Case report

1. NEONATAL SEVERE HYPERPARATHYROIDISM :A CASE REPORT.
Mahmood Shaukat, Hafiz Mahmood Ahmad, Omar
Introduction:
Neonatal severe hyperparathyroidism is a rare genetic disorder which presents within first 6
months of life usually with symptoms of lethargy, hypotonia, reluctance to feed, polyuria,
gastrointestinal disturbances, osteopenia , poor feeding and respiratory distress1
. We
present case report of a male child who presented with neonatal hyperparathyroidism and
discuss our approach to diagnosis and treatment. Informed written consent was taken from
patients’ father for publication of case report.
Case Presentation:
A male child born of consanguineous marriage presented to paediatrician at age of 26 days
of life with complaint of lethargy, hypotonia, dehydration, constipation and reluctance to
feed. The child was born via LSCS due to placenta previa at 35th
week of gestation. The child
is third born of family. The first born was a male who died in first 6 months of life due to
similar complaints. The second born is a female who is healthy and alive.
At physical examination, child was lethargic and dehydrated. Chest was clear bilaterally.
Abdomen was soft and non tender.
On investigation, skeletal survey showed reduced bone density in all visualized long bones
and spine. Metaphyseal fractures were seen in the lower end of both femur and upper ends
of tibia. There was crowding of upper ribs 1-5th
.
Vitamin D level was 20.9ng/ml. Serum calcium level was initially 22.6 mg/dl which reduced
with medical treatment 9.2 mg/dl and was raised again to 17.37 mg/dl pre operatively.

2. His serum phosphate level was 2 mg/dl (N:3-6.9 mg/dl). Serum magnesium level was 1.7
mg/dl (N:1.7-2.7 mg/dl). Urinary Calcium level was not measured. Serum Parathyroid
hormone level was 1468.5 pg/ml which reduce to 444 pg/ml pre operatively due to medical
treatment. Patient was managed medically on inj pamidronate, tab mimcipal, intravenous
fluids and lasix.

4. Ultrasound neck couldn’t localize parathyroid glands and didn’t show any lesion. Seastmibi
scan didn’t show any radiographic evidence of parathyroid uptake.
Patient was referred to us on 60th
day of life when his total parathyroidectomy was done
with implantation of half of left lower parathyroid in left sernocleidomastoid. We only used
visual magnification. No intra operative radiotracer uptake or frozen section was used due

5. to non availability and economic limitations.
Post operative serum parathyroid level was obtained which reduced to 3.5 pg/ml i.e below
normal range.
In order to avoid post operative hypocalcemia, 2kg child was loaded with 4mg of 10%
calcium gluconate and was maintained on 4mg iv 8 hourly which was reduced to 2mg iv 8
hourly on 1st POD and 1mg iv 8 hourly on 2nd post operative day. Child was given full
maintenance fluid in this duration with oral feed and injection furosemide 1mg/kg bd . Urine
output was strictly monitored 1 hourly and was maintained at 2cc/kg/hour. Calcium level
decreased to 13.64 mg/dl on 2nd
post operative day. Child was discharged on serum calcium
P 1cc PO TDS and alpha calcidiol drops 0.2 mcg/day. On 7th
post operative day,

6. serumcalcium was 9.1 mg/dl which is in normal range.
Biopsy confirmed that all four parathyroid glands have been removed

7. Discussion:
Neonatal severe hyperparathyroidism (NSHPT) is a type of familial hypercalcemic
hypocalciuria (FHH) which is caused by autosomal recessive non activitating mutation in
Calcium sensing receptor (CASR) located majorly in chief cells of parathyroid, bones and
epithelial linings of renal tubules1
. Almost 200 types of mutations of CASR gene have been
described which include both activating and non activating mutations. Their penetration in
autosomal dominant or autosomal receptor pattern dictates whether the individual will
have FHH or NSHPT2
. Genetic mutations for NSHPT are mostly located on 3p13.3 3
.
Patients with NSHPT usually present within first 6 months of life and mostly with in first few
weeks4
. Most of these children present with signs and symptoms of hypercalcemia and
hyperparathyroidism which include lethargy, reluctance to feed, hypovolemia, polyuria,
hypotonia, gastrointestinal motility disorders, hypotonia and respiratory difficulties and if
proper diagnosis is not made , the disease can be fatal in 50% cases4
.
NHSHP is characterized by markedly elevated serum parathyroid hormone levels ,
hypercalcemia, hypophosphatemia, hypocalciuria.While considering diagnosis of
hypercalcemia in infant, it is also important to rule out other causes such as iatrogenic
hypercalcemia due to calcium salts, vitamin D intoxication, William syndrome, FHH and
idiopathic infantile hypercalcemia. All these scenarios can lead to almost similar
presentations but can be differentiated further on detailed work up. 5

8. Children with William Syndrome have characteristic “elfin facies”, defect in elastin gene and
vascular anomalies6
. 25 hydroxy vitamin D levels are elevated in neonatal hypercalcemia
due to vitamin D intoxication 5,
. FHH patients have hypercalcemia with normal or mildly
raised PTH levels2
.
NSHPT can be treated medically or surgically. Medical treatment includes excessive
intravenous fluidsand various drugs such as loop diuretics such as
furosemide,bisphosphonate such as apamidronate such as pamidronate, calcitonin and
calcimemetic such as cinacalcet1,7
.
However in refractory cases, surgery remains the ultimate treatment. In order to localise
parathyroid glands exactly, various investigations such as ultrasound neck , MRI and
sestamibi scan can be used. Seastmibi scan is most sensitive (88%) and most specific (97%).8
However, some studies indicate failure of all investigations including seastmibi scan to
exactly localise ectopic glands8,9
such as in our scan. In order to avoid devastating effects of
hypercalcemia, parathyroidectomy remains the ultimate treatment which can be subtotal 1
,
total parathyroidectomy with autotransplantation or total parathyroidectomy8
. Total
parathyroidectomy must be confirmed with frozen section and intra operative parathyroid
hormone levels. If symptoms persist despite surgical intervention, missed parathyroid gland
must be looked for at previous surgical site or ectopic locations8
.
Conclusion:
NSHPT is a rare genetic disorder which usually presents in first 6 months of life and if not
addressed properly, can be life threatening. Patient should be immediately managed with
medical management on presentation and if patient doesn’t improve or remain refractory
to treatment, surgery must be performed which remains the best treatment for the patients
of this disease till to date.
References:
1. Ahmad N, Bahasan M, Al-Ghamdi BA, Al-Enizi HF, Al-Zahrani AS. Neonatal severe
hyperparathyroidism secondary to a novel homozygous CASR gene mutation. Clinical
Cases in Mineral and Bone Metabolism. 2017 Sep;14(3):354.

9. 2. Lee JY, Shoback DM. Familial hypocalciuric hypercalcemia and related disorders. Best
practice & research Clinical endocrinology & metabolism. 2018 Oct 1;32(5):609-19.
3. Gannon AW, Monk HM, Levine MA. Cinacalcet monotherapy in neonatal severe
hyperparathyroidism: a case study and review. The Journal of Clinical Endocrinology &
Metabolism. 2014 Jan 1;99(1):7-11.
4. Egbuna OI, Brown EM. Hypercalcaemic and hypocalcaemic conditions due to calcium-
sensing receptor mutations. Best practice & research Clinical rheumatology. 2008 Mar
1;22(1):129-48.
5. Rodd C, Goodyer P. Hypercalcemia of the newborn: etiology, evaluation, and
management. Pediatric Nephrology. 1999 Jul 1;13(6):542-7.
6. Nagre SW, Bhosle KN, Ravikumar V. Supravalvar Aortic Stenosis in William
Syndrome-Case Report and Review of Literature. EC Cardiology. 2017;4:04-9.
7. Gannon AW, Monk HM, Levine MA. Cinacalcet monotherapy in neonatal severe
hyperparathyroidism: a case study and review. The Journal of Clinical
Endocrinology & Metabolism. 2014 Jan 1;99(1):7-11.
8. Abdullayev T, Korkmaz M, Kul M, Koray N. A rare cause of neonatal
hypercalcemia: Neonatal severe primary hyperparathyroidism: A case report and
review of the literature. International Journal of Surgery Case Reports. 2020 Jan
1;66:365-9.
9. Al-Shanafey S, Al-Hosaini R, Al-Ashwal A, Al-Rabeeah A. Surgical management of
severe neonatal hyperparathyroidism: one center's experience. Journal of pediatric
surgery. 2010 Apr 1;45(4):714-7.