Perithyroidal cyst in a medical resident

A 35-year-old woman was referred to the endocrine clinic for evaluation of a right cervical cyst. The patient underwent cervical and thoracic spine MRI for right shoulder pain and a 3-year history of paresthesias of the upper extremities. T1-weighted images of a cervical MRI showed a 3-cm cyst abutting the inferior right lobe of thyroid gland (Figure 1).

She denied hoarse voice, sore throat or dysphagia. She denied tremor, sweating, insomnia, palpitations or changes in weight. Peripheral neuropathy workup was initiated. She was found to have positive rheumatoid factor (1:100) and anti-cyclic citrullinated peptide antibodies (1:100). Given her family history of rheumatoid arthritis, she was given plaquinol for treatment of the paresthesias. On physical examination, the patient was hemodynamically stable without thyromegaly, perithyroidal masses or cervical adenopathy.

Xiao Hui Wang

Stephanie L. Lee

T2-weighted cervical MRI showed a hyperintense oval mass within or just posterior to inferior pole of the right lobe of the thyroid (Figure 2). A hyperintense mass on T2-weighted images is consistent with a protein-rich fluid in a cyst. Thyroid ultrasound showed a simple cyst with posterior enhancing echoes measuring 3 cm × 1.5 cm × 1.5 cm adjacent to the inferior lobe of right thyroid lobe (Figures 3 and 4). There was no solid component seen, but the scalloped margins of the cyst suggested loculation. It could not be determined by imaging studies whether the cyst was within the posterior and inferior right thyroid lobe or an adjacent extrathyroidal cyst.

Ultrasound-guided fine needle aspiration (FNA) was performed. Approximately 5 mL of thin, watery, clear fluid was collected for the measurement of parathyroid hormone (PTH) and thyroglobulin levels. A blood sample was also collected for the measurement of serum intact PTH, calcium, albumin, thyroid-stimulating hormone and 25-OH(D) levels. Postaspiration ultrasound showed the complete resolution of the right cervical cyst. The patient was scheduled for follow-up in 5 days. Her cervical ultrasound showed the partial recurrence of the right cervical cyst to about 70% of the initial size (Figure 4). Her laboratory studies showed serum calcium 9.4 mg/dL, albumin 4 gm/L, 25-OH(D) 20 IU/mL and TSH 2.3 uU/mL. Her right cervical cyst fluid analyses showed intact PTH of 70 with a serum PTH of 40.

Figure 1. Coronal T1-weighted neck MRI. The parathyroid cyst appears to be hypointense and is located in the right neck between carotid artery and trachea. Fluid is hypointense on T1-weighted images. Photos courtesy of: Stephanie L. Lee, MD, PhD

Figure 2. Axial T2-weighted neck MRI. Cyst appears as a hyperintense mass located posterior to the right lobe of the thyroid. Trachea (Tr). Protein-rich fluid is hyperintense on T2-weighted images.

Figure 3. Ultrasound of the parathyroid cyst. Transverse images show a cystic mass located posterior and inferior to the right inferior pole of the thyroid (THY). Cyst was located between carotid artery (C) and trachea (TR). A. Transverse images obtained at level of the lower lobe of the thyroid shows a small hypoechoic areas posterior to the thyroid. B. Only if images are obtained caudal to the thyroid gland can the cyst be easily seen.

Figure 4. Ultrasound of the parathyroid cysts before and after FNA of fluid. Before the aspiration the cyst can be seen posterior and inferior to the thyroid gland. Most of the cyst is inferior to the thyroid. Cyst was completely aspirated by FNA but returned to about 70% of the initial volume after only 5 days.

Parathyroid cysts

Parathyroid cysts are rare cystic lesions arising in the neck and anterior mediastinum. There are fewer than 250 cases reported in the literature. Before the FNA era, most of the parathyroid cysts were identified after the surgical removal of the cysts. In 1953, Crile reported the first case of a parathyroid cyst diagnosed preoperatively using FNA. A clinical pearl is clear, thin, watery fluid aspirated from perithyroidal cyst is diagnostic of a parathyroid cyst. Most of the parathyroid cysts are nonfunctional with the gender ratio of 2.5:1 in women and men. Only about 20% to 30% of parathyroid cysts are functional with elevated circulating PTH levels. Interestingly, functional parathyroid cysts occur more often in men than women, with a ratio of 1.6:1.

Morphologically, most of the parathyroid cysts are solitary simple cysts located in the lower neck, near the lower poles of the thyroid gland. On ultrasound exam, the cysts are smooth-walled anechoic lesions with increased through-transmission on ultrasound. There is generally no internal structure but occasionally septation or loculation presents in the functional parathyroid cysts. These cysts can be mistaken as the cold thyroid nodules on radioiodine scanning if they compress the normal thyroid tissue.

The etiology of parathyroid cysts is unknown. One theory suggests parathyroid cysts develop from embryogic remnants of the third or fourth brachial pouch from where the normal parathyroid glands develop form. The other hypothesis suggests parathyroid cysts arise from the coalescence of microcysts, retention of parathyroid secretion or cystic degeneration of the existing adenomas.

Functional, nonfunctional cysts

There are histological differences between functional and nonfunctional cysts. Nonfunctional cysts are simple cysts lined by a flattened-cuboid to low-columnar epithelium usually with watery, thin, clear fluid, whereas functional cysts lack an identifiable lining. They may contain foci of hemorrhage or necrosis with brown, turbid or even bloody fluid and hemosiderin-laden macrophages. Some of the functional cysts are multilocular lesions with thin walls and are found in close association with either an adenoma or hyperplasic gland.

The differential diagnoses for parathyroid cyst are a cystic thyroid nodule, a thyroglossal duct cyst and a brachial cleft cyst. Parathyroid cyst was diagnosed by FNA with analysis of the fluid for PTH. The characteristics of the parathyroid cyst fluid are thin, clear and colorless. The PTH levels are elevated within the cyst fluid when compared with serum PTH levels in both functional and nonfunctional parathyroid cysts. Interestingly, Birnbaum and Van Herle suggest that the measurement of PTH using a mid-molecule assay, which can detect degraded forms of PTH, as well as intact PTH, may be the more appropriate test. They reported that parathyroid cysts occasionally produce PTH fragments, rather than intact PTH, and that exclusive reliance on intact hPTH assay could lead to a missed diagnosis.

The PTH hormone that is in the cyst fluid is degraded into N-terminal and C-terminal fragments that are not biologically active and are not measured on the current two-site immunometric intact PTH assay. We report an example that showed that analysis of PTH fluid measured an intact PTH level of 75 pg/mL (reference range for serum 10-65) while the C-terminal assay was extremely elevated at 24,878 pg/mL (reference range for serum 70-270). If an intact PTH level is measurable, especially if above the lower limit of the reference range for serum, it is abnormal and consistent with a parathyroid cyst.

Once the diagnosis of parathyroid cysts has been made, the management depends upon whether the cyst is functional or nonfunctional. The definitive treatment for both is surgical removal. In the nonfunctional cysts, the complete disappearance of the cysts after FNA is well documented in the literature. However, recurrence of the nonfunctional cyst occurs frequently, as shown in this case (Figure 4). In general, the observation without intervention may be appropriate for the small and asymptomatic cysts. Within the functional cysts, surgical removal with the exploration of all four parathyroid glands is recommended.

For this patient, the diagnosis of a simple nonfunctional parathyroid cyst was made. She was given vitamin D 50,000 units weekly for 12 weeks. The patient referred conservative observation or “watchful waiting.� She will be followed with periodic thyroid ultrasound, serum PTH and calcium levels.

Xiao Hui Wang, MD, is a fellow in endocrinology at Massachusetts General Hospital and Stephanie L. Lee, MD, PhD, is associate chief of the section of endocrinology, diabetes and nutrition and associate professor of medicine at Boston Medical Center.

For more information:

• Birnbaum J. J Endocrinol Invest. 1989;12:831-836.
• Crile G. Surgery. 1953;34:151-154.
• Lee SL. Thyroid. 2000;10:1125-1126.