Multiple pathological fractures and muscle atrophy caused by a parathyroid carcinoma with postoperative hungry bone syndrome: A case report.

BACKGROUND: Parathyroid carcinoma (PC) is a rare endocrine malignancy causing pathological changes such as abnormal bone metabolism, elevated serum calcium, and impaired renal function, and uncontrollable hypercalcemia is the main cause of death in PC patients. The diagnosis of PC is challenging and relying on postoperative histopathology. Radical surgery at the first time is the only effective therapy to cure PC. Hungry bone syndrome (HBS) is a relatively uncommon complication of parathyroidectomy characterized by profound and prolonged hypocalcemia, timely electrolyte monitoring and alternative interventional protocols can prevent symptomatic hypocalcemia. CASE: A 57-year-old man presented with multiple pathological fractures and muscle atrophy as the main symptoms accompanied by bone pain, hypercalcemia, elevated parathyroid hormone (PTH), and an enlarged left-sided neck mass. After consultation of multidisciplinary team, he was treated conservatively with plaster bandage fixation and infusion of intravenous zoledronic acid; and then complete resection of parathyroid mass + removal of involved tissue structures + left thyroid and isthmus lobectomy + lymph node dissection in the VI region in left neck were performed. The postoperative histopathology suggested a diagnosis of parathyroid carcinoma. Calcium and fluid supplementation and oral levothyroxine tablets were given postoperatively. Unexpectedly, the patient's PTH level decreased rapidly at 24 h postoperative, and serum calcium and phosphorus decreased continuously, and he felt numb around perioral sites and fingertips, which considered to be postoperative HBS complicated by parathyroidectomy. Then, a large amount of calcium supplementation and vitamin D were given timely and the patient got better at 1 month postoperatively. At 9-month postoperative, his bone pain and fatigue were significantly relieved compared with before with calcium, phosphorus, and PTH levels at normal range. CONCLUSION: The possibility of parathyroid disease, particularly PC, should be considered in the presence of multiple pathological fractures, muscle atrophy, generalized bone pain, hypercalcemia, and clear neck mass. Radical resection of the tumor lesions at the first surgery is a key element affecting the prognosis of PC, and the effective management of preoperative hypercalcemia and postoperative HBS is also of great significance for improving prognosis.

Persistent hypercalcaemia associated with two pathogenic variants in the CYP24A1 gene and a parathyroid adenoma-a case report and review.

Introduction: 24-Hydroxylase, encoded by the CYP24A1 gene, is a crucial enzyme involved in the catabolism of vitamin D. Loss-of-function mutations in CYP24A1 result in PTH-independent hypercalcaemia with high levels of 1,25(OH)2D3. The variety of clinical manifestations depends on age, and underlying genetic predisposition mutations can lead to fatal infantile hypercalcaemia among neonates, whereas adult symptoms are usually mild. Aim of the study: We report a rare case of an adult with primary hyperparathyroidism and loss-of-function mutations in the CYP24A1 gene and a review of similar cases. Case presentation: We report the case of a 58-year-old woman diagnosed initially with primary hyperparathyroidism. Preoperatively, the suspected mass adjoining the upper pole of the left lobe of the thyroid gland was found via ultrasonography and confirmed by 99mTc scintigraphy and biopsy as the parathyroid gland. The patient underwent parathyroidectomy (a histopathology report revealed parathyroid adenoma), which led to normocalcaemia. After 10 months, vitamin D supplementation was introduced due to deficiency, and the calcium level remained within the reference range. Two years later, biochemical tests showed recurrence of hypercalcaemia with suppressed parathyroid hormone levels and elevated 1,25(OH)2D3 concentrations. Further investigation excluded the most common causes of PTH-independent hypercalcaemia, such as granulomatous disease, malignancy, and vitamin D intoxication. Subsequently, vitamin D metabolites were measured using LC-MS/MS, which revealed high levels of 25(OH)D3, low levels of 24,25(OH)2D3 and elevated 25(OH)2D3/24,25(OH)2D3 ratios, suggesting a defect in vitamin D catabolism. Molecular analysis of the CYP24A1 gene using the NGS technique revealed two pathogenic variants: p.(Arg396Trp) and p.(Glu143del) (rs114368325 and rs777676129, respectively). Conclusions: The diagnostic process for hypercalcaemia becomes complicated when multiple causes of hypercalcaemia coexist. The measurement of vitamin D metabolites using LC-MS/MS may help to identify carriers of CYP24A1 mutations. Subsequent molecular testing may contribute to establishing the exact frequency of pathogenic variants of the CYP24A1 gene and introducing personalized treatment.

Persistent Primary Hyperparathyroidism Secondary to an Ectopic Mediastinal Adenoma in a Young Adult: A Case Report.

Primary hyperparathyroidism commonly affects elderly women. When present in the young population, it is usually asymptomatic, most frequently due to a parathyroid adenoma and the definitive management is surgical excision. Uncommonly, 5-10% of patients fail to achieve long-term cure after initial parathyroidectomy and 6-16% of them is due to an ectopic parathyroid adenoma that will require focused diagnostic and surgical approaches. We report a 21-year-old male who had bilateral thigh pain. Work-up revealed bilateral femoral fractures, brown tumors on the arms and multiple lytic lesions on the skull. Serum studies showed hypercalcemia (1.83 mmol/L), elevated parathyroid hormone [(PTH) 2025.10 pg/mL], elevated alkaline phosphatase (830 U/L), normal phosphorus (0.92 mmol/L) and low vitamin D levels (18.50 ng/mL). Bone densitometry showed osteoporotic findings. Sestamibi scan showed uptake on the left superior mediastinal region consistent with an ectopic parathyroid adenoma. Vitamin D supplementation was started pre-operatively. Patient underwent parathyroidectomy with neck exploration; however, the pathologic adenoma was not visualized and PTH levels remained elevated post-operatively. Chest computed tomography with intravenous contrast was performed revealing a mediastinal location of the adenoma. A repeat parathyroidectomy was done, with successful identification of the adenoma resulting in a significant drop in PTH and calcium levels. Patient experienced hungry bone syndrome post-operatively and was managed with calcium and magnesium supplementation. A high index of suspicion for an ectopic adenoma is warranted for patients presenting with hypercalcemia and secondary osteoporosis if there is persistent PTH elevation after initial surgical intervention. Adequate follow-up and monitoring is also needed starting immediately in the post-operative period to manage possible complications such as hungry bone syndrome.

Parathyroid carcinoma during pregnancy: a novel pathogenic CDC73 mutation - a case report.

BACKGROUND: Parathyroid carcinoma is an uncommon cause of PTH-dependent hypercalcemia. Only a handful of cases have been reported of parathyroid carcinoma during pregnancy. CASE PRESENTATION: Twenty-four - Year - old female presented with proximal myopathy was found to have hypercalcemia. Her serum corrected total calcium was - 15 mg/dl (8.5 - 10.3), serum phosphate - 2.3 mg/dl (2.5 - 4.5), intact PTH - 118 pg/ml (20 - 80), Vitamin D - 15 ng/ml and Urine Ca/Cr ratio - 2.1 (0.1 - 0.2). Her CECT-neck revealed a well-defined mass lesion posterior to the right lobe of the thyroid - 2.6 cm × 2.5 cm × 2.9 cm in size. She was started on vitamin D supplementation, and she underwent right lower focal parathyroidectomy. Her PTH levels normalized following surgery. Her histology revealed an atypical parathyroid adenoma. She was treated with calcium and vitamin D. Her follow up was uneventful. One year following initial surgery the patient became pregnant and at 16 weeks of POA, the patient presented with a rapidly enhancing neck mass for one week duration. Her biochemical investigations were suggestive of a recurrence of primary hyperparathyroidism. Her ultrasound scan of the neck revealed a well-defined discreate hypoechoic nodule, superior to the thyroid isthmus which was confirmed by a non-contrast MRI scan of the neck. She underwent an uncomplicated second trimester parathyroid tumour excision with normalization of post op PTH. Her histology revealed a parathyroid carcinoma with vascular and capsular invasion. Her genetic studies revealed a novel frameshift mutation of the CDC73 gene. She was treated with calcium and vitamin D supplementation and closely followed up with ionized calcium and PTH levels which were normal throughout the pregnancy. She had an uncomplicated caesarean section at a POA of 37 weeks. Currently she is twelve weeks post-partum, in remission of disease. CONCLUSION: This case shows the importance of stringent follow up of atypical parathyroid adenoma patients, the benefit of second trimester surgery in management of hypercalcemia due to parathyroid carcinoma during pregnancy and the importance of identifying the novel CDC73 gene mutation.

Contemporary Multimodality Imaging of Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a disorder characterized by hypercalcemia and an elevated or inappropriately normal parathyroid hormone level. Classic features include bone pain, fractures, renal impairment, nephrolithiasis, and mental disturbance. However, most cases of PHPT are now asymptomatic at diagnosis or associated with nonspecific neurocognitive changes. The most frequent cause of PHPT is a solitary adenoma that secretes parathyroid hormone without the normal suppressive effect of serum calcium. A smaller number of cases can be attributed to multigland disease. Parathyroidectomy is curative and is considered for nearly all affected patients. Although PHPT is primarily a clinical and biochemical diagnosis, imaging is key to the localization of adenomas, which can lie in conventional locations adjacent to the thyroid gland or less commonly at ectopic sites in the neck and mediastinum. In addition, accurate localization facilitates the use of a minimally invasive or targeted surgical approach. Frequently used localization techniques include US, parathyroid scintigraphy, and four-dimensional CT. Second- and third-line modalities such as MRI, PET/CT, and selective venous sampling with or without parathyroid arteriography can increase confidence before surgery. These localization techniques, along with the associated technical aspects, relative advantages, and drawbacks, are described. Local expertise, patient factors, and surgeon preference are important considerations when determining the type and sequence of investigation. A multimodality approach is ultimately desirable, particularly in challenging scenarios such as multigland disease, localization of ectopic adenomas, and persistent or recurrent PHPT. Online supplemental material is available for this article. ©RSNA, 2022.

Successful Control of Hypercalcemia with Sorafenib, Evocalcet, and Denosumab Combination Therapy for Recurrent Parathyroid Carcinoma.

Parathyroid carcinoma (PC) is a rare type of endocrine cancer. Recurrence and metastasis are common after surgery, and refractory hypercalcemia often leads to a poor prognosis. However, there are currently no specific strategies for PC recurrence. We herein report a 61-year-old Japanese man with metastatic PC who was treated with sorafenib, a multikinase inhibitor. In this case, the serum calcium level was under control for 10 months after the initiation of sorafenib. This case suggests that combination therapy with sorafenib, evocalcet, and denosumab may be an alternative, stronger management option for refractory hypercalcemia in recurrent PC.

Parathyroid carcinoma: Single centre experience.

OBJECTIVE: Parathyroid Carcinoma is a rare malignant neoplasm, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single centre regarding the management and outcome of patients with parathyroid carcinomas and revise relevant literature. DESIGN: Retrospective review of all patients with parathyroid carcinoma evaluated at a tertiary oncologic centre from 1991 until 2021. RESULTS: Seventeen patients were identified (10 males), with a mean age at diagnosis of 53 ± 16 years and a median follow-up of 16.5 years. Most patients presented with hypercalcemia (n = 15), with a mean serum calcium concentration of 13.5 mg/dl (9.6-16.5) and mean PTH of 1173 pg/ml (276-2500). Hyperparathyroidism-mediated organ damage was observed in most patients (n = 16), with predominant renal (n = 12) and skeletal (n = 9) complications. En bloc surgical resection was performed in nine patients. Three patients underwent adjuvant radiotherapy. Recurrence was observed in 8 cases (47.1%) after a median of 24 months following surgery and no independent predictors of recurrence were identified. The overall survival and disease specific survival at 5-year was 88% and 94%, respectively. CDC73 mutations were present in 38.5% of analysed patients and one patient was diagnosed with MEN1. CONCLUSION: Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Therefore, preoperatively high index of suspicion is paramount to optimize patient care. This is, to our knowledge, the largest Portuguese cohort published so far.

Correlation of perioperative biochemical variables with single adenoma weight in patients with primary hyperparathyroidism.

BACKGROUND: Single parathyroid adenoma is the main cause of primary hyperparathyroidism (PHPT), with surgery remaining the gold standard for its treatment. The ability to preoperatively predict the parathyroid adenoma size and could facilitate the decision about the extent of surgical exploration. It is reasonable to hypothesize that the perioperative levels of PHPT-related variables (i.e. calcium, parathormone, phosphate) may predict the adenoma weight or/and demonstrate whether the adenoma is successfully removed or not. Aim of this study is to explore the relationship between perioperative biochemical values and adenoma weight. Secondarily, we investigated the relationship between adenoma weight and uni-/bilateral neck exploration. METHODS: Retrospective study of all patients undergone surgery for primary hyperparathyroidism due to single adenoma in a tertiary university hospital in Germany during a 6-year period. Following variables were analyzed: preoperative serum calcium, phosphorus and parathormone, intraoperative parathormone before and after adenoma excision, intraoperative PTH decrease, postoperative serum calcium and parathormone (PTHpostop-pg/ml), calcium and PTH decrease. Bivariate correlations were calculated by the Spearman's correlation test at the 95% significance level. RESULTS: A total of 339 patients were included in the study. The median age of the patients was 60 years (range 21-90) and 77% were females. The median adenoma weight was 1 g (range 0.1-11). Adenoma weight correlated strong with maximum adenoma diameter (r = 0.72, p < 0.05), moderate with preoperative parathormone (r = 0.44) and parathormone decrease (r = 0.27), whereas there was no correlation with the intraoperative PTH decrease (r = 0.02). There was also a borderline (moderate to weak) correlation with pre- and postoperative calcium levels (r = 0.21 and r = 0.23 respectively) and a negative borderline correlation with phosphorus (r = - 0.21). Patients who required bilateral neck exploration, had significantly lighter adenomas (median weight 0.8 g vs 1.1 g, p = 0.005). CONCLUSIONS: We conclude that preoperative PTH levels may only serve as an approximate guide to adenoma weight, as direct preoperative prediction is not possible. Serum calcium levels, PTH and calcium decrease correlate only weak with adenoma weight. Patients who require bilateral neck exploration, have significantly (20-25%) lighter adenomas.

Unusual recurrent renal secondary hyperparathyroidism caused by hyperplastic autograft with supernumerary parathyroid adenoma: A case report.

RATIONALE: Secondary hyperparathyroidism (SHPT) is often complicated with chronic renal failure. Though the total parathyroidectomy (TPTX) with forearm autotransplantation (FAT) has been commonly used to treatment refractory renal SHPT, the recurrence of SHPT is not infrequent, resulting from hyperplastic autograft, remnant parathyroid tissues, and supernumerary parathyroid gland (SPG). PATIENT CONCERNS: A 67-year-old man undergoing TPTX+FAT 4 years previously for renal SHPT, who received regular hemodialysis with active vitamin D supplements of Rocaltrol treatment postoperatively, was admitted to our hospital with progressively elevated serum intact parathyroid hormone (iPTH) from 176 to 1266 pg/mL for 8 months and bilateral ankle joints pain for 1 month. Tc-sestamibi dual-phase imaging with single positron emission tomography (SPECT)/computed tomography (CT) revealed a nodule in suprasternal fossa, besides a nodule in autografted site, accompanied with intense radioactivity. DIAGNOSIS: Recurrent SHPT was easily diagnosed based on previous medical history, painful joints, increased serum iPTH level and positive findings of Tc-sestamibi imaging. Routine postoperative pathology showed that the nodules were consistent with an adenomatoid hyperplasic autograft and a supernumerary parathyroid adenoma in suprasternal fossa, respectively. INTERVENTIONS: Reoperation for removing nodules in suprasternal fossa and autografted site was performed 1 month later. Then regular hemodialysis 3 times a week with Rocaltrol was continued. OUTCOMES: During 12 months of follow-up, the joints pain improved obviously and the serum iPTH level ranged from 30.1 to 442 pg/mL. LESSONS: Although rare, recurrent renal SHPT may be caused by a coexistence of both hyperfunctional autograft and SPG after TPTX+FAT. The Tc-sestamibi parathyroid imaging with SPECT/CT is helpful to locate the culprits of recurrent renal SHPT before reoperation. To prevent recurrence of renal SHPT, the present initial surgical procedures should be further optimized in patient on permanent hemodialysis.

Gitelman syndrome and primary hyperparathyroidism: a rare association.

Gitelman syndrome(GS) is a rare autosomal recessive salt-losing tubulopathy of young adults, characterised by hypokalaemia, hypomagnesaemia, hypocalciuria and secondary hyperaldosteronism. Hypercalcaemia due to hypocalciuria in these patients is extremely rare.A 25-year-old healthy woman was referred to the Endocrinology clinic for evaluation of persistent hypokalaemia. She presented with fatigue, myalgias, cramps and paraesthesia. Her physical examination was normal. Laboratory workup revealed: K+ 2.7 mEq/L (r.v.3.5-5.1), 24 hours urinary K+ 84.7 mEq/24 hours (r.v.25-125), Mg2+ 0.71 mg/dL (r.v.1.6-2.6), 24 hours urinary Mg2+ 143.1 mg/24 hours (r.v.73-122), Ca2+ 12 mg/dL (r.v.8.4-10.2), aldosterone 47.1 ng/mL (r.v. 4-31) and active renin 374.7 uUI/mL (r.v.4.4-46.1). She was diagnosed with GS and was treated with spironolactone, oral K+ and Mg2+ supplementation. Further investigation confirmed hypercalcaemia due to primary hyperparathyroidism owing to a single parathyroid adenoma. Following parathyroidectomy serum calcium normalised.Current knowledge favours that hypomagnesaemia in patients with GS protects them from hypercalcaemia. In this context of multiple electrolyte imbalances, correction of hypomagnesaemia is a challenge and should be done carefully. Like in our patient, aetiology of hypercalcaemia should be promptly diagnosed and reversed.

Parkinsonism as presenting symptom of primary hyperparathyroidism: Improvement after surgery. / Parkinsonismo como síntoma principal de hiperparatiroidismo: recuperación tras cirugía

Introduction: Hypercalcemia can cause different neurological disorders, depending on the calcium level. We report an exceptional case of primary hyperparathyroidism presenting as neurological alteration and it has favourable outcome after parathyroidectomy. Case report: A 74-year-old woman presented with progressive cognitive deterioration and impaired motor function. The complementary tests showed hypercalcemia due to a parathyroid adenoma. Parathyroidectomy was performed with symptomatic improvement. Conclusion: Cognitive impairment of the elderly due to a parathyroid adenoma is underdiagnosed, behavioral changes and alterations of motor functions are attributed to age, dementia and frailty, representing a diagnostic challenge.

Introducción: La hipercalcemia puede causar diferentes trastornos neurológicos, dependiendo de las concentraciones de calcio. Aportamos un caso excepcional de hiperparatiroidismo primario que se manifestó con deterioro neurológico rápidamente evolutivo y se resolvió mediante paratiroidectomía. Caso clínico: Mujer de 74 años que consultó por deterioro cognitivo progresivo y alteración de las funciones motoras. Las pruebas complementarias evidenciaron hipercalcemia debida a un adenoma paratiroideo. Se realizó paratiroidectomía, con mejoría sintomática. Conclusión: El deterioro cognitivo del anciano por un adenoma paratiroideo está infradiagnosticado, pues los cambios de conducta y las alteraciones de las funciones motoras se atribuyen a la edad, la demencia y la fragilidad, suponiendo un reto diagnóstico.

Elevated parathyroid hormone levels after successful parathyroidectomy for primary hyperparathyroidism: a clinical review.

INTRODUCTION: Surgery for primary hyperparathyroidism (PHPT) is traditionally deemed to be successful if serum calcium levels return to normal 6 months after parathyroidectomy. Regular monitoring of serum calcium and parathyroid hormone (PTH) in the follow-up of patients after parathyroidectomy for PHPT has drawn attention to the presence of a normocalcemic group of patients with elevated PTH (NCePTH) during the post-operative period. The etiological factors and mechanisms underlying this condition, its consequences, and the possibility of treatment are the object of this study. MATERIALS AND METHODS: We conducted an unlimited PubMed search updated on March 31, 2017, which yielded 1628 results. We selected 37 articles, 33 of which included cases of NCePTH in their series and 23 performed statistical studies to assess factors associated with NCePTH. RESULTS: The maximum mean prevalence of NCePTH in the various series was 23.5%, ranging from 3 to 46%. Many factors were associated with NCePTH. The most important were higher pre-operative PTH, low pre-operative 25 (OH) D3, lower pre-operative creatinine clearance and greater adenoma weight. The origin of NCePTH may be multifactorial, since several factors were implicated in the etiology. NCePTH does not seem to be related to an increase in PHPT recurrence, although this possibility should not be dismissed. Vitamin D deficiency should be corrected. Treatment with calcium supplements seems to be clearly beneficial. CONCLUSION: The prevalence of NCePTH is high. The causes of secondary hyperparathyroidism should be investigated carefully. Patients require treatment and long-term follow-up.

Hiperparatiroidismo primario en adolescente. Reporte de caso / Primary hyperparathyroidism in adolescent. Case report

INTRODUCTION: The hypercalcemia is infrequent in pediatrics, its clinical is diverse, and its etiology is determined by age. Among the dependent causes of parathormone (PHT) is the hyperthyroidism, state of hypersecretion of PHT by parathyroid glands (PG). The primary hyperparathyroidism (PHPT) is rare in children, there are 200 reported cases. In older children, the causes for PHPT correspond to parathyroid adenoma, multiglandular disease and parathyroid carcinoma. OBJECTIVE: Report a case of an 11 years old male adolescent. He presents three months symptoms of constipation, anorexia, vomiting and weight loss. Urgent consultation due to an increase of his symptoms, in exams stand out: calcemia 16.67 mg/dl (NV 8.8-10.8 mg/dl), phosphatemia 2.21 mg/dl (NV 4.5-5.5 mg/dl), parathormone (PHT) 308.7 pg/ml (NV 15-68.3 pg/ml), calciuria/creatininuria 0.56 (NV < 0.2). He was hospitalized to manage his severe hypercalcemia, it was indicated hyperhydration, monopotassium phosphate, intravenous hydrocortisone and furosemide. In his study was performed a cervical ultrasound which showed a solid node in the right parathyroid gland, hypoechogenic and scintigram parathyroid compatible with right superior parathyroid adenoma. In the waiting for surgery was necessary the administration of intravenous pamidronate. In the post-operatory, he evolved with hipocalcemia that was corrected with intravenous calcium carbonate, overlapping to oral calcium and calcitriol. CONCLUSION: The PHPT is a pathology of low prevalence in pediatrics, one hundred times less than adults. In the adolescent, the most frequent cause is the parathyroid adenoma. It should be considered as a differential diagnosis in cases of symptomatic hypercalcemia in this age group

Hipometilación del gen de la PTH por elevado fósforo de la dieta: un posible agravante epigenético de la severidad del hiperparatiroidismo secundario en la enfermedad renal crónica / Hypomethylation of the PTH gene due to high dietary phosphorus: a possible aggravating of severe secondary hyperparathyroidism in chronic renal failure

Introducción: En pacientes con enfermedad renal crónica (ERC), la hiperfosfatemia agrava tanto la hiperplasia paratiroidea como la síntesis y secreción de PTH. La mayor hiperplasia se asocia a descensos en la expresión génica de los receptores de calcio (CaSR), vitamina D (VDR) y también de α-Klotho, induciendo resistencia de la glándula paratiroides para responder tanto al tratamiento como a los aumentos de FGF23. Este estudio examinó la posible contribución epigenética del fósforo elevado en agravar el hiperparatiroidismo secundario (HPTS). Material y métodos: Se comparó el grado de metilación mediante pirosecuenciación de bisulfito en secuencias ricas en CpG de los promotores en los genes del CaSR, VDR, PTH y α-Klotho en ADN de glándulas paratiroides de ratas urémicas alimentadas con dieta con contenido normal y elevado en fósforo. Resultados: La dieta rica en fósforo incrementó la expresión de PTH y causó una marcada reducción del grado de metilación en el promotor del gen de PTH. En cambio, las regiones promotoras de los genes de CaSR, VDR y α-Klotho no mostraron diferencias significativas en el porcentaje de metilación entre ambos grupos de ratas, no siendo, por tanto, éste el mecanismo determinante de la disminución de la expresión de estos genes observada en el HPTS. Conclusiones: Las alteraciones epigenéticas inducidas por la dieta rica en fósforo en el HPTS, en particular la hipometilación del gen de la PTH, podrían contribuir a los aumentos que se producen en la síntesis y secreción de esta hormona. La identificación de los mecanismos implicados permitiría diseñar mejores tratamientos para el HPTS en fases tempranas de la ERC (AU)

Introduction: Hyperphosphataemia aggravates both parathyroid hyperplasia and PTH secretion in patients with chronic kidney disease (CKD). Hyperplasia is associated with decreases in calcium receptor expression (CaSR), vitamin D (VDR) and α-Klotho, inducing resistance of the parathyroid gland to respond both to treatment and to increases in FGF23. This study examined the possible epigenetic contributions of raised phosphorus to aggravate secondary hyperparathyroidism (SHPT) in patients with (CRD). Material and methods: The degree of methylation was compared by pyrosequencing of bisulfite in CpGrich sequences of the promoters in the CaSR, VDR, PTH and α-Klotho genes in parathyroid gland DNA from uremic rats fed a normal and high phosphorus diet. Results: The diet rich in phosphorus increased PTH expression and caused a marked reduction in the degree of methylation in the promoter of the PTH gene. In contrast, the promoter regions of the CaSR, VDR and α-Klotho genes did not show significant differences in the percentage of methylation between the two groups of rats. Thus, it was not the determining mechanism for the decrease of the expression of these genes observed in the SHPT. Conclusions: The epigenetic alterations induced by the phosphorus rich diet in SHPT, particularly the PTH gene hypomethylation, could contribute to the increases that occur in the synthesis and secretion of this hormone. The identification of the mechanisms involved would allow better treatments for SHPT to be designed in the early stages of CKD (AU)

Paratirotoxicosis y tumor cervical palpable: caso clínico de cáncer de paratiroides / Parathyrotoxicosis and palpable neck mass: a clinical presentation of parathyroid cancer

Introducción: El cáncer de paratiroides es poco frecuente. Suele presentarse como hiperparatiroidismo primario, en ocasiones como crisis hipercalcémica, con malestar general, náuseas, vómitos, alteraciones del ánimo y pérdida de peso. En algunos casos se presenta como osteítis fibrosa quística, osteopenia difusa, osteoporosis y fracturas patológicas. El diagnóstico suele estar dado por biopsia quirúrgica que muestra invasión a estructuras adyacentes, o metástasis locales y distantes. El tratamiento es la resección quirúrgica del tumor, sin uso de terapias adyuvantes. Su tasa de recurrencia es alta, de 25 a 100%. Algunos factores de mal pronóstico son metástasis a linfonodos en la presentación inicial, metástasis distantes y carcinomas no funcionantes. Caso clínico: Paciente masculino de 64 años que consultó por compromiso del estado general, bradipsiquia, poliuria, cefalea y masa cervical. Además presentaba hipercalcemia y gran elevación de PTH. Se realizó resección quirúrgica de la masa cervical, con biopsia rápida con atipias y mitosis 1/10, y de un nódulo hiperplásico tiroideo. Tras esto, sus niveles de PTH disminuyeron, así como también descendieron sus niveles de calcio. Discusión: Los pacientes que presentan cáncer de paratiroides suelen tener valores más elevados de calcemia y PTH. Para su diagnóstico, no se recomienda usar biopsia por punción, por riesgo de diseminación y por el bajo rendimiento de esta técnica. Conclusión: Pese a ser poco frecuente, se debe pensar en cáncer de paratiroides en el contexto de un paciente con hipercalcemia, especialmente si presenta PTH muy elevada. La sospecha clínica de este diagnóstico tiene directa relación con la posibilidad de tratamiento y pronóstico de la enfermedad.

Introduction: Parathyroid cancer is rare. Usually presented as primary hyperparathyroidism, sometimes as hypercalcemic crisis, with general malaise, nausea, vomiting, mood disturbances and low weight. In some cases it occurs as osteitis fibrosa cystica, diffuse osteopenia, osteoporosis and pathological fractures. The diagnosis is usually made by surgical biopsy shows invasion of adjacent structures, or local and distant metastases. The treatment is surgical resection of the tumor, without the use of adjuvant therapies. Their recurrence rate is high, 25 to 100%. Poor prognostic factors are lymph node metastases at initial presentation, distant metastases and nonfunctional carcinomas. Case report: Male patient consulted for 64 years in general conditions, bradypsychia, polyuria, headache and neck mass. He also had hypercalcemia and high elevation of PTH. Surgical resection of the cervical mass was performed, with rapid biopsy atypia and mitosis 1/10, and hyperplastic thyroid nodule. After this, PTH decreased levels as well as levels of calcium. Discussion: Patients with parathyroid cancer tend to have higher serum calcium and PTH of values. For diagnosis, it is not recommended to use needle biopsy, risk of spread and the poor performance of this technique. Conclusion: Despite being rare, you should think parathyroid cancer in the context of a patient with hypercalcemia, especially if you have very high PTH. The clinical suspicion of this diagnosis is directly related to the possibility of treatment and prognosis of the disease.

Minimally invasive radioguided parathyroid surgery using low-dose Tc-99m-MIBI - comparison with standard high dose.

INTRODUCTION: Surgery remains the most effective treatment for primary hyperparathyroidism (PHPT). Minimally invasive radioguided parathyroidectomy (MIRP) is a common technique for detecting and excising abnormal parathyroid glands. The aim of this study was to compare injections of low-dose and high-dose (99m) Tc methoxy isobutyl isonitrile (MIBI) for intraoperative localisation of parathyroid adenomas by means of a gamma probe in patients with primary hyperparathyroidism (PHPT). MATERIAL AND METHODS: Thirty patients with PHPT and a preoperative diagnosis of parathyroid adenoma were enrolled between 2010 and 2012. They were considered as Group B and underwent MIRP using 5 mCi Tc-99m MIBI, and their perioperative data were compared with twenty patients treated with conventional 20 mCi Tc-99m MIBI previously (Group A). RESULTS: Group A was made up of 20 patients (mean age, 41.55 years; 14 women and 6 men), and group B included 30 patients (mean age, 40.43 years; 19 women and 11 men). The mean serum parathyroid hormone (PTH) and calcium values were recorded pre- and postoperatively. The mean follow-up period for the patients in the two groups was 18.4 and 16.5 months, respectively. Pre-operative evaluation demonstrated that the groups were statistically similar. Intraoperative data and success rate of surgery showed no difference between the two groups. No significant complication was detected after surgeries and no recurrence happened in either of the two groups during the follow-up period. CONCLUSIONS: A new protocol of MIRP using low doses of Tc-99m-MIBI resulted in an excellent success rate. Comparing results of the study, we conclude that low-dose Tc-99m-MIBI may be preferred for identification of parathyroid adenomas intraoperatively by means of a gamma probe in PHPT patients because it appears to be as effective as high-dose Tc-99m-MIBI.

Parathyroid Adenomas in Adults and Adolescents. Critical Appraisal and Surgical Strategy in 18 Cases.

Background: Our study underline scarcity of isolated case reports or small case series of parathyroid adenoma (PA) published in autochthonous medical literature,their variable clinical expression among the "historic" varieties but also the diagnostic difficulties and delays of diagnosis as well consecration of surgery as the golden therapeutic standard of this disorder. PATIENTS AND METHOD: Demographic, clinical presentations, laboratory and imaging data, operative findings and procedures together with pathology account and outcome from the case reports of 18 patients with documented PHP were retrospectively analyzed. Results: The male/female ratio was 1/5, with ages ranging from 16 to 58 (mean 46) years. Renal stones (n=9) and bone sufferings (n=6) were the most common modes of presentation. To these were added psychiatric and neuromuscular complaints, digestive disorders (pancreatitis and peptic ulcer) arterial hypertension and presence of a palpable nodule. Mean serum calcium and phospho-rus, alkaline phosphatase and PTH dosage together with parathyroid ultrasound and 99m Tc sestamibi scintigraphy are the most useful parameters for diagnosis. Eighteen adenomectomies were performed of which bilateral neck exploration was done in 16 patients and minimally invasive approach in the remaining two cases. In 9 situations concomitant thyroid exeresis for associated lesions or tactical purpose were done. Pathology revealed single adenoma consisting of main and oxyphil cells in 17 cases. In one case an atypical adenoma was identified and in another case three years after removal of a benign adenoma the subject presented a clinical ipsilateral recurrence which provided to be a carcinoma. Postoperative clinical and humoral outcome was favorable in all situations less the case of carcinoma which died after 14 months. Conclusions: Despite the rarity and difficulties of diagnosis in cases of PA, practitioners must be aware of potential existence of these lesions in order to apply as early and appropriate treatment where surgery is the gold standard.

Outcomes of minimally invasive parathyroidectomy in pediatric patients with primary hyperparathyroidism owing to parathyroid adenoma: A single institution experience.

BACKGROUND: Guidelines for treatment of primary hyperparathyroidism (PHPT) in young patients recommend surgery. Outcomes of minimally invasive parathyroidectomy (MIP) are well established in adults, but not in pediatric patients. OBJECTIVE: The objective of the study is to determine effectiveness of preoperative imaging and MIP aided by intraoperative PTH (ioPTH) measurement in children with primary hyperparathyroidism (PHPT). METHODS AND DESIGN: This is a retrospective chart review of diagnostic and follow-up data up to 12months post-MIP of patients with PHPT who underwent parathyroidectomy at the Children's Hospital of Philadelphia between January 1, 2009 and March 31, 2015. RESULTS: Data were available for 16 of 17 patients age 8-17years (11 females, 6 males): 2 had ectopic intrathymic adenomas while 14 had eutopic adenomas. Fifteen patients had ioPTH, including 14 who underwent MIP, defined as a 2cm central neck incision. All patients with data at 6months postparathyroidectomy (13/16) showed normal PTH and calcium. Ultrasound and sestamibi scans had a combined sensitivity of 87.5%. CONCLUSIONS: MIP is an appropriate alternative to standard neck exploration in pediatric patients with PHPT with a single parathyroid adenoma. ioPTH is especially useful to confirm cure and limit surgical exploration when imaging studies are negative. Sestamibi scans and ultrasound are complementary studies.

Cinacalcet hydrochloride relieves hypercalcemia in Japanese patients with parathyroid cancer and intractable primary hyperparathyroidism.

Pharmacological treatment of hypercalcemia is essential for patients with parathyroid carcinoma and intractable primary hyperparathyroidism (PHPT). Use of the calcimimetic cinacalcet hydrochloride (cinacalcet) is an option to treat such patients. We investigated the efficacy and safety of cinacalcet in Japanese patients with parathyroid carcinoma and intractable PHPT. Five Japanese patients with parathyroid carcinoma and two with intractable PHPT were enrolled in an open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated until the albumin-corrected serum calcium concentration decreased to 10.0 mg/dL or less or until dose escalation was considered not necessary or feasible. Serum calcium concentration at the baseline was 12.1 ± 1.3 mg/dL (mean ± standard deviation; range 10.4-14.6 mg/dL) and decreased to 10.1 ± 1.6 mg/dL (range 8.6-13.3 mg/dL) at the end of the titration phase with cinacalcet at a dosage of up to 75 mg three times a day. At the end of the titration phase, at least a 1 mg/dL reduction in serum calcium concentration from the baseline was observed in five patients (three with carcinoma and two with PHPT), and it decreased to the normocalcemic range in five patients (three with carcinoma and two with PHPT). Common adverse events were nausea and vomiting. One patient discontinued participation in the study because of an adverse event, liver disorder. Cinacalcet effectively relieved hypercalcemia in 60% of the Japanese patients with parathyroid carcinoma and might be effective in those with intractable PHPT. The drug might be tolerable and safe at a dosage of at most 75 mg three times a day.

Hyperparathyroidism in octogenarians: A plea for ambulatory minimally invasive surgery under local anesthesia.

BACKGROUND: With the current aging of the world's population, diagnosis of primary hyperparathyroidism is being reported in increasingly older patients, with the associated functional symptomatology exacerbating the vicissitudes of age. This retrospective study was designed to establish functional improvements in older patients following parathyroid adenomectomy under local anesthesia as outpatient surgery. MATERIALS AND METHODS: Data were collected from 53 patients aged 80 years or older who underwent a minimally invasive parathyroid adenomectomy. All patients underwent a preoperative ultrasound, scintigraphy, and were monitored for the effectiveness of the procedure according to intra- and postdosage of parathyroid hormone (PTH) at 5min, 2h and 4h. RESULTS: Mean preoperative serum calcium level was 2.8mmol/L (112mg/L) and mean PTH was 180pg/ml. Thirty-eight patients were operated under local anesthesia using minimally invasive surgery and 18 patients were operated under general anesthesia. In 26 cases, the procedure was planned on an outpatient basis but could only be carried out in 21 patients. Fifty-one patients had normal serum calcium and PTH levels during the immediate postoperative period. Two patients were reoperated under general anesthesia, since immediate postoperative PTH did not return to normal. Four patients died due to reasons unrelated to hyperparathyroidism. Five patients were lost to follow-up six months to two years postsurgery. Of the 44 patients (83%) with long-term monitoring for PTH, none had recurrence of biological hyperparathyroidism. Excluding the three asymptomatic patients, 38 of the 41 symptomatic patients (93%) with long-term follow-up were considering themselves as "improved" or "strongly improved" after the intervention, notably with respect to fatigue, muscle and bone pain. Two patients (4.9%) reported no difference and one patient (2.4%) said her condition had worsened and regretted having undergone surgery. CONCLUSION: In patients 80 years or older, minimally invasive surgery as an outpatient under local anesthesia offered an excellent risk/benefit ratio given its many advantages: simplicity, speed, absence of general anesthesia, ease of monitoring, direct voice control intraoperatively, very low morbidity, effectiveness in treating primary hyperparathyroidism in more than 95% of first intention patients, and the possibility of immediate or delayed recovery in the event of multiglandular disease going unnoticed.