ADRENAL INSUFFICIENCY

NONSO EMEGOAKORENDOCRINOLOGY UNIT

Discuss the aetiology, clinical presentation, investigation and treatment of adrenal

insufficiency

Outline

• INTRODUCTION• HPA AXIS• Renin angiotensin, aldosterone axis• Aetiology • Clinical presentation• Investigations• Treatment• Summary

INTRODUCTION

• Is a condition that results from inadequate production of steroid hormones from the adrenal glands

• The adrenal hormones include glucocorticoids, mineralocorticoids and androgens

• AI may be primary, secondary or tertiary

Hypothalamo-pituitary-adrenal axis

Primary adrenal insufficiency

• Called Addison's disease

• Results from destruction and dysfunction of the entire adrenal cortex

• Hence both glucocorticoids, mineralocorticoids and adrenal androgens are affected

• May be acute(addisonian crises) or chronic

Aetiology of chronic primary AI

• Autoimmune adrenalitis either isolated or as part of APS types 1 and 2

• Adrenal infections; TB, histoplasmosis, HIV blastomycosis, cryptococcosis, coccidiodomycosis

• Infiltrative disorders; amyloidosis, sarcoidosis, haemochromatosis, metastasis,lymphoma

• DRUGS; ketoconazole, aminoglutethimide, mitotane, methadone, busulphan

• Abdominal irradiation

• Surgical removal

• Congenital adrenal hyperplasia

• Adrenal dysgenesis

• adrenoleukodystrophy

Causes of acute primary AI

• Stress ; infection, infarction, surgery, trauma, emotional turmoil

• Sudden withdrawal of long term steroids• Bilateral adrenal haemorrhage;1. Waterhouse-friderichsen syndrome2. Complication of anticoagulant therapy,

coagulopathies, pregnancy• Bilateral adrenal artery emboli/vein

thrombosis

Causes of secondary/tertiary AI

• Exogenous steroid use• Pituitary tumors• Pituitary irradiation• Autoimmune

hypophysitis• Pituitary apoplexy• Sheehans syndrome• Pituitary infiltrations

• Pituitary surgery• Craniopharyngioma• Meningioma• Metastasis to the

pituitary or hypothalamus

• Hypothalamic tumors• Head injury

Clinical presentation

• Gradual onset with non specific features• Hyperpigmentation especially of sun exposed

areas, extensor surfaces, knuckles, elbows, knees, scars, palm creases, nail beds, mucous membranes of oral cavity

• Chronic, worsening fatigue• Muscle weakness• Weight loss

Clinical features

• Poor appetite• Nausea, vomiting and

occasional diarrhea• Dizziness, syncope• Flaccid muscle paralysis• Salt craving• Impotence• Joint and back pains

• • Confusion/depression• Abdominal pains• Loss of axillary/pubic hair• Dry itchy skin• vitiligo

Physical findings

• Generalised wasting

• Dehydration

• Loss of body hair

• Pigmentation as already described/ vitiligo

• Postural hypotension

Hyperpigmentation in buccal mucosa of a patient

Pointers to secondary hypoadrenalism

• Absence of hyperpigmentation• Alabaster colored pale skin(POMC def)• Features of panhypopituitarism e.g, reduced

thyroid and gonadal functions• Neurological features e.g headaches, blurring

of vision, bitemporal hemianopia• Lack of features of aldosterone def such as salt

craving, abdominal pains

Presentation of addisonian crises

• Severe vomiting/diarrhea• Severe lethargy• Dehydration• Hypotension or may be in shock• Sudden, severe pain in back, belly or legs• Confusion, fits, loss of consciousness• Abdominal features may present as an acute abdomen• Fever/hyperpyrexia• Features of precipitating factor

Investigations

• ACTH STIMULATION TEST• Gold standard assay for adrenal insufficiency• May distinguish primary from secondary AI• Measures cortisol response to injection of

synthetic ACTH• IM Tetracosactide 250mcg is given.• Take sample for cortisol at 0, 30 and 60mins

• Serum cortisol doubles after one hour of injection of synecthen in normal people

• Impaired response in adrenal insufficiency• Stress,recent radioisotope scans,

spironolactone, contraceptives may affect the result.

• c/I in people on glucocorticoid therapy

• Random plasma cortisol, <100nmol/l is suggestive, >550nmol/l is unlikely

Investigations

• 9am Plasma ACTH and cortisol; high level (>80ng/l) of ACTH with low cortisol confirms primary insufficiency

• Insulin tolerance test;to diagnose or exclude ACTH deficiency

• measures ACTH stress response via cortisol to hypoglycaemia

• Cortisol rises above 550nmol/l in normal people• CRH stimulation test; i.v 100mcg of CRH is given• Plasma ACTH rises by 30-40pg/ml in normal.

INVESTIGATIONS

• Serum electrolyte, urea

• Adrenal antibodies• Plasma rennin• FBC• Blood glucose• Urine and sweat Na• Chest and abdominal

x-ray• Abdominal USS/CT• Brain MRI

Treatment

• Is with replacement therapy for life except for treatable causes like TB

• Glucocorticoid replacement is with tabs hydrocortisone 20-30mg/day

• Mimic circadian rhythm• Thin patients require lower doses while obese

patients may need higher doses• Dose should be adjusted in times of stress

Treatment ctd

• Patients on medications that induce cytochrome p-450 need higher doses

• Those with decreased cortisol clearance like in liver disease are placed on lower doses

• Tabs prednisolone and dexamethasone are alternative medications used

• Adequacy of treatment is monitored with improved clinical wellbeing and serum cortisol

Treatment

• Mineralocorticoids are replaced with fludrocortisone

• Only in primary hypoadrenalism• Daily dose is titrated to maintain normal BP and

serum Na and K level• Dose adjustments are not needed in stressful

situations, however dose should be increased in hot weather

• Adrenal androgen replacement is with DHEA 25-50mg/day

OUTPATIENT CARE

• Monitor for signs of inadequate replacement e.g headaches, dizziness, weakness

• Suppression of plasma rennin activity indicate adequate mineralcorticoid replacement

• Monitor BP, weight and cushingoid features which may indicate over replacement

• Periodic bone mineral density evaluation.

Treatment Ctd

• Patients are taught how to increase steroid dose during intercurrent illness

• Advised to wear a medic-alert bracelet • Keep at least an ampoule of hydrocortisone at

home• Other treatment is dependent on aetiology e.g

anti TB• Patients with secondary AI may also need T4

replacement

Mgt of acute hypoadrenalism

• IVF N/S over 30-60mins • Subsequent liters of N/S is dependent on degree of

dehydration• I.V. hydrocortisone 100mg bolus• I.M. hydrocortisone 100mg 6hrly until patient is

clinically stable• IV dextrose for hypoglycemia• Tabs hydrocortisone 20mg 8hourly when patient can

take orally• Fludrocortisone not required in the acute period

Primary versus secondary adrenal insufficiency

primary• Increased CRH• Increased ACTH• reduced cortisol• reduced aldosterone• Hyponatremia• Hyperkalemia• Increased renin• hyperpigmentation• Glucocorticoid and

mineralocorticoid replacement

secondary• Increased CRH• Reduced ACTH• Reduced cortisol• Normal aldosterone• Normal or reduced Na• Normal or reduced K• Normal renin• No hyperpigmentation• Only glucocorticoid

replacement needed.

Conclusion

• AI is a great pretender.• It’s a potentially life threatening condition• Autoimmune destruction of the adrenals is the

commonest cause• Primary and secondary are differentiated by

ACTH levels amongst other features• Acute insufficiency is a medical emergency and

is treated with IV hydrocortisone and IV fluids

THANKS FOR LISTENING