Cushing's, Hypopituitarism and Diabetes Insipidus

Question 1

Problems that occur in Cushing’s syndrome?

Answer 1

Excess cortisol:

• Protein loss
• Altered carb/lipid metabolism causes diabetes mellitus and obesity
• Altered psyche causes psychosis and depression

Excess mineralocorticoid:

• Hypertension and oedema

Excess androgen:

• Virilism (secondary male sexual characteristics)
• Hirsutism (in females)
• Acne
• Oligo/amenorrhoea

Question 2

Consequences of protein loss in Cushing’s syndrome?

Answer 2

PROXIMAL MYOPATHY (at pelvic and shoulder girdles) and wasting

Osteoporosis and fractures

Thin skin with striae and bruising

Question 3

How to differentiate Cushing’s disease from obesity?

Answer 3

Cushing’s is characterised by:

• Thin skin
• PROXIMAL myopathy (in endocrinology, myopathy is usually proximal)
• Frontal balding in women • Conjunctival oedema (chemosis)
• Osteoporosis (this is part. suspicious in an overweight person, as extra weight actually protects bones)

Question 4

Characteristic appearance of Cushing’s disease?

Answer 4

Lemon on matchsticks appearance

Question 5

Main screening test for Cushing’s disease?

Answer 5

Suppression test by administering exogenous oral high-dose steroid (Dexamethasone)

Normally, this would lower the serum cortisol; if not, it is abnormal

Question 6

Method of the screening test for Cushing’s disease?

Answer 6

Overnight 1mg (oral) Dexamethasone suppression test

The next morning, cortisol should normally be <50 nmol/L; if >100 nmol/L, it is abnormal

Question 7

Other screening tests for Cushing’s disease?

Answer 7

Urine free cortisol (24 hour urine collection):

• Total <250 is normal
• Cortisol : creatinine ratio <25 is normal

Diurnal cortisol variation can be checked at:

• Midnight (at its lowest level)
• 8am (at highest level on waking up in the morning)

Question 8

Definitive test for Cushing’s disease?

Answer 8

2 days of 2 mg/day Dexamethasone suppression test

Cortisol <50 nmol/L 6 hours after the last dose indicates that there is no Cushing’s

Question 9

Difference between Cushing’s disease and Cushing’s syndrome?

Answer 9

Cushing’s disease is caused by an ACTH-producing pituitary tumour (majority of cases)

Cushing’s syndrome covers all the other causes

Question 10

Causes of Cushing’s syndrome?

Answer 10

Adenoma of the adrenal gland:

• Benign
• Malignant

Ectopic cortisol production from the:

• Thymus
• Lung
• Pancreas

Pseudo-Cushing’s:

• Alcohol and depression
• Steroid drugs

Question 11

Test results in the different causes of Cushing’s?

Answer 11

Question 12

Treatment of pituitary causes of Cushing’s?

Answer 12

Hypophysectomy and, if it recurs, external radiotherapy

Bilateral adrenalectomy

Question 13

Treatment of adrenal causes of Cushing’s?

Answer 13

Adrenalectomy

Question 14

Treatment of ectopic causes of Cushing’s?

Answer 14

Remove source OR bilateral adrenalectomy

Question 15

Types of drug treatment used for Cushing;s and when?

Answer 15

Metyrapone (S/E common):

• If other treatments fail
• While waiting for radiotherapy to work

Ketoconazole (hepatotoxic)

Pasireotide (a somatostatin analogue)

Question 16

Effects of hypopituitarism due to problems with the anterior pituitary?

Answer 16

GH (growth failure)

TSH (hypothyroidism)

LH/FSH (hypogonadism)

ACTH (hypoadrenal)

Prolactin (no known effects)

Question 17

Effects of hypopituitarism due to problems with the posterior pituitary?

Answer 17

Diabetes insipidus

Question 18

Causes of hypopituitarism?

Answer 18

Pituitary tumours

Secondary metastatic tumours (breast, lung)

Local brain tumours (astrocytoma, meningioma, glioma)

Granulomatous diseases (TB, histiocytosis X, sarcoidosis)

Trauma (RTAs, skull fractures)

Other causes:

• Vascular disease (polyarteritis)
• Hypothalamic disease (syphilis, meningitis)
• Iatrogenic (surgery)
• Autoimmune (Sheenan’s, which occurs post-partum, due to severe haemorrhage causing hypotension)
• Infection (meningitis)

Question 19

Symptoms anterior hypopituitarism?

Answer 19

• Menstrual irregularities (females)
• Infertility and impotence
• Gynaecomastia (males)
• Abdominal obesity
• Loss of facial hair (males) and loss of axillary and pubic hair (males and females)
• Dry skin and hair
• Hypothyroid faces
• Growth retardation (children)

Question 20

Which tests are best for the steroid axis?

Answer 20

Synacthen test and insulin tolerance test

Question 21

Different types of replacement therapy for hypopituitarism?

Answer 21

Thyroxine (100-150 mcg/day)

Hydrocortisone (10-25 mg/day (am/pm))

ADH (Desmospray (nasal) or tablets)

GH (nightly s/c injection)

Sex Steroids:

• HRT/oestrogen/progesterone tablet for female
• Testosterone for males

Question 22

Benefits of GH in adults with hypopituitarism?

Answer 22

Decreases abdominal fat and increases muscle mass, strength, exercise, capacity and stamina

Improves cardiac function

Decreases cholesterol and increases LDL

Increases bone density

Question 23

Administration of testosterone replacement?

Answer 23

IM injection every 3-4 weeks (sustanon)

Skin gel (testogel, tostran)

Prolonged IM injection 10-14 weeks (nebido)

Oral tablet, like restandol (mostly ineffective)

Question 24

Risks of testosterone replacement?

Answer 24

Prostate enlargement; it does NOT causes prostate cancer but people should be screened for this before commencement, as it causes growth of the cancer

Polycythaemia (monitor FBC)

Hepatitis (only in oral tablet use - monitory LFTs)

Question 25

Causes of cranial diabetes insipidus?

Answer 25

Familial:

• Isolated in most cases
• Wolfram syndrome (AKA DIDMOAD which is characterised by DI, DM, optic atrophy, deaf)

Acquired

• Idiopathic in 50%
• Trauma (RTAs, surgery, skull fracture)

Rare causes:

• Tumour
• Sarcoidosis
• External irradiation
• Meningitis

Question 26

Diagnostic Ix for diabetes insipidus?

Answer 26

Water deprivation test

This does not need to be done if the baseline serum osmolality is >2