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)
Pagets disease of bone definition, hx and exam and complications
DEFINITION
Increased bone turnover associated with increased
numbers of osteoblasts and osteoclasts leading to remodeling, bone enlargement, deformity,
weakness.
- cause unknown - genetic or viral trigger
HISTORY and EXAMINATION
- Asymptomatic (70%) – high ALP found incidentally
- Bone pain, joint pain – most common symptoms
- Pathological fractures
- Bony deformities of the pelvis, lumbar spine, skull,
and femur – usually affects a small number of bones, rest normal
- Abnormal gait
- Neurological symptoms
COMPLICATIONS
- Pathological fractures
- Osteoarthritis
- Nerve compression due to bone overgrowth (deafness, root compression)
- High output CCF
- Osteosarcoma
Ix and management paget disease of bone
INVESTIGATIONS
Bloods - Ca and Phosphate normal, alk phos raised
X-ray - shows localized enlargement, patchy cortical
thickening with osteolysis, sclerosis, deformity.
- Affinity for axial skeleton, long bones, skull.
MANAGEMENT
No cure
- Analgesia
- Alendronate (reduce pain)
- Sometimes surgery – osteotomy
- Lifestyle – Increase Ca diet, sun, exercise
Can screen those at high risk (fam history) with ALP
levels
Addisons disease; definition, and cause
DEFINITION
-primary adrenal insufficiency
-destruction of adrenal cortex = deficiency in
corticosteroids and mineralocorticoids
-anyone on steroids for long enough to suppress
adrenal glands is at risk
CAUSE
-80% autoimmune
-Tb (commonest worldwide)
-adrenal mets
-lymphoma
-exogenous steroids (although this is secondary
adrenal insufficiency)
Hx and exam Addisons disease + addisonian crisis
HISTORY
mineralocorticoid def:
- dehydration, hypotension : dizziness, faints , n&V abdopain
glucocorticoid def
- insulin sensitivity: hypoglycaemia, weakness, anorexia,
- myocardial weakness - reduced CO
^^ pit ACTH - increase melanocyte stim:
-pigmented palmar creases and buccal mucosa (but not in addisons 2nd to pituitary failure)
EXAMINATION
-pigmented palmar creases and buccal mucosa
-postural hypotension
-Addisonian crisis : under physiologic stress.
(profound weakness, severe abdomen very low BP, tachycardia, renal shutdown with azotemia, severe fever, shock.
Ix and treatment for addisons
INVESTIGATIONS
-low Na, high K (mineralocorticoid def)
-low glucose
-Synacthen test (synthetic ACTH) – measure cortisol before and after, should rise in healthy person but not in Addison’s
-serum ACTH – will be high in Addison’s
-adrenal autoantibodies – positive in autoimmune cases
-CXR – signs of Tb, or mets
TREATMENT
-replace steroids (hydrocortisone and
fludrocortisone in doses throughout day
-give IM hydrocortisone injection for crises
Risk factors for osteoarthritis - 12, + presenting complaint
Presentation
- Fragility fracture – fall from standing height or less
- Typically femoral neck , spine, greater trochanter, distal radius
Risk Factors
- Old age
- Family History
- Steroid Use (glucocorticoids inhibit osteoblasts + others)
- Hyperthyroid (increases bone turnover)/ hyperparathyroid/ calcinuria
- Alcohol + smoking
- Testosterone deficit F>M – (testosterone helps building bone)
- Thin (BMI <20)
- Early menopause (less estrogen – increased bone turnover and resorption)
- Renal failure (reduced vit D converted to active causes PTH increase to mobilise ca from bone to blood)
- or liver failure (mixed malnutrition, reduced vit D hydroxylation before kidney)
- Erosive/inflammatory bone disease like RA (systemic inflammation + steroid use)
- Dietary low calcium, malabsorption eg. coeliac (low vit D), T1DM (modulates osteoblast activity )
Ix, Scoring system and dx parameters for osteoporosis with potential secondary ix
Investigations
1. Bloods
- Ca, phosphate, ALP should be normal in osteoporosis
- Xray after a fracture : hypo chondral sclerosis, joint space narrowing, osteophytes, altered trabecular pattern, cortical thinning and increase radiolucency, joint
- Bone density DEXA scan in patients with
- low trauma fracture
- women <65 with 2 + risk factors
- women >65 with 1 risk factor
- prior to long term steroid use
- bone and remodelling disorders
Alternatively can use a fracture risk calculator – eg FRAX or Garvan Fracture Risk Calculator
FRAX score calculates the risk of osteoporotic fracture and hip fracture in next 10 years. IF >10% then advocate for BP treatment. Eligible for BP if hip fracture risk >3.5
- DIAGNOSIS is with T score (number of SD away from youthful average of bone mineral density)
- -1 to -2.5 is osteopenia – lifestyle advice
- > -2.5 is osteoporosis
If T score >2 consider : - renal function
- parathyroid hormone
- testosterone and SHBG in males
- LH and FSH
- Coeliac antibodies
- TSH
- Serum protein electrophoresis
Treatment - pharm and non pharm for osteoporosis with SE for bp
Non Pharmacological
- Quit smoking and reduce alcohol <2 drinks/day, >2 alcohol free days
- Weight bearing and balance exercises
- Ca and Vit D rich foods + sun exposure
- Home base fall prevention programme
Pharmacological
1. Supplemental Vitamin D if inadequate sun exposure/intake : colecalciferol 1.25mg monthly
2. Biphosphanate for pt >70 with T score -3 or less, minimal trauma fractures or prevention in long term steroid use
- Alendronate 70mg po weekly on empty stomach with water, upright for 30 minutes after .
- Fosamax plus one tab weekly has vit d added in already
- Monitoring : P1NP after 6 months– marker of bone turnover so if high not compliant, <35 is good
- CI: oesophageal abnormalities, can’t sit upright, hypocalcaemia
- Zolendronic acid infusion 5mg over 15 minutes annually
- CI is eGFR<35 ml/min, give vit D before infusion
- SE: osteonecrosis of jaw – check dentition before starting
- HRT –Raloxifene 60mg daily for women within 10 years of menopause + menopausal symptoms
- CI: MI, stroke, breast cancer, sex steroid responsive tumours, DVT - Recombinant PTH: teriparatide 20 mcg sub cut once daily for 18-24 months
- SA Indicated for T score <-3 with hx fo 2+ fractures or 1 fracture after year of bisphosphonate treatment
- CI: hypercalcaemia, GFR <35ml - Androgen replacement in hypogonadal men
- Denosumab in renal fracture on bisphosphonate but SA
Hx of hyperthyroid vs hypothyroid
Hyperthyroid
Diarrhoea, ↓weight, ↑ appetite, over-activity, sweats, heat
intolerance, palpitations, tremor, irritability, labile
emotions, oligomenorrhoea ± infertility.
Rare: psychosis, chorea, panic, itch, alopecia, urticaria.
Hypothyroid
Sleepy, tired, lethargic, ↓ mood, colddislike, weight ↑, constipation,
menorrhagia, hoarse voice,
↓memory/cognition, dementia,
myalgia, cramps, weakness.
Associations: Turner’s, Down’s, CF
