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Thymus gland and ectopic inferior parathyroid adenomas
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A 73-year-old woman from Antigua presented for a routine initial visit with a new primary care physician. Her blood pressure was 230/100 mm Hg, and she was started on hydrochlorothiazide 25 mg daily. Her ionized calcium was elevated to 7.7 mg/dL (4.5 mg/dL to 5.3 mg/dL) and the hydrochlorothiazide was switched to atenolol. Her total serum calcium remained high at 15.1 mg/dL (8.4 mg/dL to 10.2 mg/dL), with a rising creatinine of 1.7 mg/dL. The patient was admitted to the hospital.
 Emily Wood Demetriou |
 Stephanie L. Lee |
On admission, she was started on saline diuresis with IV fluids and furosemide, and the endocrine team was consulted. The patient had been feeling well and denied constipation, abdominal pain, vomiting, polyuria, depression or mental status changes. She had no history of kidney stones or fractures. She had lost 10 lb unintentionally during the preceding years. Her medications were atenolol and aspirin. She had no family history of any endocrinopathy. Physical exam was unremarkable with a BP of 140/69 mm Hg, including a normal neck exam with no palpable thyroid or parathyroid nodules. Admission lab testing revealed calcium ≥15 mg/dL (8.4 mg/dL to 10.2 mg/dL); intact parathyroid hormone level 2,439 pg/mL (11 pg/mL to 80 pg/mL); 25-hydroxyvitamin D 24 ng/mL; serum phosphorus 2.5 mg/dL (2.8 mg/dL to 4.1 mg/dL); and magnesium1.4 mg/dL (1.6 mg/dL to 2.6 mg/dL).
A neck ultrasound showed several subcentimeter spongiform nodules in the thyroid. No extrathyroidal or thyroidal masses were seen suggestive of a parathyroid adenoma. Sestamibi scan localized a focus of activity within the left anterior mediastinum (see figure 1A). CT scan demonstrated a corresponding enhancing anterior mediastinal mass (see figure 1B). Serum calcium decreased modestly after calcitonin therapy to 13.2 mg/dL and further after IV pamidronate 60 mg to 10.7 mg/dL.
A mediastinal parathyroid adenoma was removed by a median sternotomy and thymectomy. The thymus contained a rubbery, brown, well-circumscribed 3-cm mass (see figure 2). Initially, intraoperative parathyroid hormone (IOPTH) was 1,713 pg/mL at baseline. It fell to 208 pg/mL 10 minutes after removal of the mass, 187 pg/mL after 20 minutes and 107 pg/mL after 60 minutes.
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Figure 1. Mediastinal parathyroid adenoma. A.
AP–delayed technetium-99m-sestamibi scintigraphy shows a focus of tracer
uptake (red arrow) within the left anterior mediastinum inferior to the thyroid
gland (yellow arrow) and sternal notch marker (green arrow). B. Coronal CT scan
with contrast showing a 1.7 cm x 2.1 cm x 2.7 cm mass (red arrow) in the left
anterior mediastinum with contrast enhancement and small calcifications. The
thyroid gland (yellow arrow), location of sternal notch (green arrow) and
contrast in the jugular vein (*) are indicated.
Photos courtesy of: Stephanie L.
Lee, MD, PhD |
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Because the IOPTH level remained elevated, there was concern for a second parathyroid adenoma, and a neck dissection was performed. The left superior gland and right inferior gland were visualized and appeared normal. The left inferior gland was presumed to be the intrathymic parathyroid adenoma. The right superior parathyroid gland was not visualized and was presumed to be intrathyroidal and, therefore, the patient underwent a right thyroid lobectomy. Postoperatively, the serum calcium normalized without further treatment. Final pathology revealed an enlarged hypercellular parathyroid gland (3.3 cm) within the thymus without vascular or capsular invasion and a multinodular goiter. Lab testing seven months later showed normal calcium with an elevated intact parathyroid hormone 207 pg/mL and ongoing renal impairment with a creatinine of 1.7 mg/dL.
Between 11% and 22% of patients with primary hyperparathyroidism are estimated to have mediastinal adenomas, but the incidence may be as high as 38% in patients who require reoperation because of persistent hyperparathyroidism. The location of ectopic parathyroid adenomas can be predicted from the embryology of parathyroid gland development. The inferior parathyroid glands and thymus are both formed from the third pharyngeal pouch. The thymus and parathyroid glands descend together during fetal development into the lower neck. Typically, the inferior parathyroid glands stop migrating near the posterior surface of the thyroid gland with 50% to 65% located about 1 cm below the inferior thyroid artery, and 15% to 20% located just rostral or caudal to this site. One-quarter to 35% of the inferior parathyroid glands do not separate and descend with the thymus into the thoracic inlet or anterior mediastinum. For this reason, approximately 80% of mediastinal parathyroid adenomas are within or associated with the thymus. Rarely, the inferior parathyroid glands fail to descend and remain superior to the thyroid at the bifurcation of the carotid artery. The fourth pharyngeal pouch gives rise to the superior parathyroid glands. The superior parathyroid glands descend more predictably into the neck during development, with 75% to 80% located about 1 cm above the inferior thyroid artery. Approximately 5% of superior parathyroid adenomas are ectopic in location.
Technetium-sestamibi imaging is frequently used for preoperative localization of a parathyroid adenoma to permit minimally invasive surgical removal. Ultrasound can detect up to 84% of parathyroid adenomas in the evaluation of primary hyperparathyroidism; however, it is not useful for mediastinal parathyroid adenomas. The sensitivity of detection for mediastinal adenoma of the technetium-sestamibi scan has been reported to be 85%, whereas the sensitivity for CT scan localization is 92%.
IOPTH is often used to confirm removal of all hypersecreting parathyroid tissue. The most common IOPTH criterion used to predict successful surgery is a decrease in IOPTH by >50% from baseline 10 minutes after removal of the parathyroid adenoma. The accuracy of a >50% drop in IOPTH is estimated at 97% for predicting a biochemical cure (no recurrence of hypercalcemia six months postoperatively). Additionally, as in this case, some surgeons use a return to the normal parathyroid hormone range as a criterion for success. It is unclear whether there is a long-term difference in recurrence rates depending on the criteria used. One report suggested no difference in recurrence rates (as defined by elevated parathyroid hormone and hypercalcemia) after four years of follow-up; however, it was a retrospective study.
Mediastinal parathyroid adenomas are a cause of primary hyperparathyroidism that must be considered, particularly if a cervical parathyroid adenoma is not located. Once primary hyperparathyroidism is confirmed biochemically, the initial imaging test is typically a neck ultrasound exam. Approximately 84% of parathyroid adenomas can be detected by ultrasound, and the remainder of patients should have preoperative localization with technetium-sestamibi scanning with attention toward expected ectopic locations. The lower limit of the imaging field should always extend below the level of the aortic arch to identify mediastinal adenomas. If a suspected mediastinal adenoma cannot be located at the time of surgery, a thymectomy should be performed because 80% of mediastinal parathyroid adenomas are associated with the thymus.
Emily Wood Demetriou, MD, is a Fellow in Endocrinology, and Stephanie L. Lee, MD, PhD, is Associate Chief and Professor of Medicine, both in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center.
For more information:
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