Thyroid nodule or parathyroid adenoma?

Columnist recommends diagnostic ultrasound before minimally invasive surgery for a parathyroid adenoma to confirm location.

Issue: March 2008

ByStephanie L. Lee, MD, PhD, ECNU

A 48-year-old woman presented with a history of passing a renal stone of unknown composition. Testing revealed a calcium 10.2 mg/dL (reference range: 8.5-10.4), albumin 4 mg/dL, 25 hydroxy Vitamin D 24 ng/mL (reference range 20-100), and intact parathyroid hormone 62 pg/mL (reference range 10-65).

After repleting her 25 hydroxy Vitamin D to 32 ng/mL, a repeat intact parathyroid hormone level was elevated at 84 pg/mL, with a calcium of 10.4 mg/dL. A 24-hour urine collection contained calcium elevated to 630 mg/24 hrs and a creatinine 1.09 g with an oral intake of calcium of approximately 500 mg/day.

Stephanie L. Lee

Based on the 1990 NIH Consensus Statement Panels for the management of hyperparathyroidism, this patient was considered a surgical candidate due to a markedly elevated 24-hour urine calcium (>400 mg/d), age younger than 50 years old and nephrolithiasis.

Tc99m sestamibi parathyroid scan

A Tc99m sestamibi parathyroid scan (see Figure 1) demonstrated increased tracer uptake in the area of the right lobe of the thyroid gland. Further analysis with single photon emission computed tomography imaging failed to determine whether the tracer was located within or posterior to the right lobe of the thyroid gland.

She returned to the endocrine clinic for neck ultrasonography (see Figure 2) that revealed a hypoechoic mass with peripheral hypervascularity but no microcalcifications either adjacent to or within the right thyroid lobe. An ultrasound-guided fine needle aspiration biopsy of the nodule was performed with care to avoid entering the thyroid gland and revealed cells with mild nuclear pleomorphism arranged in a microfollicular pattern and occasional pseudofollicles (see Figure 3). No colloid or macrophages were noted.

In anticipation of possible difficulty with distinguishing between a thyroid and parathyroid lesion by cytology, one 25-gauge needle was washed in 1 mL of normal saline after expelling the sample for standard cytology. The wash fluid contained intact parathyroid hormone of 1,069 pg/mL.

Immunocytochemistry demonstrated cells staining for parathyroid hormone, confirming the diagnosis of a PTH adenoma. After minimally invasive parathyroidectomy, surgical pathology revealed a parathyroid adenoma abutting the capsule of the right lobe of thyroid gland.

Figure 1: Tc99m Sestamibi Parathyroid Scintigraphy. Intense tracer accumulation (arrowhead) after delayed imaging in the right paramedian neck in the region of the mid-pole of the right thyroid lobe. The sternal notch marker is indicated by an arrow. SPECT imaging could not determine if the tracer uptake with adjacent to or within the right lobe of the thyroid.

Figure 2: Transverse and longitudinal views of high resolution ultrasonography of the right thyroid lobe with a 12-MHz frequency linear array probe. The hypoechoic nodule located posterior to the mid-lobe of the right thyroid is indicated by an arrow in both the transverse and longitudinal views of the right lobe of the thyroid. TR= trachea.

Figure 3: Cytology of fine-needle aspiration biopsy of parathyroid adenoma. Smears show cells with mild pleomorphism arranged in a microfollicular pattern (arrowhead) and pseudofollicles (arrow). Considerable overlap in appearance of the cytology of thyroid and parathyroid nodules prevent conclusive diagnosis of a parathyroid adenoma.

Preoperative imaging

Imaging of parathyroid adenomas prior to surgery for primary hyperparathyroidism is controversial. Traditional bilateral neck exploration with multi-gland sampling has a success rate of 90% to 95%. If the patient has had prior thyroid or parathyroid surgery, preoperative localization studies have recently been useful to direct the surgeon to the site of the parathyroid adenoma (minimally invasive parathyroidectomy), thereby limiting the extent of surgery to a unilateral exploration of the neck.

In this case, 99mTc-sestimibi nuclear scintigraphy study raised the question of an intrathyroidal PTH adenoma. The subsequent ultrasound study could not distinguish between a parathyroid adenoma within or immediately adjacent to, the right lobe of the thyroid and a thyroid nodule. A nodule was located by ultrasound (see Figure 1) in the right paratracheal region with ultrasound characteristics typical of parathyroid adenomas, including a homogeneously hypoechoic echotexture and peripheral vascularity seen on color Doppler.

False-positive parathyroid sestamibi studies occur when there is concomitant thyroid pathology. Ultrasound-guided fine needle aspiration confirmation of masses detected by ultrasonography or by 99mTc-MIBI (methoxy-isobutyl-isonitrile) (sestamibi) scintigraphy has been recommended prior to minimally invasive surgery for hyperparathyroidism in the presence of known thyroid disease.

The cytology of parathyroid and thyroid tissue overlaps in cytomorphology and there is no single feature that is diagnostic of a parathyroid tissue. The parathyroid cytology may show cohesive 3-D groups, microfollicles, and either single cells or naked nuclei. In those cases where thyroid and parathyroid cells are admixed because the thyroid must be transversed by the biopsy needle, it can be impossible to diagnose a parathyroid lesion.

Diagnostic ultrasound with high frequency probe

Since cytology for PTH adenomas is not definitive, it is recommended that an intact parathyroid level be measured in needle washings from parathyroid FNA biopsy. Assay for parathyroid hormone from a CT-scan guided biopsy was first reported by John Doppman using 22-gauge needles, but sufficient material for PTH assay is obtained after a sample is expelled for cytology from a wash of a single 25 or 27-gauge needle. Tissue and cell debris must be removed by centrifugation to avoid damaging automated assay instrument.

In summary, a diagnostic ultrasound using a high frequency probe is recommended prior to minimally invasive surgery for a parathyroid adenoma to confirm the location. PTH adenomas usually can be located because of the typical hypoechoic ultrasound appearance and location posterior to the thyroid gland. If there is any question about the identity of the mass, especially if there is concomitant thyroid pathology, ultrasound guided biopsy with an assay of the needle wash for iPTH is recommended.

For more information:

Abraham D, Sharma PK, Bentz J, et al. Utility of ultrasound-guided fine-needle aspiration of parathyroid adenomas for localization before minimally invasive parathyroidectomy. Endocrine Practice. 2007;13:333-337.

Absher K, Truong LD, Khurana KK, Ranzy I. Parathyroid cytology: Avoiding diagnostic pitfalls. Head & Neck. 2002;24:157-164.

Dimashkieh H, Krishnamurthy S. Ultrasound guided fine needle aspiration biopsy of parathyroid gland and lesions. Cyto Journal. 2006;3:1-7.

Doppman JL, Krudy AG, Marx SJ, et al. Aspiration of enlarged parathyroid glands for parathyroid hormone assay. Radiology. 1983;148:31-35.

Erbil Y, Salmashoglu A, Kabul E, et al. Use of preoperative parathyroid fine-needle aspiration and parathyroid hormone assay in the primary hyperparathyroidism with concomitant thyroid nodules. The Am J Surgery. 2007;193:665-671.

Kamaya A, Quon A, Jeffrey R.B. Sonography of the abnormal parathyroid gland. Ultrasound Quarterly. 2006;22:253-262.

NIH Conference Panel. Diagnosis and management of asymptomatic primary hyperparathyroidism: consensus development conference statement. Ann Intern Med. 199;114:593-597.

Zheng X, Xu S, Wang P, Chen L. Preoperative localization and minimally invasive management of primary hyperparathyroidism concomitant with thyroid disease. J Zhejiang Univ . 2007;8:626-631.