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Adrenal Disorders PDF
Adrenal Disorders PDF
31 Adrenal Disorders
Dr: Fawaz Ammari
St: Alaa Samarah
12 / 11 / 2007
The adrenal gland and its disorders need tow lectures to be completely covered, but the doctor
compress this lecture to discuss the most important things about it.
Adrenal
There are two adrenal glands that located in retroperitoneal cavity and set
on the superior poles of the kidney
Each about 5 grams
o Larger at birth (5-10g)
o Susceptible to hemorrhage
o Regresses over 6 weeks
Up to 5 cm long, 3 cm wide
Venous return
o Right: directly into posterior IVC
o Left: to left renal vein then to Inferior phrenic vein
Lymphatics
o Paraaortic nodes
Nerve supply
o Medulla innervated mainly by sympathetic from T10-L1
o Cortex has no innervation
Cholesterol
Cholesterol desmolase
17-hydroxylase
Pregnenolone
17-Hydroxypregnenolone
17,20 lyase
DHEA
3 hydroxysteroid
dehydrogenase
Progesterone
17-Hydroxyprogesterone
Androstenedione
21-hydroxylase
11-Deoxycorticosterone
11-Deoxycortisol
Testosterone
11-hydroxylase
Corticosterone
Cortisol
Estradiol
Aldosterone synthase
Aldosterone
Aldosteron
Renal juxtaglomerular cells secrete renin in response to a decrease in circulating
volume and/or a reduction in renal perfusion pressure. Renin is the rate-limiting
enzyme that cleaves angiotensinogen to the angiotensin I. Angiotensin I is rapidly
converted to the angiotensin II by angiotensin-converting enzyme (ACE) in the
lungs. Angiotensin II has effects:
1) Is a potent vasopressor.
2) Stimulates aldosterone production (but does not stimulate cortisol
production).
So, the renin-angiotensin-aldosterone system is the major regulator of aldosterone
secretion.
Regulators of aldosterone secretion are:
1) Angiotensin II is the predominant regulator and stimulates aldosterone
secretion as we mention.
2) Hyperkalemia; stimulates aldosterone secretion.
3) Hypernatremia; suppress aldosterone secretion, so if we give large amount of
normal saline the aldosterone level will decrease.
4) ACTH levels also have very minimal influence on aldosterone secretion.
Binding of aldosterone to the mineralocorticoid receptor leads to:
1) Sodium reabsorption in distal tubule Fluid absorption
2) Potassium excretion.
3) Hydrogen Ion excretion by the renal tubules.
The resultant increase in plasma Na+ and decrease in plasma K+ provide a
feedback mechanism for suppressing renin and, subsequently, aldosterone
secretion.
When aldosteron production falls too low, the kidneys are not able to regulate salt
and water balance, causing blood volume and blood pressure to drop.
Aldosteron secreted in cascade of Renine (angiotensin1) (angiotensin 2)
aldosteron, and the stimulus of this cascade is hypotension (low renal blood flow),
hyponatremia, and hyperkalemia.
Hyperaldosteronism
There are two types of Hyperaldosteronism (excessive secretion of aldosterone)
1. Primary Hyperaldosteronism (conns syndrome); the primary has a problem
in the gland cortex (such as adenoma or carcinoma) that will secrete high
level of aldosteron which associated with low renine.
2. Secondary Hyperaldosteronism; here the problem not lodge in adrenal cortex
but it is due to hypersecreation of renin, and the elevated level of renin end
with hyperaldosteron.
Causes
1) Adenoma:
o Is the most common cause and accounts for about 80%.
o Female affected more than male and the age of onset between 4th5th decades of life
2) Bilateral adrenal hyperplasia
3) Adrenocortical carcinoma (rare)
4) Glucocorticoid remedial aldosteronism
o Aldosterone producing adenoma
o Responsive to renin
Diagnosis
History;
If young patient come with hypertension and manifestations of
hypokalaemia this will give high suspicion of hyperaldosteronism and
we need to prove that by biochemical lab tests.
Laboratory;
1) Low serum K+ (<3.0)
2) Serum aldosterone is high, and we try to suppress this level by
giving normal saline to the patient, and if there is no response
(suppression) this mean that is a primary problem which also
diagnosed if aldosteron level >14 micrograms/d
o In the primary Hyperaldosteronism we lose the laying/standing
elevation of aldosteron bcoz its already elevated.
3) Serum renin
o If >1.0 then unlikely primary hyperaldosteronism
After that we try to interpret the results:
Elevated aldosterone and elevated renin there is secondary
hyperaldosteronism (something wrong out of adrenal gland).
Elevated aldosterone and low renin there is primary
hyperaldosteronism (the problem within the adrenal gland).
After doing the lab tests and confirm the primary elevation of aldosteron we
must do localization by imaging studies.
Imaging studies
1. CT scan with thin cuts through adrenal (most important and enough)
2. MRI (less sensitive)
3. Adrenal scintigraphy (less accurate)
4. Adrenal vein sampling
o Gold standard
o Measure selective aldosterone levels which elevated on side of
adenoma and suppressed contralateral side.
Treatment
Medical: for Control HTN and correct electrolytes, so we give spironolactone
(aldosteron antagonist), amiloride (k+ sparing agent)
Better for bilateral adrenal hyperplasia
Prepare for surgical treatment
Gynecomastia (with spironolactone)
Surgical: for remove the localized lesion (adenoma/carcinoma)
We may treat the adenoma but the HTN is persist (not cure) in
20-25% of patients, bcoz of chronic changes that develop the
secondary HTN to primary HTN.
Epidemiology
Incidence is 2/1 000 000 population (rare), and the exogenic cause is more
than endogenous cause.
The most common cause of cushing is iatrogenic.
Female : Male 3-15 : 1
Onset at 20-40 years old
Manifestation of Cushing
Those due to changes in protein and fat metabolism;
Central obesity
Moon face
Buffalo hump
Thin skin (paper-like skin) and easy bruising due to rupture of elastic
tissues of skin, this mean that any minimal trauma may cause skin
ecchymosis.
Osteoporosis
Diabetes (polyuria and polydypsia)
Those due to changes in sex hormones;
Hirsutism (Excess hair growth in female mainly on face)
Irregular menstrual periods
Problems conceiving; mean the female has problem in pregnancy.
Impotence in male
Those due to salt and water retention;
High blood pressure
Typically, patients will have some, but not all, of
Fluid retention
the clinical manifestations of Cushing syndrome.
Diagnoses: by;
1. History;
Weight gain and fatigue.
Polyuria and polydypsia Diabetes.
Infertility and impotency.
Cachexia and loss of appetite tumor (Adrenal carcinoma).
2. Physical exam;
The diagnosis of Cushing
Obesity.
syndrome is principally clinical.
Proximal muscle weakness.
After taking history and doing Physical exam, if the patient has high suspicion of
Cushing we must improve that by measuring cortisol level in both blood and urine.
3. Investigations: there are 3 stages to investigate the patient with Cushing;
a. Screening.
b. Confirmation of the Diagnosis.
c. Differentiation of the Cause.
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Laboratory Features
1)
2)
3)
4)
5)
6)
7)
8)
2.
Pseudo-Cushings disease
Mimic clinical signs and symptoms
Non-endocrine causes;
o Alcoholism
o Major depression
o Morbid obesity
o Acute illness
Treatment:
1) Surgical treatment:
o Surgical treatment of Cushings disease
1. Transphenoidal hypophysectomy
>90% cure rate 1st time, 50% salvage cure 2nd attempt
Exploration even if no obvious adenoma
Complications:
A. Transient postoperative diabetes insipidus.
B. Adrenal insufficiency.
C. CSF rhinorrhea.
D. Meningitis.
2. Transphenoidal irradiation of adrenal gland.
High success rate in kids (80%)
Low success in adults (20%)
3. Bilateral adrenalectomy
Bilateral adrenalectomy was done in the past in any patients with
Cushings disease (be careful, Cushings disease mean that there
is pituitary adenoma, while the adrenal glands are completely
normal) but nowadays it is done only If pituitary surgery failed.
Life-long steroid replacement therapy will be required.
If bilateral adrenalectomy done, sudden and extreme drop of
cortisol level will occur, so the negative feedback effect of cortisol
on pituitary gland will canceled and Rapid growth of pituitary
adenomas occur this is called Nelsons syndrome.
Nelsons syndrome
o Rapid post-operative growth of ACTH-secreting pituitary
adenomas that can be invasive.
o Occur in 10-20% in patients with bilateral adrenalectomy.
o Sever and universal hyperpigementation of the body is one of
the manifestations of Nelsons syndrome.
o Preoperative irradiation decreases incidence.
o Surgical treatment of Adrenal lesions/carcinoma
Removal of primary lesion
Survival based on underlying disease
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ADRENAL INSUFFICIENCY
Adrenal insufficiency is categorized as primary, secondary or tertiary.
1) Primary (Addisons disease): results from destruction or impairment of
the adrenal cortex
o Thomas Addison described this rare condition in his classical
monograph published in 1855.
o Incidence: 0.8 cases per 100,000
o Prevalence: 4 to 11 cases per 100,000
o Mean age of diagnosis: 40 years
2) Secondary (Central): results from reduced ACTH secretion by the
pituitary gland
3) Tertiary: results from failure of the hypothalamus to produce CRH
(corticotrophin-releasing hormone)
Etiologies:
Primary Insufficiency (Addisons disease):
1. Autoimmunity
Autoimmune Polyglandular Syndrome; this syndrome has two types;
Type I: Addison's disease, chronic mucocutaneous candidiasis,
hypoparathyroidism.
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2.
3.
4.
5.
6.
7.
8.
Worldwide, tuberculosis is the most common cause, and in the industrialized nations,
idiopathic or autoimmune adrenal destruction is the most common cause.
Secondary Insufficiency
1. Sudden cessation of exogenous glucocorticoid therapy
Such therapy suppresses HPA axis with adrenal atrophy
Deficiency should be suspected if patient taking > 30mg/d
hydrocortisone (7.5mg/d prednisone or 0.75mg/d dexamethasone)
for >3 weeks followed by sudden cessation.
2. Failure to give stress steroids
3. Inadequate ACTH production
Usually other pituitary hormones deficient, and patients present with
partial or complete hypopituitarism (pan-hypopituitarism)
Isolated ACTH deficiency rare
o Lymphocytic hypophysitis
o Abnormal post-translational processing of POMC to ACTH
4. Removal of ACTH-secreting pituitary adenoma
Function of normal corticotrophs suppressed
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Headaches and visual symptoms may occur in patients with pituitary adenoma
due to increased intracranial pressure and compression on optic chiasm.
Adrenal Crisis
It is top emergency condition that the patient present with shock state, so any
patient comes with shock symptoms and sighs we should think with Adrenal
Crisis after exclusion of anaphylactic, cardiogenic and septic shock.
Manifestations:
Dehydration, hypotension, or shock out of proportion to severity of current
illness
Nausea and vomiting with a history of weight loss and anorexia
Abdominal pain, so-called acute abdomen
Unexplained hypoglycemia and fever
Hyponatremia, hyperkalemia, azotemia, hypercalcemia, or eosinophilia
Hyperpigmentation or vitiligo
DIAGNOSIS
If there is any suspicion of adrenal insufficiency we need to prove that
biochemically;
Basal Cortisol Level
o Avoid random level: low sensitivity
o Check morning cortisol
Greater than 18 g/dL indicates an intact axis
Less than 3 g/dL strongly suggests insufficiency
No further tests
o Intermediate values: perform cosyntropin stimulation test
There are two stimulation tests; tests that induce cortisol secretion:
1. High-Dose Cosyntropin (ACTH) Stimulation Test
This is the most specific test for diagnosing Addison's disease.
Intramuscular or intravenous administration of 250 g of cosyntropin
(exogenous ACTH) then Plasma cortisol levels are measured at 30 and 60
minutes:
o Normal response: peak plasma cortisol level > 18 g/dL
o Subnormal response: peak plasma cortisol level < 18 g/dL, and
this occur in patient with adrenal insufficiency.
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NOTE: any patient with Addison disease should have wristlet in his hand labeled
by THIS PATIENT ON STEROID REPLACEMENT THERAPY to be dealt carefully by
physicians.
2. Glucocorticoids replacement therapy in chronic adrenal insufficiency:
The aim is to mimic the normal cortisol secretion rate
Most patients can cope with less than 30mg/d of hydrocortisone (usually
15 to 25 mg/day in divided doses)
Doses are usually given on wakening, with a smaller dose in the late
afternoon
Decisions about doses of replacement therapy are largely based on end
points such as weight, well-being, and blood pressure.
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Autopsy series is about 1%; this mean that if we have 100 patients with
hypertension we will find 1 of them has pheochromocytoma.
This tumor secrete;
1. Norepinephrine.
2. Epinephrine.
3. Dopamine and other neurohormones; Rarely
Presentation
Hypertension;
o Sustained hypertension
o Sustained hypertension with paroxysm
o Paroxysmal hypertension with intermittent normotension
Flushing
Raynauds phenomenon
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Diagnosis
1. 24hr urinary catecholamines (Norepinephrine, Epinephrine, Dopamine) and
metabolites (metanephrine, normetanephrine, VMA)
2. Plasma catecholamine or metabolites during episode
o Elevated serum epinephrine suggests pheochromocytoma in medulla or
organ of Zukerkandl
Before the surgical procedure about 1-3 wks, -adrenergic antagonist (such
as Phenoxybenzamine, CCB or ACEI)
should be used to avoid
intraoperative hypertensive crisis
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Good luck
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