Adrenal Disorders

Adrenal DisordersDr Jawwad Anis KhanMBBS,MCPS,FCPS

Adrenal GlandTwo in numberWeighs 3-5 gms eachRich blood supplyAdrenal consists of outer cortex.Zona Glomerulosa :Aldosterone (Mineralocorticoid)Zona Fasiculata : Cortisol (Glucocorticoid)Zona Reticularis : DHEA (Androgen)Inner Medulla produces catecholamines.

Adrenal gland

Adrenal gland

Adrenal gland (contd..)Functions of Aldosterone: (Zona Glomerulosa)(Acts on renal tubules,intestines, sweat gland)Sodium reabsorptionK+ excretionH+ excretionWater reabsorption Increase ECF volumeIncrease blood volume & maintain blood pressure

Adrenal gland (contd..)Functions of Cortisol: (Zona Fasciculata) Effects on Carbohydrates, protein & fat metabolism.During acute trauma, exercise, infection, operations and other stresses increased cortisol increased glucose & fatty acid releases for energy.Anti inflammatory actionsMaintain adequate vascular tone during stress.

Adrenal gland (contd..)Functions of adrenal androgens: (Zona Reticularis)

Early development of male sex organs during childhood.Growth of pubic & axillary hairs Promote protein synthesis

Adrenal DisordersDisorders of adrenal Cortex:Adrenal hypofunction Addisons diseaseAdrenal hyperfunction :Cushing syndrome (Mainly hypercortisolism) Conns syndrome (Hyperaldosteronism)Congenital Adrenal Hyperplasia (CAH)Disorders of adrenal medulla:Pheochromocytoma

Addisons Disease (Primary Adrenal Insufficiency)Primary hypoadrenalism caused by destruction of adrenal cortex by any process producing deficiency of aldosterone, cortisol and adrenal androgens.Secondary hypoadrenalism is caused by deficiency of ACTH.Uncommon disorder, occurs between 20 50 yrs.Common in females 3:1.

Addisons Disease (contd..)Etiology:AutoimmuneTuberculosisGlucocorticoid treatmentSurgical bilateral adrenalectomySecondary tumour depositsFungal disorders HistoplasmosisHaemochromatosis, Amyloidosis, Sarcoidosis,

Addisons Disease (contd..)Etiology (Contd):Adrenal haemorrhage : septicaemia, anticoagulant therapy, waterhouse Friderichsen syndrome, bleeding disorders.Radiation therapy.

Clinical FeaturesGeneralized weakness, fatigue, lethergy.Anorexia, weight loss, nausea, vomiting.Dizziness, postural hypotension, dehydration, shock.Muscle, joint pain, fever.Loss of body hairs, menstrual abnormalities.Hyper pigmentationDepression.

Laboratory InvestigationsPlasma Cortisol Low to absent.Plasma ACTH High ( in primary hypoadrenalism)ACTH Stimulation Test:Morning plasma cortisolACTH ( Cosyntropin) 250 mg I/M or I/VSecond plasma cortisol level after 30, 60 mins.Cortisol level fail to rise appropriately after ACTH suggestive of Addison disease.

Laboratory Investigations (Contd..)Hyperkalaemia, hyponatraemia.Increased ureaHypoglycaemiaMild anaemia, Neutropenia, Eosinophilia.Anti adrenal antibodies.

Radiological InvestigationsChest X-ray R/O TuberculosisAbdomen X-ray R/O TuberculosisUltrasound abdomenCT abdomen

Cushings Syndrome (Hypercortisolism)Cushings syndrome refers to manifestations due to excessive glucocorticoids in the body.Generally affect young ( mean age 33 years)Common in females 5 :1

Cushings Syndrome (Hypercortisolism)Etiology:ACTH hypersecretion by pituitary ( Cushing disease) (Pituitary adenomas) ACTH hypersecretion by ACTH producing tumors (small cell carcinoma lungs, carcinoid tumors, Thymus, pancreas) Excessive cortisol secretion by adrenal neoplasm (Adrenal adenoma, carcinoma) & hyperplasia Prolonged Corticosteroid treatment

Clinical Features of Cushings Syndrome Effects of Glucocorticoid ExcessCentral obesity, moon face, dorsocervical fat pad, (buffalo hump), supraclaviculer fat pad, protuberant abdomen.Muscle waisting, weakness, fatigue.Thin skin, easy bruisability, purple striae, poor wound healing, osteoporosis.Hypogonadism, menstrual abnormalities, decrease libido.Psychosis, depression, impaired memoryChildren : Slow growth

Clinical Features of Cushings Syndrome (Contd..)Effects of androgen excess: ( if present)Hirsuitism, acne, virilization in females.Pseudoprecocious puberty in children.Effects of ACTH excess: ( if present)HyperpigmentationEffects of mineralocorticoid excess: ( if present)HypertensionHypokalaemia

Clinical Features of Cushings Syndrome (Contd..)Effects of pituitary tumour: ( if present)HeadacheVisual field defectsHypopituitarism

Laboratory InvestigationsDiagnostic approach:Establish diagnosis of hypercortisolismFind out the cause of hypercortisolismAdrenal sourcePituitary pathology ( Cushing disease)Ectopic ACTH producing tumors.

Laboratory InvestigationsTo establish the diagnosis of hypercortisolism:Plasma cortisol: In normal individuals:Morning samples at 0800 Hrs: 10 28 ug/dlEvening samples at 2000 Hrs: 5 10 ug/dlIn Cushing syndrome:Plasma cortisol highLoss of diurnal variationHigh level also found in stress, obesity, depression, pregnancy, alcoholismTo differentiate we perform DMX Suppression test.

Laboratory Investigations (Contd..)Overnight Dexamethasone Suppression Test:Best Screening Test.2mg oral dexamethasone given at 2300 Hrs.Blood specimen for plasma cortisol-next morning at 0800HrsNormal individuals: Plasma Cortisol Suppressed to < 50% of basal level.Cushing Syndrome: Failure to suppression of plasma cortisol levels

Laboratory Investigations (Contd..)Prolonged Dexamethasone Suppression Tests.Low dose: 0.5 mg six hourly for first two days. If suppressed : NormalNo suppression : Go with high dose High dose: 2.0 mg six hourly for next two days.If suppressed : Cushings diseaseNo Suppression : - Adrenal tumour - ACTH secreting tumour

Laboratory Investigations (Contd..)To find out the cause of hypercortisolism:Plasma ACTH:High plasma ACTH Pituitary Adenoma. (Cushings disease)Ectopic ACTH secretion by tumors.Low plasma ACTH Adrenal tumors

Other Laboratory investigationsUrinary free Cortisol : HighPlasma glucose : High due to anti Insulin effect of Cortisol.Serum K : low due to mineralocorticoid effects of cortisol in more severe ACTH dependent disease.Leukocytosis with lymphopenia.

Radiological InvestigationFor localization of tumorsMRI pituitary.CT Scan chest, abdomen.CT Scan Adrenals.

Radio isotopic StudiesDistinguish adrenal adenoma from hyperplaisa.

Primary Hyperaldosteronism - Conns SyndromeExcessive production of aldosteroneHypertension (usually mild), polyuria, fatique and weakness.Hypokalaemia, metabolic alkalosis.Elevated plasma & urine aldosteroneSuppressed plasma renin.Adrenal adenoma (75%), bilateral adrenocortical hyperplasia (25%).CT/MRI of adrenal.

Congenital Adrenal Hyperplasia - CAHIn born error of steroid synthesis due to enzyme deficiency. Autosomal recessive 21 hydroxylase deficiency & 11 Beta hydroxylase deficiency.1.Decreased Cortisol increased ACTH increased adrenal activity & hyperplasia.2.Deficiency of cortisol & other steroids e.g Aldosterone.3. Clinical effects of increased precursors virulization.

Congenital Adrenal Hyperplasia - CAHMay present in three forms.Simple virulism at birth/neonatal period (mild deficiency of enzyme & salt wasting not a feature)Salt wasting & virulism at birth (severe enzyme deficiency)Late onset with hirsutism and infertility.Elevated ACTH, 17-0H progesterone, progesterone, testosterone, DHEA (dehydroepi- androsterone)

PheochromocytomaCatacholamine secreting tumors of adrenal medulla.Rough rule of ten.10% cases Extra adrenal (along sympathetic nervous chain)10% cases Children10% cases Familial10% cases Bilateral adrenal involvement10% cases Metastatic10% cases Extra abdominal (Thorax, Bladder, brain)10% cases No hypertension.

PheochromocytomaParoxysmal or sustained hypertension.Sometimes postural hypotensionEpisodes of perspiration, palpitation.Headache, Anxiety, nausea, chest or abdominal pain, dyspnea, visual disturbances.Hypermetabolism with normal thyroid tests.Hyperglycaemia due to anti insulin effect of catacholamines.Elevated urinary catecholamines & their metabolites e.g. metanephrines & VMA.CT/MRI can confirm & localize the tumour.

SUMMARY Adrenal gland consist of outer cortex and inner medulla Adrenal cortex secrete Aldosterone, Cortisone and DHEA (Androgen) Addisons disease is hypofunction of adrenal gland. Causes may include Autoimmune, Tuberculosis of adrenals, Glucocorticoid treatment, Surgical adrenalectomy, Secondary tumour deposits, Haemochromatosis, Amyloidosis and Fungal disorders of adrenal gland.

SUMMARY Helpful investigations include plasma cortisol and ACTH levels, ACTH stimulation test, Antiadrenal antibodies, Ultrasonography & CT scan of adrenal. Cushings syndrome is hypercortisolism. Causes may include ACTH hypersecretion by pituitary (Cushings disease due to pituitary adenoma is the commonest cause), ACTH producing tumours in the body, Adrenal adenoma or carcinoma and prolonged corticosteroid treatment.

SUMMARY Helpful investigations include plasma Cortisol and ACTH levels, Dexamethasone suppression tests, Ultrasonography & CT scan of adrenal, CT & MRI of pituitary gland, CT scan of chest Conns syndrome is due to hyper aldosteronism Congenital adrenal hyperplasia CAH is inborn error of steroid synthesis due to enzyme deficiency resulting into decreased Cortisol, Aldosterone levels and increased ACTH & 17 OH progesterone levels Pheochromocytomas are Catacholamine secreting tumours of adrenal glands

Interactive Session

QUESTIONS What are functions of Aldosterone, Cortisol and Androgens

What is Addisons disease. Tell its causes and clinical features

QUESTIONS

Tell relevant investigations for diagnosis of Addisons disease

QUESTIONS

What is Cushings syndrome

QUESTIONS

QUESTIONS What is the etiology of Cushings syndrome

What are the clinical features of Cushings Syndrome

QUESTIONS

Tell relevant investigations for diagnosis of Cushings syndrome

QUESTIONS

THANK YOU

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