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Adrenal Gland Disorders

Adrenal Gland: Anatomy
Zona glomerulosa Zona fasciculata
Glucocorticoid Cortisol 10 to 20 mg/day Mineralocorticoids Aldosterone 100 to 150 g/day

Adrenal androgens Androgen&Estrogen 20 mg/day Catecholamine Norepinephrine (NE) Epinephrine (EPI) Bioactive amines

Zona reticularis


Hormones of Adrenal Cortex
The adrenal cortex produces three major classes of steroids: (1) glucocorticoids (2) mineralocorticoids (3) adrenal androgens

Biosynthesis of Adrenal Steroids Androgen Cholesterol pathway pregnenolon Glucocorticoid pathway progesterone 17 OH progesterone Mineralocorticoid pathway deoxycorticosterone corticosterone 17 OH pregnenolone dehydroepiandrosterone deoxycortisol 18 OH corticosterone androsterone CORTISOL ALDOSTERONE ESTRADIOL .

can act directly on tissue sites. . Aldosterone is bound to proteins to a smaller extent than cortisol.STEROID TRANSPORT     Cortisol circulates in the plasma as free cortisol. Free cortisol is a physiologically active hormone. This may explain the propensity of some synthetic analogues to produce cushingoid effects at low doses. cortisol metabolites. <5% . Normally. Most synthetic glucocorticoid analogues bind less efficiently to CBG (~70% binding). protein-bound cortisol.

and fats . 4. 3.GLUCOCORTICOID PHYSIOLOGY  1. Maintain blood pressure & cardiovascular function Slow the immune system's inflammatory response Balance the effects of insulin in breaking down sugar for energy Regulate the metabolism of proteins. carbohydrates. The principal glucocorticoid is cortisol (hydrocortisone). 2.

2. 3. . There are 3 mechanism of neuroendocrine control : Episode secretion of the cicardian rhytm of ACTH Stress responsiveness of the hypothalamicpituitary adrenal axis Feed back inhibition by cortisol of ACTH secretion 1.

CICARDIAN REGULATION  The plasma level of ACTH varies during the days as a result of its pulsatile secretion.  . It follows a cicardian pattern with a peak just prior to waking and nadir before retiring.



 . glucocorticoid should be used in the minimum effective dose for the shortest possible duration of therapy. Because of their side effect. Glucocorticoids have been used for their anti-inflammatory & immunosupressive activity in treatment of a wide variety disorders.

gastritis. digestive hemorrhage Gastrointestinal Neuropsychiatric Psychiatric disorders in general Intracranial hypertension Glaucoma Cataracts Osteoporosis Aseptic bone necrosis Myopathies Ophthalmic Musculoskeletal .Side effects of glucocorticoids Cardiovascular Arterial hypertension Congestive heart failure Esophagitis. peptic ulcer.

potassium & calcium balance. menstrual disorders. dyslipidemia. growth failure in children & adolescents. supraclavicular & posterior cervical fat deposition. negative nitrogen. delayed wound healing Vasculitides. hypokalemia. Thromboembolism Arteriosclerosis .…Side effects Endocrine/metabolic Truncal obesity. metabolic alkalosis Decrease in inflammatory response Higher susceptibility to infections Immune Cutaneous Vascular Striae. sodium retention. masculinization. hiperglycemia.acne. hirsutism.

2. 4. 3.CLINICAL USE OF ADRENAL STEROIDS 1. How serious is the disorder? How long will glucocorticoid therapy be required? Which preparation is the best? Evaluation of patients prior to initiating steroid therapy Alternate day steroid therapy Withdrawl of glucocorticoids following long-term use . 6. 5.

25 <0.3 200 20 200-1000 - .01 36-54 36-54 Des-36 Beclometasone Fludrocortisone acetate Deoxycorticosterone acetate (DOCA) Aldosterone prednisone once a day 15 0 0.01 <0.01 <0.8 4 4 5 Mineralocorticoid potency 1 0.Comparative steroid potencies Name Hydrocortisone (Cortisol) Cortisone acetate Prednisone Prednisolone Methylprednisolone Glucocorticoid potency 1 0.m 18+ 16-36 16-36 18-40 Dexamethasone Betamethasone Triamcinolone 30-40 25 5 8 puffs 4 x a day equals 14 mg oral <0.25 0. i.01 Duration of action (t1/2 in hours) 8 oral 8.8 0.

MINERALOCORTICOID PHYSIOLOGY The principal steroid with mineralocorticoid activity is aldosterone Control of Aldosterone Secretion : 2 most significant regulators 1. Concentration of potassium ions in ECF 2. Angiotensin II .

where it stimulates exchange of sodium and potassium. . The major target of aldosterone is the distal tubule of the kidney.


Excess 2. Deficiency .Adrenocortical Diseases   Relatively rare If untreated: – Morbidity and mortality Availability of effective treatment  Classified on the basis of 1.

3-hydroxysteroid dehydrogenase.Adrenocortical Diseases Glucocorticoid Excess  Cushing’s syndrome  Pseudo-Cushing’s syndromes Glucocorticoid Resistance Glucocorticoid Deficiency  Primary hypoadrenalism  Secondary hypoadrenalism  Post-chronic corticosteroid replacement therapy Mineralocorticoid Excess Mineralocorticoid Deficiency  Defects in aldosterone synthesis  Defects in aldosterone action Adenomas & Carcinomas Congenital Adrenal Hyperplasia : enzymatic deffect • 21-Hydroxylase. 17-hydroxylase. 11-hydroxylase .

Hypofunction of The Adrenal Cortex Can be divided into 2 general categories : Associated with primary inability of the adrenal to elaborated sufficient quantities of hormone Associated with a secondary failure due to inadequate ACTH formation or release 1. 2. .

by the body's own immune system. accounts for about 20% of cases of primary adrenal insufficiency in developed countries. the outer layer of the adrenal glands. Tuberculosis (TB). . Most cases are caused by the gradual destruction of the adrenal cortex. an infection which can destroy the adrenal glands.Primary adrenocortical insufficiency (Addison’s Disease) Addison's disease occurs when the adrenal glands do not produce enough of the hormone cortisol and in some cases the hormone aldosterone.

Clinical Features of Primary Adrenal Insufficiency Symptom  Weakness. tiredness. fatigue (100%)  Anorexia (100%)  Gastrointestinal symptoms (92%) – Nausea (86%) – Vomiting (75%) – Constipation (33%) – Abdominal pain (31%) – Diarrhea (16%)  Postural dizziness (12%)  Muscle or joint pains (6–13%) Sign      Laboratory Finding  Weight loss (100%) Hyperpigmentation (94%) Hypotension (<110 mm Hg systolic) (88–94%) Vitiligo (10–20%) Auricular calcification (5%) Electrolyte disturbances (92%) – Hyponatremia (88%) – Hyperkalemia (64%) – Hypercalcemia (6%) Azotemia (55%) Anemia (40%) Eosinophilia (17%)    .

normal Aldosterone increment Secondary adrenal insuficiency . subnormal Aldosterone increment Primary adrenal insufficiency Low ACTH.DIAGNOSIS Sign and symptom ↓ Screening test Plasma cortisol 30-60 min after 250 µg cosyntropin im/iv ↓ Subnormal (Normal cortisol level > 18µg/dl) Plasma ACTH and/or plasma aldosterone increment 30 min after 250 µg cosyntropin im/iv High ACTH.


due to electrolyte imbalances and resulting hypotension & cardiac failure . a lack of aldosterone is lethal.… Addison's disease.  Without treatment by mineralocorticoid replacement therapy.

05-0. and sexuality    Treat all infections if occurred Increases the dose of hydrocortisone appropriately Maximal dose of hydrocortisone for severe stress is 50 mg IV or IM every 6 hours Advice patients to wear a medical alert bracelet or medal reading ―Adrenal insufficiency—takes hydrocortisone‖ . 0.Therapy of Addison’s disease general measures  Therapy of Addison’s disease specific Hydrocortisone : 15-25 mg/d Prednisone 2-3 mg/morning 1-2 mg/early evening Fludrocortisone acetate. has a potent Na-retaining effect. mood.3 mg/d Dehydroepiandrosterone (DHEA) 50 mg/d for some women  improvement of the sense of well being.

Deficiencies of multiple pituitary hormones Much more common than primary adrenal insufficiency  . Prolonged administration of excess glucocorticoids : common 2.Secondary Adrenocortical Insufficiency  Due to ACTH deficiency : 1.

Glucocorticoid hormones. and the adrenals then fail to secrete sufficient levels of cortisol   .…Secondary Adrenal Insufficiency  When a person who has been receiving a glucocorticoid hormone for a long time abruptly stops or interrupts taking the medication. If CRH levels drop. which are often used to treat inflammatory illnesses block the release of both CRH and ACTH. the pituitary is not stimulated to release ACTH.

Diagnosis  Low ACTH (< 5 pg/mL) and cortisol suggest secondary adrenal insufficiency Patients with confirmed secondary adrenal insufficiency should have CT/MRI of the brain to rule out pituitary tumor or atrophy.  .

Protocol for glucocorticoid dose reduction & withdrawal Dose prednisone/ prednisolone Protocol reduction Interval > 20mg 10-20 mg < 10 mg 25% 2.5 mg 2.5 mg 4 days 7 days 15 days .

ACUTE ADRENOCORTICAL INSUFFICIENCY 1. Acute haemorrhagic destruction of both adrenal glands ( anticoagulant therapy / a coagulation disorder) 3.Chronic adrenal insufficiency. usually precipitated by sepsis or surgical stress 2. Rapid withdrawl of steroid from patients with adrenal atrophy owing to chronic steroid administration .

…Adrenal Crisis Clinical feature :      Dehydration. or shock out of proportion to current illness severity Nausea and vomiting with a history of weight loss and anorexia Abdominal pain  so-called acute abdomen Unexplained hypoglycemia Unexplained fever →EMERGENCY . hypotension.

.TREATMENT    Primarily toward repletion of circulating glucocorticoids and replacement of the sodium and water deficits. An alternative approach is to administer a 100-mg bolus of hydrocortisone intravenously every 6 h. Infusion of 5% glucose in normal saline solution should be started with a bolus intravenous infusion of 100 mg hydrocortisone followed by a continuous infusion of hydrocortisone at a rate of 10 mg/h.

sepsis and shock. reduced systemic vascular resistance. In such situations cortisol levels rise 4-6 fold.ADRENAL CORTICOL INSUFFICIENCY IN ACUTE ILL PATIENTS HPA axis is dramatically altered during critical illnesses such as trauma. inadequate cortisol production during critical illness can result in hypotension. shock and death. surgery. Treatment with supplementary cortisol .

. Primary aldosteronism the cause for the excessive aldosterone production resides within the adrenal gland Secondary aldosteronism the stimulus is extraadrenal. 2. 1.ALDOSTERONISM • Is a syndrome associated with hypersecretion of the mineralocorticoid aldosterone.

0.Primary Aldosteronism    A generic term for a group of disorders.Solitary aldosteroneproducing adenoma (APA. Conn’s syndrome). excessive aldosterone independently of normal Renin Angiotensin System Affects women > men. metabolic alkalosis. 3rd – 5th decades of life. 2.Bilateral hyperplasia 3. Hypertensive patients.Primary adrenal hyperplasia.Adrenal carcinoma Clinical manifestations: Hypertension. hypokalemia. hypomagnesemia .05 – 12% may have primary aldosteronism Causes: 1. 4.


.Primary Aldosteronism ...

After removal of an adenoma. BP decreases in all patients. Hyperaldosteronism in these patients can usually be controlled by spironolactone (aldosteron antagonist) . complete remission occurs in 50 to 70%.Treatment 1. thus surgery is not recommended. With adrenal hyperplasia. Tumors should be removed laparoscopically. 70% remain hypertensive after bilateral adrenalectomy. 2.

The accelerated phase of hypertension 2. An underlying edema disorder .Secondary aldosteronism An appropriately increased production of aldosterone in response to activation of the renin-angiotensin system Usually occurs in association: 1.

fibromuscular hyperplasia. with profound renal vasoconstriction (the accelerated phase of hypertension). 2. severe arteriolar nephrosclerosis (malignant hypertension). .Secondary aldosteronism in hypertensive states : 1. A primary overproduction of renin (primary reninism) An overproduction of renin secondary to a decrease in renal blood flow and/ perfusion pressure : due to a narrowing of one or both of the major renal arteries by atherosclerosis .

elevated aldosterone secretion varies depending on the severity of cardiac failure.Secondary aldosteronism is present in many forms of edema. The stimulus for aldosterone release in these conditions appears to be arterial hypovolemia and/hypotension. Thiazides and furosemide often exaggerate secondary aldosteronism via volume depletion . In congestive heart failure. • • The rate of aldosterone secretion is usually increased in patients with edema caused by either cirrhosis or the nephrotic syndrome.


.Glucocorticoid Excess Cushing's syndrome Is a hormonal disorder caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol.

Classification of Causes of Cushing’s Syndrome ACTH-Dependent  ACTH-independent       Cushing’s disease (pituitarydependent) Ectopic ACTH syndrome Ectopic CRH syndrome Macronodular adrenal hyperplasia Iatrogenic (treatment with ACTH 1–24)  Adrenal adenoma and carcinoma Primary pigmented nodular adrenal hyperplasia and Carney’s syndrome.g. dexamethasone) Pseudo-Cushing’s Syndromes Alcoholism Depression Obesity . Iatrogenic (e. pharmacologic doses of prednisolone..

 Symptoms & Signs Cushing’ syndrome Central obesity Moon face Buffallo hump Protuberant abdomen & thin extremities Oligo/amenorhea Weakness Headache Hypertension Purple striae Hyperglycemia Hypokalemia etc. .


prolonged exposure a variety of physiologic abnormalities : irritability. emotional lability & depression .Brain/CNS: Excess : initially euphoria.

Adipose tissue distribution Glucocorticoids excess increase fat deposition promotes visceral obesity, the reason for abdominal fat deposition & distribution in states of cortisol excess is unknown.

Endocrine system: Female : supress LH responsiveness to GnRH, resulting in supression of estrogens & progestin w/ inhibition of ovulation & amenorhea.

Glucocorticoids ↑ cardiac out put and peripheral vascular tone, regulate the expression of adrenergic receptors In excess, the may cause hypertension. They affect water and electrolyte balance (sodium retention, hypokalemia, hypertension, increased GFR)

.Skin/muscle/connective tissue: In excess inhibit fibroblasts. stria formation. poor wound healing). lead to loss of collagen and connective tissue resulting in thinning of the skin (easy bruising.

Glucocorticoids in excess leads to osteoporosis .Bone & calcium metabolism: Intestinal calcium absorption↓.

increased lipolysis  FFA  increased cholesterol & triglycerides. decreased HDL-cholesterol Permissive effect of other hormones increase blood glucose.   In the liver: increased glycogen deposition. increased gluconeogenesis Muscle & Fat: inhibits glucose uptake & utilization. protein & lipid catabolism .


Definitive test ACTH : Normal 20-100 pgr/ml Pituitary dependent : 80-250 Adrenal tumor : 0-40 Ectopic ACTH : > 250 .2.

3. 2. . 4.How Is Cushing's Syndrome Treated? Treatment depends on the specific reason for cortisol excess and may include 1. surgery radiation chemotherapy or the use of cortisol-inhibiting drugs.

…How Is Cushing's Syndrome Treated? If the cause is long-term use of glucocorticoid hormones to treat another disorder. the daily dose of glucocorticoid hormones may be given on alternate days to lessen side effects. . Once control is established. the doctor will gradually reduce the dosage to the lowest dose adequate for control of that disorder.

Hormones of Adrenal Medulla  Secretes 2 hormones. causes prolonged or continual sympathetic responses.   . usually from a tumor. Hypersecretion. Secreted in response to stimulation by sympathetic nerve. particularly during stressful situations. epinephrine & norepinephrine.

hemorrhage. • Dilation of the pupils • Inhibition of certain "nonessential" processes: an example is inhibition of gastrointestinal secretion and motor activity. . • Increased rate and force of contraction of the heart muscle : predominantly epinephrine acting through beta receptors • Constriction of blood vessels: norepinephrine • Dilation of bronchioles • Stimulation of lipolysis in fat cells •Increased metabolic rate: in response to epinephrine. hypoglycemia. emotional distress.Major effects mediated by epinephrine and norepinephrine Common stimuli for secretion of adrenomedullary hormones include exercise.

usually epinephrine and norepinephrine Occurs at all ages but is most common in young .Pheochromocytoma Is an adrenal medullary tumor composed of chromaffin cells .midadult. paroxysmal symptoms suggestive of seizure disorder/anxiety attacks/hypertension that responds poorly to conventional treatment.which secretes excessive amounts of catecholamines. . Most patients come to medical attention as a result of hypertensive crisis.

Clinical Manifestations Hypertension is the most common clinical manifestation of pheochromocytoma and is present in 90% to 100% of patients.   . Sustained hypertension is seen in approximately half. and normal blood pressure in less than a fifth of patients. paroxysmal hypertension in a third.

diaphoresis.…Clinical Manifestations    Paroxysmal episodes that include the classic triad of severe headaches. These episodes may occur daily or as frequently as every few months. More than 90% of patients present with at least two of the three symptoms in the classic triad . palpitations.

. and 10% malignant  .. diaphoresis..Pheochromocytoma  Hypertension. and palpitations (sensitivity 91%. 10% familial. 10% bilateral. specificity 94%) The rule of 10s for pheochromos: 10% extra-adrenal. episodic severe of headaches.