Endo Flashcards
cushings disease, acromegaly, phaeochromocytoma, osteomalacia, pagets disease of bone, osteoporosis, hyper and hypothyroid, diabetes, addisons
What are the 4 causes of cushings disease/ syndrome and the ACTH and cortisol /crh levels expected in each
1 cause: Exogenous - oral steroids
CAUSES
Cushing’s Syndrome
#1 cause: Exogenous - oral steroids: Cushing’s Syndrome
#2 cause: Endogenous – ACTH secreting pituitary
adenoma (most common), pituitary: Cushing’s Disease
#3 Pseudocushings –
stress/illness/alcoholism/depression
#4 Also consider ectopic ACTH production eg small cell lung cancer or adrenal adenoma
ACTH, Cortisol levels
Cushing’s disease: high ACTH, high cortisol
ectopic ACTH: high, ACTH, high cortisol
primary adrenal disease – low ACTH, high cortisol
Pseudocushings – high CRH, mildly high cortisol
What are the exam signs of cushings disease
EXAMINATION
- Central obesity
- Hypertensive, high blood glucose
- Plethora, moon face, buffalo neck hump
- Supraclavicular fat distribution
- Skin and muscle atrophy
- Bruises, violaceous striae
- Infection prone, poor healing
What are the IX - bloods, imaging for cushings disease
INVESTIGATIONS
Bloods:
- Pregnancy test (exclude in F)
- Blood glucose (elevated)
- 24-hour urinary free cortisol OR late-night
salivary cortisol tests to establish cortisol
levels - False positives in depression, obesity, alcohol excess.
- dexamethasone suppression tests
- (InCushing’s dexamethasone given at 11-12pm with 8-9am cortisol measured - normal pt suppressed morning cortisol, in cushings syndrome no cortisol suppression)
OR
plasma ACTH
- (if undetectable then 1*adrenal tumour, if high - pituitary or ectopic)
- if high Q6H 2mg dexamethasone for 48 hours suppression test: will cause >50% 9am cortisol fall in most pt with cushings but infrequently in ectopic
- CRH test (in pituitary disease cortisol rises, in ectopic it doesn’t)
Imaging:
- MRI pituitary, CT adrenals (looking for mass)
- don’t rely on imaging to localize source, as
many incidentalomas.
- Use localization laboratory tests.
- Inferior petrosal sinus sampling (elevated central: peripheral indicates central source).
Management of cushings disease in general and - For pituitary adenoma, adrenal adnoma, and ectopic
- Stop exogenous steroids
- Surgery or radiation therapy to remove pituitary, adrenal, or ectopic ACTH-producing tumors
Medication
- high protein intake and K administration / K sparing drugs such as spironolactone due to excess mineralocorticoid receptor stimulation by cortisol
somatostatin analogue: block ACTH secretion (pasireotide) + dopamine agonist cabergoline (block ACTH)
steroidogenesis adrenal inhibitor (ketaconazole)
glucocorticoid R antagonist (milfepristone)
- IV infusion etomidate inhibit b-hydroxylase to redue adrenal steroidogenesis: can be life saving for pt with fulminant symptoms
o Pituitary adenoma : trans-sphenoidal pituitary adenectomy. +/- radiation therapy
o Adrenal adenoma- adrenalectomy + med Tx before surgery:
o Ectopic- surgical resection of source +/- chemo/RTX. If disseminated - adrenal enzyme inhibitor - metyrapone, ketoconazole, mifepristone
Post-op hydrocortisone
What are complications of cushings disease before and after tx
- Increased vascular mortality
- HTN and hypokalaemia due to cortisol activating mineralocorticoid receptors
- Diabetes mellitus
- Osteoporosis: GC increased osteoblast and
osteoclast activity; interferes w Calcium absorp in GI tract. - nephrolithiasis
- Post Tx: adrenal insufficiency, central
hypothyroid, GH deficiency, Diabetes insipidus
definition of cushings disease/sndrome
Cushing syndrome is a constellation of clinical abnormalities caused by chronic high blood levels of cortisol or related corticosteroids.
Cushing disease is Cushing syndrome that results from excess pituitary production of adrenocorticotropic hormone (ACTH) secondary to a pituitary adenoma.
SE of ketaconazole, mifepristone, pasireotide
Pasireotide - hyperglycaemia
Mifepristone- hypokalaemia bc blocks corticosteroid, blocks action of steroid not lower its levels so monitoring hard
Ketaconazole - block corticosteroid,hepatotoxicity, QT prolongation and addisonian symptoms (adrenal insufficiency): eg, weakness, fatigue, orthostatic hypotension, hyperpigmentation).
Acromegaly definition and hx
DEFINITION
Increased secretion of GH (growth hormone) from:
- a pituitary tumour
- pituitary hyperplasia via ectopic GHR hormone from a carcinoid tumour
GH stimulates bone and soft tissue growth through
secretion of insulin like growth factor (IGI-1)
HISTORY
- Acroparaesthesia (tingling extremities)
- Shoes/rings not fitting, wonky bite, curly hair, altering appearance
- Amenorrhoea, decreased libido, headaches, increased sweating, snoring, arthralgia, backache
- OSA features
Examination and complications acromegaly
EXAMINATION
- Large hands and feet
- Tanned, acanthosis nigricans
Course face, wide nose, big supraorbital ridges
- Prognathism
- Macroglossia, spaced teeth
- Puffy lips, eyelids.
- Skin tags
- Goitre (increased vascularity)
- Proximal weakness, carpel tunnel bilateral (50%)
- Signs from pituitary mass; decreased vision, bitemporal hemianopia, seizures
COMPLICATIONS
- Impaired glc tolerance and DM
- Vascular – high BP, LVHypertorphy (+/- dilatation and CCF), arrhythmias,
- increased risk of IHD and stroke (? due to HTN +/- insulin resistance, GH-induced incr fibrinogen & decr protein S.
- Increased risk of colon cancer
Ix for acromegaly
INVESTIGATIONS
Bloods:
- Serum GH
- high glucose, high Ca and phosphate
- Don’t rely on random GH as secretion
pulsatile. Normally GH secretion is inhibited
by glucose, so perform OGTT, measuring GH
at 0,30,60,90,120 mins. If lowest GH is
>1ug/L acromegaly is confirmed.
Imaging:
- MRI to visualize pituitary fossa
Other:
- ECG
- ECHO
- Visual fields and acuity
- Old photos
Management & follow up of acromegaly
MANAGEMENT
1) Surgical removal of tumour (transsphenoidal) to reduce GH and IGF-1 to ‘safe’ levels
2) If surgery fails to correct hypersecretion, somatostatin analogues (GH inhibiting hormone) e.g. Octreotide
3) If resistant or intolerant to SSA, GH
antagonist e.g. Pegvisomant
Follow up
- Yearly GH, IGF-1, OGTT
- Yearly visual fields, vascular assessment, BMI,
photos
- Colonoscope consideration
phaeochromocytoma definition + presentation
DEFINITION
Catecholamine secreting neuroendocrine tumour of
adrenal medulla. Arise from sympathetic paraganglia cells, which are collections of chromaffin cells.
Extra-adrenal tumours are rarer, often found by
aortic bifurcation.
10% rule: 10% are malignant, 10% extra-adrenal,
10% bilateral, 10% familial.
PRESENTATION
- triad: episodic HA, sweating, tachycardia
- +/- HTN
- palpitations, skin sensations, flank pain,
visual changes, N/V/D
Ix (blood, imaging) + management + monitoring phaeochromocytoma
NVESTIGATIONS
Bloods
- plasma + 3 x 24hr urines for free metanephrines (elevated) & catecholamines (secreted intermittently)
- clonidine suppression test
MRI chest and abdo
- salt & pepper pattern
- MIBG (chromaffin seeking isotope) scan
MANAGEMENT
Medications
- a-blockade pre-op (phenoxybenzamine) used to avoid unopposed a-adrenergic stim.
- B-blocker after a blocker if heart disease or tachycardic.
- Need anesthetic consult.
Surgery
- Resection
MONITORING
- 24hr urine metanephrines 2/52 post-op, monitor BP
- lifelong f/u (malignant recurrence), genetic screening in younger patients (multiple endocrine metaplasia)
Osteomalacia definition, hx, exam and causes vs osteoporosis definition
DEFINITION osteomalacia
Normal bone mass + reduced mineral content.
Results in rickets if during bone growth,o steomalacia if after fusion of epiphysis. Basically, bones are soft.
Osteoporosis Definition: Loss in bone mass with normal mineral content. Bone loss is trabecular and cortical.
HISTORY and EXAMINATION
Bone pain, fractures (especially femoral neck),
proximal myopathy (waddling gait) due to vit D def
CAUSES
- Vitamin D Deficiency (most common)
- Calcium or phosphate deficiency
- Renal and Liver Disease
- Anticonvulsants
- High risk if low sun exposure (old people)
Ix of osteomalacia + management
INVESTIGATIONS
Bloods – low Ca and Phos, high alk phos and PTH,
low calcidiol, low vitamin D
Biopsy – bone biopsy shows incomplete mineralization
X-Ray – loss of cortical bone, non-displaced partial fractures.
MANAGEMENT
- Vitamin D and calcium supplements
(calcefort)