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Endocrine Flashcards

1
Q

HLA genes in T1DM

A

Account up to 90% of T1DM patients (uptodate)
- DR3-DQ2
- DR4-DQ8

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2
Q

HLA-associated disease in T1DM

A
  • Autoimmune thyroid disease (1 in 5)
  • Coeliac disease (1 in 12)
  • Pernicious anaemia (1 in 25)
  • Others: vitiligo, Addison’s (polyglandular autimmune syndrome type 2), RA, autoimmune hepatitis
  • ITP
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3
Q

Pathophysiology of type 1 diabetes

A

Genetic predisposition (MHC, Ins) + environemntal modifiers –> development of autoantibodies + autoreactive T cells to insulin –> beta cell injury –> insulin deficiency

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4
Q

Environmental risk factors for T1DM

A
  • Maternal enteroviral infection
  • Older maternal age
  • Enteroviral infection
  • Infant weight gain
  • Overweight or increased high velocity
  • Puberty
  • Insulin resistance
  • Psychological stress
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5
Q

Environmental protective factors for T1DM

A
  • Higher maternal vitamin D or concentrations in late pregnancy
  • Higher omega-3 fatty acids
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6
Q

Antibodies associated with T1DM

A
  • Pro-insulin - sens 40%, sepc 90%
  • GAD - sens 72%, sepc 99.3%
  • IA-2 (tyrosine phosphatase) - sens 62%, sepc 96%
  • ZnT8 - sens 65-80%, spec 98-99%
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7
Q

Beta-cell specific antigens in T1DM

A

Insulin and ZnT8

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8
Q

Risk of microvascular complications in T1DM

A

From highest to lowest
Retinopathy > Nephropathy > Neuropathy > Microalbuminuria

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9
Q

In DCCT trial, what subgroups did not demonstrate benefit with intensive therapy?

A
  • Pts with recurrent hypoglycaemia
  • Pts with macrovascular complications
  • Young children
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10
Q

Examples of ultra short acting insulin (0-4hrs)

A

Lispro insulin (Humalog)
Aspart insulin (NR, Fiasp)
Glulisine (Apidra)

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11
Q

Examples of short acting insulin (0-6 hrs)

A

Actrapid
Humulin

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12
Q

Examples of intermediate acting insulin (0-14 hrs)

A

Isophane (Protaphane, Humulin NPH)

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13
Q

Examples of long acting insulin (24 hours)

A

Glargine insulin, Detemir insulin (Optisulin/Lantus, Toujeo, Levemir)

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14
Q

Examples of ultra long acting insulin (72 hours)

A

Degludec (Ryzodeg)

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15
Q

Pharmacokinetic benefits of CSII over MDI

A
  • Reduced variation in absorption
  • Eliminates most of SC insulin depot
  • Predictable absorption
  • Stimulates normal pancreatic function
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16
Q

Clinical benefits of CSII over MDI

A
  • Reduced HbA1c
  • Reduced severe hypoglycaemia
  • Improved QoL
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17
Q

Disadvantages of CSII over MDI

A
  • Expensive
  • Major complications - site infection, DKA (dislodgement of cannula)
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18
Q

Patient selection in pancreas and islet transplantation

A
  • Usually patients with recurrent, severe hypoglycaemia with unawareness
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19
Q

Outcomes of pancreas and islet transplantation

A
  • Reduced hypoglycaemia with improved HbA1c
  • Reduced insulin dose/frequency of injections
  • Insulin independence
  • Improved QoL
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20
Q

Diagnostic criteria for LADA

A
  • Adult (30-75 yrs)
  • Diabetes
  • Evidence of islet autoimmunity (GAD Ab > 5 units)
  • Period of insulin independence (has received diet and antidiabetic therapy)
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21
Q

“Distinguishing” clinical features of LADA over T2DM

A

Usually age < 50
Acute symptoms
BMI < 25
Personal history or FHx of autoimmunity

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22
Q

Importance of detecting AI diabetes in adults

A
  • Avoidance of SGLT2 inhibitors –> risk of ketoacidosis
  • Alteration and/or escalation of oral hypoglycaemic drug treatment
  • Early commencement of insulin
  • Screening for AI conditions
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23
Q

Pathophysiology of T2DM

A

Peripheral insulin resistance occurs from genetic + environmental factors
- Central obesity –> increased FFA –> impaired insulin dependent glucose uptake in hepatocytes, myocytes and adipocytes
- Increased serine kinase activity in fat and skeletal muscle cells –> phosphorylation of IRS-1 –> decreased affinity of IRS-1 for PI3K –> decreased GLUT4 channel expression –> decreased cellular glucose uptake

Pancreatic β cell dysfunction: accumulation of pro-amylin (islet amyloid polypeptide) in the pancreas → decreased endogenous insulin production

Progression:
Insulin resistance initially compensated by increased insulin and amylin secretion
As insulin resistance progresses, insulin secretion capacity decreases

Usually presents with isolated postprandial hyperglycaemia before progressing to fasting hyperglycaemia too

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24
Q

Physiology of insulin secretion

A

Characterised by rapid first-phase insulin response (minutes), then a delayed second phase insulin response (plateaus at 2-3 hours)

Loss of first phase insulin response occurs in DM –> post glucose challenge or postprandial hyperglycaemia

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25
Q

Physiology of insulin signally

A

Insulin reacts with insulin receptors to allow glucose to enter cell through glucose transports (i.e. GLUT4)

Activation of IRS through insulin receptors leads to:
- Cell growth/differentiation via MAP kinase
- Lipid synthesis via PI-3 kinase
- Protein metabolism via Akt

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26
Q

Hypotheses of insulin resistance

A

Inflammation: increased adipocyte –> increase inflammatory markers –> acts through JNK –> inhibition of IRS-1 –> dysregulation of glucose

Lipid overload: increased fatty acyl CoA –> B oxidation of muscle cell and inhibition of IRS-1 (via accumulation of DAGs) causing glucose dysregulation

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27
Q

Metabolic contributors to hyperglycaemia in T2DM

A
  • Decreased insulin secretion
  • Decreased incretin effect
  • Increased lipolysis
  • Increased glucose reabsorption
  • Decreased glucose uptake
  • Neurotransmitter dysfunction
  • Increased hepatic glucose production
  • Increased glucagon secretion
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28
Q

Diabetic medications working on incretin pathway

A

DPP-4 inhibitors (-gliptan)
GLP1 receptor agonists (-glutide)

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29
Q

MOA of SGLT2 inhibitors

A

Increases glucose reabsorption in kidneys in proximal tubule

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30
Q

How much glucose goes through kidneys in a day?

A

(180L/day)(900mg/L) = 162g/day

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31
Q

MOA and benefit of finerenone in diabetic nephropathy

A

Nonsteroidal mineralocorticoid receptor antagonist

Reduced risk of nephropathy progression

Approved for eGFR > 25, macroalbuminuria (+ in combination with SGLT2 inhibitor)

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32
Q

Findings of UKPDS substudy

A

MF initiated in newly diagnosed pts with T2DM is associated with reduction in risk of MI

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33
Q

Findings of STENO-2

A

Multifactorial intervention targeting glycaemia, BP, dyslipidaemia, reduces CV death and microvascular endpoints in T2DM with microalbuminuria

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34
Q

Studies demonstrating empagliflozin benefits

A

EMPA-REG
EMPEROR
EMPA-REG OUTCOME

Associated with reduced death via reduction in heart failure in patients with T2DM and CVD, and in HFrEF and HFpEF

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35
Q

Studies demonstrating GLP1 agonist

A

SUSTAIN 6
HARMONY
REWIND

GLP1 agonist shown to reduce CV events but not CV death in patients with T2DM and comorbidities

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36
Q

MOA of tirzepatide

A

Dual receptor GLP1/GIP receptor agonist

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37
Q

MOA of Icodec

A

Weekly insulin analougueM

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38
Q

MOA of retatrutide

A

Triple GIP/GLP-1/glucagon receptor agonist

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39
Q

Hormones increased and reduced from adipose tissue

A

Increased:
Visfatin
Resistin
Leptin
FGF-21
RBP-4
Cortisol

Reduced:
Adiponectin

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40
Q

Cytokines released by adipose tissue

A

TNF-alpha
IL-1B
IL-6
PAI-1
MCP-1

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41
Q

Effects of leptin and adiponectin

A

Leptin - inhibits hunger
Adiponectin - increases hunger

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41
Q

Gut hormones that inhibit satiety

A

PYY
Oxyntomodulin
PP
CCK
GLP-1
Amylin
Insulin
Leptin

Pancreas specific - pancreatic polypeptide

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42
Q

Gut hormones that stimulate satiety and hunger

A

Ghrelin
ILP5

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43
Q

Effect on leptin as BMI reduces

A

Leptin reduces –> increase in appetite

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44
Q

Pharmacological treatment for obesity

A
  • Phentermine - sympathomimetic amine, affects DA and NA
  • Topiramate - monosaccharide AED
  • Orlistat - intestinal lipase inhibitor
  • Bupropion/naltrexone - combined NA/DA reuptake inhibitor + opioid receptor antagonist
  • Liraglutide - GLP1 receptor agonist
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45
Q

Pathophysiology of congenital adrenal hyperplasia

A

21-hydroxylase deficiency –> reduction in aldosterone and cortisol –> salt losing adrenal crisis

Loss of cortisol –> increase in ACTH –> hyperpigmentation and adrenal enlargement

Increase in adrenal steroid precursors –> increase in adrenal androgens (DHEAS, androstendione) –> increase in testosterone

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46
Q

Important investigation for CAH

A

17-OH progesterone
- increased in response to deficiency in 21-hydroxylase

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47
Q

Difference between non-classical CAH and classical

A

More mild form of classical CAH
Presents in female with precocious pubarche and androgen excess

Check 17-OH progesterone level in follicular phase –> may be normal otherwise

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48
Q

Other deficiencies in CAH

A

11β-hydroxylase deficiency
17α-hydroxylase deficiency

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49
Q

Factors that change plasma cortisol binding globulin concentration

A

Increased:
- Pregnancy
- Oestrogen administration
- Hyperthyroidism

Decreased:
- Inflammation/acute illness
- Hypothyroidism
- Protein deficiency
- Diminished synthetic capability
- CBG gene mutations

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50
Q

Causes of primary adrenal insufficiency

A
  • Autoimmune adrenalitis - Associated with other autoimmune endocrinopathies
  • Infectious adrenalitis - mycobacteria, viruses (CMV, HIV, HSV) , fungi (PJP)
  • Adrenal hemorrhage
  • Sepsis: especially meningococcal sepsis (endotoxic shock) → hemorrhagic necrosis (Waterhouse-Friderichsen syndrome)
  • Disseminated intravascular coagulation (DIC)
  • Anticoagulation: especially heparin (heparin-induced thrombocytopenia)
  • Venous thromboembolism, especially in antiphospholipid syndrome (APS)
  • Adrenal tumor (most commonly pheochromocytoma) → intratumoral bleeding
  • (Short-term) steroid usage
  • Trauma (mostly blunt trauma, can also occur postoperatively)
  • Tumors (adrenocortical tumors, lymphomas, metastatic carcinoma)
  • Amyloidosis
  • Hemochromatosis
  • BL Adrenalectomy
  • Cortisol synthesis inhibitors (e.g., rifampin, fluconazole, phenytoin, ketoconazole): drug-induced adrenal insufficiency
  • Checkpoint inhibitors
  • 21β-hydroxylase
  • Vitamin B5 deficiency
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51
Q

Causes of secondary and tertiary adrenal insuffiency

A

Secondary: decreased ACTH production
- sudden discontinuation of chronic GC therapy
- Hypopituitarism
- Can be caused by checkpoint inhibitors, CTLA4 inhibitor

Tertiary: decreased CRH production
- Sudden discontinuation of chronic glucocorticoid therapy.
- Rarer causes include hypothalamic dysfunction (e.g., due to trauma, mass, hemorrhage, or anorexia)

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52
Q

Diagnosis of adrenal insufficiency

A

Early morning cortisol
Short synacthen test
- cortisol > 550 excludes adrenal failure unless recent pituitary damage (i.e. haemorrhage, surgery)
Insulin tolerance test (gold standard of ACTH/GH reserved)

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53
Q

Pathophysiology of autoimmune polyglandular syndrome

A

Type 1: Deficiency in AIRE gene –> autoreactive T cells dysregulation –> AI endocrine diseases
Most commonly - Primary adrenal insufficiency, Hypoparathyroidism, Chronic mucocutaneous candidiasis, Ectodermal dystrophy of skin, nails, and dental enamel

Type 2: Associated with HLA-DR3 and/or HLA-DR4
Results in primary adrenal insufficiency with thyroid autoimmuend isease and/or T1DM

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54
Q

Presentation and diagnosis of adrenoleukodystrophy

A

X-linked recessive
Cerebral ALD
- childhood presentation
- dementia, blindness, adriplegia

Adrenomyeloneuropathy
- spasticity, distal polyneuropathy
- young men

Diagnosis via elevated very long chain fatty acids

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55
Q

Action of glucocorticoids

A

Hyperglycaemia
Muscle catabolism
Fat deposition
Anti-inflammatory
Bone catabolism
Hypertension

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56
Q

Definition of Cushing’s syndrome

A

GC excess

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57
Q

Definition of Cushing’s disease

A

ACTH producing pituitary adenoma

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58
Q

Diagnosis of Cushing’s

A

Confirm diagnosis - cortisol
Determine if ACTH independent or dependent (i.e. Cushing’s disease) - ACTH
If confirming Cushing’s disease - determine if pituitary or ectopic - MRI pituitary, BIPSS, CT pan scan, PET

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59
Q

Hyperaldosteronism diagnosis findings

A

Primary hyperaldosteronism - low renin, high aldosterone (bilateral adrenal hyperplasia, Conn, familial hyperaldosteronism)

Secondary hyperaldosteronism - high renin, high aldosterone (renal artery stenosis, diuretics, Bartter and Gitelman’s)

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60
Q

Causes of mineralocorticoid excess and ARR diagnosis

A

Low renin, low aldosterone

Exogenous mineralocorticoid
Cushing’s syndrome
Licorice
CAH/11b hydroxylase deficiency
Liddle’s

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61
Q

Medications that have minimal effects on aldosterone levels

A

Verapamil SR
Hydralazine
Prazosin

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62
Q

Drugs to avoid in ARR testing

A

Increase in ARR
- B adrenergic blockers
- a2 agonists i.e. clonidine, a-methyldopa
- NSAIDs
- Ca blockers (DHPs)
Decrease in ARR
- Diuretics
ACEi/ARBs

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63
Q

Diagnosis of primary aldosteronism

A

Hypokalaemia, aldosterone excess, HTN
Elevated ARR
Saline infusion - confirm inadequate aldosterone suppression
Adrenal CT
Adrenal vein sampling

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64
Q

Treatment of primary aldosteronism

A

Unilateral - unilateral laparoscopic adrenalectomy > medical therapy i.e. spironolactone

Bilateral - medical therapy > unilateral laparoscopic adrenalectomy

65
Q

Clinical presentation of phaechromocytoma

A

Headache
Palpitations
Sweating
Tremor
Nausea
Low BMI
Tachycardia

66
Q

Diagnosis of phaeochromocytoma

A

Plasma free metanephrines
Genetic testing
Imaging CT/PET scan - heterogenous, large, HU > 30

67
Q

Treatment of phaeochromocytoma

A

Surgery with alpha blockade (BP < 130/80) +/- beta blockade if tachyarrhythmia

68
Q

Effects of beta blocker prior to alpha blockade in phaeochromocytoma

A

Beta-blockers cancel out the vasodilatory effect of peripheral beta-2 adrenoceptors, potentially leading to unopposed alpha-adrenoceptor stimulation and thereby causing vasoconstriction and increased blood pressure.

69
Q

Causes of hypogonadism

A

Primary (LH/FSH high)
- Klinefelter syndrome
- Cryptochidism
- Myotonic dystrophy
- Irradiation, chemotherapy
- Trauma
- Orchitis
- Advanced age
- ESKD

Secondary (LH/FSH low to normal)
- Pituitary/hypothalamic tumour, trauma, surgery, diasease
- Iron overload
- Kallman syndrome, IHH
- Hyperprolactinoma
- Opioids
- GC excess
- Anabolic steroids
- Chronic illness
- Mulnutrition, obesity
- GnRH agonists

70
Q

Clues for organic hypogonadism

A

Young age
Borderline obesity
Low comorbid burden
Gynaecomastia, borderline low testicular volume
End organ deficits
Low testosterone (not responding to weight loss), low LH, mildly raised prolactin (pituitary stalk effect)

71
Q

Effects of LH and FSH on hypogonadism

A

LH –> Leydig LH-R –> testosterone
FSH –> Sertoli cell FSH-R –> spermatogenesis

72
Q

Thyroid specific genes that regulated by TSH signal

A

Sodium iodide symporter
Thyroid peroxidase
Thyroglobulin

73
Q

Pathophysiology of Grave’s disease

A

Genetic disposition (HLA DR3 + HLA B8) + autoimmunity + triggers

T cell mediated autoimmune process –> mediated by stimulating TSHr autoantibody, by product of CD4+

74
Q

Clinical features of Grave’s disease

A

Diffuse goitre + ophthalmopathy + hyperthyroidism

75
Q

Diagnosis of Graves disease

A

Thyroid receptor antibodies + TPO Ab
Tc99 scan

76
Q

Management of Grave’s disease

A
  • Thionamides (carbimazoles or PTU) –> rash, altered LFTs, neutropenia, pANCA vasculitis
  • Iodine ablation - first line in non pregnant with small goiters
  • Surgery - carries risk of parathyroid injury and cause hypothyroidism
77
Q

Approach to thionamide therapy to Graves’

A

Titrate dose to TSH or “block/replace”
Treat for at least 12-18 months
50% chance of long term remission
Most relapses occur within 6 months of drug cessation

78
Q

PTU vs carbimazole

A

PTU
- blocks conversion from T4 to T3
- Associated with fulminant inflammatory hepatitis
- Safer in first trimester

Carbimazole
- No effect on deiodinase
- Increased risk of aplastic cutis, omphalocele and other birth defects

79
Q

Pathophysiology of Graves’ ophthalmopathy/orbitopathy

A

Activated B and T cells infiltrate retro-orbital space targeting orbital fibroblasts → cytokine release (e.g. TNF-α, IFN-γ) → local inflammatory response → fibroblast proliferation and differentiation to adipocytes → production of hyaluronic acid and GAGs and increased amount of adipocytes → increase in the volume of intraorbital fat and muscle tissues → exophthalmos, lid retraction, disturbances in ocular motility (causing diplopia)

80
Q

Clinical features of Graves’ ophthalmopathy

A

Painful feeling behind globe
Pain with eye movements
Redness of eyelids
Redness of conjunctiva
Swelling of eyelids
Chemosis
Swollen caruncle
Increase in proptosis > 2mm
Decreased eye movements > 5’ any direction
Decreased VA

81
Q

Familial hypokalaemic periodic paralysis associated with Graves’

A

Due to transient severe hypokalaemia
Occurs after high carb meals or severe exercise
Seen in Asian people

82
Q

Effects of pregnancy on thyroid

A

BHCG and TSH share common alpha subunit, thus both activate TSH receptor –> mild TSH suppression and occasional thyrotoxicosis

Should test thyroid antibodies and subclinical hypothyroidism –> receive thyroxine therapy

83
Q

Treatment of hypothyroid women in pregnancy

A

Treat thyroxine dose by ~1.3x to cover increased requirement in first trimester

84
Q

Presentation of toxic nodules

A

Usually presents with thyrotoxicosis
DUe to activating somatic TSHr mutation

85
Q

Clinical features and diagnosis of thyroiditis

A

Usually asymptomatic
May present with transient thyrotoxicosis
Signs of hypothyroidism in late stages of Hashimoto’s

Low uptake on Tc99 scan

86
Q

Causes of thyroiditis

A

Idiopathic
Post pregnancy
Hashimoto’s
Amiodarone
Immune checkpoint inhibitors
Lithium

87
Q

Effects of amiodarone on thyroid

A
  • Hypothyroidism - interference of T4 synthesis and action
  • Thyrotoxicosis - due to iodine load (type 1) and/or thyroiditis (type 2)
88
Q

Iodine effect on thyroid

A

“Wolff-Chaikoff” effect - reduction in thyroid hormone in response to large amounts of iodine

“Jod-Basedow” effect - opposite effect where there is increase in thyroid hormone response, escaping the physiologic negative feedback mechanism of the Wolf-Chaikoff effect –> may reflect an autoimmune response

89
Q

Lithium effect on thyroid

A

Inhibits T4 production and secretion resulting in hypothyroidism

Can also cause transient thyroiditis

90
Q

Immune checkpoint inhibitors that may cause thyroid issues

A

Anti-CTLA4 i.e. ipilimumab, tremilimumab:
- Hypophysitis and central hypothyroidism
- Thyroiditis

Anti-PD1 i.e. nivolumab, pembrolizumab
- Thyroiditis
- Central hypothyroidism

91
Q

Effect of alemtuzumab on thyroid

A

Anti-CD52
Graves’ disease is common
Thyroiditis can also occur in rare circumstances

92
Q

Drugs that can affect thyroid

A

Iodine
Lithium
Immune checkpoint inhibitors i.e anti CTLA4, anti PD-1
Anti-CD52 inhibitors
TKI inhibitors –> hypothyroidsm
Bexarotene (RXR agonists) –> central hypothyroidism

93
Q

Indication for treatment of subclinical hypothroidism

A

Definitely treat:
- TSH > 10 or symptoms of hypoT4
- preconception or early pregnancy

Consider thyroxine if:
- Age < 65
- Heart failure
- TPO or Tg antibody positive
- Dyslipidaemia

94
Q

Indication of investigation and treatment of subclinical hyperthyroidism

A
  • TSH < 0.1
  • Symptoms of thyrotoxicosis
  • Co-existing AF or OP
95
Q

Most common thyroid carcinoma

A

Follicular carcinoma
Monitor with thyroglobulin

96
Q

Most severe thyroid carcinoma

A

Medullary carcinoma
Monitor with calcitonin

97
Q

Risk factors for thyroid follicular cell carcinoma

A
  • Previous neck radiation
  • FHx
  • Rapid growth
  • Very firm or hard nodule
  • Fixation of nodule to adjacent structures
  • Paralysis of vocal cords
  • Regional lymphadenopathy
  • Distant metastases
  • PET incidentaloma
98
Q

Suspicious features of thyroid docules

A

Irregular borders
Microcalcifications
Hypoechogenicity

99
Q

Management of follicular thyroid cancer after surgery

A

TSH suppression after surgery unless low risk
TSH-stimulated radioiodine if intermediate/high risk
Measure serum thyroglobulin to monitor for recurrence
Systemic radioiodine and/or kinase based therapies for recurrent or metastatic disease

100
Q

Genetic drivers of papillary thyroid carcinoma

A

BRAF V600E
RTX fusions - RET > NTRK > others
RAS - NRAS > HRAS> KRAS

101
Q

Pathophysiology of medullary thyroid cancer

A

C-cell hyperplasia resulting in carcinoma, causing secretion in calcitonin
Associated with RET proto-oncogene (MEN2B)

102
Q

MEN2A characteristics

A

Phaeochromocytoma
Hyperparathyroidism
Medullary thyroid carcinoma
Hirschsprung’s disease
Cutaneous lichen amyloidosis

103
Q

MEN2B characteristics

A

Mucosal neuromas
Marfanoid body habitus
Medullary carcinoma
Phaeochromocytoma

104
Q

Management of medullary thyroid carcinoma

A

Prophylactic thyroidectomy < 20 yrs recommended if RET mutation carrier

Assess for MENII before surgery

Total thyroidectomy

RET oncogene sequencing and family screening

Measure calcitonin

105
Q

Anterior pituitary hormone deficiency diagnosis

A

ACTH
- insulin tolerance –> cortisol response to stress
- Synacthen test (may be falsely abnormal) –> for primary adrenal insufficiency

TSH
- TSH AND fT4 and/or T3
- treat with thyroxine with aim to normal fT4 and ft3

LH/FSH
- low testosterone or amenorrhoea

GH
- insulin tolerance test or glucagon stimulation test
- IGF-1 (though may be normal)

Prolactin
- low serum prolactin
- treatment unnecessary

106
Q

Diagnosis of hormone secreting pituitary tumour

A

Prolactinoma
- Elevated prolactin level

Acromegaly
- Serum IGF-1
- Oral glucose tolerance test

Cushing’s disease
- 24 hour urinary free cortisol measurement
- midnight salivary cortisol measurement, high dose dexamethasone suppression test (failure to suppress), corticotropin measurement

Thyrotropin-secreting tumour
- Serum thyrotropin measurement
- free t4 measurement

107
Q

Approach to pituitary mass

A

Review endocrine function
Assess significant mass effect
- VF defect (bitemporal hemianopia, CNII)
- Oculomotor palsy (CNIII, IV, or VI)
- Imaging showing cavernous sinus invasion or mass abutting optic chiasm

108
Q

Management of non-secreting pituitary adenoma

A

Microadenoma (<10mm)
- Observe if no compressive mass effect
- Follow up with MRI and reassess if symptomatic

Macroadenoma (>10mm)
- Transsphenoidal surgery
- Annual MRI to monitor for mass persistence or recurrence)
- Pituitary reserve testing every 6 months for 2 years
- Hormone replacement as required

109
Q

Effects of non functional pituitary adenoma

A

Most stain for FSH
May cause mass effect and anterior pituitary failure
Prolactin elevated due to stalk pressure

110
Q

Clinical features of prolactinoma

A

Hypogonadism (infertility, amenorrhoea)
Breast tenderness and discharge
High serum prolactin

111
Q

Approach to prolactinoma

A

Exclude hypothyroidism (TRH stimulates release of prolactin)
Exclude drugs
Perform MRI pituitary to confirm diagnosis
Commence dopamine agonist to normalise prolactin

112
Q

Dopamine agonists for prolactinoma

A

Bromocriptine daily
Cabergoline weekly

113
Q

Side effects of dopamine agonist

A

Hypersexuality
Compulsive buying
Punding

114
Q

Common causes of hyperprolactinaemia

A

Pregnancy/lactation
Hypothyroidism
Metoclopramide
Neuroleptics
Stress
Pituitary stalk pressure
Opioids

115
Q

Pregnancy effect on pituitary

A

Pituitary size increases in pregnancy due to lactotroph hyperplasia

116
Q

Management of prolactinomas in patients planning pregnancy

A

Microadenoma –> discontinue DA and periodic VA examination during pregnancy

Macroadenoma –> surgery prior to pregnancy or bromocriptine if vision compromise
Ensure bromocriptine sensitivity prior to pregnancy
Steroids or surgery during pregnancy if vision compromise or adenoma haemorrhage

Postpartum MRI after 6 weeks

117
Q

Hypercortisolism with low ACTH

A

Exogenous steroid
Adrenal tumour

118
Q

Hypercortisolism with high or normal ACTH

A

Failed suppression to high dose dexamethasone –> Ectopic source
Investigate with CT pan scan or PET

If adequate suppression –> likely Cushing’s disease, pituitary source
Investigate with bilateral sampling of inferior petrous sinus

119
Q

Differentiating between pituitary vs peripheral ACTH

A

Desmopressin stimulating test
CRH testing

ACTH and cortisol increase –> pituitary

ACTH and cortisol don’t increase –> ectopic source

Dexamethasone suppression test

Adequate suppression –> Cushing disease

No suppression –> ectopic source

120
Q

Treatment of Cushing’s disease

A

Osilodrostat (best) - targets 11B hydroxylase
Metyrapone - targets 11B hydroxlase, often used in pregnancy
Ketoconazole - preferred over metyrapone for non-pregnant women
Avoid mitotane for women in future pregnancy

121
Q

Common cause of ectopic ACTH

A

Due to SCLC or lung carcinoid

122
Q

Cause of ectopic CRH

A

Carcinoid
Small cell carcinoma
Medullary thyroid carcinoma

123
Q

Acromegaly diagnosis and treatment

A

Elevation of IGF-1 with clinical features (acral enlargement, diabetes, OA, sleep apnoea and HTN)
Prolactin elevated if co-secretory tumour

Surgery - first line treatment
Somatostatin receptor 2/5 agonist (octreotide, lanretoide)

After surgery, if IGF-1 elevated - normalise with dopamine agonist first then octreotide or lancreotide, then pegvisomant

124
Q

Pegvisomant MOA

A

GH receptor antagonist
Daily SC injection, funded if IGF-1 elevated despite somatostatin analogue

125
Q

Comorbidities of acromegaly

A

Thyroid cancer is most common cancer
Increased risk of colon cancer
Joint damage
Cardiovascular disease more likely
Glucose intolerance

126
Q

TSHoma clinical features and diagnosis

A

Thyrotoxicosis with elevated fT4 and/or fT3 and non-suppressed TSH
Due to TSH secreting pituitary tumour

127
Q

Causes of DI

A

Central
- Head injury/surgical injury to posterior pituitary
- Hypophysitis
- Infiltrating lesions - craniopharyngioma, germinoma, histiocytosis, TB, sarcoid
- Familial (ADH gene mtuation)

Nephrogenic
- Lithium
- Familial (vasopressin receptor or aquaporin gene mutation)

128
Q

Genes causing familial pituitary tumours

A

MEN1
p27 - cyclin dependent kinase
AIP - young onset tumours, particularly GH secreting
PPKAR1A - Carney syndrome - spotty skin pigmentation, myxomas, and testicular, adrenal and/or pituitary adenomas or hyperplasia

129
Q

Pituitary apoplexy causes

A

Sudden pituitary haemorrhage
Postpartum haemorrhage - Sheehan’s syndrome
Trauma
Enlarging adenoma

130
Q

Clinical features of pituitary apoplexy

A

Frontal headache
Neuropraxias

131
Q

Approach to pituitary apoplexy

A

Hormones including prolactin
IV steroid replacement
Imaging
Surgery if indicated

132
Q

Diagnosis of diabetes insipidus

A

Water deprivation test aiming to induce pOsM > 300 to assess if uOsm > 500-600mmol/L

Hypertonic saline infusion to induce Na > 150 to assess if plasma copeptin 4.9pmol/l

133
Q

Mechanism of osteoblast

A

Makes new bone
Mineralises collagen

134
Q

Mechanism of osteocyte

A

Mechanosensor
Secretion of FGF23 and sclerostin

135
Q

Types of bone

A

Cortical bone - dense outer shell of compact bone, turnover rate of 2-3% per year

Trabecular bone - sponge like network of delicate platelets of bone

136
Q

Role of RANK ligand

A

Mediator of osteoclast formation, function and survival

137
Q

Role of OPG

A

Decoy receptor that prevents RANK ligand binding to RANK, thus inhibiting osteoclast formation/function/survival

138
Q

Osteoporosis pathophysiology

A

Excessive remodelling –> structural deterioration –> increased skeletal fragility –> increased fracture risk

139
Q

Definition of osteoporosis

A

BMD score < -2.5
Minimal trauma fracture

140
Q

Occurrence of osteoporotic fractures

A

Radiographical vertebral > wrist fracture (in younger) and hip fracture (in older)

141
Q

Risk factors for osteoporosis

A

Previous fragility fractures > 50 yrs
Age at menopause
Intercurrent illness affecting bones or falls risk i.e. DM, RA, coeliac, thyroid/parathyroid
Steroids
Smoking
EtOH
FHx
Undeweight

142
Q

Use of Z score

A

<-2 may be useful in identifying patients with underlying accelerated causes of bone loss

143
Q

Secondary causes of bone loss

A

Hypogonadism
Vitamin D deficiency
Hyperthyroidism
Hyperparathyroidism
Coeliac disease
Multiple myeloma
Drugs - corticosteroids, AEDs, GnRH agonists, aromatase inhibitors
Chronic diseases

144
Q

MOA of bisphosphonates

A

Prevents osteoclasts from resorbing bones

145
Q

MOA of SERMS/estrogen

A

Change RANK-L/OPG ratio to inhibit osteovlast formation
Binds to estrogen receptor

146
Q

MOA of Denosumab

A

Binds to RANK-L and inhibitors it

147
Q

MOA of anabolic therapy i.e. teriparatide

A

Binds to G protein coupled receptor and stimulates PTH to promote bone formation

148
Q

MOA of romosozumab

A

Monoclonal antibody against sclerostin
Acts by increasing bone formation and reducing bone resorption

149
Q

Osteomalacia pathophysiology

A

Deficiency of mineralised bone

  • Calcipenic rickets
    ↓ Calcium → ↑ PTH levels → ↓ phosphate → impaired bone mineralization
  • Phosphopenic rickets: ↓ phosphate → impaired bone mineralization
  • Direct inhibition of mineralization → impaired bone mineralization
150
Q

Osteomalacia presentation

A

Bone pain
Fractures (usually stress-type)
Myopathy (waddling gait)
Elevated ALP

151
Q

Causes of osteomalacia

A

Vitamin D and calcium deficiency
- Nutritional
- Malabsorption
- Liver disease
- Renal disease
- Nephrotic syndrome
- AEDs
- Genetic causes (VDR, CYP27B1, 25-hydroxylase)

Hypophosphataemia
- Fanconi syndrome
- Tumour induced
- Genetic cause

152
Q

Iron deficiency and FGF23

A

Iron deficiency increases FGF23 transcription
IV iron replacement prevents FGF23 cleavage

Thus iron transfusion results in increase phosphaturia –> hypophosphataemia

153
Q

Genetic cause of hypophosphataemia

A

X-linked hypophosphataemia (XLH)

Autosomal dominant - FGF23
Autosomal recessive type 1 - DMP1
Type 2 - ENPP1
Type 3 - FAM20c

154
Q

Clinical features of HLX

A

Short stature
Osteomalacia
Pseudofractures
Osteoarthritis
Enthesopathies
Spinal stenosis
Poor dentition
Hearing loss

155
Q

Paget’s disease pathophysiology

A

Increased osteoclast activity
Increased bone turnover
Thickening and weakening of affected bone
Bone overgrowth

156
Q

Clinical manifestations of Paget’s disease

A

Bone pain
Bone deformity
OA of adjacent joints
Fractures
Spinal stenosis

157
Q

Indication of treatment for Paget’s disease

A

Bone pain
Involvement of petrous temporal bone
Nerve or spinal cord compression
Cardiac failure
Involvement of critical bone
Involvement of skull
Cosmetic change
Bending of femor or tibia

158
Q

Therapy of Paget’s disease

A

Bisphosphonates
Calcitonin
Analgesia
Surgery

159
Q

Causes of hypercalcaemia

A

PTH-dependent
- Primary or tertiary hyperparathyroidism
- Abnormality of calcium-sensing receptor (FHH, autoimmune hyperclcaemia)
- Medications: lithium, thiazide diuretics, calcitriol, calcium carbonate and antacids

PTH-independent
- Cancer
- Excess calcitriol (sarcoidosis or other granulomatous disease)
- Excess GI calcium absorption (milk-alkali syndrome)
- Endocrine disorders (thyrotoxicosis, phaechromocytoma, cortisol deficiency, VIPoma)
- Immobilisation

160
Q
A

BPT Flashcards (32 decks)

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