Endocrinology Flashcards
1
Q
MOA of Denosumab
A
MAB that inhibits RANK ligand.
RANK ligand promotes osteoCLAST differentiation and activation.
Therefore Denosumab prevents osteoclast maturation.
2
Q
Steroids which do NOT have mineralocorticoid activity
A
Dexamethasone
Betamethasone
3
Q
Mechanism of Hepcidin
A
Inhibits iron transport by internalisation and breakdown of ferroporin on basolateral surface of enterocytes.
4
Q
radioiodine ablation is associated with which complication
A
worsening of graves ophthalmopathy
5
Q
Symptoms of carcinoid tumours
A
Diarrhoea, flushing, telangictasia, wheeze, valvular lesions
6
Q
Location of carcinoid tumours
A
Mid gut, bronchial
7
Q
Test for carcinoid tumour
A
24hr Urine 5-HIAA
8
Q
Effect of PTH on Ca, Phosphate, Vit D and FGF23 levels
A
Increases Ca
Decreases Ph
Increases Vit D
FGF23 decreases PTH
9
Q
MEN1
A
3P’s - above the umbilicus
- Pancreatic tumor
- Pituitary tumor
- Parathyroid hyperplasia
10
Q
MEN 2A
A
2P’s 1M - below the head
- Parathyroid hyperplasia
- Pheochromocytoma
- Medullary thyroid cancer
11
Q
MEN 2B
A
1P 2M’s
- Phaeochromocytoma
- Medullary thyroid cancer
- Mucosal neuromas
12
Q
Management of incidental adrenal mass >4cm
A
adrenalectomy + hormone evaluation
13
Q
Management of incidental adrenal mass <4cm
A
hormone evaluation
- hormonally active lesion -> adrenalectomy
- hormonally inactive -> follow up imaging
14
Q
effect of hypophosphatemia in Hb curve
A
Shift to the Left due to reduced 2,3 BPG
As 2,3 BPG works by adding a phosphate molecule to haem to stop O2 binding
15
Q
Why do obese men have lower testosterone?
A
reduced sex-hormone binding globulin.
16
Q
MOA of exenatide
A
Stimulates glucose dependant secretion of insulin by pancreatic beta cells (incretin)
17
Q
Manifestation of GH deficiency
A
short stature and reduced growth velocity
18
Q
Decreased growth hormone occurs in what state
A
hyperglycaemia
19
Q
What is sheehan syndrome
A
Damage to the pituitary, usually from hypoperfusion, in pregnancy/childbirth.
20
Q
Test for GH deficiency
A
- IGF-1
2. GHRH
21
Q
Most common cause of familial hypercholesterolemia
A
Low-density lipoprotein (LDL) receptor defect.
22
Q
How does Sarcoidosis cause hypercalcaemia.
A
Increased 1,25(OH)2-vitamin D synthesis.
23
Q
How does malignancy cause hypercalcaemia
A
Secretion of parathyroid hormone-related peptide (PTHrP).
24
Q
Carbimazole MOA
A
Thyroid peroxidase activity.
25
Haemachomatosis arthritis joints
Metacarpophalangeal.
26
Investigation of adrenal incidentalomas
1. If malignant features (>20 houndsfields, irregular shape, delayed contrast washout, >4cm, calcification) then - biopsy or interval imaging.
2. No malignant features - check plasma metanephrines, Renin:Aldo ratio, dexamethasone suppression test for functioning lesion.
3. Follow up - imaging in 6-12 months + yearly dexamethasone suppression tests and plasma metanephrines for 4 years.
27
In diabetes, sudden change in diabetic control causes which complication?
Retinopathy
28
Bone pain + muscle weakness + waddling gait = ?
Osteomalacia
29
Specific changes in Osteomalacia (that differentiate it from Osteoporosis)
1. blurred vertebral body trabeculae on imaging.
2. softening leads to a concavity of the vertebral bodies called codfish vertebrae. The vertebral disks appear large and biconvex.
3. Looser zones = Looser pseudofractures - fissures, or narrow radiolucent lines, 2 to 5 mm in width with sclerotic borders, often are bilateral, symmetric, and lie perpendicular to the cortical margins of bones. commonly found at the femoral neck, on the medial part of the femoral shaft, and in the pubic and ischial rami.
30
Causes of Osteomalacia
Vit D deficiency
Vit D resistance
Phosphate wasting conditions.
31
Management of HTN in Pheochromocytoma
- Use alpha blockers first.
- If beta blockers are used then the adrenaline can cause unopposed vasoconstrictive α-adrenergic stimulation that aggravates hypertension.
32
MOA of steroids in bone resorption
Act on osteoblasts and inhibit growth and differentiation of osteoblasts.
Inhibit osteoprotegerin production thereby preventing osteoclast inhibition. Increase NFKB and CSF1.
Inhibit ILGF.
33
MOA of Bisphosphonates
Bisphosphonates attach to hydroxyapatite binding sites on bony surfaces. When osteoclasts resorb bone, the bisphosphonate released during resorption impairs the ability of the osteoclasts to form the ruffled border, to adhere to the bony surface, and to produce the protons necessary for bone resorption.
Decrease osteoclast differentiation and increase apoptosis.
34
Next investigation of a thyroid nodule and hyperthyroidism.
Radionucleotide thyroid scan.
| Not for FNA unless non-functioning.
35
Marker in medullary thyroid cancer
Calcitonin
36
What is a VIPoma
Neuroendocrine tumor. watery diarrhea that persists with fasting. Stools are tea-colored and odorless with stool volumes exceeding 700 mL/day.
37
Whipples triad
Symptoms of neuroglycopenia
Low BSL
resolution of symptoms with treating hypoglycaemia.
NOT necessarily insulin related.
38
Thyroid changes in pregnancy
Decreased TSH
Increased TBG
Stimulation of the TSH-receptors by bHCG
Increase in TOTAL T3, T4 (not free T3, T4)
39
Pathology changes seen in Addisons disease
```
Hyperkalaemia
Hypercalcaemia
Hyperchloremia
Hyponatremia
Metabolic acidosis
Increased urea and creatinine
Anaemia
Lymphocytosis
Eosinophilia
```
40
MODY subtypes, gene and management.
memory tool --> HHH, GIN between the H's. All 4 One and 1 for all.
MODY 1 - HNF4a - reduced insulin response, treat with sulfonylureas.
MODY 2 - Glucokinase gene - defective glucokinase, treat with diet modification only.
MODY 3 - HNF1a - most common, decreased insulin secretion, glycosuria, treat with sulfonylureas.
MODY 4 - IPF1
MODY 5 - HNF1b - insulin
MODY 6 - NDF1 - insulin
41
Aim for rate of glucose decrease per hour in DKA protocol
3mmol/hr
42
Test to avoid in possible pheochromocytoma
Dexamethasone suppression test - can cause catecholamine crisis
43
When to treat subclinical hypothyroidism
1. If TSH >10
2. If TSH >7 and pt <65yrs
3. If they also have autoantibodies
4. If they have symptoms
44
What is the primary MOA of metformin
reduces liver gluconeogenesis
45
Cardiac drug which increases the risk of developing diabetes
Statins
46
Risk of Denosumab cessation
Treatment cessation is associated with risk of bone remodeling overshoot associated with increased risk of multiple vertebral fractures
47
Pasireotide MOA, uses and SE
MOA: (somatostatin analogue) - peptide inhibitor of multiple endocrine, neuroendocrine, and exocrine mechanisms. In patients with Cushing disease, pasireotide binds to somatostatin receptor (sst1-5), with highest affinity for the sst5 subtype, resulting in inhibition of ACTH secretion which leads to decreased cortisol secretion. In patients with acromegaly, pasireotide binds to sst2 and sst5, resulting in decreased GH and IGF-1.
Uses: for treatment of refractory acromegaly and Cushing’s disease
SE: Hyperglycaemia.
48
Reason for replacing GH in Growth hormone deficiency
recommended for body composition, exercise capacity, bone and CV health
49
Management of hyperprolactinemia
Cabergoline - Dopamine agonist
50
SE Cabergoline
Increased compulsive disorders - eg. gambling, sexual.
51
Treatment of Acromegaly
1. Surgical resection of pituitary tumour.
2. Octreotide
3. Pegvisomant is a GH receptor antagonist
4. Carbergoline
52
First line investigation for diabetes insipidus
hypertonic saline–stimulated plasma copeptin
NOT water deprivation test.
53
Treatments for adrenal Cushings and Cushings disease
Adrenal Cushings - Ketoconazole, Etomidate, Metyrapone
Cushings disease - Pasireotide
54
Pathophys of Pagets
Marked increase in activity of both osteoclasts and osteoblasts. Bone remodelling is increased and
disorganised, resulting in bone which is structurally impaired and prone to deformity and fracture.
55
Hormone levels in PCOS
- High LH
- Low FSH
- High testosterone
- High DHEAS
- >20% have elevated 17OHP (but usually means CAH)
- low serum SHBG concentrations
- High AMH
56
Findings in hypocalciuric hypercalcaemia
- low urine calcium
- high PTH
- High serum calcium
--> due to defect in calcium sensing receptor
57
Through what network does the hypothalamus and pituitary communicate
Hypophyseal portal system. Goes from arcuate nucleus to anterior pituitary
58
Management of insulinoma
1. Surgical resection
| 2. Somatostatin analogue for hypoglycaemia
59
At what age is HBA1c lowest in T1DM
20-30 - young adult
60
Risk of stopping denosumab
atypical vertebral fractures
61
Order of investigations for Cushings
- ACTH
If ACTH independent - adrenal CT
If ACTH dependant - Desmopressin stimulation/ dexamethasone suppression test/ pituitary MRI
Intermediate result - desmopressin test
62
Fracture risk assessment score
FRAX
63
Contraindications to bisphosphonate therapy
- esophageal disorders
- inability to follow the dosing requirements
- chronic kidney disease [eGFR] rate <30 mL/min
64
When to start anti-resorptive therapy
1. History of hip or vertebral fracture.
2. T-score ≤-2.5 (DXA) at the femoral neck or spine, after appropriate evaluation to exclude secondary causes.
3. T-score between -1 and -2.5 at the femoral neck or spine, and a 10-year probability of hip fracture ≥3 percent or a 10-year probability of any major osteoporosis-related fracture ≥20 percent based upon the United States-adapted WHO algorithm.
65
Management of atypical femoral fractures in osteoporosis on bisphosphonates
only likely due to be from bisphosphonates if treatment duration >5 years. As prolonged therapy can lead to oversuppression of bone turnover ("frozen bone")
A patient with an atypical femur fracture in one leg is at risk for a fracture in the other leg - therefore should xray other leg too. When bisphosphonates are stopped, the risk of atypical fracture declines.
66
Highest risk ethnicity for atypical femoral fractures on bisphosphonates
Asians
67
High risk HLA in T1DM
HLA DR3 and HLA DR4
68
Protective HLA in T1DM
HLA DR2
69
T1DM autoantibodies
GAD65
IAA
IA-2
ZnT8
70
Therapies for infertility in PCOS
Letrozole
Clomiphene
Gonadotrophin therapy
IVF
71
Types of Amiodarone induced thyrotoxicosis
1. Type 1 - occurs in 3-4 months post amiodarone - it is the Jod Basedow effect due to underlying multinodular goitre or graves.
2. Type 2 - occurs in 2-3 years after amiodarone and is due to a destructive thyroiditis - should be treated with steroids.
72
When is RAI contra-indicated
when there is thyroid eye disease.
73
Cinacalcet MOA
Increases sensitivity of CaSR - calcium sensing receptor
74
Treatment for adrenal carcinoma
Mitotane
