Jaundice - Case 15-3: 2-Month-Old Boy
Jaundice - Case 15-3: 2-Month-Old Boy: Excerpt from Pediatric Complaints and Diagnostic Dilemmas
I. History of Present Illness
A 2-month-old male infant was admitted for further evaluation of his jaundice
and poor growth.
II. Past Medical History
The baby was born via spontaneous vaginal delivery after an uncomplicated,
full-term pregnancy and weighed 3.0 kg at birth. On the second day of life, he
was transferred to the special care nursery because of hypoglycemia requiring
intravenous dextrose. A sepsis evaluation was performed, and the baby received
7 days of ampicillin and gentamicin. On the third day of life, his total
bilirubin level was noted to be 18.6 mg/dL (with a direct bilirubin
concentration of 2.8 mg/dL), and he received phototherapy for 4 days. His
complete blood count, blood type and antibody screen, abdominal ultrasound, and
state newborn screen were all normal. The birth hospital reported that the baby
was taken home on the ninth day of life against medical advice; his prefeed
blood sugar measurement that day was 33 mg/dL.
The baby had been seen by his pediatrician three times for weight and bilirubin
checks; blood sugar measurements at those visits were described as
“borderline.” His feeding regimen was about 2.5 ounces every 3 hours of cow's milk formula. Because of poor growth and persistent hyperbilirubinemia, he was
referred to the hospital
's gastroenterology clinic and subsequently admitted for additional evaluation.
III. Physical Examination
T, 37.3°C; RR, 24/min; HR, 140 bpm; BP, 96/60 mm Hg
Weight, 3.6 kg (less than 3rd percentile); length, 52 cm (less than 3rd
percentile); head circumference, 38 cm (10th percentile)
Physical examination revealed a cachectic, somewhat icteric 2-month-old boy in
no apparent distress. There was scleral icterus and a 5
× 5 cm anterior fontanel; the oropharynx was clear, with moist mucous membranes.
His neck was supple without lymphadenopathy or masses. Breath sounds were clear
and unlabored. His pulse was regular, and there was no murmur. The abdomen was
soft, nontender, and nondistended; the liver edge was palpable just below the
right costal margin, and a small umbilical hernia was present. The testes were
palpable (but not fully descended) bilaterally; the penis appeared small, with
a stretched penile length of 2.0 cm. The baby appeared alert with grossly
normal tone and reflexes. The remainder of the examination was unremarkable.
IV. Diagnostic Studies
Serum electrolyte measurement revealed the following: sodium, 131 mEq/L;
potassium, 4.1 mEq/L; chloride, 100 mEq/L; bicarbonate, 22 mEq/L; BUN, 14
mg/dL; creatinine; 0.2 mg/dL; and glucose, 50 mg/dL. The complete blood count
revealed 8,000 WBCs/mm
3 with 5% band forms, 30% segmented neutrophils, and 52% lymphocytes. The
hemoglobin was 9.2 g/dL, and the reticulocyte count was 1.7%. The total
bilirubin measured 10.5 mg/dL; the direct and unconjugated bilirubin levels
were 1.5 and 9.0 mg/dL, respectively. Serum albumin was normal. ALT was 46 U/L,
AST was 87 U/L, and GGT was 125 U/L.
Abdominal ultrasound examination of the liver revealed normal size, slightly
increased echogenicity, and a small, nondistended gall bladder without biliary
dilatation. The spleen and kidneys were normal. A sweat test was attempted, but
an insufficient amount of sweat was obtained to properly interpret the test.
V. Course of Illness
The infant was admitted to the hospital and given intravenous fluids containing
dextrose to maintain the blood sugar concentration greater than 60 mg/dL. Serum
amino acids,
α1-antitrypsin testing, and serology analyses for hepatitis B and C were
performed, as was a liver biopsy. None of this testing revealed a specific
hepatic or intestinal abnormality.
Discussion: Case 15-3
I. Differential Diagnosis
The susceptibility of neonates to unconjugated hyperbilirubinemia is favored by
a number of factors, including relative increases in bilirubin production and
enterohepatic circulation along with relative decreases in hepatic uptake and
conjugation. Unconjugated hyperbilirubinemia is a very common occurrence in the
newly born and is usually self-limited and benign. However, if the serum
concentration of bilirubin exceeds 17 mg/dL, the jaundice can no longer be
regarded as physiologic.
Given this predisposition of newborns to an imbalance between bilirubin
generation and hepatic excretory capacity, pathologic or prolonged neonatal
hyperbilirubinemia is often attributable to conditions that exacerbate the
imbalance. For instance, hemolytic diseases (e.g., ABO incompatibility),
polycythemia, and extravascular blood collections (e.g., cephalohematoma,
subgaleal blood, ecchymoses) are conditions that favor increased bilirubin
production. Decreased bilirubin clearance can result from inherited bilirubin
metabolism disorders (e.g., Crigler-Najjar syndrome, Gilbert disease),
hypothyroidism, and circumstances that increase enterohepatic reuptake (e.g.,
breast-feeding, delayed meconium passage). As for older children, Gilbert
syndrome (a genetic disorder of the uridine diphosphoglucuronate
glucuronosyltransferase enzyme system that occurs in about 6% of adults) and
hemolytic anemias are the most common causes of unconjugated bilirubinemia.
II. Diagnosis
The baby's persistent hypoglycemia prompted an endocrinology service consultation. Among
the array of examinations requested were thyroid function tests, which revealed
a thyroid-stimulating hormone (TSH) concentration of 1.00 mIU/mL (normal range,
0.6 to 10.0) and a thyroxine (T4) level of 5.0
µg/dL (normal range, 5.5 to 17 µg/dL). These results—a low T4 with a TSH in the low-normal range—were deemed typical for central hypothyroidism, and T4 replacement was begun. A
magnetic resonance imaging (MRI) study revealed an atrophic anterior pituitary
gland and an ectopic posterior pituitary with arrested descent. More
sophisticated biochemical testing was subsequently performed and indicated
global pituitary dysfunction consistent with
a diagnosis of panhypopituitarism.
III. Incidence and Epidemiology
Congenital hypothyroidism has been estimated to occur in about 1 of every 4,000
newborns, and about one third of these infants demonstrate prolonged
hyperbilirubinemia. It appears that T4 is necessary to the bilirubin
conjugating process. The baby in this case had hypothyroidism and protracted
unconjugated bilirubinemia as dominant features of an even rarer
endocrinopathy, congenital hypopituitarism. Of note, the hyperbilirubinemia
seen in panhypopituitarism can also be
cholestatic, particularly when growth hormone or corticotropin (ACTH) deficiencies dominate
the pathophysiology.
IV. Clinical Presentation
Prolonged neonatal jaundice may be the first sign of congenital hypothyroidism
and hypopituitarism. Feeding difficulties, apnea, noisy breathing, and overall
sluggishness are other common manifestations. Physical findings specifically
attributable to hypothyroidism can include a relatively large head, anterior
fontanel, tongue, and abdomen; umbilical hernia; edema; and a
lower-than-expected pulse and temperature. Mental and physical development
become increasingly retarded over time when hypothyroidism goes undetected and
uncorrected.
Among the physical findings that may be detected in patients with congenital
hypopituitarism are micropenis, midline craniofacial defects (e.g., cleft lip
or palate), a single central incisor, and signs of hypoglycemia or
hypocortisolism, such as lethargy or apnea. The possibility of septo-optic
dysplasia should be considered whenever congenital hypopituitarism is
diagnosed. In addition to the neuroendocrine deficiency, these patients have
optic nerve hypoplasia and agenesis of the septum pellucidum.
V. Diagnostic Approach
Testing for deficiencies of pituitary hormones and MRI of the brain are crucial
steps in evaluating suspected hypopituitarism. Standard newborn screening
programs do not always detect pituitary hypothyroidism. Thyroid function tests
in particular must be interpreted carefully. A TSH in the low-normal range, for
instance, is not appropriate when the T4 level is borderline. Because
presenting signs and symptoms of these endocrinopathies can often be quite
subtle at first, an index of suspicion and appropriate, targeted testing are
key to making the diagnosis.
VI. Treatment
Replacement of the hormones produced by the pituitary's target organs is the cornerstone of hypopituitarism therapy. Thyroid hormone
replacement should begin as soon as confirmatory testing is completed; delays
in therapy can result in increased risk of cognitive impairment. Jaundice
improves as the underlying endocrine disorder is treated.
VII. References
1. Balint JP, Balistreri WF. Jaundice. In: Kleigman RM, ed. Practical strategies in pediatric diagnosis and therapy. Philadelphia: WB Saunders, 1996:360–379.
2. Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. N Engl J Med 2001;344:581–590.
3. Gourley GR. Neonatal jaundice and disorders of bilirubin metabolism. In:
Suchy FJ, Sokol RJ, Balistreri WF, eds.
Liver disease in children, 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2001:275–314.
4. Kaplan M, Hammerman C, Maisels MJ. Bilirubin genetics for the nongeneticist:
hereditary defects of neonatal bilirubin conjugation.
Pediatrics 2003;111:886–893.
5. MacMahon JR, Stevenson DK, Oski FA. Unconjugated hyperbilirubinemias. In:
Taeusch HW, Ballard RA, eds.
Avery's diseases of the newborn, 7th ed. Philadelphia: WB Saunders, 1998:1014–1033.
6. Moshang T, Grimberg A. Neuroendocrine disorders. In: McMillan JA, DeAngelis
CD, Feigin RD, et al., eds.
Oski's pediatrics: principles and practice, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 1999:1787–1793.
Book Source Details
- Book Title: Pediatric Complaints and Diagnostic Dilemmas
- Author(s): Samir S Shah MD; Stephen Ludwig MD
- Year of Publication: 2003
- Copyright Details: Pediatric Complaints and Diagnostic Dilemmas, Copyright © 2003 Lippincott Williams & Wilkins.
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