2/19: Adrenal Hormones Flashcards
What does the adrenal hormone consist of?
Outer cortex
Inner medulla
What is the adrenal cortex essential for?
Life
What does the adrenal cortex secrete?
Corticosteroids (ex. Cortisol)
Mineralocorticoids (ex. Aldosterone)
Sex hormones (ex. DHEA)
What is 20-30% of gland tissue?
Adrenal medulla
What does the adrenal medulla secrete?
Epinephrine and norepinephrine in response to sympathetic NS stimulation
What hormones are not essential for life, but help to prepare the individual to deal with emergencies?
Adrenal medulla
Adrenal cortex secretes hormones that are made from __________
Cholesterol
What are the three layers of the cortex?
Zona Glomerulosa (~15%), Zona Fasciculata (~75%), Zona Reticularis (~10%)
What does the zona glomerulosa secrete?
Mineralocorticoids
- Secretion regulated by the
renin-angiotensin-
aldosterone system (RAAS)
What does the zona fasciculata secrete?
Glucocorticoids
- Secretion regulated by the
hypothalamic-pituitary-adrenal axis (HPA) – CRH, ACTH
What does the sona reticularis secrete?
Androgens
- secretion regulated by the HPA
What does the adrenal medulla secrete?
Catecholamines
- related to the sympathetic nervous system and
chromaffin cells secrete the catecholamines epinephrine (EPI) and norepinephrine (NE) into the blood
What are steroid hormones derived from?
Cholesterol
What does aldosterone do?
Increases renal tubular reabsorption of Na and secretion of K
Increase ECF Na+
Decrease ECF K+
What does increases of Na+ reabsorption and K+ secretion lead to?
An increase in EC fluid volume and mean arterial pressure
What is aldosterone secretion stimulated by?
Angiotensin II
Increase K+
Decrease Na+
Aldosterone has similar effect on _______ and ________ as renal tubules
Sweat glands; salivary glands
What does aldosterone increase reabsorption of?
Sodium by gland ducts
What does aldosterone increase secretion of?
Potassium by gland ducts
What is the effect of aldosterone on sweat glands important for?
To conserve body salt in hot environments
What is the effect of aldosterone on salivary glands conserve?
Sodium during high rates of salivary secretion
What causes secretion of aldosterone?
Angiotensin II
What is renin?
an enzyme released by the cells in the kidneys in response to a variety of stimuli (ex. Sympathetic Nervous system)
What is angiotensin converting enzyme (ACE) produced by?
Endothelium
What cells make up renin?
Juxtaglomerular cells in kidney
Describe the pathway of angiotensinogen to aldosterone
What does angiotensin II cause?
Vasoconstriction
ADH secretion
Thirst stimulation
What enzyme converts angiotensinogen to angiotensin I?
RENIN
What enzyme converts angiotensin I to angiotensin II?
ACE
What are causes of primary hyperaldosteronism (Conn’s syndrome)?
adrenal adenoma (benign), adrenal hyperplasia, adrenal
carcinoma (malignant)
What are signs and symptoms of primary hyperaldosteronism (conn’s syndrome?
- Hypertension
- Hypernatremia
- Headaches
- Potassium depletion
- Weakness
- Fatigue
- Polyuria
- Hypokalemic alkalosis
- Low plasma renin!!
What are tx options of primary hyperaldosternosim?
– Surgical removal of the tumor or most of the adrenal tissue when hyperplasia is
the cause.
– Pharmacological antagonism of the mineralocorticoid receptor (ex: spironolactone)
What is secondary hyperaldosteronism caused by?
Decreased blood flow and pressure in renal artery
– CHF
– Cirrhosis
– Nephrosis
– Renal artery stenosis
What are signs and symptoms of secondary hyperaldosteronism?
- High plasma renin activity
- Hypernatremia w/extracellular volume expansion
- Edema
- Decreased cardiac output
- Similar clinical findings as Primary Hyperaldosteronism-hypertension
etc.
What is the cause of the pathology of secondary hyperaldosteronism?
High plasma renin activity
When is cortisol secreted?
With any stress
What does cortisol cause?
mobilization of energy stores and suppresses the immune response
What are types of stress that increase cortisol?
- Trauma of almost any type
- Infection
- Intense heat or cold
- Injection of norepinephrine
- Surgery
- Hypoglycemia
- Psychological stress
- Almost any debilitating disease
When does cortisol secretion peak?
In the AM - it is secreted in circadian
What are the functions of cortisol?
- Gluconeogenesis
- Protein mobilization
- Fat mobilization
- Stabilizes lysosomes
When ACTH is secreted from the AP, _____________ are secreted as well
Several other hormones because the gene for ACTH forms a larger protein - a preprohormone called Proopiomelanocortin (POMC)
What doesn’t express the POMC gene?
Anterior pituitary (hypothalamus, melanocytes)
What do melanocytes have?
Processing enzymes that form MSH which stimulates formation of melanin pigment
In Addison’s disease, high levels of MSH can cause what in the oral mucosa?
Pigmentation of the mucus membranes and thin skin
Cortisol has a similar affinity for the mineralocorticoid receptor (MR) as __________
aldosterone
Cortisol is found in a higher circulating concentration, what does this cause?
Symptoms of mineralocorticoid excess
What converts cortisol to cortisone in aldosterone responsive tissues?
11betaHSD
Cortisone doesn’t bind _____ or _____ receptors with as high of an affinity as cortisol
GC; MR
What does a genetic dificiency of 11beta-HSD leads to?
AME Syndrome (Apparent Mineralocorticoid Excess)
What inhibits the activity of 11beta-hydroxysteroid dehydrogenase?
Glycyrrhetinic acid - a compound of licorice
What can overwhelm the 11beta-HSD enzyme?
High circulating cortisol levels (cushing’s syndrome)
What do carbohydrates stimulate?
Gluconeogenesis and glycogenolysis in liver (increase plasma glucose)
What are anti-insulin actions of carbohydrates?
Decreases glucose uptake in muscle and fat but not
brain and heart
How do carbohydrates make diabetes worse?
by increasing glucose levels, lipid levels, ketone
body formation and insulin secretion
What do proteins inhibit?
Protein synthesis and increases proteolysis especially in skeletal muscle (provides source of AA for gluconeogenesis)
What does excess cortisol lead to?
muscle weakness, pain due, thin skin and abdominal
striae due to protein catabolic effect
What do lipids promote?
lipolysis; shifts energy system from utilization of glucose to fatty acids in times of stress
What do lipids cause?
lipid deposition in certain areas (abdomen, interscapular “buffalo hump” and a rounded “moon face”
What does absence of cortisol contribute to?
- Circulatory failure due to loss of permissive action of catecholamines on blood vessels
- prevents mobilization of energy sources (glucose & free fatty acids) during stress &
can result in fatal hypoglycemia
What can glucocorticoids be used to treat?
Patients with diseases/conditions that involve an inflammatory process (ex: rheumatoid arthritis, glomerulonephritis, rheumatic fever, anaphylaxis)
What can glucocorticoid treatment cause?
Osteoporosis
If glucocorticoid treatment causes osteoporosis, what can this cause?
1) Stimulates bone resorption (via increased RANK-L expression)
2) Inhibits osteoblastic maturation and activity
3) Promotes apoptosis of osteoblasts and osteocytes
What are the three adrenal androgens?
- Dehydroepiandrosterone (DHEA)
- Androstenedione
- Testosterone
What effect do adrenal androgens have on males and females?
Weak effects in males, 50% active androgens in females
Conditions resulting from excess androgen production by the adrenal gland are?
– 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
What is androstenedione converted to?
Testosterone
Where does converstion to testosterone and 5-dihydrotestosterone occur in?
Peripheral tissues
In adults, hormonally active benign adrenal adenomas usually secrete
Aldosterone or cortisol
Virilizing tumors in women are more likely to be caused by
Ovarian tumors
What are signs and symptoms of virilization?
- 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
What is primary adrenal insufficiency?
Addison’s
In about 80% of cases, what is atrophy caused by?
Autoimmune destruction of all cortical zones
What is primary adrenal insufficency due to glucocorticoid, mineralcorticoid, and androgen secretion?
Loss of glucocorticoid, mineralcorticoid and adrenal androgen secretion
What is secondary adrenal insufficiency?
Pituitary gland unable to secrete enough ACTH
Secondary adrenal insufficiency is often _______ due to abrupt cessation of steroid therapy
Latrogenic
How does secondary adrenal insufficiency affect mineralcorticoid secretion?
Not affected
What are signs and symptoms of glucocorticoid deficiency?
- fatigue
- weight loss, anorexia
- myalgia
- fever
- anemia
- increased TSH
- hypoglycemia
- low BP
- hyponatremia
What are signs and symptoms of mineralcorticoid deficiency?
- abdominal pain, nausea, vomiting
- dizziness
- salt craving
- low BP
- hypotension
- increased serum creatine
- hyponatremia
- hyperkalemia
What are symptoms of adrenal androgen deficiency?
- lack of energy
- dry and itchy skin
- loss of libido
- loss of axillary and pubic hair
What are orofacial features of adrenal insufficiency (addison’s)?
skin pigmentation
o mucocutaneous junctions lips
o intraoral mucosal surfaces
o buccal mucosa
o palate
o lingual surface of the tongue
What is treatment for adrenal insufficiency?
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
What is ACTH-dependent cushing’s disease?
- 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
What is ACTH-independent cushing’s syndorme?
- Adenomas of the adrenal cortex overproducing
Cortisol - Primary nodular hyperplasia of the adrenal
gland causing overproduction of Cortisol
What are manifestations of cushings syndrome/disease?
- Moon facies with erythema
and telangiectases of cheeks
and forehead - Increased fat deposition in
the supraclavicular fossae
and dorsocervical area
(buffalo hump)
What are orofacial features of hypercortisolism (Cushing’s syndrome/disease)?
- 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
What are immunosuppressions of hypercortisolism?
- oral candidiasis
- Recurrent herpes labialis
- herpes zoster infections
- gingival and periodontal diseases
- impaired wound healing
What are the three types of adrenal diseases and what they’re associated with
Conn’s syndrome - mineralocorticoids
Pheochromocytoma- catecholamines
Cushing’s syndorme/disease - glucocorticoids
What is 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
What are signs and symptoms of excess NE and EPI?
Hypertension, Tachycardia, Palpitations, Headache, Sweating, Tremors, Weight
Loss, Hyperglycemia, Orthostatic
Hypotension
What is termed”the great masquareder”?
Pheochromocytoma
