Endocrine Flashcards
(120 cards)
1
Q
Diabetics who do NOT benefit from intensive HbA1c control
A
Patients with recurrent hypos
Patients with macrovascular complications
Young children <13 y.o
2
Q
Drug to avoid in LADA
A
SGLT2 –> DKA
3
Q
% beta cell reduction at diagnosis of T2DM
A
50%
4
Q
Insulin secretion phases
A
First phase: peak 2-4 minutes, nadir 10-15 minutes
second phase: plateaus at 2-3 hours
5
Q
Which insulin phase response is lost in DM
A
First phase response lost in both DM1 and 2 - evidenced by impaired post-prandial hyperglycaemia (OGTT)
6
Q
Cells that secrete GLP-1
A
L cells in the jejunum/ileum
7
Q
Effects of GLP-1
A
Stimulate insulin secretion
Suppress glucagon secretion
Slows gastric emptying
Improves insulin sensitivity
Decreases food intake
8
Q
Effects of DPP4
A
Increase endogenous incretin levels
Lower HbA1c by 0.5-1%
Weight neutral
CV neutral
9
Q
GLP-RA
A
Supraphysiologic incretin effect
Weight loss
Improved CV and renal benefits
-Decreased CV events but not decreased CV death
10
Q
Where is filtered glucose reabsorbed
A
90% in S1 proximal tubule
11
Q
SGLT2-i
A
Act on Na+/glucose co-transporter in PT
Genital candida affects 10%
Benefits in HFpEF and HFrEF in those with and without DM
Fewer renal outcomes
12
Q
Appetite suppressant signals
A
PYY, CCK, GLP-1, amylin, insulin, leptin
13
Q
Appetite stimulating signals
A
Ghrelin, Neuropeptide Y, AgRP
14
Q
Most effective measure for weight loss
A
Gastric bypass and banding - only interventions which show benefit beyond 2 years
15
Q
Diabetic nephropathy
A
1 cause of ESRF
Tubulointerstitial fibrosis postulated to be the major determinant of progression
Hypertension best predictor of CKD in T2DM
Proteinuria and CKD independent risk factors for CVD
16
Q
Diabetic retinopathy
A
1 cause of blindness in 20-74y.o
Non proliferative - VA normal
Proliferative - neovascularisation and macula oedema
17
Q
Treatment of diabetic retinopathy
A
Fenofibrate has some benefit
Laser
Anti-VEGF agents
Vitreo-retinal therapy
18
Q
Diabetic neuropathy
A
15% lifetime risk of amputation
Most commonly causes a distal symmetric polyneuropathy
Loss of 10g monofilament and decreased vibration predict ulcers
19
Q
Features of cardiac autonomic neuropathy
A
Resting tachycardia
Postural hypotension
20
Q
Greatest risk factor for diabetic foot disease
A
Previous ulceration or amputationM
21
Q
Management of peripheral neuropathy in diabetes
A
TCA first line
Gabapentin
Pregabalin
22
Q
Factor which has the biggest benefit for macrovascular DM complications
A
reducing systolic BP
then LDL
then HbA1c
23
Q
Goal BP in DM
A
<140/80, or <130 if high stroke risk
24
Q
Conditions associated with DM
A
Psoriasis
Osteoporosis and fracture risk
Depression
Dementia
Malignancy (liver, pancreas, endometrium, colon, breast, bladder)
PCOS
25
Malignancy which DM is protective for
Prostate
26
T1DM antibodies
Anti-GAD (most specific)
Anti-islet cell
Anti-insulin
Anti-ZnT8
27
C peptide levels in DM
Low in DM1
Normal or high in DM2
28
Features of CAH
Increased ACTH leads to hyperpigmentation and adrenal enlargement
Abnormal external genitalia
Signs of hyperandrogegism: increased growth, acne, hirsutism, premature pubarche, menstural irregularities and PCOS. Premature balding and infertility in males
29
Defect in CAH
Mutation in the gene encoding for 21-hydroxylase - usually converts adrenal precursors into aldosterone, cortisol. Instead covered to DHEA and testosterone. Autosomal recessive
30
Serum cortisol measurement vs urine and saliva cortisol measurement
Serum measures total cortisol, others measure free cortisol
31
Cortisol binding globulin
90% of cortisol is bound to CBG
32
Factors that increase CBG
Pregnancy, oestrogen, hyperthyroidismF
33
Factors that decrease CBG
Inflammation/acute illness, hypothyroid, protein deficiency, liver cirrhosis, CBG gene mutations
34
Causes of primary adrenal insufficiency
Autoimmune
Infection (mycobacteria)
Tumours
Bleeding
Bilateral adrenalectomy
Infiltrative (sarcoid, haemochromatosis)
Genetic (CAH)
Meds (ketoconazole, fluconazole, checkpoint inhibitors)
35
Causes of secondary adrenal insufficiency
Pituitary tumours
Iatrogenic (Surgery, RTx)
Trauma/vascular
36
Diagnosis of adrenal insufficiency
1. Early morning cortisol <80 (check ACTH too)
2. Short synacthen test
Consider insulin tolerance test for ACTH reserve
3. Adrenal CT if primary suspected (increased ACTH and increased renin)
37
Rationale for checking for concurrent hypocortisolism when hypothyroidism is diagnosed
Can co-exist in autoimmune polyglandular syndrome - and if thyroxine is commenced it can precipitate a life threatening adrenal crisis because thyroxine accelerates metabolic clearance of cortisol
38
Adrenoleukodystrophy
X-linked recessive
2 phenotypes
a) cerebral ALD - childhood - dementia, blindness, quadriplegia
b) adrenomyeloneuropathy - spasticity, distal polyneuropathy, young men
Diagnosis with elevated serum very long chain fatty acids
Screen any young man with adrenal insufficiency
39
Adrenal insufficiency treatment
Primary: Hydrocortisone AND fludrocortisone and consider DHEA
Secondary: hydrocortisone only
40
Addisons presentation
Weakness, fatigue, anorexia, N/V, salt craving
exam: hypotension, dehydration, hyperpigmentation
Bloods: hyponatraemia, hyperkalaemia, metabolic acidosis, decreased BGL
41
Presentation of Cushing's disease
Hyperpigmentation, easy bruising, thin skin, spinal osteoporosis
42
Treatment of Cushing's disease
Surgery
If surgery non-curative - medical osilodrostat
43
Workup for Cushing's syndrome
Perform 2 of 3 to confirm hypercortisolism
24 hr urine cortisol
overnight 1mg DST
late night salivary cortisol
Then do ACTH to see if dependent or independent
If ACTH dependent
1. High dose DST
2. Consider MRI pituitary
3. BIPPS (unless adenoma >6mm and suppression with high dose DST - then straight to surgery). Central to peripheral ACTH >2 consistent with Cushing's disease
4. GATATE imaging to localise if ectopic ACTH suspected
44
Potassium in ectopic ACTH
Very low as very high glucocorticoid excess overwhelms capacity of 11-betahydroxylase enzyme and therefore mineralocorticoid receptors ARE affected. Not affected in Cushing's disease.
45
Low renin, high aldosterone
Primary hyperaldosteronism (conns, hyperplasia)
46
high renin, high aldosterone
secondary hyperaldosteronism (renal artery stenosis, diuretics)
47
low renin, low aldosterone
mineralocorticoid excess (exogenous, Cushings, licorice)
48
Workup for hyperaldosteronism
1. normalise K+
2. liberal salt intake
3. stop offending meds (spiro etc)
4. ARR
5. If elevated, confirm with saline infusion testing
6. if Aldo not suppressed --> adrenal CT to exclude carcinoma
6. adrenal vein sampling
49
Management of unilateral adrenal hyperplasia causing hyperaldosteronism
Unilateral adrenalectomy first line
Spiro, amiloride, eplerenone 2nd line
50
Management of bilateral adrenal hyperplasia causing hyperaldosteronism
Spiro, amiloride, eplerenone first line
-Monitor renin, if remains low, increase dose
unilateral adrenalectomy second line
51
Glucocorticoid remediable hyperaldosteronism
Familial hyperaldosteronism type 1
Rare autosomal dominant condition
Aldosterone receptors responsive to ACTH
Causes arterial hypertension at a young age (rather than 3rd-6th decade in Conn's/hyperplasia)
Suspect if strong FHx of death due to CVA
52
Phaeochromocytoma presentation
Triad of headache, palpitations, sweating
53
Genes in phaechromocytoma
Genetic link 50% of the time
MEN2
vHL
NF-1
54
Features of malignancy in phaeochromocytoma
>5cm
Extra-adrenal
SDHB
Dopaminergic subtype
High Ki-67
55
Testing in phaeochromocytoma
Plasma metanephrines
Genetic testing
Ga-DOTATE-PET
56
Management of phaeochromocytoma
Surgery with alpha blockade (get BP <130/80) then beta-blockade if tachycardia
Chemo and RTx
57
Klinefelters syndrome
47 XXY
Most common cause of primary hypogonadism
Tall stature, small testes
58
Effects of testosterone replacement in hypogonadism
Improves sexual function, energy, osteoporosis, Hb, muscle mass, decreased fat mass
Does not improve spermatogenesis as this is dependent on FSH/LH
59
Conditions associated with increased SHBG
Ageing
cirrhosis
hyperthyroidism
anticonvulsants
oestrogen
HIV
60
Conditions associated with low SHBG
Moderate obesity
Nephrotic syndrome
Hypothyroidism
Glucocorticoids
Acromegaly
DM
61
Raloxifene effect on fracture risk
Decreased vertebral but not non-vertebral fractures
62
Bisphosphonates effect ono fracture risk
Decreases both vertebral and non-vertebral fractures
63
Atypical femoral fractures
Associated with bisphosphonate use, as well as steroids and PPIs
More common in Asian women
Management
-Stop bisphosphonate
-If unstable operate
-If stable and no pain - WBAT and monitor with MRI
-If stable and pain - nail fixation
64
PTH effect on bone
Continuous PTH = bone resorption
Intermitten PTH = anabolic
65
Teriparatide
Recombinant PTH
For patients with severe osteoporosis and recurrent fractures despite anti-resorptive
66
Osteomalacia presentation
Bone pain, stress fractures, myopathy (waddling gait)
67
Osteomalacia pathophysiology
Renal phosphate wasting
FGF23 regulates urinary phosphate
Iron deficiency and IV iron replacement both cause increased FGF23 and therefore decreased serum phosphate
68
X-linked hypophosphataemic rickets
PHEX gene
Pain, stiffness, gait abnormalities
Poor dental condition, short stature, hearing loss
Pseudofractures are common (femur, hands/feet)
69
X-linked hypophosphataemic rickets treatment
Burosumab - Anti-FGF23 Ab
70
Paget's disease pathophys
Primarily increases osteoclast activity
(osteoblasts activity also Increased)
Greatly increased bone turnover leading to abnormal bone, overgrowth and severe pain
71
Paget's disease presentation
Bone pain
Deformity
OA of adjacent joints
Fractures
Spinal stenosis
72
Paget's disease treatment
Bisophosphonates (zoledronic acid 5mg once yearly)
Calcitonin
Analgesics
Surgery
73
Causes of PTH dependent hypercalcaemia
Hyperparathyroidism (primary or tertiary)
Abnormality of CaSR (FHH, autoimmune)
74
Causes of PTH independent hypercalcaemia
Cancer (myeloma, PTHrP, osteolytic mets)
Increased calcitriol (sarcoid/granulomatous disease)
Excess GI calcium absorption (milk-alkali syndrome)
Endocrine (thyrotoxicosis, phaeo, Addisons)
Immobilisation
75
Medications that cause hypercalcaemia
lithium
thiazide
calcitriol
calcium carbonate
antacids
76
Indications for surgery in asymptomatic primary hyperparathyroidism
Serum Ca >0.25mmol/ ULN
CrCL <60ml/min
Urinary Ca >400mg/day (and/or nephrocalcinosis)
BMD T-score <-2.5 or vertebral fracture
Age <50
If non-surgical give bisphosphonate to reduce fracture risk
77
Graves disease antibody
TSHr auto-antibody
78
Graves disease associations
Fhx of autoimmune thyroid disease
Recent iodine exposure
Postpartum state
79
Graves disease features
Thyrotoxicosis, diffuse goitre, eye signs, pre-tibial myxoedema
80
Graves disease management
Beta-blocker for symptoms
1. Thionamides (carbimazole or PTU)
2. radioactive iodine
3. Surgery
81
Thionamides and their side effects
Carbimazole and PTU
Titrate dose to TSH
Treat for at least 12-18 months, 50% change of long-term remission
most relapses occur within 6 months of drug cessation
SE: Rash, LFT derangement, neutropenia, pANCA vasculitis
82
Radioactive iodine and its side effects
Safe except in young women and those with significant eye disease
Takes months to work
Usually causes hypothyroidism
83
Thyroid surgery and side effects
Damage to parathyroid
Graves can recur in thyroid remnant
84
PTU mechanism of actions, serious side effects and pregnancy safety
Blocks conversion of T4 to T3
Can be associated rarely with fulminant inflammatory hepatitis
Safer than carbimazole in first trimester
Enters breast milk but safe if <300mg/day
85
Carbimazole mechanism of action
Inhibits uptake of iodine by the thyroid
Can cause non-threatening cholestasis
Enters breast milk, but safe if <30mg/day
86
Risk factors for progression of Graves ophthalmolpathy
Smoking
Radioactive iodine therapy
Iatrogenic hypothyroidism
87
Management of Graves ophthalmopathy
Mild: selenium
Mod-sever: IV steroids +/- mycophenolate
Sight threatening: IV steroids and if poor response after two weeks then surgical decompression
88
How to adjust thyroxine dose going into pregnancy
Increase by 1.3x
89
Thyroiditis features
TENDER
low tc99 uptake
Use propranolol and NSAIDs/steroids
PTU and carbimazole don't work
90
Treating amiodarone thyrotoxicosis
Cease + give thionamide + steroid
Colestyramine if persistent _ serious
Surgery if no response
radioactive iodine not useful
91
Lithium effect on thyroid
Hypothyroid
92
Anti-CTLA4 effect on thyroid
Hypophysitis and central hypothyroidism (5%)
thyroiditis (2%)
93
Anti-PDL1 effect on thyroid
Thyroiditis (4%)
Central hypothyroidism (<1%)
94
Alemtuzumab effect on thyroid
Anti-CD52
Graves disease is common (15%!!!!)
95
When to treat subclinical hypothyroidism
TSH >10
Pre-conception/early pregnancy
96
When to treat subclinical hyperthyroidism
TSH <0.1
Co-existing AF/osteoporosis
Symptoms of thyrotoxicosis
97
Lenvatinib
Iodine refractory, progressive thyroid cancer not appropriate for surgery
98
Markers for recurrent disease in follicular thyroid ca and medullary thyroid ca
Follicular = thyroglobulin
Medullary = calcitonin
99
How to investigate for ACTH deficiency and how to replace
Insulin tolerance test - check cortisol response
Treat with glucocorticoid (Dex) does not need mineralocorticoid replacement
100
How to investigate for LH/FSH deficiency and how to replace if low
Diagnose based on low testosterone or amenorrhoea accompanied by low or normal LH/FSH
Treat with testosterone or OCP/HRT unless there is a history of prostate or breast cancer
For fertility use hCG for men or ovulation induction with FSH/hCG
101
How to investigate for GH deficiency and how to replace if low
Insuline tolerance test or glucagon stimulation test
Treat with daily s/c growth hormone
102
Features of prolactinoma
Hypogonadism (infertility, amenorrhoea)
Breast tenderness and discharge
High serum PRL
103
Why exclude hypothyroidism when high prolactin is found
TRH stimulates prolactin release
104
Prolactinoma management
Bromocriptine or cabergoline with aim to normalise prolactin
May withdraw treatment after 2-4 years if prolactin is normal and tumour has involuted >50% and is >5mm from optic chasm
60% will not recur within 5 years though lifelong follow-up needed
105
Features and diagnosis of acromegaly
Elevated IGF-1 (not GH) in the setting of acral enlargement, diabetes, osteoarthritis, sleep apnoea, hypertension
Thyroid cancer most common cancer associated with acromegaly
106
Management of acromegaly
Surgery first line
Can trial somatostatin receptor agonist (octreotide, lanreotide) prior to surgery
Surgical cure = normal IGF1 and GH suppression after OGTT
107
Elevated IGF-1 post surgery for acromegaly
Aim to normalise IGF1 to reduce risk of death
Dopamine agonist first line, then octreotide, then pegvisomant
108
Side effects of octreotide, lanreotide, pasireotide
Gallstones, abdominal pains
Pasireotide may cause diabetes
109
Craniopharyngoma presentation
Diabetes insipidus
Hyperphagia
Ant. pituitary deficiencies with increased prolactin
110
Craniopharyngoma mutation
Some carry BRAF mutations that respond to dabrafenib
111
Pituitary apoplexy presentation
Sudden headache +/- neuropraxia
112
Pituitary apoplexy management
IV steroid (4mg dex or 50mg hydrocort QID)
Imaging
Surgery if CN palsy present
113
GH deficiency presentation
Emotional and physical fatigue
114
Contraindications to GH replacement
Concurrent active malignancy or severe diabetic retinopathy
115
Diagnosis of diabetes insipidus
Water deprivation test to induce post >300 to see if urine Osm >500-600
or
hypertonic saline infusion to induce Na+ >150mmol to assess plasma copeptin
Copeptin >4.9 = primary polydipsia
Copeptin <4.9 = central DI
116
Management of diabetes insipidus
Tolvaptain or conivaptain
117
Carney syndrome
PPKARA1A mutation
Spotty skin pigmentation, myxomas, testicular, adrenal and/or pituitary adenomas or hyperplasia
118
T4 half life
T3 half life
TSH half life
T4 half life 7 days
T3 half life 10 hours
TSH half life 30 minutes
119
Receptor implicated in Graves orbitopathy
IGF-1
120
Medication targeting IGF-1 receptor in graves orbitopathy
Teprotumumab
