Endocrine Physiology: Case Studies in Adrenal Disorders

1. Endocrine Physiology: Case Studies in Adrenal Disorders C.W. Spellman, PhD, DO Assoc. Prof. Medicine Assist. Dean, Dual Degree Program Head, Endocrinology & Dir. Diabetes Clinics UNTHSC

2. 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/dL BUN 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

3. Reference Values, cont. ACTH 10 - 75 pg/ml TSH 0.3 - 5.0 mIU/ml a.m. Cortisol 5 - 25 g/dl ACTH Stim. cortisol >18 - 20 g/dl or 7 g/dl > baseline 24 h urine free cortisol 10 - 50 ug/24 hr Aldosterone <10 ng/dl Aldosterone : renin <20

4. 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

5. 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% Clinical Features of Cushing’s Syndrome

6. 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 gain Fatigue “Stretch marks” Shortness of breath

7. Case 1, cont. • PE: BP=180/100 HR=84 RR=20 T=99 Ht=65” Wt=250 lbs HEENT:  buccal fat Neck:  dorsal fat Chest:  supraclavicular Lung: CTA Cor: RRR, no S3 or S4, normal PMI Abd: Obese Extrem: Thin, prox. muscle weakness Skin: Wide red striae, ecchymoses Neurol: normal

8. Case 1, cont. • Lab evaluations Na 136 K 3.6 Gluc 190 Cr 0.9

9. Case 1, Questions • What do you think the diagnosis is? • If the lesion was in the pituitary, predict: ACTH Cortisol • If the disease was in the adrenals, predict: ACTH Cortisol • If the lesion was an ectopic tumor, predict: ACTH Cortisol

10. 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?

11. 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%

12. 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

13. 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.

14. Case 2, cont • PE: BP=90/60 HR=96 RR=16 T=98 Ht=68” Wt 130 lbs HEENT: nor Neck: nor Lung: nor Cor: nor Abd: nor Extrem: nor Skin: uniformly tan Neurol: nor

15. Case 2, cont • Lab Na 124 K 5.9 Glucose 70 TSH 1.55 Hb 15.4

16. Case 2, Questions • What do you think the diagnosis is? • If the lesion was in the adrenals, predict: Cortisol Aldosterone ACTH • Why is the sodium low? • Why is the potassium high? • If the lesion was in the pituitary, predict: Cortisol Aldosterone ACTH

17. 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?

18. Aldosteronism • Old name: Conn’s syndrome • 2x more common in ♀ than ♂ • Occurs 30 – 50 y age group • Si/Sx Diastolic HTN Headache Hypokalemia • LVH occurs • Renal disease 50% develop proteinuria 15% develop renal failure

19. Aldosteronism • Older data suggest that <1% of HTN is due to aldosteronism • New data suggest that up to 10% of HTN is due to aldosteronism • Suspect aldosteronism: Diastolic HTN Hypokalemia (K ~ ≤3 meq/L)

20. Causes of Aldosteronism • Aldosterone-producing adenoma 75% of cases of aldosteronism Usually solitary nodules (0.5 - 2.5 cm) Almost always benign

21. Causes of aldosteronism • Adrenocortical hyperplasia a. 25% of cases of aldosteronism b. Bilateral hyperplasia c. Rarely produces hormones other than aldosterone

22. Causes of Aldosteronism • Other causes 1. Adrenal carcinoma is extremely rare 2. Congenital adrenal hyperplasia Produces mineralocorticoids other than aldosterone 3. Secondary aldosteronism High aldosterone is secondary to high renin levels

23. 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

24. Case 3, cont. • PE: BP=170/104 HR=72 RR=16 T=98 Ht=72” Wt=195 lbs HEENT: nor Neck: nor Chest: nor Abd: nor Extrem: nor Skin: nor Neurol: nor

25. Case 3, cont. • Lab CMP normal, except K=2.9 TSH nor

26. Case 3, Questions • What do you think the diagnosis is? • How common is this disorder? • Predict the laboratory results of: Aldosterone Renin Cortisol • Why does this patient have hypertension? • Why is the potassium low?

27. Case 3, Questions • What are possible causes of the problem? Discuss primary causes Discuss secondary causes • How would you differentiate primary from secondary causes? • Can you illustrate the physiology of primary and secondary disease?

28. 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