Endo - ix Flashcards

1
Q

DI ix

A

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)

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2
Q

Fluid restriction + desmopressin administration contraindications

A

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
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3
Q

Autoantigens associated w T1DM

A
  • GAD (glutamic acid decarboxylase)
  • Insulin
  • Insulinoma-associated protein 2
  • Cation efflux zinc transporter
  • Islet cell antibodies
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4
Q

HLAs associated with T1DM

A
  • HLA DR3
  • HLA DR4
  • Islet cell antibodies
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5
Q

T1DM Ix

A
  • 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
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6
Q

T2DM Ix

A
  • 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)

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7
Q

Glucose tolerance test (OGTT)

Values for fasting + 2h after 75g oral glucose tolerance test

Normal
Prediabetes
Diabetes

A

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
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8
Q

Histological features in diabetic kidney disease

A

Glomerular mesangial sclerosis

  • Glomerular sclerosis
  • Mesangial expansion
  • BM thickening
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9
Q

DKA ix

A
  • 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
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10
Q

Why do we check U+Es in secondary hyperparathyroidism?

A

Because CKD can cause osteomalacia

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11
Q
Primary hyperparathyroidism 
Ca
PO43-
PTH
Vit D
ALP
A
Ca - increased
PO43- - decreased
PTH - increased or inappropriately normal 
Vit D - normal 
ALP - increased or normal
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12
Q
Secondary hyperparathyroidism
Ca
PO43-
PTH
Vit D
ALP
A
Ca - decreased or normal
PO43- 
   Increased if CKD
   Decreased if Vit D deficiency
PTH - increased
Vit D - decreased
ALP - increased
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13
Q

Imaging investigations in primary and secondary hyperparathyroidism

A

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
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14
Q

Vitamin D deficiency/osteomalacia ix

A

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
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15
Q

Paget’s disease Ix

A
  • 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

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16
Q

Ix for osteoporosis

A
  • 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

17
Q

Tertiary hyperparathyroidism ix

A
  • High PTH
  • High Ca
  • Hx of CKD
  • CKD - High phosphate
  • Renal transplant/chronic vitamin D deficiency - low phosphate
18
Q

Why do we check 24h-urine calcium in hyperparathyroidism?

A

• Parathyroid abnormalities are diagnosed when there are simultaneously elevated serum calcium + parathyroid hormone levels with an elevated urinary Calcium: Creatinine

19
Q

Hypothyroidism ix

A

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

20
Q

Hyperthyroidism ix

A

• 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

21
Q

SIADH Ix

A

• 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

22
Q

Prolactinoma ix

A

• 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

23
Q

Buzzwords for thyroid cancer subtypes

Papillary
Follicular
Medullary
Anaplastic
Lymphoma
A
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

24
Q

Acromegaly/excess growth hormone/ excess GH ix

A

• 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

25
Q

MEN ix

Multiple endocrine neoplasia

A

• 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

26
Q

Carcinoid syndrome ix

A

• 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
27
Q

Conn’s syndrome/Bilateral adrenal hyperplasia ix

A

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

28
Q

Cushing’s syndrome ix

A

• 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
29
Q

Phaeochromocytoma ix

A

• 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

30
Q

Primary adrenal insufficiency ix

A

• 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

31
Q

ix to carry out during an addisonian crisis

A
•	FBC
•	U+Es
	High urea
	Low sodium
	High potassium
•	CRP/ESR
•	Low glucose
•	Blood cultures 
•	Urinalysis
•	Culture + sensitivity
32
Q

Dx of PCOS

A
  • Clinical and/or biochemical signs of hyperandrogenism (hirsuitism, acne)
  • Oligo/amenorrhoea
  • Polycystic ovaries (>12 follicles in each ovary (measuring 2-9 mm))
33
Q

PCOS ix

A
  • 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

34
Q

Thyroid cancer ix

A
•	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

35
Q

Pseudohypoparathyroidism vs hypoparathyroidism biochem

A

Pseudohypoparathyroidism (end-organ resistance to PTH) - High PTH, low calcitriol, low Ca, high PO43-

Hypoparathyroidism - Low PTH, low calcitriol, low Ca, high PO43-