Primary hyperparathyroidism (PHPT) is a disorder of calcium metabolism characterized by hypercalcemia and excessive secretion of parathyroid hormone (PTH) from one or more of the four parathyroid glands. Primary hyperparathyroidism is caused by a single adenoma in 80% of cases and the remainder (15%–20%) is due to multiple-gland hyperplasia or rarely (1%) to parathyroid carcinoma.1 Primary hyperparathyroidism predominantly affects women, with a female-to-male ratio of approximately 4:1.2 Currently, most PHPT patients do not present with the classical clinical features of kidney stones or severe bone disease. Today, individuals are more often diagnosed through routine biochemical laboratory testing performed for other purposes. The diverse presentations of PHPT range from fatigue and depression through decreased concentration, memory loss, sleep problems, bone or muscle pains, and gastroesophageal reflux disease. Neither patients nor their providers may even recognize these symptoms initially as attributable to the diagnosis of PHPT, but postoperatively, there is often significant improvement in clinical features resulting in improved quality of life.3,4
Parathyroid glands are derived from the 3rd and 4th pharyngeal pouches and ectopic parathyroid adenomas (PAs) may be located anywhere from the base of the tongue to the mediastinum.5 Approximately 16% to 25% of PAs are detected in ectopic location.6 In cases when an ectopic PA is suspected, ultrasonography (US) of the neck, either as grayscale or color Doppler, and technetium-99m (99mTc)-sestamibi (MIBI) dual-phase parathyroid scan are first-line imaging modalities, despite having relatively low sensitivity and specificity.7–9 Emerging modalities include single-photon emission computed tomography (SPECT) alone or in combination with CT (SPECT/CT), which further improve PA localization.10,11 The current treatment strategy is surgical removal soon after diagnosis. Surgical exploration has become more precise by the use of advanced imaging modalities and intraoperative use of gamma probe.
A 53-year-old woman complaining of fatigue, weakness, and numbness of her feet with elevated levels of PTH was diagnosed with PHPT during her routine medical check-up. Ultrasonography was performed to determine the etiology of PHPT and indicated no evident pathology of the parathyroid glands in the neck. Subsequently, 99mTc-MIBI dual-phase parathyroid scan demonstrated a 3 × 4 × 5-mm ectopic PA located laterally to the aortic arch. She also had an aberrant origin of right subclavian artery arising as a terminal branch of the aortic arch. She had underwent posterior mediastinal exploration through a lower transverse cervical incision in an experienced center in United States, but removal of PA failed because of anatomical difficulties. She was then referred to our department for aortopulmonary location of PA, presence of aberrant right subclavian artery, and the patients' preference.
On arrival, she denied any symptoms of chest pain, shortness of breath, nausea, vomiting, diarrhea, palpitations, or headache. She also denied any history of nephrolithiasis, any bone fractures or bone pain, or familial history of HPT. Physical examination and routine laboratory investigations were normal. However, serum calcium was elevated at 11.3 mgl/dL (reference range = 8.8–10.6 mg/dL) and serum phosphorus was 3.3 mg/dL (reference range = 2.5–4.5 mg/dL). Serum PTH was elevated at 127.4 pg/mL (reference range = 12–88 pg/mL). Serum alkaline phosphatase was 62 U/L (reference range = 30–120 U/L). Serum albumin was also normal at 4.65 g/dL (reference range = 3.5–5.2 g/dL). Bone densitometry revealed osteopenic changes within intertrochanteric regions (−1.1SD of T-score). However, a well-circumscribed round PA was identified preoperatively by 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT), which showed increased focal activity at the aortopulmonary window (APW) neighboring to arcus aorta. The 18F-FCH PET/CT scan revealed no evidence of abnormal activity at the normal location of the parathyroids (Figs. 1A, B). At multidisciplinary discussion including cardiovascular surgery, general surgery, and nuclear medicine, the patient was scheduled for minimally invasive surgery.
Two hours before the operation, the patient had received intravenous injection of 370 MBq of 99mTc-MIBI. After double-lumen endobronchial intubation (Robertshaw, 35F) for single-lung ventilation a 3.5-cm upper reverse J-sternotomy with atraumatic tissue handling was performed (Fig. 2B). Left lung was deflated during mediastinal dissection. Innominate vein was identified and then suspended. Radioactivity counts were obtained from the APW using intraoperative gamma probe (Crystal probe; Crystal Photonics, Berlin, Germany). Although 200- to 250-cps ground activity was obtained from the normal tissues as a background activity, higher counts (approximately 400–450 cps) than ground activity were obtained from the region consistent with the area observed on preoperative 99mTc-MIBI and 18F-FCH PET scans. After ligation of its vasculature, the adenoma was then removed and ex vivo radioactivity count was obtained as 200 to 250 cps. Pathological examination confirmed PA sizing 3 × 5 × 6 mm (Fig. 2A). Peripheral tissues were searched using the gamma probe and no other suspicious structure was detected. After hemostasis, mediastinal hemovac drain was inserted. Tissues were approximated without tension. The examination of tissue specimens under a microscope showed oxyphil cell PA (Figs. 3A, B).
Two hours after the surgery, serum PTH was decreased to 16.0 pg/mL (reference range = 12–88 pg/mL). Serum calcium was decreased to 9.0 mgl/dL (reference range = 8.8–10.6 mg/dL) on the first postoperative day. Her recovery was uneventful and discharged home at 5th postoperative day. At the multidisciplinary meeting, we have decided to schedule the patient for bone densitometry and 18F-FCH PET/CT at 6-month follow-up.
An ectopic PA that causes PHPT can be challenging to detect despite various available imaging modalities because of ectopic location and small size. Multiple diagnostic modalities for precise imaging the parathyroid glands include US, CT, radionuclide scintigraphy, PET-CT, and PET-MRI.12 Dual-phase 99mTc-MIBI scintigraphy has similar sensitivities as US. However, when combined with US, the overall sensitivity can be increased from 88% to 95%.13 In cases of discrepant results between scintigraphy and US, it is important to rely on other diagnostic imaging modalities. Preoperative 18F-FCH PET/CT has a high sensitivity and positive predictive value for PA detection in patients with PHPT and negative or inconclusive cervical ultrasound and 99mTc-MIBI SPECT/CT results. Currently, for PA imaging, an 18F-FCH PET/CT protocol with a low injected 18F-FCH dose and a standard acquisition time seems feasible.14
With the introduction of endoscopic technologies to cardiovascular surgery, minimally invasive cardiac surgery has advanced to decrease postoperative pain, blood loss, and cerebral or respiratory complications. Although reverse J-shaped partial upper sternotomy is commonly used in aortic valve and ascending aortic surgery, superior mediastinal PA removal has rarely been reported.15
Chamberlain procedure through anterior mediastinotomy would be an alternative approach on this case, which may provide an easy way to access to the anterosuperior mediastinum. This approach is also useful for diagnosing the solid mediastinal masses and may be performed in conjunction with a cervical mediastinoscopy allowing digital palpation and assessment of the AP lymph nodes and incisional biopsy of the large anterior mediastinal masses.16 We tried to avoid to remove a rib or a piece of cartilage and longer 5- to 8-cm incisions.
Any hypercalcemia and high level of PTH without PA in the neck should alert physicians to search for ectopic locations through combination of different imaging techniques. The mediastinum should be cautiously noted because it is the very common location for an ectopic PA. Because parathyroid crisis is life-threatening and its prognosis is poor, it requires aggressive medical therapy and early surgical treatment.17
Surgical intervention under the guidance of intraoperative gamma probe is recommended in those with positive parathyroid scintigraphy and particularly in the presence of resistant or recurrent hyperparathyroidism as well as ectopic PAs. Intraoperative gamma probe shortens duration of surgery by providing an easier surgical approach. Further advantage is the fact that it confirms the success of surgery by ex vivo counts obtained by gamma probe from the tissue excised.18
In conclusion, with the guidance of parathyroid scintigraphy and PET/CT, and the use of intraoperative gamma probe, ectopic mediastinal PAs can be removed safely using targeted minimally invasive approach.
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Keywords:©2018 by the International Society for Minimally Invasive Cardiothoracic Surgery
Primary hyperparathyroidism; Parathyroid adenoma; Mediastinum; Gamma probe; PET/CT