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The many guises of primary hyperparathyroidism... An unchanged scenario.

Byline: Tasnim Ahsan, Uzma Erum, Khawaja Mohammad Inam Pal, Rukhshanda Jabeen, Saima Ghaus Qureeshi, Urooj Lal Rehman and Zeenat Banu

Abstract

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)

Introduction

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.

Conclusion

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.

Disclaimer: None.

Conflict of Interest: None.

Source of Funding: None.

References

1. Wermers RA, Khosla S, Atkinson EJ, Achenbach SJ, Oberg AL, Grant CS, et al. Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993-2001: an update on the changing epidemiology of the disease. J Bone Miner Res 2006; 21: 171-7.

2. Nussbaum S. Immunometric assays of parathyrin in the diagnosis of hypercalcemic individuals. Clin Chem 1991; 37: 142-3.

3. Molinari AS, Irvin GL, Deriso GT, Bott L. Incidence of multiglandular disease in primary hyperparathyroidism determined by parathyroid hormone secretion. Surgery 1996; 120: 934-7.

4. Givi B, Shah JP. Parathyroid Carcinoma. Clin Oncol 2010; 22: 498-507.

5. Rawat N, Khetan N, Williams DW, Baxte JN. Parathyroid carcinoma. Br J Surg 2005; 92: 1345-53.

6. Bilezikian JP, Silverberg SJ. Clinical practice. Asymptomatic primary hyperparathyroidism. N Engl J Med 2004; 350: 1746-51.

7. Biyabani SR, Talati J. Bone and renal stone disease in patients operated for primary hyperparathyroidism in Pakistan: Is the pattern of disease different from west? J Pak Med Assoc 1999; 49: 194-8.

8. Afzal A, Gauhar TM, Butt WT, Khawaja AA, Azim KM. Management of hyperparathyroidism: A five year surgical experience. J Pak Med Assoc 2011; 61: 1194-8.

9. Bhansali A, Masooodi SR, Reddy KS, Behera A, das Radotra B, Mittal BR, et al. Primary hyperparathyroidism in north India: a description of 52 cases. Ann Saudi Med 2005; 25: 29-35.

10. Gopal A, Acharya SV, Bandgar T, Menon PS, Dalvi AN, Shah NS. Clinical profile of primary hyperparathyroidism from western India: a single centre experience. J Postgrad Med 2010; 56: 79-84.

11. Jha S, Jayaraman M, Jha A, Jha R, Modi KD, Kelwadee JV. Primary Hyperparathyroidism: A changing scenario in India. Indian J Endocrinol Metab 2016; 20: 80-3.

12. Bahrami A. Primary hyperparathyroidism in Iran: a review. Int J Endocrinol Metab 2008; 1: 50-7.

13. Mazeh H, Sipple RS, Chen S. The role of gender in primary hyperparathyroidism: same disease, different presentation. Ann Surg Oncol 2012; 19: 2958-62.

14. Marques TF, Vasconcelos R, Diniz E, Rego D, Griz L, Bandeira F. Normocalcemic primary hyperparathyroidism in clinical practice: an indolent condition or a silent threat? Arq Bras Endocrinol Metabol 2011; 55: 314-7.

15. Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, Silverberg SJ. Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype. J Clin Endocrinol Metab 2007; 92: 3001-5.

16. Bilezikian, JP, Silverberg SJ. Normocalcemic primary hyperparathyroidism. Arq Bras Endocrinol Metabol 2010; 54: 106-9.

17. Lundgren E, Rastad J, Thurfjell E, Akerstrom G, Ljunghall S. Population-based screening for primary hyperparathyroidism with serum calcium and parathyroid hormone values in menopausal women. Surgery 1997; 121: 287-94.

18. Malabu UH, Founda MA. Primary hyperparathyroidism in Saudi Arabia: A review of 46 cases. Med J Malaysia 2007; 65: 394-7.

19. Amaral LM, Queiroz DC, Marques TF, Mendes M, Bandeira F. Normocalcemic versus Hypercalcemic Primary Hyperparathyroidism: More Stone than Bone? J Osteoporosis; 2012.

20. Jacob JJ, John M, Thomas N, Chacko A, Cherian R, Selvan B, et al. Does hyperparathyroidism cause pancreatitis? A South Indian experience and a review of published work. ANZ J Surg 2006; 76: 740-4.

21. Carnaille B, Oudar C, Pattou F, Combemale F, Rocha J, Proye C. Pancreatitis and primary hyperparathyroidism: forty cases. Aust N Z J Surg 1998; 68: 117-9.

22. Saliba W, Barnett O, Rennert HS, Lavi I, Rennert G. The relationship between serum 25(OH)D and parathyroid hormone levels. Am J Med 2011; 124: 1165-70.

23. Abbas F, Biyabani SR, Memon A, Talati J. Mediastinal parathyroid adenoma causing Primary hyperparathyroidism. J Pak Med Assoc 2007; 57: 93-5.

24. Muthukrishnan J, Jha S, Modi KD, Jha R, Kumar J, Verma A, et al. Symptomatic primary hyperparathyroidism: a retrospective analysis of fifty one cases from a single centre. J Assoc Physicians India 2008; 56: 503-7.

25. Smith BR, Fowler CB, Svane TJ. Primary hyperparathyroidism presenting as a "peripheral" giant cell granulomas. J Oral Maxillofac Surg 1988; 46: 65-9.

26. Aswath N, Chidambaranathan P. Primary hyperparathyroidism as a central giant cell granuloma of the jaws: pre and post operative treatment pattern of clinical and radiographic presentations. IJCRI 2012; 3: 51-6.

27. Gataa IS, Zardawi FM. Primary hyperparathyroidism presented as central giant cell granuloma of jaw bones. A report of three cases. IOSR J Dent Med Sci 2015; 14: 75-9.

28. Moline J, Eng C. Multiple endocrine neoplasia: an overview. Genet Med 2011; 13: 755-64.

29. Twigt BA, Scholten A, Valk DG, Rinkes-Borel IHM, Vriens MR. Difference between sporadic and MEN related primary hyperparathyroidism; clinical expression, preoperative work-up, operative strategy and follow-up. Orphanet J Rare Dis 2013; 8: 50.

30. Raue F, Kraimps JL, Dralle H, Cougard P, Proye C, Frilling A, et al. Primary hyperparathyroidism in multiple endocrine neoplasia type 2A. J Intern Med 1995; 238: 369-73.

31. Swanson TW, Chan SK, Jones SJ, Bugis S, Irvine R, Belzberg A, et al. Determinants of Tc-99m sestamibi SPECT scan sensitivity in primary hyperparathyroidism. Am J Surg 2010; 199: 614-20.

32. Moka D, Voth E, Dietlein M, Larena-Avellaneda A, Schicha H. Technetium 99m-MIBI-SPECT: A highly sensitive diagnostic tool for localization of parathyroid adenomas. Surgery 2000; 128: 29-35.

33. Ghasemi-Rad M, Lesha e, Abkhiz S, Mohammadi A. Primary Hyperparathyroidism: Comparing between solid and cystic adenomas and the efficacy of ultrasound and single-photon emission computed tomography in their diagnosis. Endocr Prac 2015; 21: 1277-81.

34. Wermers RA, Khosla S, Atkinson EJ, Grant CS, Hodgson SF, O'Fallon WM, et al. Survival after the diagnosis of hyperparathyroidism: a population-based study. Am J Med 1998; 104: 115-22.
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Publication:Journal of Pakistan Medical Association
Date:Apr 30, 2017
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