ENDO IV Flashcards
The two adrenal glands
each weighs ~4 grams.
They are located
superior
to each kidney
adrenal glands consist of (2)
outer cortex
inner medulla
Adrenal cortex is essential for
life
Adrenal cortex secretes (3)
Corticosteroids (ex. Cortisol) Mineralocorticoids (ex. Aldosterone) Sex hormones (ex. DHEA)
Adrenal medulla
•–% of gland tissue
20-30
Adrenal medulla secretes (2)
E and NE in response to SNS stimulation
Adrenal medullary hormones are not
essential for —, but help to
life
prepare the individual to deal with emergencies
The adrenal cortex secretes hormones that are made from –
cholesterol
The cortex has three layers: (3)
Zona Glomerulosa (~15%), Zona Fasciculata (~75%), Zona Reticularis (~10%).
Mineralocorticoids
Secretion regulated by the
renin-angiotensin- aldosterone system (RAAS).
Glucocorticoids
Secretion regulated by the
hypothalamic-pituitary-adrenal
axis (HPA) – CRH, ACTH
Androgens
Secretion is regulated by the
HPA
The adrenal medulla is related to the sympathetic nervous system and
chromaffin cells secrete (2) into the blood.
the catecholamines epinephrine (EPI) and
norepinephrine (NE)
aldersterone increases
renal tubular reabsorption of Na+ and secretion of K+.
aldosterone leads to an increase in (2)
EC fluid volume and Mean Arterial Pressure
Aldosterone has similar effect on sweat glands and
salivary glands as
renal tubules
Aldosterone greatly increases reabsorption of (2) by gland ducts
sodium and secretion of potassium
Effect on sweat glands important to conserve body — in hot environments
salt
Effect on salivary gland conserves — during high rates of salivary secretion
sodium
In addition to hyperkalemia, --- causes secretion of Aldosterone.
Angiotensin II
--- is an enzyme released by the cells in the kidneys in response to a variety of stimuli (ex. Sympathetic Nervous system).
Renin
Angiotensin Converting
Enzyme (ACE) is
produced by the —
endothelium
Primary Hyperaldosteronism (Conn’s Syndrome) Causes:
adrenal adenoma (benign), adrenal hyperplasia, adrenal carcinoma (malignant)
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Primary Hyperaldosteronism (Conn’s Syndrome)
Signs and Symptoms
- Hypertension
- Hypernatremia
- Headaches
- Potassium depletion
- Weakness
- Fatigue
- Polyuria
- Hypokalemic alkalosis
- Low plasma renin
Primary Hyperaldosteronism (Conn’s Syndrome) Tx options (2)
– Surgical removal of the tumor or most of the adrenal tissue when hyperplasia is
the cause.
– Pharmacological antagonism of the mineralocorticoid receptor (ex.
spironolactone) is another option
Secondary Hyperaldosteronism
Caused by
decreased blood flow & pressure in renal artery – CHF – Cirrhosis – Nephrosis – Renal artery stenosis
Secondary Hyperaldosteronism
Signs and Symptoms (5)
• High plasma renin activity
• Hypernatremia w/extracellular volume expansion
• Edema
• Decreased cardiac output
• Similar clinical findings as Primary Hyperaldosteronism-hypertension
etc.
cortisol is secreted with any
stress
cortisol causes
mobilization of energy stores and
suppresses the immune response.
Types of stress that increase
cortisol release include:
- Trauma of almost any type
- Infection
- Intense heat or cold
- Injection of norepinephrine
- Surgery
- Hypoglycemia
- Psychological stress
- Almost any debilitating disease
Cortisol secretion also
peaks in the
AM – it is
secreted in a circadian
When ACTH is secreted from the AP, several other hormones are secreted as well because the gene for ACTH forms a larger protein -
a preprohormone called Proopiomelanocortin (POMC).
When ACTH is secreted from the AP, several other hormones are secreted as
well because the gene for ACTH forms a larger protein - a preprohormone
called Proopiomelanocortin (POMC). (3)
– Melanocyte stimulating hormone (MSH)
– β-endorphin
– β-lipotropin
The specific proteins produced depend on the --- enzymes found in the cell. Many tissues express the POMC gene beside the anterior pituitary (hypothalamus, melanocytes).
processing
• Melanocytes have processing
enzymes that form — which
stimulates formation of melanin
pigment.
MSH
Cortisol is found in 1000-fold higher circulating
conc. (compared to aldosterone), which could
potentially cause symptoms of
mineralocorticoid
excess.
11beta-hydroxysteroid dehydrogenase (11betaHSD)
converts cortisol to — in aldosterone-
responsive tissues.
cortisone
Cortisone does not bind GC or
MR receptors with as high of an affinity as
Cortisol
A Genetic deficiency of 11β-HSD leads to the syndrome
AME (Apparent Mineralocorticoid Excess).
Glycyrrhetinic acid, a compound of licorice, inhibits the activity of
11β-
hydroxysteroid dehydrogenase.
HIGH circulating — levels (such as in Cushing’s Syndrome) can overwhelm
this enzyme.
cortisol
Effects of Cortisol on Metabolism
Carbohydrate (3)
- Stimulation of both gluconeogenesis and glycogenolysis in liver (increase
plasma glucose) - Anti-insulin action - decreases glucose uptake in muscle and fat but not
brain and heart - Makes diabetes worse by increasing glucose levels, lipid levels, ketone
body formation and insulin secretion.
Effects of Cortisol on Metabolism
Protein (2)
- Inhibits protein synthesis and increases proteolysis especially in skeletal
muscle (provides source of AA for glycoenogenesis) - Cortisol excess leads to muscle weakness, pain due, thin skin and abdominal
striae due to protein catabolic effect.
Effects of Cortisol on Metabolism
Lipid: (2)
- Promotes lipolysis; shifts energy system from utilization of glucose to fatty
acids in times of stress. - Causes lipid deposition in certain areas (abdomen, interscapular “buffalo
hump” and a rounded “moon face”.
95% of the glucocorticoid activity of the adrenal cortex
due to the secretion of
cortisol
Absence of cortisol contributes to circulatory failure
due to loss of — action of catecholamines on
blood vessels.
permissive
Lack of cortisol also prevents mobilization of energy
sources (glucose & free fatty acids) during stress &
can result in
fatal hypoglycemia
Anti-inflammatory Actions of Cortisol: (5)
- Stabilizes the lysosomal membrane
- Decreases capillary permeability
- Decreases WBC migration and phagocytosis
- Suppresses T lymphocytes proliferation
- Decreases IL-1 secretion from WBCs
Glucocorticoid treatment can
cause osteoporosis. (3)
1) Stimulates bone resorption (via increased RANK-L expression)
2) Inhibits osteoblastic maturation and
activity
3) Promotes apoptosis of osteoblasts
and osteocytes
Due to their anti-inflammatory properties, glucocorticoids can be used to treat patients with diseases/conditions that involve
an inflammatory process (ex. rheumatoid arthritis, glomerulonephritis, rheumatic fever, anaphylaxis).
The Zona Reticularis begins to secrete adrenal androgens around age 8 (adrenarche) peaking in the early 20s and then falling with age. (3)
- Dehydroepiandrosterone
(DHEA) - Androstenedione
- Testosterone
Normally, the adrenal androgens have only weak effects in
— but contribute ~50% of active androgens in —
males
females
Growth of the pubic and axillary hair and libido in females are due
to
adrenal androgens
Conditions resulting from excess androgen production by the
adrenal gland: (3)
– In pre-pubertal boys, it can cause precocious pseudopuberty (not
due to the hypothalamic- pituitary-adrenal axis)
– 21-hydroxylase deficiency can result in virilization in newborn
females and pseudo-hermaphroditism
– Androgen secreting tumors producing excess androgen result in
virilization and precocious pseudopuberty in females
DHEA and DHEA sulfate are secreted in greater quantities but --- is more important because it is more readily converted peripherally to testosterone. Conversion to testosterone and 5- dihydrotestosterone occurs in peripheral tissues.
Androstenedione
In adults, hormonally active benign adrenal adenomas usually secrete (2)
aldosterone or cortisol.
Virilizing tumors in women are more likely to be caused by
ovarian tumors.
Virilizing adrenal tumors are rare, and virilization is usually due to
hypersecretion of adrenal androgens.
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Signs and symptoms of
virilization include:
• hirsutism, • male-pattern baldness, • acne, • deep voice, • male musculature, • irregular menses or amenorrhea, • clitoromegaly, • increased libido. • rapid linear growth with advanced bone age is common in children
Primary adrenal insufficiency (Addison’s) (4)
– Primary atrophy or injury of adrenal cortex
– In about 80% of US cases, atrophy caused by
autoimmune destruction of all cortical zones
– High ACTH and low corticosteroid production
– Loss of glucocorticoid, mineralcorticoid and
adrenal androgen secretion
Secondary adrenal insufficiency (4)
– Pituitary gland unable to secrete enough ACTH
– Often Iatrogenic due to abrupt cessation of
steroid therapy
– Low ACTH and cortisol production
– Mineralcorticoid secretion not affected
Adrenal insufficiency from --- ---- treatment (which suppresses the HPA axis) is much more common, occurring in 0.5–2% of the population in developed countries.
exogenous glucocorticoid
ORAL MANIFESTATIONS OF ADRENAL INSUFFICIENCY (Addison’s
disease)
Orofacial features:
• skin pigmentation o mucocutaneous junctions lips o intraoral mucosal surfaces o buccal mucosa o palate o lingual surface of the tongue
ORAL MANIFESTATIONS OF ADRENAL INSUFFICIENCY (Addison’s
disease)
Treatment:
corticosteroids o immunosuppression o susceptibility to oral candidiasis o recurrent herpes labialis o herpes zoster infections o gingival and periodontal diseases o impaired wound healing
ACTH-dependent Cushing’s Disease (Secondary
Disorder) (3)
- Adenoma of anterior pituitary secretes large
amounts of ACTH - “Ectopic secretion” of ACTH by non-pituitary
tumor such as the lungs - “Ectopic secretion” of corticotropin-releasing
hormone (CRH) by non-pituitary tumor
ACTH-independent Cushing’s Syndrome (Primary
Disorder) (2)
- Adenomas of the adrenal cortex overproducing
Cortisol - Primary nodular hyperplasia of the adrenal
gland causing overproduction of Cortisol.
Manifestations of Cushing Syndrome/Disease (2)
Moon facies with erythema
and telangiectases of cheeks
and forehead
Increased fat deposition in
the supraclavicular fossae
and dorsocervical area
(buffalo hump).
Oral Manifestations of Hypercortisolism (Cushing
Syndrome/Disease)
Orofacial features:
Round, moon face (muscle wasting & fat accumulation)
Fragile surface capillaries susceptible to hematomas after
mild trauma
Acne and excessive facial hair (hirsutism)
Delayed growth and development (skeletal and dental
structures)
Increased pigmentation of buccal mucosa if due to ACTH
excess
Oral Manifestations of Hypercortisolism (Cushing
Syndrome/Disease)
Immunosuppression:
- oral candidiasis
- Recurrent herpes labialis
- herpes zoster infections
- gingival and periodontal diseases
- impaired wound healing
Adrenal Disease (3)
Conn’s Syndrome (Mineralocorticoids) Pheochromocytoma (Catecholamines) Cushing’s Syndrome/Disease (Glucocorticoids)
Pheochromocytoma
• Sudden releases of hormone causing sudden “attack” due to chromaffin cell
tumor in the Adrenal Medulla resulting in excessive secretion of EPI and NE.
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Signs and Symptoms of excess NE & EPI
– Hypertension, Tachycardia, Palpitations,
Headache, Sweating, Tremors, Weight
Loss, Hyperglycemia, Orthostatic
Hypotension
Pheochromocytoma
Occurs in
2-8 in 1 million person per year. Mean age of diagnosis is 40 but
tumors can occur from each childhood to late in life.
Its clinical presentation is so variable that pheochromocytoma has been termed “the great masquerader”. Among the presenting manifestations, episodes of (3) are typical, and these manifestations constitute a classic triad.
palpitation, headache, and profuse sweating
