Pituitary axis Flashcards
Acromegaly
a) Diagnostic tests
b) Management
a) Screening test:
- IGF-1 level - raised
Confirmatory test:
- OGTT - 2 hours after load, GH remains high (>20)
b) - Trans-sphenoidal resection (60% curative)
- Somatostatin analogues - neoadjuvant if large tumour, adjuvant if surgery fails to induce remission
Pseudohypoaldosteronism
Gordon’s syndrome
- Addisons biochemistry (hyperkalaemic metabolic acidosis)
- With HYPERtension
Water deprivation test
a) Procedure
b) Urine output and urine osmolality in DI
c) Serum osmolality cut-off for abandoning test
d) Test results for PPD, CDI and NDI
e) What value of urine osmolality after deprivation suggests and excludes DI
f) What should happen to urine output in PPD vs DI?
g) If serum osmolality reduces at all during test, what does this indicate?
a) - The patient is allowed fluids overnight
- The patient is deprived of fluids for 8 hours or until 5% of the body mass has been lost
- They are weighed hourly
- Plasma osmolality measured 4 hourly and urine volume and osmolality every 2h
- At the end of 8h the patient is given 2 mcg of intramuscular desmopressin and urine and plasma osmolality checked over the next 4 hours
b) - UO >3L per day
- Urine Osm <300 (inappropriately dilute)
c) - If serum osmolality rises to >305 mmol/kg the patient has diabetes insipidus and the test is stopped.
d) - PPD - Urine osmolality rises to > 400 on water deprivation (should rise to >600*), serum osmolality should remain <300
- Cranial DI - urine osmolality remains <300 but rises to >600 after desmopressin. Serum Osm rises >300
- Nephrogenetic DI - urine osmolality is <300 both before and after desmopressin (or rise by <45%). Serum Osm >300
*Chronic polydipsia causes reduced ability of kidneys to concentrate the urine
e) - <400 suggests DI (in the absence of renal tubular disease)
- >600 excludes DI
f) PPD - reduces
DI - remains polyuric
g) Patient has drank some water on the sly
Aldosterone-renin ratio (ARR)
a) Procedure
b) Medications that must be stopped (alternatives?)
c) Interpretation of results
d) Follow-up tests
e) Primary vs secondary hyperaldosteronism vs “apparent mineralocorticoid excess”
a) - Any time of day, lie recumbent for 30 mins
- Potassium should be normal range (use supplements if needed)
- If screening test positive (>800), repeat test in 4 weeks or proceed to saline infusion test
b) - Stop ACE, ARB and aldosterone antagonists for 4 weeks
- Stop BBs and diuretics for 2 weeks
- Switch to CCBs or ABs if needed for BP control
c) <800 = excludes Conn’s
800-2000 - indeterminate
>2000 = Conn’s likely (if renin low)
d) Saline infusion test:
- Take baseline plasma aldosterone + renin
- Infuse 2L over 4h NaCl 0.9%
- Repeat plasma aldosterone + renin
- If primary hyperaldosteronism, will have failure of aldosterone suppression with plasma expansion
e) - Primary - high aldosterone, low renin
- Secondary - high aldosterone, high renin (caused by any cause of low renal flow - e.g. RAS, dehydration, heart failure, cirrhosis/HRS)
- Apparent mineralocorticoid excess - low renin and low aldosterone, despite biochemical profile of hyperaldosteronism (hypokalaemic hypochloraemic* alkalosis, HTN) - causes include fludrocortisone and liquorice ingestion
*Chlorine and bicarbonate tend to oppose each other:
- Hypochloraemia in metabolic alkalosis (high bicarb)
- Hyperchloraemia in metabolic acidosis (low bicarb)
Hyperprolactinaemia
a) Drug induced - causes, prolactin level
b) Micro vs macroadenomas - prevalence, prolactin levels
c) Stalk effect
d) Other causes
e) Presentation
a) - Antipsychotics (typical especially), D2-blocking agents (metoclopramide, domperidone), omeprazole, methyldopa, verapamil, SSRIs, TCAs
- Prolactin level up to 1000 (normal prolactin levels <400)
b) Micro (90%), macro (10%)
- Microprolactinomas usually have prolactin 1000-4000
- Prolactin >5000 indicates probable macroprolactinoma
c) Compression of/damage to pituitary stalk* (e.g. head injury, craniopharyngioma, large pituitary tumour), causing inability of dopamine (prolactin-inhibitor) to reach the pituitary from the hypothalamus
- MRI scan that reveals large tumour (>1cm) with prolactin levels <5000 likely suggest non-prolactinoma with stalk effect
d) - Pregnancy, breastfeeding, nipple stimulation
- Stress, exercise
- Endocrine: PCOS, hypothyroid (TRH increase stimulates prolactin release), Cushings
- CKD (uraemia causes inhibition of dopamine release)
- Post-ictal
- Cirrhosis
- Sarcoid
- Langerhan’s histiocytosis
e) - Galactorrhoea
- Pre-menopausal women: amenorrhoea (often at lower prolactin levels, so present earlier)
- Loss of libido, sexual dysfunction
- NOT gynaecomastia
Waterhouse Friderichsen syndrome
Meningococcal sepsis
Resulting in adrenal gland haemorrhage
Causes adrenal failure
Also have characteristic pink papules/macules in 75%
Adrenal insufficiency
a) Causes
b) Antibody in Addisons
a) - Autoimmune - Addison’s
- Malignancy - mainly adrenal metastases
- Adrenalectomy
- Infection - TB, meningococcus
- Infiltration - amyloid, sarcoid
- Vascular - haemorrhage, infarction
- Congenital
b) Antibodies to 21-hydroxylase
Insulin tolerance (stress) test
a) Contraindications
b) Why is it done? Theory
c) How is it performed?
d) Normal vs. abnormal response
a) Epilepsy, arrhythmia, ischaemic heart disease, stroke, unexplained fits or collapses
b) To assess anterior pituitary function
- Theory is that hypoglycaemia should induce anterior pituitary to produce ACTH and GH
c) - Baseline glucose, cortisol and GH
- Insulin given and glucose checked until BG <2.2 and neuroglycopenic symptoms present
- Cortisol and GH levels taken
- Oral / IV glucose given and test stopped
d) - Normal ACTH function –> cortisol >500 (abnormal <400, intermediate 400-500)
- Normal GH function –> GH >20
Short synacthen test
a) Procedure
b) Normal vs. abnormal result
c) Which drugs lead to cortisol rise and may interfere with result
d) Other tests for hypocortisolism
a) - Baseline cortisol (usually morning, but can be anytime)
- Synacthen IM/IV given
- 30 min and 60 min cortisol
b) Normal:
- Doubling of cortisol/ rise to >500 at 30 or 60 mins
- May indicate secondary hypoadrenalism or normal function
Abnormal:
- Cortisol <400 at 30 and 60 mins
(if 400-500, have a degree of adrenal insufficiency - may need steroids during acute illness/stress)
c) Steroids
Oestrogens
d) - Adrenal auto-antibodies (adrenal cortex antibodies, 21-hydroxylase antibodies)
- DHEA-S - often raised in Addison’s
- ACTH level
- Renin (high), aldosterone (low)
- TFTs
- Other pituitary tests e.g. insulin stress test
- CT or MRI adrenals
Overnight dexamethasone suppression test
a) Low dose 1mg
b) High dose 8mg
c) Alternatives in screening for Cushing’s syndrome
a) To diagnose Cushing syndrome:
- Normal response in healthy patients is suppressed ACTH resulting in low 8am cortisol (<50) => low cortisol, low ACTH
- Cushing syndrome -1mg is too low a dose to suppress ACTH => high cortisol, high ACTH
b) To locate cause of Cushing’s:
- 8mg is high enough dose to suppress ACTH in Cushing disease, causing reduced cortisol by >50% = low cortisol, low ACTH
- In adrenal tumour, suppresses ACTH but does not suppress the adrenal secretion of cortisol => high cortisol, low ACTH
- In ectopic ACTH secretion, suppressed endogenous ACTH from the pituitary, but does not suppress this ectopic secretion of ACTH => high ACTH, high cortisol
Pituitary = low ACTH, low cortisol
Adrenal = low ACTH, high cortisol
Ectopic = high ACTH, high cortisol
c) Diagnosing Cushing’s:
- 2x 24h urinary cortisol levels (raised 3x above ULN) - unreliable in eGFR <60
- 2x midnight salivary cortisol levels (loss of circadian changes) - unreliable in shift workers
Identifying location of Cushing’s:
- Plasma ACTH –> if low CT adrenals, if high MRI pituitary
- Petrosal sinus sampling - if higher levels ACTH here vs serum - likely pituitary source
- Thin slice CT chest - SCLC/ carcinoid tumour
- N.B. MRI pituitary often normal as ACTH-secreting adenomas often very small and not detectable on MRI
Pseudo-Cushings
a) Causes
b) vs. True Cushing’s Syndrome
a) Alcoholism, obesity, depression
b) 24h urinary cortisol + overnight dexamethasone suppression tests should be normal in Pseudo-Cushings
DI
a) Management of cranial DI vs nephrogenic DI
b) Causes of cranial DI vs nephrogenic DI
a) Cranial DI:
Desmopressin
Nephrogenic:
- Remove precipitant (e.g. lithium) - may take years to recover/may never recover
- Salt restriction
- Thiazides and NSAIDs - help to reduce UO
b) Cranial DI causes:
- Tumours, head injury, neurosurgery
- Granulomas - sarcoid, GPA, TB, Langerhan’s cell histiocytosis*
- Vascular - stroke, haemorrhage, sickle cell, Sheehan’s
- Infections - meningo-encephalitis
- Inherited - DIDMOAD (autosomal recessive)
*In MRCP, if cranial DI with cystic lung disease, think LCH
Nephrogenic DI:
- Drugs - lithium, demeclocycline, quinolones, orlistat
- Metabolic - low K+, high Ca2+
- Renal - CKD, post-obstructive uropathy, RTA
- Inherited - X-linked mutation in V2-receptor
Incidental pituitary adenoma
a) Initial workup
b) If normal, surveillance for micro- vs macroadenomas
c) Usual first deficiencies in pituitary adenomas
a) Pituitary function tests (test for hypopituitarism, or hypersecretion)
b) If asymptomatic and pituitary function tests normal:
- Macroadenomas - MRI at 6 months, then annually if normal
- Microadenomas - MRI at 12 months, then 3-yearly if normal
c) - Sex hormones (loss of libido) and growth hormone
- TSH and ACTH lost later
- DI rare in pituitary tumours given ADH produced in hypothalamus and can be released directly from there (more common in craniopharyngioma)
Adrenal incidentaloma
a) Causes
b) Workup
c) Features on imaging suggestive of benign adenoma
d) Danger of biopsy on phaeo
a) - 60% adrenal adenoma (of which 60% non-functioning, some cortisol- and some aldosterone-secreting)
- Phaechromocytoma
- Adrenal carcinoma
- Adrenal metastases
b) - 24h plasma/urinary metanephrines
- Dex suppression test or 24h urinary cortisol
- Aldosterone: renin ratio
- Sex hormone measurement
- If history of extra-adrenal cancer, perform FDG-PET scan
- Biopsy ONLY if ruled out phaeo, suspicion of malignant disease and history of extra-adrenal cancer
- If tumour >4cm, remove
- If tumour <4cm, repeat scan in 6 months
c) - Homogenous
- Lipid-rich
- <4cm
d) Can cause life-threatening release of catecholamines
Nelson syndrome
a) Cause
a) - Post-bilateral adrenalectomy for Cushing’s disease*
- Leads to development of ACTH-secreting macroadenomas which can be invasive and life-threatening
*If the pituitary adenoma is not resectable
