Download Adrenal Update - Southern Regional AHEC

Fayetteville VA Medical Center Grand Rounds
July 10, 2015
Adrenal Update
Stanley A. Tan
MD, PhD, MPH, DTM&H, FACE, FACC, FCCP
Endocrinologist
Objectives
After this presentation, audience should be able to:
• Evaluate and manage adrenal mass
• Evaluate and manage adrenal insufficiency
• Evaluate and manage adrenal excess diseases:
hypercortisolemia (Cushing) and
hyperaldosteronism
• Evaluate and manage pheochromocytoma
Adrenal Mass Evaluation
• Functional Evaluation
– Overnight dexamethasone suppression test
– Aldosterone level
– Fractionated catecholamines or metanephrines
• “Incidentaloma”
– Under 4 cm
– Non secreting/functioning
– Stable/non growing
Adrenal Mass Surgery Indication
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Functioning Mass
Over 4 cm
Growing Mass
Malignancy
Laparoscopic Adrenalectomy
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Tumor < 10 cm
Secreting/functioning mass
Pheochromocytoma
Non secreting mass > 4 cm
Non malignant mass
Adrenal Cortical Layers
• Zona glomerulosa: mineralocorticoids (eg
aldosterone)
• Zona fasciculata: glucocorticoids (eg
cortisol)
• Zona reticularis: adrenal sex
steroids/weak androgens (eg
dehydroepiandrosterone-DHEA)
Adrenal Insufficiency
Addison’s Disease
• Addison's disease is the result of an
underactive adrenal gland (adrenal
insufficiency).
• Four in every 100,000 people have
Addison's disease.
Etiology of Addison’s Disease
• 1/2 idiopathic
• 1/3 are caused by the actual destruction of the
adrenal glands through cancer, infection (TB), or
other diseases.
• 10% auto-immune, may be associated with other
auto-immune diseases (Schmidt’s Syndrome:
polyglandular auto-immune disease)
• Prolonged use of corticosteroids as a treatment
• Certain drugs, e.g. ketoconazole, may block
production of corticosteroids in the adrenal
glands.
Addison’s Disease Presentations
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Hyponatremia and hyperkalemia, which
cause leads to the inability to produce
concentrated urine by the kidneys, leading
to polyuria, hypotension, NVD,
abdominal pain and dehydration
Increased insulin sensitivity and decreased
gluconeogenesis, leading to hypoglycemia
Decreased body’s ability to fight infection,
and to heal
Patient is at increased risk during stressful
periods, such as surgery, infection, or
injury, which may lead to Addisonian Crisis
Addison’s Disease Symptoms
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Weakness
Fatigue
Dizziness
Dark skin
Bluish-black discoloration around the nipples, mouth,
rectum, scrotum, or vagina
Weight loss
Dehydration
Lack of appetite
Muscle aches
Nausea, vomiting, diarrhea
Cold intolerance
Diagnostic Test for Addison’s
• Cosyntropin stimulation test:
–Basal cortisol
–0.25 mg cosyntropin IV or IM
–1-hr post cortisol level
–Rise of 7 mg/dl above basal with
final value of > 15 mg/dl
Laboratory Tests for Addison’s
• Blood sugar
• Electrolytes (sodium & potassium) and
Osmolarity:
– Serum Na, K, Osm
– Urine Na, K, Osm
• Increased creatinine
• TSH & free T4
Management of Addison’s
• Corticosteroids:
– Acute full stress dose: Hydrocortisone 100 mg IV q8h
– Physiologic replacement equivalents:
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Cortisone acetate 25 mg qAM 12.5 mg qPM
Hydrocortisone 20-10
Prednisone 5-2.5*
Methylprednisolone 4-2*
Dexamethasone 0.75-0.375*
*+ Fludrocortisone
• Fluid/electrolytes replacement
• Glucose
• Treat underlying diseases
Over-active Adrenal Glands
• Excess glucocorticoids
• Excess mineralocorticoids
• Excess adrenal androgens
Excess Glucocorticoids
• Cushing Disease:
– ACTH producing pituitary tumor
– Adrenal hyperplasia
– Ectopic ACTH
• Cushing Syndrome
– Adrenal tumors
– Adrenal hyperplasia
– Exogenous corticosteroids
Excess Mineralocorticoids
• Conn disease: Aldosteronoma
• Certain salt-retaining adrogenital
syndrome
• Exogenous mineralocorticoids
Cushing’s Symptoms-1
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Upper body obesity
Round face
Increased fat around neck
Thinning arms and legs
Fragile and thin skin
Stretch marks on abdomen, thighs,
buttocks, arms, and breasts
• Bone and muscle weakness
Cushing’s Symptoms-2
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Severe fatigue
High blood pressure
High blood sugar
Irritability and anxiety
Excess hair growth in women
Irregular or stopped menstrual cycles in
women
• Reduced sex drive and fertility in men
Diagnostic Tests for Cushing
• Screening
– 24-h urinary Free Cortisol
– Overnight dexamethasone suppression test:
• Dexamethasone 1 mg (2x0.5 mg) po at 11PM
• Cortisol at 8 AM the next morning: normal <5 mg/dl
• Specific steroids assay
– Serum & urine
• CRH stimulation test
• Imaging
– CT and MRI
Treatment for Cushing
• Depends upon etiology
• Surgery to remove tumors or the
adrenal glands.
• Other treatment may include
radiation, chemotherapy, and use of
certain hormone-inhibiting drugs
(opDDD, mitotane, metyrosine)
Excess Mineralocorticoids
• Conn’s Syndrome—hyperaldosteronism
– Aldosteronoma
• Secondary hyperaldosteronism—Renal
artery stenosis (hyper-reninemia)
– Increased PRA
• Certain salt retaining andrenogenital
syndrome
• Exogenous
Hyperaldosteronism
• Conn’s Syndrome (Primary
Hyperaldosteronism):
– Elevated serum or urine aldosterone level
– Suppressed plasma renin activity (PRA)
– Not suppressed by captopril:
• Captopril 25 mg po
• Aldosterone level 2 h later
• Secondary hyperaldosteronism
– Increased PRA
– Aldosterone suppressed by captopril
Hyperaldosteronism
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Hypertension
Hypernatremia
Hypokalemia
Normal blood sugar
No Cushingoid features
No hyperpigmentation or striae
No hirsutism or virilization
Hyperaldosteronism
• Aldosteronoma
– Adrenal tumor on MRI or CT
– Adrenal vein sampling for aldosterone & PRA
• Right & left adrenal veins
• Superior & inferior vena cava
• Renal artery stenosis—secondary
hyperaldosteronoma
– Adrenal arteriogram
– Adrenal vein sampling for PRA & aldosterone
Treatment for Hyperaldosteronism
• Medical:
– Spironolactone
– ACE inhibitor
– ARB
– Eplerenone
• Surgical:
– Aldosteronoma resection
– Renal artery angioplasty/stent
Pheochromocytoma
• Catecholamine producing tumors:
– Adrenal medulla pheo: Excess epinephrine
– Ganglion tumor: Excess norepinephrine
• Associated with other neuro-ectoderm
tumors:
– MEN type II (Sipple Syndrome)
– PTC: Pheochromocytoma, Thyroid medullary
CA, Parathyroid tumor
– Neurofibromatosis
Pheochromocytoma Sign/Symptom
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Headaches (severe)
Excess sweating (generalized)
Racing heart (tachycardia and palpitations)
Anxiety / nervousness (feelings of impending
death)
Nervous shaking (tremors)
Pain in the lower chest or upper abdomen
Nausea (with or without nausea)
Weight loss
Heat intolerance
Who should be evaluated for
Pheochromocytoma?
• Patients with very difficult to control hypertension
• Patients requiring more than 4 blood pressure
medications
• Patients with onset of hypertension before the
age of 35
• Patients with onset of hypertension after the age
of 60
• Patients with signs or symptoms of
pheochromocytoma
Diagnosing Pheochromocytoma
• 24-h urinary fractionated metanephrines &
catecholamines
• Plasma fractionated catecholamines (epinephrine,
norepinephrine, dopamine)
• Phentolamine test
• Clonidine suppression test
– Basal fractionated catecholamines
– Clonidine 0.3 mg po
– 2-h later: Another (suppressed) fractionated catecholamines
• MRI
• Octreoscan/MIBG
Treatment for Pheochromocytoma
• Medical
– Dibenzylin
– Clonidine
– Alpha and beta blockers
• Surgical
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Standard trans-abdominal
Thoraco-abdominal
Posterior
Retroperitoneal
Laparoscopic