Unusual Tanning By Chris Sanders

Chief Complaints Weaker and more tired over past 4 months Severe increase in past week Unable to enjoy outdoor activities Unusual tan

History of Present Illness/Previous Medical History Surgically treated appendicitis 10 years ago Seroconverted to PPD (+) 6 years ago; treated for 12 months with INH Pernicious anemia x 5 years Hypercholesterolemia x 1 year; controlled with diet and exercise 48 year old white woman Loss of appetite Progressive fatigue Mild nausea PPD: purified protein derivative (tuberculin skin test) INH: isoniazid Pernicious anemia: Inability to absorb B12

Family History No history of cancer Father died of cardiac arrest at age 65 Mother in nursing home following CVA; also RA Two sisters with Hashimoto’s thyroiditis One sister with Graves’ disease One brother alive and well CVA: cardiovascular accident (stroke) RA: rheumatoid arthritis

What is the major significance of this patient’s family history?

The Common Factor Rheumatoid Arthritis Autoimmune Disease Hashimoto thyroiditis Autoimmune Disease Graves’ disease Autoimmune Disease

Meds Cyanocobalamin, 200µg IM on 15th of each month (physician recently increased dosage) ASA → swelling of face TMP-SMX → bright red rash that covered her torso and face, reportedly with fever Cyanocobalamin: B12 supplement ASA: aspirin (acetylsalicylic acid) TMP-SMX: trimethoprim-sulfamethoxazole (antifungal/antibacterial)

Cyanocobalamin Why is the patient taking this medication? Vitamin B12 deficiency Why is oral cyanocobalamin not an option for her condition? Oral side effects may include hives, difficulty breathing, swelling of the face, headache, nausea, diarrhea

Review of Systems (-) for fever, chills, shortness of breath, night sweats, and cough (+) for weight loss of 6 pounds in the last month (+) for salt cravings before nausea developed (+) for several bouts of dizziness, one fainting spell in the last 6 months (+) for few aches and pains (-) for recent changes in vision (-) for changes in menstrual cycle (+) for prominent tanning of the skin, although she denies significant exposure to the sun

PE and Lab Tests Tired-looking, tanned Caucasian woman in NAD who appears to be her stated age BP 95/75, P 83/min sitting, right arm T 98.0º F BP 80/60, P 110/min standing, right arm HT 5 ft-6½ in RR 14/min WT 124 lbs Explain the significance of the varying blood pressure and heart rate readings with change in position by the patient.

PE and Lab Tests cont. Skin HEENT Intact, warm, and very dry Subnormal turgor Pigmented skin creases on palms of hands and knuckles Generalized tanned appearance, even at sites not exposed to the sun Sparse axillary hair HEENT PERRLA EOMI Normal funduscopic exam TMs intact Dry mucous membranes Turgor: skin elasticity HEENT: head, eyes, ears, nose, throat PERRLA: pupils equal, round, and reactive to light and accommodation EOMI: extra-ocular movements intact TM: tympanic membrane

PE and Lab Tests cont. Neck Lungs Cardiac Breasts Abdomen Supple with normal thyroid and no masses Shotty lymphadenopathy Lungs Clear, normal vesicular and bronchial lung sounds to A&P Cardiac RRR No m/r/g Breasts Equal in size without nodularity, masses, or tenderness Very dark areolae Hyperpigmentation prominent along brassiere lines Abdomen Soft and NT (-) HSM (+) BS Lymphadenopathy: swelling of lymph nodes RRR: regular rate and rhythm m/r/g: murmur/rub/gallop NT: non-tender HSM: hepatosplenomegaly (liver and spleen enlargement) BS: bowel sounds

PE and Lab Tests cont. GU Neuro MS/Ext Peripheral Blood Smear Normal external female genitalia LMP 2 weeks ago Normal pelvic exam without tenderness or masses Neuro A & O x 3 Bilateral deep tendon reflexes intact at 2+ Normal gait CNs II-XII intact MS/Ext No CCE Normal ROM Pigmented skin creases on elbows Pedal pulses moderately weak at 1+ Muscle strength 5/5 throughout Peripheral Blood Smear Normochromic, Normocytic erythrocytes GU: genitourinary LMP: last menstrual period A & O x 3: alert and oriented to person, place, and time MS/Ext: Musculoskeletal/Extremities CCE: clubbing, cyanosis, or edema ROM: range of motion

Laboratory Blood Test Results Na 126 meq/L Hct 33.2% Alk Phos 115 IU/L K 5.2 meq/L RBC 4.1 million/mm3 Bilirubin 1.2 mg/dL Cl 97 meq/L MCV 85 fL Protein 8.0 g/dL HCO3 30 meq/L Plt 410,000/mm3 Albumin 4.7 g/dL BUN 20 mg/dL WBC 6,800/mm3 Cholesterol 202 mg/dL Cr Neutros 49% Triglycerides 159 mg/dL Glu 55 mg/dL Lymphs 36% Fe 89 µg/dL Ca 8.8 mg/dL Monos 7% TSH 3.2 µU/mL Phos 2.9 mg/dL Eos Free T4 16 pmol/L Mg Basos 1% Cortisol 2.0 µg/dL Uric acid 3.6 mg/dL AST 33 IU/L ACTH 947 pg/mL Hb 11.4 g/dL ALT 50 IU/L Vitamin B12 700 pg/mL Sodium is borderline critical, usual is 135-145 meq/L Potassium is high, usual is 3.5-5.0 meq/L Eosinophils very high, usual is 1-4% Cortisol dangerously low, should be 5-20 µg/dL ACTH: adrenocorticotropic hormone – Dangerously high, should be 9-52 pg/mL

PE and Lab Tests cont. UA Imaging Antibody Testing Clear and yellow SG 1.016 pH 6.45 (-) blood Imaging Abdominal CT scan revealed moderate bilateral atrophy of the adrenal glands Antibody Testing (+) 21-hydroxylase (-) 17-hydroxylase (-) C-P450

What is your diagnosis?

Rapid ACTH Stimulation Test Condition Cortisol Assay Aldosterone Assay Pre-cosyntropin 2.0 µg/dL 3.8 ng/dL 30 min post-cosyntropin 1.9 µg/dL Normal patient levels should double in 30 minutes Diagnostic test to distinguish primary and secondary adrenal insufficiency ACTH: adrenocorticotropic hormone – Dangerously high, should be 9-52 pg/mL

Closing Questions What is the single greatest risk factor for Addison disease in this patient? What is the most likely cause of Addison disease in this patient? Why can tuberculosis be ruled out as a cause of Addison disease in this patient? Which two test results are most suggestive of the cause of Addison disease in this patient? Addison/Adrenal crisis: loss of consciousness, psychosis, convulsions, fever Genetic factors Problem free 5 years Cortisol/ACTH levels

Closing Questions Would supplementation with fludrocortisone be appropriate in this patient? Does this patient have any signs of hypothyroidism, a disorder that is commonly associated with Addison disease? There are 19 clinical signs and symptoms in this case study that are consistent with Addison disease. Identify 15 of them. Which single test result is diagnostic for Addison disease in this patient? Fludrocortisone might not be appropriate, since sodium is low and potassium is high No signs of hypothyroidism Tan, high K, low Na, low cortisol, high ACTH, familial history, fatigue, nausea, loss of appetite, shotty lymphadenopathy, increased eosinophils ACTH stimulation

Closing Questions Which test results support the assessment that the patient’s anemia is not the result of iron deficiency? Which test results support the assessment that the patient’s anemia is not the result of vitamin B12 deficiency? Why is shotty lymphadenopathy consistent with a diagnosis of Addison disease in this patient? Sufficient iron Sufficient B12 Immunological disorder