Ann Clin Biochem 1999;36:151; Nejm 2003;348:727

Cause: Primary adrenal insufficiency (Addison’s disease) can be atrophic in nature as seen in idiopathic or autoimmune with suppressor T-cell defect; or it can be characterized as destructive as seen in primary or metastatic cancer (Ann Hematol 1999;78:151); antiphospholipid syndrome (Chest 1998;113:1136); infection, especially in TB or in peds with sepsis (Arch Dis Child 1999;80:51); and meningococcemia with Friderichsen-Waterhouse syndrome; in amyloidosis; or in severe hemorrhage with hypotension (Arch Surg 1999;134:394). Secondary adrenal insufficiency occurs in those who may be panhypopit, those who are on chronic steroids—including the possibility of inhaled beclomethasone (J Allergy Clin Immunol 1999;103:956), or those who have just come off of corticosteroids and are now under stress; or autoimmune disorders in general (Clin Endocrinol (Oxf) 1998;49:779). Also seen in HIV in AIDS patients.

Epidem: In Addison’s Disease, peak incidence age 20-40 yr. Associated with HLA-B8 and DR 3/4, and thereby with pernicious anemia, myasthenia gravis, islet cell antibody IDDM, myxedema, vitiligo, alopecia, and primary gonadal failure.

Pathophys: 80% of gland must be destroyed to get symptoms. ACTH and MSH similar, hence increased pigmentation; both mineralocorticoid and glucocorticoid deficiencies create si/sx.

Sx: Loss of sense of well-being; nausea, vomiting, and diarrhea; salt craving and weight loss; galactorrhea, rarely; increased pigmentation if chronic.

Si: Hypotension; cachexia; hyperpigmentation, vitiligo, longitudinal nail pigment streaks if chronic; diminished axillary and pubic hair; remember not to rely on abdominal exam for acute abdomen if patient is on exogenous steroids.

Crs: 40% of those with Addison’s disease will develop other glandular failure (especially thyroid and gonadal).

Lab: Chemistry profile with low Na⁺, low HCO₃, elevated K⁺, order a cortisol level—if < 15 µgm%, then diagnosis most likely; check TSH (J Clin Endocrinol Metab 2000;85:1388), CBC with diff looking for eosinophilia (Lancet 1999;353:1675), consider steroid-21-hydroxylase antibody and very long chain fatty acids serum levels looking for elevation for diagnosis of idiopathic (J Clin Endocrinol Metab 1998;83:3163), consider pan culture and other ID evaluation for hypotension; EKG; Graded ACTH stimulation test diagnostic (J Endocrinol Invest 2000;23:163).

Acta Paediatr suppl 1999;88:14; Emerg Med Clin N Am 1989;7:859

Cause: IDDM with noncompliance and/or secondary infection most likely.

Epidem: Approximately 5% mortality (Med J Aust 1989;151:439,441,442)

Pathophys: Coma from CSF acidosis, hence rarer in metabolic than respiratory acidosis because CO₂ crosses blood-brain barrier easily; HCO₃ treatment may paradoxically induce/worsen coma. Atrial natriuretic peptide suppressed in children to maintain fluid and sodium (J Peds 1987;111:329).

Sx: Malaise, confusion, nausea, vomiting, abdominal pain.

Si: Kussmaul’s respirations; stupor; coma; hypotension; dehydration.

Crs: Onset over 2-3 d.

Cmplc: Cerebral edema leading to coma with 90% mortality 6-10 hr after starting treatment—especially in children (Nejm 1967;276:665) with low PaCO₂ and high serum BUN (Nejm 2001;344:264). Secondary infection with Pseudomonas pseudomallei (Melioidosis), ubiquitous in Asia (Arch IM 1972;130:268).

Diff Dx: Hypoglycemia; infection; drug intoxication; appendicitis; acute renal failure; Non-ketotic, nonacidotic hyperosmolar coma—seen in the elderly with NIDDM.

Lab: Chemistry profile and blood gas, specifically looking for bicarb < 10 and pH < 7.2 (Ped Emerg Care 1996;12:347). Look for anion gap (AG) > 15 calculating the following: Na − (Cl + CO₂) = AG (Nejm 1977;297:814). ABG vs venous blood gas—venous just as useful (Ann EM 1998;31:459). CBC with diff, and > 10% bandemia warrants search for secondary infection (Am J EM 1987;5:1). UA as quick test for ketones and hydration status and if secondary UTI. Consider pan culture and other ID evaluation
if source or febrile. Consider serum ketones or acetone level (Diabetes 1986;35:668). Consider measured and/or calculated osmoles—calculated osmoles = glucose/18 + 2 × Na + BUN/2.8.