Disorders of the Adrenals

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Disorders of the Adrenals
Cushings Syndrome Primary hyperaldosteronism Hi
rsuitism Adrenal failure Pheochromocytoma Incid
entaloma of adrenal
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Feedback Regulation
CRH
(-)
()
ACTH
(-)
()
Cortisol
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8. A.M Plasma Cortisol/ACTH Combination
Pit. Dependent Cushings
High Cortisol Normal ACTH
Low Cortisol High ACTH
Addisons
High Cortisol High ACTH
ACTH deficiency
Ectopic ACTH
Low Cortisol Low ACTH
ACTH deficiency
High Cortisol Low ACTH
Low Cortisol Normal ACTH
Adrenal Tumor
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Approach to Hypercortisolism
MRI Sella CT adrenal BIPSS
High Dose Dex test ACTH assay
24 hr urine Free Cortisol
Overnight Dex test
Localization
Pituitary dependent or not
Confirmation of Hypercortisolism
Screening for Hypercortisolism
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Overnght 1mg DEX test A post Dex- Cortisol of lt
1.8 mcg virtually excludes any form of
hypercortisolism
Sensitivity of Suppression 100
Specificity of Nonsuppresssion 70
However, a post Dex- Cortisol gt 5 mcg can be
seen in other situations besides true
hypercortisolism (Pseudo Cushings)
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UFC gt 4 times upper normal is Diagnostic of
Hypercortisolism
Sensitivity 90- 95
Specificity 85-90
UFC can be elevated in Depression, severe stress
and alcoholism- Pseudo Cushings Syndrome
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Etiology of Hypercortisolism
Pituitary Cushings Disease Microadenoma
Macroadenoma Hyperplasia Intermediate
lobe tumor
Adrenal Cushings Adenoma Carcinoma
Macronodular Carneys Food- Induced
Ectopic ACTH Syndrome Typical Small cell
CA Atypical Bronchial carcinoid
Etiologic diagnosis (1) High dose DEX
(2)Plasma ACTH
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High Dose Dexamethasone Test
Plasma Cortisol at 8. AM
A drop in the plasma cortisol by gt 50 is
defined as SUPPRESSION and implies ACTH
Dependency
8 mg dexamethasone before Sleep
Plasma Cortisol at 8 AM following Dex
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Pituitary Dependent
Atypical Ectopic ACTH
Suppression
Depression
Pseudo Cushings
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Adrenal Adenoma
Adrenal Carcinoma
Non Suppression
Ectopic ACTH
Large Pituitary Tumor
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Approach to Hypercortisolism
ODST
PC lt 5
PC gt 5
No Cushings
24 hr urine Free Cortisol
Normal
Elevated
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24 hr urine Free Cortisol
Suppressed (50 decline in PC post 8 mg)
Non suppression
Elevated
ACTH
ACTH
High Dose DST
N, Mild high
N High Low
MRI sella
CT adrenal
Ectopic
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34 year old lady with depression obese,
Hypertensive, easy bruisability FPG- 168
mg Plasma cortisol post ODST- 22 mcg
24 hr urine free cortisol 350 (n lt50)
Baseline cortisol - 34 mcg Post 8mg DEX
-24 mcg
Plasma ACTH - lt 8 pg
Adrenal CT - 4cm mass (Rt)
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How do you determine If the mass benign or
malignant?
DHEAS
Low DHEA-s implies benign mass and contralateral
adrenal suppression, While high DHEA-s is a
marker of adrenocortical carcinoma
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Patient with High 24 hr UFC Suppression to High
dose DXM Plasma ACTH normal Sellar MRI
normal What would you do next?
DD ACTH secreting pituitary adenoma too small to
visualise versus
Atypical Ectopic ACTH secreting Tumor usually a
bronchial carcinoid
Bilateral Inferior Petrosal Sinus Sampling
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Hyponatremia Volume Depletion
Na Retention Volume expansion
Renin
RAAS
Aldosterone
Renin Substrate
Angiotensin 1
Angiotensin 2
ACE
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THE FEED BACK LOOP
ALDOSTERONE
RENIN
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Approach to Hyperaldosteronism
Adenoma vs Hyperplasia
CT scan Bilateral adrenal vein sampling
Saline Loading Test 24 hr urine aldosterone
Confirmation
Plasma PA/PRA Ratio gt 40
Screening
Hypertension Hypokalemia with kaliuresis
Index of suspicion
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Hypokalemia with kaliuresis
All Hormonal Tests should be deferred Until the
Plasma K levels are normalized
Hypokalemia can lower aldosterone and raise PRA,
thus obfuscating the Dx
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Screening
Plasma PA/ PRA Ratio
PA/PRA Ratio lt 20
PA/PRA Ratio gt 40
Less Reliable
Secondary Hyperaldosteronism Essential
Hypertension
Primary Hyperaldosteronism
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Confirmation
Saline Loading Test
Basal Plasma Aldosterone 2 liters of Normal
Saline in 4 hrs Plasma aldosterone gt 8.5 ng
strongly favors the Dx Sensitivity of
90 Specificity of 80
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Localization
Distinction Between Adenoma vs Hyperplasia
CT scan 18-OH Corticosterone (high in
adenoma) Bilateral adrenal vein sampling
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24 year old female , chronic history of increased
hair growth on the upper lip chin and the
sideburn area. Menstrual periods have been
irregular.One normal delivery in the past. PE
unremarkable, except for coarse terminal hair
over the face. No signs of virilization Patient
is obese, no masses on pelvic exam.
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Clinical Assessment
Isolated Problem or a Package deal?
Menstrual irregularities Amenorrhea Infertility Ob
esity Diabetes
Chronic or short duration
Minoxidil Dyazoxide Dilantin Androgens
Just Hirsute, or virilized?
Progressive or stable?
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Most common cause for hirsuitism Hair follicles
hypersensitive to normal levels of androgens.
Menses normal
Most common cause for menstrual Irregularity and
hirsuitism. Hormonal evidence of elevated T, free
T or DHEAS
Late Onset Congenital Adrenal Hyperplasia. Elevate
d DHEAS and 17 hydroxy Progesterone
Rapid onset, virilization frequent
with amenorrhea T elevated TVUS often positive
Slow onset, virilization frequent
with amenorrhea DHEAS elevated CT often
positive
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Look for clues in the Lab data
Free Testosterone
Ovarian Tumors PCOS- Hyperthecosis
LOCAH Adrenal tumors
DHEA-s
LH/FSH ratio
PCOS
17-Hydroxy progesterone
LOCAH
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DHEA-s high
Testosterone high
Adrenal CT 17 HP level response to ACTH
Pelvic Ultrasound Transvaginal Ultrasound If neg,
Catheterisation of ovarian veins
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Classic algorithms-1
T gt200 ng
Arrhenoblastoma Hyperthecosis Ovarii PCOS Rest
cell hyperplasia Ectopic source
Ovarian Hyperandrogenism
Transvaginal Sonography
Venous cath study
Negative
Positive
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Classic algorithms-2
DHEA 3 X UPPER LIMITS OF NORMAL
LOCAH Adrenal tumor
Adrenal Hyperandrogenism
CT of both adrenals
17 alpha HP Response to ACTH
Unilateral mass
Negative
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Classic algorithms-3
T, Free T and DHEAS normal
LOCAH, PCOS and Idiopathic
Androstenedione
LH/FSH
17 alpha HP Response to ACTH
Elevated
Ultrasound
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Cortrosyn test for LOCAH
Normal
Pre Post Cortisol
Pre Post 17 alpha HP
LOCAH
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Adrenal Insufficiency
Clinical Suspicion often based on vague Sx
Fatigue Weight loss Weakness Anorexia,
Diarrhea Insomnia Dizziness Impotence Menstrual
Irregularities
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Specific Clues
Change in Skin Pigmentation Orthostatic
Hypotension Background Disease
Hyponatremia Hyperkalemia Hypoglycemia
Acute Adrenal Crisis- SHOCK
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Value of history in the evaluation of a
patient with adrenal failure
Prior use of steroids for long duration
Suppression of HPA axis
Current use of warfarin
Adrenal hemorrhage
Recent use of megace
Suppression of HPA axis
History of TB, fungal disease in past (Histo,
cocci, nocardia)
Adrenal destruction
History of cirrhosis, diabetes and heart disease
Hemochromatosis
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Value of history in the evaluation of a
patient with adrenal failure
History of cancer
Mets to the adrenal
Thyroid disease
Autoimmune or pituitary
ALD (Adrenoleukodystrophy)
Demyelinating disease
Anti Phospholipid syndrome
History of SLE
HIV disease
multifactorial
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Diagnosis of Adrenal Insufficiency
Screening for Adrenal Insufficiency

• Basal Cortisol level
• Cortrosyn Stim Test

Primary versus Secondary

• Aldo Response to cortrosyn
• Plasma ACTH level

Confirmation
Standard Cortrosyn Stim Test

• For Addisons
• CT adrenals
• Antibodies
• Test for PGA

Establishing Etiology

• For Hypopit
• MRI Sella
• Pit. reserve

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Pheochromocytoma
Incidence Location Mostly in adrenals Extra
adrenal Pheochromocytoma Organ of
Zuckerkandle, Chest, Carotid
body 10 rule (10 are bilateral, malignant
and extra adrenal)
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Clinical presentation of Pheo
Acute MI Cardiomyopathy tako-tsubo syndrome
Hypertension Paroxysmal Sustained Crisis in
pregnancy
Pheo
Catecholamine Crisis with triad
of Headache Sweating and Palpitation
Hypermetabolic Weight loss FUO
Panic Anxiety
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24 hr urine metanephrine normetanephrine
24 hr urine VMA
68 sensitivity When above 10 mg
specificity 100
90 sensitivity 85 specificity
Pheo
Plasma metaneprine Normeta nephrine
98 sensitivity 95 specificity
Clonidine suppression test
Plasma catecholamines
High sensitivity when plasma cats are gt2000
100 Diagnostic during crisis
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Pheochromocytoma
Paraganglionoma, malignant pheo
Pheo in a child
MEN 2 (RET proto Oncogene
Pheo with hypercalcemia
Pheo with a thyroid nodule
MEN 2 or 3 medullary CA
Pheo with only epinehrine secretion
Familial Pheo
MRI, MIBG
Imaging studies of choice
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60 yr old woman gets a CT scan done for
epigastric pain, and is found to have a 3
cm adrenal mass on the left side. The history
is negative for TB, fungal disease, or malignant
disease in the past. She is healthy, and
asymptomatic. PE is normal, with no signs of
Cushings, hirsuitism or virilization. The BP
and the electrolytes are normal.
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The best next step would be A. Measurement of
Urine metanephrines. B. MRI of the adrenal with
T1 and T2 weighted images. C.
Fine- needle aspiration of the mass. D.
Surgical excision of the mass. E. Watchful
waiting.
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How frequent are adrenal incidentalomas?
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1-3 of all people who undergo CT scans of the
abdomen
2-5 of all people with hypertension who
undergo CT scans of the abdomen
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2
Causes of adrenal masses
Benign adenomas
85
Secretory masses
Pheochromocytoma
Benign cysts of the adrenal
Myelolipoma
Adrenal hemorrhage
Infections
Lymphoma
Metastatic lesion
Adreno cortical carcinoma
2-5
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Adenoma
carcinoma
gt6 cm 24 lt 6cm
1-3 cm
Size
Shape
round
irregular
Hounsfield units
-10to 30
gt 30
smooth
irregular
Borders
Heterogenous hemorrhage
Homogenous no calcification
Interior
Minimal enhancement
Contrast
Minimal enhancement
T1 hypointense T2 iso or mildly hyperintese
T1 hypointense T2 hyperintese
MRI
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Adrenal Incidentaloma
Masses lt 1cm- Insignificant
Masses gt 4 cm- Hormonal W/u followed
by adrenalectomy
Masses 1-4 cm need workup to
(a) r/o hypersecretion
(b) r/o malignancy
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90 of carcinomas gt 4 cm
Only 12 adenomas gt 4 cm
Supporting data that incidentalomas gt 4 cm belong
in a bottle and not in the patient.
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Masses 1-4 cm need workup to
(a) r/o hypersecretion
(b) r/o malignancy
---Plasma Meta and nor metanephrine ---- 24 hr
urine metanephrine and normetanephrine Total
and fractionated catecholamines and VMA ----1 mg
overnite DEX with next day draw for
plasma cortisol, and DHEAs
49
Masses 1-4 cm need workup to
(a) r/o hypersecretion
(b) r/o malignancy
Characteristics on CT MRI for High signal on
T2 DHEA-s level NP 59 adrenal Scintigraphy
for discordance Change in size in 6 mo -1 yr
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Adrenal mass
Functioning
Non functioning
Surgery
gt 4 cm
lt 4 cm
Biopsy/ Surgery
Non contrast CT
1 hr contrast CT
CSMRI
No loss
Signal loss
HU gt30
HU lt30
HU lt10
HU gt10
Adenoma
MRI
Adenoma
MRI
Adenoma
BX