Int. Med J Vol. 6 No 2 December 2007

Primary hyperparathyroidism with hungry bone syndrome - A Case Report

Khairul AJ1. Norazmi K2.

1Department of Internal Medicine, International Islamic University, Malaysia.Kuantan, Pahang.

2Department of Medicine, Hospital University Kebangsaan Malaysia. Kuala Lumpur

ABSTRACT

Primary hyperparathyroidism with severe bone disease as a result  of excessive parathyroid hormone ( PTH ) release and severe hypercalcaemia can lead to 'hungry bone syndrome' (HBS) post operatively. This is due to sudden cessation of PTH and drop in serum calcium. We reported a case a young man with primary hyperparathyriodism due to a single parathyroid adenoma with severe bone disease and post operatively developed hungry bone syndrome.  

KEYWORDS: Primary hyperparathyroidism, parathyroid adenoma, hungry bone syndrome

INTRODUCTION

Primary hyperparathyroidism is one of the causes of hypercalcaemia. It is due to excessive release of parathyroid hormone (PTH) in the circulation. Eighty five percent is caused by a single adenoma of a parathyroid gland and 15 % by multiple hypertrophies of the parathyroid glands.  A very small number is due to parathyroid carcinoma.1. It is commonly found in the fifth and sixth decades of life and twice more common in females.1  Most are asymptomatic and often detected by routine biochemical assessment.  Ninety percent presented with bony involvement and more than half (54 % ) had involvement of both skeletal and renal systems. Osteitis fibrosa cystica  ( brown tumor ) of the bone is associated with severe hypocalcaemia after surgery (parathyroidectomy).   Hypercalcaemic parathyroid crisis can with serum calcium level above 3.5 mmol/L.  Preoperative imaging for localization of abnormal PTH may not be necessary if clinical and biochemical evidence point strongly towards the diagnosis.2

Case Report

An 18 year old male presented with pain in the back and lower  limbs for one year associated with lethargy.  He stopped schooling at the age of 15 and had been working since then. The pain forced him to change work frequently. There was swelling of the right side of the anterior portion of the neck (2 cm x 3 cm) which was diffuse. It was non tender with no lymphadenopathy.  He was euthyroid. His height was normal and he had no features of the carpal bones shortening. Other family members were asymptomatic. Blood investigations showed a raised serum calcium level of 2.92 mmol/L, a low serum phosphate of 0.43 mmol/L, a normal serum creatinine of 55 umol, a very high serum alkaline phosphatase of 3834 mmol/L, a normal serum albumin of 40 g/L, an elevated serum PTH of more than 273,   an elevated   24 hour urine calcium of more than 7.5 mmol / 24 hour, the random blood sugar was 4.5 mmol/L, the radiographs  of the skeletals showed severe bone disease ( figure 1) and the bone mineral density ( BMD)  of the spine and hip were within osteoporotic range.   Serum prolactin level, serum cortisol and the ultrasound of the kidneys were normal. Ultrasound of the neck revealed a 1.5 cm x 1.5 cm x 3 cm elongated lesion occupying the posterolateral aspect of the mid and lower portion of the thyroid gland. The diagnosis of primary hyperparathyroidism was made and patient was planned for parathyroidectomy.

He was started on normal saline hydration of 6 pints in 24 hours and intravenous frusemide 40 mg daily to reduce serum calcium to around 3.0 mmol/L for surgery. The serum calcium level remained high with peak level of 3.3 mmol/L. Intravenous Pamidronate 60 mg over two hour infusion had to be given twice. Despite all these measures, the serum calcium level continued to be erratic as it dropped abruptly to low levels and climbed up back to high levels just as quickly. As a result, subcutaneous calcitonin 100 mcg stat dose had to be given one day prior to surgery in an attempt to control the level. Oral vitamin D 1 mcg daily was given for one week prior to surgery in anticipation of severe hypocalcaemia post operatively from the severe bone disease. 

Right superior parathyroidectomy was performed without complication.  A large - sized adenoma (3.5 x 2.5 cm) was removed (figure 2). Histopathological finding of the resected parathyroid gland confirmed a parathyroid adenoma. Post operatively, as anticipated patient developed episodes of severe hypocalcaemia associated with perioral numbness and positive for both Chvostek and Troissier’s sign. Serum calcium level was persistently below 2.0 mmol/L. Intravenous calcium infusion had to be given guided by 6 hourly monitoring of serum calcium. Oral Vitamin D was increased to 2 mcg three times a day and oral calcium carbonate was given  3 mg 4 times a day. Serum PTH level, however showed significant improvement.

He was finally discharged after twp weeks of calcium monitoring post operatively in the ward with a stable serum calcium, serum phosphate and alkaline phosphatase level.  He was given a two weekly follow up at the endocrine clinic for serum calcium and clinical assessment.

 

Figure 1: Periosteal and subperiosteal changes with generalized osteopenia of the metacarpals.
Figure 2 : The parathyroid adenoma while being removed intraoperatively

DISCUSSION

Post operative hungry bone syndrome (HBS) is not uncommon.The incidence of HBS was 12.6 % of 198 patients with primary hyperparathyroidism. 4 HBS is characterized by prolonged and severe post operative hypocalcaemia and hypophosphataemia as a result of extensive and accelerated remineralisation of the bone following sudden decrease of parathyroid hormone.5,6 This syndrome should be anticipated when there is evidence of severe parathyroid bone disease with marked elevation of serum alkaline phosphatase and serum parathyroid hormone.7 Risk factors predicting the development of HBS include age, high levels of alkaline phosphatase, blood urea and size of adenoma. The size of adenoma is the most important predictive factor. 5,6 A well balanced approach is necessary to prevent preoperative fatal hypercalcaemic crisis and at the same time reduce the post operative hypocalcaemic consequence of HBS. The metabolic derangement of HBS following successful surgery can be minimized or reduced by prophylactic preoperative treatment. This avoids prolonged and vigorous post operative intravenous calcium infusion. Recommendations for preoperative management would be at least two weeks prior to surgical intervention. 7 Early operations is necessary if patients condition is deteriorating with recaltricant hypercalcaemia.8 A comparative study of intravenous pamidronate disodium and intravenous etidronate disodium in treatment of cancer related hypercalcaemia with normalization of serum calcium found in 70 – 100 % of patients over duration of 2 – 7 days. 9 Dialysis too has been proven to be effective in controlling hypercalcaemia.10 In pre operative management, the effect of dihydroxy – vitamin D3( calcitriol ) is variable.5 ,6 ,8 Severe HBS has been reported despite use of dihydroxy – vitamin D3 and calcitonin.5  Preoperative use of inorganic phosphate has been abandoned due to lethal complications of pulmonary, soft tissue and intravascular calcium deposition. 11 Use of biphosphonate reduces the incidence of severe post operative hypocalcaemia.12, 13  This reduces the severity of HBS and shortens the course of post operative calcium replacement. Adenoma size is a major determinant of disease severity and manner of presentation and this is related to vitamin D nutrition in India. 14

Considerable increase in bone mineral density (BMD) after parathyroidectomy could be obtained even in patients without surgical indication based on NIH criteria. Indices such as alkaline phosphatase and severity of cortical bone mass reduction are clinically useful for predicting the changes in lumbar BMD after parathyroidectomy 15. 

CONCLUSION

It is important to exercise appropriate preoperative management and to anticipate HBS prior to surgical intervention of primary hyperparathyroidism with high probability of developing HBS post operatively particularly in the presence of severe bone disease and a big tumor.  Strict monitoring of the patients’s serum calcium level pre and post operative is crucial. 

REFERENCES

  1. Lawrence Kim, MD. Hyperparathyroidism.2005; emedicine.com.

  2. Soin AS, Gupta S, Kochupillai N, Sharma. Primary Hyperparathyroidism. An Indian Study. Indian Journal of Ca 1994;  2 : 72 – 71.

  3. Ali AZ, Micheal AL.  Primary hyperparathyroidism. Lancet 1997; 349: 1233- 38.

  4. Brassier AR, Nusbaum SR. Hungry Bone Syndrome: clinical and biochemical predictors of its occurrence after parathyroid surgery . Am J Med 1988; 84: 654 – 60.

  5. Hisham AN, Meah FA, Abdullah T, Khalid BAK, Sakinah O, Tan TT. Hungry bone syndrome in a child following parathyroid surgery. Asian J Surgery 1995; 18 (2): 147 – 49.

  6. Cruz DN, Perazella MA, Biochemical Aberrations in a dialysis patients following parathyroidectomy. Am J Kidney Dis 1997; 29 (5): 759 – 62.

  7. A N Hisham, E N Aina, H Zanariah, Recognition and management of Hungry Bone Syndrome – A case report. Med J Malaysia 2000; 55(1) : 132 – 33.

  8. Murphy JP. Fatal hypercalcaemic crisis, Hospital update 1992; 18: 677 – 78.

  9. Gulap R, Ritch P , Wiernik P et al . Comparative study of pamidronate disodium and etidronate disodium in treatment of cancer related hypercalcaemia. J. Clin. Oncology 1992; 10: 134 – 42.

  10. Cardella CJ, Birkin BL, Rapoport A . Role of dialysis in the treatment of severe hypercalcaemia : Report of 2 cases treated with haemodialysis and review of literature. J. Clin. Nephrology 1979; 12: 285 – 90.

  11. Vernava AM, O’ Neal LW, Palermo V. Lethal hyperparathyroid crisis: hazards of phosphate administration. Surgery 1987; 102: 941 – 48.

  12. Kumar A, Ralston SH,. Biphosphonates prevent the hungry bone syndrome. Nephron 1996; 74 (4) : 729 .

  13. Adamson BB, Gallacher SJ, Byars, Ralston SH, Boyle IT, Boyce BF,. Mineralisation defects with pamidronate therapy for Paget’s disease. Lancet 1993; 342: 1450 – 60.

  14. D Sudhaker Rao, M. Honasoge, George W.Divine, Evelyn R et al. Effect of vitamin D Nutrition on parathyroid adenoma weight: Pathogenetic and clinical implications . Journal of Clinical Endocrinology and Metabolism 2000; 85(3): 1054 – 58.

  15. Daiki Nakaoka,Toshitsugu S et al . Prediction of bone mass change after parathyroidectomy in patients with primary hyperparathyroidism. Journal of Clinical Endocrinology and Metabolism 2000; 85 (5):1901 – 07.   

Correspondent

Assistant Prof. Dr Khairul Azhar Jaafar, MBBS (Malaya), M.Med ( UKM ).

Medical Department

IIUM, Jalan Hospital

25050, Kuantan, Pahang

095716408

0163705616

E-maiL: drkhai72@yahoo.com