Abstract
Primary hyperparathyroidism is a common endocrinology anomaly which involves head and neck region. The diagnosis and treatment of parathyroid adenoma however still remains a challenge. Giant parathyroid adenomas are rare and involve more surgical expertise. Retrospective study was carried in Departments of ENT and Endocrinology, SMS Medical College and Hospital, Jaipur. Records of patients operated between 2010 and 2019 were evaluated and analysed for size and site of parathyroid adenomas, biochemical parameters, intra-operative findings and postoperative course. Tumours with size > 3 cm were termed as giant parathyroid adenomas and this is a rarity in literature. Records of 79 patients were found to be complete. Out of these 9 had giant parathyroid adenomas: 4 left inferior, 2 right inferior, 1 ectopic location (superior mediastinum) and 1 each in left and right superior glands. The size, symptomatology and biochemical parameters are discussed in light of available literature. Giant parathyroid adenomas are a rare entity and their behaviour are same as of non giant parathyroid adenomas. In the view of literature published on pub Med, this is found to be largest case series on parathyroid Adenoma considering size more than 3 cm.
Keywords: Primary hyperparathyroidism, Raised serum calcium, Giant parathyroid adenoma, Recurrent laryngeal nerve
Introduction
Hyperparathyroidism can be classified into three forms: primary, secondary, and tertiary. Out of these, primary hyperparathyroidism (PHPT) is the most common form and is the third most common endocrine disorder [1]. Primary pathology in hyperparathyroidism is parathyroid adenoma which accounts for nearly 85% of all cases of hyperparathyroidism. Other less prevalent pathologies include parathyroid hyperplasia and carcinoma (0.5–4%) [2].
Patients of hyperparathyroidism or parathyroid adenoma are usually asymptomatic and chances of acute primary hyperparathyroidism or parathyroid crisis (PC) are very rare.
Hyperparathyroidism (parathyroid adenoma) is suspected when there are nonspecific clinical features like vague abdominal pain, neuromuscular weakness, bone disease or recurrent nephrolithiasis along with deranged serum calcium and parathyroid hormone (PTH) levels [3–5]. Various invasive and non-invasive modalities like ultrasonography (USG) of neck, parathyroid scintigraphy [5] or CT (computerised tomography) scan of neck and chest are used to localise these tumours.
Parathyroid adenomas are mostly small in size and weigh around 70 mg to 1 gm [3, 4]. Preoperative measurement of size is easily possible with the help of USG, CT and MRI scan, but measurement of weight preoperatively is a difficult task. However, volume of parathyroid gland by USG is a good indicator of their weight. Parathyroid adenomas rarely attain larger sizes and more than 3.5 g are termed as ‘Giant Parathyroid Adenoma’ [6]. Very few adenomas weighing more than 3.5 g have been described in literature. The other parameter to classify giant parathyroid adenoma is size more than 3 cm.
This article deals with our experience with giant parathyroid adenomas. We present a case series of 9 patients of giant parathyroid adenoma with greater than 3 cm in size.
Materials and Methods
We did a prospective study of 79 patients of parathyroid adenoma operated from 2010 to 2019 in SMS Medical College, a tertiary care centre in Jaipur, Rajasthan, India, with age distribution of 13–52 years. All patients were diagnosed primarily in endocrine and orthopaedic department and then referred to our department for parathyroidectomy. Patients referred from orthopaedic department, had pathological fractures that could not be treated without normalisation of blood calcium level and those who were referred from endocrine department had either renal stones or dysfunctional uterine bleeding.
Every patient was evaluated for raised serum calcium and PTH levels. Routine blood investigations were performed for anaesthesia check up. Anatomical localisation of the tumour was done with the help of ultrasonography of neck and Technitium99m Sestamibi scan. Raised calcium level was controlled by intravenous saline and bisphosphonates as per advice of endocrinologist.
Parathyroidectomy was performed by Minimal Invasive Parathyroidectomy (MIP) Technique (Fig. 1). Recurrent laryngeal nerve was preserved in all cases.
Fig. 1.
Intra-operative picture of Giant parathyroid adenoma
Intra-operative specimens were evaluated for size measurement. Parathyroid adenomas of more than 3 cm were considered to be Giant (Fig. 2).
Fig. 2.
Intra-operative measurement of parathyroid gland
After MIP, all patients were managed in ward with I.V. antibiotics, analgesics and I.V. calcium for 2 days, later on oral vitamin D3 and calcium supplements. Serum calcium and PTH levels were evaluated on 1st and 4th post operative day and normal levels were attained in all patients. Patients were discharged on 5th postoperative day on an average and those with fractures were referred back to orthopaedic department after discharge.
Results and Analysis
After performing MIP in 79 patients of parathyroid adenoma, only 9 (11.3%) patients were found to be of Giant parathyroid adenoma Table 1.
Table 1.
Biochemical parameters and sizes of giant parathyroid adenomas
| Case no. | Age/sex | Location of gland | Preoperative S. CaLevel (mg/dL) | Preoperative S.PTH level (pg/dL) | Other system involvement | Intraop size of sp.* in cm2 |
|---|---|---|---|---|---|---|
| 1 | 22/F | Right superior | 9.01 | 843 | Femur fracture | 3.5 × 1.5 |
| 2 | 32/F | Right inferior | 10.2 | 579 | Ulna fracture, nephrolithiasis | 4.5 × 2.5 |
| 3 | 33/F | Right inferior | 10.4 | 2444 | Humerus fracture | 4.5 × 2.5 |
| 4 | 13/F | Left inferior | 12.38 | 1823 | Pelvic fracture | 5.5 × 3 |
| 5 | 42/F | Right inferior | 11.2 | 1024 | Humerus fracture, nephrolithiasis | 4 × 3 |
| 6 | 36/F | Left inferior | 10.9 | 869 | Nephrolithaisis | 5.5 × 3 |
| 7 | 52/F | Left inferior | 10.7 | 577 | DUB | 3 × 2 |
| 8 | 46/M | Left inferior | 10.79 | 225 | Nephrolithaisis | 4 × 3 |
| 9 | 44/F | Ectopic location | 11.6 | 656 | Bone pain | 3.5 × 2.5 |
*Specimen
Serum PTH level assessment was done in every case after adenoma removal intra-operatively, and it was found to be less than half of the previous level. Post operative confirmation of parathyroid adenoma was done by histopathology and Carcinomatous changes were not found in any tissue.
Like many other endocrine disease, the affected patients were females, except one. Although a very rare presentation in paediatric population, one female patient of 13 year age was found to have solitary parathyroid adenoma in left inferior location. She consulted the orthopaedician for bilateral genu valgum initially and later she presented with pelvic bone fracture after a trivial fall. Preoperatively, serum calcium level in these 9 patients ranged from 9.01 to 12.08 mg/dl and was not found to have any relation with the size.
Data was analysed using open EPI software. For quantitative data analysis, mean and SD (Standard Deviation) of serum PTH were calculated and difference between the mean serum PTH of Giant Parathyroid adenoma and non Giant adenoma was calculated using unpaired t test. Mean PTH value of Giant parathyroid adenoma and non giant parathyroid adenoma patients were 1072.556 with SD 687.98 and 1120.38 with SD 721.23 respectively. Comparison between the PTH levels of giant and non-giant parathyroid adenomas were found to be non-significant (t = 0.188, p = 0.8512) Value of t test was found to be 0.188 and p value 0.8512, means no significant difference was found in mean PTH value of giant and non giant parathyroid gland.
Location of gland was inferior in majority (87.5%) of patients with left sided lesions being more common. In one patient, the gland was found to be in ectopic location in superior mediastinum.
Postoperatively serum calcium and PTH levels returned to normal in 2 days irrespective of the size of the gland. No complications were encountered even in patients with Giant Parathyroid Adenoma. Patients with giant parathyroid adenoma behaved same as non giant adenomas.
Discussion
Primary hyperparathyroidism due to parathyroid adenoma is not a rare disease. Like other endocrine diseases, it is more common in females, with an increase incidence between 50–60 years [1]. George et al. [7] studied Indian paediatric population from 1993 to 2007 and found that primary hyper parathyroidism is a very rare disease among children and often missed even with the eyes of trained paediatrician. Fortunately, even in a small time frame of the study we encountered a female patient of 13 years of age with parathyroid adenoma.
Primary hyperparathyroidism (parathyroid adenoma) presents as generalised neuromuscular weakness and bone pain. In the last century, the typical presentation of primary HPT has changed from a severe, debilitating disease towards a disease with subtle symptoms and physiologic derangements. Asymptomatic disease was defined as patients without any of the following: kidney stones, osteoporosis, or diffuse muscle pains [8].
As the disease has no specific symptoms and only a few cases present with clinical entities such as nephrolithiasis (30%), osteoporosis-osteopenia (2%), pancreatitis (1%), muscle weakness (70%), constipation (32%), polyuria (28%), peptic ulcer disease (12%), depression (15%) etc., the diagnosis of primary hyperparathyroidism rests mainly on the laboratory confirmation of increased serum calcium levels and inappropriately elevated PTH concentrations in blood [4]. However, there is no difference seen in incidence and severity of any symptoms, laboratory values due to large gland (Giant Parathyroid Adenoma) and presentation of the patient is similar to the patient with smaller gland with raised serum PTH [8].
For surgical intervention, if required, exact localisation of gland is must. It is possible with the help of cervical ultrasonography, parathyroid-scintigraphy, CECT or PDG PET [8].According to the most current guidelines from the National Institutes of Health, parathyroidectomy should be performed if, any symptoms, age younger than 50 years, serum calcium > 1 mg/dl above the upper limit of normal, creatinine clearance of < 60 ml/min, and bone density T score of less than − 2.5 at any site and/or previous fragility fracture.
Surgery is the only final treatment of parathyroid adenoma. MIP should be performed to decrease morbidity associated with surgery. However preservation of recurrent laryngeal nerve is a difficult task due to large glandular tissue obstructing the view.
As of a normal glandular tissue, a giant parathyroid adenoma should present with proportionately raised PTH and should present with severe complication due to a very high serum PTH levels, but in our study the presentation of patient was same as of smaller gland. Spanheimer et al. [9] found same result in a retrospective institutional study of 15 giant parathyroid adenoma patients. They reviewed 300 patients, but only 15 (5%) were found to have giant parathyroid adenoma without any demarcated symptom due to large gland. In 2005 Power et al. [3] reported a huge parathyroid adenoma of size 8 × 5 × 3.5 cm3 and 110 g weight and stated in support of our study that instead of raised PTH, patient presented due to local pressure symptoms.
As the Giant parathyroid adenoma is a rare presentation, small numbers of cases are reported till date and so the limitation of our study was less number of cases.
Conclusion
Diagnosis and treatment of parathyroid adenomas is a challenge. Giant parathyroid adenoma is a rare entity. The presentation, management and complications are similar to smaller sized parathyroid adenomas. However, due to bigger size we found it easier to locate the gland, which is sometimes a problem in smaller adenomas.
Compliance with Ethical Statements
Funding
Nil.
Conflicts of interest
None.
Footnotes
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