Endocrinology Flashcards

1
Q

Genetic Syndromes of hypokalaemia

A

Barters, Gitelman, Liddles

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2
Q

Which genetic syndrome of hypokalaemia is associated with High Blood Pressure

A

Liddles - rare autosomal dominant, gain-of-function mutation in ENaC leads to hereditary hypokalemia and hypertension, mimicking the syndrome of mineralocorticoid excess.

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3
Q

Which genetic syndrome of hypokalaemia mimics the action of loop diuretics?

A

Barter Syndrome

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4
Q

Which genetic causes of hypokalaemia lead to a metabolic alkalosis

A

Barter and Gitelman Syndrome

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5
Q

Features of Primary Hyperaldonstoeronism (Conn’s Syndrome)

A

Triad of Hypertension, Hypokalaemia and Metabolic Alkalosis. Excess Hyperaldosterone –> Excess excretion of Potassium (Sodium potassium exchanger in the distal convoluted tubule), metabolic alkalosis and hypertension.

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6
Q

Diagnosis in suspected Primary Hyperaldosteronism

A

Plasma Aldosterone Concentration/Plasma Renin Concentration. If significantly elevated ratio then tends to suggest Primary Aldosteronism

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7
Q

What are the four factors that increase the likelihood of underlying osteomyelitis in the context of ulcers

A

1) Grossly visible bone or ability to probe to bone
2) Ulcer size >2cm squared
3) Ulcer duration longer that one to two weeks
4) ESR >70

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8
Q

Which finding is specific for Grave’s Disease

A

Pre-tibial Myxodema

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9
Q

Best investigations for Grave’s Disease

A

1) Thyroid Antibodies - TSH receptor antibody

2) Tc 99 scan where there will be symmetrical homogenous uptake

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10
Q

Three treatment modalities for Graves Disease

A

1) Thionamides: Carbimazole/PTU
2) Radioactive Iodine
3) Thyroidectomy

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11
Q

Side effects of Thionamides

A
Itch
Rash
Agranulocytosis (Neutropenia) 
Hepatotoxicity 
pANCA vasculitis
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12
Q

Which Thionamide should be used in the first trimester of pregnancy

A

PTU

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13
Q

Which thionamide should be used after the first trimester of pregnancy

A

Carbimazole

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14
Q

Addison’s Disease metabolic changes

A

Reduced production of mineralocorticoid therefore hyperkalaemia, hyponatraemia and hypoglycaemia

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15
Q

Maintenance therapy in primary adrenal insufficiency

A

Glucocorticoids: Can use Hydrocort 15-25 (10mg/m squared) BD/TDS dosing or prednisone 3-5mg
Mineralocorticoid: Fludrocortisone: 100 units per day

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16
Q

Cardinal Features of Autoimmune Polyglandular Syndrome Type 1

A

Occurs in children, Addison’s disease associated with mucocutaneous candidiasis and hypoparathyroidism. Autosomal Recessive

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17
Q

Cardinal Features of Autoimmune Polyglandular Syndrome Type 2

A

Addison’s Disease
Type 1 diabetes
Thyroid Disease

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18
Q

Gold standard test for Primary Adrenal Insufficiency

A

Insulin Tolerance Test

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19
Q

Investigation of Primary Adrenal Insufficiency

A

Morning cortisol
Short Synacthen Test
Insulin Tolerance Test

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20
Q

Most common deficiency if Congenital Adrenal Hyperplasia

A

21 hydroxylase which leads to an increase in 17 hydroxylase (the precursor)

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21
Q

When should you investigate for Adrenoleukodystrophy? What is the screening test

A

Young males with adrenal insufficiency. Very long chain fatty acids (elevated = diagnosis)

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22
Q

What is gold standard diagnostic test for differentiating between a pituitary or ectopic cause of ACTH dependent Cushing’s syndrome

A

Bilateral Inferior Petrosus Sinus Sampling. Central step up ratio of ACTH central to perisperhal of >2 is diagnostic of pituitary cause

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23
Q

Triad of symptoms associated with phaechromocytoma

A

Episodic
Tachycardia
Diaphoresis
Headache

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24
Q

Genetic Syndromes associated with Phaechromocytoma

A

In order
MEN 2
VHL
NF1

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25
Q

Main Adverse Effect of GLP-1 receptor agonist (Exenatide or Dulaglutide)

A
  1. Nausea + Vomitting - normally transient and improves after 1-2 weeks
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26
Q

Contraindications & precautions with Exenatide/Dulaglutide

A
  1. Gastroparesis (delays gastric emptying)
  2. History of Pancreatitis with GLP-1 analogue
  3. Treatment with oral sulfonylurea or insulin (increases risk of hypo)
  4. Gallbladder disease (increase risk of needing a cholecystectomy)
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27
Q

Indication for Exenatide/Dulaglutide

A

HBA1c >7% with dual or triple oral therapy/insulin

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28
Q

PBS criteria for commencing anti-osteoperotic therapy in patients on sertoids

A

1) >7.5 of pred
2) 3 months
3) T score <1.5

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29
Q

Bisphosphonates mechanism of action

A

Binds to surface of bones –> Inhibition of osteoclast activity (loss of ruffled border and induced apoptosis)

Targets farnesyl pyrophosphate

“paints bone then leads to osteoclast apoptosis)

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30
Q

SERM mechanism of action

A

Selective Estrogen Receptor Modulator - binds to oestrogen receptors

Prevents vertebral factures (only)
Also decreases the risk of breast cancer

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31
Q

Zoledronic Acid adverse effects

A

Flu like reaction (paracetamol and NSAID’s)

? Atrial Fibrillation

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32
Q

Denosumab MOA

A

Monoclonal antibody that binds RANK ligand preventing osteoclast activation

Nb discontinuation or missing of doss –> rapid reduction of bone density (rapid bone resorption). Do not commence in someone who may be non-compliant.

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33
Q

Adverse effect of prolonged anti-resorptive therapy

A

1) Osteonecrosis of the jaw
> 8 weeks of exposed alveolar bone after dental extraction
2) Atypical femoral fracture (prodrome with thigh pain). Risk factor is treatment with glucocorticoids.

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34
Q

Treatment of Atyipical femur fracture

A

1) Discontinue anti-resorptive
2) Incomplete - prophylactic nail fixation
3) Complete - orthropods
4) Monitor risk in contralateral hip

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35
Q

Potential treatment for refractory osteoporosis

A

PTH - Skeletal anabolic steroid

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36
Q

Effect of irony infusion on phsophate

A

Loss of phosphate though the kidneys

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37
Q

Findings in osteomalacia

A

1) High ALP
2) Bone pain/fractures
3) myopathy

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38
Q

What is osteomalacia caused by

A

1) Vitamin D Deficiency

2) Low phosphate

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39
Q

Risk factors for Graves disease

A

1) Family hx of autoimmune thyroid disease
2) Recent iodine exposure
3) Post partum

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40
Q

Technetium scan in Graves Disease

A

Uniform uptake of technetium

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41
Q

Mgmt Graves disease

A

1) Beta Blocker - symptomatic
2) Control hyperthyroidism
- Thionamide (adverse effect neutropenia/rash/pANCA vasculitis)
- Radioactive iodine (contraindicated in eye disease and can be slow onset) (adverse effect hypothyroidism
- Surgery

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42
Q

Pathognomic signs of graves disease

A

1) Pretibial myxoedema

2) Graves orbitopathy

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43
Q

Adverse effects of thionamides

A

1) Neutropenia
2) Rash
3) pANCA vasculitis

PTU: Fulminant inflammatory hepatitis

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44
Q

Which thionamide to use in first trimester

A

PTU “primary trimester”

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45
Q

Risk factors for graves orbitopathy

A

1) Smoking
2) Radioactive iodine
3) Hypothyroidism (through fluid retention)

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46
Q

Treatment for grave’s orbitopathy

A

Pulse methylprednisolone
Radiotherapy if no response
Surgical debunking in the chronic phase

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47
Q

Periodic paralysis associated with graves disease precipitant and electrolyte findings

A

1) Thyrotoxicosis due to graves disease
2) High carbohydrate meal –> insulin
3) Hypokalaemia

Below the waist paralysis
Seen in patients with Asian heritage

48
Q

Dosing thyroxine in pregnancy

A

Increase dose by 1.3 times

49
Q

Subclinical hypothyroidism in pregnancy

A

Give thyroxine during pregnancy

50
Q

Toxic nodule on technetium scan

A

One major nodule with remainder of the thyroid suppressed

51
Q

Treatment for toxic nodule

A

Radioactive iodine

trapped in overactive area

52
Q

Treatment for multi nodular goitre

A

Radioactive iodine

53
Q

Thyroidits on technetium

A

No uptake + neck tenderness

54
Q

Treatment for thyroiditis

A

Propanolol for symptoms

NSAID’s/pred for pain

55
Q

Amiodarone thyroiditis

A

1) Type 1: Iodine load

2) Type 2: Thyroiditis

56
Q

Treatment for amiodarone thyroiditis

A

1) Thionamides
2) Steroids for thyroiditis
3) Colestyramine to decrease ? intrahepatic flow of thyroid hormones

57
Q

Technetium scan in amiodarone thyroiditis

A

Cold as amiodarone competes with technetium for uptake.

58
Q

Drugs that can affect the thyroid

A

1) Amiodarone - Hypothyroidism or thyroiditis
2) Lithium - Hypothyroidism or thyroiditis
3) Immune checkpoint inhibitors
- PD-1: primary thyroiditis
- Anti-CTLA4: central and secondary hypothyroidism
4) Alemtuzumab
- Graves disease common (15% of patients)
5) Interferon alpha
6) Tyrosine kinase inhibitors
7) Bexarotene (cutaneous lymphoma)

59
Q

Which drug used in MS is associated with Grave’s disease?

A

Alemtuzumab

60
Q

Findings in subclinical hypothyroidism

A

Normal T3/T4 but elevated TSH

Treat young and also pregnant
Do not treat old

61
Q

Findings in subclinical hypothyroidism

A

Normal t3/t4 but low TSH

Treat old people irrespective
Treat young people if very low TSH

62
Q

Commonest type of thyroid cancer

A

Papillary

63
Q

Thyroid scan on technetium scan

A

Cold

64
Q

Important first test when working up thyroid nodule?

A

TSH - helps differentiate toxic nodule from thyroid cancer

65
Q

Tumor marker in follicular derived thyroid cancer

A

Serum thyroglobulin

66
Q

What is given to facilitate radio-iodine post surgical removal of thyroid cancer

A

Recombitant TSH

67
Q

Treatment for radio-iodine refractory, surgery inappropriate progressive thyroid cancer

A

Lenvatinibi - multi targeted kinase inhibitor

68
Q

Most common mutation in medullary thyroid cancer

A

RET mutation

69
Q

MEN 2A

A

Phaeo
Medullary thyroid cancer
Hyperparathyroidism

70
Q

What to exclude in medullary thyroid cancer

A

Exclude phaeo with 24 hr urinary metanephrines

71
Q

Tumor marker for medullary thyroid cancer

A

Calcitonin

72
Q

MEN 2B

A

Marfarnoid habitus
Medullated corneal nerves
Aerodigestive ganglioneuromas
Medullary thyroid cancer

73
Q

Investigation for ACTH deficiency

A

Insulin tolerance test

–> hypoglycaemia –> ACTH

74
Q

GH deficiency

A

Insulin tolerance test

75
Q

Pituitary mass clinical features

A

1) Amenorrhea
2) Visual field defect
3) Occulomotor palsy

76
Q

Most common functioning pituitary adenoma

A

Porlactinoma

77
Q

Treatment for prolactinoma that does not require surgical intervention

A

Dopamine agonist: Bromacriptine/Cabergoline

78
Q

What to measure on acromegaly to screen for GH secreting adenoma

A

IGF-1

79
Q

Medical (pre-surgical) treatment for GH adenoma

A

Somatostatin analogues.

80
Q

Treatment for Acromegaly post surgery with elevated IGF-1

A

1) Dopamine agonist
2) Somatostatin analogues
3) Pegvisomant

Adverse effects of somatostatin analogies –> diabetes mellitus due to suppressive effects on Beta cells

81
Q

Acromegaly cancer association

A

1) Thyroid cancer
2) Colon cancer
- Colonoscopy from age 40 n

82
Q

Pegvisomant mechanism of action (used in Acromegaly)

A

Pegvisomant: Blocks growth hormone receptor

83
Q

ACTH excess clinical feature

A

Hyperpigmentation
Easy bruising
Wounds that don’t heal
Spinal osteoporosis

84
Q

Next best test when elevate cortisol identified on test

A

Coupled cortisol and acth to determine if ACTH dependent or ACTH independent

85
Q

How do you prevent Nelsons syndrome in ACTH excess with adrenalectomy?

A

Pituitary irradiation

86
Q

Drugs that can be used in Cushing’s disease

not complete

A

1) Ketoconazole

2) Metyrapone

87
Q

Causes of ectopic ACTH

A

Small cell lung cancer

Lung Carcinoid

88
Q

Characteristic biochemistry of TSH-oma

A

Elevated T4/T3
Normal or elevated TSH

Ddx: resistant to thyroid hormone

89
Q

Most common presenting symptom of pituitary apoplexy

A

Headache (between the eyes and acute onset)

90
Q

Most common deficiency in lymphocytic hypophysitis? (two)

A

ACTH

ADH

91
Q

Measurement for ADH

A

Copeptin

92
Q
Diabetes insipidus (central - under production of ADH) 
NOT COMPLETE
A

Central

  • Head injury
  • Hypohpysitis
  • Infiltrating lesions

Nephrogenic

93
Q

MEN1 associated diseases

A

P’s

1) Parathyroid
2) Pancreas (neurological-endocrine)
3) Pituitary

94
Q

Pituitary Apoplexy treatment

A

1) Give steroids -dex
2) Check prolactin/cortisol and other hormones
3) If prolactinaemia then give bromocriptine
4) Surgery

95
Q

HLA -Associated disease in DR4-DQ8 or DR3-DQ2

A

1) T1DM
2) Autoimmune thyrpoids (screen annually)
3) Coeliac Disease
4) Pernicious Anaemia

Other: Addisons disease, ITP, Polyglandular autoimmune syndrome type 2, RA, vitiligo and autoimmune hepatitis

96
Q

Markers of Beta cell autoimmunity - Autoantibodies in T1DM

A

Pro-insulin - beta cell specific
GAD
IA-2
Zinc Transporter 8 - beta cell specific

97
Q

Benefits of insulin glargine

A

1) Improvements in HBA1c
2) Less nocturnal hypoglycaemia

Nb: Toujeo is associated with reduced severe hypoglycaemia

98
Q

Diagnostic criteria for LADA

A

1) Diabetes
2) Adult
3) Evidence of islet cell autoimmunity: GAD antibodies > 5 units
4) Quick progression to insulin after initial period of insulin independence

99
Q

Potential clinical features of LADA

A
Age <50
Acute symptoms at onset
BMI <25
Personal autoimmune history 
Family autoimmune history
100
Q

Diagnostic criteria in T2DM in asymptomatic patients

A

1) HbA1c ≥6.5% (48 mmol/mol) on two separate occasions
or

2) FBG ≥7.0 mmol/L or random blood glucose ≥11.1 mmol/L confirmed by a second abnormal FBG on a separate day
or

3) OGTT before (fasting) and two hours after an oral 75 g glucose load is taken. Diabetes is diagnosed as FBG ≥7.0 mmol/L or two-hour post-challenge blood glucose ≥11.1 mmol/L

101
Q

Indication to commence GLP-1 agonist (exenatide/dulalgutide/semaglutide)

A

1) HBA1c > 7%
2) Dual or triple oral therapy or insulin

Weight loss
? Cardiovascular improvement in outcomes

102
Q

DPP-4 inhibitors (Gliptins)

A

Adverse effect: ?Pancreatitis (Cannot use if previous pancreatitis)

Weight neutral

103
Q

Best gliptin to use in renal failure

A

Linaglipitin

104
Q

SGLT2 site of action

A

Proximal tubule

105
Q

Contraindication for SGLT2

A

1) Renal impairment GFR <45
2) Hepatic impairment
3) ? Elderly

106
Q

Interactions of SGLT2

A

Loop diuretics

107
Q

Adverse effects of SGLT2

A

1) Polyuria
2) Genital infection - 5%
3) Hypoglycaemia (only in combo with insulin/OS)
4) Euglycaemia DKA (precipitants surgery - w/h 72 hours prior, fasting and ketogenic diets, sever intercurrent illness with reduction in oral intake, underlying autoimmune diabetes)

108
Q

Most sensitive test for early peripheral neuropathy in DM?

A

128 Hz tuning fork

109
Q

Predictor of cardiovascular death in diabetics

A

Microalbuminuria (Commence on RAAS agent if found)

110
Q

Which of the incretin drugs is associated with weight loss?

A

GLP-1 Analogues

111
Q

Main adverse effect of Glitazones

A

MOA: PPAR agonists

A/E: Heart failure

112
Q

Obesity associated malignancy

A

1) Endometrial
2) Oesophageal
3) Gall bladder
4) Renal
5) Colon
6) Breast

113
Q

Most prevalent gene associated with human obesity

A

MC4-R (dominant)

114
Q

Stimulatory signal to the hypothalamus to eat

A

Ghrelin

ILP-5

115
Q

Is leptin inhibitory or stimulatory?

A

Inhibitory

116
Q

Medications that can be used for weight loss

A

1) Phentermine: Sympathomimetic amine
2) Topiramate: Off label
3) Orlistat: Intestinal lipase inhibitor
4) Liragluatide: GLP-1 agonist.
5) Buproprine/Naltrexone: Combined NA/DO reuptake inhibitors and nicotinic receptor antagonist + opined receptor antagonist
6) Lorcaserin: Selective 5HT receptor agonist n

117
Q

Indications for bariatric surgery

A
1) BMI > 40 with no major comorbidities 
or
2) BMI > 35  
or
3) BMI 30-35 with metabolic syndrome, or uncontrollable T2DM