Endocrine Physiology: Case Endocrine Physiology: Case Studies in Adrenal DisordersStudies in Adrenal Disorders

C.W. Spellman, PhD, DOC.W. Spellman, PhD, DOAssoc. Prof. MedicineAssoc. Prof. Medicine

Assist. Dean, Dual Degree ProgramAssist. Dean, Dual Degree ProgramHead, Endocrinology & Dir. Diabetes ClinicsHead, Endocrinology & Dir. Diabetes Clinics

UNTHSCUNTHSC

Reference Lab Values for CasesReference Lab Values for Cases

Glucose Glucose 60 -110 mg/dL60 -110 mg/dLNa Na 136 -144 mEq/dL136 -144 mEq/dLKK 3.8 - 5.4 mEq/dL3.8 - 5.4 mEq/dLHCO3 23 - 26 m Eq/dLHCO3 23 - 26 m Eq/dLBUN BUN 8 - 14 mg/dL8 - 14 mg/dLCreatinineCreatinine 0.6 - 1.5 mg/dL0.6 - 1.5 mg/dLCalcium Calcium 8.5 - 10.5 mg/dL8.5 - 10.5 mg/dLHbHb 13.5-15.5 g/dL13.5-15.5 g/dL

Reference Values, cont.Reference Values, cont.

ACTHACTH 10 - 75 pg/ml 10 - 75 pg/ml

TSHTSH 0.3 - 5.0 mIU/ml 0.3 - 5.0 mIU/mla.m. Cortisol a.m. Cortisol 5 - 25 5 - 25 g/dlg/dlACTH Stim. cortisol >18 - 20 ACTH Stim. cortisol >18 - 20 g/dl org/dl or

7 7 g/dl > g/dl > baselinebaseline

24 h urine free cortisol 10 - 50 ug/24 hr24 h urine free cortisol 10 - 50 ug/24 hr

AldosteroneAldosterone <10 ng/dl <10 ng/dl

Aldosterone : renin <20 Aldosterone : renin <20

Cushing’s SyndromeCushing’s Syndrome

Cushing’s syndrome:Cushing’s syndrome: Excess glucocorticoids due toExcess glucocorticoids due to Pituitary tumorPituitary tumor 70 - 80% 70 - 80% Adrenal tumorAdrenal tumor 10 - 20% 10 - 20% Ectopic ACTH tumor 10%Ectopic ACTH tumor 10% IatrogenicIatrogenic

““Classic” syndrome: Classic” syndrome: Weight gain, Plethora, Striae, HTN,Weight gain, Plethora, Striae, HTN,Proximal muscle weaknessProximal muscle weakness

Clinical Features of Cushing’s Clinical Features of Cushing’s SyndromeSyndrome

Weight gain 90%Weight gain 90% Menses 60% Menses 60% “ “Moon face” 75%Moon face” 75% Acne Acne 40% 40% HTNHTN 75% Bruising 40% 75% Bruising 40% StriaeStriae 65% 65% Osteopenia Osteopenia 40% 40% HirsuitismHirsuitism 65% 65% Edema Edema 40% 40% Glucose intol 65%Glucose intol 65% Hyperpig. Hyperpig. 20% 20% Muscle weak. 60% K+ meta. alk. 15%Muscle weak. 60% K+ meta. alk. 15% PlethoraPlethora 60% 60%

Case 1: Young Lady With Weight Case 1: Young Lady With Weight GainGain

A 24 y lady was in good health in the A 24 y lady was in good health in the Spring of 1999. She married in August and Spring of 1999. She married in August and her husband brought her to the Endocrine her husband brought her to the Endocrine clinic in December. clinic in December. ComplaintsComplaints

80 lb weight gain80 lb weight gainFatigueFatigue““Stretch marks”Stretch marks”Shortness of breathShortness of breath

Case 1, cont.Case 1, cont.

PE: BP=180/100 HR=84 RR=20 T=99PE: BP=180/100 HR=84 RR=20 T=99 Ht=65” Wt=250 lbsHt=65” Wt=250 lbsHEENT: HEENT: buccal fat buccal fatNeck: Neck: dorsal fat dorsal fatChest: Chest: supraclavicular supraclavicularLung: CTALung: CTACor: RRR, no S3 or S4, normal PMICor: RRR, no S3 or S4, normal PMI

Abd: ObeseAbd: ObeseExtrem: Thin, prox. muscle weaknessExtrem: Thin, prox. muscle weaknessSkin: Wide red striae, ecchymosesSkin: Wide red striae, ecchymoses

Neurol: normalNeurol: normal

Case 1, cont.Case 1, cont.

Lab evaluationsLab evaluations

Na Na 136 136

K K 3.6 3.6

GlucGluc 190 190

Cr Cr 0.9 0.9

Case 1, QuestionsCase 1, Questions

What do you think the diagnosis is?What do you think the diagnosis is?

If the lesion was in the pituitary, predict:If the lesion was in the pituitary, predict:ACTHACTHCortisolCortisol

If the disease was in the adrenals, predict:If the disease was in the adrenals, predict:ACTHACTHCortisolCortisol

If the lesion was an ectopic tumor, predict:If the lesion was an ectopic tumor, predict:ACTHACTHCortisolCortisol

Case 1, QuestionsCase 1, Questions

How could you determine if this lady had How could you determine if this lady had adrenal disease? Pituitary tumor? Ectopic adrenal disease? Pituitary tumor? Ectopic tumor?tumor?

Why is the glucose elevated?Why is the glucose elevated?

Why is she weak?Why is she weak?

What are the skin changes due to?What are the skin changes due to?

Why has she gained weight?Why has she gained weight?

Why is the potassium low?Why is the potassium low?

Clinical Features of Primary Clinical Features of Primary Adrenal InsufficiencyAdrenal Insufficiency

Gradual onsetGradual onset >95%>95%Weakness & fatigueWeakness & fatigue 100% 100%Wt loss/anorexiaWt loss/anorexia 100% 100%HyperpigmentationHyperpigmentation 92% 92%Hypotension / tachycardiaHypotension / tachycardia 88% 88%HyponatremiaHyponatremia 88% 88%HyperkalemiaHyperkalemia 64% 64%Muscle, GI painMuscle, GI pain 56% 56%

Clinical Features of Secondary Clinical Features of Secondary Adrenal InsufficiencyAdrenal Insufficiency

Gradual onsetGradual onset >95%>95%

Weakness & fatigueWeakness & fatigue 100% 100%

Wt loss/anorexiaWt loss/anorexia 100% 100%

Pale Pale 100% 100%

Hair lossHair loss <50% <50%

AnemiaAnemia <50% <50%Electrolytes usually normalElectrolytes usually normal

Case 2: Medical Student with Case 2: Medical Student with Weakness, Fatigue and NauseaWeakness, Fatigue and Nausea

25 y 225 y 2ndnd y medical student develops y medical student develops weakness, fatigue and nausea. She is weakness, fatigue and nausea. She is unable to complete the OB-GYN rotation. unable to complete the OB-GYN rotation.

The OB attending briefly evaluates the The OB attending briefly evaluates the student, suspects and endocrine problem student, suspects and endocrine problem and refers her to our clinics.and refers her to our clinics.

Case 2, contCase 2, cont

PE: BP=90/60 HR=96 RR=16 T=98PE: BP=90/60 HR=96 RR=16 T=98 Ht=68” Wt 130 lbsHt=68” Wt 130 lbsHEENT: HEENT: nornorNeck:Neck: nornorLung:Lung: nornorCor:Cor: nornorAbd:Abd: nornorExtrem:Extrem: nornorSkin:Skin: uniformly tanuniformly tanNeurol:Neurol: nornor

Case 2, contCase 2, cont

LabLabNaNa 124124KK 5.95.9GlucoseGlucose 7070TSHTSH 1.551.55HbHb 15.415.4

Case 2, QuestionsCase 2, QuestionsWhat do you think the diagnosis is?What do you think the diagnosis is?If the lesion was in the adrenals, predict:If the lesion was in the adrenals, predict:

CortisolCortisolAldosteroneAldosteroneACTHACTH

Why is the sodium low?Why is the sodium low?Why is the potassium high?Why is the potassium high?If the lesion was in the pituitary, predict:If the lesion was in the pituitary, predict:

CortisolCortisolAldosteroneAldosteroneACTHACTH

Case 2, QuestionsCase 2, Questions

If the patient had secondary disease, how If the patient had secondary disease, how would the physical examination have been would the physical examination have been different?different?

If the patient had secondary disease, how If the patient had secondary disease, how would the electrolytes have been different?would the electrolytes have been different?

AldosteronismAldosteronismOld name: Conn’s syndromeOld name: Conn’s syndrome2x more common in 2x more common in ♀ ♀ than than ♂♂Occurs 30 – 50 y age groupOccurs 30 – 50 y age groupSi/SxSi/Sx

Diastolic HTNDiastolic HTNHeadacheHeadacheHypokalemiaHypokalemia

LVH occursLVH occursRenal diseaseRenal disease

50% develop proteinuria50% develop proteinuria15% develop renal failure15% develop renal failure

AldosteronismAldosteronism

Older data suggest that <1% of HTN is due Older data suggest that <1% of HTN is due to aldosteronismto aldosteronism

New data suggest that up to 10% of HTN is New data suggest that up to 10% of HTN is due to aldosteronismdue to aldosteronismSuspect aldosteronism:Suspect aldosteronism:

Diastolic HTNDiastolic HTNHypokalemia (K ~ Hypokalemia (K ~ ≤3 meq/L)≤3 meq/L)

Causes of AldosteronismCauses of Aldosteronism

Aldosterone-producing adenomaAldosterone-producing adenoma

75% of cases of aldosteronism75% of cases of aldosteronism

Usually solitary nodules (0.5 - 2.5 cm)Usually solitary nodules (0.5 - 2.5 cm)

Almost always benignAlmost always benign

Causes of aldosteronismCauses of aldosteronism

Adrenocortical hyperplasiaAdrenocortical hyperplasia

a. 25% of cases of aldosteronisma. 25% of cases of aldosteronism

b. Bilateral hyperplasiab. Bilateral hyperplasia

c. Rarely produces hormones c. Rarely produces hormones other other than aldosterone than aldosterone

Causes of AldosteronismCauses of Aldosteronism

Other causesOther causes

1. Adrenal carcinoma is extremely 1. Adrenal carcinoma is extremely rarerare

2. Congenital adrenal hyperplasia2. Congenital adrenal hyperplasia

Produces mineralocorticoids Produces mineralocorticoids other than aldosterone other than aldosterone

3. Secondary aldosteronism3. Secondary aldosteronism

High aldosterone is secondary to High aldosterone is secondary to high renin levels high renin levels

Case 3: Young Man with Case 3: Young Man with HypertensionHypertension

A 25 y male presents to the clinic as a A 25 y male presents to the clinic as a new patient. He takes no prescription new patient. He takes no prescription medications, over-the-counter products medications, over-the-counter products or “alternative substances”or “alternative substances”

He came because his wife, a PA, noted He came because his wife, a PA, noted hypertension and scheduled the visithypertension and scheduled the visit

Case 3, cont.Case 3, cont.PE: BP=170/104 HR=72 RR=16 T=98PE: BP=170/104 HR=72 RR=16 T=98

Ht=72” Wt=195 lbsHt=72” Wt=195 lbs

HEENT:HEENT: nornor

Neck:Neck: nornor

Chest:Chest: nornor

Abd:Abd: nornor

Extrem:Extrem: nornor

Skin:Skin: nornor

Neurol:Neurol: nornor

Case 3, cont.Case 3, cont.

LabLab

CMPCMP normal, except K=2.9normal, except K=2.9

TSHTSH nornor

Case 3, QuestionsCase 3, Questions

What do you think the diagnosis is?What do you think the diagnosis is?

How common is this disorder?How common is this disorder?

Predict the laboratory results of:Predict the laboratory results of:AldosteroneAldosteroneReninReninCortisolCortisol

Why does this patient have hypertension?Why does this patient have hypertension?Why is the potassium low?Why is the potassium low?

Case 3, QuestionsCase 3, Questions

What are possible causes of the problem?What are possible causes of the problem?Discuss primary causesDiscuss primary causesDiscuss secondary causesDiscuss secondary causes

How would you differentiate primary from How would you differentiate primary from secondary causes?secondary causes?

Can you illustrate the physiology of Can you illustrate the physiology of primary and secondary disease?primary and secondary disease?

Secondary AldosteronismSecondary AldosteronismSecondary aldosteronism refers to Secondary aldosteronism refers to appropriate increased production of appropriate increased production of aldosterone in response to activation of the aldosterone in response to activation of the renin-angiotensin systemrenin-angiotensin system

Primary aldosteronismPrimary aldosteronism Secondary AldosteronismSecondary Aldosteronism

VolVol

ReninRenin

AldoAldo

NaNa

VolVol

ReninRenin

AldoAldo

NaNa