Endocrine Physiology: Case Studies in Adrenal Disorders C.W. W Spellman, PhD, DO Assoc. Prof. Medicine Assist. Dean, Dual Degree Program Head, Endocrinology & Dir. r Diabetes Clinics UNTHSC
Reference Lab Values for Cases Glucose 60 -110 mg/dL Na 136 -144 mEq/dL K 3.8 – 5.4 mEq/dL HCO3 23 – 26 m Eq/dLBUN 8 – 14 mg/dL Creatinine 0.6 – 1.5 mg/dL Calcium 8.5 – 10.5 mg/dL Hb 13.5-15.5 g/dL
Reference Values, cont. ACTH 10 – 75 pg/ml TSH 0.3 – 5.0 mIU/ml a.m. Cortisol 5 – 25 µg/dl ACTH Stim. cortisol >18 – 20 µg/dl or ≥ 7 µg/dl > baseline 24 h urine free cortisol 10 – 50 ug/24 hrAldosterone <10 ng/dl Aldosterone : renin <20
Cushing’s Syndrome Cushing’s syndrome: Excess glucocorticoids due to Pituitary tumor 70 – 80% Adrenal tumor 10 – 20% Ectopic ACTH tumor 10% Iatrogenic “Classic” syndrome: Weight gain, Plethora, Striae, HTN, Proximal muscle weakness
Clinical Features of Cushing’s Syndrome Weight gain 90% ∆ Menses 60% “Moon face” 75% Acne 40% HTN 75% Bruising 40% Striae 65% Osteopenia 40% Hirsuitism 65% Edema 40% Glucose intol 65% Hyperpig. 20% Muscle weak. 60% K+ meta. alk. 15% Plethora 60%
Case 1: Young Lady With Weight Gain A 24 y lady was in good health in the Spring of 1999. She married in August and her husband brought her to the Endocrine clinic in December. Complaints 80 lb weight gainFatigue“Stretch marks”Shortness of breath
Case 1, cont. PE: BP=180/100 HR=84 RR=20 T=99 Ht=65” Wt=250 lbsHEENT: ↑ buccal fatNeck: ↑ dorsal fatChest: ↑ supraclavicularLung: CTACor: RRR, no S3 or S4, normal PMI Abd: Obese Extrem: Thin, prox. muscle weaknessSkin: Wide red striae, ecchymoses Neurol: normal
Case 1, cont. Lab evaluations Na 136K 3.6 Gluc 190Cr 0.9
Case 1, Questions What do you think the diagnosis is?If the lesion was in the pituitary, predict: ACTHCortisol If the disease was in the adrenals, predict: ACTHCortisol If the lesion was an ectopic tumor, predict: ACTHCortisol
Case 1, Questions How could you determine if this lady had adrenal disease? Pituitary tumor? Ectopic tumor?Why is the glucose elevated?Why is she weak?What are the skin changes due to?Why has she gained weight?Why is the potassium low?
Clinical Features of Primary Adrenal Insufficiency Gradual onset >95% Weakness & fatigue 100% Wt loss/anorexia 100% Hyperpigmentation 92% Hypotension / tachycardia 88%Hyponatremia 88% Hyperkalemia 64% Muscle, GI pain 56%
Clinical Features of Secondary Adrenal Insufficiency Gradual onset >95% Weakness & fatigue 100% Wt loss/anorexia 100% Pale 100% Hair loss <50% Anemia <50% Electrolytes usually normal
Case 2: Medical Student with Weakness, Fatigue and Nausea 25 y 2nd y medical student develops weakness, fatigue and nausea. She is unable to complete the OB-GYN rotation. The OB attending briefly evaluates the student, suspects and endocrine problem and refers her to our clinics.
Case 2, cont PE: BP=90/60 HR=96 RR=16 T=98 Ht=68” Wt 130 lbsHEENT: norNeck: nor Lung: nor Cor: nor Abd: nor Extrem: norSkin: uniformly tan Neurol: nor
Case 2, cont Lab Na 124 K 5.9 Glucose 70TSH 1.55 Hb 15.4
Case 2, Questions What do you think the diagnosis is?If the lesion was in the adrenals, predict: CortisolAldosteroneACTH Why is the sodium low?Why is the potassium high?If the lesion was in the pituitary, predict: CortisolAldosteroneACTH
Case 2, Questions If the patient had secondary disease, how would the physical examination have been different?If the patient had secondary disease, how would the electrolytes have been different?
Aldosteronism Old name: Conn’s syndrome2x more common in ? than ?Occurs 30 – 50 y age groupSi/Sx Diastolic HTNHeadacheHypokalemia LVH occursRenal disease 50% develop proteinuria15% develop renal failure
Aldosteronism Older data suggest that <1% of HTN is due to aldosteronismNew data suggest that up to 10% of HTN is due to aldosteronismSuspect aldosteronism: Diastolic HTNHypokalemia (K ~ ≤3 meq/L)
Causes of Aldosteronism Aldosterone-producing adenoma 75% of cases of aldosteronismUsually solitary nodules (0.5 – 2.5 cm)Almost always benign
Causes of aldosteronism Adrenocortical hyperplasia a. 25% of cases of aldosteronismb. Bilateral hyperplasiac. Rarely produces hormones other than aldosterone
Causes of Aldosteronism Other causes 1. Adrenal carcinoma is extremely rare2. Congenital adrenal hyperplasia Produces mineralocorticoids other than aldosterone 3. Secondary aldosteronism High aldosterone is secondary to high renin levels
Case 3: Young Man with Hypertension A 25 y male presents to the clinic as a new patient. He takes no prescription medications, over-the-counter products or “alternative substances”He came because his wife, a PA, noted hypertension and scheduled the visit
Case 3, cont. PE: BP=170/104 HR=72 RR=16 T=98 Ht=72” Wt=195 lbsHEENT: norNeck: nor Chest: nor Abd: nor Extrem: norSkin: nor Neurol: nor
Case 3, cont. Lab CMP normal, except K=2.9 TSH nor
Case 3, Questions What do you think the diagnosis is?How common is this disorder?Predict the laboratory results of: AldosteroneReninCortisol Why does this patient have hypertension?Why is the potassium low?
Case 3, Questions What are possible causes of the problem? Discuss primary causesDiscuss secondary causes How would you differentiate primary from secondary causes?Can you illustrate the physiology of primary and secondary disease?
Secondary Aldosteronism Secondary aldosteronism refers to appropriate increased production of aldosterone in response to activation of the renin-angiotensin system Primary aldosteronism Secondary Aldosteronism ↑ Vol ↓ Vol ↑ Na ↓ Renin ↑ Na ↑ Renin ↑ Aldo ↑ Aldo