|LETTER TO THE EDITOR
|Year : 2017 | Volume
| Issue : 2 | Page : 362-363
Utility of cinacalcet in familial hypocalciuric hypercalcemia
Bipin Kumar Sethi, V Sri Nagesh, Jayant Kelwade, Harsh Parekh, Vaibhav Dukle
Department of Endocrinology, CARE Hospital, Banjara Hills, Hyderabad, Telangana, India
|Date of Web Publication||14-Mar-2017|
Bipin Kumar Sethi
Department of Endocrinology, CARE Outpatient Centre, Road No. 10, Banjara Hills, Hyderabad - 500 034, Telangana
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sethi BK, Nagesh V S, Kelwade J, Parekh H, Dukle V. Utility of cinacalcet in familial hypocalciuric hypercalcemia. Indian J Endocr Metab 2017;21:362-3
|How to cite this URL:|
Sethi BK, Nagesh V S, Kelwade J, Parekh H, Dukle V. Utility of cinacalcet in familial hypocalciuric hypercalcemia. Indian J Endocr Metab [serial online] 2017 [cited 2020 Dec 6];21:362-3. Available from: https://www.ijem.in/text.asp?2017/21/2/362/202034
Familial hypocalciuric hypercalcemia (FHH) is caused by an inactivating mutation of the calcium-sensing receptor (CaSR) and is autosomal dominant in transmission. The CaSR enables the parathyroid gland to sense variations in the serum calcium concentration, leading to the desired changes in parathyroid hormone (PTH) secretion. In FHH, inactivating mutations in the gene encoding the CaSR lead to decreased sensitivity of the CaSR to ionized calcium (Ca ++), shifting the set point for Ca ++-regulated PTH release to the right. This set point shift is followed by an increased circulating level of PTH and subsequent hypercalcemia. However, blood calcium is usually only moderately elevated in FHH patients as is the level of serum PTH. In FHH, urinary calcium excretion is reduced and the renal tubular reabsorption of Ca ++ and ionized magnesium (Mg ++) is increased. In most cases, patients with FHH are asymptomatic or have a history of only mild symptoms such as vertigo, uneasiness, muscle soreness, or poor memory. Most patients are usually detected when evaluated routinely or for vague symptoms. Treatment is not required in most cases. However, rarely when calcium levels are very high or the symptoms are found to be consequent upon hypocalcemia, it becomes necessary to treat FHH. The calcimimetic cinacalcet is a promising option for the treatment of FHH. It is an allosteric modulator of the CaSR that increases the sensitivity and the expression of the CaSR, thus enhancing the CaSR signal transduction. Here, we present the case of a 36-year-old man with FHH, who was successfully treated with cinacalcet.
Thirty-six-year-old man was diagnosed to have hypercalcemia when evaluated routinely. Initial serum calcium was 11.2 mg/dl and corrected serum calcium was 10.72 mg/dl. His only symptom was polydipsia. On examination, his height was 167 cm and weight was 55.8 kg, pulse rate was 100/min, and blood pressure was 128/76 mmHg. Lungs were clear and he did not have any palpable neck mass or obvious bony deformity or fracture. Rest of the examination was unremarkable. After 1 week, repeat corrected serum calcium was 10.7 mg/dl. Serum Vitamin D level was 16 ng/ml. On further evaluation, ionized calcium was 6.1 mg/dl and alkaline phosphatase was 371 U/l. Initial PTH was 25 pg/ml. 1,25(OH) D levels were 76 ng/l. Thyroid profile and neck ultrasound were normal. Chest X-ray was normal. Computed tomography scan of the brain showed chronic calcification along central falx and the frontal cranial fossa. Mantoux was negative and serum angiotensin converting enzyme levels were 51.6 U/l. Urine and protein electrophoresis were normal and did not show monoclonal 'M' band peak suggestive of myeloma. PTH-related protein levels were also normal. Repeat PTH was 50.6 pg/ml with a serum calcium of 11.2 mg/dl and phosphorus of 3.2 mg/dl. 24 h urine calcium was 106 mg/day with a calcium clearance of 69.1 ml/min. Subsequent 24 h urine calcium creatinine clearance ratio was 0.009, thus confirming FHH. Screening of other family members for hypercalcemia was negative. At this point of time, the patient was started on tablet cinacalcet 30 mg twice a day. Simultaneously, the patient was also supplemented with Vitamin D. One month later, on treatment with cinacalcet, serum calcium had decreased to 9 mg/dl, and 24 h urine calcium had increased to 120 mg/day with a calcium clearance of 90.3 ml/min. 24 h urine calcium creatinine clearance ratio also increased to 0.01. Sestamibi scan of the neck was also negative for a parathyroid adenoma. Genetic analysis for CaSR mutation is being planned.
In the present case, we observed a significant reduction in the serum calcium levels and improvement calcium clearance after initiation of cinacalcet therapy. The patient also reported decrease in polydipsia. These findings are similar to previous case reports. Thus, our findings are in line with the observations of Timmers et al., Festen-Spanjer et al., Alon and Vandevoorde, and Reh et al. who all reported a similar effect of cinacalcet on biochemical profile during short-term observation. Long-term data from Rasmussen et al. also showed that the biochemical improvement toward normalization of serum calcium and S-iPTH persists for at least 36 months without side effects or the need for a change in dosage as observed in one case. Furthermore, the observations are in line with observations  from PHPT patients with a cinacalcet treatment of up to 5 years duration. Howles et al. have shown the efficacy of cinacalcet in patients with familial hypocalciuric hypercalcemia harboring the AP2S1 mutations.
In conclusion, cinacalcet proved effective for reducing the serum calcium levels in a young patient with FHH along with a self-reported improvement in symptoms. This suggests that cinacalcet may be a viable option for treatment of symptomatic FHH, instead of the usually practiced subtotal parathyroidectomy. However, to fully document the usefulness of cinacalcet treatment in FHH, a randomized controlled trial is warranted.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Schwarz P, Sørensen HA, Transbøl I. Inter-relations between the calcium set-points of Parfitt and Brown in primary hyperparathyroidism: A sequential citrate and calcium clamp study. Eur J Clin Invest 1994;24:553-8.
Brown EM. Familial hypocalciuric hypercalcemia and other disorders with resistance to extracellular calcium. Endocrinol Metab Clin North Am 2000;29:503-22.
Timmers HJ, Karperien M, Hamdy NA, de Boer H, Hermus AR. Normalization of serum calcium by cinacalcet in a patient with hypercalcaemia due to a de novo
inactivating mutation of the calcium-sensing receptor. J Intern Med 2006;260:177-82.
Festen-Spanjer B, Haring CM, Koster JB, Mudde AH. Correction of hypercalcaemia by cinacalcet in familial hypocalciuric hypercalcaemia. Clin Endocrinol (Oxf) 2008;68:324-5.
Alon US, Vandevoorde RG. Beneficial effect of cinacalcet in a child with familial hypocalciuric hypercalcemia. Pediatr Nephrol 2010;25:1747-50.
Reh CM, Hendy GN, Cole DE, Jeandron DD. Neonatal hyperparathyroidism with a heterozygous calcium-sensing receptor (CASR) R185Q mutation: Clinical benefit from cinacalcet. J Clin Endocrinol Metab 2011;96:E707-12.
Rasmussen AQ, Jørgensen NR, Schwarz P. Clinical and biochemical outcomes of cinacalcet treatment of familial hypocalciuric hypercalcemia: A case series. J Med Case Rep 2011;5:564.
Peacock M, Bilezikian JP, Bolognese MA, Borofsky M, Scumpia S, Sterling LR, et al.
Cinacalcet HCl reduces hypercalcemia in primary hyperparathyroidism across a wide spectrum of disease severity. J Clin Endocrinol Metab 2011;96:E9-18.
Howles SA, Hannan FM, Babinsky VN, Rogers A, Gorvin CM, Rust N, et al.
Cinacalcet for symptomatic hypercalcemia caused by AP2S1 mutations. N Engl J Med 2016;374:1396-8.
|This article has been cited by|
||Predictors of fatigue and persistent fatigue in early rheumatoid arthritis: a longitudinal observational study, data from the ESPOIR cohort
| ||S Rodríguez-Muguruza,B Combe,F Guillemin,B Fautrel,A Olive,S Marsal,O Valero,N Rincheval,C Lukas |
| ||Scandinavian Journal of Rheumatology. 2020; : 1 |
|[Pubmed] | [DOI]|
||Use of calcimimetics in children with normal kidney function
| ||Judith Sebestyen VanSickle,Tarak Srivastava,Uri S. Alon |
| ||Pediatric Nephrology. 2018; |
|[Pubmed] | [DOI]|
||Calcimimetic and calcilytic therapies for inherited disorders of the calcium-sensing receptor signalling pathway
| ||Fadil M Hannan,Mie K Olesen,Rajesh V Thakker |
| ||British Journal of Pharmacology. 2017; |
|[Pubmed] | [DOI]|