case report

Oman Medical Journal [2020], Vol. 35, No. 4: e164 

Use of Recombinant Human Parathyroid Hormone to Treat Hungry Bone Syndrome in Hemodialysis Patient

Chaaban Ahmed1, Fatima Kendi1, Nicole Gebran1, Clarisse Barcebal2, Khalid Dahmani1, Ali El Houni1 and Mohammad Budruddin2*

1Department of Nephrology, Tawam Hospital in affiliation with John Hopkins, Al Ain, UAE

2Seha Dialysis Services, Tawam Dialysis Centre, Al Ain, UAE

article info


We report the case of a 35-year-old female with end-stage renal disease on hemodialysis for nine years. She was diagnosed with secondary hyperparathyroidism complicated with a brown tumor in the mandible. After medical therapy failed, she underwent total parathyroidectomy (PTX), which was complicated by severe and prolonged hypocalcemia (hungry bone syndrome). Post-surgery, she required prolonged and frequent intravenous calcium and a high dose of vitamin D resulting in frequent admission with symptomatic hypocalcemia. Her serum magnesium was noted to be in the normal range. She continued to be hypocalcemic for nearly eight months post-surgery despite the intensive treatment. Recombinant human parathyroid hormone (teriparatide) 20 mg daily resulted in normalization of calcium within two weeks. The use of parathyroid hormone proved to be an effective treatment approach in this case. Proper pre-operative preparation and subtotal PTX with an adequate dose of vitamin D and calcium supplement may have been a rational option for this case.

Secondary hyperparathyroidism (SHPT) is a frequently encountered problem in the management of patients with end-stage renal disease (ESRD) on regular hemodialysis. It has been associated with poor patient outcome including accelerated atherosclerosis and metabolic bone disease.1–3

Parathyroidectomy (PTX) in ESRD is an effective method after failing medical therapy for normalization of metabolic bone disease.4 Hungry bone syndrome (HBS) is defined as prolonged and severe hypocalcemia after PTX.4 The clinical presentation of HBS is related to hypocalcemia ranging from muscle cramps, numbness, tingling sensation, neuromuscular irritability, tetany, and in severe form can lead to a seizure.

The diagnosis of HBS is done by serial measurements of serum calcium level. The treatment of HBS includes oral and intravenous calcium and vitamin D.4 We report a case of severe and prolonged hypocalcemia post-PTX that did not respond to standard therapy but responded to recombinant parathyroid hormone (PTH) therapy.

Case report

Our patient was a 35-year-old female with ESRD due to systemic lupus erythematosus on hemodialysis for nine years. She was diagnosed with SHPT complicated with a brown tumor in the mandible. She was treated with a high dose of vitamin D3 and cinacalcet 90 mg with the following laboratory results: PTH = 228.6 pmol/L (1.6–6.9), calcium = 2.1 mmol/L, phosphorous = 1.8 mmol/L, and alkaline phosphatase = 373 IU/L. Nuclear sestamibi scanning showed increased uptake at the parathyroid area (indicating hyperplasia of four parathyroid glands). After the failure of medical therapy for 18 months, she underwent total PTX, which was complicated by severe hypocalcemia an HBS. Post-surgery, she required prolonged and frequent intravenous calcium and a high dose of vitamin D resulting in frequent admission with symptomatic hypocalcemia (serum calcium level < 1.6). Despite the intensive treatment, she continued to be hypocalcemic for nearly eight months post-surgery. At this stage, her compliance to the oral home calcium supplements was questioned. Recombinant human teriparatide 20 mg given daily for seven days followed by three times per week post dialysis, resulted in complete resolution of her symptoms and serum calcium to normalize to 2.2 mmol/L, PTH = 1.9 pmol/L, and alkaline phosphatase = 60 IU/L along with complete regression of the brown tumor [Table 1]. The total duration of therapy with teriparatide was four weeks, after that she was maintained on oral calcium supplements (600 mg eight hourly daily) and vitamin D parenteral during dialysis.

The brown tumor resolved completely post-PTX, and her calcium levels stabilized through the use of teriparatide. There was no resurgence of the brown tumor throughout the observation period of 18 months post-PTX and 15 months post use of teriparatide.

Table 1: Calcium, parathyroid hormone (PTH), phosphorous, and alkaline phosphatase levels in our patient pre- and post-therapy.


Calcium level, mmol/L



Alkaline phosphatase, IU/L

Pre-PTX, Brown tumor










PTX: parathyroidectomy.


HBS is a relatively uncommon complication of PTX for severe SHPT associated with high pre-operative bone turnover. It is clinically evident by rapid, profound symptomatic hypocalcemia associated with hypophosphatemia, hypomagnesemia, and suppressed PTH levels. Hypocalcemia will be prolonged and takes weeks to normalize. The duration of HBS is the time taken to remineralize the skeleton, which is also mirrored by normalization of bone turnover markers.4

Data on the prevalence of HBS are scarce and conflicting after the original publication in 1980 of a large case series suggesting that the syndrome develops post-operatively in up to 13% of patients with SHPT.5–8

Older age at the time of surgery is a high-risk factor for HBS.9 Patients who developed HBS have higher pre-operative levels of serum calcium and almost two-fold increased levels of PTH, calcium phosphatase10,11 and radiological bone disease before surgery.12

The treatment aims to replenish the serum calcium deficit by using high dose calcium supplemented with a high dose of the active metabolite of vitamin D.13 Adequate correction of magnesium deficiency and normalization of bone turnover are required for resolution of the hypocalcemia, which may last several months after successful surgery.

Pre-operative treatment with calcium, active vitamin D, and calcimimetics has been suggested to reduce postoperative hypocalcemia,14,15 but there is no prospective study addressing this issue. Despite vitamin D and calcium supplementation, our patient continued to have persistent hypocalcemia with frequent admissions. Her serum magnesium remained within the range of 0.9 mmol/L to 1.1 mmol/L throughout the follow-up period. Hence, she was never given a magnesium supplement.

A research group in the US has performed a limited number of studies using recombinant PTH treatment. In their study, once-daily injection with PTH was compared with conventional therapy showing that normocalcemia can be maintained by PTH therapy.16–18 However, as PTH has a relatively short half-life of 5–10 minutes, another high dose is needed to maintain normocalcemia throughout the day. No report was found on the use in patients with renal disease. In our case, after the use of PTH, serum calcium normalized in two weeks. The patient was asymptomatic and required no further admissions.


The efficacy of total PTX was satisfactory with rapid normalization of PTH and resolution of the brown tumor but complicated with severe and prolonged hypocalcemia. The use of recombinant PTH proved to be an effective treatment approach. Proper pre-operative preparation and subtotal PTX with an adequate dose of vitamin D and calcium supplement may have been a rational option for this case.


The authors declared no conflict of interest.


  1. 1. Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the dialysis outcomes and practice patterns study (DOPPS). Am J Kidney Dis 2008 Sep;52(3):519-530.
  2. 2. Lim CT, Yap XH, Chung KJ, Khalid MA, Yayha N, Latiff LA, et al. Predictor of cardiovascular risks in end stage renal failure patients on maintenance dialysis. Pak J Med Sci 2015 Nov-Dec;31(6):1300-1305.
  3. 3. Foley RN, Murray AM, Li S, Herzog CA, McBean AM, Eggers PW, et al. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol 2005 Feb;16(2):489-495.
  4. 4. Goldfarb M, Gondek SS, Lim SM, Farra JC, Nose V, Lew JI. Postoperative hungry bone syndrome in patients with secondary hyperparathyroidism of renal origin. World J Surg 2012 Jun;36(6):1314-1319.
  5. 5. Arenas MD, Alvarez-Ude F, Gil MT, Moledous A, Malek T, Nuñez C, et al. Implementation of ‘K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease’ after the introduction of cinacalcet in a population of patients on chronic haemodialysis. Nephrol Dial Transplant 2007 Jun;22(6):1639-1644.
  6. 6. Aliasgarzadeh A, Ghojazadeh M, Haji-Hoseini R, Mehanfar F, Piri R, Naghavi-Behzad M, et al. Age related secretary pattern of growth hormone, insulin-like growth factor-I & insulin-like growth factor binding protein-3 in postmenopausal women. Indian J Med Res 2014 Apr;139(4):598-602.
  7. 7. Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ 2008 Jun;336(7656):1298-1302.
  8. 8. Brasier AR, Nussbaum SR. Hungry bone syndrome: clinical and biochemical predictors of its occurrence after parathyroid surgery. Am J Med 1988 Apr;84(4):654-660.
  9. 9. Zamboni WA, Folse R. Adenoma weight: a predictor of transient hypocalcemia after parathyroidectomy. Am J Surg 1986 Dec;152(6):611-615.
  10. 10. Anderberg B, Gillquist J, Larsson L, Lundström B. Complications to subtotal parathyroidectomy. Acta Chir Scand 1981;147(2):109-113.
  11. 11. Heath DA, Van’t Hoff W, Barnes AD, Gray JG. Value of 1-a-hydroxy vitamin D3 in treatment of primary hyperparathyroidism before parathyroidectomy. BMJ1979;1(6161):450-452.
  12. 12. Ajmi S, Sfar R, Trimeche S, Ben Ali K, Nouira M. Scintigraphic findings in hungry bone syndrome following parathyroidectomy. Rev Esp Med Nucl 2010 Mar-Apr;29(2):81-83.
  13. 13. Rathi MS, Ajjan R, Orme SM. A case of parathyroid carcinoma with severe hungry bone syndrome and review of literature. Exp Clin Endocrinol Diabetes 2008 Aug;116(8):487-490.
  14. 14. Hussain A, Mahmood H, Geddoa E, Hamish M, Reda AH. Parathyroid adenoma and hypercalcemia in a patient presenting with multiple pathological fractures of the long bones. Int J Surg 2008 Dec;6(6):465-468.
  15. 15. Al-Azem H, Khan AA. Hypoparathyroidism. Best Pract Res Clin Endocrinol Metab 2012 Aug;26(4):517-522.
  16. 16. Mannstadt M, Clarke BL, Vokes T, Brandi ML, Ranganath L, Fraser WD, et al. Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study. Lancet Diabetes Endocrinol 2013 Dec;1(4):275-283.
  17. 17. Winer KK, Yanovski JA, Cutler GB Jr. Synthetic human parathyroid hormone 1-34 vs calcitriol and calcium in the treatment of hypoparathyroidism. JAMA 1996 Aug;276(8):631-636.
  18. 18. Witteveen JE, van Thiel S, Romijn JA, Hamdy NA. Hungry bone syndrome: still a challenge in the postoperative management of primary hyperparathyroidism: a systematic review of the literature. Eur J Endocrinol 2013 Feb;168(3):R45-R53.