Adrenal gland Addison disease Cushing Syndrome Management

1. Diseases of Adrenal Gland
By Dr. Mahesh Pandey

3. Adrenal Cortex -
• Z. Glomerulosa – Mineralocorticoids – Aldosterone (Na+ retention)
• Z. Fasciculata – Glucocorticoids – Cortisol
• Z. Reticularis – Sex Hormones – Androgens
I. Dihydroepiandrosterone (DHE)
II. DHE Sulphate
III. Androsterone
Adrenal Medulla – Catecholamines-
• Adrenaline
• Noradrenaline

4. Causes of Adenocortical Insufficiency
A. Primary –
• Addison’s disease-Cortisol low –> ACTH high (Negative Feedback)
• Congenital/ Acquired Enzyme defects – Cortisol low –> ACTH high
B. Secondary –
• Hypothalamic/ Pituitary – ACTH low –> Cortisol low
• Glucocorticoid Therapy –> ACTH low

5. Primary -Addison’s Disease
• Female:Male = 2:1
Causes
• Autoimmune Adrenalitis
• Tuberculosis
• B/L Adrenalectomy
• B/L Adrenal haemorrhage/ Infarction ( Waterhouse Fredrichson’s
syndrome )
• Metastasis ( especially small cell CA of bronchus)
• Haemochromatosis
• Amyloidosis

6. Clinical Features
Can be due to four defects –
1. Glucocorticoid Insufficiency
• Weight loss
• Malaise
• Weakness
• Anorexia
• Nausea / Vomiting
• GIT – Diarrhoea / Constipation
• Postural Hypotension
• Hypoglycemia
2. Mineralocorticoid insufficiency
• Hypotension

8. 3. Loss of Adrenal Androgens
• Decreased body hair esp. in females
4. Increased ACTH Secretion
• Pigmentation (when present suspect Addison’s disease)
I. Sun exposed areas
II. Pressure areas – Elbows , Knees
III. Palmer Creases , Knuckles
IV. Mucous Membrane
V. Conjunctivae
VI. Recent scars
• VITILIGO

9. PIGMENTATION

10. Patient may present with an Acute / Chronic / Acute on chronic illness. Initial
symptoms – weakness / malaise / wt. loss / N/V / Diarrhoea are often
misdiagnosed. Pigmentation commonly raises suspicion of the diagnosis. BP
normal on lying down. It should be measured 1 min after standing. Postural
Hypotension is almost always +. Pigmentation is due to increased ACTH –
stimulating Melanin production. Vitiligo + 10-20% cases.
Other Autoimmune diseases may also be present like –
• Hashimoto’s thyroiditis
• Primary Atrophic Hypothyroidism
• Hypoparathyroidism
• IDDM
• Pernicious Anemia
• Primary Ovarian Failure
Surgery or other stress may precipitate Acute Adrenal Crisis or such patients
may take longer than normal to recover.

11. Investigations
1. Measurement of Plasma ACTH and Pl. Cortisol at 8:00 A.M. is most
sensitive test for Addison’s disease
P. ACTH > 80 ng /L , P. Cortisol N/
2. ACTH Stimulation Test
In Addison’s disease there is no increase in P. Cortisol following adm. of
ACTH.
In secondary failure increase P. Cortisol occurs due to adm. of ACTH.
3. Plasma Electrolytes
S. Na+ low , S. K+ high/ N , S. Urea increased

12. 4. B. Sugar low in severe Adrenal Insufficiency
5. Plasma Renin Activity almost high with P. Aldosterone low/N
6. X Ray chest to rule out Pulmonary T.B.
7. Abdominal X Ray / CT to see Adrenal Calcification (TB)
8. Blood sent for Adrenal and other organ specific antibodies e.g. Thyroid ,
Pernicious Anemia , DM

13. Management
Glucocorticoid Replacement Therapy (Mineralocorticoid +/-)
Cortisol (Hydrocortisone) in drug of choice
Hydrocortisone 20 mg P/O on getting up and 10 mg P/O at 6 P.M.
Fludocortisone (a mineralocorticoid) 0.05– 0.1 mg (50 – 100
micrograms) per day. Adequacy can be assessed by BP , S. Electrolytes
and Pl. Renin Activity estimation.
If TB present ATT should be given.

14. Advice to Patient
1. Surgery – Hydrocortisone 100 mg IM stat and 6 hourly for 24 hrs then
50 mg 6 hourly
2. Febrile Illness / Intercurrent Stress– Double doses of Hydrocortisone
3. Gastroenteritis - IV/IM Hydrocortisone
4. Steroid Card / Bracelet indicating disease and treatment
Adrenal Crisis- Hydrocortisone 100mg IV then 100mg IV 6 hourly +DNS

15. Cushing Syndrome (CS)
CS is defined as the symptoms and signs associated with prolonged
inappropriate increase of P.cortisol levels.
2 Groups –
ACTH Dependent Non ACTH Dependant
1. Cushing’s disease (pituitary 1. Adrenal Adenoma
dependent B/L Adrenal Hyperplasia)
2. Ectopic ACTH Syndrome (Benign / 2. Adrenal Ca
Malignant non endocrine tumour)
3. Iatrogenic (ACTH Therapy) 3. Iatrogenic (e.g. Prednisolone)

16. Epidemiology
Female : Male = 4 : 1
Cushing’s disease ( Pituitary dependent) accounts 80% cases of Cushing’s syndrome in adults.
Clinical Features
1. Weight gain (most common symptom)
2. Obesity (most common sign) (Centripetal – lemon on toothpicks)
3. Moon face
4. Plethora
5. Menstrual Irregularities
6. Hirsutism (increase body hair)
7. Skin Pigmentation
8. Hypertension
9. Bruising / Striae
10. Ms. Weakness (Myopathy)
11. Depression
12. Backache (osteoporosis)
13. Growth Retardation (in children)

18. Increased Gluconeogenesis – Impaired GTT
Severe Hypokalemic Alkalosis
Skin pigmentation is due to alpha-melanocyte stimulating hormone (alpha
MSH) sequence which is a part of ACTH molecule.
In patients with Cushing’s disease (Pituitary dependant - microadenoma in
Pituitary) treatment by B/L Adrenalectomy –> Development of a locally
invasive pituitary tumour with very high levels of ACTH and
hyperpigmentation (Nelson’s syndrome).
Tinea versicolour (fungal skin infection) is common.

19. Investigations-
2 stages to answer –
A. Diagnosis – Does the patient have Cushing’s Syndrome ?
B. What is the cause of Cushing’s Syndrome ?
Test (A)
1. Circadian Rhythm of P. Cortisol 8.00 hours and 24.00 hours samples – loss
of Circadian Rhythm
2. Dexamethasone Suppression Test – P. Cortisol > 180 mmol/l
3. Urinary free cortisol 24 hrs excretion - high
4. Insulin Dependent Hypoglycaemia – No rise in Pl. cortisol

20. Tests Pit Dependent Ectopic ACTH Adrenal tumour
1.P.ACTH 8.00am N / increase Or Undetectable
2. Metyrapone 750 mg
6 hourly, measure
11-deoxycortisol at
24.00hrs. Inhibits
11-deoxycortisol-
Cortisol formation
3. High dose
Dexamethasone .
P.Cortisol measurement
4. Pl. K+ Normal < 3.5 mmol/l Normal
5. Corticotrophin
Release factor P. ACTH
and cortisol over 3 hrs

21. Management
Untreated Cushing’s Syndrome - 50% 5 yrs mortality.
Tt depends on cause
• Adrenal Tumour – Adrenal Adenoma – Surgical Removal with Replacement
therapy ( Dexamethasone 0.5 mg/d )
• Adrenal Carcinoma – Resection with tumour bed irritation with Adrenolytic
drug O, P’ DDD.
Cortisol over production may be decreased by Metyrapone (250mg 8 hourly)
or Aminoglutethimide.

22. • Cushing’s Disease – Trans-sphenoidal surgery with selective removal
of adenoma (found in 75% of cases) results cure in 80% of patients.
If no tumour – If diagnosis is definitely Pituitary dependent Cushing’s
Syndrome – Radical Hypophysectomy.
It diagnosis is not certain – B/L Adrenalectomy with pit. irradiation to
prevent Nelson’s Synd.
Above tt is followed by Dexamethasone 0.5 mg/d
• Ectopic ACTH Syndrome
Benign tumours – e.g. Bronchial Carcinoid – Removed
Malignancies- e.g. small cell CA of Bronchus – Radiotherapy and
Chemotherapy
If recurrence – Metyrapone / Aminoglutethimide to prevent severe
Hypokalemia and Hyperglycaemia.