Diseases of the adrenal glands: chronic adrenal insufficiency.
Hormone active tumors. Department of Internal Medicine N2 as.-
prof. Svystun I. I. Slide 2 Anatomy of adrenal glands Localization:
the top of the kidney and weighting approximately 5 g each.
Vascularization: a.suprarenalis superior (from a. phrenica
inferior), a. suprarenalis media (from aorta abdominalis), a.
suprarenalis inferior (from a. renalis). Innervation: n.
splanchnicus major (through plexus celiacus and plexus renalis),
fibrae n. vagus and n. phrenicus. kidney Left renal artery a.
suprarenalis inferior Left adrenal vein Left adrenal gland Left
ovaria vein Ovaria arteries Right ovaria vein Rena vein Right
adrenal vein Vena cava inferior a. supranenalis superior Aorta a.
suprarenalis media a. phrenica inferior Slide 3 Anatomy of adrenal
glands The adrenals are divided into: 2) inner area or medulla
1)outer area or cortex, which includes three zones: -Glomerular
(glomerulosa) -Fascicular (fasciculata) -Reticular (reticularis)
Slide 4 Mineralocorticoids : Mineralocorticoids are a class of
steroid hormones,the primarysteroid hormones mineralcorticoid is
aldosterone. Action of regulation of electrolyte balance in the
organism: increasing the level of sodium (by sodium retention in
distal nephron, colon, salivary gland) decreasing the level of
potassium due to a ccelerated excretion of potassium ions by
excretionpotassium ions Slide 5 mineralocorticoid secretion is
regulated by the renin angiotensin system, the level of Na+, K+ in
blood, and to a lesser extent of ACTH Slide 6 Slide 7
Glucocorticoids : Corticosteroids are a class of chemicals that
includes steroid hormones naturally produced in the adrenal
cortex.steroid hormonesadrenal cortex Action: enhancing hepatic
glycogen synthesis and storage in liver and, increasing
gluconeogenesis (insulin-depending effect); decreasing of glucose
utilization by peripheral tissues; increasing of protein synthesis
in liver and decreasing of its synthesis in muscles and increasing
of protein destruction in muscles; Slide 8 Glucocorticoids
increasing of lipolisis; anti-inflammatory function and
immunomodulation; cardiovascular regulation (increasing of blood
pressure due to increasing cardiac output, periferal vascular tone
by augmenting the effects of vasoconstrictors). Bone methabolism
(directly inhibit bone formation by decreasing cell proliferation,
stimulate bone-resorbting cells, potentiate PTH action on bone)
Slide 9 Slide 10 Slide 11 Regulation of secretion glucocorticoids
and androgens secretion is regulated by hypothalamic pituitary
system. ACTH is trofic hormone of zonae fasciculata and reticularis
and major regulator of cortisol and androgen production. Slide 12
The principle urinary metabolic products of epinephrine and
norepinephrine are the metanephrines and vanillylmandalic acid
(VMA). Slide 13 Action of catecholamines : Cardiovascular effects:
increase rate and force of contraction, irritability of myocardium
by activating 1-receptors; Contractile effects on vascular smooth
muscle are regulated by 1, 2, 2 receptors; Effects on extravascular
smooth muscle due to localisation of catecholamine receptors
Metabolic effects: increase oxygen consumption and heat production;
regulate glucose and fat mobilization from storage depots;
glycogenolysis in heart muscle and in liver; antagonize insulin
action. Slide 14 Slide 15 CHRONIC ADRENOCORTICAL INSUFFICIENCY. It
is an insidious and usually progressive disease resulting from
adrenocortical hypofunction. Slide 16 Classification. 1.Primary
adrenal insufficiency is due to impairment of the adrenal glands
(Addisons disease). 2.Secondary adrenal insufficiency is caused by
impairment of the pituitary gland.pituitary gland 3.Tertiary
adrenal insufficiency is due to hypothalamic disease and decrease
in corticotropin releasing factor (CRF). Slide 17 Etiology of
adrenal insufficiency: Primary: 80% are due to an autoimmune
disease called Addison's disease or autoimmune
adrenalitis;autoimmune diseaseAddison's diseaseautoimmune
adrenalitis tuberculosis (5-10%); neoplasm, metastatic carcinoma;
inflammatory necrosis; amyloidosis; heamochromatosis; bilateral
adrenal hemorrhage or infarction, intraadrenal hemorrhage
(Waterhouse Friedrichsen syndrome following meningococcal
septicemia); bilateral adrenalectomy; Secondary: hypothalamic or
pituitary disease (primary injury of these organs leads to
insufficiency of ACTH secretion that cause the two side atrophy of
adrenal glands); glucocorticoid therapy. Slide 18 Pathogenesis.
Deficiency of adrenal hormones contributes to the hypotension and
produces disturbances in carbohydrate, fat and protein metabolism,
and severe insulin sensitivity. is stimulated by angiotensin II or
hypokalemia stimulated by ACTH Slide 19 Slide 20 Clinical
Manifestations of Primary Adrenal Insufficiency ParameterFrequency
(%) Symptoms Weakness, fatigue100 Anorexia100 Nausea86 Vomiting75
Constipation33 Diarrhea15 Abdominal pain31 Salt craving16 Postural
dizziness12 Muscle and joint pain10 Signs Weight loss100
Hyperpigmentation90 Vitiligo15 Hypotension (systolic blood pressure
Primary Aldosteronism Who Should Be Screened? stage 2
(>160179/100109 mm Hg), stage 3 (>180/110 mm Hg), or drug
resistant hypertension(3 drugs and poor control); hypertension and
spontaneous or diuretic- induced hypokalemia; hypertension with
adrenal incidentaloma; or hypertension and a family history of
early- onset hypertension or cerebrovascular accident at a young
age ( Primary Aldosteronism Ideal Screening Test Measure a morning
(8AM-10AM): Plasma aldosterone concentraton Plasma renin activity
Increased plasma aldo concentration (>15ng/dl) Decreased plasma
renin activity ( 20 ng/dl per ng/ml per hour Slide 61 OTHER
CONFIRMATORY TESTS FOR PAL Saline infusion test Urinary aldo after
oral salt loading plasma aldo following i.v. infusion of normal
saline (2L over 4h) >140- 280 pmol/L (>5-10 ng/100 ml) 24h
urinary aldo following 3 days of oral salt loading (>200 mmol
sodium/day) >12 ug/d - - Captopril challenge test aldo/renin
ratio (seated) 60 mins after oral captopril (50 mg) >30 - Slide
62 Subtype evaluation of primary aldosteronism. Young W F.
Endocrinology 2003;144:2208-2213 Slide 63 Treatment Surgery is the
treatment of choice for the lateralizable variants of primary
aldosteronism, including typical aldosteronomas, renin- responsive
adenomas (RRAs), and primary adrenal hyperplasia (PAH). Nonsurgical
therapy is also a viable treatment option in patients who have
lateralizable disease but who are poor surgical candidates because
of other coexisting comorbidities. It is also a viable treatment
option in the rare setting of bilateral functional adrenal adenomas
that would otherwise require bilateral adrenalectomy. Slide 64
ALDOSTERONE-PRODUCING CARCINOMA Slide 65 ADRENAL "INCIDENTALOMA"
ALDOSTERONE- PRODUCING ADENOMA (APA) Slide 66 Treatment Diet (a
low-salt diet, although helpful in achieving blood pressure control
in primary aldosteronism, may be associated with false-negative
results on biochemical testing). Antihypertensive agents: Calcium
channel blockers (by inhibiting the intracellular calcium flux in
the adrenocortical cells, the dihydropyridine calcium channel
blockers reduce the production of aldosterone in response to a
variety of stimulants, including potassium, corticotropin, and
angiotensin-II) ACE inhibitors and angiotensin receptor blockers
(ARBs) are also potential treatment options. Less ideal medical
treatment options include potassium- sparing diuretics. Slide 67
Mineralocorticoid antagonists 2) Eplerenone is a selective
antialdosterone agent 1) Spironolactone has estrogenlike adverse
effects including impotence and gynecomastia Slide 68
Differentiating Adrenal Adenoma from Hyperplasia Adrenal Vein
Sampling Slide 69 DIFFERENTIATING APA FROM BAH ADRENAL VENOUS
SAMPLING perform in ALL patients with PAL (except those found to
FH-I FAMILIAL HYPERALDOSTERONISM TYPE I (Glucocorticoid-Remediable
Aldosteronism) by genetic testing) the only reliable way to
separate aldo-producing adenoma (APA) from bilateral adrenal
hyperplasia (BAH) and to lateralize APAs pre-operatively Slide 70
AV SAMPLING - Definitions Lateralization: Aldo/cortisol ratio on
the other side no higher than peripheral (contralateral
suppression) Aldo/cortisol ratio on affected side at least 2 times
peripheral Successful AV cannulation: Cortisol level in the AV at
least 3 times peripheral
