SAT-334 A Genetic Cause of Primary Hyperparathyroidism

Abstract Background: Primary hyperparathyroidism is a relatively common endocrine condition, affecting up to 7 out of every 1000 adults. Median age of onset is during the sixth decade of life. When present in younger patients primary hyperparathyroidism may indicate an underlying genetic cause. Case: A 23-year-old woman is referred for evaluation of hypercalcemia that was found on labs drawn after surgery for bilateral ovarian cyst removal. At the time of presentation she felt well and was without complaint. Her medical history is otherwise unremarkable. Her family history includes multiple family members with nephrolithiasis. Physical exam revealed a well appearing Caucasian woman without a palpable neck mass. Laboratory results showed: serum calcium 11.7 mg/dL (ref 8.4–10.2), ionized calcium 1.44 mmol/L (ref 1.12–1.32) and serum PTH 192 pg/mL (ref 11–65). Technetium-99 sestamibi scan revealed a low attenuating mass with focal and persistent uptake just inferior to the left thyroid lobe. She subsequently underwent left inferior parathyroidectomy, which confirmed parathyroid adenoma, with resultant normalization of serum calcium and PTH. Due to her young age of diagnosis genetic testing was performed which revealed a mutation if CDC 73. Discussion: CDC 73 mutation is known cause of inheritable neoplasia’s with a high prevalence of parathyroid dysfunction. Although penetrance and expression is variable, the mutation is associated primarily with Hyperparathyroidism Jaw Tumor Syndrome (HPT-JT), Familial Isolated Hyperparathyroidism and sporadic parathyroid carcinoma. Our patient had an allele mutation associated with HPT-JT. This syndrome classically presents with parathyroid adenoma, ossifying tumors of the mandible and renal or uterine neoplasms. The mutation is inherited in an autosomal dominant pattern and family history plays a key role in diagnosis of this rare condition. This patient had an early age of onset for hyperparathyroidism and a family history suggestive of an inherited calcium metabolism disorder. A single parathyroid adenoma is the most common presentation and surgical resection is often curative of hyperparathyroidism. In Hyperparathyroidism Jaw Tumor Syndrome patients classically develop ossifying tumors of the mandible and renal or uterine neoplasms in addition to parathyroid lesions. Rarely patients with CDC 73 mutation can develop parathyroid carcinoma. For this reason it is recommended that all first degree relatives undergo testing for CDC 73 mutation. This patient currently has no evidence of jaw, uterine or renal tumors on screening imaging. Ovarian tumors have been described separately to be associated with CDC 73 mutation, this patient may actually have an unrecognized phenotype of CDC 73 mutation. Given the potential impact of inheritable neoplasia, all young patients with unexplained hyperparathyroidism should be considered for genetic screening.

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Hyperparathyroidism-Jaw Tumor Syndrome

Case Reports in Oncology ◽

10.1159/000510002 ◽

2021 ◽

pp. 29-33

Author(s):

Travis D. Weaver ◽

Mohamed K.M. Shakir ◽

Thanh D. Hoang

Keyword(s):

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Serum Calcium ◽

Age At Onset ◽

Young Patients ◽

Neck Mass ◽

Renal Tumors ◽

Caucasian Woman ◽

Her Family ◽

Focal Uptake

Primary hyperparathyroidism is a relatively common endocrine disorder, affecting 7 out of 1,000 adults. The median age at onset is the 6th decade of life. Our objective was to present a young patient with primary hyperparathyroidism who has a positive CDC73 mutation. A 23-year-old woman was evaluated for hypercalcemia that was found after surgery for bilateral ovarian cyst removal. Her family history included multiple family members with nephrolithiasis. The physical examination revealed a well-appearing Caucasian woman with no palpable neck mass. The laboratory results showed serum calcium at 11.7 mg/dL (ref. 8.4–10.2), ionized calcium at 1.44 mmol/L (ref. 1.12–1.32), and serum PTH at 192 pg/mL (ref. 11–65). A technetium-99 sestamibi scan revealed focal uptake inferior to the left thyroid lobe. Thyroid ultrasound showed a left parathyroid adenoma. The patient subsequently underwent left inferior parathyroidectomy, which confirmed parathyroid adenoma, with resultant normalization of serum calcium and PTH levels. Due to her young age at diagnosis, genetic testing was performed, which revealed a mutation of CDC73. Although penetrance and expression are variable, the CDC73 mutation is associated primarily with hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism, and sporadic parathyroid carcinoma. This patient currently has no evidence of jaw, uterine or renal tumors on screening imaging. Given the potential impact of inheritable neoplasia, all young patients with unexplained hyperparathyroidism should be considered for genetic screening.

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Molecular and genetic features of primary hyperparathyroidism in young patients

Problems of Endocrinology ◽

10.14341/probl20166224-11 ◽

2016 ◽

Vol 62 (2) ◽

pp. 4-11 ◽

Cited By ~ 1

Author(s):

Elizaveta O. Mamedova ◽

Natalya G. Mokrysheva ◽

Ekaterina A. Pigarova ◽

Iya A. Voronkova ◽

Sergey N. Kuznetsov ◽

...

Keyword(s):

Family History ◽

Primary Hyperparathyroidism ◽

Parathyroid Carcinoma ◽

Positive Family History ◽

Young Patients ◽

Clinical Manifestations ◽

Genetic Characteristics ◽

Men1 Gene ◽

Ion Torrent Pgm ◽

Genetic Features

When primary hyperparathyroidism (PHPT) is diagnosed in a young patient in the absence of other clinical manifestations differential diagnosis between a sporadic form of PHPT and PHPT as the first manifestation of one of hereditary syndromes may be challenging. Diagnosis of sporadic or hereditary PHPT determines the extent of surgical intervention, a strategy for further observation and treatment, and the need for examination and treatment of first-degree relatives. Aim of the study — to determine genetic characteristics of PHPT with manifestation at a young age (<40 years old) with clinically sporadic PHPT and familial isolated hyperparathyroidism (FIHP).Material and methods. 40 patients with manifestation of PHPT at the age younger than 40 years, 4 of which with FIHP, were included in the study. In 11 patients Sanger sequencing of MEN1 gene was performed (ABI 3130 Genetic Analyser, «Applied Biosystems», USA). 37 patients underwent next-generation sequencing (NGS) (Ion Torrent PGM, Thermo Fisher Scientific — Life Technologies, USA) using a panel of candidate genes (MEN1, CASR, CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D). Results. In 3 (7,5%) patients (1 of which with FIHP) we revealed germline heterozygous mutations in MEN1 gene: in exon 9 p.D418N, exon 3 p.R176Q, intron 3 с.654+1G>A. In 4 (4/40, 10%) patients we revealed germline heterozygous mutations in CDC73 gene: 3 nonsense mutations in patients with parathyroid carcinoma — in exon 3 p.R91X, exon 6 p.Q166X, exon 7 p.R229X, and 1 missense mutation in a patient with parathyroid hyperplasia in exon 8 p.R263C. Conclusions. In the majority of cases (75%) PHPT in young patients without positive family history is sporadic. Search for germline mutations in the genes, leading to development of hereditary forms of PHPT (first of all in MEN1 and CDC73), is appropriate in young patients with positive family history, or when positive family history may be suspected, and in patients with parathyroid carcinoma. In the majority (75%) of FIHP cases search for other, probably yet unknown, genes is necessary.

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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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Primary Hyperparathyroidism in Sickle Cell Disease: An Unknown Complication of the Disease in Adulthood

Journal of Clinical Medicine ◽

10.3390/jcm9020308 ◽

2020 ◽

Vol 9 (2) ◽

pp. 308

Author(s):

Elsa Denoix ◽

Charlène Bomahou ◽

Lorraine Clavier ◽

Jean-Antoine Ribeil ◽

François Lionnet ◽

...

Keyword(s):

Sickle Cell Disease ◽

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Sickle Cell ◽

Serum Calcium ◽

Elevated Serum ◽

Young Patients ◽

Cell Disease ◽

Mineral Density ◽

Cervical Surgery

Primary hyperparathyroidism (pHPT) is the third most common endocrine disorder and usually affects patients between 60 and 70 years of age. To our knowledge, this condition has never been studied in young patients with sickle cell disease (SCD). Our objective was to describe the clinical and biological characteristics of pHPT in adult patients with SCD and its management. We conducted a retrospective study that included SCD patients who were diagnosed with pHPT in four SCD referral centers. pHPT was defined by the presence of elevated serum calcium levels with inappropriate normal or increased parathyroid hormone (PTH) serum levels or histopathological evidence of parathyroid adenoma or hyperplasia. Patients with severe renal impairment (GFR <30 mL/min) were excluded. Twenty-eight patients (18 women, 64%; 22 homozygous genotype, 79%) were included. The median age at pHPT diagnosis was 41 years (interquartile range –IQR- 31.5–49.5). The median serum calcium and PTH concentration were, respectively, 2.62 mmol/L (IQR 2.60–2.78) and 105 pg/mL (IQR 69–137). Bone mineral density (BMD) revealed very low BMD (≤−2.5 SD) in 44% of patients explored (vs. 12.5% among 32 SCD patients matched for SCD genotype, sex, age, and BMI, p = 0.03). Fourteen patients (50%) received surgical treatment, which was successful in all cases, but four of these patients (29%) presented with pHPT recurrence after a median time of 6.5 years. Three of these patients underwent a second cervical surgery that confirmed the presence of a new parathyroid adenoma. These results suggest that SCD is a condition associated with pHPT in young subjects. SCD patients with pHPT have a high risk of very low BMD. A diagnosis of pHPT should be suspected in the presence of mild hypercalcemia or low BMD in SCD patients.

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A Unique Case of Primary Hyperparathyroidism

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.362 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A179-A179

Author(s):

Jessica Lucier ◽

Jawairia Shakil

Keyword(s):

Family History ◽

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Parathyroid Carcinoma ◽

Endocrine Surgery ◽

Ectopic Parathyroid Adenoma ◽

History Of ◽

Ectopic Parathyroid ◽

Brown Tumors ◽

The Right

Abstract Background: Primary hyperparathyroidism is the most common cause of hypercalcemia. It is more commonly seen in postmenopausal women, but can develop in younger individuals. Brown Tumors are an uncommon finding that can be seen in sever hyperparathyroidism. These bone findings are most often seen in the maxilla or mandible, though can affect any bone. Bone changes are reversible after parathyroidectomy. Clinical Case: An 18 year old male with a PMH of nephrolithiasis presented with a two day history of flank pain and hematuria. Endocrinology was consulted for hypercalcemia and elevated PTH. He had a family history of nephrolithiasis in his maternal uncle and grandfather, but no known family history of hypercalcemia or thyroid cancer. He was not on any medications or supplements. His initial labs were significant for a calcium of 15.0, PTH of 644, and a Vitamin D 25 of 11.7. He had no known history of hypercalcemia. He was treated with aggressive hydration, 4mg of zometa, 30mg of sensipar and two doses of 200mg calcitonin, with improvement in his calcium levels. Imaging of the abdomen and pelvis revealed multifocal solid-cystic lesions in the right superior pubic ramus and the distal femur, with smaller enhancing lesions in the left subtrochanteric, consistent with Brown Tumors. SpectCT was obtained and significant for a 2.1 by 1.4cm lesion in the anterior superior mediastinum. His overall presentation was consistent with primary hyperparathyroidism secondary to an ectopic parathyroid adenoma. Due to his relative young age at presentation and degree of primary hyperparathyroidism, there was concern for MEN1 or possible parathyroid carcinoma. MRI of the pituitary was obtained and showed a 4mm microadenoma in the right side of the pituitary. Prolactin, thyroid hormones, IGF-1, plasma metanephrines and calcitonin were all within normal limits. CDC73, a genetic marker for parathyroid carcinoma, was negative. Genetic work up for MEN1 was also negative. Endocrine surgery was consulted and he underwent a resection of the ectopic parathyroid adenoma. Discusion: Though most patients with primary hyperparathyroidism are asymptomatic, nephrolithiasis and Brown Tumors can be seen with more severe cases. It is important to rule out possible genetic causes for primary hyperthyroidism in patients with abnormal presentations, as it will change the overall long term management.

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Night Sweats as the Presenting Symptom of Primary Hyperparathyroidism

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.421 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A207-A207

Author(s):

Vanessa Williams ◽

Hadoun Jabri ◽

Michael G Jakoby

Keyword(s):

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Serum Calcium ◽

Vasomotor Symptoms ◽

Temperature Threshold ◽

Hot Flushes ◽

Parathyroid Surgery ◽

Intact Pth ◽

Patient Reported ◽

Night Sweats

Abstract Background: Approximately 25–40% of patients report night sweats in the previous month during appointments with their primary care clinicians. The differential diagnosis for night sweats is broad, with hyperthyroidism, carcinoid syndrome, pheochromocytoma, medullary thyroid carcinoma, insulinoma, and acromegaly as established endocrine causes. We present a case of primary hyperparathyroidism (PHPT) in which the patient’s chief complaint was night sweats and resolution occurred after parathyroidectomy. Case. A 39-year-old female reported one-year of daily night sweats that required changes of clothes and bedding. She denied excessive daytime sweating, frequent palpitations, tremors, nightmares, rashes, fevers, chills, cough, headaches, dizziness, abdominal pain, diarrhea, disrupted menses, or unintentional weight loss. Vital signs and examination were unremarkable. Hypercalcemia (11.0 mg/dL, 8.6–10.3) was noted and confirmed by additional serum calcium measurements. Intact PTH ranged from 27–33 pg/mL (12–88), and 24 h urine calcium (258 mg) excluded familial hypocalciuric hypercalcemia (FHH). Parathyroid scintigraphy and neck ultrasound identified a left neck mass, and the patient underwent successful resection of a left inferior parathyroid adenoma. Hypercalcemia and night sweats initially resolved after surgery, but the patient returned six weeks later with recurrence of night sweats. Reevaluation was notable for serum calcium 10.4 mg/dL, phosphorus 2.4 mg/dL (2.5–5.0), and intact PTH 104 pg/mL. A right superior parathyroid adenoma was identified on repeat parathyroidectomy, and the patient experienced durable resolution of night sweats and hypercalcemia following her second parathyroid surgery. She was screened for multiple endocrine neoplasia type 1 (MEN1) due to multiple parathyroid tumors, though no known pathogenic menin gene variants were identified. Conclusions: A title/abstract search in PubMed linking “hyperparathyroidism” and “hypercalcemia” to “night sweats,” “sleep hyperhidrosis,” “sweating,” “hot flashes,” “hot flushes,” “diaphoresis” and “vasomotor symptoms” yielded only one relevant case of a postmenopausal woman with hot flushes unresponsive to hormone replacement that resolved after parathyroidectomy for PHPT. Hypercalcemia is known to affect central nervous system function. It is possible that in rare cases hypercalcemia alters function of the medial preoptic area, lowering the temperature threshold above which peripheral vasodilatation and perspiration occur to dissipate heat. The patient’s predisposition to only night sweats is unclear, though unlike the first patient reported with PHPT and sweating, our patient is premenopausal. This case indicates that vasomotor symptoms may occur with PHPT and resolve after successful parathyroid surgery.

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Hyperparathyroidism Jaw Tumor Syndrome Presenting as Recurrent Femur Fractures in a Young Woman; a Rare Presentation of a Rare Disease

Case Reports in Endocrinology ◽

10.1155/2020/9298147 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4

Author(s):

Piyumi S. A. Wijewickrama ◽

Noel P. Somasundaram

Keyword(s):

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Rare Disease ◽

Young Patients ◽

Clinical Manifestations ◽

Rare Presentation ◽

Femur Fractures ◽

High Calcium ◽

Risk Of Malignancy ◽

Exon 1

Background. Primary hyperparathyroidism usually occurs secondary to parathyroid adenoma, multiglandular hyperplasia, or parathyroid carcinoma. The patients usually present with incidentally discovered high calcium level and systemic or skeletal manifestations. In young patients with primary hyperparathyroidism, familial syndromes including multiple endocrine neoplasia types 1, 2, and 4 and hyperparathyroidism jaw tumor syndrome should be considered. Case Description. We present a case of a 22-year-old Sri Lankan woman who presented with femur fractures in a background of childhood nephroblastoma and maxillary fibro-osseous tumor. The patient had biochemical parameters suggestive of primary hyperparathyroidism with a parathyroid mass. The histology following excision of the mass revealed a parathyroid adenoma. Based on the associated clinical manifestations, hyperparathyroidism jaw tumor syndrome was suspected, and genetic studies reported a positive CDC73 mutation with a whole-gene deletion of exon 1–17. Conclusion. Hyperparathyroidism jaw tumor syndrome is an important diagnosis to consider in a young patient presenting with classic clinical features due to the risk of malignancy, familial involvement, and need to monitor for progressive systemic manifestations. As this is a rare disease, it can often be missed due to low degree of suspicion and the ability of the jaw tumor to mimic a metastatic deposit.

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MGMT Promoter Methylation and Parathyroid Carcinoma

Journal of the Endocrine Society ◽

10.1210/js.2019-00175 ◽

2019 ◽

Vol 3 (11) ◽

pp. 2114-2122

Author(s):

Sara Storvall ◽

Eeva Ryhänen ◽

Ilkka Heiskanen ◽

Tiina Vesterinen ◽

Frank V Bensch ◽

...

Keyword(s):

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Promoter Methylation ◽

Parathyroid Carcinoma ◽

Methylation Status ◽

Mgmt Promoter Methylation ◽

Promoter Methylation Status ◽

Mgmt Promoter ◽

Atypical Parathyroid Adenoma ◽

Mgmt Promoter Methylation Status

Abstract Context Parathyroid carcinoma (PC) is extremely rare. Prognosis is poor, with no known evidence-based systemic therapies. We previously reported complete remission in a patient with metastasized parathyroid carcinoma and high tumor MGMT promoter methylation status who was treated with temozolomide. Objective To study MGMT promoter methylation status in an additional set of aggressive parathyroid tumors. Design/Setting The study included 12 patients: 7 with sporadic and 5 with familial primary hyperparathyroidism (two of the latter carried a CDC73 gross deletion). Patient 9 is the previously described patient with PC and high MGMT methylation status. Her daughter (patient 12) had surgery for severe primary hyperparathyroidism due to atypical parathyroid adenoma during pregnancy. Eleven patients thus had PC and one had atypical parathyroid adenoma. MGMT promoter methylation status was determined from DNA extracted from primary (n = 10) or metastatic (n = 2) tumors. A mean methylation level >20% was considered high. Patient 11 had metastatic PC and received temozolomide cycles. Results Only the previously published patient (patient 9) had high tumor MGMT promoter methylation status. This was not a characteristic of the atypical parathyroid adenoma of the daughter (patient 12). Patient 11 (CDC73 intragenic deletion) has disseminated PC, low MGMT promoter methylation, and stable disease on follow-up after temozolomide treatment. Conclusion High MGMT promoter methylation status seems rare in PC. However, as demonstrated in other neuroendocrine tumors, some patients with disseminated PC might benefit from temozolomide. Demonstration of high methylation status could be a predictor of positive response to temozolomide treatment.

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SAT-379 Giant Parathyroid Adenoma

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.027 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Sima Saberi ◽

Matthew J Wasco ◽

Ramin Behjatnia ◽

Beth Kimball

Keyword(s):

Vitamin D ◽

Parathyroid Adenoma ◽

Serum Calcium ◽

Parathyroid Carcinoma ◽

Width Ratio ◽

Normal Range ◽

Urine Calcium ◽

Spot Urine ◽

Parathyroid Adenomas ◽

25 Oh Vitamin D

Abstract Giant parathyroid adenoma Background: Primary hyperparathyroidism is the most common cause of hypercalcemia. On ultrasound PTH adenomas are typically homogenous, hypoechoic, oval or bean-shaped with peripheral vascularity. Clinical Case: A 60 year old woman with a history of calcium oxalate nephrolithiasis presented with fatigue, worsening depression, body aches of 3 months duration. Labs showed a serum calcium 11.1 mg/dl (normal range 8.5–10.1 mg/dl), PTH 114.3 pg/ml (normal range 12–88 pg/ml), 25 OH Vitamin D 11 ng/ml (normal range above 29 ng/ml), alkaline phosphatase 137IU/L (normal range 27–120 IU/L), spot urine calcium 34.8 mg/dl, spot urine creatinine 92.1 mg/dl (estimated 24 hour urine calcium 415 mg/dl). She was started on Vitamin D 1000 IU daily. A PTH scan with SPECT/CT showed a right parathyroid adenoma and possible thyroid nodules. A neck ultrasound demonstrated a left 1.5 cm thyroid nodule and a right 3cm lesion. She underwent FNA of the left thyroid nodule and pathology was suggestive of a benign follicular nodule. She underwent parathyroid gland exploration with resection of the right lesion which was a 3.5 x 2.5 x 1.4 cm right superior 5.68 gm PTH adenoma. Postoperatively her serum calcium normalized to 10.1 mg/dl, PTH was 8.4 pg/ml, 25 OH vitamin D was 15 ng/ml. Her Vitamin D dose was increased. Clinical Lessons: A normal parathyroid gland typically weighs 30–60 mg and is 3–4 mm in size. The differential diagnosis for large parathyroid lesions is parathyroid carcinoma vs giant parathyroid adenoma. Although there is not a definitive size cutoff to define giant parathyroid adenomas, a size greater than 3.5 gm has been used (1). On ultrasound giant parathyroid adenomas are homogenous with smooth borders whereas parathyroid carcinomas are large lobulated heterogeneous hypoechoic lesions (2). A depth/width ratio on ultrasound may be the ultrasound parameter with greatest discriminatory capacity as a depth/width ratio greater than or equal to 1 had 94% sensitivity and 95% specificity for parathyroid carcinoma (2). Whether vitamin D deficiency is a risk factor for the development of large parathyroid glands is controversial as there has been conflicting data on this (1,3). Because there is no serum calcium level that distinguishes parathyroid carcinoma from a parathyroid adenoma neck ultrasound may be a helpful tool in evaluating these patients. References: 1. Spanhemier PM, Stoltze AJ, Howe JR, et al. Do giant PTH adenomas represent a distinct clinical entity? Surgery. 2013 Oct; 154(4):714–719. 2. Hara H, Igarashi A, Yano Y, et al. Ultrasonagraphic features of PTH carcinoma. Endocr J. 2001 April 48(2):213–217. 3. Rao DS, Honasoge M, Divine GW, et al. Effect of vitamin D nutrition on PTH adenoma weight: pathogenetic and clinical implications. J Clin Endocrinol Metab. 2000 Mar 85(3): 1054–1058.

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SAT-353 Familial Hyperparathyroidism - Due to a Rare Genetic Mutation

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.470 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Adeyinka Taiwo ◽

Joseph Stephen Dillon ◽

Jennifer Stinson

Keyword(s):

Family History ◽

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Gene Mutation ◽

Parathyroid Tissue ◽

Clinical Manifestations ◽

Young Age ◽

Parathyroid Cancer ◽

History Of ◽

Familial Hyperparathyroidism

Abstract Introduction: Hyperparathyroidism occurs most commonly in middle age patients, predominantly in women. It can be caused by parathyroid adenoma, hyperplasia or parathyroid carcinoma. Genetic predisposition can be found in about 10% of primary hyperparathyroidism due to certain gene mutations. This case emphasizes the importance of taking a detailed family history when patients present with hyperparathyroidism at a young age, so that familial hyperparathyroidism, if present, can be detected and relatives screened. Clinical case: A 26 y.o. male presented with symptoms of fatigue and polydipsia for several years. He was noted to have a serum calcium of 12.4 mg/dL(8.5–10.5), with parathyroid hormone of 213 pg/ml (15–65). He denied any history of kidney stones, fractures and no palpable neck masses. The patient’s family history was significant for his paternal half-sister who had parathyroidectomy for hyperparathyroidism at 20yrs old and paternal grandmother died of parathyroid cancer in her 50s. The patient’s father died of pancreatic cancer at 41yrs old. A neck ultrasound revealed a mass posterior to the left inferior thyroid. A Sestamibi parathyroid scan revealed a parathyroid adenoma at the posteroinferior aspect of the left hemithyroid. Labs for free metanephrines and normetanephrine, prolactin and gastrin levels were all normal. Due to his young age and the possibility of having familial hyperparathyroidism, he underwent bilateral neck exploration and parathyroidectomy, with removal of his left inferior, right superior, left superior parathyroid glands and left upper thymus. Surgical pathology revealed, hypercellular parathyroid tissue. Post operatively, his calcium and vitamin D remained within the normal range. Genetic studies revealed a mutation in the parafibromin gene - CDC73 (also called HRPT2), a tumor suppressor gene, which is on chromosome 1q25. The patient currently has 6 children ranging from age 5 months to 6 years. He was advised to have his children tested any time from age 7 years for the gene mutation. The patient has remained stable 4yrs post operatively, with normal calcium and PTH levels. He does not have any history of jaw tumor. He never had an ultrasound kidney done. He is being monitored with yearly lab tests. Conclusion: CDC73 gene mutation-associated disorders are inherited as an autosomal dominant fashion, with variable penetrance. This gene mutation can be found in conditions such as hyperparathyroidism jaw tumor, familial hyperparathyroidism and parathyroid cancer. Reference: 1. CDC73-Related Disorders: Clinical Manifestations and Case Detection in Primary Hyperparathyroidism. J Clin Endocrinol Metab. 2017 Dec 1;102(12):4534–4540.

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