A two-year-old boy is admitted to the hospital for spitting up and poor feeding. He was reportedly healthy until the week of this hospital admission, although his slow growth and lack of weight gain have been a consistent problem for which no definite diagnosis has been given. He was born after a full-term pregnancy to a 24-year-old primigravida woman. Gestation was complicated by early oligohydramnios and relatively poor weight gain, but the birth weight was 3,770 g (68th percentile) and birth length was 50.8 cm (62nd percentile). Although vaginal delivery was attempted, the use of forceps was unsuccessful and cesarean delivery was necessary after a difficult and prolonged labor. There were no other complications, and two days after delivery, the newborn was discharged with his mother
Th ere is no family history of disease, the child is not taking any medications, and he has not been exposed to any unknown substances. On physical examination, weight is below the fifth percentile and height is at the 10th percentile. He has no dysmorphic features, but he is dehydrated, pale, and lethargic. He has no trauma or rashes. He has normal male genitalia with bilaterally descended testes. An X-ray of the abdomen shows calcifications that are thought to represent kidney stones. Abdominal CT is shown.
Laboratory test results:
Sodium = 114 mEq/L (136-142 mEq/L)
Potassium = 7.2 mEq/L (3.5-5.0 mEq/L)
ACTH = 2,500 pg/mL (10-60 pg/mL)
Cortisol = 1.2 μg/dL (AM serum cortisol,
17-Hydroxyprogesterone = 35 ng/dL
(AM 17-hydroxyprogesterone 60-300 ng/dL)
Plasma renin activity = 86 ng/mL per h
(0.6-4.3 ng/mL per h)
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Which one of the following diagnoses is most consistent
with the biochemical profile and CT image of this
A Allgrove syndrome
B Familial glucocorticoid deficiency
C Congenital adrenocortical hyperplasia
D Adrenal hemorrhage
E Congenital HIV infection and adrenal insufficiency
A TODDLER’S SUDDEN ILLNESS:
A Case Study from Pediatric ESAP
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The answer is:
D. Adrenal hemorrhage
Th is patient has adrenal calcifications (see arrows) caused by adrenal hemorrhage (Answer D), a well-recognized obstetric complication of the newborn, which is an increasingly rare cause of adrenal insufficiency because of the improvements in care during labor and delivery.
However, it is still an issue, and unless diagnosed and treated early, it can lead to chronic, partially compensated adrenal insufficiency or adrenal insufficiency crisis or both. In about half of the reported cases, the bleeds are bilateral and occur at birth. Gradually, the affected glands develop calcifications. Risk factors include large birth weight, hypoxia, septicemia, coagulation defects, and thromboembolism. Other causes of adrenal calcifications include tuberculosis; autoimmunity; Wolman disease ( familial xanthomatosis); Niemann-Pick disease; and masses including hemorrhagic and teratomatous cysts, ganglioneuromas, pheochromocytomas, neuroblastomas, and adrenocortical cancer. Adrenal calcification may also be an incidental finding, although then it is also attributed to perinatal adrenal hemorrhage. This patient’s history and presentation are consistent with the cases with adrenal hemorrhage that have been described in the literature, with presentation of adrenal insufficiency not at birth or shortly thereafter, but rather later in the second or third year of life. Typically, these patients compensate for their adrenal dysfunction with high ACTH levels. Partial adrenal insufficiency should be suspected in any infant who has failure to thrive and difficulty feeding, but no primary gastrointestinal disorder. Their condition may decompensate during an infection, a bout of diarrhea, or the course of any other illness, and then they present with severe adrenal insufficiency like the child in this vignette.
Patients with Allgrove syndrome (Answer A) (also known as triple A syndrome) present with alacrima, achalasia, and adrenal insufficiency, but they never develop calcifications in their adrenal glands.
Allgrove syndrome and other causes of familial glucocorticoid deficiency syndromes (Answer B) also rarely cause mineralocorticoid deficiency.
Congenital adrenocortical hyperplasia (CAH) (Answer C) associated with mineralocorticoid deficiency is an unlikely diagnosis in a fully virilized male with low 17-hydroxyprogesterone levels. Although saltlosing 21-hydroxylase deficiency would be consistent with the biochemical profile in this male toddler, the 17-hydroxyprogesterone levels would be expected to be high. Also, CAH is not known to be associated with adrenal gland calcifications.
Finally, congenital HIV infection (Answer E) can cause adrenal insufficiency, but unless it leads to tuberculosis or parasitic infections (i.e., histoplasmosis), it would not be associated with adrenal gland calcifi cations. These calcifications tend to also be unilateral in patients who develop them secondary to an infection.