Question

ADRENOCORTICAL INSUFFICIENCY: ADDISON’S DISEASE

John Kennedy is a 41-YO father of two children and holds a highly stressful job. Over the past 3 months, he has lost 15 lbs and experienced extreme fatigue. He has also noticed decreased body hair in the axillary and pubic regions, and his skin was very tanned although he has not had time to bask in the sun.

In his physician’s office, John appeared very thin, with sunken eyes and decreased skin turgor. His supine blood pressure was 90/60 with a pulse rate of 95 beats/minute. When standing, his blood pressure was 70/40 with a pulse rate of 120 beats/minute. His skin was noted to be deeply pigmented.

Laboratory Data:

Venous Blood

                             Na+                                    126 mEq/L (normal: 140 mEq/L)

                             K+                                       5.7 mEq/L (normal: 4.5 mEq/L)

                             Osmolarity                       265 mOsm/L (normal: 290 mOsm/L)

                             Fasting Glucose               50 mg.dL (normal: 70-100 mg/dL)

                             Cortisol                             Decreased

                             ACTH                                 Increased

                             Aldosterone                     Decreased

Arterial Blood

              pH                                      7.32 (normal: 7.4)

              bicarbonate                     18 mEq/L (normal: 24 mEq/L)

The ACTH Stimulation Test was negative: there was no increase in serum level of cortisol or aldosterone. Based on the symptoms, physical examination, laboratory results, and ACTH Stimulation Test results, John was diagnosed with Primary Adrenocortical Insufficiency (Addison’s Disease). John was prescribed daily treatment with hydrocortisone (a synthetic glucocorticoid) and fludrocortisones (a synthetic minetalocorticoid). John was instructed to take the hydrocortisone in a larger dose at 8 a.m. and a smaller dose at 1 p.m.

At a follow-up meeting 2 weeks later, John’s circulating ACTH level was normal, he had gained 5 lbs, his blood pressure (supine and standing) was normal, his tan started ti fade, and he had more energy.

1. Why were John’s serum cortisol, aldosterone, and ACTH levels consistent with Addison’s Disease?

2. How did the negative ACTH Stimulation Test confirm the diagnosis?

3. How did the adrenocortical insufficiency decrease John’s arterial blood pressure?

4. Why was John’s fasting blood glucose level lower than normal?

5. Why was his serum potassium ion level elevated?

6. Why was his serum sodium ion level decreased?

7. Why did John have decreased axillary and pubic hair?

8. What was the cause of the hyperpigmentation?

9. What caused his ACTH level to eturn to normal after 2 weeks of treatment?

10. Why was John instructed to take a larger dose of hydrocortisone at 8 a.m. and a smaller dose at 1 p.m.?

Answer 1

1.Addinson's  Disease is a disorder of adrenal gland.Due to the disorder adrenal gland can't produce enough hormones (cortisol & aldosterone).So aldosterone & cortisol level is decreased.

When cortisol level in blood is decreased,then hypothalamus releases corticotrophin releasing hormone(CRH) which is directed the pituitary gland to produce ACTH,for that reason ACTH level is increased.

2.ACTH is a hormone that produces in Anterior pituitary gland that stimulates adrenal gland to produce cortisol.ACTH stimulation test measures how well adrenal gland respond to ACTH hormone.If ACTH stimulation test is negetive,it means adrenal glands can't respond properly & can't produce cortisol.That confirms the diagnosis.

3.In this disease condition adrenal gland can't produce enough hormones like aldosterone & corticosteroid,which controls the water & salt level in the body.water & salt which is the main way to regulate blood volume & keep blood pressure under control.When aldosterone & cortisol level is decreased l,it can't keep water & sodium levels in balance.That makes the arterial blood pressure decrease.

4. Here cortisol deficiency increases insulin sensitivity.As a result peripheral blood glucose utilisation is incresed & hepatic glucose output is decreased,gluconeogenesis process is impaired.for that diabetes may occur.cortisol level is increased abruptly in early morning that involved in glucose metabolism,for these reason fasting glucose level is low than normal.

5.in addison's disease there is a low amount of aldosterone that retains potassium in blood,that's why serum potassium ion level elevated.

6.Deficiency of aldosterone causes large amount of sodium excretion from blood,that decreased serum sodium ion level .

7.Due to adrenal gland's poor working testosterone & DHEA/dihydroepiandosterone production is being less,which leads to pubic & axilliary hair loss.

8.Due to adrenal insufficiency ACTH is elevated.The excess ACTH level stimulated melanocytes cells to produce melanin.for that hyperpigmentation is occured.

9.The administration of hydrocortisone return the ACTH level in normal.As hydrocortisone suppresses the circulation of ACTH level.

10.In case of normal patient plasma cortisol level is highest in early morning,low in evening & lowest in 1 or 2 hour after sleeping.As cortisol has a supress effect on CRH & ACTH,so when natural cortisol production is impaired then artificial administration of hydrocortisone supress the effect of ACTH & CRH.That's why large dose of hydrocortisone administered in morning & smaller dose in evening.