Incidental finding leads to parathyroid adenoma discovery

Issue: May 2016

ByPoorani Goundan, MBBS

ByStephanie L. Lee, MD, PhD, ECNU

A 52-year-old woman with type 2 diabetes and hypertension was found to have hypercalcemia incidentally on routine blood testing. She did not have family history of hypercalcemia. She did not take excessive calcium in her diet or in the form of supplements or antacids and was not on hydrochlorothiazide or lithium. She had no history of renal stones or fragility fractures.

Diagnosis, surgery

Laboratory evaluation revealed the following: calcium 11.8 mg/dL (reference range, 8-10.5 mg/dL), albumin 4.3 g/dL, ionized calcium 6.3 mg/dL (reference range, 3.8-5.3 mg/dL), phosphorous 2.3 mg/dL (reference range, 2.3-3.7 mg/dL), creatinine 0.69 mg/dL, 25-hydroxyvitamin D 13 ng/mL (optimal range, 30-60 ng/mL) and parathyroid hormone 214 pg/mL (PTH; reference range, 11-90 pg/mL).

Stephanie L. Lee

These laboratory results were consistent with primary and vitamin D deficiency-related secondary hyperparathyroidism.

Figure 1: Ultrasound of large parathyroid adenoma. A heterogeneous, isoechoic mass with a more hypoechoic echotexture at the periphery was located inferior to left thyroid lobe, measuring 4.9 x 2.7 x 2.1 cm (longitudinal x anterioposterior x transverse) with a prominent vascular supply. (A) Transverse view with Doppler. (B) Longitudinal view with Doppler. All figures reprinted with permission from: Stephanie L. Lee, MD, PhD, ECNU

An ultrasound of the neck showed a multinodular goiter and a 4.9-cm lobulated mass just inferior to and separate from the left thyroid lobe. The mass was centrally heterogeneous and isoechoic, but the periphery of the nodule was more hypoechoic. Doppler imaging showed a prominent vascular flow into the periphery of the nodule (Figure 1).

Due to the discordance between the large size of the lesion, the peripheral vascular flow and the relatively mild PTH elevation (also in the setting of vitamin D deficiency), a fine-needle aspiration of the mass with two passes of a 25-guage needle was performed. The needle washout with 1 cc normal saline contained an intact PTH level of 1,975 pg/mL consistent with parathyroid tissue.

Figure 2: Surgical specimen of a 16-g parathyroid gland. This adenoma is about 500 times the normal size of a parathyroid gland.

The patient then underwent a focused parathyroidectomy with intraoperative PTH levels falling from 811 pg/mL to 33 pg/mL, 10 minutes after the removal of a well-circumscribed 16-g mass (Figure 2). The final pathology confirmed the diagnosis of a parathyroid adenoma (Figure 3).

Parathyroid imaging

We have come far from the previous practice of full neck exploration for the identification of all four parathyroid glands before the surgical removal of a parathyroid adenoma. Ultrasound technetium-99m sestamibi scan and 4-D CT provide preoperative localization to reduce operative time and complications of surgery. Office ultrasound is becoming the first-line modality of imaging and, in experienced hands, has a sensitivity of up to 80% to 90% in localizing parathyroid adenomas.

Figure 3: Histopathology of the parathyroid adenoma shows (A) parathyroid adenoma with predominantly clear cells, (B) the capsule of the parathyroid adenoma (PA) containing many blood vessels, including a large-caliber artery (yellow arrows), and (C) a thin rim of residual normal parathyroid tissue (red arrows) adjacent to the hypercellular parathyroid adenoma (PA).

The average size of the normal parathyroid gland is approximately 4 mm to 6 mm in length, 2 mm to 4 mm in width and 1 mm to 2 mm in thickness, making detection by ultrasound difficult. However, enlargement of one or more of the parathyroid glands, due to an adenoma, for example, allows visualization by ultrasound.

Most adenomas are seen outside the thyroid gland with a hyperechoic line of the thyroid capsule separating the two structures. The superior parathyroid is usually found posterior to the upper two-thirds of the thyroid gland but may also be in the tracheoesophageal groove. The inferior parathyroid, which is more variable in its location, is commonly found near the inferior thyroid pole, but can be located anywhere along the pathway between the bifurcation of the carotid and as low as an intrathoracic position in or near the thymus. The thin parathyroid capsule is usually not distinctly visualized. The adenoma can create an indentation of the posterior capsule of the thyroid gland and mold due to pressure of surrounding structures into various shapes, including lobulated, oval, crescent-shaped, fusiform and irregular.

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A parathyroid adenoma viewed on ultrasound is typically described as homogeneously hypoechoic; however, isoechoic, hyperechoic, cystic and heterogeneous lesions are also seen. Doppler assessment of vascular flow of the suspected parathyroid adenoma may show a polar feeding vessel and a “vascular arc” or arborization pattern of blood flow into the adenomatous tissue. Posterior adenomas, for example, in the tracheoesophageal groove, may be difficult to visualize by ultrasound, but asking the patient to cough or perform a Valsalva maneuver may change the position of the adenoma and aid in identification.

An ultrasound pattern of parathyroid adenoma with an isoechoic core with a surrounding hypoechoic zone has been described by investigators. Very rarely, calcifications can be seen in parathyroid adenomas on ultrasound. Infrequently, the adenoma may have a purely cystic appearance and is clinically not associated with hyperparathyroidism or hypercalcemia.

Identification caveats

A clinical pearl is that the fluid from a perithyroidal parathyroid cyst is crystal clear and thin, like water. If confirmation is required, a fine-needle aspiration can be performed with PTH analysis of the syringe washings.

As ultrasound is being used frequently in the evaluation of hypercalcemia, we are seeing parathyroid adenomas with both the classical appearance as well as those that do not fit the typical description, including heterogeneous and isoechoic adenomas, as seen with this patient. With this operator-dependent imaging technique, careful observation and an index of suspicion are required to be able to identify lesions. Ultrasound does, however, provide a relatively quick, clinic-based and noninvasive method to localize parathyroid adenomas. An ultrasound-guided thin-needle aspiration and measurement of PTH hormone can be helpful to identify parathyroid adenomas with atypical ultrasound appearance.

References:
Acar T, et al. Med Ultrason. 2015;doi:10.11152/mu.2013.2066.172.tka.
Yeh MW, et al. Endocr Pract. 2006;12:257-263.

For more information:
Stephanie L. Lee, MD, PhD, ECNU, is an Endocrine Today Editorial Board member. She is associate professor of medicine and director of thyroid health in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center. She can be reached at Boston Medical Center, 88 E. Newton St., Endocrinology Evans 201, Boston, MA 02118; email: stephanie.lee@bmc.org. Lee reports no relevant financial disclosures.
Poorani Goundan, MBBS, is an endocrine fellow at Boston Medical Center. She reports no relevant financial disclosures.