Adrenal Hormones
Adrenal Hormones
Adrenal Hormones
HORMONES
M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.
Adrenal glands Small, triangular glands loosely attached to the kidneys Divided into two morphologically distinct regions - adrenal cortex (outer) - adrenal medulla (inner)
Steroid Hormones
Steroid hormones are produced by the gonads and adrenal cortex. Steroid hormones are made from cholesterol in the smooth endoplasmic reticulum and mitochondria of endocrine cells.
Steroid hormones cannot be stored in vesicles in the endocrine cells that produce them. As soon as steroid hormones are produced, they diffuse out of the endocrine cell and enter the bloodstream. Steroid hormones are lipid soluble and their receptors are located in the cytoplasm target cell.
Steroid hormone transport Lipid soluble hormones require transport proteins albumin and transthyretin (prealbumin) specific transport molecules (steroidbinding globulin)
only unbound form can enter the cell Steroid and thyroid hormones are 99% attached to special transport proteins
Adrenal Medulla an extension of the sympathetic nervous system acts as a peripheral amplifier activated by same stimuli as the sympathetic nervous system (examples exercise, cold, stress, hemorrhage, etc.)
Tyrosine Synthesis of (1) Tyrosine hydroxylase Catecholamines (+)O2 Dopa PLP CO2 Dopamine Cu++ (3) Dopamine hydroxylase Vit C Norepinephrine SAM (4) N-METHYL TRANSFERASE SAH Epinephrine SAM (5) Catechol-O-methyl transferase SAH Metanephrine (6) Mono amino oxidase VMA (Vanillyl mandalic acid) (2) Dopa decarboxylase
Mechanism of Action receptor mediated adrenergic receptors peripheral effects are dependent upon the type and ratio of receptors in target tissues
Receptor ++ ++++ Norepinephrin +++++ e Epinephrine ++++
Pheochromocytoma a catecholamine-secreting tumour of chromaffin cells of the adrenal medulla adrenal pheochromocytoma (90%) paraganglioma a catecholamine secreting tumour of the sympathetic paraganglia extra-adrenal pheochromocytoma
Signs and Symptoms of Pheochromocytoma treatment resistant hypertension (95%) headache classic triad sweating palpitations chest pain anxiety glucose intolerance increased metabolic rate
Diagnosis and Treatment diagnosed by high plasma catecholamines and increased metabolites in urine no test for adrenal or extra-adrenal treatment is surgical resection
Adrenal Cortex Hormones produced by the adrenal cortex are referred to as corticosteroids. These comprise mineralocorticoids, glucocorticoids and androgens.
Zona Glomerulosa
Outermost zone just below the adrenal capsule Secretes mineralocorticoids.
Zona Fasciculata
Middle zone between the glomerulosa and reticularis Primary secretion is glucocorticoids.
Glucocorticoids, as the term implies, are involved the increasing of blood glucose levels. However they have additional effects in protein and fat metabolism.
The naturally synthesized glucocorticoid of most importance is cortisol.
Zona Reticularis
Innermost zone between the fasciculata and medulla Primary secretion is androgens. Androgenic hormones exhibit approximately the same effects as the male sex hormone testosterone.
Hormones of the Adrenal Cortex all adrenal cortex hormones are steroids
HO CH2OH C=O OH HO
O O
testosterone
cortisol
Aldosterone
a steroid hormone
Effects of Aldosterone
Renal and circulatory effects covered (ECF volume regulation, sodium and potassium ECF concentrations) Promotes reabsorption of sodium from the ducts of sweat and salivary glands during excessive sweat/saliva loss. Enhances absorption of sodium from the intestine especial. colon. absence leads to diarrhea.
Regulation of Aldosterone Release direct stimulators of release - increased extracellular K+ - decreased osmolarity - ACTH indirect stimulators of release - decreased blood pressure - decreased macula densa blood flow
Glucocorticoids - Cortisol
a steroid hormone
- plasma bound to corticosteroid binding globulin (CBG or transcortin) essential for life (long term)2hr
Anti-inflammatory Effects of Cortisol reduces phagocytic action of white blood cells reduces fever suppresses allergic reactions
Regulation of Cortisol Release Enhanced release can be caused by: physical trauma infection extreme heat and cold exercise to the point of exhaustion
Adrenal Cortex Dysfunctions Hypoadrenalism Addisons Disease adrenal cortex produces inadequate amounts of hormones caused by autoimmunity against cortices 80% also caused by tuberculosis, drugs, cancer plasma sodium decreases and may lead to circulatory collapse
Mineralocorticoid Deficiency
Lack of aldosterone:
Increased sodium, chloride, water loss Decrease ECF volume Hyperkalemia Mild acidosis Increase RBC concentration Decrease cardiac output shock - death within 4 days to a 2 weeks if not treated
Glucocorticoid Deficiency
Loss of cortisol
Disruption in glucose concentration Reduction in metabolism of fats and proteins Patient is susceptible to different types of stress Sluggishness of energy mobilization result in weak muscle even when glucose and other nutrients are available cortisol is needed for metabolic function
Melanin Pigmentation
Characteristic of Addisons disease is uneven distribution of melanin deposition in thin skin eg. Mucous membranes, lips, thin skin of the nipples. Feedback and effect on MSH
Treatment
Total destruction, if untreated, could lead to death with a few days. Treatment small quantities of mineralocorticoids and glucocorticoids daily.
caused by exogenous glucocorticoids and by tumours (adrenal or pituitary) zg tumour increases aldosterone -increased sodium, blood pressure -80% suffer from hypertension zr tumour increases cortisol - excess protein catabolism, redistribution of fat
Characteristics
Buffalo torso
Redistribution of fat from lower parts of the body to the thoracic and upper abdominal areas
Moon Face
Edematous appearance of face Acne & hirsutism( excess growth of facial hair)
What Would the Feedback Loop Look Like for Cushings Syndrome?
Cushings Syndrome
moon face
striae
Treatment
Removal of adrenal tumor if this is the cause Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop
21 Hydroxylase Deficiency:
21 Hydroxylase Deficiency is the most common type, where the production of cortisol is totally absent. The lack of feedback leads to increased androgen synthesis. This would result in Virilization of female children who develop ambiguous genitalia. precocious puberty is seen in male children. Early diagnosis and supplementation of cortisol is effective in children.
11-Hydroxylase Deficiency:
7) Metyrapone test :
metyrapone inhibits the hydrolase enzyme. when it is given, cortisol is not formed. Then there is no feedback inhibitory effect. Hence, alternate pathways of sex steriods are more operative and the urinary excretion of 17ketosteriods tends to elevate. 8) CRH test: The test is of importance in establishing the cause of adrenal hyperfunction ( primary, secondary or tertiary)
Normal ranges:
Aldosterone : 6 20 ng/ml Corticosterone : 130- 820ng/dl Cortisol : in 9 AM 5-25microgram/dl midnight 2-5 microgram/dl Progesterone: 12- 30 ng/ml Epinephrine 10- 100pg/ml nonEpinephrine70-700pg/ml
NORMAL VALUE OF CORTISOL : plasma 9 AM -------------------------130 600 nmol / L MIDNIGHT---------------30 - 130 nmol / L
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