Cushing's, Hypopituitarism and Diabetes Insipidus Flashcards
Problems that occur in Cushing’s syndrome?
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
Consequences of protein loss in Cushing’s syndrome?
PROXIMAL MYOPATHY (at pelvic and shoulder girdles) and wasting
Osteoporosis and fractures
Thin skin with striae and bruising
How to differentiate Cushing’s disease from obesity?
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)
Characteristic appearance of Cushing’s disease?
Lemon on matchsticks appearance
Main screening test for Cushing’s disease?
Suppression test by administering exogenous oral high-dose steroid (Dexamethasone)
Normally, this would lower the serum cortisol; if not, it is abnormal
Method of the screening test for Cushing’s disease?
Overnight 1mg (oral) Dexamethasone suppression test
The next morning, cortisol should normally be <50 nmol/L; if >100 nmol/L, it is abnormal
Other screening tests for Cushing’s disease?
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)
Definitive test for Cushing’s disease?
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
Difference between Cushing’s disease and Cushing’s syndrome?
Cushing’s disease is caused by an ACTH-producing pituitary tumour (majority of cases)
Cushing’s syndrome covers all the other causes
Causes of Cushing’s syndrome?
Adenoma of the adrenal gland:
- Benign
- Malignant
Ectopic cortisol production from the:
- Thymus
- Lung
- Pancreas
Pseudo-Cushing’s:
- Alcohol and depression
- Steroid drugs
Test results in the different causes of Cushing’s?
Treatment of pituitary causes of Cushing’s?
Hypophysectomy and, if it recurs, external radiotherapy
Bilateral adrenalectomy
Treatment of adrenal causes of Cushing’s?
Adrenalectomy
Treatment of ectopic causes of Cushing’s?
Remove source OR bilateral adrenalectomy
Types of drug treatment used for Cushing;s and when?
Metyrapone (S/E common):
- If other treatments fail
- While waiting for radiotherapy to work
Ketoconazole (hepatotoxic)
Pasireotide (a somatostatin analogue)
Effects of hypopituitarism due to problems with the anterior pituitary?
GH (growth failure)
TSH (hypothyroidism)
LH/FSH (hypogonadism)
ACTH (hypoadrenal)
Prolactin (no known effects)
Effects of hypopituitarism due to problems with the posterior pituitary?
Diabetes insipidus
Causes of hypopituitarism?
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)
Symptoms anterior hypopituitarism?
- 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)
Which tests are best for the steroid axis?
Synacthen test and insulin tolerance test
Different types of replacement therapy for hypopituitarism?
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
Benefits of GH in adults with hypopituitarism?
Decreases abdominal fat and increases muscle mass, strength, exercise, capacity and stamina
Improves cardiac function
Decreases cholesterol and increases LDL
Increases bone density
Administration of testosterone replacement?
IM injection every 3-4 weeks (sustanon)
Skin gel (testogel, tostran)
Prolonged IM injection 10-14 weeks (nebido)
Oral tablet, like restandol (mostly ineffective)
Risks of testosterone replacement?
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)
Causes of cranial diabetes insipidus?
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
Diagnostic Ix for diabetes insipidus?
Water deprivation test
This does not need to be done if the baseline serum osmolality is >2
