Adrenal Hormones Quiz

Adrenal Glands Introduction

• The human body needs a well-regulated extracellular environment
• Adrenal glands play a vital role in maintaining this environment
• Two adrenal glands, each weighing approximately 4 grams
• Each gland is made up of two endocrine organs: the adrenal cortex (80%) and the adrenal medulla (20%)
• The adrenal cortex develops from mesoderm, while the adrenal medulla develops from neural crest
• Each gland secretes hormones belonging to different chemical categories
• These hormones differ in function, mechanism of action, and regulation

Adrenal Cortex Introduction

• The adrenal cortex is made up of three layers: Zona glomerulosa, Zona fasciculata and Zona reticularis
• The cortex produces adrenocortical hormones. The distribution of enzymes differs throughout the layers
• Mineralocorticoids: Primarily aldosterone (Zona glomerulosa)
• Glucocorticoids: Primarily cortisol (Zona fasciculata and Zona reticularis)
• Sex hormones: Primarily DHEA (Zona fasciculata and Zona reticularis), produced in greater abundance in the gonads

Adrenocortical Hormones Introduction

• Adrenocortical cells release only small amounts of aldosterone, cortisol, and DHEA at any given time
• The cells produce and release these hormones on demand rather than storing them
• These hormones are lipophilic and diffuse into the bloodstream after synthesis
• Steroid hormones are extensively bound to plasma proteins such as CBG and albumin, which prevents hormone entry into cells and excretion
• Unbound hormones interact with cell receptors, and are then cleared from the bloodstream
• Bound hormone dissociates from the binding protein, replenishing the pool of circulating free hormone
• Free hormone binding makes a hormone-receptor complex move to the nucleus and bind to complementary hormone response elements on DNA
• This process initiates gene transcription and the synthesis of new proteins

Average Daily Production of Hormones by Adrenal Cortex

• The average daily production amounts for hormones are different
  • Cortisol: 20 mg/day
  • Aldosterone: 0.1 mg/day
  • DHEA: 30 mg/day
• Hormone amounts can vary based on physiological state

Aldosterone Function

• Aldosterone works in the distal and collecting tubules of the kidney
• It regulates sodium and potassium elimination during urine formation
• It promotes sodium retention, which secondarily increases the osmotic retention of water, expanding ECF volume
• Aldosterone is essential for long-term blood pressure regulation

Aldosterone Production and Secretion

• Factors stimulating renin-angiotensin-aldosterone system (RAAS) activation are related to a decrease in sodium and drop in blood pressure
• Angiotensin II is a potent stimulator of aldosterone production
• Other stimulating factors include:
  • Rise in plasma potassium which depolarizes glomerulosa cells, opens voltage-sensitive calcium channels, and stimulates aldosterone production
  • Acute elevated ACTH
• Inhibitory factors include:
  • Atrial natriuretic peptide (ANP), which is secreted by the heart, acts directly on zona glomerulosa cells to inhibit aldosterone production
  • Chronic elevated ACTH
• Aldosterone escape response is a physiological process to limit fluid retention and prevent hypertension despite high levels of aldosterone

Cortisol Function

• Metabolic: Increases blood glucose, at the expense of protein and fat, in response to fasting, inhibits glucose uptake by many tissues (especially sparing the brain), and increases hepatic gluconeogenesis (particularly important to replenish hepatic glycogen stores between meals)
• Metabolic: Stimulates protein degradation, especially in the muscles, providing amino acids for gluconeogenesis, and facilitates lipolysis (increasing free fatty acids and glycerol)
• Permissive Actions: Increases the responsiveness of cells to glucagon and catecholamines.
• Stress Adaptation: In acute situations, cortisol's catabolic mechanisms provide energy to the body. Reproduction involves substantial energy expenditure, and cortisol reduces reproductive axis function at the hypothalamus, pituitary, and gonads..
• Anti-inflammatory & Immunosuppressive Effects: Cortisol holds immune responses in balance, excessive responses can cause harm.
• Glucocorticoid Therapy / Rheumatoid Arthritis & Prevention of Organ Transplant Rejection: Used only when warranted. Suppresses the body’s immune system but involves troublesome side effects and potentially irreversible atrophy of cortisol-secreting cells.

Cortisol Secretion

• ACTH stimulates growth and secretory output of the zona fasciculata and zona reticularis
• ACTH secretion is controlled by hypothalamic CRH
• Feedback mechanisms using cortisol inhibit ACTH and CRH
• Diurnal rhythm and stress influence hypothalamic CRH secretion

Adrenal Cortex & Sex Hormones

• Both sexes produce androgens and estrogens in the adrenal cortex although, normally in smaller quantities
• Under normal conditions, these levels are not high enough to induce significant effects, but DHEA is the adrenal sex hormone with biological significance
• Males have very high testosterone levels so adrenal androgens have limited significance
• In females, DHEA is a precursor for intracellular estrogen and androgen production, hence important for androgen-dependent processes

Adrenal Sex Hormones Secretion

• ACTH controls adrenal secretion of sex hormones, but adrenal sex hormones do not feed back on the hypothalamus-pituitary-adrenal (HPA) axis
• DHEA inhibits gonadotropin-releasing hormone (not CRH)
• There is a surge of adrenal androgen secretion at puberty, peaking between 25-30 years of age. Levels decline later in life.

Disorders of the Adrenal Cortex

• Many disorders of adrenal cortex function exist, but are generally uncommon
• Hormone levels can be too high or too low
• Specific disorders for discussion include:
  • Aldosterone hypersecretion
  • Cortisol hypersecretion (Cushing's syndrome)
  • Adrenogenital syndrome
  • Adrenocortical insufficiency

Aldosterone Hypersecretion Causes & Symptoms

• Causes:
  • Primary hyperaldosteronism (Conn's syndrome) - hypersecreting adrenal tumor
  • Secondary - inappropriately high activity of RAAS (renin-angiotensin-aldosterone system).
• Symptoms:
  • Increased whole body sodium, fluid, and circulating blood volume
  • Excessive potassium depletion (hypokalemia)
  • Weakness and fatigue
  • Hypertension (high blood pressure)

Cortisol Hypersecretion (Cushing Syndrome)

• Causes:
  • Pituitary adenomas secreting excessive ACTH leading to adrenal hyperplasia and excess cortisol secretion
  • Ectopic ACTH secretion, e.g from tumors (especially lung tumors)
  • Adrenal cortical adenomas (tumors)
  • Exogenous corticosteroid use
• Symptoms
  • Related to the exaggerated physiological effects of glucocorticoids
    • Excessive gluconeogenesis, hyperglycemia (high blood glucose) and glucosuria (glucose in urine)
    • Adrenal diabetes
    • Protein shortage
    • Body fat deposition (characteristic locations like abdomen, above shoulder blades, face)
    • Muscle wasting
    • Tendency to weight gain
    • Muscle weakness and fatigue
    • Other skin, blood vessel and skeletal effects

Adrenogenital Syndrome

• Adrenal androgen hypersecretion, a masculinizing condition seen more frequently than excess adrenal estrogen secretion
• Symptoms depend on the age and sex of the individual when hyperactivity begins
• Cause: Inherited defect in the cortisol pathway
• Symptoms in newborn females and adult females include:
  • Infants manifest male-type external genitalia. This can become a major cause of female pseudohermaphroditism.
  • Hirsutism (excessive hair growth) in adult females
  • Other male secondary sexual characteristics
• Symptoms in Prepubertal males and adult males include:
  • Precocious pseudopuberty (abnormally early puberty)
  • Males may also show very high testosterone levels

Adrenocortical Insufficiency

• One gland becomes non-functional/removed, sometimes the other can take over via hypertrophy/hyperplasia
• Both glands must be affected for the disease to manifest
• Primary Adrenocortical Insufficiency (Addison's Disease):
  • All layers of the cortex under-secrete
  • Aldosterone and cortisol levels are deficient
  • Cause: Autoimmune destruction of the adrenal cortex
• Secondary Adrenocortical Insufficiency:
  • Pituitary or hypothalamic abnormality
  • Insufficient ACTH (adrenocorticotropic hormone) secretion
  • Only cortisol is deficient

Primary Adrenocortical Insufficiency (Addison's Disease) Symptoms

• Aldosterone deficiency
  • Most life-threatening
  • Primarily loss of adrenal function develops slowly
  • Retention of potassium (hyperkalemia) reducing loss in the urine
  • Disturbs cardiac rhythm
• Sodium depletion (hyponatremia)
  • Excessive urinary loss of sodium
  • Reduced ECF blood volume
  • Low blood pressure (hypotension)

Primary Adrenocortical Insufficiency/Addison's Disease Symptoms & Treatment

• Cortisol deficiency
  • Reduced response to stress
  • Hypoglycemia (Low blood glucose)
  • Reduced gluconeogenesis
  • Darkening of the skin (hyperpigmentation)
  • Excessive ACTH resulting from the absence of cortisol
    • ACTH binds to related α-MSH receptors rather than intended receptors
  • Combined lack of glucocorticoid and mineralocorticoid can lead to life-threatening complications
• Treatment:
  • Reversal of hypotension, electrolyte abnormalities
  • Administration of saline, dextrose in saline
  • Administration of Cortisol and mineralocorticoid replacement therapy

Adrenal Medulla Introduction

• The adrenal medulla consists of modified postganglionic sympathetic neurons called chromaffin cells
• Chromaffin cells do not have axonal fibers terminating on effector organs
• The cells release adrenaline (80%) and noradrenaline directly into the circulatory system after preganglionic stimulation
• Adrenaline is produced exclusively by the adrenal medulla; noradrenaline is mostly produced by sympathetic postganglionic fibers

Function of Catecholamines: Effects on Organ Systems

• The sympathetic nervous system and adrenomedullary adrenaline participate in the "fight-or-flight" response, increasing heart rate and cardiac output, blood pressure, and reducing digestive activity, and inhibiting bladder emptying.
• Adrenaline and noradrenaline dilate coronary and skeletal muscles blood vessels and dilate airways.

Function of Catecholamines: Metabolic Effects

• Catecholamines prompt the mobilization of stored carbohydrates and fats to provide energy for muscular work. These include hepatic gluconeogenesis and glycogenolysis, muscle glycogenolysis, lipolysis, and the inhibition of insulin release with concurrent stimulation of glucagon release to provide adequate fuel.

Function of Catecholamines: Other Effects

• Catecholamines promote arousal, increased alertness, and sweating to reduce body temperature
• Catecholamine secretion is triggered by sympathetic input to the gland, in response to injury, anger, anxiety, pain, cold, strenuous exercise, and hypoglycemia.
• Chromaffin cells release hormones into the circulatory system when stimulated

Summary: Adrenal Hormones

• Adrenal Cortex: Regulates sodium, potassium, and blood pressure via RAAS; cortisol increases glucose and has anti-inflammatory actions; abnormalities can lead to Cushing's syndrome. DHEA is a significant androgen precursor.
• Adrenal Medulla: Secretes adrenaline and noradrenaline (catecholamines); these hormones regulate stress responses, increasing heart rate, blood pressure and glycogenolysis.