Disorder adrinal cortex
- 2. Applied aspects The important applied aspects in relation to the adrenal gland, which need mention include: • Hyperactivity of adrenal cortex and • Hypoactivity of adrenal cortex.
- 3. Hyperactivity of adrenal cortex Disorders of hyperactivity of adrenal cortex include: • Cushing’s syndrome (hypercortisol state), • Conn’s syndrome (hyperaldosteronism) and • Adrenogenital syndrome (excessive secretion of adrenal androgens).
- 4. 1. Cushing’s syndrome Cushing’s syndrome refers to the group of clinical conditions occurring due to prolonged excessive levels of glucocorticoids. Causes Causes of Cushing’s syndrome can be divided into two groups: I. ACTH-dependent Cushing’s syndrome is more common (80% cases and occurs due to hyperplasia of adrenal cortex—secreting excessive glucocorticoids) caused by excess of ACTH in following conditions: • Hyperactivity of pituitary as seen in tumours of pituitary cells, particularly of basophils, which secrete ACTH. The resulting condition of pituitary origin is also called Cushing’s disease.
- 6. • Ectopic ACTH production as seen in benign and malignant nonendocrine tumours, e.g. cancer of lungs or abdominal viscera. • Excessive ACTH secretion in hypothalamic disorders associated with excess of CRH secretion. • Excessive ACTH therapy (iatrogenic).
- 7. II. ACTH-independent Cushing’s syndrome is less common (20% cases) and occurs in following conditions: • Adrenal origin Cushing’s syndrome is caused by glucocorticoid secreting tumours such as adrenal adenoma and adrenal carcinoma. • Excessive glucocorticoid administration (i.e. iatrogenic) for diseases such as rheumatoid arthritis. • Abnormal expression of receptors by adrenocortical cells for: - Gastric inhibitory peptide (GIP), - β adrenergic agonists, - Interleukin-I (IL-1) and - Gonadotropin-releasing hormone (GnRH).
- 8. Characteristic features Characteristic features of Cushing’s syndrome are): 1. Truncal or centripetal obesity. It occurs due to redistribution of body fat from extremities (which is in the abdominal wall, back and face) producing following characteristic features: • Buffalo hump, due to collection of fat at upper back, • Moonface, due to fat collection on the face and • Purple striae or cutaneous abdominal striae or livid stretch marks. The skin and subcutaneous tissue becomes thin due to protein catabolism. The stretching of abdominal skin due to excessive subcutaneous fat deposition causes rupture of subdermal tissues producing reddishpurple striae
- 9. 2. Muscle weakness and backache due to protein catabolism. 3. Sodium and water retention may cause weight gain, oedema and hypertension. 4. Hyperglycaemia occurs due to gluconeogenesis and inhibition of peripheral utilization of glucose. It may lead to glycosuria and adrenal diabetes. 5. Hirsutism and menstrual irregularity may occur due to increased adrenal androgens. 6. Susceptibility to osteoporosis and bone fracture is increased due to protein
- 13. 7. Susceptibility to infections is increased due to immunosuppression. 8. Psychological, emotional and personality changes may occur due to CNS effects of glucocorticoids. 9. Blackening of skin may occur due to pigmentation caused by MSH- like effects of excessive ACTH. 10. Susceptibility to peptic ulceration is increased
- 14. Tests for Cushing’s syndrome A. Tests to confirm diagnosis of Cushing’s syndrome • Plasma cortisol level is raised and there is loss of diurnal pattern, i.e. circadian rhythm is lost. • Dexamethasone suppression test is not able to suppress plasma cortisol level. • Insulin-induced hypoglycaemia, which raises plasma cortisol in normal persons, fails to raise it in Cushing’s syndrome. • The 24-h urinary free cortisol levels are raised.
- 16. Hyperaldosteronism Hyperaldosteronism refers to overproduction of the hormone aldosterone, a major sodium-retaining hormone. Causes. Depending upon the cause, hyperaldosteronism may be: 1. Primary hyperaldosteronism or Conn’s disease occurs due to tumour or hyperplasia of zona glomerulosa of adrenal cortex. 2. Secondary hyperaldosteronism occurs due to some extra adrenal cause, which stimulates renin–angiotensin–aldosterone system, e.g. nephrotic syndrome, cirrhosis of liver, congestive heart failure and toxaemia of pregnancy.
- 18. Characteristic features may occur due to secretion of more amount of H+ intorenal tubules and metabolic alkalosis may produce hypocalcaemia causing tetany. of hyperaldosteronism are: • Sodium and water retention leading to hypertension and oedema. It is important to note that marked hypernatraemia and oedema do not occur because Na+ excretion is soon normalized despite hypersecretion of aldosterone (escape phenomenon,). • Hypokalaemia may occur due to increased potassium excretion producing muscle weakness and periodic muscle paralysis, whereas prolonged depletion of potassium may cause renal damage producing polyuria. • Metabolic alkalosis
- 20. Adrenogenital syndrome When secreted in large amounts as in tumour of zona reticularis of adrenal cortex, the following abnormal features may be produced: • In prepubertal males, the excessive androgens produce precocious pseudopuberty • In males, the oestrogen producing cells may produce female-like secondary sexual characters such as enlargement of breasts (gynaecomastia), atrophy of testes, loss of libido and feminine body. • In females, they cause development of male secondary sexual characteristics, such as beard, muscular body, breaking of voice, maletype hair growth, enlargement of clitoris and amenorrhea
- 21. Hypoactivity of adrenal cortex Adrenocortical deficiency (insufficiency), depending upon the site oflesion, can be divided into two types: i. Primary adrenocortical deficiency occurs due to involvement of adrenal cortex and is associated with high ACTH levels due to feedback mechanism. The conditions producing primary adrenocortical deficiency include: • Addison’s disease and • Congenital adrenal hyperplasia. ii. Secondary adrenocortical deficiency occurs due to involvement of pituitary or due to exogenous glucocorticoid administration and is associated with low ACTH level due to less production. iii. Tertiary adrenal deficiency is caused by hypothalamic disorders.
- 22. Addison’s disease Causes. Addison’s disease is an important condition of primary adrenocortical deficiency, occurring due to the following causes: • Autoimmune disease causing adrenal cortex atrophy, • Tuberculosis, fungal and cytomegalovirus infections producing adrenal cortex destruction, an uncommon but well recognized complication in patients with AIDS , • Bilateral adrenalectomy, but failure to take hormone therapy and • Malignant tumours producing destruction of hormone producing cells in adrenal cortex.
- 23. Characteristic features occur due to chronic deficiency of hormones secreted by all the three zones of the adrenal cortex: 1. Glucocorticoid insufficiency produces weight loss, malaise, anorexia,nausea, vomiting, weakness and diarrhoea. Since glucocorticoids are essential for adaptation to stress, therefore in Addison’s disease exposure to any type of stress, e.g. even mild infection may be fatal. 2. Mineralocorticoid deficiency produces hyponatraemia, hyperkalaemia, acidosis and decreased ECF volume with hypotension. 3. Loss of androgens causes sparse hair in females. 4. Increased ACTH secretion occurs due to feedback mechanism and causes diffused pigmentation of the skin and mucous membranes (because of its MSH-like actions).
- 27. Tests for Addison’s disease Tests to diagnose hypoadrenalism: 1. Plasma cortisol levels are low. 2. Plasma aldosterone levels are low or normal. 3. Serum sodium levels are low. 4. Serum potassium is high or normal.
- 30. 5. Blood glucose is low in severe disease. 6. Plasma renin activity is high. ii. Tests to differentiate between primary (Addison’s disease) and secondary hypoadrenalism: 1. Basal ACTH level. High in Addison’s disease and low in pituitary or hypothalamic disease 2. ACTH stimulation test. 0.25 mg ACTH is given intravenously and blood samples are tested after 30 and 60 min. In Addison’s disease, plasma cortisol level does not rise, while in pituitary or hypothalamic disease there occurs a subnormal rise
- 31. Treatment of Addison’s disease consists of replacement therapy: • Glucocorticoid replacement. Oral prednisolone 20 mg in the morning and 10 mg in the evening is the drug of choice. • Mineralocorticoid replacement. Fludrocortisone 0.05–0.1 mg/day is adequate to maintain blood pressure, electrolytes and renin activity
- 32. Addisonian crisis or adrenal crisis It refers to acute adrenal insufficiency characterized by sudden collapse. The condition becomes fatal if not treated in time. Causes. Acute adrenal insufficiency may occur in following conditions: • Acute precipitation of Addison’s disease under the effect of any stress, e.g. infection, haemorrhage, etc. • Major surgical operation or trauma. • Sudden withdrawal of glucocorticoid treatment.
- 34. Treatment. It is a medical emergency requiring immediate treatment with: • Glucocorticoids, • Mineralocorticoids, • Fluids, electrolytes and • Treatment of precipitating factor.
- 36. Secondary and tertiary adrenal insufficiency Secondary and tertiary hypoaldosteronism is usually milder than primary adrenal insufficiency. The plasma ACTH level is low, therefore skin pigmentation does not occur. Hypoaldosteronism. Isolated cases of aldosterone deficiency have also been reported in patients with renal disorders and low circulating renin. This condition is also referred as hyporeninemic hypoaldosteronism . Pseudohypoaldosteronism occurs when aldosterone secretion is normal but there is resistance to its action.
- 37. Characteristic features. The patients of hypoaldosteronism have marked hyperkalaemia. Congenital adrenal hyperplasia Causes. Congenital adrenal hyperplasia is caused by congenital deficiency of one of the enzymes involved in the biosynthesis of glucocorticoids, particularly 21-hydroxylase deficiency and deficiency of 11-hydroxylase
- 38. Pathophysiological features include: • Cortisol and 11-deoxycortisol levels are decreased due to reduced synthesis. • 17-Hydroxyprogesterone, which is substrate for 21- hydroxylase, is raised. • ACTH levels are raised due to feedback mechanism excited by low cortisol levels. ACTH leads to hyperplasia of adrenal cortex. • Adrenal androgen (e.g. DHEA) levels are increased because deficiency of 21-hydroxylase causes excess of 17- hydroxyprogesterone, which serves as a major precursor for adrenal androgens). The increased androgen levels cause sexual abnormalities
- 39. Characteristic features occurring because of above pathophysiological changes are virilism and excessive body growth. In boys, adrenal hyperplasia leads to a congenital condition known as macrogenitosomia praecox. It is characterized by: • Precocious body growth leading to stocky appearance called infant Hercules. • Precocious sexual development with enlarged penis even at age of 4 years. • In female fetus, high plasma androgen levels cause masculinized pattern of development (virilism). Sometimes, the female fetus may be born with male-type external genitalia. This condition is called pseudohermaphroditism.