Transcript Adrenal Disease

Adrenal Disease
Jennii Stephens, PA-C
Diseases of the Adrenal Gland
 Anatomy

and Physiology
Decreased adrenal function

Cortex
• Addisons Disease
• Secondary hypoadrenalism (pituitary dysfunction)

Increased adrenal function

Cortex:
• Cushings Syndrome/Disease
• Conn Syndrome

Medulla: Pheochromocytoma
Adrenal Gland
Adrenal Anatomy
“salt”
“sugar”
“sex”
“GFR”—salt, sugar, sex, the deeper you go the sweeter it gets
Adrenal Cortex Layers

Glomerulosa

Mineralocorticoids, aldosterone
• maintains sodium and potassium water balance via the
distal tubules of the kidney

Fasciculata

Glucocorticoids, cortisol
• regulates carbohydrate, protein and fat metabolism
Adrenal Cortex Layers


Reticularis

Androgens and estrogens

These are produced in far greater abundance in gonads
No other tissues have the capability of producing
either mineralocorticoids or glucocorticoids
Adrenal medulla

Inner portion of adrenal gland
 Secretes epinephrine and norepinephrine
 Acts to reinforce activity of the sympathetic
nervous system
 Not vital to life (its absence does NOT cause
disease)
Mineralocorticoids
 Aldosterone
 Site
of action is distal tubules of kidney
 Retain Nablood volumeblood
pressure
 Crucial for sodium conservation in




Kidney
Salivary glands
Sweat glands
Colon
 Absolutely
essential for life
Aldosterone regulation
 BP
Direct renin inhibitor
(Tekturna, aliskiren)
Renin
Angiotensinogen
Angiotensin I
ACE
ACE inhibitors (‘pril’:
lisinipril, captopril…)
Angiotensin II
ALDOSTERONE
 Na reabsorption
 Blood volume
Angiotensin receptor
blocker (ARB),
(‘sartan’: valsartan,
losartan…)
 BP
Glucocorticoids (cortisol)






blood glucose
 hepatic gluconeogenesis
 glucose uptake and use by many tissues, but
not the brain
 protein degradation which frees amino acids for
gluconeogenesis
 lipolysis, releasing fatty acids which can act as
an alternative metabolic fuel for tissues
Frees glucose for brain usage
 Anti-inflammatory

and immunosuppressant
Synthetic forms maximize these characteristics
allowing us to use them clinically
Pituitary-Adrenal Axis
Glucocorticoids (cont)
 Secretion
of cortisol is controlled by ACTH from
the anterior pituitary


pro-opiomelanocortin is broken down to form ACTH
and melanocyte-stimulating hormone (MSH)
Thus, high ACTH means high MSHincreased skin
pigmentation
Androgens
 Produced
by the
zona reticularis
 Primary area of
androgen production
in women
Diseases of the Adrenal Gland
 Anatomy

and Physiology
Decreased adrenal function

Cortex
• Addisons Disease
• Secondary hypoadrenalism (pituitary dysfunction)

Increased adrenal function

Cortex:
• Cushings Syndrome/Disease
• Conn Syndrome

Medulla: Pheochromocytoma
Primary v Secondary
 Primary

disease
Pathology at the organ
 Secondary


disease
Pathology somewhere other than the organ
The organ has the ability to function normally
Addison’s
 1-4
in 100,000 people
 Most common in adults 30-50 yo
 Primary hypoadrenalism

Pay attention to the distinction between primary
and secondary characteristics
Pathophysiology of Addisons


Due to destruction of >90% of bilateral adrenal cortices
(80% of cases)
Types

Usually autoimmune
• Can be associated with other autoimmune diseases (Graves, type I DM,
pernicious anemia…)
• Takes months to years to destroy this much cortex






Thrombosis
Hemorrhage
Infectious causes (HIV, Tb, fungal…)
Cancer
Certain drugs
Affects both glucocorticoid and mineralocorticoid function
Pathophysiology of Secondary
hypoadrenalism

Due to lack of ACTH



Results in deficiency of cortisol
Thus, aldosterone is NOT affected
Causes





Pituitary disease, such as tumor
Prolonged use of steroid medication is discontinued
without appropriate taper
Infection
Head trauma
Pituitary infarction (Sheehan’s syndrome)
Effects of low aldosterone
Addison’s disease

Na excretion
  K secretion
 Thus,
get rid of Naget rid of
watervolume depletionlow BP
Effects of cortisol deficiency
Addison’s disease or Secondary hypoadrenalism
 Carbohydrate
metabolism disturbed
 Hypoglycemiaweakness
 Addison’s disease


ACTH is increased in response to low cortisol
This stimulates MSH (melanocyte stimulating
hormone)hyperpigmentation
Chronic presentation
 Hyperpigmentation
of skin and mucous
membranes


Caused by ACTH stimulatory effect on
melanocytes
Most prominent on
• sun-exposed areas
• Knuckles, elbows, knees and new scars
• Palmar creases, nail beds, oral cavity, vaginal and
perianal mucosa
Hyperpigmented fingers and
nails
Fingers of a 28-year-old white woman with Addison's disease (underneath) compared to
those of a normal woman (top). There is hyperpigmentation of the skin and increased
pigmentation of the distal half of the nails that occurred during the period of adrenal
insufficiency. The proximal half of the nails are hypopigmented, a reflection of the reduction
in ACTH secretion after the institution of glucocorticoid therapy. Courtesy of David N Orth,
MD.
A
Caucasian
Addison’s
patient
Hyperpigmented
scars
Chronic presentation









Progressive weakness
Chronic, worsening fatigue
Poor appetite, craving of salty foods
Weight loss
Hypotension (Addison’s)
GI symptoms (n/v/d)
Dizziness (orthostatic hypotension)
Irritability and depression
Myalgia and flaccid muscle paralysis (from
hyperkalemia)  decreased/absent reflexes

Addison’s disease only
Chronic presentation
 Men


Impotence
Decreased libido
 Women


Decreased body hair (from decreased
androgens)
Irregular menses or amenorrhea
• Due to chronic ill health/ weight loss/ autoimmune
destruction of ovarian tissue
Lab Studies

BMP

Hyponatremia, Hyperkalemia, Mild non-anion gap
metabolic acidosis (Addison’s only)
• due to lack of sodium-retaining and potassium and hydrogen
ion-secreting action of aldosterone

Elevated BUN and creatinine (Addison’s only)
• due to hypovolemia, a decreased GFR, and decreased renal
plasma flow


Hypercalcemia (unknown mechanism)
Hypoglycemia (Both primary and secondary dz)
• Caused by increased peripheral utilization of glucose and
increased insulin sensitivity

Urinary and sweat sodium elevated (Addison’s only)
Diagnosis of Adrenal Insufficiency

ACTH stimulation test (Cortrosyn)

1.
2.
3.
4.



Assesses functional capacity of adrenal glands to
make cortisol
Draw cortisol level
Inject ACTH
Wait 30-60 minutes
Draw cortisol levels
If normal adrenal functionhigher cortisol
If abnormal adrenal functionno change
If secondary diseasecan be no change to
higher levels depending on the chronicity of the
disease
Imaging Studies
 CT—depends



on cause
Infectious—will often show enlarged adrenals
TB, histoplasmosis—calcification of adrenals
Autoimmune—atrophic adrenals
Other studies
 EKG—changes
due to hyperkalemia
Acute presentation
Addisonian Crisis
 Prominent
n/v
 Vascular collapse (shock)
 Confused
 Cyanotic
 Hyperpyrexia (may reach 105ºF)
 Abdominal
symptoms may appear like an
acute abdomen
Acute causes


Stress (infection, trauma, surgery, emotional turmoil)
with failure to increase steroids in patient with chronic
Addison’s
Abrupt cessation of chronic oral steroids


Bilateral adrenal hemorrhage


Fulminant meningococcemia
Bilateral adrenal artery emboli


COPD patient
Sepsis, DIC
Medications: rifampin, ketoconazole, phenytoin
Treatment of Acute Adrenal Crisis
 Begin
immediate treatment with salt, fluids
and glucocorticoids
 draw random plasma cortisol level (before
any glucocorticoids given)
Treatment
 Replace

cortisol
Acute adrenal crisis: IV
• Clinical improvement (BP response) should be
seen within 4-6h of tx
• Taper dose after response

Chronic
• Daily oral replacement of both mineralocorticoid
and corticosteroid
• For lifetime (can’t ever stop)
• Will have to increase doses during periods of
stress
Chronic meds
 Hydrocortisone




Drug of choice for acute and chronic tx in
Addison’s
Has both glucocorticoid and mineralocorticoid
properties
Titrate to patient’s general well being and
presence of symptoms
Patients should be told to double or triple their
steroid replacement doses in stressful
situations (common cold, tooth extraction…)
Chronic Meds (cont)
 Fludrocortisone




Very potent mineralocorticoid
Oral med
Titrate to maintain normal BP, Na, and K
levels
No dose adjustment in stressful situations
Miscellaneous
 Should
consult endocrinologist
 Patient should wear medical ID bracelet
 Prognosis: with adequate therapy, normal
lives
Diseases of the Adrenal Gland
 Anatomy

and Physiology
Decreased adrenal function

Cortex
• Addisons Disease
• Secondary hypoadrenalism (pituitary dysfunction)

Increased adrenal function

Cortex:
• Cushings Syndrome/Disease
• Conn Syndrome

Medulla: Pheochromocytoma
Cushings




13 per million patients
Usually due to exogenous glucocorticoids
5 women:1 man
Usually 25-40 yo

Two distinctions:


Syndrome--A group of conditions caused by
increased production of cortisol hormones or by the
administration of glucocorticoid hormones
Disease—a form of Cushing’s syndrome caused by
an ACTH-secreting pituitary tumor
Presentation
 Increased




adipose tissue
moon facies
buffalo hump (on upper back at base of neck)
supraclavicular fat pads
truncal obesity
 facial
plethora (flushed)
 purple striae


usually >1cm in width
Most commonly abdomen, buttocks, lower
back, upper thighs and arms, breasts
Moon Facies
30-year-old woman with Cushing's disease showing round,
plethoric "moon" face, facial hirsutism, and increased
supraclavicular fat pads. Williams Textbook of Endocrinology, 8th
ed, Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia,
1996.
Moon
facies
Buffalo hump
Striae
Signs/ Symptoms
SKIN
Striae
CARDIOVASCULAR
Hypertension
Edema
Atherosclerosis
GI
Peptic ulcers
ENDOCRINE
Hypothyroidism
Galactorhea
Menstrual irregularities
MUSCULOSKELETAL
Proximal muscle weakness
Osteoporosis
PSYCHOLOGICAL
Emotional lability
Fatigue
Depression
Pathophysiology
 Caused

by excess levels of cortisol
Exogenous
• Most common cause
• Usually from oral steroids

Endogenous
•
•
•
•
Tumors of the adrenal gland
Mets
Cushing’s Disease—pituitary tumor
Lung cancer
Lab Studies
 24h



Urinary Free Cortisol (UFC) test
Screening test
Indicator of overall daily cortisol production
Values >3X upper normal suggest Cushings
 Why
do we not check random serum
cortisol?

Because it fluctuates too much
Lab Studies
 Tests


to determine cause
Serum ACTH
Overnight dexamethasone suppression test
Other lab signs of Cushings



Leukocytosis
Elevated fasting glucose
Low potassium (if adrenal adenoma secreting
aldosterone)
Imaging
 Only

after lab screening tests
Why? 10% incidence of nonfunctioning
pituitary or adrenal adenomas
 CT
abdomen (if suspect primary adrenal
problem)
 MRI pituitary (if suspect pituitary problem)
Treatment
 Dependent
on the cause
 Exogenous steroid

Reduce the cortisol to lowest possible amount
 Endogenous


steroid
Surgical resection of causative tumor
Ketoconazole: inhibits key steps in
mineralocorticoid and glucocorticoid synthesis
Other considerations
 Pts

on steroids > 4-6wks
Need meds to prevent bone loss
Surgery Results
Before
After
Hypercortisolism
 Stress






response
Women in last 3 months of pregnancy
Athletes during times of intense training
Depressed patients
Alcoholics
Malnourished patients
Panic disorder
Diseases of the Adrenal Gland
 Anatomy

and Physiology
Decreased adrenal function

Cortex
• Addisons Disease
• Secondary hypoadrenalism (pituitary dysfunction)

Increased adrenal function

Cortex:
• Cushings Syndrome/Disease
• Conn Syndrome

Medulla: Pheochromocytoma
Conn Syndrome

Primary hyperaldosteronism
 Up to 1% of HTN pts
 Characterized by



Causes



HTN
Hypokalemia (fatigue, muscle cramps, h/a,
palpitations)
Adenoma or cancerous growth
Hyperplasia
Treatment depends on the cause
Diseases of the Adrenal Gland
 Anatomy

and Physiology
Decreased adrenal function

Cortex
• Addisons Disease
• Secondary hypoadrenalism (pituitary dysfunction)

Increased adrenal function

Cortex:
• Cushings Syndrome/Disease
• Conn Syndrome

Medulla: Pheochromocytoma
Pheochromocytoma






Rare catecholamine-secreting
tumor from the adrenal gland
1-8 cases per million persons
Up to 0.2% of hypertensive
individuals
10% of these are
malignantmaking the diagnosis is
critical
Occurs in all races and equally
among sexes
Peak incidence is between 3rd and
5th decades
Pathophysiology
 Due
to excess catecholamines
(epinephrine and norepinephrine)
 Elevated blood pressure
 Increased cardiac contractility
 Elevated heart rate
 Glycogenolysis
 Gluconeogenesis
Rule of 10s
 10%
are bilateral
 10% occur in children
 10% are outside the adrenal glands
 10% are familial
 10% without blood pressure elevation
 10% are malignant (may be closer to 25%)
Clinical Presentation

Spells with





headache
palpitations
diaphoresis
in association with severe hypertension
Spells


may occur monthly to several times a day
Duration of spells may be seconds to hours

With time, spells worsen in severity and become
more frequent

May present in association with Von-hippel Lindau,
Neurofibromatosis, and MEN II syndrome
Lab Studies
A


24hour urine collection for
vanillylmandelic acid (VMA)
Metanephrines
Indications for workup
 HTN
refractory to multiple meds
 Wide swings in blood pressure
 Unexplained spells of dizziness
 Orthostatic hypotension in the absence of
medication
 Family history of pheochromocytoma
 Incidental adrenal mass (4-6.5% of
patients with adrenal mass will have pheo)
Imaging

90% are in adrenals,
98% in abdomen and
pelvis
 Once found, may
want to rule out
familial syndromes
Treatment

Alpha and beta-blockade prior to surgery
 Surgical resection usually results in resolution of htn
Case Presentation 1

42yo male presented to his PCP for


fatigue (increasing and worse later in the day)
weight loss (40lb over 5yr)

Previous episodes of fatigue were attributed to
hypothyroidism due to increased TSH and his
levothyroxine was increased.
 PE




Patient appeared ill
BP 96/66
Generalized hyperpigmentation of sun-exposed areas
f/u 2 mos later, same hyperpigmentation with BP of
80/74, weight stable
Case 1 (cont)
 Lab





Na 127 (136-142)
Chloride 93 (96-106)
TSH 12.4 (0.5-5.0)
CBC nl
Morning cortisol 1.5 (6-24)
 What
are you suspicious of?
 Addison’s disease
Questions


What test should be ordered?
ACTH stimulation test

Results revealed cortisol levels less than 1 with NO response to
ACTH

Outcome: patient was placed on hydrocortisone and
referred to endo. 1 month later was seen for follow-up,
BP had improved to 92/62, he reported feeling better,
was able to ‘play football with my son for the first time in
years’, and had gained 9 pounds.

What etiology do you suspect with both thyroid and
adrenal hypofunction?
Autoimmune destruction

Case presentation 2





A 43-year-old white man presents for evaluation of a 2
year history of recurrent episodes of palpitations,
diaphoresis, headache, and acute anxiety
Admitted for a-fib which resolved with medical
treatment
Over 2 years, the attacks became more frequent
increasing to two times per week.
During asymptomatic times, his BP was nl.
During one episode in the office, his blood pressure
was 200/120 which resolved as his sxs resolved.
Questions
 What
test should be ordered?
 Urine VMA and metanephrines

The results reveal elevated levels of both
 What
further testing should be done?
 Abdominal CT/MRI

Abdominal CT reveals a large complex right
adrenal mass
Questions

What is the diagnosis?
 Pheochromocytoma

What is the treatment?
 Surgery

Outcome: this patient had complete resolution of
symptoms with alpha and beta blockade prior to
surgery. His HTN and symptoms were
completely resolved without medicine following
surgical removal of the benign tumor.
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Update on Risk Groups, Diagnosis, and Management”