endocrine physiology: case studies in adrenal disorders c.w. spellman, phd, do assoc. prof. medicine...
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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