Hiperparatiroidismo primario por carcinoma paratiroideo: caso problema y revisión / Primary hyperparathyroidism by parathyroid cancer: case report and review

El carcinoma paratiroideo (CP) es una neoplasia maligna con una incidencia de 0,015 cada 100.000 habitantes por año. Representa el 1% de los diagnósticos de hiperparatiroidismo primario y se manifiesta entre la 4.a y 5.a década de la vida, con una incidencia similar entre hombres y mujeres. La etiología del CP es incierta, ha sido asociada a formas esporádicas o familiares. Está caracterizado por altos niveles séricos de calcio y PTH y el desafío clínico-quirúrgico es el diagnóstico diferencial con otras entidades benignas como el adenoma o la hiperplasia de paratiroides. Aunque el diagnóstico de certeza es anatomopatológico, la sospecha clínica y el uso de métodos de baja complejidad (ecografía) con operadores avezados permite una correcta localización y abordaje pertinente del paciente para dirigir el tratamiento quirúrgico adecuado (resección en bloque) evitando persistencias y recurrencias de enfermedad. Se presenta el caso clínico de un paciente masculino que ingresa por síndrome de impregnación asociado a hipercalcemia, su abordaje diagnóstico, tratamiento y manejo interdisciplinario con discusión y revisión bibliográfica. (AU)

Parathyroid carcinoma (CP) is a malignant disease with an incidence of 0.015 per 100,000 inhabitants per year. It accounts for 1% of primary hyperparathyroidism diagnoses and occurs between the 4th and 5th decade of life, with a similar incidence between men and women. The etiology of CP is uncertain and has been associated with sporadic or family forms. CP is characterized by high serum calcium and PTH levels and the clinical-surgical challenge is the differential diagnosis with other benign entities such as parathyroid adenoma or hyperplasia. Although the diagnosis of certainty is achieved by pathological anatomy examination, the clinical suspicion and the use of low complexity methods (ultrasound) by experienced operators allows a correct localization and a patient-specific approach to direct the appropriate surgical treatment (block resection), avoiding persistence and recurrences of disease. The clinical case of a male patient admitted for severe hypercalcemia with multiple organ disfunction, the diagnostic approaches, treatment, and interdisciplinary management, together with review and discussion of the current literature are presented. (AU)

Persistent Hypercalcemia Crisis and Recurrent Acute Pancreatitis Due to Multiple Ectopic Parathyroid Carcinomas: Case Report and Literature Review of Mediastinal Parathyroid Carcinoma.

Mediastinal parathyroid carcinoma (PC) is a rare entity in primary hyperparathyroidism. The aim of this report is to demonstrate a case of mediastinal PC, and to provide a systemic literature review of this rare condition. A 34-year-old woman who had already undergone two cervical operations for hyperparathyroidism suffered from another recurrence, presenting with recurrent acute pancreatitis and persistent hypercalcemic crisis. Technetium-99 methoxyisobutylisonitrile imaging (MIBI) and computed tomography scanning (CT) identified three possible parathyroid tumors, one of which was the recurrence of residual tumor locating in the thyroid region, while the other two were ectopic tumors locating in the suprasternal fossa and thymus region, respectively. Pathological examination confirmed the diagnosis of PC. We conducted a systemic literature review by searching the PubMed MEDLINE from 1951 to 2019 for studies of all types in the English language only, using terms "mediastinal, mediastinum, parathyroid, carcinoma." Including our reported case, a total of 21 cases with ectopic mediastinal PCs were assessed for demographic data, tumor location and size, biochemical findings, and symptomatology, etc. Two thirds of the patients were men, with a mean age of 44 years old, a mean serum calcium of 14.2 mg/dl, and a mean serum intact parathyroid hormone of 1,216 pg/ml. We identified 89.5% of carcinomas in the anterosuperior mediastinum, and 10.5% in the middle mediastinum, with a mean diameter of 54 mm, and a mean weight of 216 g. MIBI and CT were the most commonly used methods to localize these mediastinal tumors, with 69.2 and 100% sensitivity, respectively. Half of the patients underwent more than one operation. Diagnosis and treatment of mediastinal PCs represent a challenge. Early suspicion, appropriate preoperative localization studies, and the cooperation of endocrinologists and surgeons are crucial in the effective management.

The Usefulness of Maximum Standardized Uptake Value at the Delayed Phase of Tc-99m sestamibi single-photon emission computed tomography/computed tomography for Identification of Parathyroid Adenoma and Hyperplasia.

Tc-99m sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has been used to help surgeons explore the location of parathyroid diseases, but quantitative parameters have not been systemically investigated for this purpose. We aimed to establish objective criteria for adenoma and hyperplasia using the standardized uptake value (SUV) in patients with hyperparathyroidism.Thirty-nine hyperparathyroid patients (male/female: 17/22, age: 58.33 ±â€Š11.69 years) with at least 1 uptake-positive lesion of any degree by visual assessment in preoperative Tc-99m sestamibi quantitative SPECT/CT were included from Oct 2015 to Oct 2017. Pathologically, 44 lesions (32 adenomas and 12 hyperplasia) were identified. All patients experienced normalized levels of intact parathyroid hormone immediately after surgery. Quantitative SPECT/CT was performed at 10 minute and 2 hour post injection of Tc-99m sestabmibi (dose = 740 MBq), and maximum SUV (SUVmax) was measured for the parathyroid lesions. Experienced pathologists evaluated the percentage cellular proportions of chief cells, oxyphil cells, and clear cells.SUVmax (g/mL) of adenomas, hyperplasia, and reference thyroid tissue were 12.92 ±â€Š6.68, 7.90 ±â€Š5.49, and 7.01 ±â€Š2.62 at 10min (early phase), decreasing to 7.46 ±â€Š5.66, 4.65 ±â€Š3.14, and 2.21 ±â€Š1.07 at 2 hour (delayed phase), respectively. The adenomas showed significantly higher SUVmax than both the hyperplasia (P = .0131) and reference thyroid tissue (P < .0001) along the early and delayed phases, but the SUVmax of the hyperplasia did not differ from that of the reference thyroid tissue (P = .4196). The adenomas and hyperplasia were discriminated from the reference thyroid tissue using a cutoff SUVmax of 3.26 at the delayed phase. The adenomas had lower %proportions of oxyphil cells than the hyperplasia (P = .0054), but its SUVmax at the delayed phase was positively correlated with the %proportions of mitochondria-abundant oxyphil cells (rho = 0.418, P = .0173). The hyperplasia showed no correlation between SUVmax and cellular proportions.SUVmax at the delayed phase in the Tc-99m sestamibi quantitative SPECT/CT was useful for the identification and differentiation of parathyroid lesions causing hyperparathyroidism.

HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: New and future perspectives for parathyroid carcinoma.

This report summarizes published data on parathyroid cancer, with the inclusion of topics discussed at MEN2019: 16th International Workshop on Multiple Endocrine Neoplasia, 27-29 March 2019, Houston, TX, USA. An expert panel on parathyroid cancer was constituted by the Steering Committee to address key questions in the field. The objectives were to recap open forum discussion of interested parties from multiple disciplines. The expert panel met in a closed session to consult on the data to be highlighted on the evidence-based results and on the future directions. Preceding the Conference, members of the expert panel conducted an extensive literature search. All presentations were based upon the best peer-reviewed information taking into account the historical and current literature. Questions were developed by the expert panel on parathyroid carcinoma. A comprehensive literature search for relevant studies was undertaken. This report represents the expert panel's synthesis of the conference material placed in a context designed to be relevant to clinicians and those engaged in cutting-edge studies of parathyroid carcinoma. This document not only provides a summary of our current knowledge but also places recent advances in its management into a context that should enhance future advances in our understanding of parathyroid carcinoma.

Gender Predilection in Sporadic Parathyroid Adenomas.

Primary hyperparathyroidism is a common endocrinopathy that is mainly caused by benign parathyroid adenomas. The frequency, clinical presentation and complications of the disease show significant differences between genders, with the majority of cases being reported in postmenopausal women. Due to this gender predilection, several studies have investigated the role of sex hormones in the pathogenesis of the disease and their potential use as targets for optimal and gender-specific management. Epigenetic mechanisms that regulate gene transcription may also contribute to these differences between genders. In this review, we outline what is currently known regarding the role of sex hormones and the recent data on the role of non-coding RNAs in the differences between genders in primary hyperparathyroidism due to sporadic parathyroid adenomas.

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.

Parathyroid carcinoma arising from auto-transplanted parathyroid tissue after Total Parathyroidectomy in chronic kidney disease patient: a case report.

BACKGROUND: Secondary hyperparathyroidism is a common complication in patients with chronic kidney disease that requires vigilant treatment due to its high mortality rate. Pharmacologic therapy is recommended as an initial treatment; if there is no response, a total parathyroidectomy is performed. In some cases, surgery is accompanied by auto-transplantation of parathyroid tissue. CASE PRESENTATION: The patient was diagnosed with chronic kidney disease and received a kidney transplant. However, due to rejection of the transplanted kidney, medical nephrectomy was carried out and routine hemodialysis was initiated and observed. At this time, secondary hyperparathyroidism with elevated parathyroid hormone and hyperphosphatemia developed and pharmacologic treatment was applied. However, there was no response to pharmacologic treatment; therefore, total parathyroidectomy with auto-transplantation was performed. Eight years after surgery, a growing mass was observed in the transplantation site, accompanied by an elevation of parathyroid hormone. A complete resection of the mass was performed, and the patient was diagnosed with parathyroid carcinoma. Additional adjuvant radiation therapy was ordered, and the patient is being monitored. CONCLUSIONS: This is a rare but remarkable case of parathyroid carcinoma arising from auto-transplanted parathyroid tissue after total parathyroidectomy in a patient with secondary hyperparathyroidism. We suggest caution should be taken when choosing to auto- transplant parathyroid tissue and that careful postoperative observation should be performed.

Current concepts in parathyroid carcinoma: a single Centre experience.

BACKGROUND: Parathyroid carcinoma is a rare neoplasm that may present sporadically or in the context of a genetic syndrome. Diagnosis and management are challenging due to the lack of clinical and pathological features that may reliably distinguish malignant from benign disease. METHODS: From January 2013 to December 2017, from 358 consecutive patients affected by parathyroid diseases, 3 patients with parathyroid carcinoma were treated at our academic Department of General Surgery. We present our experience as illustrative of the different features of clinical presentation of parathyroid carcinoma and review its management considering the recent relevant literature. RESULTS: Case 1: A 62-year-old man was hospitalized for left-sided palpable neck mass, hypercalcemia and elevated PTH. US-guided FNA was suspect for parathyroid carcinoma. A large cystic mass was excised in bloc with total thyroidectomy and central neck dissection. Genetic studies framed a pathologically confirmed parathyroid carcinoma within MEN1 syndrome. Case 2: A 48-year-old woman with hypothyroidism had total thyroidectomy performed for a suspect for right follicular thyroid lesion. Pathology revealed parathyroid carcinoma. Case 3: A 47 year-old man was admitted for hypercalcaemic crisis and renal failure in the context of PHPT. A lesion suggestive on US and MIBI scan for parathyroid adenoma in the right lower position was removed by mini-invasive approach. Pathology revealed parathyroid cancer and patient had completion hemythyroidectomy and central neck dissection. CONCLUSION: Parathyroid cancer is a particularly rare endocrine malignancy, however it should be suspected in patients with primary hyperparathyroidism when severe hypercalcemia is associated to cervical mass, renal and skeletal disease. Parathyroid surgery remains the mainstay of treatment. Radical tumour resection and expedited treatment in a dedicated endocrine Center represent crucial prognostic factors.

Polyclonal origin of parathyroid tumors is common and is associated with multiple gland disease in primary hyperparathyroidism.

BACKGROUND: Parathyroid tumors are mostly considered monoclonal neoplasms, the rationale for focused parathyroidectomy in primary hyperparathyroidism. We reported that flow sorting parathyroid tumor cells and methylation-sensitive polymerase chain reaction (me-PCR) of polymorphic human androgen receptor gene and phosphoglycerate kinase gene alleles in deoxyribonucleic acid reveals that ≤35% of parathyroid tumors are polyclonal. We sought to confirm these findings and assess for clinical relevance. METHODS: Parathyroid tumors from 286 female primary hyperparathyroidism patients were analyzed for clonal status. Tumor clonal status was compared with clinical variables and operative findings. Statistical analysis was performed and significance was established at P < .05. RESULTS: In the study, 176 (62%) patients were informative for human androgen receptor gene and/or phosphoglycerate kinase gene. Assignment of clonal status was made in 119 (68%) tumors, of which 64 (54%) were monoclonal and 55 (46%) were polyclonal. Comparison of tumor clonal status to clinical variables in patients with complete operative data (N = 82) showed that while clinical features were the same between tumor types, patients with polyclonal tumors more often had multiple gland disease (risk ratio 4.066, confidence interval, 1.016-16.26; P = .039) potentially missed at unilateral neck exploration. CONCLUSION: This work confirms that primary hyperparathyroidism is often the result of polyclonal tumors and that parathyroid tumor clonal status may be associated with multiple gland disease.

Comparative Diagnostic Performance of Ultrasonography and 99mTc-Sestamibi Scintigraphy for Parathyroid Adenoma in Primary Hyperparathyroidism; Systematic Review and Meta- Analysis

Objective: Ultrasonography (US) and parathyroid scintigraphy (PS) with 99mTc-MIBI are common methods for preoperative localization of parathyroid adenomas but there discrepancies exist with regard to diagnostic accuracy. The aim of the study was to compare PS and US for localization of parathyroid adenoma with a systematic review and meta-analysis of the literature. Methods: Pub Med, Scopus (EMbase), Web of Science and the reference lists of all included studies were searched up to 1st January 2016. The search strategy was according PICO characteristics. Heterogeneity between the studies was accounted by P < 0.1. Point estimates were pooled estimate of sensitivity, specificity and positive predictive value of SPECT and ultrasonography with 99% confidence intervals (CIs) by pooling available data. Data analysis was performed using Meta-DiSc software (version 1.4). Results: Among 188 studies and after deletion of duplicated studies (75), a total of 113 titles and abstracts were studied. From these, 12 studies were selected. The meta-analysis determined a pooled sensitivity for scintigraphy of 83% [99% confidence interval (CI) 96.358 -97.412] and for ultra-sonography of 80% [99% confidence interval (CI) 76-83]. Similar results for specificity were also obtained for both approache. Conclusion: According this meta- analysis, there were no significant differences between the two methods in terms of sensitivity and specificity. There were overlaps in 99% confidence intervals. Also features of the two methods are similar.

Effectiveness of Intraoperative Parathyroid Monitoring (ioPTH) in predicting a multiglandular or malignant parathyroid disease.

AIM: The main goal of our study was to confirm the usefulness of intra-operative parathyroid hormone (PTH) monitoring (ioPTH) when using minimally invasive techniques for treatment of sporadic Primary hyperparathyroidism (pHTP). Furthermore, we aimed to evaluate if ioPTH monitoring may help to predict the etiology of primary hyperparathyroidism, especially in malignant or multiglandular parathyroid disease. METHODS: A retrospective review of 125 consecutive patients with pHPT who underwent parathyroidectomy between 2001 and 2016 at the Department of General Surgery was performed. For each patient, the specific preoperative work-up consisted of: high-resolution US of the neck by a skilled sonographer, sestamibi parathyroid scan, laryngoscopy, and serum measurement of PTH, serum calcium levels, and serum 25(OH)D levels. RESULTS: The study included 125 consecutive patients who underwent surgery for pHPT. At the histological examination, we registered 113 patients with simple adenomatous pathology (90,4%), 5 atypical adenomas (4%), 3 cases of parathyroid carcinoma (2,4%),, , and 4 histological exams of different nature (3,2%). Overall, 6 cases (4,8%) of multiglandular disease were found. We reported 10 cases (8%) of recurrent/persistent hyperparathyroidism: 1/10 in a patient affected by atypical adenoma, 9/10 in patients with benign pathology. Regarding these 10 cases, in three (30%) patients, ioPTH wasn't dosed (only frozen section (FS) exam was taken), in 5 cases (50%) ioPTH dropped more than 50% compared to basal value (false negative results), and in 2 (20%) cases, ioPTH did not drop >50% from the first samples taken, the extemporary exam had confirmed the presence of adenoma and the probable second hyperfunctioning adenoma was not found. CONCLUSIONS: IoPTH determinations ensure operative success of surgical resection in almost all hyperfunctioning tissue; in particular it is very important during minimally invasive parathyroidectomy, as it allows avoiding bilateral neck exploration. The use of ioPTH monitoring offer increased sensitivity in detecting multiglandular disease and can minimize the need and risk associated with recurrent operations, and may facilitate cost-effective minimally invasive surgery. Moreover, intraoperative PTH monitoring could be a reliable marker to predict a malignant disease during parathyroidectomy, showing higher ioPTH baseline value and superior drop compared to benign disease.

Filamin A is reduced and contributes to the CASR sensitivity in human parathyroid tumors.

Parathyroid tumors display reduced sensitivity to extracellular calcium ([Ca2+]o). [Ca2+]o activates calcium-sensing receptor (CASR), which interacts with the scaffold protein filamin A (FLNA). The study aimed to investigate: (1) the FLNA expression in human parathyroid tumors, (2) its effects on the CASR mRNA and protein expression, and (3) on ERK signaling activation, (4) the effect of the carboxy-terminal CASR variants and (5) of the treatment with the CASR agonist R568 on FLNA-mediated ERK phosphorylation in HEK293 cells. Full-length FLNA immunostaining was variably reduced in parathyroid tumors. Immunofluorescence showed that FLNA localized in membrane and cytoplasm and co-localized with CASR in parathyroid adenomas (PAds)-derived cells. Cleaved C-terminus FLNA fragment could also be detected in PAds nuclear protein fractions. In HEK293 cells transfected with 990R-CASR or 990G-CASR variants, silencing of endogenous FLNA reduced CASR mRNA levels and total and membrane-associated CASR proteins. In agreement, FLNA mRNA levels positively correlated with CASR expression in a series of 74 PAds; however, any significant correlation with primary hyperparathyroidism severity could be detected and FLNA transcript levels did not differ between PAds harboring 990R or 990G CASR variants. R568 treatment was efficient in restoring 990R-CASR and 990G-CASR sensitivity to [Ca2+]o in the absence of FLNA. In conclusion, FLNA is downregulated in parathyroid tumors and parallels the CASR expression levels. Loss of FLNA reduces CASR mRNA and protein expression levels and the CASR-induced ERK phosphorylation. FLNA is involved in receptor expression, membrane localization and ERK signaling activation of both 990R and 990G CASR variants.

[CDC73 mutations in young patients with primary hyperparathyroidism: A description of two clinical cases]. / Mutatsii v gene CDC73 u molodykh patsientok s pervichnym giperparatireozom (opisanie dvukh klinicheskikh sluchaev).

The article describes two clinical cases of severe primary hyperparathyroidism (PHPT) caused by parathyroid carcinoma in young female patients who underwent molecular genetic testing to rule out the hereditary forms of PHPT. In both patients, heterozygous germline nonsense mutations of tumor suppressor gene CDC73 encoding parafibromin (p.R91X and p.Q166X) were identified using next-generation sequencing with Ion Torrent Personal Genome Machine (Thermo Fisher Scientific - Life Technologies, USA). It is the first description of CDC73 mutations in Russia, one of the mutations is described for the first time in the world. Identification of germline mutations in the CDC73 gene in patients with PHPT necessitates regular lifelong screening for other manifestations of hyperparathyroidism-jaw tumor syndrome (HPT-JT), PHPT recurrence due to parathyroid carcinoma as well, and identification of mutation carriers among first-degree relatives.

[Multiple Endocrine Neoplasia I (Wermers Syndrome), Forms of Clinical Manifestation, 5 Case Studies]. / Mnohocetná endokrinní neoplazie I (Wermeruv syndrom) - formy klinické manifestace: 5 kazuistik.

Multiple Endocrine Neoplasia (MEN) is a condition in which several endocrine organs of an individual are affected by adenoma, hyperplasia and less often carcinoma, either simultaneously or at different stages of life. Two existing syndromes, MEN1 and MEN2 (2A, 2B), in literature is also mentioned MEN4, are associated also with other non-endocrine disorders. MEN1 (Wermer syndrome) affects the pituitary, parathyroid, and pancreatic area. 95 % of patients show very early manifestation of hyperparathyroidism, often before 40 years of age. Multiple adenomas gradually involve all four parathyroid glands. The first clinical sign of MEN1 includes recurrent nephrolithiasis. The second most frequent manifestation of MEN1 is pancreatic area (pancreas, stomach and duodenum), again multiple malignancies of varying degree which can metastasize. Most often gastrinomas and insulinomas are involved. Pituitary adenomas occur in about one third of MEN1 patients and tend to be larger and less responsive to treatment. Tumors appearing most often are prolactinomas, tumors producing growth hormone, or afunctional adenomas. The other endocrine tumors include carcinoids and adrenal lesions. In the last year we have registered four MEN1 syndrome patients in our center and one patient has been already followed since 2008. In four out of five patients, nephrolithiasis after 30 years of age was the first clinical symptom, but only one of theses cases resulted in MEN1 diagnosis. In all patients, the clinical symptoms intensified and the diagnosis was established between 36 and 40 years of age. A crutial factor is a cooperation with the urology examination of kidney stones formation in young individuals with nephrolithiasis in order to reveal the potential cases of MEN1 syndrome very early on. Consider the MEN1 genetic diagnostics if recurrent primary hyperparathyroidism or recurrent gastroduodenal ulcer disease appear in patients under 40 years of age.Key words: carcinoid - gastrinoma - hyperparathyroidism - insulinoma - MEN1 - multiple endocrine neoplasia - nefrolithiasis - neuroendocrine tumor - pancreatic area - pituitary gland.

Assessment of operative treatment of patients with tertiary hyperparathyroidism after kidney transplantation.

INTRODUCTION: The purpose of the study was to assess the results of operative treatment of patients with tertiary hyperparathyroidism (tHPT) after kidney transplantation. MATERIAL AND METHODS: The study included 30 patients in whom kidney transplantation was performed between 2006 and 2013, and in whom parathyroidectomy had to be performed at a later time because of tHPT. There were 17 (56.7%) women and 13 (43,3%) men in the group, aged 18-64, mean 46.1 years. In order to locate the lesion before the operation, all patients had to undergo USG, and 14 had scintigraphy MIBI in addition. Serum levels of PTH, ionised calcium, and creatinine were determined together with glomerular filtration rate (GFR). The results of control tests were compared with those performed one day before parathyroidectomy (PTX) and three days after the operation. RESULTS: Among 30 patients, 19 (63.3%) underwent total resection of three parathyroid glands and 3/4 of the fourth. Two parathyroid glands were resected in eight (26.7%) patients, and one in the remaining three (10%) patients. Histopathological examination showed one parathyroid adenoma in six (20%) patients, and one parathyroid adenoma and hyperplasia of the remaining glands in one (3.3%) patient. Five (16.7%) patients had hyperplasia of two parathyroid glands whereas no changes were observed in two patients. On the other hand, hyperplasia of all glands was noted in 18 (60%) patients. Serum PTH level was significantly lower compared to the level before operation (p < 0.001), being 5.5-58.5 pg/mL, on day 3 postoperatively. Differences in the levels of serum-ionised calcium were also significant (p < 0.0001) after eight months. CONCLUSIONS: Surgical resection of parathyroid glands is a management of choice in patients after kidney transplantation accompanied by hypercalcaemia lasting longer than one year. Resection of 3 3/4 parathyroid glands because of hyperplasia in patients with hyperparathyroidism after kidney transplantation enables restoration of normal calcium metabolism. Moreover, resection of 3 3/4 parathyroid glands can allow avoidance of autotransplantation, which is necessary in cases of total resection of parathyroid glands.

Parathyroid adenoma in patients with Graves' disease: a report of 21 cases.

Graves' disease (GD) is frequently associated with mild hypercalcemia. The hypercalcemia may be due to the activation of osteoclastic bone resorption caused by the excess thyroid hormone. In some cases of GD, the hypercalcemia can be attributable to concomitant parathyroid diseases. In this study, 21 patients with a history of GD developed parathyroid adenoma based on histology, intraoperative parathyroid hormone (IOPTH) monitoring, and other clinical features. There were 11 patients with a history of radioactive iodine therapy (RAI) for GD. The latency time of RAI was from 12 to 41 years. The case cohort was divided into two groups: patients with (group GR: 11 patients) and patients without a history of RAI (group G: 10 patients). Mean age of patients in group GR was 54.8 years compared to 62.2 years of group G (P = 0.08). There were no statistically significant differences regarding the parathyroid weight, serum calcium, and pre- and post-parathyroidectomy PTH levels. There was no histopathologic difference between the two groups. In conclusion, we report 21 cases of parathyroid adenoma in patients with Graves' disease. There may be a possible link between GD patients with a RAI history and an increased risk of parathyroid adenoma. The parathyroid adenomas showed no clinicopathological differences between GD patient with and without a history of RAI.

11C-methionine PET/CT after inconclusive 99mTc-MIBI-SPECT/CT for localisation of parathyroid adenomas in primary hyperparathyroidism.

AIM: To investigate the efficacy of PET/CT with 11C-methionine for localizing parathyroid adenomas in patients with suspected primary hyperparathyroidism and inconclusive results of cervical ultrasonography and 99mTc-MIBI-SPECT/CT. PATIENTS, METHOD: Retrospective analysis of imaging data of 18 patients and correlation with clinical outcome, in particular intraoperative findings and histopathology of excised tissue. RESULTS: 12 of 18 patients received surgery. In 10 patients single parathyroid adenomas were found (diameter: 5-20 mm), 2 patients presented parathyroid hyperplasia (5 excised hyperplastic glands (diameter: 2-12 mm). PET/CT correctly localized all adenomas and 1 of 5 hyperplastic glands. The sensitivity per patient was 91.7% (11 of 12), the sensitivity per lesion 73.3% (11 of 15). All lesions missed by PET/CT had a size smaller than 9 mm and a volume of less than 0.2 ml. In 6 patients no surgery was performed. Five of them had a negative or atypical PET/CT. Further follow-up indicated familial hypocalciuric hypercalcemia in 3 of them (thus, PET/CT true negative), in the remaining 2 patients no validation is available. One patient with 2 highly suggestive lesions rejected surgery so far. CONCLUSION: PET/CT with 11C-methionine is a very sensitive method for the detection of parathyroid adenomas, even if they are too small to be visualized by 99mTc-MIBI-SPECT/CT.

Brown tumors of the femur and pelvis secondary to a parathyroid carcinoma: report of one case.

Brown tumors result from excess osteoclast activity and consist of collections of osteoclasts intermixed with fibrous tissue and poorly mineralized woven bone. They are secondary to hyperparathyroidism (HPT). Their incidence is higher in primary than in secondary hyperparathyroidism. We report a 69 years-old male, admitted in a state of confusion, lethargy and bedridden, with a pathological fracture of the femur caused by a brown tumor. The laboratory examination revealed a hypercalcemia (8.85 mEq/L), with high levels of ionized Ca (5.48 mEq/L), serum alkaline phosphatases (416 U/L) and serum parathormone (120 pg/mL). Ultrasound examination of the neck showed a large parathyroid tumor, probably corresponding to a carcinoma. A primary HPT was diagnosed. The patient was hydrated and high doses of diuretics and bisphosphonates were administered. After correction of serum calcium and neurologic symptoms, the patient was operated, performing an extensive resection of the tumor. The pathology report confirmed the diagnosis of parathyroid carcinoma.

Thyroid and parathyroid tumours in patients submitted to X-ray scalp epilation during the tinea capitis eradication campaign in the North of Portugal (1950-1963).

Tinea capitis attained epidemical proportions in the fifth and sixth decades in Portugal, as in other countries. Before starting the utilization of griseofulvin in 1959, the best approach to treat tinea capitis infection was X-ray scalp epilation combined with topical antimycotic ointments. A long-term side effect of this therapy is thyroid disease, namely thyroid cancer; data on parathyroid lesions (hyperplasia, adenoma and carcinoma) are scarce. We observed clinically 1,375 individuals irradiated in childhood for tinea capitis treatment in the North of Portugal with the main purpose of evaluating thyroid and parathyroid tumours as possible sequelae of the irradiation treatment. For each individual, a cervical ultrasound and a serum calcium measurement were proposed. Fine needle aspiration cytology was suggested whenever ultrasound thyroid nodules presented suspicious features. We observed a 54 % frequency of thyroid nodules and a 2.8 % frequency of thyroid carcinoma (38/1,375). Nineteen of the 38 (50 %) carcinomas were diagnosed by us, whereas the remaining 19 carcinomas had been diagnosed and treated prior to our observation. The carcinomas were significantly more frequent in women than in men. Benign excised lesions were also significantly more frequent in women and in patients irradiated at younger ages. Seven women, considered asymptomatic until our clinical observation, had laboratory signs of hyperparathyroidism. The data we have obtained, namely high thyroid cancer frequency, corroborate previous data from childhood irradiated cohorts and highlight the need for the close follow-up of these populations in order to identify and treat early undiagnosed head and neck lesions. No evidence of increased parathyroid disease was found in this cohort of head and neck X-irradiated patients.

Brown tumors of the femur and pelvis secondary to a parathyroid carcinoma: Report of one case / Tumores pardos de fémur y pelvis secundarios a carcinoma de paratiroides: Informe de un caso

Brown tumors result from excess osteoclast activity and consist of collections of osteoclasts intermixed with fibrous tissue and poorly mineralized woven bone. They are secondary to hyperparathyroidism (HPT). Their incidence is higher in primary than in secondary hyperparathyroidism. We report a 69 years-old male, admitted in a state of confusion, lethargy and bedridden, with a pathological fracture of the femur caused by a brown tumor. The laboratory examination revealed a hypercalcemia (8.85 mEq/L), with high levels of ionized Ca (5.48mEq/L), serum alkaline phosphatases (416 U/L) and serum parathormone (120 pg/mL). Ultrasound examination of the neck showed a large parathyroid tumor, probably corresponding to a carcinoma. A primary HPT was diagnosed. The patient was hydrated and high doses of diuretics and bisphosphonates were administered. After correction of serum calcium and neurologic symptoms, the patient was operated, performing an extensive resection of the tumor. The pathology report confirmed the diagnosis of parathyroid carcinoma.

Los tumores pardos son una consecuencia de una actividad osteoclástica excesiva y consisten en osteoclastos mezclados con tejido fibroso y tejido óseo mal mineralizado. Son secundarios a hiperparatiroidismo y más comunes en hiperparatiroidismo primario. Informamos de un hombre de 69 años que ingresa confuso y letárgico con una fractura patológica del fémur causada por un tumor pardo. El laboratorio mostró hipercalcemia de 8,85 mEq/L, fosfatasas alcalinas de 416 U/L y parathormona de 120 pg/mL. La ecografía del cuello mostró un tumor paratiroideo sospechoso de carcinoma. Se diagnosticó un hiperparatiroidismo primario. El paciente se hidrató y estabilizó con diuréticos y bifosfonatos. Una vez estabilizado, se operó efectuando una extensa resección del tumor. El estudio anatomopatológico confirmó el diagnóstico de cáncer de paratiroides.