Addison's disease - Clinicals, Diagnosis, and Management

Endocrinology, Metabolism and Nutrition

Clinicals - History

Fact Explanation
Fatigue It is a cardinal symptom. Due to adrenocortical insufficiency caused by gradual adrenal destruction. Symptoms have insidious onset. Along with the progressive impairment of adrenal function, the patient becomes progressively fatigued. Fatigue
It is a cardinal symptom. Due to adrenocortical insufficiency caused by gradual adrenal destruction. Symptoms have insidious onset. Along with the progressive impairment of adrenal function, the patient becomes progressively fatigued.
Anorexia, Nausea, Vomiting Due to gastrointestinal abnormalities due to progressive adrenocortical insufficiency. Anorexia, Nausea, Vomiting
Due to gastrointestinal abnormalities due to progressive adrenocortical insufficiency.
Weight loss Due to Gastrointestinal symptoms and due to chronic disease. Weight loss
Due to Gastrointestinal symptoms and due to chronic disease.
Postural dizziness Due to hypovolaemia and sodium loss. Postural dizziness
Due to hypovolaemia and sodium loss.
Darkening of skin complexion Due to skin pigmentation. Present in over 90% of patients. ACTH secretion is increased in Addison's disease, therefore melanocyte stimulating hormone like substances which are secreted along with ACTH are also increased and causes pigmentation by dispersion of melanocytes. Darkening of skin complexion
Due to skin pigmentation. Present in over 90% of patients. ACTH secretion is increased in Addison's disease, therefore melanocyte stimulating hormone like substances which are secreted along with ACTH are also increased and causes pigmentation by dispersion of melanocytes.
Darkening of mucosa of the mouth Also due to pigmentation caused by melanocytes like substances. Darkening of mucosa of the mouth
Also due to pigmentation caused by melanocytes like substances.
Episodes of faintness or syncope Caused by hypoglycemia or hypotension. Episodes of faintness or syncope
Caused by hypoglycemia or hypotension.
History of other Autoimmune diseases such as Type 1 Diabetes mellitus, Thyroiditis, Vitiligo Addison's disease can be caused by Autoimmune adrenalitis causing adrenal cortex destruction History of other Autoimmune diseases such as Type 1 Diabetes mellitus, Thyroiditis, Vitiligo
Addison's disease can be caused by Autoimmune adrenalitis causing adrenal cortex destruction
Symptoms of Pulmonary Tuberculosis Tuberculosis remains the most
common cause of Addison disease worldwide. Symptoms of Chronic cough, Haemoptysis, Evening pyrexia, loss of weight. Also contact history of Tuberculosis ,
Symptoms of Pulmonary Tuberculosis
Tuberculosis remains the most
common cause of Addison disease worldwide. Symptoms of Chronic cough, Haemoptysis, Evening pyrexia, loss of weight. Also contact history of Tuberculosis ,

Clinicals - Examination

Fact Explanation
General wasting Due to Chronic disease, hypoglycaemia and salt loss. General wasting
Due to Chronic disease, hypoglycaemia and salt loss.
Dehydration Due to sodium loss and hypovolaemia. Dehydration
Due to sodium loss and hypovolaemia.
Pigmentation Specially of palmar creases and of new scars. May appear as dull, slaty, grey-brown. Hyper pigmentation is absent if adrenal destruction is rapid, eg; in bilateral adrenal hemorrhage Pigmentation
Specially of palmar creases and of new scars. May appear as dull, slaty, grey-brown. Hyper pigmentation is absent if adrenal destruction is rapid, eg; in bilateral adrenal hemorrhage
Buccal pigmentation Above reasons of pigmentation. Buccal pigmentation
Above reasons of pigmentation.
Postural Hypotension Due to sodium loss and hypovolaemia. Postural Hypotension
Due to sodium loss and hypovolaemia.
Loss of body hair Due to loss of adrenal androgens. Loss of body hair
Due to loss of adrenal androgens.
Goitre May be associated with other autoimmune conditions such as thyroiditis. Goitre
May be associated with other autoimmune conditions such as thyroiditis.
Vitiligo May be associated with other autoimmune conditions such as vitiligo. Vitiligo
May be associated with other autoimmune conditions such as vitiligo.
Respiratory system - Signs of Pulmonary Tuberculosis Tuberculosis remains the most
common cause of Addison disease worldwide. Pleural effusions, bronchial breathing over upper zones due to cavitation, etc
Respiratory system - Signs of Pulmonary Tuberculosis
Tuberculosis remains the most
common cause of Addison disease worldwide. Pleural effusions, bronchial breathing over upper zones due to cavitation, etc

Investigations - Diagnosis

Fact Explanation
09:00 hours Plasma ACTH level A high Plsma ACTH level (>80ng/l) with low or low-normal Cortisol confirms primary hypoadrenalism 09:00 hours Plasma ACTH level
A high Plsma ACTH level (>80ng/l) with low or low-normal Cortisol confirms primary hypoadrenalism

Investigations - Management

Fact Explanation
Serum Cortisol levels Adequacy of Glucocorticoid dose is assumed by normal cortisol levels during the day while on hydrocortisone replacement. Along with Clinical well being and restoration of weight Serum Cortisol levels
Adequacy of Glucocorticoid dose is assumed by normal cortisol levels during the day while on hydrocortisone replacement. Along with Clinical well being and restoration of weight
Serum electrolytes - Sodium, Potassium Used as a para meter for adequacy of Fludrocortisone replacement is assessed by restoration of electrolytes to normal levels Serum electrolytes - Sodium, Potassium
Used as a para meter for adequacy of Fludrocortisone replacement is assessed by restoration of electrolytes to normal levels
Plasma renin activity Used as a para meter for adequacy of Fludrocortisone replacement is assessed by suppression of Renin activity to normal levels Plasma renin activity
Used as a para meter for adequacy of Fludrocortisone replacement is assessed by suppression of Renin activity to normal levels
Hyponatraemia Due to many reasons. 1.) Aldosterone deficiency causes loss of sodium with urine 2.) movement of sodium into the intracellular compartment.
3.) Elevated plasma vasopressin and angiotensin
II levels may contribute to the hyponatremia by impairing free
water clearance
Hyponatraemia
Due to many reasons. 1.) Aldosterone deficiency causes loss of sodium with urine 2.) movement of sodium into the intracellular compartment.
3.) Elevated plasma vasopressin and angiotensin
II levels may contribute to the hyponatremia by impairing free
water clearance
Hyperkalaemia Due to many reasons such as,
1.) aldosterone
deficiency,
2.) impaired glomerular filtration,
3.) acidosis
Hyperkalaemia
Due to many reasons such as,
1.) aldosterone
deficiency,
2.) impaired glomerular filtration,
3.) acidosis
Hypoglycaemia Due to Adrenal insufficiency causing low glucocorticoid levels. Glucocorticoids are necessary for Gluconeogenesis. Therefore Frequent hypoglycemia is seen in Addison's disease due to reduced gluconeogenesis. Patients with Addison's disease also suffer from severe anorexia, nausea and vomiting therefore low level of nutrition also contributes to hypoglycemia. Hypoglycaemia
Due to Adrenal insufficiency causing low glucocorticoid levels. Glucocorticoids are necessary for Gluconeogenesis. Therefore Frequent hypoglycemia is seen in Addison's disease due to reduced gluconeogenesis. Patients with Addison's disease also suffer from severe anorexia, nausea and vomiting therefore low level of nutrition also contributes to hypoglycemia.
Hypercalcaemia Present in 10% - 20%, causes not clear Hypercalcaemia
Present in 10% - 20%, causes not clear
Anaemia Usually Normochromic normocytic due to anemia of Chronic disease. These patients also suffer from Anorexia, nausea and vomiiting frequently therefore reduced nutrition may contribute to Iron deficiency Anemia. Addison's disease is also associated with other auto immune diseases therefore Pernicious anemia may be associated and cause anemia Anaemia
Usually Normochromic normocytic due to anemia of Chronic disease. These patients also suffer from Anorexia, nausea and vomiiting frequently therefore reduced nutrition may contribute to Iron deficiency Anemia. Addison's disease is also associated with other auto immune diseases therefore Pernicious anemia may be associated and cause anemia
Short ACTH stimulation test Screening test for Addison's disease, however Impaired cortisol response only confirms presence of hypoadrenalism but does not help in differentiating from Addison's disease, ACTH deficiency, Iatrogenic suppression by steroid medication as a cause of hypoadrenalism Short ACTH stimulation test
Screening test for Addison's disease, however Impaired cortisol response only confirms presence of hypoadrenalism but does not help in differentiating from Addison's disease, ACTH deficiency, Iatrogenic suppression by steroid medication as a cause of hypoadrenalism
single cortisol measurements Little value. However a random cortisol level below 100nmol/l during the day is highly suggestive of hypoadrenalism single cortisol measurements
Little value. However a random cortisol level below 100nmol/l during the day is highly suggestive of hypoadrenalism
Adrenal antibodies Present in many cases of autoimmune adrenalitis Adrenal antibodies
Present in many cases of autoimmune adrenalitis
Chest Xray May show evidence of Pulmonary tuberculosis In earlier times tuberculosis was responsible for 70–90% of cases, but the most frequent cause now is idiopathic atrophy Chest Xray
May show evidence of Pulmonary tuberculosis In earlier times tuberculosis was responsible for 70–90% of cases, but the most frequent cause now is idiopathic atrophy
Abdominal Xray May show evidence of Adrenal calcification. In earlier times, tuberculosis was responsible for 70–90% of cases, but the most frequent cause now is idiopathic atrophy Abdominal Xray
May show evidence of Adrenal calcification. In earlier times, tuberculosis was responsible for 70–90% of cases, but the most frequent cause now is idiopathic atrophy
Plasma Renin activity High due to Low serum aldosterone Plasma Renin activity
High due to Low serum aldosterone

Management - Supportive

Fact Explanation
Managment of Acute Hypoadrenalism Intra venous fluids (Normal saline), Given with IV Hydrocortisone, Correction of Low blood Glucose, Monitoring vital parameters till stable Managment of Acute Hypoadrenalism
Intra venous fluids (Normal saline), Given with IV Hydrocortisone, Correction of Low blood Glucose, Monitoring vital parameters till stable
Dehydroepiandrosterone (DHEA) To assist in alleviating hypogonadism Dehydroepiandrosterone (DHEA)
To assist in alleviating hypogonadism

Management - Specific

Fact Explanation
Hydrocortisone As Glucocorticoid replacement therapy.
20 -30mg daily, eg - 10mg on waking, 5mg at 12 noon, 5mg at 18:00 hours
Hydrocortisone
As Glucocorticoid replacement therapy.
20 -30mg daily, eg - 10mg on waking, 5mg at 12 noon, 5mg at 18:00 hours
Prednisolone As Glucocorticoid replacement therapy. 7.5mg daily. eg - 5mg on waking, 2.5mg at 18:00 hours. Prednisolone
As Glucocorticoid replacement therapy. 7.5mg daily. eg - 5mg on waking, 2.5mg at 18:00 hours.
Fludrocortisone As Mineralocorticoid replacement therapy. 50-300 micrograms daily Fludrocortisone
As Mineralocorticoid replacement therapy. 50-300 micrograms daily
Treatment of Tuberculosis if it is the cause of Hypoadrenalism Anti-tuberculosis therapy (isoniazid, rifampin, pyrazinamide and ethambutol) along with hydrocortisone and Fludrocortisone supplementation Treatment of Tuberculosis if it is the cause of Hypoadrenalism
Anti-tuberculosis therapy (isoniazid, rifampin, pyrazinamide and ethambutol) along with hydrocortisone and Fludrocortisone supplementation

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