Endocrinology Flashcards
Work up of an incidental adrenal mass
Wilsons Disease Protein deficiency and what this does
ATP7B deficiency (autosomal recessive)
= impaired biliary excretion of copper
Whipple’s triad of hypoglycaemia
- Hypoglycaemic symptoms
- Documented low BGL at time of Sx
- Resolution of symptoms when the glucose is raised to normal
- When capturing episode of hypoglycaemia
- assess insulin and Cpeptide
- May be done co-incidentally or with a 72 hour fast
- looking for discordance between insulin and BGL (ie insulin staying up when BGL low)
Which thyroid drug(s)
- Prevent synthesis of new thyroid hormone
- Inhibit T4 to T3 conversation
- Reduce sympathetic hyperactivity
- How does lugol solution work
Which of the following is LEAST likely to be present in a euthyroid patient with a severe illness
A. Raised FT4
B. Raised FT3
C. Low FT3
D. Low TSH
E. Raised TSH
B. Raised FT3
When can a presumptive diagnosis of osteoporosis be made
All individuals over the age of 50 who sustain a fracture following minimal trauma (standing height or less) should be considered to have a presumptive Dx of osteoporosis
A presumptive Dx can also be made with spinal compression fraction in patient with nil history of significant trauma/patient is high risk of OP. Caution with presumptive Dx if only mild deformity or pt <60years
What cleaves the C-peptide from alpha and beta insulin molecules to form insulin?
Carboxypeptidase E helps cleave the C-peptide to form insulin
What 3 things must you check before giving someone IV zoledronic acid (or IV bisphosphonates)
With what malignancy is Hashimoto Thyroiditis associated?
Thyroid lymphoma
- rare
With what is mutation of the HRPT2 gene associated?
HRPT2 encodes parafibromin
- unclear action, appears to regulate gene expression and inhibit cell proliferation
Found in sporadic parathyroid cancer and hyperparathyroidism-jaw tumour syndrome (HPT-JT)
- HPT-JT syndrome associated with germline mutations in HRPT2
- 10-15% of sporadic parathyroid cancers bear HRPT2 mutations
HPT-JT
- ossifying fibromas of jaw
- cystic and neoplastic renal lesions
- uterine tumours
- parathyroid neoplasia
- occurs in ~15% with HPT-JT
With what is MEN4 associated?
Subset of MEN1 with mutations in CDKN1B
Tumours of
- reproductive
- renal
- adrenal
- thyroid
Why is it important to treat those with fragility fractures for osteoporosis?
Cascade effect whereby one who’s suffered a fragility fracture is 3-5x more likely to have another fracture in the next year c/w someone who’s never had one
Treatment can stop them from suffering multiple -> morbidity/mortality
Only 1/3 of vertebral fractures come to clinical attention
- Wedge = 20% loss of height compared to the front or middle of the vertebra
- *- increases risk of both vertebral and hip fracture**
Why is isolated ACTH deficiency hard to diagnose?
Likely due to autoimmune destruction of ACTH-secreting cells
Very rare and presents very non-specifically
- doesn’t have hyperpigmentation, salt craving, or hypotension seen in Addison’s
Usually confusion, fever, weight loss
Hypercalcaemia is often the finding that leads to diagnosis
- note that hypercalcaemia is rare in Addison’s
Why is fever part of the classic presentation of addison’s disease?
Lack of IL-1 inhibition
Why does commencement of thyroxine without replacing corticosteroid lead to adrenal crisis in those with co-existing primary hypothyroidism and adrenal insufficiency?
Thyroxine accelerates metabolic clearance of cortisol
When they were hypothyroid their cortisol was hanging around longer and because it developed slowly they were compensating
Replacement of thyroxine -> rapid reduction in cortisol -> crisis
Why does anion gap resolution lag behind serum ketone detection in treated DKA?
Blood glucometers measure beta-hydroxybutyrate
- Insulin causes beta-hydroxybutyrate to convert to acetoacetate
Ketonaemia/ketonuria takes up to 36hrs to resolve due to slower removal of acetoacetate and acetone
Why does addison’s cause metabolic acidosis?
- Sodium resorption in the collecting duct associated with hydrogen ion excretion
- Less aldosterone -> less sodium resorption -> less hydrogen excretion -> metabolic acidosis
Who’s at highest risk of central pontine demyelination?
85% had sodium <115
87% had correction >12mmol/L in 24hrs
ETOH is definitely a risk factor
Symptoms
- confusion, seizure, drowsiness, pseudobulbar palsy, tetraparesis
- onset 2-6 days post presentation
Diagnosis
- MRI most sensitive
- May not show in first 2 weeks
Who should be screened for osteoporosis?
Which types of pituitary tumours tend to be functioning vs non-functioning?
Functioning = secrete hormones
- Usually microadenomas = <1cm
- Symptoms via specific syndrome depending on the hormone
- Prolactinomas respond well to dopamine agonists, the rest usually need surgery
Non-functioning = don’t secrete hormones
- Usually macroadenomas = >1cm
- Symptoms via mass effect
Which subtype of patients with impaired glucose regulation are more likely to develop T2DM and cardiovascular disease?
Impaired fasting glucose
- hepatic insulin resistance
Impaired glucose tolerance
- muscle insulin resistance
- higher risk
Which subsection of calcium concentration is the most important determinant of PTH secretion? How does the PTH response to increased need for production?
Ionised calcium the important determinant
Response
- Release of preformed hormone
- Increased PTH mRNA expression by sustained hypocalcaemia
- Protracted challenge leads to cellular replication with increased parathyroid gland mass
Which site on DEXA best predicts overall fracture risk? Who should be investigated for osteoporosis?
Proximal femur
- less affected by osteoarthritis which may elevate BMD
Investigate
- >50 with risk factors
- >70
- fragility fracture
Which secondary causes result in hypertriglyceridaemia vs hypercholesterolaemia
Hypercholesterolaemia
- nephrotic syndrome
- cholestasis
- hypothyroid
- anorexia nervosa
Hypertriglyceridaemia (the rest)
- diabetes
- obesity
- alcohol
- CRF/CKD
- drugs: thiazides, protease inhibitors, non-selectived beta-blockers, unopposed oestrogen
- liver disease
Which pituitary hormone is under constant suppression?
- *Prolactin**
- constantly being suppressed by dopamine
Which ovarian cells produce which hormones and how?
Which oral hypoglycaemics are risky in heart failure?
Thiazolidinediones “glitrazones”
- Fluid retention
- concomitant insulin increases risk
Metformin
- Increased risk of fatal metabolic acidosis
Which of overnight dexamethasone suppression vs 24hr urinary free cortisol is more sensitive for Cushing’s Syndrome?
Overnight dexamethasone suppression most sensitive
- LR+ 16.4, LR- 0.06
24hr UFC
- LR+ 10.6, LR- 0.16
Which medications can cause or worsen diabetes?
- Glucocorticoids
- HIV protease inhibitors
- Calcineurin inhibitors (tacrolimus > cyclosporin)
- Atypical antipsychotics
- GnRH agonists
- Oral contraceptives
- Niacin
- Thiazide diuretics - Typically at doses >=25mg day HCT
- Beta blockers, clonidine, calcium channel blockers
- Alcohol
Which medications are known to cause impaired glucose tolerance?
- thiazides, frusemide (less common)
- steroids
- tacrolimus, ciclosporin
- interferon-alpha
- nicotinic acid
- atypical antipsychotics e.g. olanzapine
Which is the first line therapy for hypertension in diabetes? What should be added if control isn’t reached? What about timing?
ACEI first line
- More data around for ACEI so preferred first line
- If not tolerated then ARB
Should monitor creatinine and eGFR
- Expect an initial drop (>30% may mean look for underlying cause)
- Usually reflects those who will achieve protection
(ACCOMPLISH, NEJM 2008)
- ACEI + amlodipine better than ACEI + HCT
>=1 antihypertensive at night better than all in morning
Which is better between semmes-weinstein monofilament and 128Hz tuning fork for the detection of peripheral neuropathy and risk of ulceration?
Tuning fork more sensitive for early peripheral neuropathy
- but less predictive of ulceration
Semmes-Weinstein monofilament more sensitive for protective sensation
Which hormones are made in which parts of the adrenal gland?
Glomerulosa, fasciculata, reticularis
Which hormones act via G protein coupled receptors?
Glycoprotein hormones
- TSH, LH, FSH, hCG
Catecholamines
- adrenaline and noradrenaline
- dopamine
ACTH
PTH
Calcium
Which hormones act via an intracellular nuclear receptor?
Oestrogen and testosterone
Glucocorticoids, mineralocorticoids
Thyroid hormone
Vitamin D
e.g. thyroid hormone
Which gene mutations are associated with familial paraganglionoma syndromes?
Which mutations cause adrenergic vs noradrenergic/dopaminergic paraganglionomas?
Succinate dehydrogenase (SDH)
- mutations in A, B, C, and D parts of the gene lead to different forms of disease
75% of paragangliomas are sporadic; 25% hereditary
- hereditary more likely to be multiple and at an earlier age
97% are benign
- cured with resection
Which features of established graves’ opthalmopathy necessitate urgent referral to opthalmology?
Unexplained deterioration in vision
Awareness of change in intensity or quality of colour vision
Globe subluxation
Obvious corneal opacity
Cornea visble with eyelids closed
Disc swelling
Which drugs most commonly cause false positives in metanephrines/catecholamines when assessing for phaeochromocytoma? What can be done to confirm the diagnosis?
-
Levodopa, sympathomimetics, diuretics, TCAs, a/b blockers
- i.e. you’d stop the possible offending agents and re-test
- Clonidine suppression test
Which conditions increase and decrease sex hormone binding globulin (SHBG)?
Increase
- aging
- cirrhosis
- hyperthyroidism
- oestrogens
- HIV
- anorexia
- pregnancy
Decrease
- moderate obesity
- nephrotic syndrome
- hypothyroidism
- glucocorticoid, progestin, androgenic steroids
- diabetes
- PCOS
Which agents are used pre-operatively in cushing’s disease?
metyrapone
- inhibits 11beta hydroxylase
- AEs: GI, rash, dizziness, oedema
ketoconazole
- inhibits multiple steps of steroidogenesis
- AEs: GI, transaminitis, rarely severe hepatotoxicity
mifepristone
- not really used due to difficult with dosing and monitoring
pasireotide if failed the above
- high affinity somatostatin analogue for SSR5 subtype
- expensive and causes diabetes
When is nuclear scintography used in thyroid nodules? What are the typical findings in the various subsets?
Not used routinely in the evaluation of those with thyroid nodules
- Should be performed if TSH is low to assess for functioning thyroid nodules
Hot nodules are almost never malignant
5-10% of cold nodules are malignant
Graves
- Enlarged gland with homogenously increased tracer uptake
Subacute/silent thyroiditis
- Low/no uptake
- Reflects discharge of preformed thyroid hormone rather than increased synthesis
- In later stages there’s no uptake due to follicular cell damage and TSH suppression
- Normal uptake returns after function has normalised
Hashimoto’s
- Early may have increased
- Late may have single or multiple areas of reduced uptake
Toxic adenomas
- Focal areas of increased uptake with suppressed uptake in remainder
- Toxic MNGs show enlarged gland with distorted architecture
- Functioning and non functioning nodules with suppressed thyroid parenchyma
When and how should testosterone be replaced? What are the things to look out for on follow up? Contraindications?
- Persistently low testosterone with symptoms in absence of contraindications
Method
- transdermal, gel or injectable
- Aim to restore testosterone to the mid-normal range
Monitoring
- Expect ~ 3% increase in haemoglobin due to suppressed hepcidin, increased iron availbililty and increased erythropoiesis
- discontinue if Hct rises above 54%
Rise in PSA >1.4 in any one year should prompt urgent urological evauation
Contraindications
-
Absolute
- hormone-dependent malignancies (prostate, breast)
- haemtocrit >55%
-
Relative
- haemtocrit > 52%
- untreated sleep apnoea
- severe obstructive symptoms of BPH
- advance CHF
-
Fertlitiy
- supression of spermatogenesis in eugonadal men
wot dis
Pretibial myxoedema - described as shiny, orange peel skin
Seen in Graves’ disease
What’s the screening panel for hyponatraemia?
What’s the relative efficacy of the weight management interventions?
lifestyle, pharmacotherapy, gastric band, roux-en-y, gastric sleeve
- bariatric surgery with maintained lifestyle changes - most effective
What’s the relationship between BMI and risk for diabetes (T2DM)?
What’s the pathophysiology of osteopetrosis?
Marble bone disease
- Defective osteoclast function -> failure of normal resorption
-
Thick, dense bones prone to fracture
- bone pain and neuropathy common
- Investigations
- calcium, phosphate, ALP normal
What’s the leading cause of ESRF? What’s the rough relative risk?
DIABETUS
(GN is second)
What’s the largest cause of morbidity and mortality in diabetes? Does diabetes convey independent risk? Are men or women at higher risk?
Cardiovascular
- 2-3x risk compared with those without diabetes
- Women at higher risk than men ~(7x compared to 3x)
What’s the HbA1c target in T1DM? Why?
- With increasing HbA1c you get more complications (retinopathy, nephropathy, neuorpathy and microalbuminuria)
Study which looked at - intensive control 7.4% vs control 9.1%
- Everyone ~7.9% after DCCT
- Significant reduction in macrovascular complications in the following 10yrs
Australian diabetes society targets:
- general < 7%
- recurrent severe hypog;ycaemi and hypoglycaemic unawareness - < 8%
- patients with major co-morbidities with limited life expetancy - symptomaytic therapy of hyperglycemia and avoid ketosis
Please find attached the American Diabetes Association guidelines
What’s the evidence for intensive glycaemic control in T2DM?
Not clear why the ACCORD study demonstrated and INCREASE in mortality.
The follow up of the initial RCTs suggests lasting benefit to intensive glycaemic control that isn’t well shown in the inital RCTs
What’s the definition of osteoporosis? What happens to the risk of fracture with change in SD (standard deviation)?
What is the Z score? When might it be useful?
Dx: T score <= -2.5 or occurrence of a minimal trauma fracture >50yrs
- Characterised by low bone mass and disruption of microarchitecture of bone -> leads to increased fracture risk
Z-score
- Compared to age matched population
- secondary causes
What’s the class of diabetic medications with the most weight loss?
SGLT2 inhibitors > metformin
Due to caloric loss from glycosuria
- HbA1c decrease 0.8-1%
- works better with worse HbA1c (higher filtered load -> more loss in urine)
What’s the benefit of gliptin (DPP-4 inhibitor) + metformin vs sulfonyluria + metformin?
Weight loss instead of weight gain
Much less hypoglycaemia
What’s osteomalacia? Classic presentation and investigations? Management?
Normal bony tissue with decreased mineral content (soft bones)
- termed rickets when growing
- osteomalacia after epiphysis fusion
Aetiology
- vit d deficiency or resistance: nutrition, absorption, liver disease, renal disease, anti-epileptics
- hypophosphataemia: fanconi from myeloma or tenofovir, for example
Features
- bone pain, fractures
- muscle tenderness, proximal myopathy
- classic presentation: bone pain + weakness after iron infusion
- iron induces hypophosphataemia by increasing FGF23 -> induces renal phosphate excretion
Investigations
- low calcium, phosphate, 25OH vit D
- high urinary phosphate in phosphate wasting
- raised ALP
- translucent bands (Looser’s zone) on x-ray - see image
Management
- calcium/vit d
What occurs in hyperproteinaemic hyponatraemia?
What underlies the increased hepatic gluconeogenesis that’s seen in diabetes (T2DM)?
What set of features characterise Carney complex?
Due to mutation in PPKAR1A
- regulates protein kinase A
- What ranges of hypercalcaemia are associated with what types of symptoms?
- How should it be treated?
>2.9-3.0mmol/L usually required for symptoms
- Stones, bones, psychiatric moans, abdominal groans
- Short QT, arrhythmias
>3.2mmol/L with calcifications in various organs
>3.7mmol/L may present with coma or arrest
Identification and treatment of the underlying cause is important
- Malignancy usually due to bone resorption so decreased intake doesn’t help
- Vitamin D toxic can be helped by restriction
Bisphosphonate
- Concentrated in areas of high turnover
- Pamidronate 30-90mg returns to normal in 24-48hrs and lasts for weeks in 80-100%
- Zoledronate 4-8mg more rapid and sustained
Calcitonin
- Inhibits osteoclasts
- Acts within hours
- Tachyphylaxis after 24hrs
Denosumab
- Blocks RANK ligand dramatically reducing osteoclast number and function
Glucocorticoids
- Useful only in malignancy through antitumour effect; or vitamin D toxicity/sarcoid
- MM, leukaemia, lymphomas, breast carcinomas
- Do nothing in normal patients or those with hyperparathyroidism
Dialysis
- Often required in severe hypercalcaemia complicated by renal failure
- Need to replace phosphate carefully so hypophosphataemia doesn’t aggravate hypercalcaemia
What proportion of women develop gestational diabetes? What proportion develop T2DM in the next 10-20yrs?
~10% get GDM
35-60% develop T2DM over the next 10-20yrs
What proportion of insulin response is lost by the time diabetes (T2DM) has developed?
- *Aetiology**
- partly loss of beta cells
- partly functional loss of beta cells (due to adipose tissue)
