ENDOCRINE: Pituitary/ HPA problems incl adrenals andCushings Flashcards
What is Addisons disease?
Primary adrenal insufficiency. Destruction of the adrenal gland or genetic defects in steroid production
What are the symptoms of Addison’s disease?
Very non-specific:
* Nausea
* Abdo pain
* Weight loss
* Fatigue
* Weakness
* Cramps
* Reduced libido
* salt craving
* Dizziness and hypotension due to mineralocorticoid deficiency (aldosterone)
* Hypoglycaemia due to glucocorticoid deficiency
* Pigmentation due to ACTH excess from reduced cortisol
How do you treat an Addisonian Crisis?
1 litre IV fluids - saline over 30-60 mins
100mg IM or IVhydrocortisone
Continue hydrocortisone 6 hourly until pt stable.
After 24hrs = start oral replacement, reducec to maintence over 3-4 days
What is the most common cause of Addison’s disease in the UK?
Autoimmune
What is the relevance of TB to Addison’s disease?
TB can cause Addison’s- most common cause in developing countries
What is the gold standard investigation for Addison’s disease?
What other inv may you do?
ACTH test aka Short Synacthen
Other inv:
* first line - U+Es and serum cortisol (see hyponatraemia, hyperkalaemia and low serum cortisol if unwell)
* renin and aldosterone levels (renin would be high, aldosterone would be low)
* glucose
* blood gas
* adrenal auto-antibodies
* CXR
* CT scan adrenal glands
* MRI brain
In an unwell Addison’s pt, what would blood gas show?
Hyperkalaemic, hyponatraemic hypoglycaemic metabolic acidosis.
Differential diagnosis for adrenal insufficency?
- Chronic fatigue syndrome: Presents with persistent fatigue, cognitive difficulties, and other non-specific symptoms
- Dehydration or septic shock: Hypotension and tachycardia can mimic adrenal insufficiency
- Primary psychiatric illnesses: Depression or other psychiatric illnesses may present with fatigue, decreased appetite, and weight loss.
- Graves disease
How is adrenal insufficency / Addison’s managed?
- replace what is missing - need hydrocortisone (to replace glucocorticoids) and fludrocortisone (to replace mineralocorticoids)
- patient education on sick day rules - carry steriod card and wear medical alert bracelet
- double regular steriod meds dose during any intercurrent illness
- regular screening for complcations - adrenal crisis and osteoporosis.
What are the complications of addison’s disease?
- addisonian crisis
- severe elcetrolyte imbalances
- cardovascular collapse
- hypoglycaemia
- side effects of long term corticosteriod use - osteoporosis, secondary cushings
What are the effects of a prolactinoma in a) women and b) men
a) Women- amenorrhea, galactorrhea and infertility
b) Men- erectile dysfunction, gynocomastia, reduced sex drive and less body hair
What is the most common cause of primary adrenal failure?
Autoimmune, usually have positive adrenal antibodies present
What are the hallmark biochemical features of primary adrenal failure?
Hyperkalaemia, hyponatraemia, raised urea and mild anaemia, hypoglycaemia
Why does ACTH deficiency present like SIADH?
Cortisol deficiency leads to increased ADH secretion
Where is the pituitary gland situated?
In pituitary fossa at the base of the brain
What anatomy lies a) superior and b) laterally to the pituitary gland?
a) Superior - optic chiasm. b) Laterally - cavernous sinus
What nerves/ blood vessels are in the cavernous sinus?
Occulomotor, Trochlear , trigeminal Va, Vb, abducens, internal carotid artery.
How is growth hormone secreted?
Pulsatile manner. Peak pulses during REM sleep
Name the hormones positively and negatively controlling GH
Positive = GHRH. Negative = somatostatin
Describe the adrenal axis
CRH stimulates ACTH release. ACTH release is circadian - peak pulses early in the morning and lowest at midnight. ACTH stimulates cortisol release. Cortisol has negative feedback on ACTH
What are LH and FSH stimulated by and inhibited by?
Pulsatile GnRH stimulates. Testosterone and oestrogen inhibit
What hormones does prolactin inhibit?
LH and FSH - directly inhibit.
What are the 2 ways that pituitary tumours can present?
Compressive - compress surrounding structures - vision, cranial nerves, all hormones can be reduced. (non-functional pituitary tumour).
Excessive hormone production (functional pituitary tumours).
How is prolactin predominantly controlled?
Mostly under negative control by dopamine and weak stimulatory control by TRH
How can functional pituitary tumours present?
Acromegaly. Cushing’s disease. Prolactinoma. TSHoma.
Pituitary tumours compressing optic chiasm cause which visual defect?
Bi-temporal hemianopia
What should be assessed in pt with suspected pituitary tumour?
Assessment of visual fields
Biochemical assessment- divided into basal (prolactin, TSH, LH and FSH) and dynamic tests (synacthen test and insulin tolerance test)
What time of day should LH, FSH and basal testosterone be checked in men?
0900 when deficiency is suspected.
When should LH, FSH be tested in women?
Measured within 1st 5 days of the menstrual cycle
IGF-1 is a marker of GH. What do a) low levels and b) high levels of IGF-1 show?
a) low levels - GH deficiency
b) high levels - excess GH.
What is synacthen test?
Give synthetic ACTH to assess primary adrenal failure. Test how well adrenal glands work by measuring cortisol.
What is the Insulin Tolerance Test?
Gold standard to test ACTH and GH reserve.
Cause insulin - induced hypoglycaemia. Should see ACTH and GH rise (from the reserve).
Which patients should you NOT do insulin tolerance test for?
Pt with IHD - can triggery coronary ischemia
Pt with epilepsy - can trigger seizures
What imaging would you order for pathology of pituitary gland?
MRI
CT if unable to have MRI
Distinguish between micro and macro adenomas
Micro - less than a cm. More common in women
Macro - more than a cm. More common in men
Name ddx for a finding of hyperprolactinaemia
Pregnancy - needs to be excluded first Medications - antiemetics, anti-psychotics Hypothyroidism (rare) PCOS Large pituitary tumour Stress Renal failure, adrenal insufficiency.
How do micro-prolactinomas present?
Menstrual disturbance
Hypogonadism in men
Galactorrhoea
Infertility
How is PCOS distinguished from prolactinoma?
The presence of androgenic symptoms
Less elevated prolactin (<1,000 miU/L)
Absence of pituitary lesion on MRI
How are prolactinomas treated?
Dopamine D2 agonists
Name a D2 agonist
Cabergoline- given once or twice weekly, and better tolerated than bromocriptine
Bromocriptine- given daily
Name common side effects of cabergoline
Nausea, postural hypotension
Rare - psych disturbance
What is risk associated to reducing size of lesion/ tumour bulk of prolactinoma?
When size reduces rapidly, can get CSF leak which gives potential risk of meningitis
What causes acromegaly?
Excessive growth hormone.
Most common cause if unregulated GH secretion by pituitary adenoma
Can also be secondary to malignancy elsewhere e.g lung or pancreatic cancer secreting ectopic GHRH or GH
What can untreated acromegaly lead to?
Disfiguring features
CVD → premature death
Increased risk of bowel cancer
How does acromegaly present?
Increased size of hands and feet
Frontal bossing of forehead
Protrusion of chin
Widely spaced teeth
Enlargement of tongue and soft palate due to soft tissue swelling - sleep apnoea, snoring
Puffiness of hands - carpal tunnel syndrome
Name specific features of active GH hypersecretion
Sweating, headaches, HTN, DM
What investigation would you do for suspected acromegaly? And what would you see?
Oral glucose tolerance test. Failure to supress GH after OGTT ad elevated IGF-1.
List management options available for acromegaly
Surgery - remove adenoma
Medical - somatostain analogue or dopamine agonist.
External beam or stereotactic radiotherapy- stereotactic radiotherapy only suitable for lesions well away from the optic chiasm
How does the chance of remission differ between patients with pituitary micro-adenomas vs macro-adenoma
Micro-adenoma, high chance of remission
Macro-adenoma- only achieved in 60% of patients
How is acromegaly monitored?
Repeat OGTT after surgery
Long term follow up needed - to control GH and IGF-1 levels.
Periodic screening colonoscopy as there is risk of neoplasia.
Assess for sleep apnoea, DM, CVD risk, symptoms of recurrance
What are Non-functioning pituitary adenomas (NFPA)?
Biochemically inactive tumours
How do non-functioning pituitary adenoma present?
Visual field loss, headache, hypopituitarism
How does hypopituitarism present?
Non specific - lethargy, weight gain, sexual dysfunction
Can present with hypo-adrenal crisis - hyponatraemia, hypotension - MEDICAL EMERGENCY
Short stature in children
How is hypopituitarism investigated?
Exclusion of adrenal insufficiency
Investigate levels of all hormones.
MRI could show empty fossa or pituitary tumour
How is hypopituitarism treated?
Depends on the deficiency - ACTH-hydrocortisone replacement
TSH-thyroxine replacement
gonadotropin- Men- testosterone via gel or injection
Women- oestrogen and progesterone via COCP or HRT
GH- daily subcut injection
Differentiate between Cushings syndrome and Cushing’s disease
Cushing’s syndrome- collection of symptoms
Cushing’s disease- excessive ACTH secretion from a PITUIATARY adenoma, can cause cushings syndrome
How does Cushing’s syndrome present?
Central obesity
Dorso-cervical fat pad
Increased roundness of the face
Pt has red face, thin skin, proximal myopathy
May be HTN, premature osteoporosis, DM, depression, cardiac hypertrophy (due to too much stress hormone)
Why is it dangerous to leave Cushing’s syndrome untreated?
Significant morbidity. 5-yr mortality approaching 50%
What are the causes of Cushing’s syndrome?
Exogenous steroids
Cushing’s disease
Adrenal adenoma
Paraneoplastic Cushing’s (ectopic ACTH secretion e.g. small cell lung cancer)
What investigations would you do for suspected Cushing’s syndrome?
24hr urine free cortisol, low dose dexamethasone suppression test, overnight dexamethasone suppression test.
Screening tests - alcoholism and severe depression can make pts look like they have cushings syndrome but tests come back as normal
Explain the dexamethasone supression tests.
Low dose 1mg- give dexamethasone at 10pm, check free cortisol at 9am. NORMALLY, should be suppressed, in Cushing’s SYNDROME, it will not be suppressed, therefore you now do the HIGH dose to find out the underlying cause
High dose dexamethasone supression test 8mg. Process is same as above:
Cortisol is surpressed- cushing’s disease- pit adenoma
Cortisol is NOT supressed but ACTH is surpressed- adrenal adenoma (secreting cortisol independently)
Neither cortisol or ACTH surpressed- ectopic ACTH
Name differential for Cushings syndrome
Pituitary, adrenal or ectopic ACTH
What may be in pt’s Hx to point towards them having ectopic ACTH secretion, causing Cushings syndrome?
Hypokalaemia
SMoking Hx
Weight loss
By lung cancer or other malignancy.
What presenting complaint directly points towards adrenal tumour?
Significant, accelerated hirsutism
How is adrenal tumour managed?
Adrenalectomy
How is cushings disease managed?
Trans-sphenoidal removal of pit adenoma
What are some side effects of long term steroid use - many think of a few from different systems
endocrine: impaired glucose regulation increased appetite/weight gain hirsutism hyperlipidaemia
Cushing’s syndrome:
moon face
buffalo hump
striae
musculoskeletal:
osteoporosis
proximal myopathy
avascular necrosis of the femoral head
immunosuppression:
increased susceptibility to severe infection
reactivation of tuberculosis
psychiatric: insomnia mania depression psychosis
gastrointestinal:
peptic ulceration
acute pancreatitis
ophthalmic:
glaucoma
cataracts
suppression of growth in children
intracranial hypertension
neutrophilia
What is Sheenhan’s syndrome? What causes it?
What?
Ischaemia of pituitary gland causes necrosis of secretory cells - get panhypopituitarism.
Leads to : amenorrhea, failure to lactate and death
Cause?
Hypotension/ hypovolaemia due to obstetric haemorrhage. Pituitary gland becomes large and vascular during pregnancy so is vulnerable to hypotension and hypoxia.
What is a pituitary apoplexy? What causes it? What is commonly lost? Tests?
What?
Endocrine Emergency —-> Haemorrhage / infarction of a pituitary tumour
Cause?
Commonly hypertension or surgery
Commonly lost?
Anterior pituitary hormones- especially ACTH.
Causes 2ndary Adrenal Insufficiency
Tests: Electrolytes / Pit hormones / Glucose / MRI or CT if none
How would a patient with pituitary apoplexy present?
Sudden onset severe headache (thunderclap) retro-orbital
Nausea, vomiting, reduced consciousness
Opthalmoplegia (paralysis / weakness of 1 or more extraocular muscles)
Visual disturbance - bitemporal hemianopia most common
+ deficiency in Ant Pit hormones - especially ACTH
Most common functioning tumour of the anterior pituitary gland?
Prolactinoma
How large is a macroadenoma of the pituitary? what sign might a patient have ?
> 10mm
Bitemporal hemianopia due to compression of optic chiasm
What is 1st line treatment for Prolactinomas in men and women? 2nd line?
1st line:
Dopamine agonist - Cabgergoline reduce tumour size and prolactin level
2nd line: Trans sphenoidal surgery if medical treatment not tolerated or unsuccessful
How does Prolactinoma present in men vs women
Men: Loss of libido Lethargy Galactorrhea impotence hypogonadism (small testes)
Women:
- Menstrual disturbance: Amenorrhea/Oligomenorrhea/Menorrhagia
- Infertility
- Galactorrhea
How might a non-functioning adenoma present?
Compression might cause:
Visual disturbance - bitemporal hemianopia
Headache / vomiting / papilloedema (ICP +)
Oligomenorrohea and amenorrhea in women
Reduced libido and fertility in men
Cranial nerve palsy
How might a non functioning pituitary adenoma cause hyperprolactineamia?
Non functioning can cause as it removes the dopaminergic inhibition of prolactin release
What investigations for Hyperpituitarism ? (4)
- Visual
Optic chiasm - bitemporal hemianopia
Cavernous sinus - diplopia
2. Blood hormones (morning ) TSH / thyroxine Prolactin ILGF-1 FSH / LH / oestrogen / testosterone ACTH / Cortisol
- Imaging
MRI / CT
radio-labelled dopamine antag. can visualise prolactinoma - SUPPRESSION tests (reduced -ve feedback)
Oral glucose tolerance test - should normally suppress GH
ACTH in response to dexamethesone should suppress CRH and ACTH
What drugs can cause hyperprolactinaemia?
D2 antagonists
Antipsychotics 1st + 2nd:
Haloperidol 1st
Clazapine 2nd
Cyclic Antidepressants:
Amytryptilline
SSRIs:
Citalopram
Anti emetics:
Domperidone
Metoclopramide
How does a prolactinoma lead to infertility?
Prolactin interferes with GnRH release. This inhibits the release of LH and FSH causing hypogonadism
What outside of the pituitary gland in surrounding tissues could cause hypopituitarism?
Tumours of surrounding tissues that could compress.
Gliomas (in optic chiasm)
Meningiomas
Craniopharyngiomas
Mets - breast, bronchus, kidney
What is the medical treatment of hyperprituitarism? (4) Risk of treatment?
All risk of inducing hypopituitarism
Cabergoline - dopamine antagonist to reduce prolactin
Somatostatin analogue - Octreotide to reduce GH
Surgical removal
Irradiation to prevent recurrence
What is a microadenoma?
adenoma <10mm
more common
What investigations needed to diagnose hypopituitarism?
Visual field assessment
Basal blood tests
MRI or CT
STIMULATION TESTS
GH - does GH rise in response to insulin tolerance test?
Cortisol - does it rise after ACTH (Synacthen)
LH / fSH in response to GnRH or clomifene (anti oestrogen)
What is the treatment for Pituitary Apoplexy?
High dose IV hydrocortisone
Transsphenoidal surgical decompression w/in 1 week
( Surgery for pts with neuro-opthalmic signs / deteriorating consciousness)
Group the major disorders of the anterior pituitary into 2 main categories
- Hormone excess due to functioning adenomas
e. g. GH- acromegaly, ACTH- Cushing’s disease - Hormone deficiency due to non functioning adenoma (SOL). Present later as a macroadenoma - compress secretory cells or portal vessels
List 4 ways that pituitary tumours can present
- Visual disturbance / headache
- Inappropriate hormone excess ACTH- Cushing’s disease, Prolactinaemia, GH- acromegaly
- hormone hypo / hyper secretion due to compression
- Amenorrhea or loss of libido
What are some infective / inflammatory cause of pituitary failure?
Infective:
TB / syphyllis
Inflammatory:
sarcoidosis
haemochromatosis
What investigations needed to diagnose hypopituitarism?
STIMULATION TESTS
What are the differentials of Diabetes Insipidus clinical presentation?
Psychogenic polydipsia, DM, Diuretic use, Hypercalcaemia ( as serum calcium is elevated)
Acid base balance in addisons/adrenal insufficiency?
Hyperkalaemic metabolic acidosis
Treatment for ectopic Cushing’s syndrome?
Treat underlying malignancy
Why are ACTH levels low in an adrenal cause of Cushing’s syndrome?
Increased cortisol causes negative feedback.
What are levels of ACTH in Cushing’s syndrome caused by pituitary adenoma or paraneoplastic?
Normal or high
Pit adenoma= excessive ACTH secretion
Paraneoplastic= tumour secreting ACTH that is NOT pit adenoma
What are cortisol levels following high dose dexamethasone suppression test in a pituitary adenoma?
Reduced cortisol
What are cortisol levels following high dose dexamethasone suppression test in ectopic Cushing’s syndrome?
No suppression - cortisol remains high.
Following High dose DST for pituitary adenoma secreting ACTH, what is next step in management ?
MRI of the pituitary gland.
If MRI of pituitary gland in Cushing’s syndrome does not show pituitary adenoma, what is next step?
Inferior Petrosal Sinus Sampling = shows clear gradient between central and peripheral ACTH levels after an injection with CRH. (Sampling the veins that drain the pituitary gland)
In suspected ectopic ACTH in Cushing’s syndrome, what is next step following High Dose DST?
Whole body CT scan or PET imaging - to find carcinoma.
Note: common place = thorax.
Medical treatment options for Cushing’s syndrome?
Metyrapone - block steroid synthesis pathway
Ketocanazole - adrenolytic agent
Radiotherapy - help reduce size of tumours before surgery. Or mainstay of treatment if tumours are unresectable.
