Giant parathyroid adenoma: a case report and review of the literature
Giant parathyroid adenoma is a rare type of parathyroid adenoma defined as weighing > 3.5 g. They present as primary hyperparathyroidism but with more elevated laboratory findings and more severe clinical presentations due to the larger tissue mass. This is the first reported case of giant parathyroid adenoma from the Middle East.
A 52-year-old Indian woman presented with a palpable right-sided neck mass and generalized fatigue. Investigations revealed hypercalcemia with elevated parathyroid hormone and an asymptomatic kidney stone. Ultrasound showed a complex nodule with solid and cystic components, and Sestamibi nuclear scan confirmed a giant parathyroid adenoma. Focused surgical neck exploration was done and a giant parathyroid adenoma weighing 7.7 gm was excised.
Giant parathyroid adenoma is a rare cause of primary hyperparathyroidism and usually presents symptomatically with high calcium and parathyroid hormone levels. Giant parathyroid adenoma is diagnosed by imaging and laboratory studies. Management is typically surgical, aiming at complete resection. Patients usually recover with no long-term complications or recurrence.
KeywordsGiant parathyroid adenoma Parathyroidectomy Primary hyperparathyroidism Minimal invasive parathyroidectomy Atypical parathyroid adenoma
Complete blood count
Fine-needle aspiration cytology
Giant parathyroid adenoma
Intraoperative parathyroid hormone
Minimally invasive parathyroidectomy
US National Institutes of Health
The normal parathyroid gland weighs approximately 50–70 mg. Parathyroid adenomas (PTAs) are usually small, measuring < 2 cm and weighing < 1 gm . Giant PTAs (GPTAs), although rare, are most commonly defined as weighing > 3.5 gm, with some reports describing weights up to 110 gm [2, 3]. Both PTA and GPTA present with the syndrome of primary hyperparathyroidism (PHPT), the third most common endocrine disorder . The pathophysiology of PHPT is autologous secretion of parathyroid hormone (PTH) by one or more of the parathyroid glands . Although PHPT can be caused by parathyroid hyperplasia or carcinoma, however, around 85% of cases of PHPT are due to PTAs, and the majority of these are because of solitary PTAs, of which GPTA comprise a small number .
To the best of our knowledge, this case report describes the first case in the Middle East of a patient with non-ectopic GPTA presenting with visible neck swelling. This case report also reviews the published literature to report on the clinical characteristics and typical presentation of GPTA as well as diagnosis and treatment.
A 52-year-old Indian woman was referred to our Surgical Endocrinology clinic at Hamad General Hospital in Doha, Qatar. She complained of a neck swelling and generalized fatigue. Laboratory results showed hypercalcemia and elevated PTH. Her past social, environmental, family, and employment history (housewife) were unremarkable. She did not smoke tobacco and never consumed alcohol. There was no past history of symptomatic kidney stones; however, a recent computed tomography (CT) scan of her abdomen and pelvis showed a 2 mm non-obstructing calculus in the lower pole calyx of her right kidney with no hydroureteronephrosis. Her past medical history indicated that she had dyslipidemia, controlled with medication; however, she was not on any other medication. On physical examination, a right-sided neck swelling was obvious on inspection; on palpation a mobile non-tender nodule could be felt, approximately 3 cm in size. The rest of the physical examination was unremarkable. A neurological examination was unremarkable. On admission, her pulse, blood pressure and temperature were normal.
Serology laboratory tests showed corrected calcium of 3.12 mmol/L, an intact PTH of 503 ng/L, vitamin D of 19.97 nmol/L, and normal thyroid-stimulating hormone (TSH) level. Her renal functions were within normal limits, serum creatinine was 67 μmol/L, and 24-hour urine calcium was 4.30 mmol/L per 24 hours. Her complete blood count (CBC) and liver laboratory findings were within normal limits. Microbiology laboratory tests were not deemed necessary.
A 52-year-old woman presented with a visible palpable right-sided neck mass and generalized fatigue. Ultrasound showed a complex nodule with solid and cystic components, and a Sestamibi nuclear scan confirmed a GPTA. Focused surgical neck exploration was done and a GPTA weighing 7.7 gm was excised. This case of non-ectopic GPTA is unusual in that it presented mainly with visible palpable right-sided neck mass, which was large to the extent that the initial ultrasound suggested that it could be a thyroid nodule.
PTAs are well-reported tumors that cause PHPT. However, when their weight exceeds 3.5 gm, they are classified as GPTA . Ours weighed 7.7 gm, and is considered a smaller GPTA in relation to other reported cases [7, 8, 9].
Literature review: Case studies of giant parathyroid adenoma (2009–2019)
Ca (mmol/L)/PTH (ng/L)
Aggarwal et al., 2009 
Visible swelling, palpable nodule, bone pain, R humerus and R pelvic fractures
US: well-defined hypoechoic lesion, posterior to left lobe thyroid
Parathyroidectomy (not specified)
95 × 50 × 35
Chief cell adenoma
Salehian et al., 2009 
Visible swelling, bone pain, nausea, vomiting, weight loss
US neck: heteroechoic mass, inferior right lobe (2 × 4.8 × 3 cm); 99mTc-MIBI: abnormal collection of tracer in R side of neck
Neck exploration and parathyroidectomy (collar neck incision)
55 × 35 × 20
Sisodiya et al., 2011 
US: large hypoechoic lesion in right paratracheal region with retrosternal extension
low anterior cervical approach
Mentioned in discussion
39 × 20 × 17
Asghar et al., 2012 
US: large cyst (6 × 3.7 cm) on left side with thrombosis of IJV; MIBI: cystic lesion in left side neck displacing the thyroid gland on the right; CT: large hypodense lesion left side of neck with peripheral enhancement, retrosternal extension and mass effect with deviation of trachea and thrombosis of LIJV
Parathyroidectomy T-shaped incision
10 suspicious-looking lymph nodes also removed from levels 7 and 8 (by ENT and thoracic surgery teams)
110 × 70 × 60
PTA with prominent cystic degeneration; no lymph node metastasis
Vilallonga et al., 2012 
US: 47 × 22 mm nodule in left thyroid lobe
Hemithyroidectomy (it was intrathyroidal)
Available, not used
Max. diameter 30
Calcium IV d1, oral d2
Neagoe et al., 2014 
C 1: Bone pain, abdominal pain, nausea, palpable nodule
C 2: Parathyroid crisis, palpable nodule
C 3: Recurrent kidney stones, brown tumor of tibia
MIBI: detected adenomas in the 3 cases
Bilateral neck exploration and parathyroidectomy
C 1: 50 × 30 × 20
C 2: 55 × 40 × 30
C 1: 30.6
C 2: 35.2
C 3: > 30
2 PTA; 1 partially cystic PTA
C 1: Hungry bones syndrome
C 2: Mild hypocalcemia and hungry bones syndrome
C 3: Mild hypocalcemia
Haldar et al., 2014 
US: 6 cm mass in L inferior cervical location; MIBI: persistent activity in same location; SPECT: tubular structure in superior mediastinum
4 cm left collar neck incision
65 × 30 × 15
Garas et al., 2015 
Bone pain, palpable nodule
US: lobular well-defined hypoechoic lesion behind L lower pole of thyroid gland; MRI: left inferior PTA, extends deep into mediastinum
Parathyroidectomy (transverse cervical incision)
Done – 94% reduction in 25 minutes
Max. diameter 70
Chief cell PTA
Rutledge et al., 2016 
Enlarging neck mass, constipation, palpable nodule
MIBI: lesion posterior to right lobe of thyroid with concentrated tracer
R thyroid lobectomy and parathyroidectomy with level 6 neck dissection (suspected carcinoma)
80 × 55 × 30
Symptomatic hypocalcemia, hungry bone syndrome
Krishnamurthy et al., 2016 
Recurrent attacks of acute pancreatitis, palpable fullness
CT: 6 × 4 cm mass in L paratracheal region with extension to superior mediastinum; PET–CT: isolated uptake, left paratracheal region; MIBI: localized to L inferior parathyroid gland; Preoperative FNA-C was doned
Parathyroidectomy via transcervical approach
Max. diameter 60
Castro et al., 2017 
Asymptomatic, palpable nodule
US: solid lesion behind L thyroid lobe; SPECT: intense uptake, back of L thyroid lobe in early and late phases
Parathyroidectomy (not specified)
Done, 90% reduction
64 × 16 × 20
Sahsamanis et al., 2017 
US: enlarged parathyroid gland on lower side of cervical region; MIBI: large concentrations of radiotracer in the same location
Minimally invasive parathyroidectomy
33 × 20 × 14
Mantzoros et al., 2018 
Neck swelling, bone pain
US: hypoechoic nodule at inferior pole of the right thyroid; MIBI: hyper functioning rightlower parathyroid gland
Minimally invasive parathyroidectomy
Done, 95% reduction 20 minutes after removal
50 × 25 × 25
Hungry bone syndrome
Migliore et al., 2013 
CT: 7 cm mass in posterior mediastinum; MIBI: confirmed the CT finding
Taghavi Kojidi et al., 2016 
Anorexia, nausea, bone pain, constipation, symptomatic kidney stones, polydipsia
US: multiple isoechoic nodules, no parathyroid glands seen; MIBI: focal radiotracer accumulation, midline anterior chest wall; CT: soft tissue density mass, mild enhancement, anterior midline, xiphoid level
Surgical removal (not specified) f
Active parathyroid lesion
Pecheva et al., 2016 
Depression, severe osteoporosis (T = −3.2)
US: no parathyroid lesion; MIBI: no evidence of PTA; CT: complex cystic solid mass in the mediastinum
Parathyroidectomy via VATS
Not used, emergency
Hoarseness, bovine cough
Talukder et al., 2017 
US: no abnormal parathyroid gland; MIBI: tracer-avid lesion in anterior mediastinum; PET-CT: ectopic parathyroid tissue in anterior mediastinum behind manubrium sterni
Parathyroidectomy via cervical collar incision and hemisternotomy
40 × 30 × 20
Neuroendocrine cell tumor
Garuna Murthee et al., 2018 
Anorexia, lethargy, abdominal cramps, constipation, weight loss
CXR: sizeable mediastinal mass; CT: 9 cm solid cystic anterior mediastinal tumor; MIBI: heterogeneous tracer uptake in the mediastinal mass
Medial sternotomy and total thymectomy
Maximum diameter 78
Miller et al., 2019 
Asymptomatic renal stones
MIBI: linear region of increased intensity in the left mediastinum
Parathyroidectomy via transcervical excision
Done, 81% reduction after 10 minutes
80 × 30 × 30
In terms of physical examination, the majority of GPTAs in the neck had a visible and palpable mass in the neck [7, 11, 13, 14, 17, 19, 20, 24, 25]. Their large size is one of the reasons a clinician may suspect thyroid disease before reviewing the laboratory results, as palpable nodules are more common in the thyroid. In our case, a swelling was readily visible on inspection and palpable on physical examination.
As for diagnostic laboratory studies, GPTA investigations start with serum calcium and PTH and proceed to imaging for localization (Table 1). Hypercalcemia and elevated PTH are hallmarks of PHPT , in agreement with our review where all cases had elevated calcium and PTH laboratory values . A positive correlation between the size of a PTA and preoperative PTH and calcium levels has also been reported [2, 26, 27]. Calva-Cerqueira et al. (2007) concluded that if preoperative PTH is > 232 ng/L, there is 95% likelihood of finding a PTA weighing > 250 mg . This is valuable, as surgeons can have an idea of tumor size preoperatively. As for histopathology, although FNA cytology (FNA-C) is increasingly used in the diagnosis of parathyroid pathology , its limitation is that FNA-C cannot distinguish between different types of parathyroid disease . Our preoperative FNA-C was non-diagnostic, similar to others where preoperative FNA-C was non-diagnostic .
In terms of imaging, localizing a GPTA is imperative to guide management. The most commonly used method is a combination of neck ultrasound and 99mTc-sestamibi scintigraphy (MIBI) scan. The limitation of neck ultrasound in GPTA is that it may not show the extent of a lesion; when the GPTA is ectopic, a neck ultrasound will show no finding . In mediastinal GPTA, neck ultrasound only rules out a neck lesion but does not otherwise aid in localization [20, 21, 22]. In neck GPTA, the combination of a MIBI scan and neck ultrasound effectively localizes the GPTA and allows for guided neck exploration . Ultrasound alone predicts GPTA location with 79% accuracy; combining ultrasound, MIBI, and CT increases the accuracy of localization to 82% . We agree, as in our patient, that combining neck ultrasound and MIBI scan accurately localizes the GPTA preoperatively. MIBI scans are more likely to localize GPTA in patients with higher preoperative PTH and larger GPTA size; an adenoma correctly localized by MIBI has a 95% likelihood of weighing > 5.5 gm . As for the location, in agreement with most studies, our GPTA was not ectopic ; however, Table 1 shows that the mediastinum is a common location for ectopic GPTAs, suggesting that such GPTAs arise in the inferior gland [31, 32].
For the management, the 2014 US National Institutes of Health (NIH) guidelines for PTA management are either medical or surgical if it fulfills specific criteria . As with all the cases in Table 1, our case fulfilled the symptoms and laboratory criteria for surgery. We undertook MIP, in agreement that it is the preferred procedure , and ioPTH monitoring, to confirm removal of the PTA before closure. Although the MIP/ioPTH combination is a gold-standard treatment, comparable outcomes of MIP with and without ioPTH monitoring have been reported , with some studies suggesting the benefit of ioPTH monitoring is only for patients with equivocal imaging . This might be an important feature to consider when institutions seek resource utilization and cost savings. In agreement with the point that ioPTH might be beneficial only in equivocal imaging findings, ioPTH monitoring seems to have limited use in GPTA. Only in five instances was ioPTH monitoring undertaken [5, 13, 17, 19, 23] (Table 1), probably because preoperative imaging and intraoperative visualization in GPTA leave little doubt about the location , and because of a high likelihood of single gland disease . At our institution, PTA standard intraoperative practice is ioPTH monitoring and frozen section to confirm excision.
Postoperatively, larger sized PTAs may be associated with a higher incidence of postoperative hypocalcemia . Table 1 agrees with this, showing that hypocalcemia occurred in cases of larger GPTA. Hungry bone syndrome, a severe but rare form of postoperative hypocalcemia, occurred in four cases (Table 1), all of which had GPTAs weighing > 30 gm. Patients with smaller GPTAs were less likely to have postoperative hypocalcemia. Our patient presented with a 7.7 gm GPTA, considered a smaller GPTA in relation to other reported cases [7, 8, 9], which could explain why it had a less severe presentation as well as outcome after surgery compared with the other cases. Postoperatively, our patient, due to the smaller GPTA, became normocalcemic with normal PTH, and was not discharged on any calcium repletion therapy. Our patient was followed for a total of 3 years postoperatively and she remained asymptomatic and normocalcemic, without recurrence. This fits with outcomes reported in a study following patients for an average of 40 months, where all patients remained normocalcemic and there was no recurrence during this time, even in those with suspicious histologic features .
GPTA is a rare subset of PTAs that weigh > 3.5 gm, it is benign, but can manifest with the symptoms of extreme hypercalcemia. From our literature review, we conclude that GPTA generally presents symptomatically, with high preoperative PTH and serum calcium directly proportional to the adenoma weight. The most accurate method for localizing a GPTA is a combination of neck ultrasound and MIBI scan. MIP with intraoperative PTH monitoring is the suggested management, although the need for the ioPTH monitoring is debatable in GPTA due to their large size and accuracy of preoperative imaging.
MM and WEA drafted the manuscript; AA contributed to the writing of the manuscript. MM, AA, and MAH acquired the clinical data. WEA, MM, and AA developed the structure and arguments of the paper. WEA, MM, AA, and MAH made important revisions and approved the final version of the manuscript. All authors agreed with the manuscript conclusions and reviewed and approved the final manuscript.
Ethics approval and consent to participate
Ethics approval and consent to publish provided: Medical Research Centre review board, Institutional Review Board (IRB), protocol #0419113, Hamad Medical Corporation, Doha, Qatar.
Consent for publication
Ethics approval and consent to publish provided (Medical Research Centre review board, IRB, #0419113, Hamad Medical Corporation, Doha, Qatar). Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The authors declare that they have no competing interests.
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