First Japanese Patient Treated with Parathyroid Hormone Peptide Immunization for Refractory Hypercalcemia Caused by Metastatic Parathyroid Carcinoma

Abstract Primary hyperparathyroidism (PHPT) is a rare endocrine disease in the pediatric population. Sporadic parathyroid adenomas remain the most common cause of pediatric PHPT. Parathyroid carcinoma (PC) is an extremely rare cause of pediatric PHPT. We report a 16-year-old boy presenting with a nonhealing fragility fracture of the right leg along with florid features of rickets. Examination revealed a neck mass, mimicking a goiter. Biochemical findings were consistent with PHPT. Imaging was suggestive of a right inferior parathyroid mass infiltrating the right lobe of thyroid. The patient underwent en bloc surgical excision of the parathyroid mass along with the right lobe of thyroid. Histopathology was suggestive of a PC. He achieved biochemical remission with normalization of serum calcium and parathyroid hormone levels. At follow-up, there was no biochemical or imaging evidence of recurrence or metastasis. Genetic analysis revealed heterozygous germline deletion of CDC73. An extensive literature search on PC was conducted, with an emphasis on the pediatric population. Thirteen cases of pediatric PC were identified. The median age of presentation was 13 years; there was no sex predilection. All cases were symptomatic; 31% had a visible neck mass. The median serum calcium and intact parathyroid hormone levels were 14.3 mg/dL and 2000 pg/mL, respectively. All patients underwent surgical excision, with 27% showing metastatic relapse. Our findings indicate that the preoperative features that could point toward a diagnosis of PC in a child with PHPT are a tumor size of >3 cm, thyroid infiltration on imaging, and severe hypercalcemia at presentation.

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Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high-dose denosumab

Acta Endocrinologica ◽

10.1530/eje-14-0166 ◽

2014 ◽

Vol 171 (1) ◽

pp. K1-K5 ◽

Cited By ~ 26

Author(s):

Dharshini Karuppiah ◽

Gaya Thanabalasingham ◽

Brian Shine ◽

Lai Mun Wang ◽

Gregory P Sadler ◽

...

Keyword(s):

Parathyroid Hormone ◽

Surgical Resection ◽

Medical Management ◽

Parathyroid Carcinoma ◽

Nuclear Factor Κb ◽

High Dose ◽

Nuclear Factor ◽

Receptor Activator ◽

Effective Option ◽

Monthly Injection

ObjectiveHypercalcaemia is an important cause of increased morbidity and mortality in patients with parathyroid carcinoma. Surgical resection is the mainstay of treatment but, equally, managing hypercalcaemia is of paramount importance. At present, few therapies have been shown to be effective in the most severe cases. This report describes the efficacy of denosumab in a patient with parathyroid carcinoma when conventional therapies had been shown to be relatively ineffective.Subject, methods and resultsA 50-year-old man presented with symptomatic hypercalcaemia 1 year after the surgery for his parathyroid carcinoma. Investigations revealed raised serum calcium and parathyroid hormone concentrations consistent with the recurrence of the disease. Imaging failed to localise any surgically remediable foci. Medical management with loop diuretics, calcimimetics and bisphosphonates failed to provide a sustained response. Denosumab, as a monthly injection, led to a gradual decrement in his peak calcium concentrations with the values now persistently below 3 mmol/l.ConclusionsDenosumab, a fully human MAB that binds to the ‘receptor activator of nuclear factor κB ligand (RANKL)’, was shown to have a profound effect in modulating malignant hypercalcaemia. This medication should be considered as an effective option in patients with refractory hypercalcaemia secondary to parathyroid carcinoma.

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An Unusual Simultaneous Existence of Parathyroid Carcinoma and Papillary Thyroid Carcinoma: Case Report and Review of Literature

Case Reports in Endocrinology ◽

10.1155/2020/2128093 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

César Ernesto Lam-Chung ◽

Diana Lizbeth Rodríguez-Orihuela ◽

Jazmín De Anda González ◽

Armando Gamboa-Domínguez

Keyword(s):

Parathyroid Hormone ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Parathyroid Carcinoma ◽

Laboratory Evaluation ◽

Medical Attention ◽

Papillary Thyroid ◽

Thyroid Lobe ◽

Very High ◽

Left Thyroid Lobe

Synchronous parathyroid and papillary thyroid carcinoma are extremely rare. To our knowledge, only 15 cases have been reported in the last four decades. We describe a 50-year-old female without significant past medical or family history and no previous trauma presented with left heel pain that prompted her to seek medical attention. Physical examination was notable for a painless nodule at the left thyroid lobe. Laboratory evaluation showed a serum calcium level of 14.3 mg/dL (8.6–10.3 mg/dL) and intact parathyroid hormone level of 1160 pg/mL (12–88 pg/mL). 99Tc-sestamibi dual-phase with single-photon emission computed tomography fused images showed increased uptake at the left-sided inferior parathyroid gland. Neck ultrasound showed a 1.4 cm heterogeneous nodule in the middle-third of the left thyroid gland and a solitary 1.9 cm vascularized and hypoechoic oval nodule that was considered likely to represent a parathyroid adenoma. Due to its clinical context (severe hypercalcemia and very high levels of PTH), parathyroid carcinoma (PC) was suspected although imaging studies were not characteristic. The patient underwent en bloc resection of the parathyroid mass and left thyroid lobe and central neck compartment dissection. Pathology analysis revealed classical papillary thyroid carcinoma of classical subtype and parathyroid carcinoma. Immunohistochemical staining was positive for cyclidin D1 and negative for parafibromin. High clinical suspicion is required for parathyroid carcinoma diagnosis in the presence of very high level of parathyroid hormone, marked hypercalcemia, and the existence of any thyroid nodule should be approached and the coexistence of other carcinomas should be considered.

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Hormonal and Biochemical Normalization and Tumor Shrinkage Induced by Anti-Parathyroid Hormone Immunotherapy in a Patient with Metastatic Parathyroid Carcinoma

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2003-031911 ◽

2004 ◽

Vol 89 (7) ◽

pp. 3413-3420 ◽

Cited By ~ 77

Author(s):

D. Betea ◽

A. R. Bradwell ◽

T. C. Harvey ◽

G. P. Mead ◽

H. Schmidt-Gayk ◽

...

Keyword(s):

Parathyroid Hormone ◽

Parathyroid Carcinoma ◽

Tumor Shrinkage

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Atypical Parathyroid Adenoma in a Young Man

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.368 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A182-A182

Author(s):

Elizabeth R Bowen ◽

Joseph Stephen Dillon

Keyword(s):

Parathyroid Hormone ◽

Parathyroid Adenoma ◽

Mitotic Activity ◽

Parathyroid Carcinoma ◽

Sudden Onset ◽

Lytic Lesion ◽

Brown Tumor ◽

Adjacent Structures ◽

Parathyroid Adenomas ◽

Atypical Parathyroid Adenoma

Abstract Patient is a 38-year-old man who developed sudden onset of pain in the upper left arm while carrying a case of water. The pain recurred periodically over the next few months. He presented to the emergency department where imaging showed a pathologic fracture in the proximal left humerus through a lytic lesion. Laboratory testing showed: calcium 13.8 mg/dL (8.5–10.1 mg/dL), 25-OH vitamin D 8 ng/mL (31–100 ng/mL), parathyroid hormone 1583.1 pg/mL (18.5–88 pg/mL). Neck ultrasound showed a complex nodule in the left neck measuring 4.2 x 1.7 x 2.5 cm. Subsequent biopsy of the left arm lesion showed a Brown tumor. The patient was referred to endocrinology. There was concern for parathyroid carcinoma given the elevated parathyroid hormone and large neck lesion. Technetium-99m sestamibi scan showed a 4.1 x 2.6 x 2.5 cm mass posterior to the left thyroid lobe. He subsequently underwent left hemithyroidectomy and parathyroidectomy. Pathology revealed a 3.1 cm parathyroid mass with scattered fibrous bands, foci of prominent nucleoli and foci of sheet-like trabecular and spindled architecture. It was without necrosis, lymphovascular invasion, perineural invasion, increased mitotic activity, atypical mitoses or invasion into adjacent structures. Thus, it was classified as an atypical parathyroid adenoma. Primary hyperparathyroidism is the third most common endocrine disorder, but fewer than 2% occur as a result of an atypical parathyroid adenoma. Patients with an atypical parathyroid adenoma tend to have a more dramatic clinical presentation compared to those with classic adenoma. We see higher calcium and parathyroid hormone levels. Atypical parathyroid adenomas are classified as such due to other features which place the lesion at a higher risk for malignant behavior including higher mitotic activity, adherence to adjacent structures, banding fibrosis and a growth pattern that is either solid or trabecular. In contrast to parathyroid carcinoma, atypical parathyroid adenomas do not show invasion into the surrounding tissues or lymphatic/vascular vessels, and there should be no evidence of metastatic disease. The exact definition of an atypical parathyroid adenoma varies among institutions, and recognition of the defining features (or lack thereof) necessitates an experienced endocrine pathologist. Due to their uncertain malignant potential, patients with an atypical parathyroid adenoma should undergo routine surveillance for recurrence. Routine follow-up of calcium, parathyroid hormone and imaging is indicated to detect for recurrence. A CDC73 germline mutation is associated with recurrence compared to CDC73-negative patients. Parafibromin expression is also thought to play a role although studies so far have had discrepant results.

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Parathyroid carcinoma survival: improvements in the era of intact parathyroid hormone monitoring?

Rare Tumors ◽

10.4081/rt.2013.e12 ◽

2013 ◽

Vol 5 (1) ◽

pp. 44-48 ◽

Cited By ~ 6

Author(s):

Miya E. Allen ◽

Alison Semrad ◽

Anthony D. Yang ◽

Steve R. Martinez

Keyword(s):

Parathyroid Hormone ◽

Parathyroid Carcinoma ◽

Intact Parathyroid Hormone ◽

Parathyroid Hormone Monitoring

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Simultaneous Incidental Parathyroid Carcinoma and Intrathyroid Parathyroid Gland in Suspected Renal Failure Induced Hyperparathyroidism

The Surgery Journal ◽

10.1055/s-0037-1599072 ◽

2017 ◽

Vol 03 (01) ◽

pp. e23-e24 ◽

Cited By ~ 3

Author(s):

Andrew Pappa ◽

Trevor Hackman

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Parathyroid Carcinoma ◽

Parathyroid Tissue ◽

Central Compartment ◽

Thyroid Lobectomy ◽

Intraoperative Pth ◽

Preoperative Expectation ◽

Intraoperative Parathyroid Hormone ◽

Surgery Management

AbstractHyperparathyroidism is a common disorder affecting more than hundreds of thousands of people annually. While most commonly secondary to an adenoma, it may also arise from four-gland hyperplasia or malignancy. In the case of primary hyperparathyroidism, the number of glands involved may be unknown prior to surgery. In contrast, the metabolic disorder associated with renal failure induced hyperparathyroidism ensures a hyperplasia picture. Despite the uniform hyperplasia seen in tertiary disease and the preoperative expectation for four-gland exploration, our case demonstrates the continued need for a surgeon's vigilance during dissection to identify all glands and appropriately use intraoperative parathyroid hormone (PTH) testing. In addition, while intraoperative PTH assessment is an effective method for confirming adequacy of treatment for hyperparathyroidism, only surgical pathology can confirm malignancy, which should be considered with PTH levels > 1,000. The case also underscores the importance of comprehensive surgery management and mindful interpretation of intraoperative PTH levels in the management of hyperparathyroidism. Standard surgical technique includes complete exploration of the central compartment, and thyroid lobectomy when the aforementioned exploration fails to reveal the necessary parathyroid tissue, especially with a persistently elevated PTH. Without a standardized progressive compartment exploration and judicious use of intraoperative hormone testing, intrathyroidal parathyroid glands can be missed.

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The Ratio of Parathyroid Hormone as Measured by Third- and Second-Generation Assays as a Marker for Parathyroid Carcinoma

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-2791 ◽

2010 ◽

Vol 95 (8) ◽

pp. 3745-3749 ◽

Cited By ~ 40

Author(s):

Etienne Cavalier ◽

Adrian F. Daly ◽

Daniela Betea ◽

Pamela Nicoleta Pruteanu-Apetrii ◽

Pierre Delanaye ◽

...

Keyword(s):

Parathyroid Hormone ◽

Parathyroid Carcinoma ◽

Second Generation

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Atypical parathyroid adenoma: clinical and anatomical pathologic features

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02123-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Alessandro Galani ◽

Riccardo Morandi ◽

Mira Dimko ◽

Sarah Molfino ◽

Carla Baronchelli ◽

...

Keyword(s):

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Serum Calcium ◽

Parathyroid Carcinoma ◽

Ki 67 ◽

Pathologic Features ◽

Atypical Parathyroid Adenoma ◽

High Concentrations ◽

Group B

Abstract Background Primary hyperparathyroidism is an endocrine pathology that affects calcium metabolism. Patients with primary hyperparathyroidism have high concentrations of serum calcium or high concentrations of parathyroid hormone, or incorrect parathyroid hormone levels for serum calcium values. Primary hyperparathyroidism is due to the presence of an adenoma/single-gland disease in 80–85%. Multiple gland disease or hyperplasia accounts for 10–15% of cases of primary hyperparathyroidism. Atypical parathyroid adenoma and parathyroid carcinoma are both responsible for about 1.2–1.3% and 1% or less of primary hyperparathyroidism, respectively. Methods We performed a retrospective cohort study and enrolled 117 patients with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy. Histological and immunohistochemical examination showed that 107 patients (91.5%) were diagnosed with typical adenoma (group A), while 10 patients (8.5%) were diagnosed with atypical parathyroid adenoma (group B). None of the patients were affected by parathyroid carcinoma. Results Significant statistical differences were found in histological and immunohistochemical parameters as pseudocapsular invasion (p < 0.001), bands of fibrosis (p < 0.001), pronounced trabecular growth (p < 0.001), mitotic rates of > 1/10 high-power fields (HPFs) (p < 0.001), nuclear pleomorphism (p = 0.036), thick capsule (p < 0.001), Ki-67+ > 4% (p < 0.001), galectin-3 + (p = 0.002), and protein gene product (PGP) 9.5 + (p = 0.038). Conclusions Atypical parathyroid adenoma is a tumor that has characteristics both of typical adenoma and parathyroid carcinoma. The diagnosis is reached by excluding with strict methods the presence of malignancy criteria. Atypical parathyroid adenoma compared to typical adenoma showed significant clinical, hematochemical, histological, and immunohistochemical differences. We did not find any disease relapse in the 10 patients with atypical parathyroid adenoma during 60 months of follow-up time.

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