Endocrinology Flashcards
1
Q
Work up of an incidental adrenal mass
A
2
Q
Wilsons Disease Protein deficiency and what this does
A
ATP7B deficiency (autosomal recessive)
= impaired biliary excretion of copper
3
Q
Whipple’s triad of hypoglycaemia
A
- 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)
4
Q
Which thyroid drug(s)
- Prevent synthesis of new thyroid hormone
- Inhibit T4 to T3 conversation
- Reduce sympathetic hyperactivity
- How does lugol solution work
A
5
Q
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
A
B. Raised FT3
6
Q
When can a presumptive diagnosis of osteoporosis be made
A
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
7
Q
What cleaves the C-peptide from alpha and beta insulin molecules to form insulin?
A
Carboxypeptidase E helps cleave the C-peptide to form insulin
8
Q
What 3 things must you check before giving someone IV zoledronic acid (or IV bisphosphonates)
A
9
Q
With what malignancy is Hashimoto Thyroiditis associated?
A
Thyroid lymphoma
- rare
10
Q
With what is mutation of the HRPT2 gene associated?
A
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
11
Q
With what is MEN4 associated?
A
Subset of MEN1 with mutations in CDKN1B
Tumours of
- reproductive
- renal
- adrenal
- thyroid
12
Q
Why is it important to treat those with fragility fractures for osteoporosis?
A
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**
13
Q
Why is isolated ACTH deficiency hard to diagnose?
A
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
14
Q
Why is fever part of the classic presentation of addison’s disease?
A
Lack of IL-1 inhibition
15
Q
Why does commencement of thyroxine without replacing corticosteroid lead to adrenal crisis in those with co-existing primary hypothyroidism and adrenal insufficiency?
A
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
16
Q
Why does anion gap resolution lag behind serum ketone detection in treated DKA?
A
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
17
Q
Why does addison’s cause metabolic acidosis?
A
- Sodium resorption in the collecting duct associated with hydrogen ion excretion
- Less aldosterone -> less sodium resorption -> less hydrogen excretion -> metabolic acidosis
18
Q
Who’s at highest risk of central pontine demyelination?
A
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
19
Q
Who should be screened for osteoporosis?
A
20
Q
Which types of pituitary tumours tend to be functioning vs non-functioning?
A
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
21
Q
Which subtype of patients with impaired glucose regulation are more likely to develop T2DM and cardiovascular disease?
A
Impaired fasting glucose
- hepatic insulin resistance
Impaired glucose tolerance
- muscle insulin resistance
- higher risk
22
Q
Which subsection of calcium concentration is the most important determinant of PTH secretion? How does the PTH response to increased need for production?
A
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
23
Q
Which site on DEXA best predicts overall fracture risk? Who should be investigated for osteoporosis?
A
Proximal femur
- less affected by osteoarthritis which may elevate BMD
Investigate
- >50 with risk factors
- >70
- fragility fracture
24
Q
Which secondary causes result in hypertriglyceridaemia vs hypercholesterolaemia
A
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
25
Which pituitary hormone is under constant suppression?
* *Prolactin**
- constantly being suppressed by dopamine
26
Which ovarian cells produce which hormones and how?
27
Which oral hypoglycaemics are risky in heart failure?
**Thiazolidinediones "glitrazones"**
* Fluid retention
* concomitant insulin increases risk
**Metformin**
* Increased risk of fatal metabolic acidosis
28
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
29
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
30
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
31
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**
32
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**
33
Which hormones are made in which parts of the adrenal gland?
Glomerulosa, fasciculata, reticularis
34
Which hormones act via **G protein coupled receptors?**
**Glycoprotein hormones**
* TSH, LH, FSH, hCG
**Catecholamines**
* adrenaline and noradrenaline
* dopamine
**ACTH
PTH
Calcium**
35
Which hormones act via an intracellular nuclear receptor?
Oestrogen and testosterone
Glucocorticoids, mineralocorticoids
Thyroid hormone
Vitamin D
e.g. thyroid hormone
36
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
37
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
38
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**
39
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
40
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
41
Where does thyroid hormone act?
**Nuclear receptor** which directs the **transcription of thyroid dependent genes**
42
Where does the majority of calcium absorption occur? Active or passive? What's special about alkalotic gastric environments?
20-70% active transport the majority in the proximal small bowel
Poorly absorbed in alkalotic environments
* Calcium citrate preferable due to better dissociation
Sustained periods of low calcium intake can lead to inability to cover obligate losses
* **PTH/1,25OHD activate osteoclasts** leading to progressive bone loss
Sustained high intake overrides maximal downregulation
* hypercalciuria, nephrocalcinosis, progressive renal failure, hypercalcaemia
* so called milk-alkali syndrome
43
When should those with **subclinical hypothyroidism** be treated?
If TSH \<10 then there's no evidence of benefit in placebo control studies
Definitely **treat if TSH \>10, pregnant, contemplating pregnancy**
Consider treating if
* \<65yrs, heart failure, TPO/Tg Ab +ve, dyslipidaemia
**Epidemiology**
* 7.5% women, 2.8% of men; 17.4% of \>75
* Higher in higher iodine intake, Down syndrome, T1DM
40-60% have antithyroid antibodies
Most likely **consequence is progression to overt hypothyroidism**
44
When ought you consider testing for **primary aldosteronism**?
Hypertension with hypokalaemia
Resistant hypertension
Adrenal incidentaloma and hypertension
Onset of hypertension \<20yrs
Severe hypertension
When considering secondary hypertension
45
When is synacthen test useful?
For investigation of hypopituitarism in the chronic phase
- not useful for some months after pituitary surgery due to adrenals remaining primed for a time
46
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
47
When is calcium supplementation recommended?
Dietary intake insufficient
Taking osteoporosis medication
Taking glucocorticoids \>=7.5mg/day for \>=3 months
Elderly, housebound, or in residential care
Otherwise recommended to get **RDI via diet**
- debate ranges about whether supplemental calcium increases cardiovascular disease
48
When is calcitonin of significance?
* A tumour marker in sporadic and hereditary cases of **medullary thyroid carcinoma**
* Can be used as adjunctive treatment in **severe hypercalcaemia** and **Paget's disease of bone**
* **Acts (opposite to PTH)**
* Primary via inhibition of osteoclast mediated bone resorption
* Secondarily via stimulation of renal calcium clearance
49
When does peak bone mass occur? What factors account for the majority of its peak? Is age or BMD a greater risk factor for fracture?
**3rd decade of life**
**Major factor:**
* Genetics: 60% of peak BMD attributable to genetics in monozygotic/dizygotic twin studies
* Role of childhood exercise, childhood calcium intake, onset of puberty not fully determined
* Onset of puberty negatively correlated with BMD at skeletal maturity
* **Age** is a greater determinant o**f fracture risk than bone mass**
50
When does macroalbuminuria tend to occur in diabetes? For what is microalbuminuria a potent risk factor?
What can be done to improve outcomes?
**5-10yrs after onset of microalbuminuria**
* 50% reach renal failure 5-10yrs following onset of proteinuria
**Potent risk factor for CVD**
**Treatment**
* **Glycaemic control:** Strong evidence in T1DM; less so in T2DM
* **Hypertension:** Aim **\<130/85**. Evidence that adding non DPCCB to RAAS improves outcomes
* **RAAS inhibition**: Slows progression independent of any effect on BP. Decreases glomerular hypertension
51
When can bisphosphonates be initiated post fracture?
Multiple studies have shown **no difference between early and delayed commencement o**f bisphosphonates post fracture
Administration **at 2 weeks post is reasonable**. Many wait until 4-6 weeks post, but the necessity for this is not borne out in the literature.
52
When are the DPP-4 inhibitors particularly useful?
eg. linagliptin and sitagliptin
**Renal failure**
* Sitagliptin can be used with dose reduction in CRF
* **Linagliptin doesn't need dose adjustment in CRF**
53
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
54
wot dis
**Pretibial myxoedema** - described as shiny, orange peel skin
Seen in **Graves' disease**
55
What's the underlying pathophysiology of gestational diabetes?
**Increased insulin resistance**
* **placental growth hormone**, human placental lactogen, TNFa
* decreased GLUT4 expression in skeletal muscle
56
What's the treatment aim in hypothyroidism? What risk does overreplacement convey?
**Normal TSH (0.5-5)**
* if still having symptoms and sitting in the upper end of normal can consider increasing dose to aim for TSH in lower half of range
**Overreplacement increases risk of atrial fibrillation (AF) by 3x**
Subclinical hyperthyroidism increases **bone loss**
Severely suppressed **TSH \<0.03 carries the risk** of heart disease, abnormal heartbeat patterns and bone fractures compared to patients whose TSH levels are in the normal range
57
What's the screening panel for hyponatraemia?
58
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
59
What's the relationship between BMI and risk for diabetes (T2DM)?
60
What's the physiological difference between IGT and T2DM?
Both have the same **insulin sensitivity**
**IGT has higher insulin levels** than T2DM
* i.e. when the beta cell volume decreases and they lose maximal insulin secreting ability they progress to diabetes
61
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
62
What's the most successful approach to weight loss in the severely obese?
Which conditions improve?
* VLED (very low energy diet) with meal replacement of 2 meals
* Dinner of protein + non-starchy vegetables + salad with oil
* Within 2 days they're in ketosis which suppresses hunger
* Continue until amount of weight loss desired is reached.
* On resumption of diet can introduce appetite suppressive medication when out of ketosis as that's when hunger returns.
**Improved**
* Diabetes
* Lipids (TG and HDL especially)
* OSA (if due to obesity)
* PCOS
* Hypertension (Not always to normal)
* Survival (Swedish obesity study)
63
What's the most prevalent monogenetic cause of obesity?
* Mutation in the m**elanocortin 4 receptor (MCR-4)**
* **autosomal dominan**t inheritance
* Thought to account for **2-4% of obesity**
64
What's the most common thyroid malignancy? Next most?
**Papillary thyroid carcinoma**
* makes up **80%** of differentiated
* 80% metastasise to the LNs
* \<10% spread beyond the neck
* **Prognostic features**
* \>40yrs, \>4cm, local extension/distant metastases eg. Lung, bone, brain, liver, adrenals
**Follicular thyroid carcinoma**
* **10%** of differentiated
* Differentiated from follicular adenoma by capsular and vascular invasion
* Spreads haematogenously to - lung, bone, brain, liver, skin
* **Prognostic features**
* Age, tumour size, level of invasion, presence of distant metastases
65
What's the most common cause of hypoadrenalism? Presentation?
**Autoimmune primary in 80%**
* *Presentation**
- lethargy, weakness, anorexia, N/V, weight loss, salt craving
- hyperpigmentation (palmar creases), vitiligo, loss of female pubic hair
- hypotension
* *Crisis**
- collapse, shock, fever
* *Other causes**
- infection
- metastases (lung mainly)
- HIV, antiphospholipid syndrome
66
What's the mechanism for hyperglycaemic hyponatraemia? What's the formula for correction?
Relative hyponatraemia due to dilutional effect of water equilibrating the increased solutes
Correct by **dividing BGL by 3 and adding to sodium**
67
What's the major risk factor for mortality in T1DM?
Nephropathy
68
What's the leading cause of ESRF? What's the rough relative risk?
DIABETUS
| (GN is second)
69
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)
70
What's the key gene underlying testis development?
What controls development of mullerian vs wolffian structure?
SRY = sex determining region on the Y chromosome
* Mutation prevents development in 46,XY
* Translocation in 46,XX enough to induce testis development and male phenotype
* *Anti-mullerian hormone** from **Sertoli cells** causes **regression of mullerian structures (the female structures)**
* *Testosterone** from **Leydig cells** supports development of **wolffian structures (male reproductive structures)**
Female phenotype develops in absence of gonad
71
What's the issue with using denosumab in those with stage 4/5 CKD?
Renal failure -\> can't activate 25OHD -\> **1,25OHD deficiency**
- will often have quite a **normal 25OHD** level
You then give them **denosumab,** which switches off their ability to mobilise calcium from bone, that they've been reliant on, causing **hypocalcaemia**
**Most endocrinologists wouldn't give to those with severe CKD**
72
What's the issue with pregnancy in those with pituitary adenomas? How are they managed?
* Pituitary size **increases** in normal pregnancy due to **lactotroph hyperplasia**
* Especially troublesome in those with **prolactinomas**
**Management**
* microadenoma:
* discontinue dopamine agonist -\> periodic visual exams -\> post partum MRI at 6 weeks
* macroadenoma:
* consider surgery prior to pregnancy
* ensure bromocriptine sensitive prior to pregnancy
* follow visual fields frequently
* continue bromocriptine if vision previously affected by tumour
* give bromocriptine if vision compromised
* if **vision threatened or adenoma haemorrhages** during pregnancy **steroids + surgery**
* MRI at 6 weeks postpartum
73
What's the ingredient in **liquorice t**hat can cause **hypokalaemia** and **hypertension**?
11-beta hydroxysteroid dehydrogenase type 2 inhibition
74
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
75
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
76
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
77
What's the definition of an osteoporotic/fragility fracture?
**Fracture with minimal trauma**
* from standing height or less
**Sites**
* vertebral 46%
* hip 16%
* wrist 16%
78
What's the classic presentation of insulinoma?
**Most common pancreatic endocrine tumour**
* 10% malignant, 10% multiple
* if multiple 50% have MEN1
**Features**
* hypoglycaemia typically in the early **morning** or before a meal
* rapid weight gain
* high insulin, raised proinsulin:insulin ratio
* high c-peptide
**Diagnosis**
* supervised prolonged fast (72hrs)
* CT pancreas
**Management**
* surgery
* somatostatin and diazoxide if not candidates
79
What's the classic presentation of Hashimoto's Thyroiditis?
* Hypothyroidism
* Firm, non-tender goitre
* **Anti-thyroid peroxidase/anti-Tg antibodies**
* **F**:M **10**:1
* May have transient thyrotoxicosis in the acute phase
80
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)
81
What's the best treatment for diabetic ESRF?
* Transplant from a living related donor
* Haemodialysis in diabetics even worse than in baseline population
* Hypotension
* Difficult access
* Acceleration of retinopathy
82
What's the best indicator of diabetic CKD progression?
**GFR**
* Low variability
* High specificity
* Infrequent regression
* Best **index of kidney function**
83
What's the benefit of gliptin (DPP-4 inhibitor) + metformin vs sulfonyluria + metformin?
Weight loss instead of weight gain
Much less hypoglycaemia
84
What's osteomalacia? Classic presentation and investigations? Management?
Normal bony tissue with decreased mineral content **(soft bones)**
* termed **rickets** when growing
* **osteomalacia a**fter 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
85
What's Liddle Syndrome?
Very rare autosomal dominant disorder causing **pseudohyperaldosteronism**
**Features (early and severe)**
* hypertension
* low renin activity, metabolic alkalosis, hypokalaemia
* low-normal aldosterone
Due to a mutation in **ENaC** resulting i**n reduction in degradation and chronic overexpression in the cortical collecting duct** -\> **hyperaldosteronism like state**
* aldosterone usually responsible for creating and inserting these channels
**Management**
* low salt diet
* potassium sparing diuretic (not spironolactone)
86
What's interesting about the effect of raloxifene on fractures?
Raloxifene - selective estrogen receptor modulator (SERM) and therefore a mixed agonist–antagonist of the estrogen receptor (ER) used in prevention and treatment of OP in postmenopausal women.
## Footnote
Reduces **vertebral fracture risk by 36%**
- in p**ostmenopausal women with osteoporosis**
**_Doesn't appear to prevent non-vertebral fractures_**
87
What occurs in hyperproteinaemic hyponatraemia?
88
What's **familial hypercholesterolaemia**?
**Autosomal dominant c**ondition due to mutations in the gene encoding **LDL(apo B/E)-receptor**
* thought ~1:500 (homozygotes 1:1,000,000)
* high TC and LDL-C from birth, predisposition to **tendon xanthomata, and early onset CVD**
* similar phenotype can occur with mutations in **PCSK9** or gene coding for **apo B**
**Pathophysiology**
* impaired **LDL-r** -\> **reduced LDL clearance** -\> elevated **plasma LDL-C**
* increased **uptake of modified LDL** by macrophage scavenger receptors -\> **foam cells**
**Diagnosis - based on table**
* Definite \>8; probably 6-8; possible 3-5; unlikely 0-2
**Management**
* Maximum dose atorva/rosuva/simvastatin
* no role established for additional drugs (PCSK9i mabs - Approved for familial hypercholestrolemia
* screen 1st degree relatives
89
What underlies the increased hepatic gluconeogenesis that's seen in diabetes (T2DM)?
90
What transports **iodide** into the **thyroid cell**?
**Sodium-iodide symporter in basal membrane**
* Stimulated via **TSH receptor** (directly and increased mRNA transcription)
* **Inhibited by iodine** (directly and decreased mRNA transcription)
* Allows for **concentration ~15x that of the rest of the bod**y
91
What study looks at the prevalence of Diabetes and its complications in the Australian Population?
What is the overall prevalence of Diabetic Retinopathy in Australia?
The Australian Diabetes, Obesity and Lifestyle Study (Ausdiab).
Baseline 1999/2000, f/u in 2004/2005, f/u in 2011/2012.
Overall DR prevalence 25.4%, proliferative DR 2.1%.
92
What should you think in **high BMD readings on DEXA**?
* *Degenerative change** commonly causes spuriously high BMD readings
* *- think in OA**
93
What should happen to thyroglobulin post thyroid ablation/removal?
**Should disappear**
* Can do stimulation test with withdrawal of thyroid hormone or dose of recombinant TSH
* **If Tg shows up again it means the tumour is back**
Not helpful in anything less than total thyroidectomy
94
What should be done to replacement thyroid hormone dose in pregnancy?
* Foetus reliant on maternal thyroid for **first 12 weeks** of pregnancy
* **Increase dose by 50% for pregnancy**
95
What set of features characterise Carney complex?
Due to mutation in PPKAR1A
- regulates protein kinase A
96
* 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
97
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**
98
What proportion of older people who survive a hip fracture return to premorbid level of independence?
* *~1/3**
- 50% require some kind of help
- 25% require full time care
99
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)
100
What proportion of hypertension in adults is directly attributable to obesity?
**60-70%**
**Central** more important than peripheral
101
What proportion of euthyroid people have anti TPO/Tg antibodies? Do they convey any risk?
Of what significance are TSH receptor antibody and thyroid stimulating immunoglobulin in pregnancy?
* 5-15% women
* 2% men
* Increased risk of thyroid dysfunction
* TRAb and TSI used to predict risk of neonatal thyrotoxicosis
* Level in the last trimester is predictive of risk (\>3x upper limit of normal)
