Thyroid Research and Practice

: 2017  |  Volume : 14  |  Issue : 3  |  Page : 130--132

A challenging case of neonatal hyperparathyroidism

Vivek Aggarwal1, Manish Sahni2, Neeraj Gupta3, Deepak Khandelwal4,  
1 Department of Endocrinology, Maharaja Agrasen Hospital, Punjabi Bagh; Department of Endocrine Surgery, B.L. Kapoor Superspeciality Hospital, New Delhi, India
2 Department of Endocrine Surgery, B.L. Kapoor Superspeciality Hospital, New Delhi, India
3 Department of Paediatrics, Sir Ganga Ram Hospital, New Delhi, India
4 Department of Endocrinology, Maharaja Agrasen Hospital, Punjabi Bagh, New Delhi, India

Correspondence Address:
Deepak Khandelwal
Department of Endocrinology, Maharaja Agrasen Hospital, Punjabi Bagh, New Delhi - 110 026


Neonatal severe primary hyperparathyroidism (NSPHT) is rare disease in neonates, characterized by hypercalcemia, failure to thrive, skeletal demineralization and often multiple fractures. NSPHT induced hypercalcemia is often refractory to conventional medical therapy and may demand technically challenging surgery. We herein report a case of a neonate with NSPHT, due to novel mutation, who failed medical therapy including calcimimetics and underwent total parathyroidectomy with tracheostomy in our setup.

How to cite this article:
Aggarwal V, Sahni M, Gupta N, Khandelwal D. A challenging case of neonatal hyperparathyroidism.Thyroid Res Pract 2017;14:130-132

How to cite this URL:
Aggarwal V, Sahni M, Gupta N, Khandelwal D. A challenging case of neonatal hyperparathyroidism. Thyroid Res Pract [serial online] 2017 [cited 2022 May 26 ];14:130-132
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Full Text


Neonatal severe primary hyperparathyroidism (NSPHT) is rare disease in neonates, characterized by hypercalcemia, failure to thrive, skeletal demineralization and often multiple fractures.[1],[2] The management of hypercalcemia as a result of NSPHT is often challenging in spite of newer medications such as calcimimetics. Surgical intervention is often required as a radical and rescue therapy.

 Case Report

A 4-week, female infant was admitted to our hospital with poor feeding and lethargy for 2 days and seizures for 4 h. She was born at 39 weeks, uneventfully, to third-degree consanguineous parents with birth weight of 3.4 Kg. At admission, she required invasive ventilation, due to her poor respiratory drive. Her weight at admission was 2.2 Kg. On evaluation she was detected to have markedly elevated serum calcium (Ca) level (30 mg/dL; normal range-8.5–10.2 mg/dL) with low phosphorus (1.6 mg/dL; normal range-5.0–7.8 mg/dL). Her renal functions were deranged; blood urea was 29 mg/dL (normal range-5–17 mg/dL) while serum creatinine was 1.5 mg/dL (normal range-0.2–0.5 mg/dL). Aggressive hydration with saline along with forced diuresis with furosemide and also steroids and calcitonin were started on admission in view of life threatening hypercalcemia. On further work up she was detected to have very high intact parathyroid hormone levels (1128 pg/ml; normal range-25–50 pg/ml). Serum 25 (OH) Vitamin D level was normal (27.66 ng/ml; normal range-25–70 ng/ml). A biochemical diagnosis of primary hyperparathyroidism (HPT) was made in view of parathyroid hormone (PTH) dependent hypercalcemia. The maternal metabolic profile was normal ruling out transient neonatal HPT. Skeletal survey was suggestive of subperiosteal bone resorption with diffuse osteoporosis and low bone mineral density of 0.506 g/cm 2 (normal range 0.84–1.08 g/cm 2). NSPHT was suspected based on clinical and biochemical parameters, and diagnosis was eventually confirmed by genetic analysis suggesting a novel homozygous mutation in exon 4 of the Ca sensing receptor (CASR) gene (c.736_749delTACTCTGATGAGGA p. Tyr246Argfs*27). Meanwhile, for refractory hypercalcemia, we also used cinacalcet (calcimimetic) and bisphosphonates, which result in only transient improvement in serum Ca and PTH levels followed by biochemical worsening [Figure 1]. Finally, total parathyroidectomy with tracheostomy, in one stage, was performed after discussion with the family. The child had dramatic improvement in biochemical parameters postsurgery and rather had postoperative hypocalcemia as expected and required treatment with intravenous Ca and calcitriol. Histological examination confirmed primary HPT caused by chief-cell hyperplasia. She was gradually weaned off from ventilator and tracheostomy and was discharged 50 days after surgery on oral Ca and calcitriol. Tracheostomy was successfully decannulated after 9 months of age. On extended follow-up of 2 years child is doing well, she weighed 12 Kg (at the age of 26 months) with normal serum Ca levels on oral Ca and calcitriol supplementation.{Figure 1}


Ca in human body is controlled by major regulatory hormones such as PTH, calcitonin, and Vitamin D. Hypercalcemia is defined as a serum Ca level >10.5 mg/dL, which could be mild (10.5–11.9 mg/dL), moderate (12–13.9 mg/dL), or crisis situation when serum Ca crosses 14 mg/dL. There could be various causes of hypercalcemia in infancy [Table 1].{Table 1}

The CASR is a G protein-coupled receptor, which allows the parathyroid chief cells, the thyroidal C-cells, and the ascending limb of the loop of Henle to respond to changes in the extracellular Ca concentration, located on chromosome 3q2. The activity of CASR is mainly responsible for PTH secretion and Ca absorption in the loop of Henle. Familial hypocalciuric hypercalcemia (FHH) and NSPHT are uncommon but important human disorders due to loss-of-function mutations in CASR gene. Defective gene dosages account for varied presentations of FHH and NSPHT. FHH is benign condition with mild hypercalcemia with single defective allele as compared to NSPHT, where two alleles are abnormal leading to severe hypercalcemia manifesting in infancy. Additional features of NSPHT include failure to thrive, bony under-mineralization, multiple fractures, and ribcage deformity.[1],[2] In our patient, PTH-mediated severe hypercalcemia in neonatal period indicated the possibility of NSPHT. In addition, there was a history of third-degree consanguinity in parents.

Hypercalcemia in NSPHT is often refractory to medical management and requires surgical intervention. In our patient, we tried hyper-hydration, loop diuretics, calcitonin, glucocorticoids as well as bisphosphonates as standard management of severe hypercalcemia. Child also required prolonged ventilatory support due to marked muscular weakness often seen in NSPHT. Due to refractory hypercalcemia, cinacalcet (calcimimetic agent) was also used, as it is known to activate CASR in the parathyroid glands and by lowering the threshold for CASR activation by extracellular Ca ions may decrease PTH secretion and serum Ca. There are very limited reports of use of cinacalcet for the treatment of NSPHT in the literature with variable response.[3],[4],[5],[6] In view of her refractory hypercalcemia, total parathyroidectomy with tracheostomy was done as single-stage procedure. Total or subtotal parathyroidectomy is the advocated treatment for NSPHT. Lutz et al. described the first case treated with total parathyroidectomy with autotransplantation of parathyroid tissue.[7]

Our case is unique in many aspects as novel mutation of CASR gene was identified and also calcimimetic drug was explored in the management of NSPHT. To the best of our knowledge, this is the youngest successfully surgically managed case of NSPHT from India.

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Conflicts of interest

There are no conflicts of interest.


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