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

Reference Lab Values for Cases Glucose mg/dL Na mEq/dL K mEq/dL HCO m Eq/dL BUN mg/dL Creatinine mg/dL Calcium mg/dL Hb g/dL

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

Cushing’s Syndrome Cushing’s syndrome: Excess glucocorticoids due to Excess glucocorticoids due to Pituitary tumor % Pituitary tumor % Adrenal tumor % Adrenal tumor % Ectopic ACTH tumor 10% Ectopic ACTH tumor 10% Iatrogenic Iatrogenic “Classic” syndrome: Weight gain, Plethora, Striae, HTN, Proximal muscle weakness

Clinical Features of Cushing’s Syndrome Weight gain 90%  Menses 60% Weight gain 90%  Menses 60% “Moon face” 75% Acne 40% “Moon face” 75% Acne 40% HTN 75% Bruising 40% HTN 75% Bruising 40% Striae 65% Osteopenia 40% Striae 65% Osteopenia 40% Hirsuitism 65% Edema 40% Hirsuitism 65% Edema 40% Glucose intol 65% Hyperpig. 20% Glucose intol 65% Hyperpig. 20% Muscle weak. 60% K+ meta. alk. 15% Muscle weak. 60% K+ meta. alk. 15% Plethora 60% Plethora 60%

Case 1: Young Lady With Weight Gain A 24 y lady was in good health in the Spring of 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

Case 1, cont. PE: BP=180/100 HR=84 RR=20 T=99 Ht=65” Wt=250 lbs 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 Abd: Obese Extrem: Thin, prox. muscle weakness Skin: Wide red striae, ecchymoses Neurol: normal Neurol: normal

Case 1, cont. Lab evaluations Na 136 K 3.6 Gluc 190 Cr 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 2 nd 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 lbs Ht=68” Wt 130 lbs HEENT: nor Neck:nor Lung:nor Cor:nor Abd:nor Extrem:nor Skin:uniformly tan Neurol:nor

Case 2, cont Lab Na124 K 5.9 Glucose70 TSH1.55 Hb15.4

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 syndrome 2x more common in ♀ than ♂ Occurs 30 – 50 y age group Si/Sx Diastolic HTN HeadacheHypokalemia LVH occurs Renal disease 50% develop proteinuria 15% develop renal failure

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)

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

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

Causes of Aldosteronism Other causes 1. Adrenal carcinoma is extremely rare 2. Congenital adrenal hyperplasia Produces mineralocorticoids other than aldosterone Produces mineralocorticoids other than aldosterone 3. Secondary aldosteronism High aldosterone is secondary to high renin levels 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 lbs Ht=72” Wt=195 lbs HEENT:nor Neck:nor Chest:nor Abd:nor Extrem:nor Skin:nor Neurol:nor

Case 3, cont. Lab CMPnormal, except K=2.9 TSHnor

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 causes Discuss 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  Renin  Aldo  Na  Vol  Renin  Aldo  Na