Test #5 Notes 3

Adrenal Cortex

Introduction Anatomy – zonation Z. Glomerulosa, Z. Fasciculata, Z. Reticularis

Hormones Produced – Glucocorticoids (cortisol); Mineralocorticoids (aldosterone), Androgens (DHEA)

Steroids Secreted by the Human Adrenal Cortex Steroid Cortisol Aldosterone

Secretion rate (mg/day) 12-30 0.05-0.15

DHEA

7-15

DHEA-sulfate

10-25

Hormone Biosynthesis  Role and Sources of Cholesterol  Pathways of Hormone Production 1. Mineralocorticoid Synthesis 2. Glucocorticoid Synthesis 3. Androgen Synthesis

Steroidogenic pathways in the zona glomerulosa (within broken lines) and zona fasciculata-zona reticularis (within solid lines) of the human adrenal cortex. The major secretory products are shaded.

Zona reticularis and fasciculata

Zona glomerulosa

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Secretion and Distribution of Adrenal Hormones Secretion – Determined by rate of synthesis Circulation – Extensive protein binding (transcortin, CBG)

Actions of Adrenal Hormones  Mechanism of Action – lipophilic hormones  Glucocorticoids 1. Physiological 2. Pharmacological 

Glucocorticoid Effects and Target Tissues Effect Site of Action Stimulates gluconeogenesis Liver Increases hepatic glycogen Liver Increases blood glucose Liver Increases lipolysis Adipose tissue Catabolic (negative nitrogen balance) Muscle, liver Blocks inflammatory response Suppresses immune system

Multiple sites Multiple sites

Carb ohy dr ate and pr otei n meta bol is m  Corticosteroids protect dependent tissues, e.g., brain and heart from starvation.  Stimulates the liver to form glucose and…  Net result: increase glucose levels  Mechanism: translocation of the glucose transporter from the plasma membrane to an intracellular location.  Problem: glucocorticoids can worsen glycemic control in patients with diabetes

Lip ids  Redistribution of body fat (Cushing’s syndrome) back of the neck (buffalo bump), face (moon facies)  Truncal adipocytes respond predominantly to insulin and Glucocorticoids-induced hyperglycemia.

CNS Acute  Mood elevation  Euphoria  Insomnia  Increase motor activity Chronic  Anxious  Depressed  Psychosis Neurosteroids regulate neural excitability

Mineralocorticoids Bl ood pr essur e r e gul atio n El ectr ol yte bal ance Mineralocorticoid Effects and Target Tissues Effect Site of Action Stimulates Na+ reabsorption Kidney, salivary glands, sweat glands Stimulates K+ excretion Kidney, salivary glands, sweat glands Stimulates H+ excretion Kidney

Regulation of Hormone Secretion Glucocorticoid (Cortisol) Negative feedback system

Diurnal rhythm

Diurnal rhythm of plasma cortisol concentrations

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Stress Mechanism of action of ACTH cAMP

B. 1. 2.

Mineralocorticoid (Aldosterone) Reni n - Angi otensi n Sys tem Pl asma Potassi um

Regulation of aldosterone secretion by the zona glomerulosa of the adrenal cortex (+, stimulation; -, inhibition; ECF, extracellular fluid)

Pathophysiology of Adrenal Cortex Cushing’s Syndrome Hypercortisolism 1.

Symptoms Symptom

Centripetal obesity Hypertension Hyperglycemia Amenorrhea Hirsutism Purple striae “Moon” facies Osteoporosis Personality change

Frequency of Occurrence (%) 95 82 80 75 75 65 60 60 55

2.

Causes

B.

Adrenocortical Insufficiency 1. 1°(Addison’s Disease) vs. 2°

2.

Symptoms of Addison’s Disease

Symptom Weakness and fatigability Weight loss Hyperpigmentation Hypotension Hyponatremia Hyperkalemia 3.

Frequency of Occurrence (%) 100 100 92 88 88 65

Differential Diagnosis – 1°vs. 2°

Hyperaldosteronism 1° (Conn’s Syndrome) – adrenal tumor 2° - many causes 3.

Symptoms

4.

Differential Diagnosis

Pathogenesis of Primary vs. Secondary Hyperaldosteronism Primary Hyperaldosteronism ↑ Aldosterone → ↑ Na+ retention →

↑ ECF volume + → ↓ Renin ↑ Renal perfusion pressure

Secondary Hyperaldosteronism ↑ Na+ retention ↓ Renal perfusion pressure → ↑ Renin → ↑ Aldosterone → + ↑ ECF volume

Congenital Adrenal Hyperplasia (Adrenogenital Syndrome)  1. Cause – enzymatic defect in adrenal gland  2. Symptoms - varied  3. Treatment – replace missing hormones

Consequences of a 21-hydroxylase (enzyme number 3) deficiency on adrenocortical steroidogenesis. The shaded area contains the hormones that cannot be synthesized as a result of the defect.