Endocrine System: Adrenal Glands Flashcards
(a) Adrenal medula = ?
- Secretes = ?
(b) Adernal cortex = ?
- Zona glomerulosa secretes = ?
- Zona fasciculata secretes = ?
- Zona reticularis secretes = ?
Adrenal Glands
(a) Adrenal medulla (20% of tissues)
- Secretes catecholamines (epinephrine and norepinephrine)
(b) Adrenal cortex (80% of the tissue)
- Secrete a number of hormones collectively called as adrenocorticoids
- Hormones belong to chemical class of compounds called steroids
- Zona glomerulosa = mineralocorticoids
- Zona fasciculata = glucocorticoids
- Zona reticularis = androgens
Adrenocorticoids
- Include hormones of three types = ?
Adrenal Glands
Adrenocorticoids
(1) Mineralocorticoids
- Regulate reabsorption of Na+
- Secretion of K+ by kidneys
- Water balance
- Blood pressure
(2) Glucocorticoids
- Major glucocorticoids in human is cortisol (hydrocortisone)
- Regulate body’s response to stress, protein, lipid and carbohydrate metabolism, blood glucose levels, immune/ inflammatory response
(3) Adrenal androgens
- (DHEA and androstenedione), sex hormones
- Regulate reproductive function, and pubic and axillary hair growth
Structure of adrenocortical steroids = ?
Adrenal Glands
Structure of adrenocortical steroids
- All steroids of adrenal cortex are chemical modification of basic nucleus, shown in the structure of cholesterol.
- Basic nucleus is carbon skeleton, with carbons numbered from 1 through 21 and 4 labeled rings.
Biosynthesis pathway of adrenal cortex
Adrenal Glands
Biosynthesis pathway of adrenal cortex:
(a) Cholesterol desmolase stimulated by ACTH
- Precursor is cholesterol - provided to adrenal cortex via circulation and small amount is synthesized in adrenal cortex, stored in cytoplasmic vesicles until it is time for synthesis of steroid hormones.
- Cholesterol is present in all layers and cholesterol desmolase is the rate limiting enzyme
- Corticosterone is also a glucocorticoid so cortisol is not absolute necessary to sustain life as long as corticosterone is being synthesized.
- If production of cortisol and corticosterone is blocked then life threatening without hormone replacement therapy.
(b) Notes:
- Increase in aldosterone levels, it leads to increased sodium retention and potassium excretion by the kidneys.
- Decrease in aldosterone levels can lead to sodium wasting and potassium retention by the kidneys.
Regulation of secretion of adrenocortical steroids:
- Secretion of glucocorticoids and androgens, by the zonae fasciculata / reticularis, is regulated = ?
- Zona glomerulosa, which secrete mineralocorticoid, depends on = ?
Adrenal Glands
Regulation of secretion of adrenocortical steroids:
(a) Secretion of glucocorticoids and androgens by the zonae fasciculata / reticularis is regulated excessively by,
- The hypothalamic-pituitary axis
- Negative feedback
(b) Zona glomerulosa which secrete mineralocorticoid, majorly depends on,
- ACTH for the first step in steroid synthesis
- Otherwise is controlled separately by renin-angiotensin-aldosterone system.
Describe what regulates the scecretion of adrenocortical steroids = ?
Adrenal Glands
Regulation of secretion of adrenocortical steroids:
- Pulsatile, Diurnal (daily)
- Average of 10 secretory bursts daily during a 24 hr period
- Lowest secretory rates occur during evening hours and just after falling sleep
- Higher secretory rates occur just before awakening in the morning
- ACTH also exhibits the same diurnal pattern
- Internal clock that drives the diurnal pattern can be shifted by altering the sleep wake cycle.
- Diurnal pattern is abolished by coma, constant exposure to either light/ dark
Action of Mineralocorticoids:
- Aldosterone has three actions = ?
- Results of an increase in aldosterone levels = ?
Adrenal Glands
Action of Mineralocorticoids:
(a) Aldosterone has three actions on late distal tubule and collecting ducts of the kidney
- Increases sodium reabsorption
- Increases potassium secretion
- Increases hydrogen secretion
(b) Increase in aldosterone levels
- ECF volume expansion and hypertension
- Hypokalemia
- Metabolic alkalosis
What regulates of aldosterone secretion = ?
Adrenal Glands
Regulation of aldosterone secretion:
(a) Primary regulation of aldosterone is through changes in ECF via two systems described below:
(1) Renin-angiotensin II-aldosterone:
- Angiotensin II increases the synthesis and secretion of aldosterone by stimulating cholesterol desmolase (first step) and aldosterone synthase (last step) in the pathway.
- Decrease in extra cellular fluid (ECF) - stimulate aldosterone secretion- stimulate Na+ reabsorption- ECF volume increases
(2) Serum K+ concentration:
- Increase serum K+ increases aldosterone secretion
- Aldosterone increases K+ excretion by the kidney and decreases serum K+ concentration towards normal
Functions of Glucocorticoids = ?
Adrenal Glands
Functions of Glucocorticoids:
- Stimulates glucose production
- Decreases tissue glucose utilization
- Increases breakdown of proteins
- Increases mobilization of fats
- Decrease capillary permeability and inhibit edema formation
- Inhibit immune responses
- Anti-inflammatory effects
- Inhibit bone formation
- Stimulate gastric secretion
- Contribute to effective stress response
Actions of adrenal androgens = ?
Adrenal Glands
Actions of Adrenal Androgens:
(a) Adrenal cortex produces the androgenic compounds (DHEA and androstenedione), which are converted to testosterone and estrogen.
- In males, adrenal androgens play only a minor role because denovo synthesis of testosterone from cholesterol in the testes is much greater than testosterone synthesis from adrenal androgenic precursors.
- In females, adrenal androgens are major androgens (testosterone, estrogen and progesterone).
What tests adrenal function = ?
Adrenal Glands
Test of adrenal function:
- Blood levels of ACTH, cortisol, aldosterone, CRH
- Urine specimen: excretion of metabolic products of adrenal hormones
Adrenal cortical insufficiency:
- Primary = ?
- Secondary = ?
- Tertiary = ?
Adrenal Glands
Adrenal cortical insufficiency:
(a) Primary
- Disorder within the adrenal gland (Addison’s disease)
- Destruction of adrenal gland
(b) Secondary:
- Lack of ACTH
- Disorder of pituitary gland
- Hypopituitarism
- Surgical removal of pituitary gland
- Rapid withdrawal of corticosteroid drugs
(c) Tertiary:
*Lack of CRH
* Hypothalamic defects
(d) Acute adrenal crisis:
- Trauma
- Hemorrhage
- Thrombosis
(e) Notes:
- Serious, life threatening, severe hypotension, shock and death.
Addison’s disease
- What is it = ?
- Causes = ?
Adrenal Glands
Addison’s disease:
(a) What is it?
- Primary adrenal insufficiency, due to
- Adrenal cortical hormones are deficient, and
- ACTH levels are elevated
(b) Causes:
- Autoimmune destruction = most common cause
- Tuberculosis
- Infection like fungal, Cytomegalovirus (CMV)
- Adrenal hemorrhage in people taking anti-coagulants
- AIDS
(c)
- Rare disorder
- Most serious endocrine disorder
- Can lead hypotension, shock and death
Addison’s disease:
- Clinical manifestations = ?
Adrenal Glands
Addison’s Disease - Clinical manifestations:
(i) Symptoms not apparent until 90% of gland has been destroyed
(a) Mineralocorticoid deficiency
- Hyponatremia (low sodium)
- Loss of extracellular fluid
- Decreased cardiac output
- Hyperkalemia (arrythmias, cardiac arrest).
- Orthostatic hypotension
- Dehydration
- Weakness
- If severe hyponatremia then cardiovascular collapse and shock.
(b) Glucocorticoid deficiency
- Poor tolerance to stress
- Hypoglycemia
- Lethargy
- Weakness
- Fever
- GI symptoms (nausea, vomiting, weight loss)
(c) Androgens deficiency
- Women have sparse axillary and pubic hair
- Increased levels of ACTH
- Pigmentation of skin and mucous membrane
- Skin bronze / suntanned
Notes:
- Pigmentation: melanin, increased secretion of melanocyte stimulating hormone, occurs with increased secretion of ACTH.
- Commonly seen over extensor surfaces, such as backs of hands, lips, mouth
- White: slight tan / few black freckles / intense generalized pigmentation
- Blacks: slate-gray color
Summation:
- Addison’s Disease typically presents with symptoms once around 90% of the adrenal gland is damaged.
- The manifestations include mineralocorticoid deficiency, leading to symptoms like hyponatremia, dehydration, weakness, and orthostatic hypotension, along with potentially severe consequences like cardiovascular collapse and shock due to extreme hyponatremia.
- Glucocorticoid deficiency results in poor stress tolerance, hypoglycemia, lethargy, weakness, fever, and gastrointestinal symptoms such as nausea, vomiting, and weight loss.
- Androgen deficiency in women can lead to sparse axillary and pubic hair, while increased levels of ACTH can cause pigmentation of the skin and mucous membranes, resulting in a bronze or suntanned appearance, which varies in intensity depending on skin type.
Addison’s Disease:
- Adrenal glands make too little cortisol and, often, too little of another hormone, aldosterone.
Adrenal Crisis: Red Flag
- What is it = ?
- Typical symptoms = ?
- What should we do = ?
Adrenal Glands
Adrenal Crisis: Red Flag
(a) An adrenal crisis is the result of an extreme physical or emotional stress that occurs without the necessary steroid coverage to meet that stress.
(b) It is a potentially life‐threatening medical emergency that requires management in a hospital or emergency department.
(c) Typical symptoms are:
- Severe drop in blood pressure causing dizziness, lightheadedness and possibly loss of consciousness
- Nausea and vomiting
- Confusion and lethargy
- Muscle weakness, cramps, headaches
(d) Adrenal insufficient patient should be equipped with a glucocorticoid injection kit for emergency use and be educated on how to use it.
- (Solu‐Cortef Act‐O‐Vial, 100mg hydrocortisone)
- Medical alert id
(e) What should you do?
- Administration of synthetic cortisol by a physician, patient or trained provider
- Call 911 to get to the patient to the Emergency Department
Diagnosis and Treatment:
- Adrenal Crisis = ?
Adrenal Glands
Diagnosis and Treatment
(a) Diagnosis:
- Sodium, potassium levels, and corticosteroid levels remain depressed after administration of ACTH.
(b) Treatment
- Replacing fluids, electrolytes, glucose and cortisol
- In acute illness, IV fluid replacement along with hydrocortisone
(c) Lifetime replacement therapy
- Oral replacement therapy: should have glucocorticoid and mineralocorticoid activities
- Hydrocortisone
- DHEA in female patients
Glucocorticoid Hormone Excess:
- High levels of cortisol due to different reasons = ?
Adrenal Glands
Glucocorticoid Hormone Excess:
(a) Excess glucocorticoid production by the body from any cause
- Endogenous or exogenous
(b) Cushing Syndrome / Disease / Hypercortisolism
- High levels of cortisol due to different reasons.
- Hormonal disorder that occurs when the body produces too much cortisol over a long period of time
(c) Endogenous causes:
- Tumor of pituitary gland = excessive production of ACTH
- Cushing’s disease
- Adrenal gland tumor
- Ectopic production of ACTH / CRH from s tumor at distant site.
(d) Exogenous causes: Taking glucocorticoid drugs (hydrocortisone, cortisol derivate like dexamethasone)
- Decrease deleterious effects of chronic inflammation; long term use suppresses the cortisol production by renal cortex and should not be discontinued abruptly.
- As a therapist, you will see people who have developed Cushing’s syndrome because of medications – large doses of cortisol (hydrocortisone) or cortisol derivatives.
Glucocorticoid Hormone Excess - Cushing’s disease:
- Clinical Manifestations = ?
Adrenal Glands
Glucocorticoid Hormone Excess - Clinical Manifestations:
(a) Protein breakdown:
- Muscle wasting,
- Weakness
- Protuberant abdomen
- Slender limbs
- Thin skin.
(b) Altered fat metabolism:
- Abnormal fat distribution
- Moon shaped face
- Dorso cervical fat pad (buffalo hump)
- Truncal obesity
- Thinning of skin with purple striae on breast
(c) Altered calcium metabolism:
- Osteoporosis
- Back pain
- Fractures
- Renal calculi.
(d) Poor wound healing:
- Inhibition of collagen formation with cortiscisteriods.
- Decreased immune response
- Increased susceptibility to infection
- ” “ ulcerations
(e) Altered glucose in tolerance:
- Persistent hyperglycemia
- “steroid diabetes”
(f) GI:
- Increases gastric acid secretion
- Gastric ulceration/ bleeding
- Increase mineralocorticoid Hypokalemia, hypernatremia (hypertension)
(g) Increase in androgens levels along with glucocorticoids:
- Hirsutism (excessive body and facial hair), changes in pattern of pubic and axillary hair growth
- Memory/ concentration/ cognitive
- Difficult to recognize facial changes
Cushing’s disease:
Diagnosis = ?
Treatment = ?
Adrenal Glands
Cushing’s disease: Hypercortisolism, is a hormonal disorder that occurs when the body produces too much cortisol over a long period of time
Diagnosis:
- 24 hour urinary cortisol levels
- Late night salivary cortisol (11-midnight: <100ng/dL)
- Imaging of pituitary, adrenal glands
Treatment:
(a) Remove (of pituitary adenoma) / correct the source of hypercortisolism
- Surgery
- Irradiation
- After removal, cortisol replacement therapy
(b) Drugs: that block steroid synthesis if there is tumor (e.g. ketoconazole).
(c) Precautions to minimize infections
Actions of Adrenal Hormones:
- Mineralocorticoids = ?
- Glucocorticoids = ?
- Adrenal sex hormones = ?
- Epinephrine and norepinephrine = ?
Adrenal Glands
Actions of Adrenal Hormones:
(a) Mineralocorticoids (aldosterone)
- Regulates sodium and potassium levels
- ” “ water balance
- ” “ blood pressure
(b) Glucocorticoids (cortisol)
- Regulates metabolism of glucose, fats, proteins
- Inflammatory / immune response and stress response.
(c) Adrenal sex hormones
- Pubic and axillary hair growth in women
(d) Epinephrine and norepinephrine
- Sympathetic response
Addison’s vs. Cushings:
- Signs and symptoms = ?
Adrenal Glands
Addison’s vs. Cushings:
(a) Addison’s Disease:
- Personality changes
- Anorexia, nause, vomiting
- Hyper-pigmentation
- Cardiac insufficiency, hypotension
- Adrenal atrophy:
- Autoimmune
- Infection
- Tumor metatasis
- Diarrhea, abdominal pain
- Muscle Weakness
(b) Cushing’s Disease:
- Thinning of scalp hair
- Emotional instability
- Acne
- Moon face
- Increased facial hair
- Buffalo hump
- Osteoporosis
- Cardiac hypertrophy & Hypertension
- Adrenal:
- Hyperplasia
- Tumor
- Truncal obesity
- Striae of skin
- Easy bruising
- Muscle Wasting:
- Weakness
- Thin extremities
- Diabetes mellitus
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