Pituitary Tumours Flashcards
At what size does an adenoma of the pituitary cross from a microadenoma to a macroadenoma?
<1cm = microadenoma >1cm = macroadenoma
What structures can a non-functioning pituitary adenoma compress?
Optic chiasma
Cranial nerve 3,4,6
What effect does a non-functioning pituitary adenoma have on hormone release from the pituitary?
Too little hormone is released:
- Hypoadrenalism
- Hypothyroidism
- Hypogonadism
- Diabetes Insipidus
- GH deficiency
What symptom do patients usually notice if the pituitary adenoma is compressing the optic chiasm?
Bitemporal Hemianopoia
Loss of vision in both temporal fields
What are the 3 categories which cause a Prolactinoma?
Physiological
Drugs
Pathology
What physiological changes in the body cause a rasied prolactin?
breast feeding
pregnancy
stress
sleep
What drugs/medications are known to cause a raised prolactin?
- Dopamine antagonists eg metoclopramide
- Antipsychotics eg phenothiazines
- antidepressants eg TCAs, SSRIs
- other = oestrogens, coccaine
What pathological conditions cause a raised prolactin?
- Hypothyroidism
- Stalk lesions (iatrogenic/croad accident)
- Prolactinoma
Males usually present early with prolactin related disease, whilst females present late. TRUE/FALSE?
FALSE
females notice symptoms much earlier than men
e.g. irregular/no periods + infertility
What symptoms do males usually present with in a prolactinoma?
Impotence
Visual field abnormal
Headache
What symptoms do females experience in a prolactinoma?
Galactorrhoea (milk production)
Irregular/no periods
Infertility
How can a prolactinoma be tested for?
Serum prolactin concentration (Blood Test)
Pituitary MRI
What class of drugs are used to inhibit release of prolactin?
Dopamine agonists
What dopamine agonist is most commonly used?
Cabergoline (Dostinex)
- Once to Twice per week oral
- Least side effects
What are the advantages of dopamine agonists?
Prolactin level = normalised in 96%
Menstruation regained in 94%
Pregnancy rate 91% (Warn pts about this!)
Tumour shrinkage
What side effects are caused by dopamine agonists?
Nausea / Vomiting
Low Mood
Fibrosis (heart valves/retroperitoneal) {only at high doses e.g. used in parkinsons disease
In acromegaly, what hormone is in excess?
Growth Hormone
What can result if acromegaly presents before bones have fused?
Gigantism
What soft tissues are often found to be thickened in acromegaly?
skin
large jaw
large hands
What symptom is caused by a thickened nasopharynx in acromegaly?
Snoring/ Sleep Apnoea
What cardiovascular complications can arise from acromegaly?
Hypertension (heart), cardiac failure
Early CV Death
Patients with acromegaly are at risk of colonic polyps and colon cancer. TRUE/FALSE?
TRUE
What is the peripheral hormone that Growth Hormone stimulates?
IGF-1
What suppression test can be carried out to test for excess growth hormone?
Glucose Tolerance Test
75g Oral Glucose
Check at 0, 30, 60, 90, 120 min)
NORMALLY: GH suppresses to <0.4ug/l after glucose
Acromegaly: GH unchanged/no suppression
=> GH remains >1ug/l after glucose
Surgery is the first line treatment for acromegaly. TRUE/FALSE?
TRUE
can sometimes also have radiotherapy alongside surgery
How many micro and macroadenomas are cleared by surgery?
90% cure if microadenoma
50% cure if macroadenoma
What drugs can be used to treat acromegaly?
Somatostatin Analogues
Dopamine Agonists
GH Antagonists
How are somatostatin analogues usually administered?
Injection (IM or SC)
What are the advantages of somatostatin analogues
- Tumour shrinkage
- Can be used pre-op
- relieves headache in 1 hr
- Improved outcome
What are the short term adverse effects of somatostatin analogues?
- Local Stinging
- Flatulence
- Diarrhoea
- Abdominal pains
What is the main long term side effect of somatostatin analgoues?
Gallstones (60%)
When can dopamine agonists be used to treat a pituitary tumour in acromegaly?
If the tumour co-secretes GH and prolactin
Why are GH antagonists not commonly prescribed in acromegaly?
No decrease in tumour size (possible slight increase)
Expensive (£36,000 a year)
What should be checked at an acromegaly follow up?
- Check other pituitary hormones especially thyroid
- Cancer surveillance (Colon and tubulo-villous adenoma)
- Cardiovacular risk factors
- Sleep apnoea
What is responsible for the headache symptom experienced in acromegaly?
Turbulent blood flow through vasculature
Cushing’s syndrome occurs as a result of what hormone excess?
Cortisol
What are the main indications of protein loss in Cushing’s syndrome?
Myopathy; wasting
Osteoporosis; fractures
Thin skin; striae, bruising
What can the altered carbohydrate and lipid metabolism in Cushing’s Disease cause?
Diabetes mellitus
Obesity
What pschyiatric problems do Cushing’s patients present with?
Psychosis
depression
What can excess mineralocorticoid result in?
hypertension
oedema
What symptoms do patients experience if they have excess androgens?
- Virilism (females develop secondary male characteristics)
- Hirsutism (excess body hair in both genders)
- Acne
- oligo/amenorrhoea
What features differentiate Cushing’s from obesity?
- Thin Skin
- Proximal myopathy
- Frontal balding in women
- Conjunctival oedema (chemosis)
- Osteoporosis
What facial symptoms are often seen in Cushings?
Moon face
with red/plethoric cheeks
In Cushing’s syndrome patients experience central obesity with very slim limbs. TRUE/FALSE?
TRUE
thin arms and legs due to muscle wasting
What suppression test can be used as screening test for cushings?
Overnight 1mg dexamethasone suppression test (oral)
What other tests are used to screen for Cushing’s syndrome?
- Urine free cortisol (24h urine collection)
- Diurnal cortisol variation (Midnight/8am)
How does a dexamethasone suppresion test work?
Dexamethasone = exogenous steroid
=> should take place of cortisol and inhibit CRH/ ACTH to produce less cortisol
Explain the difference between the normal and abnormal overnight dexamethasone suppression tests
<50nmol/l next morning = normal
> 100nmol/L = ABnormal
Why is a diurinal cortisol variation test used?
Cortisol is lowest at midnight and highest in the morning
=> sample should be taken before patient has had anything to eat/drink to determine if levels = consistently high
What test can DIAGNOSE Cushiing’s?
Low dose Dexamethasone Suppression Test
2mg/day for 2 days
Cortisol <50 nmol/l 6 hrs after last dose = Normal
Cortisol >130 nmol/l = Cushings
What is the difference between Cushing’s Disease and Cushing’s syndrome?
Cushing’s DISEASE affects pituitary
All other manifestations = Cushing’s syndrome
Aside from pituitary disease, what other pathologies can cause Cushing’s?
- Adenoma of adrenal gland
- Ectopic Tissue
=> Thymus
=> Lung
=> Pancreas
What can cause Pseudo-Cushing’s?
Alcohol and Depression
Steroid medication
What levels of ACTH would differentiate between pituitary, adrenal or ectopic disease?
<300 = pituitary disease <1 = adrenal disease >300 = ectopic disease (i.e. ACTH being secreted from elsewhere)
How are the pituitary causes of Cushing’s treated?
- Hypophysectomy
- external radiotherapy if recurs
- Bilateral adrenalectomy
How are the Adrenal causes of Cushing’s treated?
Adrenalectomy
How are the ectopic causes of Cushing’s usually treated?
Remove source
OR bilateral adrenalectomy
What non-surgical treatments can be used in Cushing’s?
Metyrapone
- if other treatments fail
- while waiting for radiotherapy to work
Ketoconazole (hepatotoxic)
Pasireotide LAR (10-20mg monthly)
- somatostatin analogue - receptor 2 and 5 blocked
Describe the concept of Pan Hypopituitarism
Decrease in all hormonal output from the pituitary
What can a decrease in all pituitary hormones cause?
Anterior Pituitary GH = growth failure TSH = hypothyroidism LH/FSH = Hypogonadism ACTH = hypoadrenal Prolactin = **none known**
Posterior Pituitary
Diabetes Insipidus
What are the main causes of hypopituitarism
- Pituitary Tumours
- Secondary metastatic lesions (lung, breast)
- Local brain tumours
- Granulomatous diseases
- Vascular diseases
- Trauma
- Hypothalamic diseases
- Iatrogenic (surgery)
- Autoimmune
- Infection
What hypothalamic diseases can result in hypopituitarism?
Syphilis
meningitis
What granulomatous diseases can result in hypopituitarism?
TB
Histiocytosis X
sarcoidosis
What local brain tumours can give rise to hypopituitarism?
Glioma
Meningioma
Astrocytoma
What symptoms present in hypopituitarism if only the anterior pituitary is affected?
- Menstrual irregularities (F)
- Loss of axillary and pubic hair (M&F)
- Infertility, impotence
- Gynaecomastia (M)
- Loss of facial hair (M)
- Abdominal obesity
- Dry skin and hair
- Hypothyroid faces
- growth retardation (children)
What dose of thyroxine is used as replacement therapy in pan hypopituitarism?
100-150mcg daily
How is cortisol replaced in the body in panhypopituitarism?
Hydrocortisone 10-25 mg/day (am/pm)
What formulations are available for ADH replacement?
Desmospray (nasal) or tablets
How is growth hormone replacement usually administered and when?
nightly subcutaneous injection
How are sex hormones replaced in pan hypopituitarism?
HRT/Combined pill for female
Testosterone for males
In what ways can testosterone be administered?
IM injection every 3-4 weeks (Sustanon) Skin gel (Testogel, Tostran) Prolonged IM injection 10-14 wks (Nebido) RARE = Oral tablets (Restandol)
What are the drawbacks of testosterone replacement?
- Prostate Enlargement
=> Does NOT cause cancer but may make it grow
Polycythaemia (thickened blood)
=> more at risk of MI/Stroke
Hepatitis (only for oral tablets) -
What are the usual causes of Diabetes Insipidus?
Familial
- Sometimes DIDMOAD (DI, DM, optic atrophy, deaf)
Acquired
- Idiopathic in 50%
- Trauma; road accidents, surgery, skull fracture
RARE
- Tumour, sarcoid, ext irradiation, meningitis
How is a water deprivation test usually carried out?
serum and urine osmolalities for 8h, and then 4h after giving IM Desmopressin (vasopressin)
If Ur/Serum Osmol ratio >2 = normal
=> otherwise DI
How can Diabetes insipidus be treated?
Desmospray (nasal) Desmopressin tablets (oral) Desmopressin injection (only used in emergency or post pituitary sugery)
