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RACP 2024 > Endocrine > Flashcards

Endocrine Flashcards

1
Q

What serology supports a diagnosis of type 1 diabetes?

A
  • low or undetectable c-peptide levels
  • anti-GAD5
  • insulin autoantibody
  • Anti-IA-2, anti-IA-2B (tyrosine phosphatases)
  • anti-ZnT8
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2
Q

What HLA types are strongly associated with Type 1 diabetes?

A

HLA-DR3
HLA-DR4

(HLA-DR2 = protective)

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3
Q

What is the most common autoimune disease associated with type 1 diabetes?

A

Autoimmune thyroid disease

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4
Q

What is the most common form of auotimmune polyendocrine syndrome?

A

Type 2 (polygeneic, Addison’s, Type 1 diabetes, chronic thyroiditis)

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5
Q

What are features of autoimmune polyendocrine syndrome type 1?

A
  • AR inheritance
  • AIRE gene on Chr 21
  • asplenism
  • commonly: canididaisis, hypoparathyroidism, Addisons
  • also associated with type 1 diabetes
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6
Q

What are features of autoimmune polyendocrine syndrome type 2?

A
  • polygeneic
  • addison’s disease, type 1 diabetes, chronic thyroiditis
  • female predominance
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7
Q

What processes are enhanced by insulin?

A
  • glucose uptake into muscle and adipose
  • glycolysis
  • glycogen synthesis
  • protein synthesis
  • K+ and phosphate uptake
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8
Q

What processes are inhibited by insulin?

A
  • gluconeogenesis
  • glycogenolysis
  • lipolysis
  • ketoneogenesis
  • proteolysis
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9
Q

What effects does insulin have on the liver?

A
  • inhibits glycogenolysis
  • inhibits ketoneogenesis
  • inhibits gluconeogenesis
  • promotoes glycogen synthesis
  • increases triglyceride synthesis and VLDL formation
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10
Q

What effects does insulin have on muscle cells?

A
  • promotes amino acid transport
  • increases ribosomal protein synthesis
  • promotes glucose transprt
  • induces glycogen synthesis
  • inhibits phosphorylase
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11
Q

What effects does insulin have adipose tissue?

A
  • induces lipoprotein liase to hydrolyze triglycerides in circulating lipoprotein to deliver fatty acids to adipocytes
  • promotes glucose transport into cell, allowing esterification of fatty acids
  • inhibits intracellular lipase
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12
Q

What are the benefits of insulin analogues over human insulin?

A
  • less hypoglycaemia
  • less weight gain
  • lower HbA1c
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13
Q

What is the typical starting dose of insulin for a type 1 diabetic?

A

0.5 units/kg/day
50% basal dose

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14
Q

What are the insulin carbohydrate ratio and insulin sensitivity factor?

A

Insulin carbohydrate ratio: how many grams of carb are covered by 1 unit of insulin

Insulin sensitivity factor: how much 1 unit of rapid acting insulin with lower a blood glucose over 2-4 hours

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15
Q

What is the effect of metformin in type 1 diabetes?

A
  • small reduction in weight and lipids
  • no effect on HbA1c
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16
Q

What is the target HbA1c in type 1 diabetes?

A

Individualised but typically 7% (53 mmol/mol)

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17
Q

What is the lag between interstitial and capillary glucose levels?

A

10 minutes

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18
Q

What is the diagnostic criteria of diabetic keotacidosis?

A
  • BSL > 11 or known diabetes
  • Ketones > 3.0 or 2+ ketonuria
  • venous pH < 7.3 or HCO3 < 15
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19
Q

What features identify severe DKA?

A
  • ketones > 6
  • pH < 7.2 or HCO3 < 5
  • K < 3.5
  • GCS < 12
  • Sats < 92%
  • SBP < 90
  • HR > 100 or < 60
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20
Q

What are the management principles of DKA?

A
  • correct hypovolaemia and dehydration with IV fluids
  • restore carbohydrate metabolism with IV insulin (+ Q1H BSL)
  • monitor and correct electrolyte deficiencies especially potassium
  • investigate and treat precipitant
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21
Q

What 8 factors contribute to the pathogenesis of type 2 diabetes?

A
  1. decreased insulin secretion
  2. Increased glucagon secretion
  3. Increased hepatic glucose production
  4. Neurotransmitter dysfunction
  5. Decreased glucose uptake by muscle
  6. Increased glucose reabsorption in kidney
  7. Increased lipolysis
  8. Decreased incretin effect in intestine
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22
Q

What are the complications fo diabetes?

A

Microvascular:
- retinopathy (non proliferative, pre proliferative and proliferative)
- Nephropathy
- Neuropathy (glove and stocking = distal symmetric neuropathy, multineuritis multiplex, autonomic)

Macrovascular:
- brain
- heart
-extremities

Autonomic:
- cardiovascular
- gastrointestinal
- sudomotor
- genitourinary

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23
Q

What are the definitions of microalbuminuria and clinical albuminuria?

A

microalbuminuria = 3-30 mg/mmol

clinical albuminuria = >3 mg/mmol

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24
Q

What is the lieftime risk of a diabetic developing a foot ulcer?

A

25% (15-34%)

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25
Q

What diabetes complications contribute to diabetic foot disease?

A
  • somatic sensory neuropathy
  • somatic motor neuropathy
  • autonomic neuropathy
  • peripheral artery disease
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26
Q

What are treatment options for type 2 diabetes?

A

1st line = diet + exercise
2nd line = metformin (biguanide)
3rd line:
- sulphonylurea (gliclazide, glipizide)
- DDP-IV inhibitors (vildagliptin)
- Alpha glucosidase inhibitors (acarbose)
- thiazolidinediones (Pioglitazone)
- SGLT2 inhibitors (empagliflozin)
- GLP-1 receptor agonists (dulaglutide)
- insulin

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27
Q

What is the mechanism of action of SGLT2i?

A

Impair the reabsorption of glucose in the proximal tubule of the kidneys

(SGLT2 is responsible for 90% glucose reabsorption)

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28
Q

What are the benefits of SGLT2i?

A
  • lower HbA1c
  • weight loss
  • lower BP
  • decrease MACE
  • decrease HF hospitalisations
  • reno protective
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29
Q

What are the risks of SGLT2i?

A

-GU infections
- DKA
- amputations
- fractures
- volume depletion
- AKI

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30
Q

What dose of SGLTi is associated with CV benefit?

A

10 mg for both empagliflozin and dapagliflozin

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31
Q

What eGFR must patients have before commencing SGLT2i?

A

Empagliflozin > 30
Dapagliflozin > 25

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32
Q

What is the mechanism of DKA with SGLT2i use?

A

Result in relative insulin deficiency due to lowering of plasma glucose, which results in increased action of glucagon

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33
Q

What is the mechansim of action of GLP1 receptor agonists?

A
  • increase insulin secretion (decrease glucagon)
  • increase glucose uptake in muscle and adipose
  • increase natriuresis of kidney
  • decrease appetite
  • delays gastric emptying
  • reduces gastric acid secretion
  • increase HR, contractility and decrease BP
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34
Q

What GLP-1 receptor agonists have demonstrated CV benefit?

A

Dulaglutide
Semaglutide

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35
Q

What are risks of GLP-1 receptor agonists?

A
  • acute pancreatitis
  • hypoglycaemia
  • accumulation in renal impairment (dulaglutide >15, semaglutide >30)
  • increase in HR
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36
Q

What endocrine factors contribute to PCOS?

A
  • abnormal pulsatile GnRH release
  • causes elevated LH and FSH levels
  • results in ovary dysfunction: hyperandrogenism and follicular arrest
  • insulin resistance
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37
Q

What is the Rotterdam criteria for the diagnosis of PCOS?

A

Any 2 of 3 features:
- hyperandrogensim ( clinical = acne, hair loss, hirsutism, biochemical = non diagnostic on hormonal contraception)
- ovulatory dysfunction (primary amenorrhoea or irregular cycles)
- polycystic ovaries (follicle number per ovary >20)

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38
Q

What diagnoses need to be excluded to make a diagnosis of PCOS?

A
  • nonclassical congenital adrenal hyperplasia (17-OH-progesterone)
  • Androgen-secreting tumours (androgen profile)
  • Hyperprolactinaemia
  • thyroid disorders
  • drug induced androgen excess
  • syndromes of severe insulin resistance
  • Cushing syndrome
  • hypogonadotrophic hypogonadism
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39
Q

What is the role of anti-mullerian hormone in the diagnosis of PCOS?

A

As an alternative to pelvic ultrasound where a diagnosis of PCOS is not otherwise met with the Rotterdam criteria

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40
Q

How can hirsutism be treated in PCOS?

A
  • COCP = most effective, increases SHBG which binds free androgens
  • Androgen blockade = spirinolactone, cyproterone acetate
  • metformin
  • non pharmacological
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41
Q

How can menstrual irregularities be treated in PCOS?

A
  • cocp
  • POP
  • mirena
  • cyclical progestin (aiming 4 bleeds/year for endometrial protection)
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42
Q

How can infertility be treated in PCOS?

A
  • letrozole to promote ovulation
  • GnRH agonist with USS if fails to ovulate
  • IVF
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43
Q

How should metabolic disease be treated in PCOS?

A
  • CVD risk assessment and management of risk factors as per guideline
  • screening for T2DM (OGTT)
  • weight management
  • smoking cessation
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44
Q

What is the typical pattern of puberty in women?

A
  1. Thelarche = breast pudding
  2. Pubarche = pubic ahir
  3. Menarche = menstruation starts
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45
Q

Amenorrhoea asscoiated with low oestrogen, low FSH and no hypothalamic-pituitary pathology is typically due to what cause?

A

Hypogonadotrophic hypogonadism

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46
Q

Amennprrhoea presenting with normal oestrogen, normal FSH and normal prolactin is typically due to what cause?

A

PCOS

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47
Q

Amenorrhoea presenting with low oestrogen and high FSH is typically due to what cause?

A

Gonadal failure

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48
Q

What is the DICER1 syndrome?

A

AD associated with Sertoli-Leydig tumour of ovaries with androgenism and multi-nodular goitre

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49
Q

What are clinical features of functional hypothalamic amenorrhoea?

A
  • stress, weight loss and excercise
  • low LH, FSH and oestrogen
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50
Q

How is functional hypothalamic amenorrhoea treated?

A
  • lifestyle advice
  • CBT
  • oestrogen replacement
  • ovulation induction or IVF or IUI for pregnancy
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51
Q

What are the anatomical relations to the pituitary gland?

A

-Located in sella turcica
-Has anterior and posterior lobes
-Anterior conntected to hypothalamus by hypothalamo-hypophyseal portal system (venous)
- posterior connected to hypothalamus by axons
- located above optic chiasm
- ICA and CN nuclei of III, IV, V1, V2, anf VI located laterally

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52
Q

What is the best imaging modality for the pituitary?

A

MRI (T1 and T2)

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53
Q

What size in a pituitary microadenoma?

A

< 1 cm

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54
Q

What are the 6 hormones made by the hypothalamus?

A
  • CRH (ACTH)
  • TRH (TSH)
  • GnRH (LH, FSH)
  • GHRH (GH)
  • Somatostatin (inhibits GH)
  • Dopamine (inhibits Prolactin)
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55
Q

What are the 6 hormones made by the anterior pituitary?

A
  • ACTH (adrenal, cortisol)
  • TSH (thyroid, fT4 and fT3)
  • LH (gonads)
  • FSH (gonads)
  • GH (liver, IGF-1)
  • prolactin (breast)
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56
Q

What hormones are released by the posterior pituitary?

A

Oxytocin (contracts uterus, releases milk)
Vasopressin

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57
Q

What hormone acts on V1 and V2 receptors and what effect do these have?

A

Vasopressin (AVP)

V1 = vasoconstriction

V2 = AQP2 insertion and water reabsorption collecting duct

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58
Q

What hormone is typically lost first following pituitary irradiation?

A

Growth hormone

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59
Q

What are clinical features of low ACTH?

A

Lethargy
Anorexia
Postural dizziness

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60
Q

What are clinical features of low GH?

A

Increased fat mass
Reduced muscle mass
Reduced vitality
Poor quality of life
Social isolation

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61
Q

How is ACTH deficiency diagnosed?

A
  • Low early morning cortisol with low/N ACTH
  • Failure to respond to short synacthen test (requires several weeks for adrenals to atrophy)
  • insulin tolerance test (gold standard) with failure of cortisol to rise
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62
Q

What tests support a diagnosis of TSH deficiency?

A

Low fT4 and low/N TSH

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63
Q

What tests support LH/FSH deficiency?

A
  • Man: low T, low/N LH and FSH
  • pre menopause: low oestradiol, low/N LH and FSH
  • post menopause: low/N LH and FSH (oestradiol already low)
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64
Q

What tests support GH deficiency?

A
  • insulin tolerance test
  • glucagon stimulation test
    (both measure GH response to stimulation)
    (IGF-1 not sensitive)
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65
Q

How is ACTH deficiency managed?

A

Replace with 10-20 mg hydrocortisone in 2-3 doses/day
(don’t need mineralocorticoid replacement)

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66
Q

What is sick day plan for ACTH deficiency?

A
  • double or triple hydrocortisone
  • 100 mg subcut or IM if cant swallow
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67
Q

How is TSH deficiency managed?

A

Thyroxine 1.6 microgram/kg/day, aiming fT4 to half normal upper range
(don’t use TSH to titrate as will always be low)

68
Q

How is FSH/LH deficiency treated?

A

Men: Testosterone 1g IM Q12weekly or 50 mg 1% transdermal OD

Woman: Transdermal oestrogen + progesterone

69
Q

How is GH deficiency treated?

A

Subcut GH nocte aiming IGF-1 in normal range

70
Q

What is the Copeptin stimulation test?

A

Test to diagnose AVP deficiency

Copeptin is cleaved from AVP precursor 1:1, should increase after hypertonic saline or arginine stimulation

71
Q

How is AVP deficiency treated?

A

Desmopressin = V2 selective

72
Q

What are the indications for treatment of non-functioning pituitary adenomas?

A

Visual loss
Features of mass effect

Typically transphenoidal hypophysectomy
Transcranial for large tumours

73
Q

What is the most common complication of pituitary radiotherapy?

A

Hypopituitarism

74
Q

What are complications of acromegaly?

A

Hypertension
Diabetes
OSA
Cardiomyopathy
Colonic polyps/cancer
Carpal tunnel syndrome
Arthritis

75
Q

What is the most common secretory pituitary adenoma?

A

Prolactinoma

76
Q

How is acromegaly diagnosed?

A
  • IGF-1
  • 75g OGTT (GH fails to suppress)
  • MRI pituitary
77
Q

How is acromegaly treated?

A

1st line = transsphenoidal surgery
2nd line = somatostain analogue targeting SST2 (octreotide, lanreotide Q28 days)

3rd line:
- carbegoline if co-secretes prolactin
- pasireotide (SST5, causes hyperglycaemia)
- pegvisomant (GH receptor antagonist, no effect on adenoma)
- radiotherapy

78
Q

What is macroprolactin and how can it be differentiated from true hyperprolactinaemia?

A

Macroprolactin = Ig that binds prolactin and makes it inactive, results in raised levels on measurement

If add polythethylene glycol will bind large complex and only measure free prolactin

79
Q

How can adenoma size help assess for prolactinoma vs stalk compression?

A

Stalk compression = macroadenoma with prolactin 2-5x ULN

Macroprolactinoma = macroadenoma + prolactin 10x ULN

Microprolactinoma = microadenoam with prolactin 2-5x ULN

80
Q

How are prolactinomas treated?

A

1st line Dopamine agonists:
- bromocripitne (D1 + D2)
- cabergoline (D2)

2nd line = transsphenoidal hypophysectomy

3rd line = radiotherapy

81
Q

What are side effects of dopamine agonists used to treat prolactinomas?

A
  • acute: nausea, postural hypotension
  • impulse control disorders
  • cardio valvulopathy (only high dose cabergoline due to 5HT3 receptors)
82
Q

What proprotion of Cushing syndrome is due to pituitary adenoma?

A

70%
(adrenal 20%)

83
Q

What are clinical features of Cushing syndrome?

A

Central adiposity
Moon facies
Buffalo hump
Supraclavicular fullness
Thin skin
Proximal muscle weakness
Facial plethora
Violaceous striae

84
Q

What are complications of Cushing’s syndrome?

A

Hypertension
Diabetes
VTE
Osteoporosis
Fungal infections
Mood change
IHD

85
Q

How is Cushing syndrome diagnosed?

A

Dexamethasone suppression test
OR late night salivary cortisol
OR 24h urinary free cortisol

ACTH level
CT adrenals if ACTH low

If ACTH level normal/high:
- MRI pituitary
- high dose (8 mg) dexamethasone suppression test if macroadenoma
- inferior petrosal sampling if micro or no adenoma
- CT CAP or gadolinium PET if above consistent with ectopic

86
Q

What result on inferior petrosal sinus sampling indicates a pituitary source for Cushing’s syndrome?

A

Central to peripheral ACTH ration >3 post CRH

87
Q

How is Pituitary Cushing’s treated?

A

1st line = transsphenoidal surgery

88
Q

How does thyroid hormone resistance present and what is it’s cause?

A

Hyperthyroidism or hypothyroidism

Mutation in thyroid hormone receptor beta, need higher fT3 to switch off TSH production

89
Q

How are TSHoma diagnosed and treated?

A

High T4,T3 with High/N TSH
+/- macroadenoma on MRI
Raised SHBG

1st line = transsphenoidal surgery
2nd line = octreotide

90
Q

What is the main differential diagnoses for post partum hypopituitarism?

A
  • Sheehan syndrome
  • lymphocytic hyophysitis (homogenous mass on MRI with thickened stalk)
91
Q

What is the role of leydig and sertoli cells?

A

Leydig produce testosterone
Sertoli = spermatogenesis

92
Q

What is the function of LH and FSH in the male HP-gonad axis?

A

LH stimulates leydig cells to make testosterone
FSH stimulates sertoli to make sperm

93
Q

What are the function of 5a-reductase and aromatase?

A

5A-reducatse converts testosterone to Dihydrotestosterone

Aromatase converts testosterone to oestradiol

94
Q

What is the most common genetic cause of primary hypogonadism?

A

Kleinfelters

95
Q

What are contraindications to testosterone replacement therapy?

A

Hormone responsive tumours (prostate and breast cancer)

Precaution in OSA, uncontrolled CHF and recent MI

96
Q

What is the most common ADR to testosterone?

A

Erythrocytosis

97
Q

What is the embryological origin of the adrenal medulla and cortex?

A

Medulla = neural crest
Cortex = meothelial

98
Q

What are the layers of the adrenal cortex and what do they produce?

A

GFR
Glomerulosa = mineralocorticoid
Fasiculata = glucocorticoid
Reticularis = androgens

99
Q

What regulates cortisol production in pregnancy?

A

Placental CRH

100
Q

Where do adrenal cells regenerate from?

A

Subcapsular cells

101
Q

What enzyme converts cholesterol to pregnenolone?

102
Q

What is the incidence of adrenal incidentalomas in the population?

103
Q

What adrenal adenomas need no further imaging?

A

< 3 cm AND < 10 HFU
Non functioning

104
Q

What testing is required in all adrenal incidentaolma?

A

Plasma or urine metanephrines
Aldosterone : renin ratio
1 mg overnight dex suppression test

105
Q

What treatment options are there for larger adrenal incidentalomas?

A

> 6 needs to be removed
Repeat imagining 6-12 months, and remove if growth > 20% OR remove

106
Q

What mutation drives bilateral macronodular hyperplasia?

A

ARMC5 mutation

107
Q

What is the 5-year survival of adrenocortical carcinoma?

108
Q

What hormone excess features are most commonly seen with adrenocortical carcinoma?

A

Hypercortisolaemia
(often with androgen)

109
Q

What drug is anti-mitotic and used in adrenocortical carcinoma?

A

Mitotane - cause adrenal necrosis

110
Q

Why is mineralocorticoid deficiency not seen in secondary adrenal insufficiency?

A

ACTH is not a longterm driver of aldosterone

111
Q

What electrolyte abnormalities are seen in adrenal insufficiency?

A

Hyponatraemia
Hypokalaemia
(hypoglycaemia and hypercalcaemia in adrenal crisis)

112
Q

What is the secretory pattern of cortisol?

A

Pulsatile and circadian

113
Q

What is the pattern of hormone loss in autoimmune adrenal disease?

A

Outer to inner
1. Mineralocorticoid = increased renin, increased K, reduced Na
2. Cortisol: increased ACTH, reduced cortisol

Increased renin is first sign

114
Q

What antibody is most commonly seen in Autoimmune adrenal insufficiency?

A

Anti-21-OH

115
Q

What enzyme is deficient in CAH? What are the consequences

A

21-hydroxylase

Deficiency in aldosterone and cortisol
Androgen excess
Raised ACTH

116
Q

How is CAH treated?

A

Replace mineralocorticoids and glucocorticoids

117
Q

What are the treatments of primary aldosteronism?

A

Medical = amiloride, spirinolactone, eplerenone

Surgical = unilateral only

Glucocorticoid replacement in GRA (AD disease, aldosterone synthase has ACTH response element)

118
Q

What treatments are available for persistent cushings?

A

Pituitary:
- radiotherapy
- pasireotide (SSRA-5)
- Cabergoline (D2R)

Adrenal:
- bilateral adrenalectomy
- mitotane
- ketoconazole (blocks 21-OH)
- metyrapone
- etomidate
- mifepristone (GR blockade)

119
Q

What is the mechanism of acton of phentermine for weight loss?

A

Appetite suppression through noradrenaline, dopamine and MOA
(3.6 kg weight loss vs placebo)

120
Q

What is the mechanism of action of locaserin used for weight loss?

A

5-HT2c-R agonist
(2.4 kg, metabolic and BP benefits)

121
Q

What is the mechanism of action of naltrexone/bupropion for weight loss?

A

5-HT2c R agonist
(5 kg weight loss, metabolic benefits)

122
Q

What is the mechanism of action of phentermine/topiramate for weight loss?

A

5HT2cR agonist
(8kg weight loss, metabolic and BP benefits)

123
Q

What is the mechanism of action for liraglutide for weight loss?

A

GLP-1 agonist
(5.6 kg weight loss, metabolic and BP benefits, increases HR)

124
Q

What proportion of calcium is ionised (Free)?

125
Q

What is the stimulus for PTH secretion and what is its action?

A

Low calcium as sensed by CaSR

Bone - resorption
Kidney - reabsorption (DCT), vit D activation increases GI absorption

126
Q

How does calcium sensing receptor work?

A

G-protein coupled receptor
Ionised calcium binds, causes structural change and release of calcium at ER, formation of cAMP

CaSR binding by calcium reduces PTH and increases calcium excretion in urine

127
Q

What is the mechanism of action of cincalcet?

A

Calcimimetics binds CaSR and increases sensitivity to extracellular calcium (to reduce PTH secretion)

Does not have evidence that reduces death or CV events

128
Q

What is the mechanism of action of PTH on bone?

A

Binds PTH-R on osteoblasts, alter cytokine expression and promotes osteoclast function via RANK/RANK-L

(RANK-L on osteoblast matures osteoclast)

129
Q

What is the most common cause of primary hyperparathyroidism?

A

solitary adenoma (85%)

130
Q

What is familial hypocalciuric hypercalcaemia?

A

Inactivating germline mutation in calcium sensing receptor, reduces parathyroid cell inhibition by calcium

131
Q

What patients with primary hyperparathyroidism should be referred for surgery?

A

Any of:
Symptomatic of hypercalcaemia
Calcium > 2.85
Osteoporosis T < -2.5 or prior fracture
Age < 50
Renal
- egFR < 60
- urine calcium > 10 in 24h
- renal calculi

132
Q

What monitoring is required for primary hyperparathyroidism who do not undergo surgery?

A
  • annual serum calcium + creatinine
  • BMD assessment every 2 years
  • 24 h urine calcium and renal imaging if stones
133
Q

What is the effect of ionised calcium on the heart?

A

Positive ionotrope

134
Q

What is pseudohypoparathyroidism?

A

Parathyroid hormone resistance syndrome due to gene imprinting an methylation defect
- hypocalcaemia
- hyperphosphataemia
- no response to PTH

Type 1A
- short stature
- intellectual impairment
- maternal inheritance also get TSH resistance
- paternal inheritance= osteodystrophy but no endocrine defects =
Pseudopseudohypoparathyroidism

Type 1B
- hypocalcaemia, no osteodystrophy or intellectual impairment

135
Q

What is the pathway of vitamin D activation?

A
  1. 7-dehydrocholesterol activated by UVB in skin to form Vitamin D3
  2. Vitamin D3 is metabolised in liver by CYP2R1 enzyme to 25-OH-D3
  3. In kidney CYP27B1 enzyme metabolises to 1,24,25(OH)3D3 = active form

Inactivated by CYP24 enzyme

136
Q

What is the action of vitamin D on target sites?

A

Binds vitamin D receptor element
- increases bone resorption
- increase GI calcium absorption

137
Q

What are common causes of hypophosphataemia?

A

Redistribution:
- resp alkalosis
- insulin
- refeeding
- treated ketoacidosis
- sepsis
- hungry bone

Renal phosphate wasting:
- congenital: PHEX (x-linked), FGF23 (AD), AR vit D receptor mutation
- Acquired: hyperparathyroidims, Fanconi syndrome, Vit D deficiency, thiazides

138
Q

Where and how is phosphate reabsorbed in the kidney?

A

70% in proximal tubule via Na/phosphate cotransporter driven by Na-K ATPase

139
Q

What factors influence renal handling of phosphate?

A
  • PTH inhibits Na/phosphate transporter
  • FGF23 binds FGFR with klotho (cofactor) to inhibits Na/phosphate transporter
140
Q

What is the consequence of X-linked hypophasphataemic rickets?

A
  • X-linked mutation in PHEX gene increases FGF-23 due to decreased breakdown
  • results in increased phosphate wasting in urine and decreased 1,25OH vitD, so hypophosphataemia

Treatment:
- burosumab (anti-FGF23 prevents binding to receptor)
- elemental phosphate
- calcitriol
- monitor hearing
- consider thiazide and low sodium diet to influence co-transporter function

141
Q

How is osteoporosis defined?

A

T score on BMD scan
-1 to -2.5 = osteopenia
< -2.5 = osteoporosis

142
Q

What is the relationship between fracture risk and t score?

A

Fracture risk doubles for every 1 SD decrease in t score

143
Q

What is the difference between T and Z scores for BMD?

A

T score is referenced to post menopausal women
Z score is age, sex and weight matched

Z score guides who needs investigation for secondary bone loss

144
Q

What fractures are more common in obese women?

A
  • upper arm
  • ankle
145
Q

What is FRAX and how is it used?

A

10 year fracture risk assessment

Treatment indicated if osteoporotic fracture risk > 20% or hip fracture > 3%

146
Q

What is the mechanism of action of denosumab?

A

Bind RANK-L on osteoblasts, prevents activation of osteoclasts

147
Q

What is responsible for negative feedback in thyroid hormone?

A

T3
Somatostatin

148
Q

What is the function of TSH?

A

Stimulates Na-iodide pump for uptake into cell

149
Q

What process describes uptake of thyroglobulin by follicular cell in thryoid?

A

Pinocytosis

150
Q

What is the mechanism of alemtuzumab induced graves disease?

A

Anti-CD52 mAb depletes lymphocytes, reconstitution phase with loss of immunological tolerance to self antigen
- graves most common side effect in MS (less common in RA)

151
Q

What is biotin and how does it cause abnormal TFTs?

A

Vitamin B7 (pregnancy dose shouldn’t interfere)

Binds to streptavidin
- falsely low TSH (normally biotinylated so binds)
- falsely high T4 (binds antibody and inversely proportional)

152
Q

What is the effect of heparin and enoxaparin on TFTs?

A

Release lipoprotein lipase, displaces T4 and T3 from binding protein giving falsely high free T4 and T3

153
Q

What is the effect of carbemazepine and phenytoin on TFTs?

A

Increase metabolism of thyroid hormone causing low T4 and T3

154
Q

What is the half life of amiodarone?

155
Q

What is the most common thryoid dysfunction seen with amiodarone use?

A

Hypothyroidism

156
Q

How can type 1 and type 2 amiodarone induced thyrotoxicosis be distinguished?

A

Type 1: Jod baseldow
- early after starting amiodarone
- thyroid autoantibodies positive
- normal doppler
- slow response

Type 2: direct toxic effect
- more common
- late (30 months)
- reduced vascularity on doppler
- quick response to prednisone (T4 halved in 2 weeks)

157
Q

What endocrine side effects are commonly seen with ipilimumab?

A
  • hypophysitis
  • secondary hypothyroidism
158
Q

What endocrine side effects are commonly seen with anti-PD1?

A
  • primary hypothyroidism
  • hyperthyroidism
159
Q

What endocrinopathies are associated with lithium use?

A
  • hypothyroidism (goitre)
  • parathyroid hyperplasia (hypercalcaemia)
  • nephrogenic diabetes insipidus
160
Q

How does lithium cause hypothyroidism?

A

Inhibits pinocytosis of thyroglobulin from colloid

161
Q

What is the effect of cholestyramine of thyroid hormone?

A

Increases elimination

162
Q

What is the most common cause of hypothyroidism?

A

Hashimotos thyroiditis (anti-TPO)

163
Q

What patients with subclincial hypothyroidism should be treated?

A

TSH < 0.1
TSH < 0.4 if > 65 years

164
Q

What is the pathophysiology on non-thyroidal illness?

A

Inhibition of type 1 deiodinase enzyme causes rapid reduction in T3 (rise in rT3).

TSH can rise, but usually to less than 10

165
Q

What is the effect of heterophile antibodies on TFTs?

A

TSH:
- bind detection antibody to capture antibody= falsely high
- bind capture antibodya nd prevent detection binding = falsely low

RACP 2024 (15 decks)

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