Substernal oxyphil parathyroid adenoma producing PTHrP with hypercalcemia and normal PTH level

Abstract Background: Patients with normocalcemic primary hyperparathyroidism (PHPT) share similar risks of osteoporosis and nephrolithiasis with patients having hypercalcemic PHPT. The prevalence and natural history of normocalcemic PHPT is not well defined. Parathyroid microadenomas weighing < 100 mg may present as special clinical challenges in both the diagnosis and surgical resection. Clinical Case: A 55-year-old woman presented for an evaluation of osteoporosis following a non-traumatic L1 compression fracture at the age of 50 years. Noting an initial serum calcium of 10 mg/dL, we diagnosed her with normocalcemic PHPT based on a concurrent parathyroid hormone (PTH) level of 112 pg/mL (12-88 pg/mL) and a lack of other causes for an elevated PTH, including a normal eGFR, serum 25-hydroxyvitamin D, 24-hour urine calcium, and autoantibodies for celiac disease. Initial dual-energy x-ray absorptiometry (DXA) scan from 2015 showed normal bone mineral density (BMD) and T-scores in the L-spine, total hip, and femoral neck. Neck imagings, including ultrasound, sestamibi scan, and 4D CT, failed to localize a parathyroid adenoma. In the absence of a target and indications for parathyroidectomy other than osteoporosis, she was treated with bisphosphonates. While her serum calcium remained normal (9.6-10.2 mg/dL) despite an elevated PTH level (92-116 pg/mL) over a two-year period, subsequent DXA scans showed a significant loss in BMD on the bisphosphonates, prompting a peripheral DXA scan, which revealed severe osteoporosis at the distal third of the forearm (BMD 0.450 g/cm2, T-score -3.7), consistent with PTH-associated bone resorption. Following a 4-gland exploration with removal of 2 parathyroid microadenomas (63 and 100 mg), intra- and post-operative PTH levels normalized. She now awaits a repeat DXA scan at 1 year after a successful parathyroidectomy. Conclusion: Although many patients with normocalcemic PHPT may progress to develop hypercalcemia, some remain normocalcemic over an extended period. We report a patient who maintained normocalcemia for over 2 years. To correctly establish the diagnosis of normocalcemic PHPT, a comprehensive evaluation must be performed to exclude secondary causes of an elevated PTH (renal insufficiency, hypovitaminosis D, hypercalciuria, and malabsorption). Since significant osteoporosis may be preferentially seen in the cortical bone, BMD at the distal 1/3 of forearm should be evaluated in addition to the L-spine, hips and femoral necks. When a parathyroid adenoma cannot be localized in patients with normocalcemic PHPT, a careful 4-gland exploration for parathyroid microadenoma(s), paying special attention to the size, texture, and shape of the glands, and guided by intraoperative PTH levels, ensures the successful removal of the culprit gland(s).

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Abstract #838: A Case of Parathyroid Adenoma with Normal PTH Level: A Special Entity for Primary Hyperparathyroidism

Endocrine Practice ◽

10.1016/s1530-891x(20)45172-9 ◽

2016 ◽

Vol 22 ◽

pp. 181

Author(s):

Ilgin Yildirim Simsir ◽

Hatice Ozisik ◽

Banu Pinar Sarer Yureli ◽

Ilker Altun ◽

Mehmet Erdogan ◽

...

Keyword(s):

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Pth Level

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ONCOCYTIC INTRATHYROID PARATHYROID ADENOMA MASQUERADING AS HURTHLE CELL NEOPLASM: FINE NEEDLE ASPIRATION CYTOLOGY OF TWO CASES

10.36106/ijsr/0430540 ◽

2021 ◽

pp. 57-58

Author(s):

Mega Lahori ◽

Hua Chen

Keyword(s):

Parathyroid Adenoma ◽

Thyroid Tissue ◽

Parathyroid Tissue ◽

Needle Aspiration ◽

Thyroid Lobe ◽

Cell Adenoma ◽

Hürthle Cell ◽

Hypoechoic Nodule ◽

Left Thyroid Lobe ◽

Pth Level

Ectopic parathyroid adenomas in thyroid tissue are uncommon (0.7 - 6%), and their oncocytic variants are exceedingly rare. We report two cases of intrathyroid parathyroid adenoma which were diagnosed as Hurthle cell adenoma on cytology. Case 1 is a 49-year-old female with a 2.4 cm hypoechoic nodule in the left lateral neck. Electrochemiluminescent immunoassay of the aspirate revealed PTH level of 422 pg/ml, conrming the presence of hyperfunctional parathyroid tissue. Subsequent resection of the left thyroid lobe revealed an enlarged intrathyroidal parathyroid. Case 2 is a 58-year-old female with a 2.1 cm hypoechoic nodule in the posterior-mid left thyroid lobe. Strong overexpression of parathyroid hormone and Chromogranin A genes and low expression of thyrocyte-related genes suggested parathyroid origin of the cells sampled. MEN1 mutation and multiple copy number alterations indicated the neoplastic nature of the nodule. Parathyroid oxyphil cells and oncocytic thyrocytes share cytomorphological ndings and distinguishing them by cytology alone is challenging, especially when the targeted lesion is intrathyroidal. Distinguishing intrathyroid oncocytic parathyroid adenoma from oncocytic thyroid follicular lesions has signicant clinical implications as Bethesda-IV category lesions have 20%–30% risk of malignancy. While stippled chromatin or intracytoplasmic fat vacuoles may be suggestive of parathyroid origin, these are not specic. Classifying the origin of a nodule as parathyroid vs thyroid rests upon the detection of PTH in aspirate material by ECL, immunocytochemistry or next-generation sequencing. In parathyroid aspirates, PTH level 100 pg/mL is suggestive of the presence of PTH-secre ≥ ting tissue at the site biopsied or along the needle track.

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A Parathyroid Adenoma: Benign Disease Presenting with Hyperparathyroid Crisis

Case Reports in Medicine ◽

10.1155/2010/596185 ◽

2010 ◽

Vol 2010 ◽

pp. 1-4

Author(s):

A. S. Tahim ◽

J. Saunders ◽

P. Sinha

Keyword(s):

Parathyroid Adenoma ◽

Epigastric Pain ◽

Cystic Mass ◽

Benign Disease ◽

Thyroid Lobe ◽

Ultrasound Studies ◽

Rare Manifestation ◽

Parathyroid Disease ◽

Endocrine Surgeon ◽

Pth Level

Hyperparathyroid crisis is a rare manifestation of parathyroid disease. We present the case of a 53-year-old gentleman with a review of the current literature. He presented in acute renal failure with epigastric pain and vomiting. His serum-corrected calcium (CCa2+) was raised at 5.2 mmol/L, in addition to a massively raised parathyroid hormone (PTH) level (3957 ng/L). Ultrasound studies of the neck revealed a 2 cm well-defined mass inferoposterior to right thyroid lobe. CT scans of the neck showed a normal mediastinum and confirmed no associated lymphadenopathy. Having undergone medical resuscitation for 9 days, a neck exploration revealed a cystic mass, which was excised. Histological investigations revealed a 9.25 g, cystic parathyroid adenoma with no features of malignancy. His PTH and CCa2+returned to normal postoperatively. This suspicious presentation of benign disease, including a marked elevation in PTH, highlights the challenges facing the endocrine surgeon in dealing with parathyroid disease.

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PARATHYROID ADENOMA LOCALISATION: DEPENDING ON PTH LEVEL, WHICH IMAGING MODALITY SHOULD BE USED PRE-OPERATIVELY?

Clinical Nuclear Medicine ◽

10.1097/00003072-199110000-00048 ◽

1991 ◽

Vol 16 (10) ◽

pp. 797

Author(s):

D Picard ◽

D Synnott ◽

E Nassif ◽

P D??Amour ◽

M Picard ◽

...

Keyword(s):

Parathyroid Adenoma ◽

Imaging Modality ◽

Pth Level

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MON-925 A Wolf in Sheep’s Clothing: Intermittent Hypercalcemia from an Intrathyroidal Parathyroid Carcinoma

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1634 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Jonathan Trejo ◽

Lyan Gondin Hernandez ◽

Joy Wortham ◽

Brenda Sandoval ◽

Gustavo R Armaiz-Pena ◽

...

Keyword(s):

Vitamin D ◽

Parathyroid Adenoma ◽

Parathyroid Carcinoma ◽

Thyroid Tissue ◽

Laboratory Evaluation ◽

Thyroid Ultrasound ◽

Uncommon Presentation ◽

Sestamibi Scan ◽

Pth Level ◽

Benign Thyroid

Abstract Parathyroid carcinomas have an estimated prevalence of <0.1% of all cancers and is found in <1% of patients with primary hyperparathyroidism (PHPT). While they frequently present with PTH- mediated hypercalcemia, they are often distinguished by severe hypercalcemia and markedly elevated PTH levels compared to their benign counterparts. Parathyroid cancers most often arise from existing parathyroid glands, making them identifiable with standard imaging modalities such as parathyroid sestamibi scan, thyroid ultrasound, and 4-D CT scan. There are reports of non-functioning parathyroid carcinomas, including those that are intrathyroidal. Most of the reported cases are found de novo. We present a case of an intrathyroidal parathyroid carcinoma with intermittent hypercalcemia. A 72-year-old man with a history of Graves’ disease and RAI ablation in the 1970’s was found to have hypercalcemia up to 14.1 mg/dL (8.5 - 10.1) with a PTH level of 223 pg/mL (14 - 64). He denied any constipation, bone pain, fractures, renal stones, or changes in mental status. Thyroid ultrasound demonstrated a 3.9 cm R lobe complex nodule reported as TI-RADS 4, and a hypoechoic 1.0 cm nodule in the L lobe. No definitive parathyroid adenoma was reported. A parathyroid sestamibi scan showed persistent uptake in area of the L 1.0 cm nodule favoring a PTH adenoma while the R nodule had initial radiotracer uptake with delayed washout but no technetium uptake. Laboratory evaluation demonstrated a 24-hour urinary calcium of 338 mg/24hr, low 25-OH vitamin D, and normal vitamin D 1,25 levels. Osteoporosis was diagnosed by BMD with T-score of -3.2 at the femoral neck. Repeat serum corrected calcium level was 9.7 mg/dL and PTH was 93 pg/mL. FNA cytology of the R thyroid mass was reported as benign thyroid tissue. Due to size of the R thyroid nodule, the patient underwent a R hemithyroidectomy with L parathyroidectomy. Intraoperative PTH levels decreased from 154 to 120 pg/mL after removal of L parathyroid adenoma; PTH level decreased further to 12.9 pg/mL after R hemithyroidectomy. Surgical pathology revealed 4.5 cm R parathyroid carcinoma without thyroid tissue with positive margins, and a hypercellular L parathyroid gland. PHPT resolved. After review of all aspects of the case and discussion with patient, the decision was made to monitor his calcium and PTH levels and repeat BMD 1 year from resection. This is an uncommon presentation of a rare endocrine malignancy. To our knowledge, there are few case reports of non-functional parathyroid carcinomas that were initially reported as thyroid cancer or benign thyroid tissue after biopsy. This report underscores the importance in keeping this rare diagnosis in the evaluation of PTH-mediated hypercalcemia.

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SAT-341 Hyperparathyroid Crisis Precipitated by Rapid Correction of Symptomatic Hypercalcemia in an Occult Ectopic Parathyroid Adenoma

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.803 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Vanessa Goyes Ruiz ◽

Nidhi Bansal

Keyword(s):

Renal Insufficiency ◽

Parathyroid Adenoma ◽

Mental Status ◽

Calcium Sensing ◽

Ectopic Parathyroid Adenoma ◽

Parathyroid Adenomas ◽

History Of ◽

Ectopic Parathyroid ◽

Pth Level ◽

Rapid Correction

Abstract Background: Parathyroid adenomas (PA) are typically benign, slow-growing tumors causing gradual increase in parathyroid hormone (PTH) and serum calcium (s.Ca) levels. Hyperparathyroid crisis is a rare and potentially fatal syndrome, which occurs due to rapid elevation of PTH and s.Ca levels (s.Ca >15mg/dL). This can potentiate severe metabolic derangements, manifesting as altered mental status (AMS), renal insufficiency and cardiac arrhythmias. We present a case of hyperparathyroid crisis in the setting of an occult ectopic parathyroid adenoma. Case: 75 year old female with a medical history of osteoporosis, hypertension and Parkinson’s disease, presented to our hospital with AMS and one week history of diarrhea. She was recently hospitalized for pneumonia and treated with antibiotics. Biochemical analysis revealed corrected s.Ca 15.4mg/dL (8.2- 9.6mg/dL; 7 days prior s.Ca was 9.7mg/dL), renal insufficiency (Cr 2.26mg/dL; baseline 1.2) with normal serum phosphorus, magnesium, 25-hydroxyvitamin D and alkaline phosphatase. PTH was found to be elevated at 75pg/mL (15-65pg/mL). She was treated with aggressive intravenous hydration and calcitonin 200mg BID for 3 days. Her s.Ca appropriately trended down. However, her PTH level continued to rise: 319pg/mL 12 hours later, 591pg/mL on day 2 and peaked to 1,242pg/mL on day 3. CT angiography neck showed an incidental finding of a heterogeneous, possibly necrotic, soft tissue nodule in the left paraesophageal region. Additional work-up with technetium 99 Sestamibi scan revealed persistent activity in the upper tracheoesophageal groove consistent with an ectopic PA. She underwent parathyroid exploration with excision of an enlarged ectopic left superior parathyroid adenoma, confirmed on histopathological analysis. The remaining parathyroid glands were normal. PTH declined to 34pg/mL postoperatively. Her mental status improved significantly returning to baseline within a few days with normal PTH and s.Ca levels. Discussion: Secretion of PTH is mediated by s.Ca via the calcium sensing receptors (CaSR). Studies have shown that patients with PA have decreased expression of the CaSR leading to an autonomous rise in PTH secretion and a higher PTH-calcium set point. In our case, the patient initially presented with a mildly elevated PTH level and symptomatic hypercalcemia. The rapid correction of s.Ca levels precipitated a remarkable rise in PTH levels. We postulate that this was caused by a possible upregulation mechanism in calcium sensing by adenomatous parathyroid tissue that is responsive to acute lowering of s.Ca levels, triggering a hyperparathyroid crisis. Reference: (1) Corbetta S., et al. Calcium-sensing receptor expression and signaling in human parathyroid adenomas and primary hyperplasia. Clinical Endocrinology. 2000; 52(3):339-48.

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An Unusual Presentation of Primary Hyperparathyroidism: Ectopic Parathyroid Gland and Multiglandular Disease

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.367 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A181-A182

Author(s):

Sonia Helen Perez-Cavero ◽

Marlon Augusto Yovera Aldana ◽

Carlos Zubiate

Keyword(s):

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Thyroid Tissue ◽

Unusual Presentation ◽

Multiglandular Disease ◽

Intact Pth ◽

Blood Calcium ◽

Parathyroid Disease ◽

Very High ◽

Pth Level

Abstract Primary hyperparathyroidism (PHPT) can be associated as a single parathyroid adenoma in approximately 85% of patients, the remaining 15% of them correspond to individuals with hyperplasia. The multiglandular parathyroid disease varies in range 7–33% and contribute a persistent PHPT. We report a case of primary hyperparathyroidism with an unusual presentation of ectopic mediastinal parathyroid. The case was of a 54-year-old female, who started her illness 3 years ago, with frequent headache, regular fatigue and muscle pain, denied losing weight. She was admitted to emergency room for a urinary infection. During the hospitalization showed bilateral nephrocalcinosis, hypercalcemic crisis. She has a background of total thyroidectomy and subtotal parathyroidectomy because a thyroid adenomatous hyperplasia and parathyroid hyperplasia with removal of a total of three parathyroid glands. She had very high PTH level. Laboratory: serum calcium: 16.8mg/dl; ionic calcium: 2.37 mmol/L; P: 1.9 (2.7–4.5g/dL); Hb: 9 g/dL; Platelets: 558 000 per microliter; Leukocytes 9 600 cells/mcL; Albumin: 4g/dl; TSH: 0.06 mU/L; fT4: 1.29 (L-T4 doses were 100 ug). Four months after parathyroid surgery, the intact PTH level dropped from 1602 ng/l to 550 (15–65 ng/L). Computed tomography and Tc-sestamibi scintigraphy - SPECT revealed a residual cervicothoracic mass in retroesophageal region (D1-D2) (Fig1 -2). The patient underwent a new surgery and the intact PTH dropped 39ng/L. Histopathology revealed characteristic features of a parathyroid adenomatous (10 gram weight) (Fig.3); additionally a retroesternal ectopic thyroid tissue. There was not reappearance of high blood calcium and parathormone levels more than 6 months after second surgery for PHPT. An unusual case of PHPT caused by a multiglandular disease parathyroid varies (four glands and a ectopic gland), reliable histopathologic adenomatous and hyperplastic parathyroid disease, and persistent primary hyperparathyroidism with very high serum intact PTH level. Reference: (1) Masi L. Primary Hyperparathyroidism. Brandi ML (ed): Parathyroid Disorders. Focusing on Unmet Needs. Front Horm Res. Basel, Karger, 2019, vol 51, pp 1–12. (2) Pecheva M, Mahendran K, Kadlec J, Lofthouse M1, Van Tornout F. Mediastinal giant parathyroid adenoma-a minimally invasive mediastinal surgical approach for an emergency presentation. Ann Cardiothorac Surg. 2016 Jan;5(1):70–3. (3) Cakmak H 1, Tokat AO, Karasu S, Özkan M. Adenoma paratiroideo mediastínico gigante. Tuberk Toraks. 2011; 59 (3): 263–5. (4)Thier M, Daudi S, Bergenfelz A, Almquist M. Predictors of multiglandular disease in primary hyperparathyroidism. Langenbecks Arch Surg. 2018;403(1):103–109.

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