THE ROLE OF THE ROLE OF

UNILATERAL ADRENALECTOMYUNILATERAL ADRENALECTOMY IN IN

ACTH-INDEPENDENT MACRONODULAR ACTH-INDEPENDENT MACRONODULAR ADRENAL HYPERPLASIA ADRENAL HYPERPLASIA

(AIMAH)(AIMAH)

M IacoboneM Iacobone,,G Viel, S Zanella, M Frego, G Viel, S Zanella, M Frego,

G FaviaG Favia

Department of Endocrine Surgery University of Padua, Italy

Cushing’s SyndromeCushing’s Syndrome

ACTH dependentACTH dependent (80%)(80%)

PituitaryPituitary EctopicEctopic

ACTH independent ACTH independent (20%)(20%)

UnilateralUnilateral (Adenoma, Carcinoma)(Adenoma, Carcinoma)

BilateralBilateral- - PPNADPPNAD

- - ACTH-Independent Macronodular ACTH-Independent Macronodular

Adrenal HyperplasiaAdrenal Hyperplasia (AIMAH)(AIMAH)

ACTH-Independent Macronodular ACTH-Independent Macronodular Adrenal Hyperplasia Adrenal Hyperplasia (AIMAH)(AIMAH)

Slowly Progressing DiseaseSlowly Progressing Disease Mild HypercortisolismMild Hypercortisolism Bilateral MacronodulBilateral Macronoduleess

Ectopic Receptors Ectopic Receptors

(GIP, Catecholamines, LH/hCG)(GIP, Catecholamines, LH/hCG)

AIMAH - TherapyAIMAH - Therapy

Bilateral Adrenalectomy Bilateral Adrenalectomy Lifetime steroid Lifetime steroid

replacementreplacement

Octreotide Octreotide PropanololPropanololLeuprolideLeuprolide

Subtotal Subtotal

UnilateralUnilateral

Medical TreatmentMedical TreatmentEctopic ReceptorsEctopic Receptors

Partial adrenalectomiesPartial adrenalectomies

AIM of the STUDYAIM of the STUDY

Long-term results Long-term results

of of UUnilateral nilateral AAdrenalectomydrenalectomy for for AIMAHAIMAH

PATIENTS and METHODS (1)PATIENTS and METHODS (1)

Unilateral Adrenalectomy and AIMAHUnilateral Adrenalectomy and AIMAH

DIAGNOSIS:

Clinical, Laboratory, Imaging, Pathology

(n=7)Males: 2 ; Females: 5

Age: 55 yr (36 – 71)

Cushing’s Syndrome

Jan 01-Dec 05

PATIENTS ET METHODS (2)PATIENTS ET METHODS (2)

CT/MRI + I-131 norcholesterol Scintigraphy

Asymmetric involvement

Unilateral adrenalectomy

PATIENTS ET METHODS (3)PATIENTS ET METHODS (3)

• Hormonal Parameters

• Blood Pressure

• Glycometabolic Parameters

• Body Mass Index (BMI)

• Subjective Perception of Quality of Life (SF-36: MCS + PCS)

•Serum ACTH and Cortisol•UFC•Circadian rhythm•DMX suppression test

•OGTT•HbA1c

Morbidity: 0%Morbidity: 0%RESULTS (1)RESULTS (1)

CURE: 86%

Persistent hypercortisolism: 1 case

Completion contralateral adrenalectomy

•Large contralateral remaining adrenal

•Symmetric uptake at scintigraphy

RESULTS (2)RESULTS (2)

CURE: 6 PATIENTS

HORMONAL PARAMETERS

Normal range

Serum ACTH

Serum Cortisol

Urinary free Cortisol

Normal Circadian rhythm

Normal DMX suppression test

Follow-up: Follow-up: 53 months (range 27-68)53 months (range 27-68)

RESULTS (2)RESULTS (2)

CURE: 6 PATIENTS

•“Small” contralateral remaining adrenal

•Asymmetric uptake at scintigraphy

Follow-up: Follow-up: 53 months (range 27-68)53 months (range 27-68)

RESULTS (3)RESULTS (3)

PRE-OPPRE-OP POST-OPPOST-OP pp

ACTHACTH(nv 10-50 ng/L)(nv 10-50 ng/L)

77 ++ 22 2828 ++ 1111 0,00,00606Urinary Free Urinary Free CortisolCortisol

(n(nvv 28-214 nmol/day28-214 nmol/day))

12061206 ++ 10381038 5959 ++ 1166 0,040,04

HORMONAL PARAMETERS

0

200

400

600

800

1000

1200

1400

Pre-Op Post-Op

0

5

10

15

20

25

30

Pre-Op Post-Op

Pre-Op

Post-Op

UFCACTH

RESULTS (4)RESULTS (4)

PRE-OPPRE-OP POST-OPPOST-OP pp

SystolSystolic BPic BP (mmHg) (mmHg) 115252 ++ 1 155 130 130 ++ 88 0,00,00066DiastoliDiastolic BPc BP

(mmHg)(mmHg)9922 ++ 55 79 79 ++ 4 4 0,000,0011

BLOOD PRESSURE

HYPERTENSIONRECOVERY: 50%

DRUG REDUCTION: 50%

RESULTS (5)RESULTS (5)

PRE-OPPRE-OP POST-OPPOST-OP pp

OGTTOGTT ( (nnvv <7.1 mmol/L <7.1 mmol/L) ) 8.8.6 6 ++ 22 6.76.7 ++ 1 1 0,000,0055

HbA1cHbA1c (n (nvv 3,7–6,1%) 3,7–6,1%) 7.47.4 ++ 1 1%% 55..8 8 ++ 1 1%% 0,0020,002

GLUCOSE METABOLISM

DIABETESRECOVERY: 40%

DRUG REDUCTION: 40%

RESULTS (6)RESULTS (6)

PRE-OPPRE-OP POST-OPPOST-OP pp

BMI BMI (n(nvv<25 kg/mq)<25 kg/mq) 28,7 28,7 ++ 5 5 25,25,88 ++ 3,5 3,50,00,033

BODY MASS INDEX

0

5

10

15

20

25

30

35

Pre-Op Post-Op

Pre-Op

Post-Op

RESULTS (7)RESULTS (7)

SF-36 QUALITY OF LIFE

41,5

28,9

54,1

43,4

0

10

20

30

40

50

60

PCS MCS

Pre-op

Post-Op

Mental Component

SummaryPhysical Component

Summary

* p<0,01

*

*

CONCLUSIONS (1)CONCLUSIONS (1)

AIMAHAIMAHAsymmetric adrenal involvementAsymmetric adrenal involvement

““Small” remaining glandSmall” remaining gland

(case selection)(case selection)

Unilateral adrenalectomyUnilateral adrenalectomy

EFFECTIVE TREATMENTEFFECTIVE TREATMENT

Author Number of cases

Follow-up (months) Postoperative adrenal insufficiency

(length)

Outcome

Lamas [9] 4 74(range 30-137)

2 cases(60 and 14 months)

Cure of CS (4 cases)    Normalization of serum cortisol, UFC and ACTH   Abnormal circadian cortisol rhythm   Abnormal responsiveness to dexamethasone suppression test   No enlargement of the remaining gland

Vezzosi [12] 1 7 1 case(6 months)

Cure of CS    Normalization of UFC, serum cortisol   Normal responsiveness to dexamethasone suppression test

Lacroix [2, 6] 1 36 1 case(15 months)

Cure of CS    Normalization of UFC, serum cortisol   Subnormal ACTH   Abnormal circadian cortisol rhythm   No enlargement of the remaining glandSato [13] 1 8 1 case

(8 months)Cure of CS    Subnormal serum cortisol and UFC   Subnormal ACTH

Ogura [11] 1 24 - Cure of CS    Normal ACTH, serum cortisol   Normal circadian cortisol rhythm   Subnormal UFC   Unchanged BMI and BP   Improvement of glycemic control   No enlargement of the remaining gland

Imohl [10] 1 27 1 case(6 months)

Cure of CS    Normalization of serum cortisol and circadian cortisol rhythm   Abnormal responsiveness to dexamethasone suppression test   No enlargement of the remaining gland

N’Diaye [7] 1 12 1 cases(12 months)

Cure of CS    Subnormal, serum cortisol and UFC   Subnormal ACTH   Mild enlargement (3 mm) of the remaining gland

Doppmann [8] 1 64 - Cure of CS

Present series

(WJS 2008)

7 53(range 7-68)

2 cases(7 and 24 months)

Persistent CS (1 case) C Cure of CS (6 cases)    Normalization of ACTH, serum cortisol, circadian cortisol rhythm and UFC   Normal responsiveness to dexamethasone suppression test   Improvement of BP, glycemic control and BMI   No enlargement of the remaining gland

Cure of hypercortisolism Cure of hypercortisolism

BP improvement BP improvement

BMI decrease BMI decrease

Glycemic control improvementGlycemic control improvement

Quality of life improvementQuality of life improvement

CONCLUSIONS (2) CONCLUSIONS (2) Unilateral adrenalectomy for Unilateral adrenalectomy for AIMAHAIMAH