Endo - ix Flashcards
DI ix
Water deprivation test (8h) + desmopressin (ADH analogue) administration
- Conc after water deprivation - should be >700mOsm/kg
- Conc after water deprivation in DI pt - <400 mOsm/kg
- plasma osmolality >300 mOsm/kg + urine osmolality <600 mOsm/kg
DDAVP administration
- Cranial DI - concentrated urine after ADH administration [urine osmolatrity increases by >50%]
- Nephrogenic DI - urine remains dilute [urine osmolatrity increases by <45%]
Before test consider whether there is true polyuria (>3L/24h) !!!!
Test is only performed if patient’s sodium is in the normal range + urine osmolarity is <300 mOsm/kg [Normal urine osmolarity following fluid depletion should be >850mOsm/kg]
It’s a dangerous as hypovolaemia can cause AKI
- monitor patients weight throughout test and if it drops >3% stop test
- Urine dipstick
To exclude DM, UTI
- Urine osmolarity - Low
- Serum osmolarity/Na - High
- 24h urine collection - >3L
- MRI of hypothalamus, pituitary, surrounding tissues
- Serum calcium
- Serum potassium
(Hypercalcaemia + hypokalaemia can cause nephrogenic DI)
(in DI you get hypernatraemia)
Fluid restriction + desmopressin administration contraindications
This test is carried out to assess whether the DI is cranial or nephrogenic
Contra-indications
- Renal insufficiency
- Co-existing adrenal/thyroid hormone insufficiency
- Uncontrolled DM
- Hypovolaemia
Autoantigens associated w T1DM
- GAD (glutamic acid decarboxylase)
- Insulin
- Insulinoma-associated protein 2
- Cation efflux zinc transporter
- Islet cell antibodies
HLAs associated with T1DM
- HLA DR3
- HLA DR4
- Islet cell antibodies
T1DM Ix
- Fasting plasma glucose >7mM
- Random plasma glucose >11.1mM
- OGTT >11.1mM
- HbA1c - >6.5%, >48 mmol/mol*
- MSU - ketonuria, glycosuria, microalbuminuria
Ix to consider
- Plasma C-peptide (low <0.2nanomol/L)
- Autoimmune markers (autoantibodies to GAD, insulin, insulinoma associated protein 2, cation efflux zinc transporter, islet cell antibodies)
- reflects exposure to glucose/degree of hyperglycaemia over the last 3 months
therefore in a newly diabetic patient it is likely to be normal
also not accurate in haemolytic anaemias, haemoglobinopathies
T2DM Ix
- Fasting plasma glucose >7mM
- Random plasma glucose >11.1mM
- OGTT >11.1mM
- HbA1c - >6.5%, >48 mmol/mol
To differentiate between T1DM/T2DM
- Plasma C-peptide
Will be low in T1DM (<0.2 nanomol/L)
Will be high in T2DM (>1 nanomol/L)
Glucose tolerance test (OGTT)
Values for fasting + 2h after 75g oral glucose tolerance test
Normal
Prediabetes
Diabetes
Normal
- Fasting 4-5.9mmol/L or <6.1mmol/L
- 2-h/OGTT <7.8mmol/L
Pre-diabetes- Fasting
- 6.1-6.9 mmol/L- 2h/OGTT
- 7.8-11.0 mmol/L
Diabetes
- Fasting >7 mmol/L
- 2h/OGTT >11.1mmol/L
Histological features in diabetic kidney disease
Glomerular mesangial sclerosis
- Glomerular sclerosis
- Mesangial expansion
- BM thickening
DKA ix
- Urinalysis
Glucose, ketones - FBC
Increased plasma glucose
Increased plasma ketones (>3mmol/l)
WCC might be increased in the absence of infection
-ABG
Metabolic acidosis (pH <7.3, HCO3 <15mmol/L)
Large anion gap (>13 mmol/L)
Hyperkalaemia
- Plasma osmolarity - high
Higher in HHS
>290 mOsm + ketonaemia/ketonuria- DKA
>320 mOsm + no ketanaemia/ketonuria - HHS
Why do we check U+Es in secondary hyperparathyroidism?
Because CKD can cause osteomalacia
Primary hyperparathyroidism Ca PO43- PTH Vit D ALP
Ca - increased PO43- - decreased PTH - increased or inappropriately normal Vit D - normal ALP - increased or normal
Secondary hyperparathyroidism Ca PO43- PTH Vit D ALP
Ca - decreased or normal PO43- Increased if CKD Decreased if Vit D deficiency PTH - increased Vit D - decreased ALP - increased
Imaging investigations in primary and secondary hyperparathyroidism
X-ray/CT - extent of bone disease
CT KUB - renal stones
Cervical US - before surgery
DEXA scan
Primary HPT
- pepper pot skull
- brown tumours
- rugger jersey spine
- subperiosteal bone resorption in phalanges + long bones
Secondary HPT - Rickets Bone bossing Rachitic rosary Bowed legs Knock knees - Looser's pseudofractures - vascular + visceral calcification - soft tissue calcification - osteopenia - coarse trabeculae - codfish vertebrae
Vitamin D deficiency/osteomalacia ix
Bloods
• N/low Ca
• High PTH
• low 25-hydroxyvitamin D
o Major circulating form of vitamin D used to determine vitamin D status
• Phosphate
o high in CKD (because kidneys are not working to excrete the phosphate)
o low in vitamin D deficiency (because as a response to vitamin D deficiency, more PTH is released which increases the excretion of phosphate)
• Increased ALP
Imaging - Rickets Bone bossing Rachitic rosary Bowed legs Knock knees - Looser's pseudofractures - vascular + visceral calcification - soft tissue calcification - osteopenia - coarse trabeculae - codfish vertebrae
Paget’s disease Ix
- Increased ALP - The only abnormality
- Everything else is normal - Except if immobilised - immobilisation can lead to hypercalcaemia
• Xray
o Enlarged deformed bones with mixed lytic/sclerotic appearance
o Lack of distinction between cortex and medulla
o Skull – osteoporosis circumscripta, enlargement of frontal + occipital areas associated with a “cotton wool” appearance (suggests multifocal sclerotic patches)
o Lytic lesions (radiolucency)
o Incomplete fractures
o Thickened bone cortices
o Later stage – sclerotic picture predominates over osteolytic
o Blade of grass lesion – classical V shaped pattern between healthy + diseased long bones
o Cotton wool pattern – in skull, suggests multifocal sclerotic patches
• Radionuclide bone scans (Tec99)
o Not specific for dx
o To assess the extent of skeletal involvement
o Pagetic bone lesions - focal areas of markedly increased uptake (hot spots)
o Hot spots = lytic areas
• Bone biopsy
o Confirmatory diagnostic test
o To exclude malignancies
o Rarely indicated
• CTX (serum C-terminal propeptide of type 1 collagen)
o Used as a marker of bone resorption
o Used as an index for treatment response
o Initially elevated, treatment may normalise values
• Urine hydroxyproline
o Used as a marker of bone resorption
o Used as an index for treatment response
o Initially elevated, treatment may normalise values
• P1NP (serum procollagen 1 N-terminal peptide)
o Used as a marker of bone formation
o Used as an index for treatment response
o Initially elevated, treatment may normalise values
Ix for osteoporosis
- Bloods are NORMAL
- Dx based on prior fragility fracture or low bone mineral density
• DEXA scan
o Gold standard technique for diagnosis
o T-scores determined by measuring bone density at the hip so are best for predicting hip fracture
o Osteoporosis = T-score 2.5 S.D. below peak bone mass achieved by healthy adults
• X-ray
o Used to diagnose fractures when symptomatic
• Isotope bone scans
o Can highlight stress or microfractures
o Not commonly used
Tertiary hyperparathyroidism ix
- High PTH
- High Ca
- Hx of CKD
- CKD - High phosphate
- Renal transplant/chronic vitamin D deficiency - low phosphate
Why do we check 24h-urine calcium in hyperparathyroidism?
• Parathyroid abnormalities are diagnosed when there are simultaneously elevated serum calcium + parathyroid hormone levels with an elevated urinary Calcium: Creatinine
Hypothyroidism ix
Blood
- TFT
Primary - Low T3/T4, raised TSH
Secondary - Low T3/T4, low TSH (or inappropriately normal TSH)
Subclinical hypothyroidism- N T4/T3, raised TSH
- FBC - Normocytic anaemia , macrocytic anaemia which is non-megaloblastic
- U&Es - may show low sodium
- Cholesterol - May be increased
- Raised CK - hypothyroid myopathy
- ECG
Sinus bradycardia
Low voltage complexes
In suspected secondary cases:
Pituitary function tests
Pituitary MRI
Visual field testing
If you are suspecting Hashimoto’s thyroiditis –> request TPO antibodies
Hyperthyroidism ix
• TFT
Primary - Raised T3 + T4, low TSH
Secondary - Raised T3, T4, high or inappropriately normal TSH
Subclinical hyperthyroidism- N T4/T3, low TSH
• Thyroid imaging
If toxic nodule or thyroiditis is suspected - radioisotope thyroid scan
Toxic nodule/adenoma - high level of uptake - appears as a hot spot (only one area of the gland), lack of uptake by the normal dormant gland
Toxic multinodular goitre - high level of uptake - multiple small nodules
De Quervain’s/post-partum/amiodarone-induced Thyroiditis - low/no uptake
Graves - diffusely increased uptake (all of the gland appears “hot”)
Cold nodules are more likely to be malignant thyroid tumours that hot nodules – both are still more likely to be benign rather than malignant
Graves
• Thyroid autoantibodies
TRAb (TSH receptor antibodies)
Unusual to look for pathogenic thyroid stimulating antibodies because of the high cost of the test – this may be required in a pregnant woman w hyperthyroidism - the Ab can cross the placenta - thyrotoxic fetus that will require special care at the time of delivery
Raised antithyroid peroxidase – not pathogenic but usually correlates with the presence of the pathogenic thyroid stimulating antibodies
SIADH Ix
• Decreased plasma osmolarity (<280 mosmol/kg)
o If serum osmolarity >280 mosmol/kg –> pseudohyponatraemia
• Decreased blood Na (<135 mmol/L)
- Increased urine osmolality (>100 mosmol/kg)
- Increased urine sodium (>40 mmol/L)
• + absence of hypovolaemia/hypotension, oedema, renal failure, adrenal insufficiency, hypothyroidism are required for a dx of SIADH (rules out any other causes of hyponatraemia)
• Glucose, Serum protein, lipids – to exclude pseudohyponatremia seen with hyperglycaemia, hyperlipidaemia, hyperproteinaemia
o With hyponatraemia you would expect the serum osmolarity to be low
o High or normal serum osmolarity indicates a “pseudohyponatremia”
o Hyperglycaemia would cause a high serum osmolarity
o Hyperlipidaemia + hyperproteinaemia would cause a normal serum osmolarity
- Free T4 and TSH – to exclude hypothyroidism
- synACTHen test – to exclude adrenal insufficiency
• Rule out Hypovolaemia
o Rule out appropriate release of AVP secondary to extracellular volume depletion (hypovolaemia due to GI or renal loss – present with tachycardia, orthostatic hypotension, dry mucous membranes, poor skin turgor)
• Rule out hypervolemia
o Rule out intravascular volume depletion (= hypervolemia due to CCF, cirrhosis of the liver, nephrotic syndrome)
• Ix for cause – CXR, CT CAP, MRI/CT head
SIADH does not cause hypokalaemia
Prolactinoma ix
• Serum prolactin – first line test (check at least 3x)
• Pituitary gadolinium-enhanced MRI
o Need to confirm elevated serum prolactin prior to performing pituitary imaging!!
• Visual field examination – bitemporal hemianopoia
- TFTs (hypothyroidism can result in hyperprolactinaemia because TRH stimulates prolactin secretion)
- Exclude pregnancy
Before starting work up for prolactinaemia, exclude other aetiologies - pregnancy, lactation, hypothyroidism
Buzzwords for thyroid cancer subtypes
Papillary Follicular Medullary Anaplastic Lymphoma
Papillary Orphan Annie nuclei Psammoma bodies Young female Most common Radiation exposure e.g. for HL
Folliclar
Hurthle cells
Metastasises to lungs
Medullary
MEN2
Calcitonin
Anaplastic
Giant cells
Pleomorphic hyperchromatic nuclei
Pressure symptoms
Not responsive to treatment - poor prognosis
Grows very rapidly
might be painful due to infiltration of surrounding structures e.g. otalgia due to vagus nerve involvement
Lymphoma
Occurs after pre-existing Hashimoto’s thyroiditis
patients with malignancy are almost always euthyroid
Acromegaly/excess growth hormone/ excess GH ix
• Increased Serum insulin-like growth factor 1 (IGF-1)
o Blood levels stable throughout the day
o In adolescence + pregnancy IGF-1 are physiologically elevated – will cause false positive readings
• Oral glucose tolerance test (OGTT)
o Standard method to confirm diagnosis
o Lack of suppression of growth hormone during the oral glucose tolerance test (75g glucose)
o Glucose normally inhibits GH
o Failure to suppress GH levels <1μg/L 2h after OGTT
• MRI to detect pituitary adenoma
First measure IGF-1, if abnormal –> OGGT
We don’t measure GH bc GH secretion is pulsatile
MEN ix
Multiple endocrine neoplasia
• DNA testing to confirm the clinical diagnosis mutation in MEN1/RET genes
AD
MEN1
MEN1 gene on Chr 11
Tumour suppressor gene
MEN 2A, MEN 2B
RET gene on Chr 10
Proto-onco gene
• test for the hormones that the syndromes produce
Carcinoid syndrome ix
• Increased Urinary 5-hydroxyindoleacetic acid (5-HIAA)
o Metabolite of serotonin (metabolised in the liver)
o 24h urine collection
• Increased Serum chromogranin A/B
• SPECT (somatostatin receptor scintigraphy +/- somatostatin single PET scan)
o Somatostatin receptor type 2 is present in 70-90% of carcinoid tumours
o Identifies areas of somatostatin receptor positive tumour
• MIBG scintigraphy
o Identifies areas of tumour through MIBG take-up
• CT/MRI to localise tumour
• CT CAP + liver
o Routine staging to be performed every 4-6 months
o Identifies location of primary tumour + presence of liver metastases
- Look for underlying MEN1
- Histology - Identifies tumour type and stage
- Bloods – niacin (vitamin B3) deficiency
Conn’s syndrome/Bilateral adrenal hyperplasia ix
Screening tests
• U+Es
Raised Na
Low K
Na might also be normal due to parallel increase in the water content of the blood
• Increased K in urine
• Aldosterone + renin levels
High aldosterone
Low renin
High Aldosterone : renin ration
The ratio should be regarded as a screening test only before deciding whether to go on to a suppression test to definitely confirm or exclude the dx
Should be calculated after stopping anti-hypertensives (6weeks for spironolactone, 2 weeks for other hypertensives)
If anti-hypertensive therapy is required while waiting for the test ^ doxazosin (i.e. an α blocker)
Confirmatory tests
• Salt loading
o In patients with repeatedly elevated aldosterone/renin ratios - confirm or exclude dx by suppressing aldosterone with fludrocortisone or salt (oral/IV 0.9% NaCl)
o Failure to suppress aldosterone confirms primary hyperaldosteronism
• Posture stimulation testing
o Plasma aldosterone, renin activity + cortisol measured
o Measured with the patient lying at 8am
o Repeated after 4h of the patient sitting upright at 12pm
o Adrenal adenoma (mostly ACTH sensitive) - decrease in aldosterone secretions
o Bilateral adrenal hyperplasia - rise in aldosterone + renin
• Selective adrenal venous sampling
o Gold standard for localising the cause of primary hyperaldosteronism (Conn’s syndrome vs bilateral adrenal hyperplasia)
o Conn’s syndrome - aldosterone production 1) lateralises to one adrenal + 2) the other side is suppressed
If both of the facts^ can’t be proved, then you assume bilateral disease and treat them medically
o Bilateral adrenal hyperplasia - production is bilateral
o Sample from IVC - aldosterone + cortisol have to be lower from both adrenal veins
o Measure both cortisol + aldosterone – cortisol should be high this shows you that you are in the adrenal vein and not anywhere else
• CT/MRI adrenal
o CT is first-line
o To locate an adrenal adenoma
o To pick up hyperplasia
• Adrenal selenocholesterol scanning
o Detection of unilateral isotope uptake in patents with aldosterone-producing adenoma
o Unilateral uptake - adrenal adenomas
o Bilateral uptake - bilateral adrenal hyperplasia
Cushing’s syndrome ix
• Late night salivary cortisol
• 24h urinary free cortisol
o >50 μg/24h
• Low dose (1mg) dexamethasone suppression test
o First line
o Positive test - cortisol not suppressed (morning cortisol >50 nanomol/L)
• ACTH plasma levels
o Low – adrenal adenomas, adrenal carcinomas, bilateral adrenal hyperplasia, exogenous glucocorticoids
o High – Cushing disease, ectopic ACTH production
• High dose (8mg) dexamethasone suppression test
o Cushing’s disease
Low dose cortisol not suppressed
High dose cortisol suppressed
High dose ACTH levels fall to N from high
Next Ix - MRI pituitary
o Adrenal adenoma/carcinoma secrete cortisol (Cushing's syndrome) Low dose cortisol not suppressed High dose cortisol not suppressed High dose ACTH remains low Next ix – CT CAP
o Ectopic ACTH (Cushing's syndrome) Low dose cortisol not suppressed High dose cortisol not suppressed High dose ACTH remain high Next ix – CT CAP
• Metyrapone
o Stops adrenal cortisol production
o If cortisol is still high, then the source of ACTH is ectopic e.g. lung tumour
• Inferior petrosal sinus sampling
o For patients with confirmed Cushing’s syndrome but without an obvious pituitary lesion on MRI
o Sample blood from inferior petrosal sinus + peripheral blood simultaneously
o Conc of ACTH in petrosal sinus > peripheral blood (>2:1 or >3:1 after CRH administration) - pituitary ACTH secretion
o If conc of ACTH in petrosal sinus =peripheral blood - ectopic ACTH secretion
• CRH stimulation test – give synthetic CRH
o Rise in ACTH + cortisol - pituitary responds to CRH - Cushing’s disease
Next ix – MRI pituitary
o No rise in ACTH + cortisol - ectopic ACTH secretion
Next ix – CT CAP
- MRI pituitary – if high plasma ACTH
- CT adrenals – if low plasma ACTH
- Urinary pregnancy test – exclude pregnancy as a cause of hypercortisolism
- Serum glucose – Cushing’s syndrome leads to DM + glucose intolerance
- Hypokalaemia + HTN but low aldosterone + renin levels
- Metabolic alkalosis
Phaeochromocytoma ix
• 24h urine collection for catecholamines (vanillylmandelic acid), metanephrines, normetanephrines and creatinine // 24-hour urinary vanillylmandelic acid
o First line test
o Preferably collected immediately after a crisis
o Urinary creatinine measured to verify an adequate collection
o Certain drugs may increase measured catecolamines e.g. TCA, levodopa
• Serum metanephrines + normetanephrines
• Plasma catecholamines (adrenaline, noradrenaline, dopamine)
o Released episodically unlike metanephrines which are released continually
- Genetic testing
- CT AP (CT>MRI)– to detect adrenal phaeochromocytomas [BMJ], capsule lecture mentioned CT adrenal
• Raised chromogranin A
o Protein stored with + secrete with catecholamine release
• I-123 MIBG scintigraphy
o For large (>10cm) phaeochromocytomas , paragangliomas, If CT/MRI is negative but dx considered likely due to clinical and biochemical evidence)
o I-123 MIBG has a similar structure to NA
o High uptake in catecholamine-producing tissues
• gallium 68 dotatate - to look for mets
• Screen for associated conditions
o MEN 2 – serum calcium, calcitonin (primary hyperparathyroidism)
o NF 1 – neurofibromas, café-au-lait spots, axillary freckling
o VHL – ophthalmoscopy, MRI posterior fossa, renal USS
• Hypokalaemia – can be seen in the setting of high catecholamines
• Blood glucose – raised
Primary adrenal insufficiency ix
• Electrolytes
o Sodium - low
o Potassium - high
o Calcium - high
• Cortisol - low
o Take bloods bn 8am 9am (levels highest then)
270-900nmol/L - Normal
100-150 nmol/L - further investigation
<100 nmol/L - Diagnostic of adrenal insufficiency
o Short synACTHen test - primary adrenal insufficiency
IM 250mg tetrocosactrin (synthetic ACTH)
ACTH should increase cortisol >600nmol/L
Addison’s cortisol <550nmol/L at 30 mins
o Long synACHTen test – secondary adrenal insufficiency or suppression by steroids
Measure cortisol at 1, 4, 8, 24h after synacthen administration
Primary renal insufficiency (Addison’s) – cortisol will never exceed 550 nmol/L
Secondary/Tertiary adrenal insufficiency – cortisol is likely to surpass 550 nmol/L but the response is delayed
o Investigate cause of adrenal insufficiency
Adrenal autoantibodies (against 21-hydroxylase)
MRI of hypothalamus + pituitary
CT/MRI abdo
Biopsy for TB
AXR – adrenal calcification may indicate previous TB infection
o Check TFTs
ix to carry out during an addisonian crisis
• FBC • U+Es High urea Low sodium High potassium • CRP/ESR • Low glucose • Blood cultures • Urinalysis • Culture + sensitivity
Dx of PCOS
- Clinical and/or biochemical signs of hyperandrogenism (hirsuitism, acne)
- Oligo/amenorrhoea
- Polycystic ovaries (>12 follicles in each ovary (measuring 2-9 mm))
PCOS ix
- High LH
- High LH:FSH ratio (>3)
- High testosterone, androstenedione, DHEAS (dehydroepiandrosterone sulfate)
- Low SHBG
Exclude
• Hyperprolactinaemia - Serum prolactin
• Hypo/hyperthyroidism - TFTs
• Congenital adrenal hyperplasia - 17-OH progesterone (excludes 21-hydroxylase deficiency which also results in excess androgens)
• Look for impaired glucose tolerance/type 2 DM Fasting glucose (N - <6.1, impaired fasting glucose – 6.1-6.9, diabetes >7) HbA1c (>6.5%, >48mm) If either of these are abnormal, do an OGTT
• Fasting lipid profile – - total cholesterol, LDL, triglycerides, low HDL – dyslipidaemia sign of PCOS
• Transvaginal/pelvic USS
o >12 follicles in each ovary (measuring 2-9 mm)
and/or
o Increased ovarian volume >10mL in either or both ovaries
Thyroid cancer ix
• US – suspicious features o Microcalcifications o More tall than wide shape o Hypervascularity o Marked hypo-echogenicity o Irregular margins
• FNA
• Technetium scan
o Cold nodule
• Serum calcitonin
o High in medullary cancer
patient is usually eurthyroid
Pseudohypoparathyroidism vs hypoparathyroidism biochem
Pseudohypoparathyroidism (end-organ resistance to PTH) - High PTH, low calcitriol, low Ca, high PO43-
Hypoparathyroidism - Low PTH, low calcitriol, low Ca, high PO43-
