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Iran J Pediatr

Case Report Sep 2008; Vol 18 ( o 3), Pp:277-280

Severe Neonatal Hypercalcemia due to Primary

Hyperparathyroidism; A Case Report
Siamak Shiva*1, MD, Pediatric Endocrinologist; Alireza Nikzad1, MD, General Physician;
Saeid Aslanabadi2, Pediatric Surgeon; Vahid Montazeri3, MD, Thoracic surgeon;
Mohammad-Reza Nikzad1, MD, General Physician
1. Department of Pediatrics, Tabriz University of Medical Sciences, IR Iran

2. Department of Pediatric Surgery, Tabriz University of Medical Sciences, IR Iran
3. Department of Thoracic Surgery, Tabriz University of Medical Sciences, IR Iran
Received: 25/01/08; Revised: 22/05/08; Accepted: 06/06/08
Abstract
Background: Neonatal primary hyperparathyroidism (NPHP) is a rare disease characterized by
marked hypercalcemia, diffuse parathyroid hyperplasia and skeletal demineralization. These
patients have symptoms of chronic hypercalcemia such as failure to thrive, irritability,
abdominal pain and anorexia. It is often fatal unless parathyroidectomy is performed.
Treatment with drugs usually is inadequate and often results in chronic hypercalcemia and
death.
Case presentation: A 10-day-old, 2.9 kg male newborn was hospitalized for anorexia, poor
feeding, cyanosis, hypotonia, lethargy and severe dehydration. Diagnosis of severe
hypercalcemia due to primary hyperparathyroidism was established and surgical approach
selected because of failure of medical therapy to control hypercalcemia. The baby was
successfully treated by total parathyroidectomy with autotransplantation.
Conclusion: Although neonatal primary hyperparathyroidism (NPHP) is a rare disease, it must
be considered for differential diagnosis in neonates with severe hypercalcemia. Early diagnosis
and total parathyroidectomy with autotransplantation can be life-saving.
Key Words: Primary hyperparathyroidism; Neonate; Parathyroidectomy; Autotransplantation
Introduction fatal unless a prompt diagnosis is made and

urgent surgical intervention instituted[2]. It is
Neonatal primary hyperparathyroidism associated with hypotonia, respiratory
(NPHP) is a rare disease that presents in the distress, irritability, lethargy, failure to thrive,
first 6 months of life[1]. It is almost invariably constipation and severe hypercalcemia with
* Correspondence author;
Address: Children Hospital, Sheshgelan Ave, Tabriz,IR Iran
E-mail: [email protected]
278 Neonatal Hypercalcemia due to Primary Hyperparathyroidism; S Shiva, et al
elevated parathyroid hormone (PTH) levels[1]. parts of femur, humerus and ribs along with
Radiographs show severe bone lung calcification were seen (Fig 1).
demineralization[1,3]. The etiology is genetic[4]
and results from inactivating mutation of
calcium sensing receptor gene, in which the
inhibitory effect of extracellular calcium on the
secretion of PTH by chief cell is absent[1]. All
reported cases of NPHP have been due to
parathyroid chief cell hyperplasia[1-6].
Surgical treatment with subtotal parathyro-
idectomy, total parathyroidectomy or total
parathyroidectomy with autotransplantation,
is preferred modality. The mortality rate with
this modality is 24%[7]. About 50 neonates with
NPHP have been reported and it has been
suggested as a possible contributor to a small
number of cases of the Sudden Infant Death
Syndrome[2,4]. The authors report on a case
presenting in a male neonate, review the world
literature and discuss the clinical
manifestations, investigators' findings and the
management options available.
Fig 1- Skeletal survey of patient, demonstrating

multiple fractures and generalized osteopenia
Case Presentation
A 10-day-old 2.9 kg male newborn was Ultrasound revealed medullary nephro-
hospitalized for anorexia, poor feeding, calcinosis; echocardiography was normal.
cyanosis, hypotonia, lethargy and severe 99M-TC-sestaMIBI scan showed homogeneous
dehydration. He was a full term baby at birth uptake of the radiotracer in parathyroid
weighing 3400 grams and his parents were glands with no evidence of parathyroid
related (cousins). Despite rehydration, he had adenoma. Combination of clinical, laboratory
hypercalcemia with Ca concentration of 18.2 and radiological findings were consistent with
mg/dl (normal, 8.6 to 10.3). Other laboratory the diagnosis of NPHP. Since patient did not
findings were serum PTH level of 996 pg/ml respond to the medical therapy and his
(Normal, 7 to 82), phosphorus level of 1.6 symptoms persisted, surgical approach was
mg/dl (Normal, 4 to 6.5) and alkaline considered. We performed total parathyroid-
phosphatase level of 1322 IU/L (Normal, 180 ectomy with autotransplantation. After
to 1200). Urine Ca excretion was 12 mg/kg/d. removing all 4 parathyroid glands, a portion of
Evaluation of mother for serum levels of Ca, P a gland was autotransplanted in
and PTH showed normal values. With sternocleidomastoid muscle. Because of
vigorous medical management using saline hypocalcemia (serum Ca 7.5 mg/dl) we
diuresis, furosemide, hydrocortisone and started calcium supplementation and vitamin
intravenous pamidronate 1mg/kg/d for 3 D therapy during the second day after surgery.
days, serum Ca level remained between 13-15 Two months after surgery patient was
mg/dl. Full skeletal survey revealed severe eucalcemic and had no need for vitamin D
and generalized osteopenia. Bone density was supplementation. Histological examination of
diffusely decreased and multiple regions of parathyroid glands revealed diffuse chief cell
pathologic fractures in proximal and distal hyperplasia (Fig 2).
Iran J Pediatr, Vol 18 (o 3); Sep 2008 279
contrast, NPHP can be life-threatening if left

untreated[1]. Mutations in the calcium-sensing
receptor (CASR) gene which lead to loss of
normal function of these receptors can be seen
in both FHH and NPHP. Activation of CASR by
extracellular calcium inhibits secretion of PTH
by the chief cells[1,9]. In NPHP, medical therapy
is inadequate and surgical modality should be
considered[3-5]. This intervention must be
undertaken immediately to avoid death or
irreversible long term complications such as
nephrocalcinosis, cardiac abnormalities, bone
resorption, or central nervous system
Fig 2- Microphotograph of parathyroid tissue
alterations[4].
shows diffused chief cell hyperplasia. Note the
As in our case many other reports show
uniform appearance of parathyroid chief cells
that the treatment of choice is total parathyro-
(hematoxylin & eosin stained)
idectomy with autotransplantation[4,10-13].
Without parathyroidectomy, affected infants
will usually die by the age of three months[10].
Medical therapy without surgical intervention
Discussion has a mortality rate of 70% to 87% and severe
long term complications in the survivors[4].
Neonatal primary hyperparathyroidism Ross et al reported that seven of eight patients
(NPHP) is a rare disease, which is often fatal. treated medically for primary hyperpara-
This condition results from chief cell thyroidism died in infancy, with a mortality
hyperplasia and excessive secretion of PTH[3- rate of 87.5% and the mortality rate among
6]. Usually symptoms manifest in the first days patients treated surgically was reduced to
after birth[4]. Symptoms include poor feeding, 24%[7]. Meeran et al reported a case with
irritability, constipation, polyuria, hypotonia, NPHP who survived without parathyroid-
respiratory distress and bone abnormality ectomy to an age of nine months, in whom no
such as osteopenia, subperiosteal bone fractures were observed and the hyper-
resorption, pathologic fracture and failure to calcaemia became masked by vitamin D
thrive almost in all cases[4,5]. NPHP is deficiency[10]. These patients are critically ill at
characterized by marked hypercalcemia, presentation and initial therapy with
hypophosphatemia, hyper-phosphaturia, hydration, furosemide, steroids, and intra-
hypercalciuria and elevated PTH level[3,4]. In venous pamidronate are not enough to control
differential diagnosis other causes of hypercalcemia completely[11,14].
hypercalcemia should be considered Despite the intensive medical therapy it
including: iatrogenic hypercalcemia (calcium was not easy to prepare the severely ill patient
salts), idiopathic infantile hypercalcemia, for parathyroidectomy. Three possible
Williams syndrome, vitamin D intoxication surgical procedures for these patients are:
and familial hypocalciuric hypercalcemia total parathyroidectomy, subtotal parathyro-
(FHH). FHH manifests with elevated serum idectomy or total parathyroidectomy with
levels of calcium and magnesium. Patients autotransplantation. Total parathyroidectomy
with this disease have normal phosphate and leads to hypoparathyroidism with a life-long
calcitriol levels with no hypercalciuria. need to calcium and vitamin D supple-
PTH level could be normal or mildly mentation. In total parathyroidectomy with
elevated[3-5]. Hypercalcemia lasts life-long; autotransplanttation all 4 parathyroid glands
patients have no other problems[5]. Most are removed and a small portion of a gland is
patients do not require any treatment. In implanted into intramuscular pockets[1-5,8].
280 Neonatal Hypercalcemia due to Primary Hyperparathyroidism; S Shiva, et al
Excellent results obtained in our patient 6. Gabbett MT, Jones K, Cowell CT, et al.
demonstrate that total parathyroidectomy Neonatal severe hyperparathyroidism:
with autotransplantation could successfully an important clue to the aetiology. J
regulate calcium homeostasis in severe Paediatr Child H. 2006;42(12):813-6.
primary hyperparathyroidism. However, we 7. Ross AJ, Cooper A, Attie MF, et al.
should not forget that hypercalcemia may Primary hyperparathyroidism in infancy.
recur in this patient in the future. J Pediatr Surg. 1986;21(6):493-9.
8. Cakmak O, Agis ER, Tezic T, et al.
Primary hyperparathyroidism in infancy:
A case report. J Pediatr Surg
1996;31(3):437-8.
Conclusion 9. Cole DEC, Janicic N, Salisbury SR, et al.
Although NPHP is a rare disease, it must be Neonatal severe hyperpara-thyroidism,
secondary hyperparathyro-idism, and
considered for differential diagnosis in
familial hypocalciuric hypercalcemia:
neonates with severe hypercalcemia. Early Multiple different phenotypes associated
diagnosis and total parathyroidectomy with with an inactivating Alu insertion
autotransplantation can be life-saving. mutation of the calcium-sensing receptor
gene. Am J Med Genet. 1998;71(2):202-
10.
10. Meeran K, Husain M, Puccini M, et al.
Neonatal primary hyperparathyroidism
References masked by vitamine D deficiency. Clin
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Surg. 1991;1(2):110-4. transplantation of cryopreserved para-
3. Rodd C, Goodyer P. Hypercalcemia of the thyroid tissue. Acta Pediatrica.
newborn: etiology, evaluation, and 1986;75(1):179-82.
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13(6):542-7. Khusaiby S. Spontaneous improvement
4. Janik JE, Bloch CA, Janik JS. Intrathyroid of severe neonatal hyperparathyroidism
parathyroid gland and neonatal primary after failed total parathyroidectomy.
hyperparathyroidism. J Pediatr Surg. Indian Pediatr. 2003;40(3):255-7.
2000;35(10):1517-9. 14. Darcan S, Coker M, Aydinok Y, et al.
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Iran J Pediatr

Case Report Sep 2008; Vol 18 ( o 3), Pp:277-280

Severe Neonatal Hypercalcemia due to Primary

1. Department of Pediatrics, Tabriz University of Medical Sciences, IR Iran

Received: 25/01/08; Revised: 22/05/08; Accepted: 06/06/08

Key Words: Primary hyperparathyroidism; Neonate; Parathyroidectomy; Autotransplantation

Introduction fatal unless a prompt diagnosis is made and

Fig 1- Skeletal survey of patient, demonstrating

contrast, NPHP can be life-threatening if left

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