index of suspicion
Case 1: Raccoon Eyes in an 8-Month-Old Infant
The reader is encouraged to write
possible diagnoses for each case before
turning to the discussion.
The reader is encouraged to write
possible diagnoses for each case
before turning to the discussion. We
invite readers to contribute case
presentations and discussions. Please
inquire first by contacting Dr Deepak
Kamat at DKamat@med.wayne.edu.
Author Disclosure
Drs Bavle, Balasa, Chan, El-Kadri, Ng,
and Torchinsky have disclosed no
financial relationships relevant to this
article. This commentary does not
contain discussion of unapproved/
investigative use of a commercial
product/device.
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Case 2: Jaundice in a Teenage Girl
Case 3: Extreme Muscle Weakness in a 10-Year-Old
Boy
Case 1 Presentation
An 8-month-old boy presents to the
emergency department with a right-
sided facial droop for 1 day and
blackish bruising around both his
eyes resembling raccoon eyes for
a week. His mother reports that the
child had fallen from a couch 2 weeks
earlier. The child has also been fussy,
with decreased feeding for 3 days. He
has no history of fever, and findings
from a review of his systems are oth-
erwise unremarkable. Medical history,
family history, and social history are
also unremarkable.
On examination, the child is fussy
but alert. Vital signs are normal: tem-
perature, 98.7°F (37.0°C); heart rate,
108 beats per minute; respiratory rate,
32 breaths per minute; and blood
pressure, 98/60 mm Hg. Anterior
fontanelle is soft and flat. There is
right-sided ptosis and drooping of
the right side of the mouth, especially
apparent when the child cries. There
are no other focal deficits, and the rest
of the neurologic examination find-
ings are normal. Ecchymoses are seen
extending, approximately a centime-
ter, circumferentially around both
eyes. The liver is firm and palpable 3
cm below the right costal margin.
The rest of the physical examination
findings are normal.
Initial laboratory evaluation reveals
the following: hemoglobin, 7.7 g/dL
(77 g/L); mean corpuscular volume,
80.7 fL; white blood cell count,
12,390/mL (12.39  109/L); and
platelet count, 298  103/mL (298
 109/L). Computed tomography
(CT) of the head without contrast re-
veals no evidence of intracranial bleed-
ing. Further investigations reveal an
explanation for the child’s constella-
tion of symptoms and anemia.
Case 2 Presentation
A 13-year-old girl presents to the
emergency department with a 2-week
history of fatigue, jaundice, and pruri-
tus. She describes being dizzy. She has
no history of fever, vomiting, diarrhea,
trauma, easy bruising, nosebleeds, ar-
thralgia, or headaches. Her urine is
dark yellow, but her stool color has
not changed. Her history includes
travel to Pakistan 3 months ago. She
has not menstruated for 3 months
and denies any sexual activity or drug
or alcohol use. There is no family his-
tory of known liver disease or autoim-
mune conditions.
On examination, her vital signs are
normal. She has scleral icterus but
otherwise looks well. Cardiac exami-
nation reveals a gallop rhythm and
loud grade 3/6 pansystolic murmur
at the left sternal border. Her abdo-
men is mildly distended, but there
is no hepatosplenomegaly. There are
no rashes, bruises, clubbing, or stig-
mata of chronic liver disease.
Laboratory findings reveal ele-
vated unconjugated bilirubin (2.6
mg/dL [44.5 mmol/L]; reference
range, 0.60–1.40 mg/dL [10.3–
24.0 mmol/L]) and conjugated bili-
rubin (0.53 mg/dL [9.1 mmol/L];
reference range, £0.20 mg/dL [3.4
mmol/L]) levels. The aspartate ami-
notransferase level is 62 U/L (refer-
ence range, £36 U/L), the alanine
aminotransferase level is 38 U/L
(reference range, £40 U/L), the
g-glutamyltransferase level is 58 U/L
(reference range, £45 U/L), the
Pediatrics in Review Vol.35 No.4 April 2014 169
index of suspicion
lactate dehydrogenase level is 1048
U/L (reference range, 380–640 U/L),
and the albumin level is 2.1 g/dL
(21 g/L) (reference range, 3.2–
5.6 g/dL [32–56 g/L]). Her partial
thromboplastin time is 39 seconds
(reference range, 24–36 seconds),
and her international normalized ra-
tio (INR) is 1.8 (reference range,
0.8–1.2). The alkaline phosphatase,
amylase, and ammonia levels are nor-
mal. The Coombs test and autoim-
mune hepatitis antibody test results
are negative. Her initial hemoglobin
level is 5.1 g/dL (51 g/L), and the
absolute reticulocyte count is 231.0
 103/mL (231.0  109/L) (refer-
ence range, 10–100  103/mL [10–
100  109/L]). Her white blood cell
count is 8200/mL (8.2  109/L)
with a normal differential, and her
platelet count is 127  103/mL
(127  109/L). Additional evalua-
tion reveals the diagnosis.
Case 3 Presentation
A 10-year-old boy is brought to the
emergency department because of ex-
treme muscle weakness; his parents
have to carry him because he cannot
walk. He used to be physically active
and frequently played soccer, but he
has preferred to stay in bed for the
past week. He also has decreased ap-
petite, stomachaches, increased thirst,
and constipation for a month, and he
has been experiencing bone pains at-
tributed to growing pains for 4 years.
Physical examination reveals a tired-
looking boy. His temperature is 98.0°F
(36.7°C), heart rate is 79 beats per
minute, blood pressure is 138/84
mm Hg, respiratory rate is 16 breaths
per minute, weight is 34 kg (50th per-
centile), height is 144 cm (50th to
75th percentile), and body mass index
is 16.3 (25th to 50th percentile). He
has symmetric muscle weakness. The
remaining findings on his physical ex-
amination are normal.
170 Pediatrics in Review Vol.35 No.4 April 2014
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Laboratory tests reveal a serum cal-
cium level significantly elevated at
18.7 mg/dL (4.67 mmol/L), a low
phosphorus level at 3.1 mg/dL
(1.00 mmol/L), an alkaline phospha-
tase level of 237 U/L, and a 25-
hydroxyvitamin D level of 23 ng/mL
(57 nmol/L). Renal function test
and urinalysis results are normal. Spot
urine for calcium to creatinine ratio is
1.2 mg/mg (reference range, <0.22
mg/mg), and 24-hour urine calcium
output is 12 mg/kg/d (reference
range, <4 mg/kg/d). Renal ultrasonog-
raphy reveals increased echogenicity
of both kidneys. Two additional stud-
ies establish the diagnosis.
Case 1 Discussion
The findings of raccoon eyes, nor-
mocytic anemia, and hepatomegaly
prompted abdominal ultrasonogra-
phy, followed by CT of the abdomen
and pelvis with contrast, which re-
vealed a left suprarenal mass and
masses in the liver suggestive of me-
tastasis. Excisional biopsy of the mass
confirmed the diagnosis of neuroblas-
toma with favorable histologic fea-
tures, and there was no amplification
of the N-myc gene. Urine catechol-
amine studies revealed elevation of
the vanillylmandelic acid to creatinine
ratio, homovanillic acid to creatinine
ratio, and dopamine to creatinine ra-
tio. Bilateral bone marrow biopsies re-
vealed metastatic neuroblastoma. A
meta-iodobenzylguanidine scan re-
vealed marked uptake in the temporal
bones bilaterally, which explained the
right facial nerve paralysis. The scan
also showed increased uptake in the
liver, left suprarenal mass, skull base,
ribs, vertebral column, and the long
bones of the upper and lower extremi-
ties. These findings confirmed the di-
agnosis of a stage IV neuroblastoma.
Facial nerve paralysis is most com-
monly idiopathic, in which case it is
called Bell palsy. Known causes of
nerve VII paralysis include the follow-
ing: (1) infections such as herpes zos-
ter reactivation, herpes simplex virus,
Lyme disease, and human immuno-
deficiency virus; (2) central nervous
system disorders such as stroke and
Guillain-Barre syndrome; (3) conditions
such as mastoiditis and cholesteatoma;
(4) neoplasms such as parotid gland
tumors, central nervous system leukemia,
and tumors with central nervous me-
tastasis; (5) sarcoidosis (Heerfordt syn-
drome); and (6) head injury.
Raccoon eyes or bilateral ecchymo-
ses are a classic presentation of neuro-
blastoma, seen because of periorbital
hemorrhage caused by orbital metasta-
sis. However, raccoon eyes are most
commonly caused by basal skull frac-
tures or basilar head bleeds and should
raise a red flag for child abuse.
Normocytic anemia in infancy can
be due to transient erythroblastope-
nia of infancy, bacterial or viral infec-
tions, hemorrhage, red blood cell
membrane or enzymatic defects,
bone marrow disorders, and hemoly-
sis due to hemoglobinopathies. Iso-
lated normocytic anemia should
also raise suspicion for a malignant
tumor as in our patient, who likely
had hemorrhage in his tumor.
The Condition
Neuroblastoma is the most common
extracranial solid tumor in children
and the most common tumor of in-
fancy. The peak incidence of this can-
cer is at 2 years of age, with 75% of
patients being younger than 4 years
at the time of diagnosis.
Neuroblastoma generally presents
as a tumor in the sympathetic neural
pathway, with 65% of the tumors oc-
curring in the adrenal glands. Common
presenting symptoms are abdominal
pain and constipation when the tumor
is present in the abdomen, respiratory
symptoms when the tumor is present
in the chest, and neurologic symptoms

when the tumor is present in the head
and neck area or close to the spinal
cord. The most common presentation
is an asymptomatic abdominal mass,
with metastases in the liver causing he-
patomegaly in infants or the primary tu-
mor presenting as a flank mass. Attacks
of flushing, headaches, palpitations,
and hypertension caused by excessive
catecholamine secretion can also be
seen. Neuroblastoma can also present
with opsoclonus (ie, rapid involuntary
movement of the eyes in all directions),
ataxia, and myoclonus (ie, frequent, ir-
regular jerking of the limbs and trunk).
All children with opsoclonus-myoclonus
should have a complete workup for
neuroblastoma. High-volume secre-
tory diarrhea with associated hypoka-
lemia is a paraneoplastic syndrome
associated with excessive vasoactive
intestinal peptide secretion.
Diagnosis
The International Neuroblastoma Stag-
ing System Conference criteria for diag-
nosis of neuroblastoma are as follows:
(1) unequivocal pathologic diagnosis
made from tumor tissue and/or in-
creased urine or serum catecholamines
or metabolites (dopamine, homovanil-
lic acid, and/or vanillylmandelic acid)
and (2) bone marrow aspirate or tre-
phine biopsy specimen showing un-
equivocal tumor cells and increased
urine or serum catecholamines or
metabolites.
The primary tumor site should be
identified and evaluated with CT
and/or magnetic resonance imaging.
The following areas should be evaluated
for possible metastasis: (1) bone mar-
row (bone marrow aspirates and biopsy
specimens should be obtained from
multiple sites), (2) bone, (3) lymph
nodes, (4) abdomen, and (5) chest.
Staging
The International Neuroblastoma
Staging System Conference staging
system classifies neuroblastoma as
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stage 1, 2A, 2B, 3, 4, and 4S based
on extent of metastasis, degree of
gross excision, and involvement of
lymph nodes.
Treatment and Prognosis
The mode of treatment is based on
the age of the patient, stage of the
cancer, and surgical resectability of
the tumor. Patients are classified as be-
ing at low, intermediate, or high risk
based on staging, age, and the pres-
ence of poor risk factors, such as Shi-
mada histologic findings that are
unfavorable, positive N-myc amplifica-
tion, and DNA ploidy. Low-risk pa-
tients undergo surgery and/or
chemotherapy. However, high-risk
patients need more aggressive ther-
apy, which can include chemotherapy,
surgery, radiation therapy, immuno-
therapy, and stem cell transplantation.
Therapy is also modified based on the
extent of response of tumor to induc-
tion chemotherapy.
Event-free survival is 85% to 90%
for patients with low-risk neuroblas-
toma and 60% to 75% for those with
intermediate risk. The relapse rate ap-
proaches 50% for high-risk patients.
Lessons for the Clinician
• Raccoon eyes can be seen in pa-
tients with neuroblastoma and
basilar head bleeding (possibly be-
cause of child abuse).
• One may consider malignant tu-
mors in the presence of normo-
cytic anemia.
(Abhishek Bavle, MD, Vinod V. Balasa,
MD, Department of Pediatrics, Uni-
versity of Louisville, Louisville, KY)
Case 2 Discussion
Our patient received blood transfu-
sions because of fatigue, cardiac flow
murmur, and a low hemoglobin level.
Her coagulopathy was treated with
index of suspicion
intravenous vitamin K. Abdominal ul-
trasonography revealed a slightly en-
larged spleen at 12.6 cm and ascites.
The liver was diffusely heterogeneous
and multinodular but showed no evi-
dence of cholelithiasis or abdominal
masses.
Differential Diagnosis
The differential diagnosis of acute
liver disease with coagulopathy in
a teenager includes infections, includ-
ing the viral hepatitides, especially
with chronic hepatitis B and C infec-
tions; inflammatory and autoimmune
disorders, such as autoimmune hepa-
titis and primary sclerosing cholangi-
tis; primary biliary malformations,
including Alagille syndrome, congen-
ital hepatic fibrosis, and Caroli disease;
and vascular lesions, such as congeni-
tal heart failure in the presence of
a flow murmur, congestive pericardi-
tis, and Budd-Chiari malformations.
A number of toxic causes are pos-
sible. Drugs, such as acetaminophen,
oral contraceptive pills, estrogen, an-
abolic steroids, penicillin, erythromy-
cin, and chlorpromazine, can cause
cholestatic liver disease. Alcohol can
cause severe acute hepatitis through
direct damage to mitochondria and
subsequent apoptosis. This empha-
sizes the importance of a drug and al-
cohol toxicology screen for teenagers
with evidence of cirrhosis.
A number of metabolic disorders
may cause cholestatic jaundice, includ-
ing carbohydrate metabolism disor-
ders (eg, fructosemia), a1-antitrypsin
deficiency, and disorders of metal me-
tabolism (eg, Wilson disease). Finally,
cirrhosis can be idiopathic.
Because of the elevated INR, hyper-
bilirubinemia, and evidence of advanced
liver disease on ultrasonography, the
gastrointestinal service was consulted
and Wilson disease was suspected. Im-
mediate evaluation by the ophthalmol-
ogist in the emergency department
demonstrated the presence of Kayser-
Pediatrics in Review Vol.35 No.4 April 2014 171
index of suspicion
Fleisher rings. Subsequent results of
an extremely low serum ceruloplasmin
level (<4 mg/dL [<40 mg/L]) and
extremely elevated 24-hour urinary
copper levels were confirmatory for
Wilson disease. The risks and benefits
of a liver biopsy with histopathologic
analysis were discussed extensively
and deferred in this patient because
of the low serum ceruloplasmin level
(<20 mg/dL [<200 mg/L]).
The Condition
Wilson disease is an autosomal reces-
sive disorder of copper metabolism
caused by a malfunction of the
ATP7B protein. Hepatic presenta-
tions of Wilson disease include acute
hepatitis, fulminant liver failure,
chronic hepatitis, portal hyperten-
sion, asymptomatic elevation of se-
rum aminotransferase levels, and
gallstones. The disease affects 1 in
30,000 individuals. Copper silently
accumulates in the liver during child-
hood. Clinical symptoms of liver dis-
ease virtually never occur before 3
years of age. Most people present in
their teens or 20s after copper accu-
mulates in the liver. For a list of clin-
ical manifestations, see the Table.
Fulminant hepatic failure is a rare
but potentially devastating presenta-
tion of Wilson disease. Fulminant he-
patic failure usually occurs in an
adolescent teenager as an acute ic-
teric hepatitis that evolves in a few
days to several weeks and may appear
identical to that encountered in acute
fulminant viral hepatitis or after in-
gestion of a hepatotoxin. Wilson dis-
ease may also present as acute liver
failure with an associated Coombs-
negative hemolytic anemia.
The diagnosis of Wilson disease is
established by a combination of clini-
cal and biochemical findings: the pres-
ence of Kayser-Fleisher rings, a decrease
in serum ceruloplasmin level, elevated
24-hour urinary copper levels, and el-
evated hepatic tissue copper content.
172 Pediatrics in Review Vol.35 No.4 April 2014
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However, the presence of Kayser- transplantation may be the only option
Fleisher rings and a reduced serum for cure of the Wilson disease.
ceruloplasmin level are sufficient to
establish the diagnosis.
Clinical
Table.
Management Features of Wilson
Diseasea
Without treatment, Wilson disease is
uniformly fatal. The mainstay of med-
ical management is reducing or chelat-
Hepatic
ing the stored copper and preventing
• Asymptomatic hepatomegaly
copper from reaccumulating. This is • Isolated splenomegaly
accomplished through one of several • Persistently elevated serum
copper-chelating agents, a low-copper aminotransferase activity (AST,
diet, and possibly antioxidants as ALT)
adjunctive therapy. Copper-chelating • Fatty liver
• Acute hepatitis
medications available include D- • Resembling autoimmune
penicillamine and triethylenetetramine hepatitis
dihydrochloride (trientine). Zinc is • Cirrhosis: compensated or
used because it blocks intestinal ab- decompensated
sorption of dietary copper. Trientine • Acute liver failure
and zinc must be given at least 1 hour Neurologic
• Movement disorders (tremor,
apart from each other and meals. The involuntary movements)
timing and strictness of the regimen • Drooling, dysarthria
reduce patient adherence. Antioxi- • Rigid dystonia
dants, such as vitamin E, have also • Pseudobulbar palsy
been used as adjunctive therapy. • Dysautonomia
• Migraine headaches
Our patient was prescribed copper • Insomnia
chelation therapy with trientine, • Seizures
500 mg twice daily, and zinc, 25 mg Psychiatric
twice daily. She tolerated the treatment • Depression
well. Baseline neuropsychological test- • Neurotic behaviors
ing revealed normal cognition and be- • Personality changes
• Psychosis
havior. Intravenous vitamin K was given
Other systems
to improve the coagulopathy. The as- • Ocular: Kayser-Fleischer rings,
partate aminotransferase and alanine sunflower cataracts
aminotransferase levels remained slightly • Cutaneous: lunulae ceruleae
elevated at 60 to 90 U/L, the uncon- • Renal: premature osteoporosis
jugated bilirubin decreased to 0.88 and arthritis
• Cardiomyopathy, dysrhythmias
mg/dL (15.0 mmol/L), and the • Pancreatitis
conjugated bilirubin decreased to • Hypoparathyroidism
0 mg/dL (0 mmol/L) while the pa- • Menstrual irregularities,
tient was hospitalized. infertility, repeated miscarriages
Liver transplantation is established • Coombs test–negative hemolytic
anemia
as a life-saving therapy for patients with
Wilson disease with acute fulminant Abbreviations: ALT=alanine aminotransferase;
AST=aspartate aminotransferase.
liver failure, those with fulminant he- a
Data are from Roberts EA, Schilsky ML;
patic failure after discontinuing copper American Association for Study of Liver
Diseases (AASLD). Diagnosis and treatment
chelation therapy, and those with de- of Wilson disease: an update. Hepatology.
compensated cirrhosis unresponsive to 2008;47(6):2089–2111. Copyright (C)
2008 American Association for the Study of
medical therapy. For patients in whom Liver Diseases: John Wiley and Sons.
pharmacologic treatment fails, liver

Lessons for the Clinician
• It is important to recognize the
potential diagnosis of fulminant
liver failure (also known as pediat-
ric acute liver failure) in children
without known preexisting liver dis-
ease presenting with coagulopathy
and signs or symptoms of liver
disease (jaundice being the most
common). Immediate administra-
tion of intravenous vitamin K with
repeat INR levels is critical.
• Wilson disease is a great masquer-
ader. It can manifest with hepatic,
neurologic, psychiatric, and oph-
thalmologic manifestations.
• Clinical manifestations of chronic
liver disorder in a teenager should
suggest the diagnosis of Wilson
disease.
• Prompt ophthalmology referral can
confirm the presence of Kayser-
Fleisher rings and aid in the diag-
nosis of Wilson disease.
(Kevin Chan, MD, Department of
Pediatrics, Memorial University,
St. John’s, Newfoundland, Canada,
Abdul El-Kadri, MD, Vicky Ng, MD,
Department of Pediatrics, University of
Toronto, Toronto, Ontario, Canada)
Case 3 Discussion
The immune-radiometric assay re-
vealed a serum level of intact para-
thyroid hormone (PTH) to be
significantly elevated at 809 pg/mL
(809 ng/L). Ultrasonography com-
bined with Doppler sonography of
the entire neck revealed a 2.2-cm nod-
ule located 1.5 cm inferior to the right
thyroid lobe. Diagnosis of primary hy-
perparathyroidism due to parathyroid
adenoma was established.
Increased echogenicity of the kid-
neys on ultrasonography signaled
nephrocalcinosis. The patient’s ra-
diographs obtained a year ago when
he fractured his forearm revealed
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osteopenia characterized by decreased
bone radiodensity that could be seen
even on plain radiographs, indicative
of at least 30% bone loss.
One of the important advances in
understanding metabolic bone dis-
ease was identification of biochemical
parameters that reflect rates of bone
formation and resorption. For exam-
ple, urinary calcium excretion and
collagen cross-links are markers of
bone resorption, whereas serum al-
kaline phosphatase and osteocalcin
are markers of bone formation.
Our patient had high urine calcium
and normal serum alkaline phospha-
tase levels, which indicated that the
dominant effect of continuously high
PTH levels was to stimulate bone re-
sorption rather than bone formation.
Administration of pamidronate,
1 mg/kg intravenously for 6 hours,
enabled us to decrease the serum cal-
cium level to 10.8 mg/dL (2.70
mmol/L) within 3 days in prepara-
tion for surgery. Subsequently, an ab-
normal parathyroid gland was
removed. The serum PTH level de-
creased from 405 to 20 pg/ml
(405–20 ng/L) within 10 minutes,
and the calcium level normalized
within 24 hours after resection. The
patient required large doses of cal-
cium and phosphorus because of
hungry bone syndrome and recov-
ered completely.
The Condition
Primary hyperparathyroidism is one
of the rarest endocrine disorders in
children, with an incidence of 2 to
5 per 100,000 population. It is most
often sporadic due to a single ade-
noma; however, it may also be caused
by multiple parathyroid adenomas or
hyperplasia, such as in multiple endo-
crine neoplasia (MEN) syndromes.
MEN I is characterized by tumors
of the parathyroid glands, pancreatic
islet cells, and pituitary, caused by in-
activating mutation of the tumor
index of suspicion
suppressor gene. MEN II is character-
ized by thyroid medullary carcinoma,
parathyroid adenomas or hyperpla-
sia, and pheochromocytoma, caused
by activating mutation of the RET
proto-oncogene.
The symptoms of primary hyper-
parathyroidism may be divided into
those due to hypercalcemia and
those due to skeletal changes. Hy-
percalcemia leads to fatigue, muscle
weakness, headache, nausea, ab-
dominal pain, anorexia, vomiting,
constipation, renal stones, increased
thirst, and depression. Skeletal changes
manifest with generalized demineral-
ization, subperiosteal erosions of cor-
tical bone most evident in the phalanges,
irregular cystlike areas, slipped capital
femoral epiphyses, and pathologic frac-
tures, which cause bone pain. The
nonspecific nature of symptoms and
infrequency of screening tests in pedi-
atrics often result in a delay of 2 to 4
years between onset of symptoms
and the time of diagnosis.
Muscle weakness in hypercalcemia
is due to depressed electrical excit-
ability of the nervous system because
an increase in concentration of posi-
tively charged calcium ions reduces
neuronal membrane permeability to
sodium ions and impedes initiation
of membrane action potentials. Pe-
ripheral nerve fibers become so de-
pressed that they conduct fewer
impulses to the muscles.
Diagnosis
The diagnosis of primary hyperpara-
thyroidism is based on demonstration
of inappropriately high intact PTH
levels in the presence of high serum
calcium levels. Genetic testing is re-
quired to rule out MEN syndromes.
Primary hyperparathyroidism should
be differentiated from familial hypo-
calciuric hypercalcemia due to inacti-
vating mutation of the calcium-sensing
receptor gene. PTH-independent hyper-
calcemia is characterized by suppressed
Pediatrics in Review Vol.35 No.4 April 2014 173
index of suspicion
PTH levels, which should prompt
evaluation for occult malignant tumors
and other causes, including vitamin D
intoxication.
After the diagnosis of primary hy-
perparathyroidism is made, the next
step is to localize the abnormal para-
thyroid, which may be a challenge
because up to 1 in 5 parathyroid
glands is ectopic. Combining ultra-
sonography with Doppler sonography
and technetium Tc 99m sestamibi
scanning improves the accuracy of
preoperative localization. Magnetic
resonance imaging or single-photon
emission CT or CT of the neck and
upper mediastinum and selective
venous sampling for PTH may be
used to localize elusive parathyroid
glands.
Treatment and Prognosis
The treatment of primary hyperpara-
thyroidism in children is surgical
removal of hyperfunctioning parathy-
roid tissue. Patients who have clinical
symptoms or severe hypercalcemia, de-
fined as a serum calcium level greater
than 14 mg/dl (3.50 mmol/L), need
urgent therapy. Isotonic saline is given
intravenously to correct dehydration
Answer Key for April 2014 Issue:
Chlamydia: 1. A; 2. D; 3. B; 4. E; 5. A.
Car Safety: 1. A; 2. C; 3. C; 4. B; 5. B.
Endocarditis: 1. D; 2. D; 3. E; 4. D; 5. C.
174 Pediatrics in Review Vol.35 No.4 April 2014
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due to osmotic diuresis associated with Lessons for the Clinician
hypercalciuria.
• Primary hyperparathyroidism is an
Hypercalcemia in hyperparathy-
unusual disorder in children in
roidism can be rapidly alleviated by
which delay in diagnosis results
intravenous bisphosphonates, which
in end-organ damage, such as
decrease bone resorption by inhibit-
nephrolithiasis, nephrocalcinosis,
ing osteoclast activity and shortening
and skeletal changes.
their life span. Potential adverse ef-
• Muscle weakness may be a sign of
fects include local pain at the infusion
hypercalcemia.
site, low-grade fever, transient lym-
• A history of bone fractures or evi-
phopenia, and hypocalcemia after
dence of osteopenia on radiogra-
the infusion. A single dose of pamid-
phy should alert the clinician to
ronate, 0.5 to 1 mg/kg administered
the possibility of a disorder of min-
intravenously for 4 to 6 hours, ap-
eral metabolism.
pears to be safe, well tolerated, and
• Serum calcium measurement is a
effective. Serum calcium levels usu-
useful screening test that should
ally decline to nadir within 3 days af-
be included in the evaluation of chil-
ter the infusion. The use of diuretics
dren with nonspecific symptoms.
should be avoided because they can
• Early diagnosis of primary hyper-
worsen already existing extracellular
parathyroidism is crucial to pre-
volume depletion.
vent severe disease and shorten
After successful surgery, calcium
metabolic recovery.
and phosphorus supplements are
given to replenish mineral stores de-
(Michael Yuri Torchinsky, MD, Uni-
pleted by PTH action, and vitamin D
versity of Mississippi School of Medi-
is added for children with vitamin D
cine, Jackson, MS)
deficiency. Most patients recover com-
pletely. Postoperative complications, To view Suggested Reading lists
such as hypoparathyroidism and vocal for these cases, visit http://pedsinreview.
cord paralysis, are rare in the hands of aappublications.org and click on the
the skilled endocrine surgeon. “Index of Suspicion” link.
 Index of Suspicion
Abhishek Bavle, Kevin Chan, Michael Yuri Torchinsky, Vinod V. Balasa, Abdul
El-Kadri and Vicky Ng
Pediatrics in Review 2014;35;169
DOI: 10.1542/pir.35-4-169

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 Index of Suspicion
Abhishek Bavle, Kevin Chan, Michael Yuri Torchinsky, Vinod V. Balasa, Abdul
El-Kadri and Vicky Ng
Pediatrics in Review 2014;35;169
DOI: 10.1542/pir.35-4-169

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/content/35/4/169

Data Supplement at:

http://pedsinreview.aappublications.org/content/suppl/2014/03/20/35.4.169.DCSupplementary_Data.ht
ml

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