

Some localized or multisystem diseases as well as congenital anomalies occasionally involve thyroid and unusual findings will be identified during thyroid ultrasonography. Recognition of these entities will minimize unnecessary complementary examination and lead to appropriate management for patients. Therefore, we aim to review sonographic features of these extrathyroidal diseases that affect thyroid in adults. Our review derives from cases diagnosed in our hospital and published literature, with pictures accessible using as illustration. These disorders included intrathyroidal parathyroid adenoma, intrathyroidal cystic findings of nonthyroid origin, metastases to the thyroid, esophageal diverticulum, paratracheal air cysts, and ossification of anterior longitudinal ligament.

Parathyroid Carcinoma.

Parathyroid carcinoma (PC) is a rare endocrine malignancy, accounting for <1% of all cases of sporadic primary hyperparathyroidism (PHPT) and up to 15% in the hereditary hyperparathyroidism-jaw tumor syndrome. Genomic alterations identified in PC are mostly represented by CDC73 gene mutations, codifying for a loss-of-function protein termed parafibromin. Whole exome sequencing identified mutations in other genes, such as mTOR, KMT2D, CDKN2C, THRAP3, PIK3CA, and EZH2 genes, CCND1 gene amplification. The diagnosis of PC is quite difficult due to the lack of reliable clinical diagnostic criteria, and in the majority of cases is made postoperatively at histological examination. The clinical manifestations of PC are primarily due to the excessive secretion of PTH by the tumor rather than spread to local or distant organs. En bloc resection of the parathyroid tumor represents the initial mainstay treatment of patients with PC. Multiple surgical procedures may be required, although surgical morbidity should be taken into account. A 5- and 10-year survival between 77-100 and 49-91%, respectively, has been reported. When the tumor is no more resectable, medical treatment of hypercalcemia has a pivotal role in the management of these patients.

Acute kidney injury associated with hypercalcaemic crisis in a patient with primary hyperparathyroidism.

Parathyroid or hypercalcaemic crisis is a rare presenting manifestation of primary hyperparathyroidism and usually seen in relation to parathyroid carcinoma and multiple myeloma. We present a middle-aged woman with extreme hypercalcaemia due to parathyroid adenoma presenting as acute kidney injury. This case highlights the need to consider primary hyperparathyroidism in differentials of a patient presenting with severe hypercalcaemia and renal dysfunction. Also this is the second reported case in literature of a patient surviving such extreme hypercalcaemia due to parathyroid adenoma.

Role of calcium-sensing receptor, Galectin-3, Cyclin D1, and Ki-67 immunohistochemistry to favor in the diagnosis of parathyroid carcinoma.

BACKGROUND: As histopathological findings of parathyroid carcinoma are not certain, the diagnosis of tumors with degenerative changes may be difficult. In these cases, immunohistochemical markers are beneficial. We aimed to research the acceptability of calcium-sensing receptor (CaSR), Galactin-3, Cyclin D1, and Ki-67 as helpful markers in parathyroid tumors in cases which are difficult to diagnose. MATERIALS AND METHODS: Those cases who had been diagnosed with atypical parathyroid adenoma and parathyroid carcinoma between 2010 and 2015 were reevaluated. Immunohistochemical markers were applied to this cases. RESULTS: About 21 cases were parathyroid adenoma, 14 were atypical adenoma, and 10 cases were parathyroid carcinoma. According to the immunohistochemical results, global loss of CaSR staining was seen in 50% (5/10) of the patients with carcinoma while there was no loss of staining in those with parathyroid adenoma (P = 0,001). Global loss of CaSR staining was found in only one out of 14 cases with atypical adenoma. The expression of Galactin-3 was found to be positive in 40% (4/10) of carcinoma cases, 71.4% (10/14) of those with atypical adenoma, and 14.3% (3/21) of those with adenoma (P = 0,002). Cyclin D1 expression was determined to be positive in 70% (7/10) of patients with carcinoma, 71.4% (10/14) of atypical adenoma cases, and 23.8% (5/21) of those with adenoma. The Ki-67 proliferation index was seen to be above 5% in 50% (5/10) of carcinoma cases and 35,7% (5/14) of those with atypical adenoma. CONCLUSION: In these studies, it has been emphasized that the global loss of CaSR staining was used as a negative marker in the diagnosis of carcinoma. In this study, we have also confirmed that the global loss of CaSR staining is a useful marker to determine potential increased malignancy.

Four-dimensional Computed Tomography (4DCT) for Preoperative Localization of Parathyroid Adenomas.

BACKGROUND: Four-dimensional parathyroid computed tomography (4DCT) is a relatively new parathyroid imaging technique that provides functional and highly detailed anatomic information about parathyroid tumors. OBJECTIVES: To assess the accuracy of 4DCT for the preoperative localization of parathyroid adenomas (PTAs) in patients with biochemically confirmed primary hyperparathyroidism (PHPT) and a history of failed surgery or unsuccessful localization using 99mTc-sestamibi scanning and ultrasonography. METHODS: Between January 2013 and January 2015, 55 patients with PHPT underwent 4DCT at Hillel Yaffe Medical Center, Hadera, Israel. An initial unenhanced scan was followed by an IV contrast injection of nonionic contrast material (120 ml of at 4 ml/s). Scanning was repeated 25, 60, and 90 seconds after the initiation of IV contrast administration. An experienced radiologist blinded to the earlier imaging results reviewed the 4DCT for the presence and location (quadrant) of the suspected PTAs. At the time of the study, 28 patients had undergone surgical exploration following 4DCT and we compared their scans with the surgical findings. RESULTS: 4DCT accurately localized 96% (27/28) of abnormal glands, all of which were hypervascular and showed characteristic rapid enhancement on 4DCT that could be distinguished from Level II lymph nodes. Surgery found hypovascular cystic PTA in one patient who produced a negative 4DCT scan. All patients had solitary PTAs. The scan at 90 seconds provided no additional information and was abandoned during the study. CONCLUSIONS: 4DCT accurately localized hypervascular parathyroid lesions and distinguished them from other tissues. A three-phase scanning protocol may suffice.

MicroRNAs in parathyroid physiopathology.

Parathyroid glands regulate calcium homeostasis through synthesis and secretion of parathormone (PTH). They sense the extracellular calcium concentration through the G-protein coupled calcium sensing receptor (CASR) and release PTH in order to preserve calcium concentration in the physiological range. Tumors of the parathyroid glands are common endocrine neoplasia associated with primary or secondary/tertiary hyperparathyroidisms. Small non-coding RNAs are regulators of gene expression able to modulate hormone synthesis, hormone release and endocrine cell proliferation. In this scenario, microRNA (miRNA) expression profiles have been investigated in parathyroid tumors, while miRNAs are involved in hypocalcemia and uremia-induced PTH release from normal parathyroid cells. Here we reviewed data about the role of miRNAs in the regulation of: 1) PTH synthesis and secretion; 2) CASR expression; 3) parathyroid cell tumorigenesis. Though studies about miRNAs in parathyroid gland pathophysiology are limited, they contribute in elucidating regulatory pathways involved in PTH release and parathyroid cell tumorigenesis.

Childhood parathyroid adenoma: a rare but important cause of nephrolithiasis.

Primary hyperparathyroidism is very rare in children and adolescents. The management of a 12-year-old boy with renal calculi due to parathyroid adenoma is discussed. The single tumor after localization with sestamibi scintigraphy and SPECT-CT scan was excised with amelioration of symptoms. The case is reported due to the rarity of the disease and successful unilateral exploration. The association with hypopigmented areas of skin has also not been previously reported in literature.

Preoperative localization of hyperfunctioning parathyroid glands with 4D-CT.

Primary hyperparathyroidism (pHPT) is almost exclusively the result of a solitary parathyroid adenoma. In most cases, the affected gland can be surgically removed, but precise preoperative imaging is essential for adenoma localization prior to surgical intervention. In this study, we evaluated the diagnostic value of four-dimensional computed tomography (4D-CT) as a preoperative imaging tool in relation to the localization of pathologic parathyroid glands in patients with pHPT and negative sestamibi scans. This study included 43 consecutive patients with pHPT referred for parathyroidectomy at the Department of Head and Neck Surgery of Copenhagen University Hospital Rigshospitalet in 2011 and 2012. All patients had a 4D-CT performed prior to parathyroidectomy. CT localization of the suspected adenoma was correlated to the actual surgical findings and subsequent histological diagnosis was also available as references for the accuracy of this imaging tool. Hyperfunctioning parathyroid glands were found in 40 patients. 4D-CT identified 32 solitary hyperfunctioning parathyroid glands located on the correct side of the neck (PPV 76 %) and 21 located within the correct quadrant (PPV 49 %). Unilateral resection was performed in 72 % of patients due to the localization findings of preoperative imaging. 4D-CT can, therefore, be considered an effective method for the preoperative localization of parathyroid adenomas and is an important tool in surgical intervention for patients referred to parathyroidectomy.

Adenoma paratiroideo ectópico poco frecuente / Uncommon Ectopic Parathyroid Adenoma

No disponible

Functional evaluation of parathyroid adenoma using 99mTc-MIBI parathyroid SPECT/CT: correlation with functional markers and disease severity.

OBJECTIVES: In parathyroid adenoma, uptake of technetium-99m-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been suggested to have a correlation with functional markers. The purpose of this study was to evaluate the feasibility of (99m)Tc-MIBI parathyroid single photon emission computed tomography/computed tomography (SPECT/CT) in evaluating the function and disease severity of parathyroid adenoma. PATIENTS AND METHODS: Twenty-three patients with surgically confirmed parathyroid adenoma were retrospectively enrolled. A parathyroid planar scan and SPECT/CT were performed before parathyroidectomy. Functional and clinical makers reflecting the disease severity of parathyroid adenoma were also evaluated, including serum intact parathyroid hormone, calcium, bone mineral density, and creatinine clearance. The pathologic volume (V(P)) of the adenoma was measured after parathyroidectomy. On parathyroid SPECT/CT, metabolic volume (V(M)) was measured using an isocontour method. Maximum uptakes of parathyroid adenoma and mean uptakes of contralateral thyroid tissue were measured to calculate the parathyroid adenoma-to-background ratio on parathyroid SPECT/CT (PBR(SCT)) and planar scan (PBR(PL)). RESULTS: V(M) significantly correlated with V(P) (r=0.669, P=0.0005). Serum intact parathyroid hormone level significantly correlated with PBR(PL), PBR(SCT), V(M), and V(P) (P=0.0004, 0.005, 0.003, and 0.025, respectively). However, serum calcium level correlated only with V(M) (P=0.012). Regarding the surgical indication criteria, PBR(SCT) and PBR(PL) were significantly higher in the young-aged group (P=0.0004 and 0.024, respectively) and V(M) was significantly higher in the high calcium level group (P=0.049), whereas V(P) was not different between groups on the basis of any criteria. CONCLUSION: Quantitative indices of parathyroid SPECT/CT closely correlate with laboratory functional markers and disease severity of parathyroid adenoma. Thus, parathyroid SPECT/CT could be used for evaluation of the underlying functional state and disease severity of parathyroid adenoma, particularly for decision pertaining to surgical treatment.

Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia.

Parathyroid adenomas (PAs) causing primary hyperparathyroidism (PHPT) are histologically heterogeneous yet have been historically viewed as largely monotypic entities arising from clonal expansion of a single transformed progenitor. Using flow cytometric analysis of resected adenomatous parathyroid glands, we have isolated and characterized chief cells, oxyphil cells, and tumor-infiltrating lymphocytes. The parathyroid chief and oxyphil cells produce parathyroid hormone (PTH), express the calcium-sensing receptor (CASR), and mobilize intracellular calcium in response to CASR activation. Parathyroid tumor infiltrating lymphocytes are T cells by immunophenotyping. Under normocalcemic conditions, oxyphil cells produce ∼50% more PTH than do chief cells, yet display significantly greater PTH suppression and calcium flux response to elevated calcium. In contrast, CASR expression and localization are equivalent in the respective parathyroid cell populations. Analysis of tumor clonality using X-linked inactivation assays in a patient-matched series of intact tumors, preparatively isolated oxyphil and chief cells, and laser-captured microdissected PA specimens demonstrate polyclonality in 5 of 14 cases. These data demonstrate the presence of functionally distinct oxyphil and chief cells within parathyroid primary adenomas and provide evidence that primary PA can arise by both clonal and polyclonal mechanisms. The clonal differences, biochemical activity, and relative abundance of these parathyroid adenoma subpopulations likely reflect distinct mechanisms of disease in PHPT.

Highly efficient localization of pathological glands in primary hyperparathyroidism using contrast-enhanced ultrasonography (CEUS) in comparison with conventional ultrasonography.

INTRODUCTION: Preoperative detection of parathyroid gland adenoma in the presence of primary hyperparathyroidism (pHPT) represents a diagnostic challenge. We present the first prospective study with contrast-enhanced ultrasonography (CEUS) as the central diagnostic tool for the preoperative localization of parathyroid gland adenoma in pHPT in comparison with conventional ultrasonography. METHODS: Between July 2010 and December 2011, 75 consecutive patients underwent surgery for pHPT. In all patients, conventional ultrasonography and CEUS were performed prospectively for localization of pathological parathyroid glands. Twenty-five patients suffered from a concomitant goiter (CG), and 12 patients had undergone previous neck surgery due to thyroid pathologies. The sensitivity of both diagnostic tools was analyzed in comparison with intraoperative and histological findings. RESULTS: CEUS had a sensitivity of 97% for the detection of the correct quadrant of the pathological parathyroid gland and of 99% for the correct side in comparison with 70% for conventional ultrasonography. In multivariate regression analysis, CG, gland size, and body mass index had a relevant impact on incorrect findings by conventional ultrasonography as compared with CEUS. Follow-up with a minimum of 6 months after surgery showed normal serum levels of calcium and PTH in all 75 patients. CONCLUSIONS: CEUS represents a highly reliable, noninvasive and nonradioactive diagnostic tool for localization of pathological parathyroid glands in patients with pHPT. Even in the presence of CG, previous neck surgery, or double adenomas, CEUS has a high sensitivity.