The many guises of primary hyperparathyroidism... An unchanged scenario.
Objective: To study the causes, characteristics and outcome of treatment of patients with primary hyperparathyroidism.
Methods: This retrospective cohort analysis was conducted at the Jinnah Postgraduate Medical Centre, Karachi, and comprised data of patients with primary hyperparathyroidism between 2004 and 2014..SPSS 17 was used for data analysis.
Results: Of the 25 patients,1(4%)was male and 24(96%) were female. The overall mean age was 41.72+-15.9 years, with a mean duration of symptoms of 4.1+-3.3 years. The mean pre-operative parathyroid hormone level was 879.48+-793.51 pg/ml. Skeletal manifestations were reported in 17(68%) patients, whereas 4(16%) patients had renal stone disease. Besides, 2(8.0%) patients presented with severe abdominal pain, 1(4%) had asymptomatic hypercalcaemia and 1(4%) patient presented with headache and was diagnosed as parathyroid adenoma in the context of multiple endocrine neoplasia type 2A. All patients underwent parathyroidectomy. A solitary adenoma was reported in 23(92%) patients, carcinoma in 1(4%) and an adenoma with hyperplasia of other glands in 1(4%) patient.
Conclusion: A high index of suspicion is required for early diagnosis of primary hyperparathyroidism.
Keywords: Primary hyperparathyroidism, Parathyroidectomy, Hypercalcaemia. (JPMA 67: 580; 2017)
Primary hyperparathyroidism (PHPT) occurs as a result of unregulated over-production of parathyroid hormone (PTH) secreted from the parathyroid glands, leading to an inappropriate calcium homeostasis. PHPT per se is considered a rare disease with a variable prevalence; but data from the Rochester Epidemiological Project reported the incidence of PHPT as 21.6 cases per 100,000 person-years.1 Approximately 90% of patients with PHPT have significantly high serum PTH concentrations, while 10-20% may have only minimally elevated PTH levels.2 The commonest underlying aetiology is a solitary adenoma, accounting for almost 80-85% of the cases, whereas multi-glandular disease has been reported in 5% of patients with PHPT.3 Hyperplasia of parathyroid gland and carcinoma are less frequently seen, with a reported prevalence of 30 ng/ml###16.27+-14.3###4.00-59.6
Patients were divided into three groups based on the serum Ca level, i.e.7 (28%) normocalcaemic patients (serum Ca = 8.5-10.5 mg/dl), 17(68%) hypercalcaemic patients (serum Ca> 10.5 mg/dl), and 1(4.0%) hypocalcaemic patient (serum Ca50 nmol/L (i.e. 20ng/ml) is sufficient for prevention of secondary hyperparathyroidism in persons with normal renal function.22
Parathyroid glands are known to vary in anatomic location, and typical ectopic sites include intra-thyroidal, lateral neck and mediastinum. An ectopic location of parathyroid adenoma is a very rare cause of hyperparathyroidism, reported in 1-2% of all cases. A study from Pakistan reported three cases with ectopic parathyroid location among 70 patients operated for PHPT over a 20-year period.23 However, 4 cases of PHPT with ectopic adenoma were encountered in this small cohort of patients. The ectopic location of parathyroid adenoma is recognised as an important cause of persistent PTH elevation due to failed neck exploration surgery, especially in cases with equivocal/failure to localise through all pre-operative modalities. An Indian study has reported 7 ectopic parathyroid adenomas out of 51 cases operated for PHPT.24 One patient with jaw mass had a giant cell granuloma, which is rarely seen as a sole manifestation of PHPT.
Very few cases have been reported, where a prior diagnosis of peripheral giant cell granuloma has led to the identification of PHPT subsequently.25-27 Brown tumours can present as giant cell reparative lesions, therefore if any patient presents with a suspicious intraoral lesion, either soft tissue mass or involvement of jaw bone, it is mandatory to keenly investigate for PHPT by all possible means. A significant proportion of patients develop PHPT as a part of MEN syndrome.28 MEN-related hypercalcaemia and parathyroid hormone levels are comparatively lower than sporadic PHPT.29,30 Though the demographic and biochemical features of our patient with MEN-2A closely resemble those reported in literature, due to the paucity of data on MEN-2A as well as PHPT from our region, it is difficult to portray the clinical pattern of PHPT in context of MEN syndrome.
Various non-invasive imaging tools for localising PHPT are available, however, Technetium (TC-99m) sestamibi is the most authentic and widely used modality. Accurate localisation was achieved in 65.2% of our patients. However, it has been suggested that the uptake of MIBI in hyper-functioning parathyroid is dependent on gland size and the amount of cellular components. Studies have also reported the overall true-positive cases for sestamibiscans at 56% to 87%; the positivity being related in part to the adenoma size and pre-operative ionised calcium level.31,32 A negative MIBI scan has been reported in 50% of cystic and 27.7% of solid parathyroid adenomas with an overall Tc MIBI scan efficacy of 67%.33 It has been postulated that MIBI uptake is reduced in the presence of uraemia, and one of our patients with negative sestamibi scan also had chronic kidney disease, which evolved over the course of uncontrolled hyperparathyroidism.
This was the only patient with hypocalcaemia despite markedly elevated PTH levels, as a result of low bone reserve on account of severe complex bone disease.
Although patients with more severe disease, as manifested by severe hypercalcaemia, may have an increased risk of death, the overall survival is not adversely affected among patients with mild degree of PHPT.34 The severe form of disease seen in this study may in part be related to the delay in seeking medical care due to lack of awareness and paucity of adequate health care facilities for low socio-economic group patients in this country.
A high index of suspicion is required for clinching the early diagnosis of primary hyperparathyroidism. Concomitant vitamin D deficiency masks the hypercalcaemia, related to elevated PTH levels, thus leading to a delay in diagnosis. Therefore, hypercalcaemia must not be used alone as a screening tool for PHPT. In addition, long-standing vitamin D deficiency may cause hyperplasia/and or adenoma of parathyroid glands due to PTH dysregulation.
Conflict of Interest: None.
Source of Funding: None.
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|Publication:||Journal of Pakistan Medical Association|
|Date:||Apr 30, 2017|
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