Week 4

The adrenal glands, located on the cephalad portion of each kidney and consist of a  Cortex  Medulla The adrenal cortex and adrenal medulla each have separate endocrine functions.

Cortex >Zona glomerulosa >Zona fasciculata >Zona reticularis Medulla >Modified post-ganglionic neurons intimately connected to sympathetic neurons.

Adrenal glands interact with the hypothalamus and pituitary gland in the brain.  The hypothalamus makes corticotropin-releasing hormone (CRH).  This stimulates the pituitary gland to make adrenocorticotropic hormone (ACTH).  The ACTH stimulates the adrenal glands to make and release hormones into the blood.  Both the hypothalamus and the pituitary gland can sense whether the blood has the right amount of a hormone in it.  If there is too much or too little cortisol, these glands change the amount of CRH and ACTH they release.

The adrenal cortex produces • Glucocorticoids (primarily cortisol) • Mineralocorticoids (primarily aldosterone) • Androgens

• Promote and inhibit gene transcription in many cells and organ systems. • Prominent effects include anti-inflammatory actions and increased hepatic gluconeogenesis.

• Regulate electrolyte transport across epithelial surfaces, particularly renal conservation of sodium in exchange for potassium.

• Chief physiologic activity occurs after conversion to testosterone and dihydrotestosterone.

Affects glucose, protein, fat metabolism.  Inhibits synthesis of protein in tissues.  Promotes the use of fatty acids as energy source and decreases the use of glucose.  Stimulates liver cells to synthesize glucose from non-carbohydrates (gluconeogenesis) and increases blood glucose concentrations

Regulate adaptive immunity by inhibiting lymphocyte activation and promoting lymphocyte apoptosis. At high concentrations, glucocorticoids also inhibit the production of B cells and T cells. Glucocorticoids have potent anti-inflammatory and immunosuppressive properties.

 Affects the body's ability to regulate blood pressure.  It sends the signal to organs, like the kidney and colon, that can increase the amount of sodium the body sends into the bloodstream or the amount of potassium released in the urine.  The hormone also causes the bloodstream to re-absorb water with the sodium to increase blood volume

The major sex hormone in men is testosterone, which is produced mainly in the testes

 Composed of chromaffin cells, which synthesize and secrete catecholamines (mainly epinephrine and lesser amounts of norepinephrine).  Chromaffin cells also produce bioactive amines and peptides (eg, histamine, serotonin, chromogranins, neuropeptide hormones).  Epinephrine and norepinephrine, the major effector amines of the sympathetic nervous system, are responsible for the “flight or fight” response

Most adrenal deficiency syndromes affect output of all adrenocortical hormones

In Addison’s disease,  There is increased excretion of Na and decreased excretion of K, chiefly in the urine  Low blood concentrations of Na and Cl and a high concentration of serum K result. Inability to concentrate the urine, combined with  changes in electrolyte balance,  produces severe dehydration,  plasma hypertonicity, acidosis, decreased circulatory volume, hypotension, and circulatory collapse.

Mineralocorticoid deficiency Mineralocorticoids stimulate sodium reabsorption and potassium excretion:  Deficiency results in increased excretion of sodium and decreased excretion of potassium, chiefly in urine but also in sweat, saliva, and the gastrointestinal tract.  A low serum concentration of sodium (hyponatremia) and a high concentration of potassium (hyperkalemia) result. Glucocorticoid deficiency  Contributes to hypotension and causes severe insulin sensitivity and disturbances in carbohydrate, fat, and protein metabolism.  In the absence of cortisol, insufficient carbohydrate is formed from protein; hypoglycaemia and decreased liver glycogen result.  Weakness follows, due in part to deficient neuromuscular function. Glucocorticoid deficiency Decreased cortisol blood levels result in increased pituitary ACTH production and  increased blood levels of lipotropin, which has melanocyte-stimulating activity and produces the hyperpigmentation of skin and mucous membranes characteristic of Addison’s disease.

Abnormal serum electrolyte levels  including low Na (< 130 mmol/L),  high K (> 5 mmol/L),  low HCO3 (15 to 20 mmol/L)  and high BUN  Diagnosed by demonstrating failure to increase plasma cortisol levels, or urinary free-cortisol excretion, upon administration of ACTH

Patients with secondary adrenal insufficiency are not hyperpigmented, as are those with Addison's disease.  They have relatively normal electrolyte levels.  Hyperkalaemia and elevated BUN generally are not present because of the near-normal secretion of aldosterone in these patients.

 ACTH Stimulation Test  CRH Stimulation Test

Distinct clinical syndromes depending on the hormone involved:  Hypersecretion of aldosterone results in hyperaldosteronism.  Hypersecretion of glucocorticoids results in Cushing syndrome.  Hypersecretion of androgens results in adrenal virilism.  Hypersecretion of epinephrine and norepinephrine results in symptoms of pheochromocytoma.

 is a disease in which the adrenal gland(s) make too much aldosterone which leads to hypertension (high blood pressure) and low blood potassium levels.  Increases the renal distal tubular exchange of sodium for potassium and hydrogen  Progressive depletion of potassium and hydrogen leads to hypokalemia and acidosis  Excess sodium reabsorption leads to hypertension Classification  Primary – excess secretion by the adrenal glands  Secondary – renin-mediated secretion  Seen in congestive heart failure, nephritic syndrome, cirrhosis, renal artery hypertension, severe arteriolar nephrosclerosis, rare renin-secreting tumors

Mechanisms by which this can occur are many:  1) an adrenal tumour that autonomously secretes aldosterone;  2) unilateral or bilateral hyperplasia of the zona glomerulosa that oversecretes aldosterone;  3) or germline or somatic mutations that induce aldosterone hypersecretion

Patients with primary aldosteronism typically hav:  High plasma aldosterone > 15 ng/dL (> 0.42 nmol/L)  Low levels of PRA, with a ratio of plasma aldosterone (in ng/dL) to plasma renin activity (in ng/mL/h) > 20. Electrolytes  Low K+ and high Na+

Caused by something outside the adrenal glands.  Occurs in states of low effective arterial blood volume, which activates the renin-angiostensin concentration and stimulates the distal reabsorption of sodium by the kidney to restore blood volume.

Is a syndrome in which excessive adrenal androgens cause virilisation Causes: Androgen-secreting adrenal tumours • secrete excess androgens, cortisol, or mineralocorticoids (or all three). Adrenal hyperplasia • usually congenital; delayed virilising adrenal hyperplasia is a variant of congenital adrenal hyperplasia. • Both are caused by a defect in production of androgens. • The defect is only partial in delayed virilising adrenal hyperplasia, so clinical disease may not develop until adulthood.