Introduction
Primary hyperparathyroidism (PHPT) is an endocrine disorder caused by autonomous overproduction of parathyroid hormone (PTH), which leads to hypercalcemia and disrupts normal calcium metabolism. Most PHPT is diagnosed when a routine calcium test is high, which then prompts a PTH measurement and confirms the diagnosis [ 1 , 2 ]. Single benign adenomas account for approximately 80 to 85% of all PHPT cases, multiglandular hyperplasia accounts for 10 to 15%, and parathyroid carcinoma accounts for less than 1% [ 3 ].
Excess PTH increases bone resorption. It also raises renal calcium reabsorption and boosts intestinal calcium absorption through vitamin D activation. Together these raise blood calcium, and patients can develop musculoskeletal pain, fatigue, or other constitutional symptoms, and some lose weight [ [4] , [5] , [6] , [7] ]. Long-term cohort studies link it to higher rates of cardiovascular and renal disease, more fractures, kidney stones, renal parenchymal calcification, and progressive loss of kidney function [ 4 , 8 , 9 ]. PHPT is characterized by persistent hypercalcemia together with a PTH level that remains elevated or fails to suppress appropriately. Either finding, alone or in combination, is suggestive of the diagnosis, but secondary causes and familial hypocalciuric hypercalcemia must be excluded first [ 10 , 11 ].
Most parathyroid adenomas are small, even in large surgical series. One recent report of 517 patients who had single-gland parathyroidectomy found a median adenoma weight of 500 mg and an average maximum diameter of 15 mm [ 12 ], with a giant parathyroid adenoma (GPA) defined only when the weight exceeds about 3.5 g [ 13 ]. GPAs often cause higher calcium and PTH levels, and many patients are symptomatic, but several studies found no consistent link between tumor size and how severe the biochemistry or symptoms are [ [14] , [15] , [16] ].
Large size inevitably raises the question of adenoma versus carcinoma: parathyroid carcinoma typically presents with very high calcium and PTH levels, a palpable neck mass, and invasive features, whereas GPAs remain noninvasive and are usually curable by simple excision. That distinction needs to be considered before surgery, because suspected carcinoma requires a different operative plan than a straightforward adenoma resection [ 1 , 13 , [15] , [16] , [17] ].
The importance of this case lies not in the adenoma itself, but in how narrowly the diagnosis was missed. Fatigue, weight loss, and nocturia are common but nonspecific signs of PHPT. They could easily be blamed on dietary change, dehydration from extra protein intake, or overtraining. These overlapping explanations are likely what delayed measurement of his serum calcium [ 18 ].
History alone often cannot separate weight loss caused by disease from weight loss caused by training load. Hypercalcemia accompanied by renal impairment keeps malignancy, and multiple myeloma in particular, on the differential. Once biochemical investigation confirmed hypercalcemia, the next step was to find the mass in the neck. Neck ultrasonography and Technetium-99m sestamibi scintigraphy (Tc-99m sestamibi scintigraphy) are the usual methods for this. Recent reports put ultrasonography sensitivity at around 77%, while that of sestamibi is about 89%. Using both together gives a higher localization rate than either method alone [ 19 , 20 ]. For a tumor of this size, with mediastinal extension raising a structural question in addition to the localization problem, an 18 F-FDG PET-CT was obtained as an adjunct to conventional imaging to delineate the inferior extent of the lesion and to help distinguish a large ectopic adenoma from more aggressive disease [ 21 , 22 ]. 18 F-FDG PET-CT is not a first-line investigation for parathyroid adenoma localization. It was employed here as an adjunct to exclude locoregional lymphadenopathy and assess for local invasion. Contrast-enhanced 4D-CT was deferred given concurrent acute kidney injury (serum creatinine 1.89 mg/dL), rendering iodinated contrast inadvisable, and 18F-FDG PET-CT was selected on the basis of the clinical circumstances at presentation.
Here, we report the case of a young, physically active man whose GPA went unrecognized while his symptoms were attributed to his training regimen and protein supplementation. We describe how multimodality imaging, including ultrasonography, Tc-99m sestamibi scintigraphy, and PET-CT, was used to localize and characterize the lesion before surgery, and how the perioperative plan anticipated the risk of hungry bone syndrome.
Case presentation
A 36-year-old man working as a physical fitness trainer presented to the nephrology clinic with a six-month history of unintentional weight loss totaling approximately 13 kg, two weeks of generalized weakness, and one week of nocturia. He had been taking oral protein supplements for approximately six months prior to presentation, and both he and the physicians who first evaluated him had regarded his training schedule and supplementation as a sufficient explanation for the change in body weight and fatigue. There was no personal or family history of endocrine disease, and physical examination, including palpation of the neck, was unremarkable.
Initial laboratory evaluation showed severe hypercalcemia, with a serum calcium of 16.4 mg/dL (reference range 8.4–10.2), together with a serum creatinine of 1.89 mg/dL (reference range 0.6–1.2) and a blood urea of 55 mg/dL (reference range 15–40), consistent with acute kidney injury. Serum potassium was mildly elevated at 5.4 mmol/L (reference range 3.5–5.0), and 24-hour urinary calcium excretion was markedly increased at 812 mg per day (reference range 100–300); parathyroid hormone was markedly elevated at 1127.4 pg/mL (reference range 15–65). Abdominopelvic ultrasonography showed increased cortical echogenicity and loss of corticomedullary differentiation in both kidneys, in keeping with acute kidney injury, together with small bilateral renal calculi measuring up to 6 mm on the right and 4 mm on the left.
Because hypercalcemia of this severity with concurrent renal injury can also reflect a paraproteinemic process such as multiple myeloma, kappa and lambda free light chains and serum protein electrophoresis were obtained. The kappa free light chain was mildly elevated at 50.7 mg/L (reference range 3.3–19.4), while the lambda free light chain was within normal limits at 22.1 mg/L (reference range 5.7–26.3); both were in a polyclonal pattern with a normal kappa-to-lambda ratio, and electrophoresis showed no monoclonal band. These findings argued against a paraproteinemic cause and supported proceeding with a parathyroid-directed work-up. Initial laboratory results are summarized in Table 1 . Table 1 Initial laboratory investigations . Table 1 dummy alt text Investigation Result Reference range Unit Serum calcium 16.4 8.4–10.2 mg/dL Serum creatinine 1.89 0.6–1.2 mg/dL Blood urea 55 15–40 mg/dL Serum potassium 5.4 3.5–5.0 mmol/L 24-h urine calcium 812 100–300 mg/day Serum parathyroid hormone (PTH) 1127.4 15–65 pg/mL Kappa free light chain 50.7 3.3–19.4 mg/L Lambda free light chain 22.1 5.7–26.3 mg/L Serum protein electrophoresis (SPE) Polyclonal gamma-globulin pattern No monoclonal gammopathy N/A
Table 1
Initial laboratory investigations .
| Investigation | Result | Reference range | Unit |
| Serum calcium | 16.4 | 8.4–10.2 | mg/dL |
| Serum creatinine | 1.89 | 0.6–1.2 | mg/dL |
| Blood urea | 55 | 15–40 | mg/dL |
| Serum potassium | 5.4 | 3.5–5.0 | mmol/L |
| 24-h urine calcium | 812 | 100–300 | mg/day |
| Serum parathyroid hormone (PTH) | 1127.4 | 15–65 | pg/mL |
| Kappa free light chain | 50.7 | 3.3–19.4 | mg/L |
| Lambda free light chain | 22.1 | 5.7–26.3 | mg/L |
| Serum protein electrophoresis (SPE) | Polyclonal gamma-globulin pattern | No monoclonal gammopathy | N/A |
Neck ultrasonography showed a hypoechoic, elongated lesion with a few internal hyperechoic foci extending from the lower pole of the right thyroid lobe to the supraclavicular fossa and measuring 2.3 × 2.3 × 5.9 cm, with a prominent feeding vessel at its superior pole ( Fig. 1 A ). Color Doppler imaging showed moderate internal vascularity with a prominent feeding vessel at the upper pole of the lesion, and spectral Doppler showed a low-resistance arterial waveform ( Fig. 1 B ). The overall appearance was considered consistent with a parathyroid adenoma. Fig. 1 (A) Grayscale ultrasonography of the right neck lesion. Caliper measurements give dimensions of 2.3 × 2.3 × 5.9 cm and a calculated volume of 17.18 cm³; (B) color and spectral Doppler ultrasonography of the right neck lesion. The lesion is hypoechoic and elongated and lies posterior to the lower pole of the right thyroid lobe, and the long-axis caliper in (A) records its full 5.9 cm craniocaudal extent. The low-resistance arterial waveform in (B) arises from a single dominant feeding vessel entering at the upper pole, a pattern more typical of a parathyroid adenoma than of a thyroid nodule. Fig 1 dummy alt text
18 F-FDG PET-CT subsequently identified an FDG avid, smoothly marginated soft-tissue lesion posterior and inferior to the right thyroid lobe, abutting the brachiocephalic trunk and extending into the right paratracheal region, measuring approximately 20 × 23 × 49 mm ( Fig. 2 ). This study was obtained both to map the inferior extent of the lesion and to assess for features suggestive of malignancy, given that a mass of this size warrants consideration of parathyroid carcinoma in the differential diagnosis. Uptake was focal, with a maximum standardized uptake value (SUVmax) of 8.65. The features taken as reassuring against carcinoma were the smooth, well-defined margins, the absence of infiltration of the trachea, esophagus, thyroid, or adjacent great vessels, and the absence of enlarged cervical or mediastinal nodes. Smooth margins and FDG avidity do not by themselves separate adenoma from carcinoma, and the distinction here rested finally on the operative findings and on histopathology. Fig. 2 18 F-FDG PET-CT scan of the right paratracheal lesion. An FDG avid, smooth margined soft-tissue lesion is seen posterior and inferior to the right thyroid lobe, abutting the brachiocephalic trunk and extending into the right paratracheal region, measuring approximately 20 × 23 × 49 mm. The lesion is smoothly marginated, with no infiltration of the trachea, esophagus, thyroid, or great vessels and no enlarged cervical or mediastinal nodes, and its inferior extent reaches the upper mediastinum. Fig 2 dummy alt text
Tc-99m sestamibi scintigraphy confirmed increased tracer uptake in the same location at 20 minutes that persisted at two hours, a pattern consistent with a right-sided parathyroid adenoma extending into the upper mediastinum ( Fig. 3 ). With all three studies in agreement, a focused right-sided neck exploration was planned in preference to bilateral exploration. Fig. 3 Tc-99m sestamibi scintigraphy. Increased tracer uptake is seen in the inferior aspect of the right thyroid lobe extending into the upper mediastinum on the early images at 20 minutes, and persisting on the delayed images at two hours. Retention of tracer on the delayed images, while activity washes out of the thyroid, is the finding that identifies the lesion as parathyroid tissue. The appearance is consistent with a right-sided parathyroid adenoma extending into the upper mediastinum. Fig 3 dummy alt text
The patient underwent right parathyroidectomy under intraoperative parathyroid hormone monitoring. At operation, the right recurrent laryngeal nerve was identified coursing superficial to a 6 × 3 cm adenoma that extended from the mid-thyroid into the mediastinum, posterior to the innominate artery. The nerve was carefully dissected free of the lesion, and the inferior thyroid vessels supplying the gland were identified and ligated. The gland lay deep to the recurrent laryngeal nerve, which is the position expected of a superior gland, while its supply from the inferior thyroid vessels and its descent from the lower thyroid pole into the mediastinum are more typical of an inferior gland. Because these features point in opposite directions, the gland of origin could not be assigned with confidence, and the lesion is described throughout this report by its anatomical location rather than by presumed embryological origin. No invasion of adjacent structures and no suspicious central compartment lymphadenopathy were identified ( Fig. 4 ). Serum parathyroid hormone was 2233 pg/mL immediately before excision and decreased to 172 pg/mL at ten minutes after excision, exceeding the usual intraoperative criterion for biochemical cure. Serum calcium had normalized to 9.0 mg/dL by the fourth postoperative day, without the need for intravenous calcium supplementation. Fig. 4 Intra-operative findings. Top, the operative field shows the right-sided parathyroid adenoma (white circle) extending from the mid-pole of the thyroid into the mediastinum, with the right recurrent laryngeal nerve (white arrow) running superiorly over the adenoma. Bottom, the resected specimen, a single grey-brown soft-tissue mass measuring 53 × 26 × 18 mm and weighing 18 g. Fig 4 dummy alt text
The resected specimen was a single, grey-brown soft-tissue mass measuring 53 × 26 × 18 mm and weighing 18 g, exceeding the conventional 3.5 g threshold for GPA. Histopathology showed a well-encapsulated nodule composed of chief cells and oxyphil cells arranged in a macrofollicular pattern, with a fine capillary network and scattered degenerative nuclear change, but no mitotic activity, necrosis, capsular invasion, or vascular invasion. Immunohistochemistry was positive for GATA3, a transcription factor supporting parathyroid origin, and the Ki-67 proliferation index was low at 3 to 4% ( Fig. 5 A & B ). The diagnosis of a benign adenoma rested on the absence of capsular and vascular invasion together with the absence of mitoses and necrosis. The low Ki-67 index was supportive but is not on its own a criterion for benignity. The postoperative course was uncomplicated. The patient did not develop clinically significant hypocalcemia and was discharged with normalized serum biochemistry. Fig. 5 (A & B) Histopathology of the resected lesion. Top, H&E staining shows a cellular, encapsulated nodule with a delicate capillary network. Bottom, Ki-67 immunohistochemistry shows only rare positively stained (brown) nuclei against a background of negative cells, consistent with a low proliferation index of 3 to 4%. Capsular and vascular invasion were absent throughout the sections examined, and this, rather than the Ki-67 index, is the basis for the benign diagnosis. Fig 5 dummy alt text
Discussion
In this case, the diagnosis of GPA was delayed by an unusually plausible alternative explanation for the patient's symptoms. Weight loss, fatigue, and nocturia are symptoms commonly associated with PHPT, but they are also the expected consequences of intensive physical training and dietary change, and our patient's protein supplementation and training schedule gave both him and his initial physicians a coherent and clinically reassuring account of the patient's presenting symptoms. Severe hypercalcemia independently produces anorexia and nausea, so weight loss attributable to training and weight loss attributable to an underlying tumor can be clinically indistinguishable from the history alone. Diagnostic delay arising from this kind of symptom overlap has been reported previously in PHPT, generally in patients whose weight loss was attributed to aging or to a presumed gastrointestinal disorder [ 18 ]. We did not find a previous report in which the confounder was the patient's own training regimen. That observation rests on a single patient and should not be read as evidence that exercise masks the biochemical abnormality. The calcium and parathyroid hormone values were grossly abnormal whenever they were measured. What was delayed was the decision to measure them.
Before imaging confirmed a parathyroid origin, the differential diagnosis for hypercalcemia of this severity, particularly in the presence of renal injury, still had to include malignancy. Multiple myeloma is the principal alternative diagnosis to consider in this setting, which is why kappa and lambda free light chains and serum protein electrophoresis were obtained alongside calcium and parathyroid hormone. The polyclonal light chain pattern, normal kappa-to-lambda ratio, and absence of a monoclonal band on electrophoresis were sufficient to set aside a paraproteinemic cause and to proceed with a parathyroid-directed evaluation. Excluding myeloma before assuming a diagnosis of PHPT is appropriate practice when hypercalcemia is this severe.
Once the biochemical diagnosis was secure, the relevant clinical question became the size and anatomical extent of the underlying lesion. GPAs are generally associated with higher preoperative serum calcium and parathyroid hormone levels than smaller adenomas, but adenoma size and biochemical severity do not consistently parallel symptom burden, and large adenomas are not invariably accompanied by a more florid clinical course [ 14 , 23 ]. Tumor size alone, however, raises parathyroid carcinoma as a differential consideration, which has direct implications for the extent of surgery the operating team needs to be prepared to perform [ 17 , 24 ].
In this case, ultrasonography first raised the likelihood of a parathyroid adenoma, and this impression was independently corroborated by both positron emission tomography-computed tomography and Tc-99m sestamibi scintigraphy, with the former additionally delineating the mediastinal extent of the lesion and showing no features of local invasion. GPAs and parathyroid carcinomas can both present as large parathyroid tumors, but comparative series show most giant lesions are benign adenomas, and careful preoperative evaluation is needed to rule out carcinoma and plan the right operation [ 19 , 20 ]. Differential considerations for the neck mass, including thyroid nodules, cervical lymphadenopathy, and parathyroid hyperplasia, were also entertained and were set aside on the basis of the imaging characteristics and biochemical pattern described above.
18 F-FDG PET-CT is not a recognized step in the standard parathyroid localization algorithm. In this patient, it served a different purpose: the gland had already been localized concordantly by ultrasonography and sestamibi scintigraphy, and PET-CT was obtained to map the mediastinal extent of the lesion and to evaluate for locoregional invasion [ 22 , 25 ]. In this case, 4D-CT was deferred because of concurrent AKI (serum creatinine 1.89 mg/dL) at presentation, making an iodinated contrast study unattractive.
The FDG study was used as an adjunct rather than as a substitute for parathyroid-specific imaging. Its purpose was to map the mediastinal extent of a lesion that ultrasonography and sestamibi imaging had already localized concordantly, and to look for features of local invasion, not to establish the localization itself. In a patient with normal renal function, or where the initial studies disagree, four-dimensional CT or a parathyroid-specific tracer would be the better choice.
Other reported GPAs have presented with dysphagia, odynophagia or dyspnea when the mass compresses the esophagus or airway, reflecting the potential for large parathyroid lesions to cause local obstructive symptoms in addition to biochemical disease [ [26] , [27] , [28] , [29] , [30] ]. The adenoma in this case, despite its mediastinal extension, produced none of these symptoms, which likely contributed to the unremarkable findings on neck examination and to the diagnosis depending almost entirely on biochemical and imaging data, without a contributory physical sign.
With the lesion precisely localized and malignancy considered unlikely on imaging grounds, a focused excision under intraoperative parathyroid hormone monitoring was judged preferable to bilateral neck exploration. The greater than ninety percent intraoperative fall in parathyroid hormone, together with the subsequent normalization of serum calcium, confirmed biochemical cure, and the absence of capsular and vascular invasion on histopathology established the benign nature of the lesion, with the low Ki-67 index as a supporting finding.
Large parathyroid adenomas with very high preoperative PTH and calcium levels are recognized as carrying a high risk of postoperative hungry bone syndrome [ 26 , 28 , 29 , 31 , 32 ]. In the present case, serum calcium normalized smoothly without intravenous calcium supplementation or a prolonged hospital stay. This could reflect a smaller cumulative skeletal calcium deficit than the parathyroid hormone value alone might suggest, or it could reflect that close postoperative monitoring identified and corrected a milder deficit before it became clinically apparent. We cannot tell which explanation is correct from this case alone. Either way, the practical message is the same: a GPA with a PTH level this high needs planned, frequent calcium monitoring after surgery, with calcium and calcitriol on hand. A technically successful excision does not guarantee an uncomplicated recovery.
The pathogenesis of a GPA of this kind is generally considered to reflect autonomous neoplastic transformation of parathyroid chief and oxyphil cells, with size correlating with duration of unchecked growth rather than with a fundamentally different biological process from smaller adenomas [ 33 , 34 ].
The absence of capsular or vascular invasion and the low proliferation index in this specimen were consistent with that interpretation.
This report has the limitations inherent to a single case. The frequency with which a physically active lifestyle obscures the presentation of PHPT cannot be estimated from one patient, and the timeline of symptoms reported here depends on the patient's recollection and on the documentation of the physicians who saw him before referral, both of which carry the usual uncertainty of a retrospective history. Serial post-operative biochemical follow-up confirmed cure at the six-week mark: serum PTH 12.7 pg/mL (12/06/2026); serum calcium 9.55 mg/dL (19/06/2026) and 9.0 mg/dL (04/07/2026); serum albumin 3.8 g/dL and serum phosphorus 3.8 mg/dL (04/07/2026), all within reference limits. These follow-up data do not affect the biochemical, imaging, or histopathological findings reported at initial presentation, which were directly observed, but they do limit how far the central observation of this report, that an ordinary and health-promoting explanation can obscure a serious underlying disorder, can be generalized beyond the case described.
Conclusion
This case illustrates a GPA with mediastinal extension in a young man whose constitutional symptoms were initially, and reasonably, attributed to physical training and dietary supplementation rather than to an underlying pathological process. The key clinical teaching point is that weight loss, fatigue, and nocturia in a physically active patient do not exclude PHPT, and that a serum calcium and parathyroid hormone level are warranted when these symptoms persist, regardless of how plausible a lifestyle explanation may seem. From a localization standpoint, concordant findings on ultrasonography, Tc-99m sestamibi scintigraphy, and positron emission tomography-computed tomography supported confident, focused surgical planning even for an adenoma of unusual size and anatomical extent, and a markedly elevated preoperative parathyroid hormone level should prompt anticipatory postoperative calcium monitoring regardless of how straightforward the operation itself proves to be. Post-operative biochemical follow-up at four to six weeks confirmed sustained normalization of serum PTH and calcium, consistent with biochemical cure.
Declaration of generative AI and AI-assisted technologies in the writing process
During the preparation of this work, the authors used an AI-assisted writing tool to help structure and draft the manuscript text from the authors' original clinical data, laboratory results, imaging findings, and surgical and pathological reports. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.
Patient consent
Complete written informed consent was obtained from the patient for the publication of this study and accompanying images.
References
1 Walker M.D. Silverberg S.J. Primary hyperparathyroidism Nat Rev Endocrinol 14 2 2018 115 125 28885621 10.1038/nrendo.2017.104 PMC6037987
2 Machado N.N. Wilhelm S.M. Diagnosis and evaluation of primary hyperparathyroidism Surg Clin 99 4 2019 649 666 10.1016/j.suc.2019.04.006 31255197
3 DeLellis R.A. Mazzaglia P. Mangray S. Primary hyperparathyroidism: a current perspective Arch Pathol Lab Med 132 8 2008 1251 1262 18684024 10.5858/2008-132-1251-PHACP
4 Lila A.R. Sarathi V. Jagtap V. Bandgar T. Menon P.S. Shah N.S. Renal manifestations of primary hyperparathyroidism Indian J Endocrinol Metab 16 2 2012 258 262 22470864 10.4103/2230-8210.93745 PMC3313745
5 Weber T. Hillenbrand A. Peth S. Hummel R. Symptoms of primary hyperparathyroidism in men and women: the same but different? Visc Med 36 1 2020 41 47 32110656 10.1159/000505497 PMC7036559
6 Khan M., Jose A., Sharma S. Physiology, parathyroid hormone. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499940/
7 Brown E.M. The pathophysiology of primary hyperparathyroidism J Bone Miner Res 17 Suppl 2 2002 N24 N29 12412774
8 Yu N. Donnan P.T. Flynn R.W.V. Murphy M.J. Smith D. Rudman A. Increased mortality and morbidity in mild primary hyperparathyroid patients: the Parathyroid Epidemiology and Audit Research Study (PEARS) Clin Endocrinol 73 1 2010 30 34 10.1111/j.1365-2265.2009.03766.x 20039887
9 Yu N. Donnan P.T. Leese G.P. A record linkage study of outcomes in patients with mild primary hyperparathyroidism: the Parathyroid Epidemiology and Audit Research Study (PEARS) Clin Endocrinol 75 2 2011 169 176 10.1111/j.1365-2265.2010.03958.x 21158894
10 Pallan S. Khan A. Primary hyperparathyroidism: update on presentation, diagnosis, and management in primary care Can Fam Physician 57 2 2011 184 189 21321169 PMC3038812
11 Bilezikian J.P. Khan A.A. Silverberg S.J. El-Hajj Fuleihan G. Marcocci C. Minisola S. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the Fifth International Workshop J Bone Miner Res 37 11 2022 2293 2314 36245251 10.1002/jbmr.4677
12 Dream S. Yen T.W.F. Doffek K. Evans D.B. Wang T.S. Variation in parathyroid adenoma size in patients with sporadic primary hyperparathyroidism: small gland size does not preclude single gland disease Langenbecks Arch Surg 407 5 2022 2067 2073 35538172 10.1007/s00423-022-02539-z
13 Garas G. Poulasouchidou M. Dimoulas A. Hytiroglou P. Kita M. Zacharakis E. Radiological considerations and surgical planning in the treatment of giant parathyroid adenomas Ann R Coll Surg Engl 97 4 2015 e64 e66 26263956 10.1308/003588415X14181254789682 PMC4473887
14 Puri G. Ranjan P. Singh B.K. Khadgawat R. Damle N. Priyadarshini P. Giant parathyroid adenomas: a 28-year experience at a tertiary super-specialty hospital World J Surg 49 7 2025 1811 1819 40468583 10.1002/wjs.12627
15 Castro M.A. Abad López A. Fragueiro L.M. García N.P. Giant parathyroid adenoma: differential aspects compared to parathyroid carcinoma Endocrinol Diabetes Metab Case Rep 2017 2017 17 0041 10.1530/EDM-17-0041 PMC5420060 28491324
16 Wong H.K.G. Shipman K. Allan K. Ghabbour A. Borumandi F. Giant parathyroid tumours in primary hyperparathyroidism: a systematic review Langenbecks Arch Surg 407 2 2022 501 516 35039921 10.1007/s00423-021-02406-3
17 Aziz H. Hussein Z. Giant parathyroid adenoma versus parathyroid carcinoma: differentiating two entities J ASEAN Fed Endocr Soc 36 1 2021 104 107 34177097 10.15605/jafes.036.01.11 PMC8214351
18 Dhamija B. Kombogiorgas D. Hussain I. Solanki G.A. Posterior fossa arachnoid cyst masking a delayed diagnosis of hyperparathyroidism in a child Case Rep Endocrinol 2012 2012 931371 10.1155/2012/931371 PMC3512258 23227372
19 Shah R.F. Malik A.A. Wani M.A. Lone Z.G. Shabir U. Mushtaq A. Comparative accuracy of ultrasonography and sestamibi scintigraphy in preoperative localization of parathyroid adenomas: a retrospective observational study JMS SKIMS 28 3 2025 5 10
20 Ghaffar T. Kanwal S. Aamir A.H. Din N. Diagnostic accuracy of ultrasonography and 99m-Technetium Sestamibi scintigraphy for the preoperative localization of parathyroid adenoma keeping histopathological findings as reference standard Pak J Med Sci 40 10 2024 2405 2409 39554654 10.12669/pjms.40.10.8575 PMC11568711
21 Krishnamurthy A. Raghunandan G.C. Ramshankar V. A rare case of giant parathyroid adenoma presenting with recurrent episodes of pancreatitis Indian J Nucl Med 31 1 2016 36 26917892 10.4103/0972-3919.172355 PMC4746839
22 Kluijfhout W.P. Pasternak J.D. Drake F.T. Beninato T. Gosnell J.E. Shen W.T. et al.Use of PET tracers for parathyroid localization: a systematic review and meta-analysis Langenbecks Arch Surg 401 7 2016 925 935 27086309 10.1007/s00423-016-1425-0 PMC5086346
23 Navari L. Li M. Lott Limbach A. Seim N. Giant parathyroid adenoma causing primary hyperparathyroidism Otolaryngol Case Rep 29 2023 100555
24 Gossili F. Carlé A. Andersen T.B. Zacho H.D. Giant parathyroid tumor: parathyroid adenoma versus parathyroid carcinoma Case Rep Endocrinol 2022 2022 7712097 10.1155/2022/7712097 PMC9629939 36339511
25 Sayed S. Das A. Turner B. Wadhwa V.S. Pathak K.A. Role of four-dimensional computed tomography (4D-CT) in non-localising and discordant first-line imaging in primary hyperparathyroidism Ann R Coll Surg Engl 105 8 2023 739 746 36748800 10.1308/rcsann.2022.0126 PMC10618046
26 Ziaeean B. Sohrabi-Nazari S. Huge parathyroid adenoma with dysphagia presentation: a case report from southern Iran Iran J Med Sci 41 5 2016 446 449 27582595 PMC4967490
27 Chaudhry B.R. Pantawong N.J. Lazarova L. Dhakshinamoorthy B. Dey D. Giant cystic parathyroid adenoma: a rare culprit of anterior compressive neck swelling, primary hyperparathyroidism, and hypercalcemia Endocr Abstr 109 2025 63
28 Ahsayen F.Z. Haddadi Z. El Aggari H. Benramdane H. Aichouni N. Nasri S. Dysphagia revealing a giant cystic parathyroid adenoma Radiol Case Rep 17 10 2022 3556 3558 35923333 10.1016/j.radcr.2022.06.044 PMC9340078
29 Whitson B.A. Heckmann R. Manivel C. Lassig A.A. D’Cunha J. Acute airway compromise from a hemorrhagic posterior cervical-mediastinal mass: rare presentation of a parathyroid adenoma J Thorac Dis 3 1 2011 68 70 22263063 10.3978/j.issn.2072-1439.2010.11.7 PMC3256495
30 Davoli F. Rena O. Pirondini E. Casadio C. Giant functioning mediastinal parathyroid cyst: an unusual cause of exertional dyspnea and mild dysphagia Arch Bronconeumol 49 9 2013 369 412 23542045 10.1016/j.arbres.2013.01.007
31 Baby S. Pereira N. Kim S. A rare case of a giant parathyroid adenoma in a young male patient Cureus 17 4 2025 e82489 10.7759/cureus.81911 PMC12061484 40342445
32 Al-Hassan M.S. Mekhaimar M. El Ansari W. Darweesh A. Abdelaal A. Giant parathyroid adenoma: a case report and review of the literature J Med Case Rep 13 2019 1 9 31722742 10.1186/s13256-019-2257-7 PMC6854700
33 Cinque L. Pugliese F. Salcuni A.S. Scillitani A. Guarnieri V. Molecular pathogenesis of parathyroid tumours Best Pract Res Clin Endocrinol Metab 32 6 2018 891 908 30477753 10.1016/j.beem.2018.11.001
34 Spanheimer P.M. Stoltze A.J. Howe J.R. Sugg S.L. Lal G. Weigel R.J. Do giant parathyroid adenomas represent a distinct clinical entity? Surgery 154 4 2013 714 719 23978594 10.1016/j.surg.2013.05.013 PMC3787983
Acknowledgments: The authors sincerely acknowledge Medical Writer for her valuable guidance, support, and assistance in the preparation and writing of this work. No funding was received for this study.
Competing Interests: The authors have declared that no competing interests exist.