Pituitary Disorders Flashcards
What is a pituitary adenoma?
Benign tumour derived from cells of anterior pituitary
What is the aetiology of pituitary adenoma?
sporadic or associated with MEN1
What are micro-adenomas?
- adenomas<1cm
- much less aggressive than macroadenomas
What are macroadenomas?
- adenomas >1cm
- can present with visual field defects due to compression of the optic chiasma
- can cause pressure atrophy of normal surrounding cell tissue
- infarction can lead to panhypopituitarism
What are aggressive pituitary adenomas?
- a subset of adenomas behave aggressively and enlarge more rapidly (but don’t metastasise as still benign)
- features which indicate an aggressive lesion include lots of mitotic figures and p53 mutations
What are pituitary carcinomas?
- rare, account for <1% of pituitary tumours
- often functional (prolactin or ACTH usually)
- metastasise late after multiple recurrences
What is the presentation of a pituitary adenoma?
Non-functioning adenomas
- present due to mass effects
Functioning adenomas
Functioning pituitary adenomas are classified by cell type/hormone produced:
- prolactin (20-30%) - most common
- FSH/LH (10-15%)
- GH (5%) → GIGANTISM (Children) or acromegaly (adults)
- ACTH - usually a microadenoma → Cushing’s, bilateral adrenocortical hyperplasia
- can produce more than one hormone
- hormone production may be at subclinical levels
What is the investigation for a pituitary adenoma?
Prolactinoma
- serum prolactin raised
- MRI pituitary - micro vs macro, involvement of pituitary stalk/optic chiasm
- visual fields - bitemporal hemianopia
- other pituitary hormone tests to assess whether other hormones are being affected
What is the management of a prolactinoma?
- Bromocriptine - three times a day oral
- Quinagolide - once a day oral
- Cabergoline - once to twice per week oral - least side effects
What is acromegaly?
Growth hormone (GH) stimulates skeletal and soft tissue growth - GH excess therefore produces gigantism in children (if acquired before epiphyseal fusion) and acromegaly in adults
What is the aetiology of acromegaly?
nearly always due to a GH-secreting pituitary adenoma
What is the presentation of acromegaly?
- giant (before epiphyseal fusion)
- thickened soft tissues - skin, large jaw, sweaty, large hands
- snoring/sleep apnoea
- hypertension, cardiac failure → early CV death
- headaches (vascular)
- diabetes mellitus
- local pituitary effects - visual fields, hypopituitarism
What are the investigations for acromegaly?
- IGF1 - age and sex matched, nearly always raised
- Gold standard - GTT suppression test
- 75g oral glucose - check GH at 0, 30, 60, 90, 120 min
- Normally GH suppresses to <0.4 yg/l after glucose
- acromegaly indicated if GH unchanged/no suppression or paradoxical rise
- Visual fields
- CT/MRI Pituitary scan to check size of adenoma
- Pituitary function tests for other hormones
What is the management of acromegaly?
1st line - pituitary surgery
2nd line - Somatostatin analogues
3rd line - dopamine agonists
4th line - GH Antagonists
Describe pituitary surgery for acromegaly?
- transsphenoidal approach first line
- 90% cure if microadenoma
- 50% cure if macroadenoma
Describe the management of acromegaly using pharmacological management.
- Somatostatin analogues e.g., sandostatin LAR reduce GH in most patients, can be used before surgery to relieve symptoms and marginally improve outcomes
- given by subcutaneous injection
- side effects → diarrhoea, abdominal pains, gallstones and risk of biliary colic
Dopamine Agonists:
- Cabergoline up to 3g weekly
- works in around 10-15% of patients
- better if co-secreting prolactin
GH Antagonists:
- Pegvisomant
- SC injection - 10-30mg
- binds to GH receptor - blocks GH activity
- Tumour size does not decrease - occasional small increase in tumour size
- IGF-1 decreases but serum GH concentrations may increase
What are the complications of acromegaly?
- GH excess can result in the formation of colon polyps and colon cancer - may be presenting feature
- Increased risk of hypertension and cardiac failure can lead to early CV death
What is hypopituitarism?
Inadequate production of one or more pituitary hormone as a result of damage to the pituitary gland and/or hypothalamus
What is the aetiology of hypopituitarism?
- Pituitary tumours - non-functioning pituitary macroadenomas are the most common cause of hypopituitarism among adults
- Other local brain tumours - astrocytomas, meningiomas, gliomas, clival chordoma
- Iatrogenic - surgery or radiation
- Secondary metastatic lesions - lung, breast
- Traumatic brain injury
- Vascular diseases - polyarteritis
- Subarachnoid haemorrhage
- Hypothalamic diseases - syphilis, meningitis
- Autoimmune - Sheenan (post pregnancy)
- Granulomatous inflammation - sarcoidosis, histiocytosis X tuberculosis, meningitis
- Infarction/haemorrhage
What are the consequences of hypopituitarism?
- ↓ GH → growth failure
- ↓ TSH → secondary hypothyroidism
- ↓ LH/FSH → hypogonadism
- ↓ ACTH → hypoadrenal
- ↓ prolactin → unknown
- ↓ ADH → diabetes insipidus
What is panhypopituitarism?
- Refers to deficiency of all anterior pituitary hormones
- It is most commonly caused by pituitary tumours, surgery or radiotherapy
What is the presentation of hypopituitarism?
- Variable - depend on the specific hormone deficiency, age of onset, the rate at which hypopituitarism develops, and the underlying cause of hypopituitarism
- As well as hormonal effects, intra/parasellar masses (e.g. pituitary macroadenomas, craniopharyngiomas) can present with headaches and visual field defects (bitemporal hemianopia)
- Secondary hypothyroidism, hypoadrenalism, hypogonadism and GH deficiency lead to tiredness and general malaise, and reduced quality of life
What is the presentation of hypothyroidism?
Hypothyroidism causes weight gain, slowness of thought and action, dry skin, cold intolerance, constipation and potentially bradycardia and hyperthermia
What is the presentation of hypoadrenalism?
Hypoadrenalism causes mild hypotension, hyponatraemia and CV collapse (during severe intercurrent stressful illness)
What is the presentation of hypogonadism?
Hypogonadism leads to loss of libido, loss of secondary sexual hair, amenorrhoea and erectile disfunction, and eventually osteoporosis
What are the investigations for hypopituitarism?
Basal Tests
- LH, FSH, oestradiol/testosterone
- IGF-1
- Prolactin
- TSH, free T4, T3
- ACTH, cortisol
- Plasma/urine osmolality
Dynamic Tests
- Growth - insulin tolerance test, glucagon test
- HP-adrenal - insulin tolerance test, short ACTH stimulation test
- Water deprivation test
Imaging
- If a pituitary hormone deficiency is identified, perform cranial imaging (preferably MRI) to identify pituitary adenomas
What is the management of TSH deficiency?
levothyroxine
What is the management of ACTH deficiency?
- Hydrocortisone
- Cortisol is the most important hormone to replace because its deficiency can make patients the most unwell and often presents with an ‘Addisonian’ type clinical picture
What is the management of growth hormone deficiency?
- Needs to be given in children for growth
- May be considered in adults to improve work capacity and psychological well-being
- Decreases abdominal fat, increases muscle mass, strength, exercise, capacity and stamina, improves cardiac function, decreases cholesterol, increases LDL, increases bone density
- Daily SC injection
What is the management for hypogonadism?
- HRT/oest/prog pill for female
- Testosterone for males - sustanon (IM every 3-4 weeks) or skin gel (testogel, tostral) or nebido (prolonged IM injection 10-14 weeks)
What happens in diabetes insipidus?
Kidneys are unable to concentrate urine
What is the aetiology of diabetes insipidus?
Cranial DI
- Occurs when there is insufficient levels of circulating ADHFamilial - very rare
- Isolated in most causes
- DIDMOADAcquired
- Idiopathic in 50% - often autoimmune
- Tumours - craniopharyngioma, hypothalamic tumour, metastases, pituitary (very rare)
- Trauma - road accidents, skull fracture, external irradiation
- Infiltrations - sarcoidosis
- Infections - tuberculosis, meningitis, inflammatory disorders of hypothalamus and pituitary
What is the presentation of diabetes insipidus?
- Polydipsia
- Polyuria with dilute urine
What are the investigations of diabetes insipidus?
Water deprivation test
- After obtaining baseline lab values, patients stop drinking water for 2–3 hours before the first measurement
- Check serum and urine osmolarities hourly for 8hr, then 4hr after giving DDAVP
- If Ur/serum osmol ratio >2 it is normal, otherwise DI
- If Ur/serum osmol ratio is low and improves after DDAVP then it is due to cranial DI (not nephrogenic)
Imaging
- If CDI is diagnosed, a CT scan or MRI of the head should be conducted to rule out brain tumours (especially craniopharyngioma)
What is the management of diabetes insipidus?
- Desmospray (nasally) or desmopressin oral tablets
- Desmopressin IM injection - generally reserved for emergency or post pituitary surgery
