Diagnostic Fine-Needle Aspiration Biopsy of an Intrathyroidal Parathyroid Gland and Subsequent Eucalcemia in a Patient with Primary Hyperparathyroidism

ObjectiveTo present the clinical course of a patient with persistent primary hyperparathyroidism (PHPT) whose intrathyroidal parathyroid gland was diagnosed by ultrasound-guided fine-needle aspiration biopsy (FNAB).MethodsWe describe the clinical course and laboratory, radiographic, and microscopic findings of a patient with persistent PHPT due to an intrathyroidal cystic parathyroid gland and review the relevant literature.ResultsA 74-year-old man with PHPT (presenting serum calcium concentration, 16.2 mg/dL; intact parathyroid hormone [PTH] concentration, 341 pg/mL) had surgical excision of the right superior, right inferior, and left inferior parathyroid glands, but the left superior parathyroid gland remained unidentified. Microscopic examination revealed parathyroid hyperplasia. Technetium Tc 99m sestamibi single-photon emission computed tomography imaging showed uptake in 2 foci, 1 on each side of midline in the neck. Reoperation with attention to the left neck failed to locate another parathyroid gland. Neck ultrasonography demonstrated a complex nodule within the right lower lobe of the thyroid. Results from FNAB of the solid component were consistent with parathyroid cells, and cystic fluid PTH concentration was greater than 1800 pg/mL. Nine months later, neck ultrasonography showed a hypoechoic area located posterior to the inferior pole of the right thyroid. The patient remained eucalcemic 16 months postprocedure.ConclusionAutoinfarction of the parathyroid gland and aspiration of cystic fluid may explain resolution of hypercalcemia. Although PHPT due to functioning parathyroid cysts is rare, and PHPT due to cystic parathyroid hyperplasia has been described, this is the first case report of a patient with persistent PHPT due to a functional parathyroid cyst whose diagnosis by FNAB was followed by eucalcemia. (Endocr Pract. 2008;14:80-86)     

An Unusual Case of Recurrent Hyperparathyroidism and Papillary Thyroid Cancer

ObjectiveTo report an unusual occurrence of recurrent hyperparathyroidism due to papillary thyroid carcinoma.MethodsWe describe the clinical history, physical examination findings, laboratory values, imaging findings, and pathologic findings of a woman who developed recurrent hyperparathyroidism 13 years after successful parathyroidectomy.ResultsA 59-year-old woman presented to our clinic with recurrent primary hyperparathyroidism. In 1994, she presented with nephrolithiasis and underwent resection of a right superior parathyroid adenoma that resulted in clinical and biochemical cure. Her clinical course had been followed at periodic intervals, and she had been symptom-free and normocalcemic. In 2007, she again developed nephrolithiasis and was documented to have recurrent hyperparathyroidism. Imaging studies suggested a parathyroid adenoma near the right inferior pole of the thyroid. The patient had reoperative neck exploration. No obvious parathyroid adenoma was found and a right thyroid lobectomy was performed, which resulted in normalization of intraoperative intact parathyroid hormone levels, and the incision was closed. Final pathology demonstrated no parathyroid adenoma, but instead, a 1-cm papillary thyroid carcinoma that stained positive for parathyroid hormone. More than 6 months after surgery, she remains clinically and biochemically cured.ConclusionsRecurrent hyperparathyroidism occurs secondary to multiple causes. This case demonstrates the challenge a surgeon faces in managing recurrent disease and highlights a rare phenomenon of papillary thyroid cancer causing recurrent hyperparathyroidism. (Endocr Pract. 2009;15:349-352)     

Multiglandular Parathyroid Carcinoma: Case Report and Review of The Literature

ObjectiveTo report the fifth case of multiglandular parathyroid carcinoma and highlight the necessity of bilateral neck exploration in some circumstances.MethodsWe report a case of simultaneous bilateral and multiglandular parathyroid carcinoma in a 48-yearold woman presenting with primary hyperparathyroidism. Ultrasonography revealed a 24-by 24-by 34-mm nodule on the right lobe of the thyroid and a 20-by 20-by 32-mm parathyroid gland inferior to the left thyroid lobe. Technetium Tc 99m sestamibi scan revealed bilateral increased uptake consistent with the parathyroid glands. She was treated with bilateral neck exploration and parathyroidectomy with en bloc resection of the adjacent thyroid lobe in the right lower gland and parathyroidectomy with resection of surrounding soft tissue in the left lower gland.ResultsThe presence of a thick fibrous capsule, invasion of surrounding tissues, trabecular and solid growth pattern without necrotic foci, and vascular invasion on pathology slides enabled the diagnosis of parathyroid carcinoma of both glands. Her calcium and parathyroid hormone levels were within normal limits during a follow-up period of 4 years.ConclusionSince surgical resection offers the only curative treatment and initial operation may be the determinant of survival, a high index of suspicion for carcinoma both clinically and intraoperatively is vital. We aim to reemphasize that bilateral neck exploration in select cases of parathyroid carcinoma should be considered if there is concrete evidence of a second tumor, since parathyroid carcinoma can coexist with hyperplasia, adenoma, or even carcinoma of other parathyroid glands. (Endocr Pract. 2011;17:e79-e83)     

Synchronous Parathyroid Carcinoma,Parathyroid Adenoma,and Papillary Thyroid Carcinoma in a Patient with Severe and Long-Standing Hyperparathyroidism

ObjectiveTo describe a patient presenting with the rare constellation of synchronous parathyroid carcinoma, parathyroid adenoma, and papillary thyroid carcinoma.MethodsWe summarize the clinical presentation, diagnostic work-up, surgical management, and pathologic features of our patient and review the pertinent literature.ResultsThe patient was a 59-year-old man who presented with severe clinical manifestations of long-standing primary hyperparathyroidism, a serum calcium concentration of 14.4 mg/dL, and a parathyroid hormone level of 2,023 pg/mL. He was found to have a 3.4-cm parathyroid carcinoma on the left side and a 3.2-cm papillary carcinoma in the right thyroid lobe. In addition, a 917-mg parathyroid adenoma was found on the right side.ConclusionSynchronous parathyroid and thyroid carcinomas are extremely rare. To our knowledge, our patient is the first documented case with a parathyroid adenoma in addition to synchronous parathyroid and thyroid carcinomas. The presence of concurrent parathyroid carcinoma and parathyroid adenoma can cause diagnostic confusion and should be considered in patients presenting with severe hyperparathyroidism. Any concomitant thyroid nodules must be investigated to rule out thyroid carcinoma. (Endocr Pract. 2009;15:463-468)     

Recurrent Hyperparathyroidism and a Novel Nonsense Mutation in a Patient with Hyperparathyriodism-Jaw Tumor Syndrome

ObjectiveTo present the case of a hyperparathyroidism-jaw tumor (HPT-JT) patient with a novel nonsense mutation of the CDC73 gene.MethodsWe present the case of a patient with a history of three prior maxillectomies and two prior parathyroidectomies who presented with recurrent primary hyperparathyroidism (PHPT). We also briefly review the literature pertaining to HPT-JT.ResultsGenetic analysis revealed a novel nonsense mutation (c.85G>T; pGlu29) in exon 1 of CDC73. The patient’s son underwent genetic testing for a CDC73 mutation and was found to be negative.ConclusionHPT-JT is a rare condition characterized by PHPT and benign tumors of the mandible and maxilla. Up to 15% of HPT-JT patients with PHPT have parathyroid carcinoma. HPT-JT is associated with an inactivating mutation of CDC73, a gene that codes for the tumor suppressor protein parafibromin. This report expands our understanding of the genetics underlying this rare disorder and emphasizes the importance of early detection in order to prevent hypercalcemic complications such as parathyroid carcinoma. (Endocr. Pract. 2013;19:e134-e137)     

Intraoperative Diagnostic Strategy to Distinguish Parathyroid Adenomas from Metastatic Thyroid Cancer

ObjectiveTo report the limitations of frozen section examination and the value of intraoperative tissue aspiration for parathyroid hormone assay to distinguish parathyroid adenomas from metastatic thyroid carcinoma.MethodsWe describe 2 patients with a biochemical diagnosis of primary hyperparathyroidism who underwent intraoperative frozen section analysis of suspected parathyroid tumors. Parathyroid gland aspiration for parathyroid hormone was also performed for confirmation.ResultsThe intraoperative frozen section examination of the suspected parathyroid tumors inaccurately identified the tumors as follicular carcinomas. The parathyroid gland aspirate, however, accurately substantiated the presence of parathyroid adenomas, rather than follicular cancers.ConclusionAspiration of a suspected parathyroid tumor for parathyroid hormone assay accurately determines whether a nodule is a parathyroid gland and facilitates intraoperative decision making, especially when frozen section diagnosis is misleading. (Endocr Pract. 2009; 15:454-457)     

Imaging Localization and Surgical Approach in the Management of Ectopic Parathyroid Adenomas

Objective: (1) Review the anatomy and epidemiology of ectopic parathyroid adenomas (EPAs), (2) summarize the role of relevant imaging modalities in the localization of EPAs, and (3) characterize surgical approaches for various ectopic locations.Methods: Literature review of published English-language articles from 1995 through August 2017.Results: Summary of the literature indicates that the prevalence of EPA is approximately 20% in unexplored patients with primary hyperparathyroidism, but it is as high as 66% in re-operative patients. EPAs may be located anywhere from the carotid bifurcation to the aorto-pulmonary window. Ultrasound has limited accuracy in identifying EPAs except near the thyroid and thyrothymic ligament and requires expert experience from the user. Among dual-phase ^99mTc sestamibi scintigraphy techniques, hybrid imaging with both single-photon emission computed tomography (SPECT) and computed tomography (CT) (SPECT/CT) is superior to planar scintigraphy or SPECT alone at localizing EPAs. Four-dimensional computed tomography (4DCT) precisely delineates important anatomic relationships and is highly sensitive in localizing EPAs. Although 4DCT requires radiation, intravenous iodinated contrast, and reader experience, it is well-equipped to detect lesions at various ectopic sites and guide the surgical approach. EPAs frequently require alternative surgical approaches. Re-operative parathyroidectomy may be attempted in patients having previously undergone bilateral neck exploration by an experienced surgeon once the lesion is colocalized by 2 repeat imaging modalities. Removal of nonlocalized disease requires a careful and systematic exploration of superior and inferior gland locations.Conclusion: EPAs pose challenges during both localization and surgical removal. High-volume experience and multidisciplinary care are necessary for optimal outcomes.Abbreviations: CT = computed tomography; 4DCT = 4-dimensional CT; EPA = ectopic parathyroid adenoma; EPG = ectopic parathyroid gland; PHPT = primary hyperparathyroidism; RLN = recurrent laryngeal nerve; SPECT = single-photon emission computed tomography; TE = tracheo-esophageal     

Receiver Operating Characteristic Analysis of Intraoperative Parathyroid Hormone Monitoring to Determine Optimum Sensitivity and Specificity: Analysis of 896 Cases

Objective: While intraoperative parathyroid hormone (IOPTH) monitoring with a ≥50% drop commonly guides the extent of exploration for primary hyperparathyroidism (pHPT), receiver operating characteristic (ROC) analysis has not been performed to determine whether other criteria yield better sensitivity and specificity. The aim of this study was to identify the optimum percent change of IOPTH following removal of the abnormal parathyroid pathology, in order to predict biochemical cure. Secondary aims were to identify patient subgroups with increased area under the ROC curve (AUC) and the need for moderated criteria.Methods: A retrospective review was performed on patients undergoing primary parathyroid surgery for sporadic pHPT between 1999 and 2010 at a tertiary center for endocrine surgery. Eight hundred and ninety-six patients with primary hyperparathyroidism were included. Multigland disease (MGD) was defined as the intraoperative detection of more than 1 enlarged hypercellular gland or persistent disease after single gland excision. ROC analysis was used to determine the value with the best performance at predicting MGD, following bilateral exploration.Results: MGD was diagnosed in 174 patients (19.4%). ROC analysis demonstrated an AUC of 0.69. An IOPTH drop of 72% was the point of optimal discrimination with a sensitivity of 55% and specificity of 76% for predicting MGD. Subgroup analysis by preoperative calcium, preoperative PTH, localization studies, or pre- and post-excision IOPTH, did not identify any factors associated with an improved AUC.Conclusion: To our knowledge, this is the first study to use ROC analysis in a large patient cohort. An IOPTH drop of 72% was found to have optimal discriminating ability. We failed to identify a subset of patients for whom there was substantial improvement in the AUC, sensitivity, or specificity.Abbreviations: AUC = area under the ROC curve; BE = bilateral neck exploration; FE = focal parathyroid exploration; IOPTH = intraoperative parathyroid hormone; MGD = multigland disease; MIBI = Tc99m-sestamibi I-123 subtraction single-photon emission computed tomography/computed tomography; pHPT = primary hyperparathyroidism; ROC = receiver operating characteristic; SGD = single gland disease; US = surgeon-performed neck ultrasound     

Thyroid-Related Factors that Influence Preoperative Localization of Parathyroid Adenomas

ObjectiveTo evaluate the effect that thyroid-related factors have on the preoperative localization of parathyroid adenomas.MethodsThis retrospective study included adult patients who were referred for further evaluation of primary hyperparathyroidism between December 2005 and October 2009 at a teaching and research hospital in Turkey. High-frequency ultrasonography and sestamibi scintigraphy (MIBI) were performed in all patients. Surgical procedure involved focal or bilateral exploration on the basis of concordant or discordant imaging studies. Selection of patients for minimally invasive parathyroidectomy was made based on the presence or absence of a single parathyroid adenoma detected by both ultrasonography and MIBI scan. Patients with negative or discordant imaging studies and a concomitant thyroid nodule underwent bilateral neck exploration.ResultsTwo hundred and forty-eight patients with primary hyperparathyroidism who underwent parathyroidectomy were included in the study. Parathyroid gland abnormalities were successfully detected preoperatively by ultrasonography in 231 patients and by MIBI scan in 152 patients. When used together, ultrasonography and MIBI scan were unsuccessful in detecting an abnormality in 11 cases. MIBI scan visualized a lesion in 6 cases that remained undiagnosed by ultrasonography. Fifty-six of 85 patients with lesions detected by ultrasonography, but not by MIBI scan, had thyroid nodules. The frequency of thyroid nodules was higher in the 96 patients in whom a MIBI scan could visualize a parathyroid lesion than in the 152 patients in whom MIBI scan was successful (P = .004). No difference was observed regarding ipsilateral thyroid lobe involvement or nodule volume. Parathyroid adenomas were significantly smaller in patients with negative MIBI scans (P < .001).ConclusionOur results suggest that ultrasonography is more sensitive than MIBI scan in the detection of parathyroid adenomas, particularly in the presence of small parathyroid adenomas or other thyroid related-factors. (Endocr Pract. 2012;18:26-33)     

HRPT2- (CDC73) Related Hereditary Hyperparathyroidism: A Case Series From Western India

Objective: To describe a case series of HRPT2- (CDC73) related hereditary primary hyperparathyroidism (PHPT) from western India.Methods: We present a case series of 4 families (7 patients) with PHPT caused by CDC73 gene mutations.Results: The mean age of presentation of the 4 index cases was 27.25 ± 9.8 years. Two family members were identified through biochemical screening (Cases 1b and 2b), while 1 mutation-positive family member did not manifest any features of PHPT or hyperparathyroidism jaw tumor syndrome (HPT-JT) syndrome (Case 2c). Biochemistry showed increased serum calcium (mean: 13.21 ± 1.24 mg/dL), low serum phosphorus (mean: 1.78 ± 0.44 mg/dL), and high parathyroid hormone (PTH, mean: 936 ± 586.9 pg/mL).All patients had a uniglandular presentation and underwent single adenoma excision initially except Cases 2a and 2b, who underwent subtotal parathyroidectomy at baseline. Two cases experienced PHPT recurrence (Cases 3 and 4), while 1 remained uncured due to parathyroid carcinoma (Case 1a). Other associated syndromic features like ossifying jaw fibromas were present in 2 patients, renal cysts in 3 patients, and uterine involvement in 2 patients. Two families had novel germline CDC73 mutations (Families 1 and 3), while the other 2 had reported mutations. Family 2 had familial isolated PHPT without any other features of HPT-JT syndrome.Conclusion: Our findings reaffirm the need for genetic analysis of patients with PHPT, especially those with younger age of disease onset; recurrent disease; and associated features like polycystic kidneys, endometrial involvement, ossifying jaw tumors, or parathyroid carcinoma.Abbreviations: FIHP = familial isolated hyperparathyroidism HPT-JT = hyperparathyroidism jaw tumor syndrome PHPT = primary hyperparathyroidism PTH = parathyroid hormone ⁹⁹Tc = ⁹⁹Technetium     

Endoscopic Ultrasound-Guided Fine-Needle Aspiration With Aspirate Assay to Diagnose Suspected Mediastinal Parathyroid Adenomas

ObjectiveTo describe our experience with mediastinal parathyroid adenomas diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUSFNA) and measurement of parathyroid hormone.MethodsWe describe the clinical and pathologic findings and diagnostic techniques used in 2 study patients.ResultsPatient 1 was a 54-year-old man with persistently elevated serum calcium and parathyroid hormone concentrations despite removal of a right inferior parathyroid adenoma. An echoendoscope was used to identify the lesion and to perform FNA. The parathyroid hormone concentration measured in the aspirated material was 1800 pg/mL. Pathologic examination of the resected specimen revealed a 29.7-g parathyroid adenoma. Patient 2 was an 86-year-old woman with recurrent hyperparathyroidism. A linear array echoendoscope was used to perform FNA of the lesion in her mediastinum. The parathyroid hormone concentration measured in the aspirated specimen was 6905 pg/mL.ConclusionsPreoperative localization of recurrent or persistent hyperparathyroidism is often difficult. EUSFNA allows evaluation of masses, such as those found in the mediastinum, that are poorly evaluated by other imaging modalities. This technique may be a useful adjunct in diagnosing mediastinal parathyroid adenomas. (Endocr Pract. 2010;16:437-440)     

Neuroendocrine Thymic Carcinoma Metastatic to the Parathyroid Gland that was Reimplanted into the Forearm in Patient with Multiple Endocrine Neoplasia Type 1 Syndrome: A Challenging Management Dilemma

ObjectiveTo describe a unique case of a metastatic thymic carcinoma to the hyperplastic parathyroid gland and to present a challenging management dilemma.MethodsOur patient is 60-year-old, intellectually disabled man with history of the multiple endocrine neoplasia type 1 (MEN1) syndrome, a surgery in 1985 for hypercalcemia with removal of one parathyroid gland, surgery in 2007 with findings of extensively necrotic well differentiated neuroendocrine carcinoma (carcinoid tumor) of the thymus. In 2012, he presented with persistent hypercalcemia (calcium level 11.7 mg/dL [range, 8.6-10.2]), and a parathyroid hormone (PTH) level of 225 pg/mL (range, 15-65 pg/mL). He underwent a repeat neck exploration with removal of 2 small inferior and a large left superior 4.5 × 2.5 × 1.5cm parathyroid glands, all of which showed hyperplasia on intraoperative frozen section. A small portion of the superior gland was reimplanted into the patient’s forearm. Final pathology showed the presence of a focus of neuroendocrine tumor within the left superior parathyroid gland with immunostain identical to the thymic carcinoma. His postoperative PTH level was 14 pg/mL and calcium 8.5 mg/dL. A positron emission tomography – computed tomography (PET-CT) and octreotide scans revealed an extensive metastatic disease within the lung, mediastinum, and bones.ResultsWe decided to leave a portion of the reimplanted parathyroid gland with possible metastatic thymic carcinoid in his forearm because of the presence a widespread metastatic disease and his intellectual disability that would result in noncompliance with calcium replacement in case of permanent hypocalcemia.ConclusionMetastatic thymic carcinoma to the parathyroid gland has never been reported in the literature. We have described the first case and presented a challenging management dilemma. (Endocr Pract. 2013;19:e163-e167)     

Intrathyroidal Parathyroid Carcinoma as Cause of Hypercalcemia and Pitfall of Localization Techniques: Clinical and Biologic Features

ObjectiveTo describe an unusual case of intrathyroidal parathyroid carcinoma (PC), which was retrospectively diagnosed in a woman who underwent surgical treatment of a recurrent nodular goiter.MethodsWe report the clinical and biologic features of an intrathyroidal PC, discuss the challenges with distinguishing PC from parathyroid adenoma, and review the related literature.ResultsA 67-year-old woman sought medical attention for dysphagia attributable to the recurrence of a normal functioning multinodular goiter. Thyroid ultra-sonography disclosed a 3-cm solid inferior nodule. Because she refused surgical treatment and a trial of levothyroxine was unsuccessful, periodic follow-up examinations were scheduled. At 1-year follow-up, hypercalcemia (12.1 to 12.6 mg/dL) and low phosphorus levels (2.0 to 2.3 mg/dL) were found, and parathyroid hormone (PTH) levels were profoundly increased (481 to 721 pg/mL). Neck ultrasonography showed a large hypoechogenic solid nodule, not clearly cleaved from the right thyroid lobe, which was possibly compatible with an enlarged parathyroid gland; however, a sestamibi scan was negative. During total thyroidectomy, intraoperative frozen sections of the intrathyroid nodule were compatible with nodular goiter with cellular pleomorphism. Final histologic examination showed cellular nests with nuclear pleomorphism and invasive behavior into the thyroid tissue and likely into the vessels, in conjunction with immuno-histochemical negativity for thyroglobulin and strong positivity for PTH. These findings were highly suggestive of and supported the diagnosis of PC. Postoperatively, calcium levels normalized, and PTH values declined considerably but remained slightly increased. Vitamin D supplementation helped normalize the PTH levels. The patient has undergone follow-up for 5 years and has shown no morphologic or biochemical signs of tumor recurrence.ConclusionPC is a rare entity but should be suspected in patients with hypercalcemia, substantially increased PTH levels, and a neck mass. In such patients, techniques such as sestamibi scanning may fail to localize the neoplasm. Surgical treatment remains the preferred technique for an optimal outcome of the disease. Nevertheless, lifelong follow-up is necessary. (Endocr Pract. 2007;13:176-181)     

Three large, functioning cystic parathyroid adenomas

ObjectiveTo report a very rare case of 3 large, functioning cystic parathyroid adenomas causing primary hyperparathyroidism.MethodsWe present the history, clinical findings, laboratory test results, radiologic findings, endocrine workup results, intraoperative surgical challenges, and surgical pathology report of the study patient. We review the literature and discuss the importance of intraoperative parathyroid hormone (PTH) measurement in such cases.ResultsA 79-year-old woman presented with primary hyperparathyroidism and elevated levels of calcium and PTH. Localization studies confirmed the presence of a large right upper parathyroid adenoma. On exploration, a very large cystic parathyroid gland was identified at that location. Because intraoperative PTH levels remained elevated, further exploration was pursued, which revealed 2 more large cystic glands on the left side that were resected. This resulted in an adequate but slow PTH drop. The right lower gland appeared normal. On follow-up 4 days and 6 weeks after surgery, the calcium and PTH levels had normalized.ConclusionThis case highlights the aspects of intraoperative PTH use and underscores the need to exclude multigland disease even in the setting of a very large parathyroid cyst with concordant localization studies. (Endocr Pract. 2012;18:e14-e16)     

Genome-Wide and Locus Specific Alterations in CDC73/HRPT2-Mutated Parathyroid Tumors

Mutations in the hyperparathyroidism type 2 (HRPT2/CDC73) gene and alterations in the parafibromin protein have been established in the majority of parathyroid carcinomas and in subsets of parathyroid adenomas. While it is known that CDC73-mutated parathyroid tumors display specific gene expression changes compared to CDC73 wild-type cases, the molecular cytogenetic profile in CDC73-mutated cases compared to unselected adenomas (with an expected very low frequency of CDC73 mutations) remains unknown. For this purpose, nine parathyroid tumors with established CDC73 gene inactivating mutations (three carcinomas, one atypical adenoma and five adenomas) were analyzed for copy number alterations and loss of heterozygosity using array-comparative genomic hybridization (a-CGH) and single nucleotide polymorphism (SNP) microarrays, respectively. Furthermore, CDC73 gene promoter methylation levels were assessed using bisulfite Pyrosequencing. The panel included seven tumors with single mutation and three with double mutations of the CDC73 gene. The carcinomas displayed copy number alterations in agreement with previous studies, whereas the CDC73-mutated adenomas did not display the same pattern of alterations at loci frequently deleted in unselected parathyroid tumors. Furthermore, gross losses of chromosomal material at 1p and 13 were significantly (p = 0.012) associated with parathyroid carcinomas as opposed to adenomas. Quantitative PCR-based copy number loss regarding CDC73 was observed in three adenomas, while all the carcinomas were diploid or showed copy number gain for CDC73 gene. Hypermethylation of the CDC73 gene promoter was not observed. Our data could suggest that CDC73-mutated parathyroid adenomas exhibit a partly unique cytogenetic profile in addition to that of carcinomas and unselected adenomas. Furthermore, CDC73-mutated carcinomas displayed losses at 1p and 13 which are not seen in CDC73-mutated adenomas, making these regions of interest for further studies regarding malignant properties in tumors from CDC73-mutated cases. However, due to the small sample size, validation of the results in a larger cohort is warranted.     

Parathyroid Carcinoma in Multiple Endocrine Neoplasia Type 1 with a Classic Germline Mutation

ObjectiveTo report the case of a patient with multiple endocrine neoplasia type 1 (MEN 1) syndrome with concomitant parathyroid carcinoma and a classic MEN1 germline mutation.MethodsWe present the clinical findings, laboratory results, imaging studies, and surgical histopathologic features in a woman with MEN 1 syndrome and concomitant parathyroid carcinoma. We also review the literature regarding patients with similar clinical entities and the use of adjuvant radiotherapy for parathyroid carcinoma.ResultsA 53-year-old woman presented with nausea and severe primary hyperparathyroidism. Computed tomography revealed parathyroid masses, shown later to be bilateral parathyroid carcinomas and adenomas. Magnetic resonance imaging demonstrated a pituitary macroadenoma, and gastrinomas were confirmed by computed tomography and a secretin stimulation test. She was successfully treated with total thyroidectomy, subtotal parathyroidectomy, and adjuvant radiotherapy. Genetic analysis revealed a classic MEN1 germline mutation.ConclusionThis report describes a patient with parathyroid carcinoma occurring in conjunction with MEN 1, further characterizing this rare condition. In contrast to previously described patients, our patient is the first with a classic MEN1 germline mutation, confirming that parathyroid cancer can occur in association with classic MEN 1 genetics. (Endocr Pract. 2009;15:567-572)     

Identifying Parathyroid Hormone Disorders and their Phenotypes through a Bone Health Screening Panel: It's not Simple Vitamin D Deficiency!

Objectives: To determine the utility of bone health screening panels in identifying disorders of parathyroid gland secretions.Methods: A retrospective analysis of biochemical parameters in a bone health screening panel (BHSP) was conducted. Low and high cutoffs were applied to determine hypofunctioning and hyperfunctioning conditions related to parathyroid hormone. Clinical phenotypes of parathyroid gland abnormalities were determined using a combination of levels of calcium, 25-hydroxyvitamin D, and intact parathyroid hormone (iPTH). A PTH nomogram was applied to calculate the maximum expected PTH for existing levels of 25-hydroxyvitamin D. Medical records of patients were reviewed for clinical validation of biochemical findings.Results: Sixty-eight percent of subjects showed abnormal PTH secretion. Primary hyper- and hypoparathyroidism were detected in 1% (n = 5) and 0.4% (n = 2) of subjects, respectively. Normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high-normal PTH were identified in 8.5% (n = 37) and 2% (n = 10) of subjects, respectively. All subjects with primary and normocalcemic hyperparathyroidism had higher measured PTH than calculated maximum PTH using the PTH nomogram. Secondary hyperparathyroidism and functional hypoparathyroidism were present in 18% (n = 88) and 39% (n = 194) of subjects, respectively. High prevalence of bone pains, renal stones, and low bone mineral density were identified in patients with abnormal PTH secretion.Conclusion: Panel testing is useful in early diagnosis of metabolic bone disorders related to PTH. A BHSP helps identify normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high PTH.Abbreviations:25OHD = 25-hydroxyvitamin DAKUH = Aga Khan University HospitalBHSP = bone health screening paneliPTH = intact parathyroid hormonemaxPTH = maximum parathyroid hormoneMBD = metabolic bone diseaseNCHPT = normocalcemic hyperparathyroidismPHPT = primary hyperparathyroidismPTH = parathyroid hormoneSHPT = secondary hyperparathyroidismVDD = vitamin D deficiency     

Optimization of Minimally Invasive Radio-Guided Parathyroidectomy: The Importance of Neck Ultrasonography and Intraoperative Parathyroid Hormone Assay

ObjectiveTo determine whether close collaboration between a neck ultrasound–certified endocrinologist and a skilled endocrine surgeon can optimize minimally invasive radio-guided parathyroidectomy (MIRP) surgical outcomes.MethodsOutcome data were collected on patients with primary hyperparathyroidism whom we intended to treat with MIRP at the induction of anesthesia between October 1, 2005, and December 31, 2007. Patients underwent preoperative gamma camera sestamibi scanning (GCSS), intraoperative gamma probe sestamibi scanning (IOSS), and preoperative neck ultrasonography. Intraoperative parathyroid hormone (PTH) monitoring was performed. Postoperative surgical success was defined as a serum calcium concentration between 8.0 and 10.4 mg/dL within 4 weeks of surgery.ResultsDuring the study period, MIRP was planned for 46 patients. Of the 46 patients, 39 had preoperative neck ultrasonography; 7 underwent evaluation by an endocrinologist or internist who was not ultrasound certified and they therefore did not undergo preoperative ultrasonography. IOSS correctly identified 1 adenomatous gland in 38 of 46 patients (83%), while GCSS correctly localized 1 adenomatous gland in 30 of 46 patients (65%). In 11 GCSS–negative patients, IOSS identified the abnormal gland in 7 (64%), while ultrasonography identified the abnormal gland in 8 (73%). The surgical approach was converted to traditional parathyroidectomy in 3 patients. Every patient exhibited at least a 51% drop in intraoperative PTH levels with resection of the final adenoma; average decrement for the entire group was 79 ± 8% from the highest baseline level. Forty-five patients (98%) demonstrated sustained normalization of serum calcium within several days of surgery.ConclusionA collaborative endocrinology and surgical endocrine oncology practice arrangement, emphasizing careful preoperative physician-supervised neck ultrasonography and the use of intraoperative PTH measurement, optimizes MIRP outcomes. (Endocr Pract. 2008;14: 856-862)     

Pre-Operative Localization of Parathyroid Adenoma: Performance of 4D Mri Parathyroid Protocol

Objective: Accurate pre-operative image localization is critical in the selection of minimally invasive parathyroidectomy as a surgical treatment approach in patients with primary hyperparathyroidism (PHPT). Sestamibi scan, ultrasound, computed tomography, and conventional magnetic resonance imaging (MRI) has varying accuracy in localizing parathyroid adenoma (PTA). Our group has previously shown that four-dimensional (4D) MRI is more accurate than conventional imaging in identifying single adenomas. In this study, we set out to determine if it is possible to accurately localize the quadrant of the adenoma using 4D MRI.Methods: We analyzed and matched the quadrants of PTA identified by pre-operative 4D-MRI with the operative findings during parathyroidectomy for PHPT at our institution during the study period. All resections were confirmed to be successful with an adequate decrease in intraoperative parathyroid hormone as defined by the Miami criterion.Results: A total of 26 patients with PHPT underwent pre-operative localization with the 4D MRI parathyroid protocol. Fourteen patients had true single-gland adenoma (SGA) and 12 patients had multi-gland disease (MGD). 4D MRI accurately identified all the SGA. Using this method, we were also able to localize the adenoma in the correct quadrant in 14 of the 18 patients with SGA. All 3 double adenomas were accurately identified using 4D MRI; however, MGD was only accurately identified 67% of the time. The 4D MRI had an overall 85% accuracy in distinguishing SGA from MGD.Conclusion: 4D MRI accurately identified single and double adenomas in their respective quadrants. However, accuracy was lower with MGD.Abbreviations: BNE = bilateral neck exploration; CT = computed tomography; IOPTH = intra-operative parathyroid hormone; MGD = multi-gland disease; MIBI = sestamibi; MIP = minimally invasive parathyroidectomy; MRI = magnetic resonance imaging; PHPT = primary hyperparathyroidism; PTA = parathyroid adenoma; PTH = parathyroid hormone; SGA = single-gland adenoma; SPECT = single photon emission computed tomography; 4D = four-dimensional     

Unusual Manifestation of Parathyroid Carcinoma in the Setting of Papillary Thyroid Cancer

ObjectiveTo describe a rare manifestation of parathyroid carcinoma in association with papillary thyroid carcinoma.MethodsWe describe the clinical history, findings on physical examination, results of laboratory studies, imaging findings, and histopathologic features of a woman with 2 previously palpable thyroid nodules and mild hypercalcemia.ResultsA 79-year-old woman presented to our endocrinology clinic for reevaluation of 2 thyroid nodules and long-standing hyperparathyroidism. She initially had undergone assessment 6 years previously, at which time an intact parathyroid hormone level was 89 pg/mL (reference range, 10 to 69) and the serum calcium concentration was 10.4 mg/dL (reference range, 8.2 to 10.2) in conjunction with normal alkaline phosphatase, creatinine, and 25-hydroxyvitamin D levels. Subsequently, she was found to have multifocal papillary thyroid cancer in the right thyroid lobe and a 5-cm parathyroid carcinoma in the left side.ConclusionSynchronous parathyroid and thyroid carcinomas are extremely rare. To our knowledge, our current case is the first documented patient with parathyroid carcinoma who had a clinical presentation consistent with longstanding mild adenoma in addition to synchronous papillary thyroid carcinoma. (Endocr Pract. 2010;16:664-668)