Adrenal Gland Flashcards
Anatomy of adrenal glands
The adrenal glands are also called the suprarenal glands and they sit on top of the kidneys. The adrenal glands weigh just 5 grams and have a dense fibrous capsule which attaches each gland to the kidney. They are pyramidal in shape.
Arterial supply of adrenal glands
Inferior phrenic artery (superior supra renal artery)
Aorta (middle supra renal artery)
Renal artery (inferior supra renal artery)
Very vascular organ
Histology of the Adrenal Gland
The suprarenal gland consist of a cortex (mesoderm) and a medulla (made up of neuroectodermal cells). The cortex has three areas which produce three different hormones:
Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
Adrenal Histology & Hormones
Adrenal cortex:
Zona Glomerulosa: Aldosterone (15%)
Zona Fasciculata: Cortisol (80%)
Zona Reticularis: Androstenedione and dehydroepiandrosterone (5%)
Adrenal medulla: Adrenaline and noradrenaline
Adrenocortical hormones
We know that adrenocortical hormones are derived from cortisol.
Function of aldosterone
The aldosterone stimulates the conservation of sodium and eliminates potassium. The retention of sodium enhances the absorption of water by the kidneys and other glands, like the sweat in the salivary glands.
Feedback of aldosterone
Reduced renal prefusion leads to production of renin in the kidneys. The angiotensinogen is produced in the liver combines with renin to produce angiotensin I. This is then converted into angiotensin II in the presence of the angiotensin converting enzyme (ACE) which occurs in the lungs. The angiotensin II is an important stimulator of aldosterone. Aldosterone as previously stated acts on renal tubules leads to conversion of sodium, loss of potassium, and water retention to decrease blood pressure.
Biosynthesis of aldosterone
Aldosterone produced by the cells of Zona Glomerulosa. Angiotensin II binds to a membrane surface receptor on the cell of the Zona Glomerulosa and through protein kinase C and calcium, promotes conversion of cholesterol to aldosterone through the mitochondria of a cell of Zona Glomerulosa. This isn’t one step, but multiple steps.
Aldosterone directly enters the system directly through the blood.
Disease of Adrenal Cortex
Hormonal over production :
Zona Glomerulosa: mineralcorticoid excess (Conn’s syndrome)
Zona Fasciculata: glucocorticoid excess (Cushing’s syndrome)
Hormonal under-production:
Primary: Addison’s disease
Secondary: Hypopituitarism
Incidentalomas
Adrenal Carcinoma
Primary Hyperaldosteronism
Primary hyperaldosteronism is the term used to describe excess aldosterone which can lead to hypertension, hypokalaemia and metabolic alkalosis.
Conn’s syndrome
Primary hyperaldosteronism (adenoma)
Renal Na+ & K+ loss
Hypokalaemic alkalosis
2% of patients with hypertension
Hypertension resistant to medication, hypokalaemia
Hypertension < 40 years of age
Conn’s Syndrome: Diagnosis and Management
Diagnosis: High levels of aldosterone/Renin ratio
CT/MRI scan
Adrenal vein sampling: allows differentiation between unilateral & bilateral aldosterone production
Surgical Rx: Adrenalectomy
Medical Rx: Aldosterone antagonist (spironolactone, amiloride & triamterene)
Glucocorticoids (Cortisol)
Glucocorticoids (cortisol) is the middle layer of the cortex which produces a hormone called cortisol (glucocorticoids).
Regulation of Cortisol
Cortisol is produced in the adrenal cortex. It’s mainly stimulated by the ACTH (adrenocorticotrophin hormone) which is produced from the anterior pituitary. The anterior pituitary gland is under control of the hypothalamus which releases a hormone called CRH (corticotrophin releasing hormone) which acts on the anterior pituitary stimulating the production of ACTH (adrenocorticotrophin hormone) which acts on the adrenal gland. This leads to cortisol secretion and at a certain cortisol level, there is a negative feedback within the anterior pituitary gland and hypothalamus that allows cortisol to remain in physiological levels.
Biosynthesis of Cortisol
ACTH (adrenocorticotrophin hormone) binds to a cell surface receptor on the cells of zona fasciculata and via cyclic AMP and protein kinase converts cholesterol ester to cholesterol via a lipase enzyme. The cholesterol then enters the mitochondria of the cell of the Zona fasciculata and undergoes a series of steps leading to the production of cortisol which is released into the systemic circulation.
Functions of cortisol
Functions of cortisol include:
Stress
Blood loss
Severe Infection
Trauma
Burns
Illness
Surgery
Cortisol have various effects on intermediary metabolism
What type of metabolism does cortisol effect?
Carbohydrate Metabolism
Lipid Metabolism
Protein Metabolism
Cortisol Effects on Carbohydrate Metabolism
Gluconeogenesis
Hepatic glycogen synthesis
Inhibits peripheral glucose uptake
Cortisol Effects of Lipid Metabolism
Lipolysis
Increased appetite
Fat deposition (central areas)
Cortisol Effects on Protein Metabolism
Protein catabolism
Decreased protein synthesis
Cushing’s syndrome
Increased ACTH (adrenocorticotrophin hormone) released from anterior pituitary gland leading to increase cortisol.
Cortisol hypersecretion
Diagnosis of Cushing’s Syndrome
Confirm cortisol hypersecretion (Cushing’s syndrome) then determine the source of high cortisol
24-hour urine free cortisol
Salivary cortisol
Midnight cortisol
Overnight dexamethasone suppression test
Serum ACTH
CRH/ high dose dexamethasone suppression test
Pituitary MRI scan
Inferior petrosal sinus sampling
CT scan adrenals
Adrenal Insufficiency
Primary adrenal insufficiency (rare, 0.8/100000)
Autoimmune adrenalitis
Infections (TB, histoplasmosis, Candidiasis, CMV, HIV)
Neoplastic infiltration & metastasis
Infiltration - hemochromatosis, amyloid
Thrombosis (antiphospholipid syndrome)
Adrenal haemorrhage (anticoagulants)
Secondary adrenal insufficiency
Pituitary disease
Drugs (long-term steroids)
Adrenal Insufficiency: Clinical Features
Anorexia, wight loss & fatigue
Skin pigmentation (light-exposed & areas of pressure)
Dizziness & postural hypotension
Loss of mineralocorticoid effect of aldosterone
Loss of permissive effect of cortisol on vasopressor effects of catecholamines
Hypoglycaemia
Other endocrine functions
Diagnosis of Adrenal Insufficiency
Hyponatraemia & hyperkalaemia
Inappropriately low cortisol for the levels of stress <500nmol/L
Short synacthen test (30 minute cortisol <500nmol/L)
Anti-adrenal antibodies
Other endocrine tests (thyroid & pituitary hormones)
Imaging (CT abdomen & MRI pituitary)
Management of Adrenal Insufficiency
Life threatening conditions:
Correct volume deficit (intravenous fluids)
Initial treatment: IM/IV hydrocortisone
Later oral hydrocortisone & fludrocortisone
DHEA: may help vitality, fatigue & sexuality
Double steroids in stressful situations/ intercurrent illness
Patients are encouraged to carry a medic-alert bracelet.
Adrenal Androgens
The Zona Reticularis is the inner most layer of the cortex and is responsible for production of androgens. The cells in the inner most layer of the adrenal cortex form a irregular network of chords and clusters of landless cells separated by numerous wide capillaries.
The main adrenal androgens are the dehydroepiandrosterone (DHEA) and androstenedione which are stimulated to be release by Zona Reticularis by ACTH (adrenocorticotrophin hormone) from the anterior pituitary gland.
When does dehydroepiandrosterone peak
Dehydroepiandrosterone (DHEA) peaks at 25 years of age.
When does masculinization occur?
Masculinization occurs when secreted in excessive amounts
What happens if there is excess adrenal androgens?
In pre-pubertal boys excess adrenal androgens may lead to precocious development of sexual characteristics
In females, foetus excessive adrenal androgens may led to pseudo hermaphroditism.
Hormones of adrenal medulla
Catecholamines
The predominant catecholamines are epinephrine (>75%) and norepinephrine (<25%).
Release of Catecholamines
In the presence of stress, there is sympathetic stimulation and then this leads to stimulation of the adrenal medullary cells, which then release epinephrine and norepinephrine which directly enters systemic circulation. These two hormones then act on adrenal receptors in the heart, blood vessels, bronchioles and muscles leading to an energetic response. The adrenaline is responsible for fight and flight response. Remember that the adrenal gland is believed to be a modified sympathetic plan.
Biosynthesis of catecholamines
Catecholamines are formed from hydroxylation and decarboxylation of tyrosine
Tyrosine is transported into catecholamine-secreting neurons & adrenal medullary cells
Converted into DOPA & Dopamine in the cytoplasm
Catecholamines are released from autonomic neurons& adrenal meduallary cells by exocytosis.
Actions of catecholamines
Mobilization of glycogen reserves
Breakdown of glycogen to glucose
Break down of fats to fatty acids
Increased rate & force of muscle contraction
Enables body to deal with physical & physiological stress.
What is pheochromocytoma
Adrenal medullary catecholamine secreting tumour.
Clinical presentation: hypertension, palpitations, sweating, heat intolerance, pallor, flushing, pyrexia & headache
Pheochromocytoma crisis: precipitated by straining, exercise, pressure on abdomen, surgery & drugs
Rare < 0.1% cause of hypertension
Equal sex distribution: 3rd to 4th decade
90% sporadic (10% inherited)
90% are benign & 90% are in the adrenal gland.
Pheochromocytoma: Diagnosis
Increase 24 hr urine catecholamine secretion
Increase plasma meta & normetanephrines
MRI/CT scan
Meta-iodobenzylguanidine (MIBG) scan
Initial management: alpha and beta blockers
Treatment: surgery
