This article is more than 5 years old. Information may no longer be current.
Treating hyperparathyroidism with two extrathyroidal masses
A 58-year-old female was self-referred 6 years ago for a second opinion regarding her hyperparathyroidism. She was told of an elevated parathyroid hormone of 97 pg/mL and 24-hour urinary calcium of 350 mg with a normal creatinine and serum calcium.
Stephanie L. Lee
She has no history of bone fractures or renal stones but a DXA bone density 1 year previously in 2007 showed osteoporosis in the hip (see Table).
After being started on vitamin D and hydrochlorothiazide for her hypercalciuria, she came to Boston Medical Center for a second opinion. A history was obtained that was significant for a daily calcium intake >1,600 mg of elemental calcium and vitamin D intake of about 4,000 units/day.
Laboratory testing showed a normalized parathyroid hormone (PTH) level of 63 pg/mL (normal 11-80), 25-hydroxyvitamin D level of 34.9 ng/mL, an elevated calcium level of 11.2 mg/dL, and albumin level of 4 g/dL. After reducing her daily calcium intake to 500 mg/day to 600 mg/day, her serum and 24 hr urine calcium normalized to 10.2 mg/dL and 225 mg/day, respectively. DXA bone density showed osteopenia in the lumbar spine and osteoporosis in the femoral neck density (see Table).
Osteoporosis, secondary hyperparathyroidism
At this time, the opinion stood that the patient had osteoporosis and secondary hyperparathyroidism corrected with vitamin D therapy. She also had primary PTH autonomy but did not currently fit the criteria for primary hyperparathyroidism.
Figure 1. Right thyroid and parathyroid ultrasound. A. Transverse image of the lower right thyroid lobe showing a hypoechoic mass located posterior to the inferior lobe of the thyroid. P = parathyroid adenoma. THY = thyroid. TR = trachea. CA = carotid artery. B. Sagittal image of the right thyroid lobe and parathyroid adenoma. C. Sagittal image with Doppler analysis. The hypoechoic mass is outside the hyperechoic thyroid capsule with a feeding vessel (green arrow) with arching arborization of intranodular vascular flow (red arrow). A: transverse measurement. B, D: anteroposterior measurement. C: Sagittal measurement. Reprinted with permission from: Stephanie L. Lee, MD, PhD
She was treated with two annual doses of IV zoledronic acid 5 mg in September 2008 and October 2009 with stable bone density (see Table). The patient was followed with normal calcium and parathyroid levels but intermittently showed elevated urinary calcium levels related to excess calcium intake >1,200 mg/day.
She did not return for follow-up between 2010 and 2013, but eventually returned because of progression of her osteoporosis (see Table). With this history, there was concern for worsening of her parathyroid autonomy, and a thyroid/parathyroid ultrasound was performed.
Ultrasound findings
The ultrasound showed a normal thyroid in size and echotexture. There was a 1-cm x 0.9-cm x 0.6-cm (sagittal x anteroposterior x transverse) hypoechoic mass located posterior to the inferior right thyroid lobe, consistent with a right inferior parathyroid adenoma (Figure 1). A second 1-cm x 0.3-cm x 0.5-cm hypoechoic mass was located posterior to the mid-left lobe, consistent with a left superior parathyroid adenoma (Figure 2).
Figure 2. Left thyroid and parathyroid ultrasound. A. Transverse image of the mid-left thyroid lobe showing a hypoechoic mass located posterior to the thyroid. P = parathyroid adenoma. THY = thyroid. TR = trachea. CA = carotid artery. B. Sagittal image with Doppler analysis. The hypoechoic mass is outside the hyperechoic thyroid capsule with intranodular vascular flow (red arrow).
Both masses had the appearance of parathyroid adenomas with a feeding polar vessel with arborization and internal vascularity. Laboratory tests at this visit showed the development of primary hyperparathyroidism and hypercalcemia with a serum calcium level of 11.8 mg/dL (optimal, 8.6 mg/dL-10.5 mg/dL), albumin level of 4.5 g/dL, magnesium level of 2.7 mg/dL, creatinine level of 0.7 mg/dL, 25-(OH)D level of 59 ng/mL (optimal, 30 ng/mL-60 ng/mL) and PTH level of 102 pg/mL (optimal, 15 pg/mL-65 pg/mL).
The patient was referred for resection of double parathyroid adenoma. Intraoperative parathyroid level fell from 125 pg/mL at baseline and to 38 pg/mL after 5 minutes and 25 pg/mL after 20 minutes of resection of both adenomas. The intraoperative PTH fell by 75% at 5 minutes and 80% after 20 minutes of resection to a normal level consistent with complete resection of the double parathyroid adenomas. Pathology showed both masses were hypercellular parathyroid tissue with a surrounding rim of normal parathyroid cells consistent with a double parathyroid adenomas weighing 380 mg (right lower parathyroid adenoma) and 200 mg (left upper parathyroid gland). Postoperatively, her levels of calcium (10 mg/dL) and parathyroid hormone (56 pg/mL) returned to normal.
Double parathyroid adenomas
Double parathyroid adenomas occur in about 7% (range, 2%-15%) of cases of primary hyperparathyroidism. Small cases studies and this patient suggest there is a preferential cross-bilateral distribution of double parathyroid adenomas (both upper, both lower and bilateral upper and lower), but the two adenomas may occur in any combination.
In nearly all patients, intraoperative parathyroid levels dropped by at least 50% from baseline after removal of both abnormal parathyroid glands. But because there is often a disparity between the sizes of the two adenomas, one series showed two-thirds of the patients showed a false-positive 50% decline in intraoperative parathyroid levels after the resection of the first adenoma, which is usually the largest, but without normalization of the intraoperative parathyroid level.
When the second smaller adenoma was removed, nearly all of the intraoperative parathyroid levels normalized. To avoid persistent hyperparathyroidism from double adenomas, it has been suggested that preoperative imaging should be examined for multigland disease, and besides a 50% decrease in intraoperative parathyroid levels after removal of an adenoma, the level should normalize.