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* Correspondence author;
Address: Children Hospital, Sheshgelan Ave, Tabriz,IR Iran
E-mail: [email protected]
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
Neonatal primary hyperparathyroidism
(NPHP) is a rare disease that presents in the
first 6 months of life[1]. It is almost invariably
fatal unless a prompt diagnosis is made and
urgent surgical intervention instituted[2]. It is
associated with hypotonia, respiratory
distress, irritability, lethargy, failure to thrive,
constipation and severe hypercalcemia with
Case Report Iran J Pediatr
Sep 2008; Vol 18 ( �o 3), Pp:277-280
278 Neonatal Hypercalcemia due to Primary Hyperparathyroidism; S Shiva, et al
elevated parathyroid hormone (PTH) levels[1].
Radiographs show severe bone
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.
Case Presentation
A 10-day-old 2.9 kg male newborn was
hospitalized for anorexia, poor feeding,
cyanosis, hypotonia, lethargy and severe
dehydration. He was a full term baby at birth
weighing 3400 grams and his parents were
related (cousins). Despite rehydration, he had
hypercalcemia with Ca concentration of 18.2
mg/dl (normal, 8.6 to 10.3). Other laboratory
findings were serum PTH level of 996 pg/ml
(Normal, 7 to 82), phosphorus level of 1.6
mg/dl (Normal, 4 to 6.5) and alkaline
phosphatase level of 1322 IU/L (Normal, 180
to 1200). Urine Ca excretion was 12 mg/kg/d.
Evaluation of mother for serum levels of Ca, P
and PTH showed normal values. With
vigorous medical management using saline
diuresis, furosemide, hydrocortisone and
intravenous pamidronate 1mg/kg/d for 3
days, serum Ca level remained between 13-15
mg/dl. Full skeletal survey revealed severe
and generalized osteopenia. Bone density was
diffusely decreased and multiple regions of
pathologic fractures in proximal and distal
parts of femur, humerus and ribs along with
lung calcification were seen (Fig 1).
Fig 1- Skeletal survey of patient, demonstrating
multiple fractures and generalized osteopenia
Ultrasound revealed medullary nephro-
calcinosis; echocardiography was normal.
99M-TC-sestaMIBI scan showed homogeneous
uptake of the radiotracer in parathyroid
glands with no evidence of parathyroid
adenoma. Combination of clinical, laboratory
and radiological findings were consistent with
the diagnosis of NPHP. Since patient did not
respond to the medical therapy and his
symptoms persisted, surgical approach was
considered. We performed total parathyroid-
ectomy with autotransplantation. After
removing all 4 parathyroid glands, a portion of
a gland was autotransplanted in
sternocleidomastoid muscle. Because of
hypocalcemia (serum Ca 7.5 mg/dl) we
started calcium supplementation and vitamin
D therapy during the second day after surgery.
Two months after surgery patient was
eucalcemic and had no need for vitamin D
supplementation. Histological examination of
parathyroid glands revealed diffuse chief cell
hyperplasia (Fig 2).
279 Iran J Pediatr, Vol 18 (�o 3); Sep 2008
Fig 2- Microphotograph of parathyroid tissue
shows diffused chief cell hyperplasia. Note the
uniform appearance of parathyroid chief cells
(hematoxylin & eosin stained)
Discussion
Neonatal primary hyperparathyroidism
(NPHP) is a rare disease, which is often fatal.
This condition results from chief cell
hyperplasia and excessive secretion of PTH[3-
6]. Usually symptoms manifest in the first days
after birth[4]. Symptoms include poor feeding,
irritability, constipation, polyuria, hypotonia,
respiratory distress and bone abnormality
such as osteopenia, subperiosteal bone
resorption, pathologic fracture and failure to
thrive almost in all cases[4,5]. NPHP is
characterized by marked hypercalcemia,
hypophosphatemia, hyper-phosphaturia,
hypercalciuria and elevated PTH level[3,4]. In
differential diagnosis other causes of
hypercalcemia should be considered
including: iatrogenic hypercalcemia (calcium
salts), idiopathic infantile hypercalcemia,
Williams syndrome, vitamin D intoxication
and familial hypocalciuric hypercalcemia
(FHH). FHH manifests with elevated serum
levels of calcium and magnesium. Patients
with this disease have normal phosphate and
calcitriol levels with no hypercalciuria.
PTH level could be normal or mildly
elevated[3-5]. Hypercalcemia lasts life-long;
patients have no other problems[5]. Most
patients do not require any treatment. In
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
alterations[4].
As in our case many other reports show
that the treatment of choice is total parathyro-
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
has a mortality rate of 70% to 87% and severe
long term complications in the survivors[4].
Ross et al reported that seven of eight patients
treated medically for primary hyperpara-
thyroidism died in infancy, with a mortality
rate of 87.5% and the mortality rate among
patients treated surgically was reduced to
24%[7]. Meeran et al reported a case with
NPHP who survived without parathyroid-
ectomy to an age of nine months, in whom no
fractures were observed and the hyper-
calcaemia became masked by vitamin D
deficiency[10]. These patients are critically ill at
presentation and initial therapy with
hydration, furosemide, steroids, and intra-
venous pamidronate are not enough to control
hypercalcemia completely[11,14].
Despite the intensive medical therapy it
was not easy to prepare the severely ill patient
for parathyroidectomy. Three possible
surgical procedures for these patients are:
total parathyroidectomy, subtotal parathyro-
idectomy or total parathyroidectomy with
autotransplantation. Total parathyroidectomy
leads to hypoparathyroidism with a life-long
need to calcium and vitamin D supple-
mentation. In total parathyroidectomy with
autotransplanttation all 4 parathyroid glands
are removed and a small portion of a gland is
implanted into intramuscular pockets[1-5,8].
280 Neonatal Hypercalcemia due to Primary Hyperparathyroidism; S Shiva, et al
Excellent results obtained in our patient
demonstrate that total parathyroidectomy
with autotransplantation could successfully
regulate calcium homeostasis in severe
primary hyperparathyroidism. However, we
should not forget that hypercalcemia may
recur in this patient in the future.
Conclusion
Although 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.
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