Endocrine

ADRENAL GLANDS

• Objectives
• At the end of this lecture, the student should be able to:
• Describe the anatomy of adrenal glands.
• State the synthesis and secretion of adrenal hormones.
• Explain the functions of the adrenal hormones.
• Identify the pharmacological actions and therapeutic principles of corticosteroids.
• List the side effects of steroid abuse.
• Recognize the importance of steroid tapering after prolonged use.

Anatomy and Function

Capsule
Cortex (outer) has 3 zones:
1- Zona glomerulosa : mineralocorticoids, mainly aldosteron, responsible for the regulation of BP. It affects the distal convoluted tubule and collecting duct of the kidney (increased reabsorption of Na + and excretion of both K + and H + ions.
2- Zona fasciculata: glucocorticoids, such as
11-deoxycorticosterone, corticosterone, and cortisol in humans.

3- Zona reticularis: produces androgens, mainly dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and androstenedione (the precursor to testosterone) in humans.

Medulla (core of the gland)

It secretes norepinephrine and epinephrine. Catecholamines (aa tyrosine ), water-soluble, the major hormones underlying the fight-or-flight response.
Receives input from the sympathetic nervous system through preganglionic fibers originating in the thoracic spinal cord from T5–T11.
Cortisol also promotes epinephrine synthesis.

History

1855 – Addison's disease


1856 – Adrenal glands essential for life



1930 – Cortex > medulla


1932 – Cushing’s syndrome


1949 – Steroids in rheumatoid arthritis


1952 – Aldosterone

• Basal secretions

• Group
• Hormone
• Daily secretions
• Glucocorticoids
• Cortisol
• Corticosterone
• 5 – 30 mg
• 2 – 5 mg
• Mineralocorticoids
• Aldosterone
• 11- deoxycorticosterone
• 5 – 150 mcg
• Trace
• Sex Hormones
• Androgen
• Progestogen
• Oestrogen
• DHEA
• Progesterone
• Oestradiol
• 15 – 30 mg
• 0.4 – 0.8 mg
• Trace

Cholesterol

Pregnenolone
Progesterone

Corticosterone

11-Desoxy-corticosterone
18-Hydroxy- corticosterone
ALDOSTERONE

17-α- Hydroxy pregnenolone

11- Desoxy- cortisol
17- Hydroxy progesterone
21,β hydroxylase

CORTISOL

11,β hydroxylase


Dehydro-epi androsterone
Andro-stenedione

Oestrone

Oestriol

TESTOSTERONE

OESTRADIOL

ACTH

Pharmacological Actions
• Carbohydrate
• Protein
• Lipid
• Electrolyte & water
• CVS
• Sk. Muscle
• CNS
• Stomach
• Blood
• Anti-inflammatory
• Immunosuppressant
• Respiratory system
• Growth & Cell Division
• Calcium metabolism


Actions: Carbohydrate and protein metabolism
Gluconeogenesis ( in early fasting)
Peripheral actions (from AA, glycerol, lactate)
Hepatic actions ( glycogenolysis by passive influence on glucagon and activation of glycogen phosphorylase)
Peripheral utilization of glucose

Glycogenesis ( increase glycogen deposition in liver from unused glucose in late fasting) by activation of hepatic glycogen synthase.

Proteolysis and muscle wasting.

Negative nitrogen balance & hyperglycemia

Redistribution of Fat

Buffalo hump
Supraclavicular fat
Moon face

Stimulation of fat breakdown in adipose tissue

Actions: Lipid metabolism


Cortisol sodium and water absorption and potassium excretion in the intestines.
Aldosterone is more important, acts on D.T. & C.D. of kidney
Na+ reabsorption
Urinary excretion of K+ and H+

Actions: Electrolyte and water balance

Actions: Cardiovascular system
Restrict capillary permeability
Maintain tone of arterioles
Enhance myocardial contractility
Hypertension

Addison's disease: weakness & fatigue is due to

Prolonged use:

Actions: Skeletal Muscles

Needed for maintaining the normal function of Sk. muscle
inadequacy of circulatory system
Steroid myopathy


Direct:
Mood
Cortisol works with epinephrine to create memories of short-term emotional events; this is the proposed mechanism for storage of flash bulb memories.

Actions: CNS

ICP (pseudotumor cerebri) - Rare

Aggravate peptic ulcer. May be due to

Acid & pepsin secretion

Immune response to H.Pylori

Actions: Stomach

RBC: Hb & RBC content

(erythrophagocytosis )

WBC: Lymphocytes, eosinophils, monocytes,

basophils

Actions: Blood

Recruitment of WBC & monocyte- macrophage
into affected area & elaboration of chemotactic
substances
Lipocortin
Production of IL12, (INF)- gamma and alpha, (TNF)- alpha from phagocytic cells and (Th)1 cells.
Upregulate IL4, 10, 13 by Th 2 cells.
Response of T cell to IL1 so unable to produce IL2.
Formation of Plasminogen Activator
Fibroblastic activity
Expression of cyclooxygenase II

Actions: Anti-inflammatory

Phospholipids
Arachidonic acids
lipoxygenase
Cycylooxygenase
Leukotriene
Prostaglandins,
Thromboxane
Prostacyclins
Phospholipase A2
Lipocortin (it supresses Phospholipase A2)
Corticosteroids

Anti-inflammatory actions of corticosteroids

Corticosteroid inhibitory effect

Immunosuppressive & anti-allergic actions

Suppresses all types of hypersensitivity & allergic phenomenon.
At High dose: Interfere with all steps of immunological response.
Causes greater suppression of CMI (graft rejection & delayed hypersensitivity).
Transplant rejection: antigen expression from grafted tissues, delay revascularization, sensitization of T lymphocytes.

Inhibit cell division or synthesis of DNA.

Delay the process of healing.
Retard the growth of children.
Actions: Growth & Cell division

Intestinal absorption

Renal excretion

Excessive loss of calcium from spongy bones (e.g., vertebrae, ribs )

Actions: Calcium metabolism

Not bronchodilators

Most potent and most effective anti-inflammatory.
Effects not seen immediately (delay 6 or more hrs).
Inhaled corticosteroids are used for long term control.

Actions: Respiratory system