A 3-year-old female with septo-optic dysplasia and panhypopituitarism was traveling on vacation. She had become acutely ill with emesis in the early hours of the morning. The emesis became more frequent so her parents brought her to the small community emergency room that was closest to their hotel. In the ER, she was alert and responsive but was mottled with a capillary refill of 4 seconds. Her respiratory rate was 38/minute, temperature of 37.8° and a blood pressure of 72/44. She had a mild dysconjugate gaze which was normal per her parents. Her heart and lungs were normal. She had slightly hyperactive bowel sounds and mildly diffuse abdominal pain and no organomegaly. She denied any suprapubic, costovertebral or McBurney’s point tenderness.
While an IV was established and fluids begun, her parents said that she had had been well and had taken all of her medications the day before. In retrospect her parents said that she probably had been drinking less the day before and seemed more tired, but they had attributed that to the traveling. She had been diagnosed early in life with septo-optic dysplasia and was treated by a multispecialty team at a children’s hospital. She had done relatively well and had not had any major crises so the family had decided to take a car trip across part of the country to visit relatives.
They had brought with them her emergency steroid medicine in case of adrenal crisis. The father said, “We know it’s supposed to be given in her leg muscle, but we’ve never done it and don’t want to do it.” The physician took the box along with an emergency treatment letter from the child’s doctor. He and the hospital pharmacist checked the emergency instructions and the IM hydrocortisone dosing. They calculated an appropriate IV dosing based on the emergency treatment letter and the pharmacist virtually ran back to the emergency room with the medication. In the meantime, the patient’s laboratory evaluation showed a sodium of 128 mEq/L, potassium of 4.4 mEq/L, and a glucose of 53 mg/dL. She also was now febrile and her blood pressure was not increasing. The physician ordered an additional .9 normal saline bolus along with piggyback fluids of D25W. At the same time, the physician was arranging a transfer to the regional children’s hospital. As the child appeared stable but getting sicker, an airflight ambulance was sent. While still in the ER, her blood pressure started to drop and pressor medications were begun which stablized her.
The physician found out a few weeks later that in the patient’s clinical course she had culture-negative sepsis that precipitated her adrenal crisis. She needed vasopressors for 48 hours but responded well to the antibiotics. She finished her course of antibiotics and was released with followup with her regular physicians.
Septo-optic dysplasia (SOD) is a disorder of midline prosencephalic development early in gestation. It causes agenesis of the septum pellucidum and/or thinning or absence of the corpus callosum and pituitary hormone deficiencies. It has an incidence of 1:10,000 live births. Most cases appear to be due to a combination of genetic and environmental factors but there are rare familial cases which are most often autosomal recessive.
The phenotype is variable and diagnosis can occur at birth with more severe problems or later with milder ones. Patients must have at least 2 of 3 problems for diagnosis including uni- or bi-lateral optic nerve hypoplasia, midline brain defects (e.g. septum pellucidum absence or agenesis of the corpus callosum) and hypopituitarism (which is a hypothalamic hypopituitarism not a primary dysfunction of the gland itself). Patients have poor visual function, developmental delay, sleep problems, seizures and various endocrine deficiencies. The most common endocrinopathy is growth hormone deficiency, then thyroid stimulating hormone deficiency, then adrenocorticotropic hormone (ACTH) deficiency. The endocrinopathies do not have to be present at birth but can develop later. Patients with SOD are at risk for adrenal insufficiency (AI) as they obviously do not have the normal capacity to increase ACTH during stress.
The hypothamic-pituitary-adrenal axis is important for maintaining homeostasis in the metabolic and immune systems. Normally the hypothalamus secrets corticotrophin-release hormone (CRH) and argenine vasopressin (AVP). These stimulate the anterior pituitary to secrete adrenocorticotropic hormone (ACTH). ACTH causes the adrenal gland to secrete aldosterone and cortisol along with androgenic steroids. Normally during stress, CRH, AVP and norepinephrine act to increase ACTH release. Cortisol, a glucocorticoid, maintains serum glucose. Aldosterone, a mineralocorticoid, maintains electrolyte balance and catecholamine balance for blood pressure modulation.
Adrenal insufficiency (AI) is defined as “…inadequate cellular corticoisteroid activity for the severity of the patient’s illness, [and] is the result of either a decrease in adrenal steroid production or tissue resistance to glucocorticoids.” In acute adrenal insufficiency or adrenal crisis, patients can have hypoglycemia, hyponatremia, hyperkalemia, hypotension, dehydration, altered mental status and thermodysregulation. Patients may also present with more nonspecific symptoms such as anorexia, nausea, vomiting, abdominal pain, weakness, fatigue, lethargy, and fever. It is a medical emergency requiring multispecialty treatment often in an intensive care setting in consultation with an endocrinologist.
- For hypotension and dehydration, aggressive fluid resuscitation with isotonic saline with dextrose (usually D5 .9 normal saline) should be begun. Resuscitation must be carefully monitored to prevent water retention.
- For hypoglycemia, additional dextrose (D25W) may be needed in addition to the dextrose in the other fluids.
- Glucocorticoids can be given intravenously or intramuscularly. Intravenous is preferred as intramuscular injection may have a slower uptake because of decreased perfusion and dehydration.
- Hydrocortisone (cortisol) is recommended because of its mineralocorticoid affect and should be given in stress doses – 50-75 mg/M2 x 1 dose initially, followed by 50-75 mg/M2 given daily divided into 4 doses.
- Alternatives are methylprednisolone 10-15 mg/M2 and dexamethasone 1.5-2 mg/M2. Dexamethasone does not cross-react with hydrocortisone and so it can be used if AI is suspected and it will not confound confirmatory testing.
Careful monitoring of glucose, sodium, and potassium are needed. Other testing which can help includes cortisol, ACTH, aldosterone and renin levels. Underlying triggers of adrenal crisis need to be aggressively sought and treated.
Questions for Further Discussion
1. What disease processes cause adrenal insufficiency?
2. What triggers can cause adrenal crisis?
- Disease: Adrenal Crisis | Addison’s Disease | Adrenal Gland Disorders | Pituitary Disorders | Septo-optic Dysplasia
- Symptom/Presentation: Vomiting
- Age: Preschooler
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Adrenal insufficiency: still a cause of morbidity and death in childhood. Shulman DI, Palmert MR, Kemp SF; Lawson Wilkins Drug and Therapeutics Committee. Pediatrics. 2007 Feb;119(2):e484-94.
The empty sella. Naing S, Frohman LA. Pediatr Endocrinol Rev. 2007 Jun;4(4):335-42.
Adrenal crisis provoked by dental infection: case report and review of the literature. Milenkovic A, Markovic D, Zdravkovic D, Peric T, Milenkovic T, Vukovic R. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Sep;110(3):325-9.
Septo-optic dysplasia. Fard MA, Wu-Chen WY, Man BL, Miller NR. Pediatr Endocrinol Rev. 2010 Sep;8(1):18-24.
Adrenal dysfunction in critically ill children. Karagüzel G, Cakir E. Minerva Endocrinol. 2014 Dec;39(4):235-43.
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital