Case Presentation by Alex Weissman, MD
Chief Complaint: “I feel terrible.”
History of Presenting Illness:
The patient is a 32-year-old female presenting with complaint of feeling “terrible and weak.” She states that this has happened to her twice in the last 24 hours. The first episode occurred upon awakening at 3 AM this morning with a sensation of doom, shortness of breath, chest pain, and in a cold sweat with chills. Subsequently she passed out. She ate some corn, felt better, and went back to sleep. Today, prior to arrival, the patient had another episode where she went into a cold sweat with chills and had a sensation of doom with chest pain and shortness of breath; however, this time she did not pass out. She called EMS, who found her capillary blood sugar was 32 mg/dL. The patient denies being sick recently. She denies insulin or sulfonylurea use. She denies abnormal stress in her life. She states that she has been eating normally. Last menstrual period was 3 years ago, the patient has always had irregular menses. The patient denies associated headache, sudden change in vision, abdominal pain, nausea, vomiting, diarrhea, constipation, dysuria, pain or numbness in the extremities, recent illness, or recent travel.
Review of System:
Constitutional: Complains of cold sweats and chills
HEENT: Denies headache
CVS: Complains of substernal chest pain
Lungs: Complains of SOB
Abdomen: Denies abdominal pain
Musculoskeletal: Denies pain in the extremities
Genitourinary: Denies dysuria
Skin: Denies rash
Neurologic: Denies numbness
Psychiatric: Denies depression
Past Medical History:
Bronchitis, splenomegaly, anemia, thrombocytopenia
Past Surgical History:
Bone marrow biopsy
The patient denies use of tobacco, alcohol, or illicit drugs past or present.
Family Medical History:
Addison’s disease in her mother
Vitals: Blood pressure: 100/75, Pulse: 60, Respiratory rate: 18, Pulse Oximetry: Not initially recorded, Temperature: 36.2 degrees Celsius
General: Alert and oriented x3, no acute respiratory distress
Head: normocephalic, atraumatic
Eyes: PERRL, EOMI, bilateral conjunctival pallor, no scleral icterus
ENT: No cervical lymphadenopathy, no pharyngeal edema, mucous membranes moist
Cardiovascular: regular rate and rhythm, no appreciable murmurs, capillary refill <2 seconds
Respiratory: no tachypnea, no retractions, clear to ausculation bilaterally, no appreciable wheezes, rhonchi, or rales
Gastrointestinal: normoactive bowel sounds, nondistended, no tympany to percussion, soft and nontender to palpation
Musculoskeletal: Extremities are atraumatic, dorsalis pedis and radial pulses 2+ and regular bilaterally, no peripheral edema
Skin: no rashes or lesions
MENTAL STATUS: awake, alert, oriented
CRANIAL NERVES: face symmetric, pupils 3mm -> 2mm bilaterally, PERRL, EOMI, visual fields full to confrontation
MOTOR: patient moving all four extremities spontaneously, gait normal
SENSORY: intact to light touch
Initial CBG – 32 mg/dL
TSH: 3.586 Micro IU/mL
Serum pregnancy: negative
Insulin: <0.5 mcUnits/mL
Random cortisol: 2.2 mcg/dL
1) What are the classic physical exam and laboratory findings in primary adrenal insufficiency (Addison’s Disease)?
a) High blood pressure, high serum potassium, high serum sodium, low random cortisol, low serum glucose
b) Low blood pressure, high serum potassium, low serum sodium, low random cortisol, low serum glucose
c) High blood pressure, high serum potassium, low serum sodium, high random cortisol, high serum glucose
d) Low blood pressure, low serum potassium, low serum sodium, low random cortisol, low serum glucose
2) What laboratory test is used to diagnose adrenal insufficiency, what distinguishes primary versus secondary adrenal insufficiency, and what test value would you expect in primary adrenal insufficiency?
a) ACTH stimulating test; ACTH; low or normal ACTH level
b) Random cortisol; cortisol; low cortisol
c) ACTH stimulating test; ACTH; high ACTH level
d) Random cortisol; ACTH; low or normal ACTH level
3) What are some basic differences in symptomatology between primary and secondary adrenal deficiency?
a) Primary: Hypokalemia, hypernatremia, hypoglycemia, dehydration, hypotension, Cushingoid habitus
Secondary: Hyperkalemia, hyponatremia, normotension, hyperpigmentation, hyperglycemia
b) Primary: Hyperkalemia, hyponatremia, hypoglycemia, dehydration, hypotension, hyperpigmentation,
Secondary: Hypokalemia, hyper/hyponatremia, +/- Cushingoid habitus, hypoglycemia
c) Primary: Hypokalemia, hyponatremia, dehydration, hypotension, +/- Cushingoid habitus, hyperglycemia
Secondary: Hypernatremia, hyperkalemia, hyperpigmentation, normotension
d) Primary: Hyperkalemia, hyponatremia, hyperglycemia, normotension
Secondary: Hypokalemia, hypernatremia, hypoglycemia, hypotension, dehydration, hyperpigmentation, +/- Cushingoid habitus
Bonus Question 1. What is the preferred steroid treatment for adrenal crisis and what vital sign abnormality should raise the ED physician’s clinical suspicion for an adrenal crisis?
a) Hydrocortisone – unexplained hypotension
b) Prednisone – unexplained hypertension
c) Dexamethasone – unexplained hypotension
d) Hydrocortisone – unexplained hypertension
Bonus question 2: What is the most common infectious cause of primary adrenal insufficiency in the US?
Answers & Discussion:
1) Correct answer: B
Primary adrenal insufficiency is characterized by failure of the adrenal gland to produce sufficient steroids including glucocorticoids (namely cortisol), mineralocorticoids (namely aldosterone), and gonadocorticoids (namely estrogen and testosterone). It can be associated with infectious disease states (HIV, tuberculosis, adrenal hemorrhage, sepsis), autoimmunity (polyglandular autoimmune syndrome type I or II), inflammatory diseases (sarcoidosis, hemochromatosis, amyloidosis, lymphoma, etc.), congenital/hereditary causes (congenital adrenal hyperplasia, adrenal hypoplasia, adrenal leukodystrophy, familial glucocorticoid deficiency), or secondary to non-steroid drugs (ketoconazole, mitotane, aminoglutethimide, hemorrhage from warfarin, prolonged IV infusions of etomidate, etc.). It often presents with a shock state due to the body’s inability to produce the stress hormone, cortisol, as well as the lack of aldosterone. Patients typically have low blood pressure, low glucose, low serum sodium, low cortisol levels, and high serum potassium. A random cortisol level less than 3 mcg/dL is diagnostic. The low blood pressure, low serum sodium, and high serum potassium are related to decreased aldosterone levels that are secondary to the adrenal gland failure. Decreased cortisol also leads to decreased blood pressure as well as decreased glucose. Vague GI complaints, salt craving, and postural syncope are common complaints. Another result of adrenal insufficiency is decreased estrogen and testosterone levels.
Secondary adrenal insufficiency occurs when there is failure of the hypothalamus-pituitary-adrenal axis typically at the level of the hypothalamus or pituitary gland, instead of singular failure of the adrenal gland as seen in primary adrenal insufficiency. It is most commonly is due to abrupt withdrawal of long-term high dose steroids. Only cortisol will be low, as opposed to low cortisol and low aldosterone in primary adrenal insufficiency. Other causes of secondary adrenal insufficiency are Sheehan syndrome, head trauma, pituitary disease, infectious diseases affecting the hypothalamus or pituitary (tuberculosis, HIV, meningitis, etc.), or inflammatory diseases affecting the hypothalamus or pituitary (sarcoidosis, cancer, hemochromatosis, etc.).
2) Correct answer: C
Recall that the hypothalamus secretes corticotropin-releasing factor that causes the pituitary to release ACTH, thus resulting in the adrenal gland secreting cortisol. Therefore, the rapid cosyntropin (synthetic ACTH) stimulation test is utilized to diagnose adrenal insufficiency, and the level of plasma ACTH is used to distinguish between primary (a.k.a. adrenal gland failure) and secondary (a.k.a. hypothalamus or pituitary failure) adrenal insufficiency. The cosyntropin test is performed by drawing a baseline cortisol level (18-20 mcg/dL is a normal random cortisol in healthy people), then administering 0.25 mg IV ACTH, and checking plasma cortisol at 30 minutes and 1 hour after administration. In normal people, the plasma cortisol should rise by at least 7 mcg/dL at 30 minutes and peak at >18 mcg/dL at 1 hour. A high ACTH level is indicative of primary adrenal insufficiency, hence the adrenal glands are not producing sufficient cortisol despite the hypothalamus and pituitary telling them to do so. Since there is no feedback inhibition from circulating cortisol, more and more ACTH is released. A low or normal ACTH level is suggestive of secondary adrenal insufficiency, indicating a problem at the level of the hypothalamus or pituitary gland.
3) Correct answer: B
Primary adrenal insufficiency is characterized by both aldosterone deficiency and cortisol deficiency. Aldosterone deficiency confers hypotension and hyponatremia with hyperkalemia. Cortisol deficiency confers weakness, lethargy, hypotension, hyperpigmentation (due to unopposed ACTH production) and hypoglycemia.
Secondary adrenal insufficiency has intact aldosterone presence, therefore unless the patient is in an adrenal crisis, blood pressure is typically normal. Hypernatremia can result since aldosterone function is intact, unless there is a dilutional hyponatremia secondary to retained water. Hypokalemia results from the unchecked aldosterone effect. There is often hypoglycemia secondary to the lack of ACTH stimulation on cortisol release.
EKG changes can occur secondary to the potassium disturbances: U waves from hypokalemia, or peaked T waves with QT prolongation or even heart block can occur due to hyperkalemia.
Bonus 1: Correct answer: A
High dose steroid administration is the mainstay of therapy for adrenal crisis, regardless of cause or level of dysfunction in the hypothalamic-pituitary-adrenal axis, in addition to supportive care and treatment of the underlying etiology. Hydrocortisone 100 mg IV is the preferred steroid because it has both mineralocorticoid and glucocorticoid effects. If an ACTH stimulating test is going to be ordered, then Dexamethasone 4 mg IV can be used instead because it does not interfere with the test results. Prednisone is not strong enough for a patient with an adrenal crisis. Unexplained hypotension should increase the clinician’s suspicion for an adrenal pathology, especially hypotension refractory to fluids and vasopressors. This occurs secondary to the lack of cortisol. Of course, fluids (dextrose 5% with 0.9% normal saline or hypertonic saline if needed) and vasopressors (norepinephrine, dopamine, or phenylephrine) should absolutely be given in addition to steroids during an adrenal crisis.
Bonus 2 Correct answer: D
HIV (and especially HIV related infections) is the most common cause of primary adrenal insufficiency in the US, but worldwide the most common cause is tuberculosis.
- Tintinalli, Judith E, et al. Tintinalli’s Emergency Medicine, 7th Ed. San Francisco: McGraw-Hill, 2011. Print. Chapter 225: Adrenal Insufficiency and Adrenal Crisis, 1453-1456.
- Marx, John A, et al. Rosen’s Emergency Medicine, 7th Ed. Philadelphia: Mosby Elsevier, 2010. Print. Chapter 126: Thyroid and Adrenal Disorders, 1671-1675.