index of suspicion

Case 1 Presentation

The reader is encouraged to write
possible diagnoses for each case
before turning to the discussion.
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case presentations and discussions.
Please inquire first by contacting
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A 4-year-old boy has had 6 days of
intermittent nausea and vomiting
without diarrhea or fever. Two days
into the illness, he was given
promethazine suppositories for presumed viral gastroenteritis; overnight the vomiting subsided. He
now experiences an unsteady gait
and needs help to stand still for urination. He says that he sees “two
daddies.” There has been no weight
loss, headache, mental status
changes, upper respiratory tract
symptoms, skin lesions, or trauma.
On physical examination, his
weight, height, and head circumference are appropriate for age. His vital
signs are normal, and he appears
comfortable, talkative, and playful,
although slightly pale. His abdomen
is soft and nontender with normoactive bowel sounds. He has a wellhealed scar resulting from pyloromyotomy in the first postnatal
month. Despite the acute history of
ataxia and diplopia, a thorough
neurologic evaluation reveals normal
findings, as does the rest of the examination.
An imaging study reveals the
cause of his vomiting, ataxia, and diplopia.

Case 2 Presentation
A 15-year-old girl who experienced
menarche at age 13 years has had no
menstrual periods for 7 months. Her
only symptom is an occasional headache occurring at the end of the day.
She denies sexual activity, medication use, and substance abuse and has
had no recent weight change, heat or
cold intolerance, skin or hair problems, difficulties with vision, or fainting. The patient’s family history includes a granduncle who has
acromegaly.
On physical examination, she
looks well. Her height is in the 50th
68 Pediatrics in Review Vol.25 No.2 February 2004

percentile, weight is in the 75th percentile, blood pressure is 113/
62 mm Hg, and pulse is 90 beats/
min. Her skin is not flushed or dry,
and she has no rashes or abnormalities of hair pattern or hirsutism. Extraocular movements, visual fields by
confrontation, and pupils all are normal. Heart, lung, abdominal, and
neurologic examinations yield normal findings. Breasts and external
genitalia are at sexual maturity rating
4 and normal, with a patent vagina
and palpable uterus.
Normal laboratory findings include follicle stimulating hormone,
4.5 mIU/mL (4.5 IU/L); luteinizing hormone, 6.6 mIU/mL
(6.6 IU/L); testosterone, 46 ng/dL
(1.6 nmol/L); dehydroepiandrosterone sulfate, 122 mcg/dL (3.3
mcmol/L); thyroid-stimulating hormone, 1.28 mcIU/mL; thyroxine,
8.9 mcg/dL (114.5 nmol/L); and
total cholesterol, 186 mg/dL
(4.8 mmol/L). A pregnancy test is
negative. Pelvic ultrasonography reveals a normal uterus and no free
fluid. Two final studies reveal the origin of the patient’s amenorrhea.

Case 3 Presentation
An 8-year-old girl presents with the
acute onset of severe right lower
quadrant colicky pain and mild right
flank pain associated with nausea and
vomiting. She has no fever, dysuria,
or diarrhea. Yesterday she had a similar but milder episode that lasted for
a few hours and resolved spontaneously. At the age of 2 years, she underwent an uneventful bilateral inguinal hernia repair.
On physical examination, the girl
is in severe pain. Her temperature is
97.6°F (36.1°C), pulse is 93 beats/
min, blood pressure is 100/62 mm
Hg, and respirations are 22 breaths/
min. Her abdomen is soft and nondistended. Bowel sounds are normal.

index of suspicion

There is mild right lower quadrant
tenderness to deep palpation without
any peritoneal signs. Neither costovertebral tenderness nor palpable
masses are present.
Normal values are found on a
complete blood count and measurements of serum electrolytes, glucose,
and urea nitrogen. Urinalysis reveals
5 to 10 red blood cells per highpower field.
One additional test helps to determine the cause of her illness.

Case 1 Discussion
Computed tomography (CT) of the
brain revealed a 2.5 cm⫻3.0 cm posterior fossa mass that occupied the
fourth ventricular space and extended into the foramen of Luschka
on the left. Subsequent magnetic resonance imaging (MRI) revealed the
presence of blood products of various ages in the fourth ventricle and in
the posterior fossa region in very
close proximity to a venous angioma
of the left cerebellar hemisphere.
From these findings, an arteriovenous malformation (AVM) with
acute and subacute hemorrhage was
diagnosed.

Differential Diagnosis
The combination of ataxia and diplopia, as experienced by this child,
should alert the physician to the likelihood of a lesion in the posterior
fossa.
The differential diagnosis of ataxia
includes congenital, infectious, toxic,
neoplastic, metabolic, degenerative,
and traumatic causes, most of which
were not relevant to this child’s situation.
Diplopia occurs from malalignment of the visual axes, which may
result from heterophoria, cranial
nerve palsy, or proptosis. Other
causes of double vision include increased intracranial pressure, pitu-

itary or optic chiasm tumors, orbital
tumors, other brain tumors, orbital
cellulitis, and myasthenia gravis.
General depression of cerebral function, as in alcohol intoxication, can
cause dysconjugate gaze and diplopia. Monocular diplopia results from
dislocation of the lens or a defect in
the media or macula.

Making the Diagnosis
The first step in searching for the
cause of this child’s ataxia and diplopia is to take a careful history, which
will provide information that allows
the clinician to focus on the most
likely possible causes. Given his prior
good health, normal growth and development, and family history devoid
of anyone having ataxia, congenital
causes were low on the list of possibilities. There was no history of mental status changes, seizures, headaches, or ingestions. There was no
trauma history or any reason to suspect nonaccidental trauma. Infectious causes, such as labyrinthitis and
acute cerebellar ataxia, as well as mass
lesions, remained most likely. The
initial search was for a posterior fossa
tumor or mass lesion affecting the
cerebellum and compressing cranial
nerve IV or VI, leading to diplopia,
with increased intracranial pressure
causing the vomiting.
Neuroimaging is essential in evaluating any child suspected of having
an intracranial tumor or mass lesion.
CT reveals acute intracranial trauma,
cerebral edema, hemorrhage, and
hydrocephalus. MRI is superior to
CT for detecting the age of hemorrhages, structural abnormalities in
the posterior fossa, and brainstem
anomalies. It also is useful in delineating the relationship between vascular malformations and the surrounding neural structures. On
MRI, AVMs typically appear as several dilated and torturous arteries
supplying a tangled vascular mass,

from which one or more draining
veins emerge.
It should be noted that signs and
symptoms can vary with any posterior fossa lesion, whether AVM or
tumor.

The Condition
AVMs are congenital communications of dilated, thin-walled arteries
and veins that characteristically lack
connecting capillaries and can occur
in many organs. Symptomatic AVMs
are detected at a rate of approximately 1 per 100,000 person-years.
AVMs may be found in several areas
of the brain, including the cerebrum,
corpus callosum, cerebellum, basal
ganglia, and brainstem.
The most common presenting
signs of intracranial AVMs are manifestations of hemorrhage or seizures,
although more subtle findings such
as headache and focal neurologic deficits also may be presenting signs and
symptoms. Fifty percent of intracranial AVMs present with rupture of
the fragile abnormal vessels. The risk
of hemorrhage is 2% to 4% per year.
The average risk of death after an
initial rupture of an AVM is 10%.
This risk escalates with each subsequent hemorrhage. The incidence of
a new neurologic deficit occurring
with each hemorrhage is approximately 50%.
The prognosis depends largely on
the size and the location of the mass
and its accessibility to surgical correction. Persistent neurologic dysfunction is a risk of both AVM hemorrhage and its surgical correction.
Younger patients may have a lower
degree of risk due to their potential
for reorganization of the brain.

Treatment
Microsurgical removal of this patient’s AVM was undertaken, with
successful resection of the abnormal
vessels. This technique is used most
Pediatrics in Review Vol.25 No.2 February 2004 69

index of suspicion

commonly to remove AVMs that
have hemorrhaged or caused seizures. Other therapeutic techniques
include endovascular embolization
and radiotherapy. Endovascular embolization is performed by introducing thrombosing agents that block
blood flow through the abnormal
vessels. This technique can reduce
the size of the malformation but
rarely accomplishes total obliteration. Embolization often is used in
combination with surgery or focused
radiation. Radiosurgery can be effective in treating AVMs smaller than
3 cm in diameter. Gamma knife, proton beam, or linear accelerator methods can deliver high-beam radiation
directly to the AVM noninvasively,
with minimal effects on the surrounding normal tissue.

Lessons for the Clinician
Although the differential diagnosis
of ataxia includes almost every organ
system, a careful history and physical
examination can narrow the choices
significantly. The clinician must
search for other symptoms and signs
of increased intracranial pressure in
any child who presents with vomiting
and neurologic dysfunction. This
search should involve eliciting a history of headaches, examining the
eyes for papilledema, testing the gait,
and monitoring vital signs. If a brain
lesion is suspected, neuroimaging is
essential, and the clinician should obtain an MRI quickly, if possible, or
CT if MRI is not available. (Therese
M. Marren, MD, Edward J. Epstein,
MD, University of California Medical Center at San Diego, San Diego,
CA)

Case 2 Discussion
The patient’s prolactin level was
120 ng/mL (120 mcg/L) (normal,
1 to 20 ng/mL [1 to 20 mcg/L]).
MRI of her head revealed a 1-cm
70 Pediatrics in Review Vol.25 No.2 February 2004

low-signal area in the midline extending eccentrically to the left, consistent with an adenoma within the
pituitary fossa. Cabergoline was administered to treat the presumed
prolactinoma. The prolactin level
normalized, and menses resumed after initiation of therapy.

The Hormone
Prolactin is a hormone that is produced and stored by the anterior pituitary gland. It stimulates milk production after childbirth and the
production of progesterone by the
corpus luteum. Prolactin is produced
intermittently, with peak production
occurring during sleep. Secretion is
inhibited by dopamine concentrations. As the dopamine level rises, the
prolactin level falls. Excessive prolactin secretion may cause galactorrhea.
Hyperprolactinemia occurs in
normal states, including during pregnancy and the initial postpartum period, when there is stress, with breast
stimulation, after eating, and with
exercise. It is seen with the use of
drugs such as risperidone, phenothiazines, amitriptyline, cimetidine,
and haloperidol. Hypothyroidism,
polycystic ovary syndrome, pituitary
tumor, hyperplasia of lactotropes,
and hypothalamic disease are among
the endocrinologic causes of hyperprolactinemia. Chronic renal disease,
renal and bronchogenic carcinomas,
herpes zoster, atopic dermatitis of
the chest, and chest wall trauma are
other causes. In some patients, hyperprolactinemia is idiopathic.

The Underlying Cause
Prolactinomas are pituitary tumors
that produce prolactin. They are the
most common type of pituitary tumor in adolescents but occur infrequently in children and are more
common in women than men. Males
more often have a macroadenoma at
presentation. Prolactinomas in fe-

males of reproductive age may become symptomatic earlier because of
the disruption of normal menses and
presentation with amenorrhea.

Clinical Presentation
The functional effects of a prolactinoma result from increased serum
concentrations of prolactin and from
the mass effect of the tumor on
nearby structures and pituitary function. The mass effect of the tumor
can suppress gonadotropin secretion
as well as locally compress or destroy
pituitary tissue. This destruction may
create other hormonal effects, including growth changes and delayed
or arrested puberty.
Prolactinomas are rare in prepubertal children and may present with
headache, visual problems, and
growth failure. Pubertal women display amenorrhea, galactorrhea, headache, halted pubertal development,
and rarely, visual problems. Pubertal
men who have prolactinomas may
present with headaches, visual disturbances, gynecomastia, and hypogonadism.

Diagnosis
Clinical evaluation of a patient who
has secondary amenorrhea should include discussion of menstrual history, pregnancies, drug use, acne,
hirsutism, symptoms of thyroid disease, headaches, and vision difficulties. The physical examination
should focus on signs of thyroid disease, hirsutism, visual field defects,
breast discharge, funduscopic findings, neurologic signs, evidence of
androgen excess, and vaginal estrogenization.
Hyperprolactinemia may indicate
a range of problems, including pituitary hyperplasia, tumors, and cysts.
A pituitary tumor is suggested by
blood prolactin levels greater than
100 ng/mL (100 mcg/L). The level
of serum prolactin often corresponds

index of suspicion

to the size of the prolactinoma.
A large tumor associated with minimal elevation of prolactin is consistent with a nonprolactin-secreting
tumor causing pituitary stalk compression. Insulin-like growth factor-1
concentrations should be measured if
acromegaly is present. Other neuroendocrine testing is indicated for
macroprolactinomas and preoperatively. Estrogen status should be
evaluated because of the risk of low
bone density in patients who have
hyperprolactinemia and low serum
estradiol levels.
Pituitary lesions are visualized
best by using MRI, which allows
clear views of the pituitary region and
depicts anatomy of the region in
three dimensions. Prolactinomas are
classified based on diameter as either
microadenomas (⬍1.0 cm) or macroadenomas (⬎1.0 cm).

Management
Several different strategies are employed to control growth of prolactinomas, to reverse or halt deleterious
hormonal effects, and to restore vision and menses. The modality used
is based on the clinical presentation.
Important considerations include tumor size, estrogen status, presence or
absence of galactorrhea, contraception use, and desire for fertility.
Medical management employing
dopamine agonists is the treatment
offered most commonly for macroadenomas. A lack of treatment
risks an increase in the size of the
tumor, pituitary dysfunction, and visual problems. Common dopamine
agonists include bromocriptine and
cabergoline. These medications decrease tumor volume and prolactin
concentrations. They also are effective in treating estrogen deficiency,
promoting fertility, and stopping galactorrhea. Although tumor size generally is reduced with these medications, dopamine agonists must be

used continuously. The primary disadvantages of bromocriptine are
nausea, emesis, headache, fatigue,
and postural hypotension. Cabergoline requires administration only
once or twice per week and has fewer
adverse effects than bromocriptine.
Teenagers who have microadenomas may be estrogen-deficient,
which creates a high risk for bone
loss. These patients usually are
treated with dopamine agonists to
restore normal menses. Some patients can discontinue dopamine
agonists after 2 to 4 years of therapy.
Treatment with cyclic conjugated estrogens and medroxyprogesterone
or low-dose oral contraceptives may
be an alternative, but close follow-up
is required. Patients desiring pregnancy are treated with bromocriptine
or cabergoline. Dopamine agonists
should be stopped once the patient
becomes pregnant. Patients having
microadenomas are unlikely to experience adverse effects, but those having macroadenomas may have a more
complicated pregnancy course. After
delivery, prolactin levels decline and
breastfeeding may occur; patients
may need to resume dopamine agonist medications.
If a patient cannot tolerate the
adverse effects of dopamine agonist
medication, if the tumor grows or
fails to shrink after a medication trial,
if the patient has visual loss and chiasmal compression, or if sudden pituitary failure occurs, clinicians may
consider surgery. Transsphenoidal
surgery is the favored surgical strategy for prolactinomas. Radiotherapy
is used infrequently to treat prolactinomas. When used, it is reserved for
large prolactinomas that have failed
to respond to medical and surgical
therapy.

Lessons for the Clinician
When evaluating a patient who has
secondary amenorrhea, it is impor-

tant to look for hyperprolactinemia.
Prolactinomas are diagnosed by serum prolactin testing and radiologic
studies and usually are treated with
dopamine
agonist
medication.
Long-term follow-up includes monitoring prolactin levels as well as performing serial examinations and
MRIs. Treatment may need to be
lifelong, but it can afford patients
more comfortable lives. (Stacey
Maslow, MD, Southboro Medical
Group, Framingham, MA)

Case 3 Discussion
CT of the abdomen showed ovarian
enlargement, small peripheral follicles, and some intraperitoneal fluid.
These findings were consistent with
the diagnosis of ovarian torsion. At
surgery, the right ovary and fallopian
tube were found to be torsed and
infarcted. A large, hemorrhagic follicular cyst occupied the right ovary.
Abdominal pain is the most common chief complaint of patients seen
in pediatric emergency departments.
The causative condition often is obscure, with an unconfirmed or uncertain diagnosis reported in more than
40% of patients.
Ovarian torsion is a well-known
yet poorly recognized clinical entity
that can involve the fallopian tube,
ovary, and ancillary structures. It is
the fifth most common gynecologic
emergency, with a reported incidence of 3% in one series of acute
gynecologic complaints. However,
the diagnosis of ovarian torsion often
is missed. The diagnosis is delayed in
most affected patients because of failure to consider this condition, which
can have nonspecific clinical findings.

Pathophysiology
Adnexal torsion typically is associated with a mass such as a cyst, which
is most likely, or a benign or malignant tumor. Functional ovarian cysts
Pediatrics in Review Vol.25 No.2 February 2004 71

index of suspicion

in children usually develop following
hormonal stimulation that occurs
during two peak periods: the first
year of life and around the time of
menarche. Even cysts that occur normally with ovulation may cause ovarian enlargement and predispose to
torsion, as can large hemorrhagic
cysts. It is believed that the increase
in the weight and the size of the
ovary may alter the anatomy of the
fallopian tube and cause twisting.
Adnexal torsion presents as severe
sudden pain due to twisting of the
ovary, the fallopian tube, or a paratubal cyst. The most common form
of torsion involves the ovary and the
distal aspect of the fallopian tube,
wherein the ovary rotates on its pedicle and compromises the blood supply. Torsion of the ovary initially interferes with the venous and
lymphatic circulation. If unrelieved,
torsion of the ovary progresses rapidly to occlusion of the arterial circulation, which may be irreversible and
lead to necrosis. Because necrosis can
lead to loss of fertility, infection, sepsis, and death, torsion is considered a
surgical emergency.

Clinical Features
The symptoms and signs associated
with ovarian torsion are variable, often are nonspecific, and can be misleading. The classic history in ovarian
torsion is the abrupt onset of colicky
pain in a lower quadrant, with radiation to the flank or groin that mimics
renal colic. The pain associated with
torsion is acute, severe, and unilateral. Most patients have nausea,
vomiting, and lower quadrant pain,
but these findings are associated with
many other abdominal causes of pain
and are not specific for ovarian torsion. Objective findings also are variable and rarely impressive in patients
experiencing ovarian torsion. This
paucity of objective findings may
suggest the need to consider ovarian
72 Pediatrics in Review Vol.25 No.2 February 2004

torsion. Patients who have ovarian
torsion generally present without fever and have a normal white blood
cell (WBC) count and differential
count, although some may have an
elevated WBC count or low-grade
temperature. The patient may describe a prior history of similar episodes.
The ability to diagnose adnexal
torsion depends on the physician’s
consideration of the condition in the
differential diagnosis, which is especially important when a patient has
an ovarian mass. It is important to
remember that even if the patient is
pregnant, ovarian torsion still may
occur. Ovarian torsion has been reported in patients who underwent
untwisting of the ischemic adnexa
when they were 6 to 20 weeks pregnant. It also is very important in
pregnant patients to differentiate torsion from an ectopic pregnancy,
which can present as severe abrupt
pain and an adnexal mass.

Differential Diagnosis
The first priority in evaluating a child
who has abdominal pain is to determine if he or she requires immediate
surgical intervention. Besides ovarian
torsion, the differential diagnosis of
acute lower abdominal pain in a girl
must include acute appendicitis, ectopic pregnancy, intussusception, intestinal obstruction, and ruptured
ovarian cyst. Significant pain also can
be caused by renal stones, pelvic inflammatory disease, constipation,
gastroenteritis, mittelschmerz, and
urinary tract infection.
Ovarian torsion should be considered in patients who have moderateto-severe unilateral adnexal pain and
tenderness. In addition, an adnexal
mass often is palpable. A history of
prior torsion is important. Patients
may present with recurrent episodes
of pain over several months, which
may be caused by incomplete tor-

sions that resolve. It is important to
realize that prepubertal girls can experience torsion of the ovary; the clinician should not discount this condition in a young girl who has a
compatible clinical picture.
Gastroenteritis is the most common cause of abdominal pain not
requiring surgery; appendicitis is the
most common cause for which surgery is necessary. Acute appendicitis
is the condition misdiagnosed most
frequently in patients who have adnexal torsion. In many cases, torsion
is indistinguishable from acute appendicitis on clinical grounds. Initially, patients who have appendicitis
often report poorly defined, constant
pain in the periumbilical region. As
the disease progresses, the pain shifts
from the periumbilical region to the
right lower quadrant. Anorexia, nausea, vomiting, and fever often follow
the pain. The differentiation of appendicitis from adnexal torsion often
requires imaging studies.
It is difficult to diagnose ectopic
pregnancy accurately by history and
physical examination alone. Abdominal pain associated with amenorrhea
is the most common presenting
complaint. Diagnostic accuracy has
improved with the combination of
serum quantitative beta-human chorionic gonadotropin assays and transvaginal ultrasonography.

Laboratory Testing
General laboratory studies usually are
not helpful in diagnosing ovarian
torsion, but they may help to diagnose other conditions. A pregnancy
test must be performed in the emergency department on all female patients of reproductive age who have
abdominal pain, regardless of their
sexual or menstrual history, which
may be unreliable. In a variety of
situations, it is essential that clinicians consider adolescent girls pregnant until they have been tested. Ec-

index of suspicion

topic pregnancy is a fatal condition
without intervention and is the leading cause of death in the first trimester of pregnancy. A pregnant patient
having abdominal pain must be considered to have an ectopic pregnancy
until proven otherwise.
This patient had microscopic hematuria, which has been noted in
several case reports of adnexal torsion. The hematuria may be related
to the retroperitoneal inflammation
associated with torsion, similar to
what occurs in cases of retroperitoneal appendicitis.
Ultrasonography is the primary
modality used to diagnose torsion
and reveals the affected ovary, usually
as a uniformly echogenic mass. Sonographic findings consistent with torsion include a solid, cystic, or complex pelvic mass with or without a
fluid collection in the pouch of
Douglas. A more specific finding is
the demonstration of multiple follicles (8 to 12 mm in size) in the
cortical portions of a unilaterally enlarged ovary. This finding is attributed to the transudation of fluid into
the follicles as part of the congestion
of the ovary that results from circulatory impairment. Sonographic identification of a normal ovary in its normal position may help to exclude the
diagnosis of torsion. Because most
cases of torsion are due to large ovar-

ian cysts or masses, the finding of a
normal-size ovary makes adnexal torsion unlikely.
Doppler ultrasonography commonly is used to evaluate suspected
adnexal torsion. When torsion is
present, the lack of blood flow on
Doppler examination probably indicates that an ovary is beyond salvage.
CT often reveals a complex ovarian mass and can demonstrate or exclude other abdominal and pelvic
disease, such as appendicitis. However, the definitive diagnosis and
management of torsion require laparotomy.

copy often is performed when an adnexal mass is not demonstrated on
physical examination or on imaging
studies and the diagnosis is unclear.
Salpingo-oophorectomy may be necessary if there is evidence of necrotic
tissue and was the treatment of
choice for all torsions in the past;
however, multiple studies support
the concept of untwisting nonnecrotic adnexa if possible. When
unilateral torsion is diagnosed,
oophoropexy (plication) of the contralateral adnexa may be indicated.

Lessons for the Clinician
Management
Prompt diagnosis is important both
to establish the diagnosis and to increase the rate of salvage of the ovary.
An ovarian salvage rate of less than
10% has been reported. The interval
between the onset of symptoms and
the necrosis of adnexal structures is
not known, but in the case of testicular torsion, irreversible changes may
occur after only 4 hours. Early surgical intervention is required in both
entities to preserve fertility.
Treatment of ovarian torsion
mandates early surgical exploration
and may require unilateral salpingooophorectomy. When the diagnosis
remains unclear, laparoscopy can assist in making the diagnosis. Laparos-

Ovarian torsion is a cause of acute
abdominal pain that requires prompt
surgical intervention and always
should be considered in the differential diagnosis of a girl who has acute
abdominal pain. Considering torsion
is especially relevant when evaluating
patients who are being observed for
the possibility of appendicitis. Early
diagnosis of adnexal torsion is imperative to preserve fertility. Time is critical when ovarian torsion is present.
A high level of clinical suspicion and
expeditious imaging may decrease
the surgical delay and improve the
likelihood of ovarian salvage. (Muhammad Waseem, MD, Sandhya
Ganti, MD, Joel Gernsheimer, MD,
Lincoln Hospital, Bronx, NY)

Pediatrics in Review Vol.25 No.2 February 2004 73