ghazal Each Adrenal gland lie superior to each kidney Pyramidal in shape 3 5 cm in height 3 cm in width less than 1 cm thick Mass 35 5 g Gland differentiate in two distinct regions ID: 908248
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Slide1
Adrenal disease
Dr.
bandar
ghazal
Slide2Each Adrenal gland lie superior to each kidney .
Pyramidal in shape .
3- 5 cm in height , 3 cm in width , less than 1 cm thick
Mass 3.5 - 5 g
Gland differentiate in two distinct regions
large ( 80 % ) cortex ( mesoderm )
Small ( 20 % )medulla (ectoderm )
Capsule covering the gland
Highly vascularized structure .
Slide3Slide4Adrenal hormones
Zona Glomerulosa : mineralocorticoids
Major : ALDOSTERONE
Regulate blood volume , pressure , NA and K .
Also promote H excretion in urine .
Aldosterone secretion stimulated by renin- angiotensin- aldosterone pathway .
And to lesser extent by ACTH .
Slide5Zona Fasciculata: glucocorticoids
Cortisol (hydrocortisone ) account for 95 %
Cortisone ,
Corticosterone
CRH
corticotropin releasing hormone promote secretion of ACTH (adrenocorticotropic hormone)Function of corticosteroids :Protein breakdown : increase amino acid in blood Glucose formation : gluconeogenesis Lipolysis : breakdown triglycerides Resistance of stress Makes blood vessel sensitive to other hormone causing vasoconstriction such increase BPAnti inflammatory , alteration of wound healing Depression of immune system .
Slide6Glucocorticoid: -cortisol level are highest in the morning and lowest in the middle of the night ( diurnal rhythm )
cortisol rises dramatically during stress (
e.x:illness
, starvation)
Most of cortisol circulates in blood attached to cortisol binding
protein
, with small amount circulate as biologically active free hormone .Zona reticularis : produce small amount of androgen .DHEA ( dehydroepiandrosterone )Weak androgen with peripheral conversion to testosterone .
Slide7Cushings syndrome
Excessive activation of glucocorticoid receptors. ( syndrome ) regardless the cause .
Exogenous- Prolonged administration of Prednisolone.
2. Endogenous.
Cushing disease : endogenous high cortisol due to high ACTH from pituitary tumor
Slide8ACTH-dependent
:
• Pituitary adenoma secreting ACTH (Cushing's disease)
• Ectopic ACTH syndrome (bronchial carcinoid, small-cell lung carcinoma, other
neuro-endocrine tumor) Non-ACTH-dependent :• Adrenal adenoma • Adrenal carcinoma • ACTH-independent macronodular hyperplasia; primary pigmented nodular adrenal disease .
Slide9Signs and symptoms
Slide10Striae
:especially reddish > 1 cm width
Easy bruising
Facial plethora
Dorsocervical
and supraclavicular fat pads .
Slide11Slide12Slide13Initial testing
1)Urine free cortisol: 24-hr timed collection, elevated if above
reference
range for assay
2)late night salivary cortisol 11 pm – 12 pm at least 2 different nights
Loss of diurnal rhythm .
3)overnight dexamethasone suppression test: 1 mg orally at 11 pm, measure plasma cortisol at 8:00 am (<50 nmol/l ) exclude cushing syndrome . >138nmol/l considered positive When suspicion of cushing is low , single test if negative makes cushing syndrome is unlikely .When suspicion of cushing is high ???Two different test are recommended
Slide14Pseudo
cushings
:
Occur with major depression , anxiety , psychosis ,
poorly
controlled DM and sever visceral obesity
Slide15Confirmatory test
1)Low
dose
dexamethason
suppression test: Serum cortisol is measured following administration of 0.5 mg 6-hourly for 48 hour (<50
nmol
/l ) exclude Cushing syndrome 2)High dose dexamethasone suppression test: Serum cortisol is measured following administration of 2 mg 6-hourly for 48 hour3)Measuring plasma ACTH:<1.1 pmol/L ACTH-independent cause > 3.3 pmol\L ACTH-dependant cause
Slide16Adrenal CT scan or MRI
Pituitary MRI
In case of ACTH dependent
If no tumor , or if tumor is less than 6 mm
High dose dexamethasone suppression test to evaluate for ectopic ACTH
Slide17Management
• Most patients are treated surgically, but medical therapy may be given in severe cases for a few weeks prior to operation to improve the clinical state. A number of drugs are used to inhibit corticosteroid
biosynthesis, including
metyrapone
and ketoconazole.
• If the patient have
cushing disease --- transphenoidal surgery
Slide18Slide19hyperaldosteronism
Slide20PATHOPHYSIOLOGY
Stimuli
of aldosterone secretion
:
1- angiotensin II ( the principal stimulus
) . 2- increased K+ .3. decreased volume .4. lesser extent by ACTH .suppressors of aldosterone secretion : 1- hypervolemia 2- hypokalemia
Slide21RAAS ( RENIN ANGIOTENSIN ALDOSTERONE SYSTEM)
Renin : a
proteolytic
enzyme , released by the kidneys , in which the primary site of it’s storage and release is the JGA
.
It’s release is stimulated by : 1- sympathetic activation .2- renal artery hypo perfusion 3- decreased Na delivery to the distal tubules
Slide22Slide23PRIMARY HYPERALDOSTERONISM
-Increased mineralocorticoid secretion from the adrenal cortex .
-
Low renin levels but high
aldosterone levels
Slide24Etiology
Idiopathic bilateral adrenal hyperplasia .
Tow third of cases
-
Adrenal adenoma secreting aldosterone (Conn’s syndrome)
.
One third of cases
Slide25Slide26hypertension
.
hypokalemia ,muscle weakness or even paralysis
. ( 40 % )
Hypernatremia
.Excess thirst , polyuria due low K level Higher cardiovascular mortality and morbidity noted in primary hyperaldosteronism compared to PT with essential HTN with similar BP .
Slide27PA ???
HTN > 140 /90 on three drug therapy
HTN with spontaneous hypokalemia or diuretic induce hypokalemia.
Untreated HTN with sustained BP >150 /100
HTN with incidental adrenal mass
HTN in setting of first degree relative with PA .
HTN in setting of family history of HTN onset age < 40.
Slide28Investigations
Biochemical
–
Routine
blood tests
-
Aldosterone: renin ratio ( ARR ) Mid morning seated sample If pt taking ACEI ,ARBS , spironolactone ?? An ARR greater than 20 with plasma aldosterone concentration of at least 15 ng / dl is considered a positive test confirmatory test : suppression tests ( normal saline , fludrocortisone ,NaCl tabs )Infuse 2 liter 0.9% over 4 hours or 10 -12 g daily of NACL tab for 3 days Blood level : plasma aldosterone >5ng /dl confirm diagnosis Hr urine collection for aldosterone , creatinine and NA Aldosterone in urine >10 microg/24 hr confirm diagnosis
Slide29Adrenal CT :
Result :
NL
Hyperplasia
Unilateral or bilateral adenoma
Incidental adrenal mass may or may not related to primary
aldosteronism Adrenal vein sampling to measure aldosterone .
Slide30Management
- Mineralocorticoid receptor antagonist ( spironolactone , eplerenone ) for hypertension and
hypokalemia
other anti HTN medications .
For unilateral disease :
Laparoscopic adrenalectomy 40 % of PT cured after surgery others BP significantly improve .Persistent HTN after surgery may occur due to primary HTN or due to vascular changes caused by HTN .
Slide31SECONDARY HYPERALDOSTERONISM
• high renin and aldosterone levels
.
Etiology :
1-
Inadequate renal perfusion ( HF , RA stenosis , diuretic therapy ) 2- renin-secreting renal tumor ( very rare)
Slide32Slide33Adrenal insufficiency
Slide34-It results from inadequate secretion of cortisol and/or aldosterone
.
PRIMARY
Endogenous Failure of adrenal gland to secret hormones
Presence of hyperpigmentation due to stimulation of melanocytes by high ACTH .
SECONDARY
most common cause and its due to ACTH deficiency usually due to inappropriate steroids withdrawal , or pituitary tumor ADRENAL CRISIS Potentially fatal and variable in its presentation , usually precipitated by acute illness or replacement of thyroid hormone in un recognized chronic adrenal insufficiency
Slide35Causes of adrenal insufficiency
Primary adrenal insufficiency (High ACTH
)
1-Addison’s disease
Autoimmune .( most common ) destruction of all 3 layers , most
pt
have positive 21 – hydroxylase antibodies . 50 % of these pt may develop autoimmune endocrine disorder (primary hypothyrodism , celiac disease type 1 DM , hypoparathyrodism )2-Other causes : TB , fungal infection HIV/AIDSSarcoidosis , hemochromatosis Metastatic carcinoma ( lung cancer , renal cell cancer ) lymphoma Bilateral adrenal hemorrhage, sepsis and DIC , anticoagulation protein C deficiency .
Slide36Slide37Slide382- Corticosteroid biosynthetic enzyme defects
–
- Congenital
adrenal
hyperplasia's.
21 hydroxylase deficiency
Slide39Secondary adrenal insufficiency (Low ACTH
):
-sudden Withdrawal
of glucocorticoids
therapy
. -Hypothalamic or pituitary disease.
Slide40CLINICAL ASSESSMENT
In
addison’s
disease, either glucocorticoid or mineralocorticoid deficiency might come first, but eventually all patients fail to secrete both.
Patients
may present with chronic features (weakness, fatigue and hyperpigmentation) and/or in acute circulatory shock.
These symptoms are often misdiagnosed as chronic fatigue syndrome or depression. Adrenocortical insufficiency should be considered in patients with hyponatremia even in the absence of symptoms.
Slide41CLINICAL
FEATURES in primary disease
(SYMPTOMS CAUSED BY GLUCOCORTICOID INSUFFICIENCY)
Weight
loss
Anorexia fatigueNausea and vomiting Diarrhoea or constipation Postural hypotension Shock .Hyponatremia .hypoglycemia
Slide42ADDISON’S DISEASE CLINICAL FEATURES (CAUSED BY MINERALOCORTICOID INSUFFICIENCY)
Hypotension
.
Shock .
Hyponatremia
. Hyperkalemia.
Slide43SYMPTOMS
ARE DUE TO ADRENAL ANDROGEN INSUFFICIENCY)
Decreased body
hair
Loss of libido especially in
female
Slide44Secondary disease
All symptoms mentioned above .
Pt
don’t develop hyperpigmentation .
no hyperkalemia .
Slide45ADRENAL CRISIS
-
Primary
acute
hypoadrenalism
.
sever fatally symptoms -Causes: stress, rapid withdrawal of steroids, adrenal hemorrhage, surgery and infection. -Circulatory shock with severe hypotension, hyponatremia, hyperkalemia. In some instances hypoglycemia .
Slide46Slide47Treatment should not be delayed to wait for results in patients with suspected acute adrenal crisis.
If the patient’s condition permits, it may be appropriate to perform a short ACTH stimulation test before administering hydrocortisone.
Investigations should be performed before treatment is given if the patient’s symptoms suggest chronic adrenal insufficiency
Slide48MANAGEMENT OF ADRENAL CRISIS
1-correct volume depletion with IV saline to normalise BP
2-replace glucocorticoids
3-correct other metabolic abnormalities
4-Identify and treat the underlying cause
Slide49Random plasma cortisol is usually low in patients with adrenal insufficiency but it may be within normal range, yet inappropriately low, for a seriously ill patient
.
ACTH stimulation test is more
useful:
Cortisol levels fail to increase in response to exogenous ACTH in primary adrenal insufficiency.
Slide50MANAGEMENT
-
Glucocorticoid replacement (always
):
oral hydrocortisone 15-20 mg daily in divided doses
. -Mineralocorticoid replacement (usually): Fludrocortisone 0.05-0.15 mg daily. -Androgen replacement (beneficial in women): DHEA (DeHydro EpiAndrosterone)50mg/day During stress or illness corticosteroids should be in increase 2 to 3 times .
Slide51Adrenal
ct
scan in case of primary disease
Brain MRI in case of secondary disease in absence of steroids intake
If
pt
on steroids therapy for 3 weeks or more , dose should be tapered off gradually