Clinical (Week 4 - Pituitary and Adrenal) Flashcards
1
Q
What is the commonest childhood symptoms of new T1DM?
A
Secondary nocturnal enuresis
2
Q
What is the commonest childhood symptoms of new T1DM?
A
Secondary nocturnal enuresis
3
Q
The following features are typical of what in T1DM:
- Vomiting
- Abdominal pain
- Altered consciousness
- Acidotic breathing
A
DKA
4
Q
What are the DKA guidelines for children under the age of 16?
A
Based on weight
Careful fluid resuscitation:
- Avoid cerebral oedema!
Insulin 1 hour after IV fluids
5
Q
What are the HbA1c targets in children?
A
6
Q
What early vascular changes are seen in kids with T1DM?
A
Microalbuminaemia
Autonomic neuropathy
Cheirarthropathy
7
Q
What paediatric patients should be identified as high risk?
A
Those not seen for >6 months
High HbA1c
DKA admissions
Social work involvement
8
Q
What are primary causes of congenital thyroid disease?
A
Dysplastic gland +/- abnormal site:
- eg. Sublingual
Inborn error of T3 and T4 metabolism
9
Q
What are some secondary and tertiary causes of congenital thyroid disease?
A
Congenital pituitary disease
Hypopituitarism:
- GH deficiency
- ACTH deficiency
- Gonadotropin deficiency
10
Q
Which of the following is not a feature of congenital thyroid disease:
- Jaundice on birth
- Poor feeding but increased ‘normal’ weight
- Hypotonia (Umbilical hernia + constipation)
- Skin and hair changes
A
Jaundice on birth:
- It is delayed with congenital disease
11
Q
What screening test is done for congenital thyroid disease?
A
Guthrie test:
- Day 5 - Capillary blood spot -> Measure TSH +/or T4
12
Q
When should children be treated for congenital thyroid disease?
A
Ideally by 2 weeks of age
Window can extend to 2-3 months old
13
Q
What happens is a child with congenital thyroid disease aren’t treated before 3 months of age?
A
Cretinism
14
Q
What happens is a child with congenital thyroid disease aren’t treated before 3 months of age?
A
Cretinism
15
Q
The following features are typical of what in T1DM:
- Vomiting
- Abdominal pain
- Altered consciousness
- Acidotic breathing
A
DKA
16
Q
What are the DKA guidelines for children under the age of 16?
A
Based on weight
Careful fluid resuscitation:
- Avoid cerebral oedema!
Insulin 1 hour after IV fluids
17
Q
What are the HbA1c targets in children?
A
18
Q
What early vascular changes are seen in kids with T1DM?
A
Microalbuminaemia
Autonomic neuropathy
Cheirarthropathy
19
Q
What paediatric patients should be identified as high risk?
A
Those not seen for >6 months
High HbA1c
DKA admissions
Social work involvement
20
Q
What can cause secondary adrenal underactivity in children?
A
Pituitary disease
Suppression secondary to high dose steroids
21
Q
What are some secondary and tertiary causes of congenital thyroid disease?
A
Congenital pituitary disease
Hypopituitarism:
- GH deficiency
- ACTH deficiency
- Gonadotropin deficiency
22
Q
Which of the following is not a feature of congenital thyroid disease:
- Jaundice on birth
- Poor feeding but increased ‘normal’ weight
- Hypotonia (Umbilical hernia + constipation)
- Skin and hair changes
A
Jaundice on birth:
- It is delayed with congenital disease
23
Q
What screening test is done for congenital thyroid disease?
A
Guthrie test:
- Day 5 - Capillary blood spot -> Measure TSH +/or T4
24
Q
When should children be treated for congenital thyroid disease?
A
Ideally by 2 weeks of age
Window can extend to 2-3 months old
25
How can ambiguous genitalia be diagnosed?
CAH/Steroid abnormalities
Gene/Chromosomal defects
Congenital defects
26
What happens is a child with congenital thyroid disease aren't treated before 3 months of age?
Cretinism
27
What can cause an acquired thyroid disease in the young?
```
Delayed congenital
Post-infection
Autoimmune
Iodine deficiency
T1DM
```
28
A 15 year old girl sees the GP wondering why she hasn't menstruated yet. She says she has generally been ill one and off for as long as she can remember and she struggles in school. On examination you note that she is not attaining the growth expected. On neck palpation you notice a swelling.
Hypothyroidism (Treat with T4 for life)
29
An 8 year old girl is brought to the GP as she has had her first menstrual cycle. The mother notes that her daughter was always difficult to get to sleep and has been very hyperactive. On examination her pulse is high and you note a swelling in her neck.
Hyperthyroidism
30
What is the initial therapy for hyperthyroidism in children?
β-blockers
31
What are the suppressant therapies for hyperthyroidism in children?
```
1st two years:
- Carbimazole
- +/- T4
Permanent cure:
- Radio-iodine
- Surgery
```
32
What can cause primary adrenal underactivity in children?
```
Adrenal hypoplasia:
- Absent/Destroyed
- Dysplastic
Inborn metabolic error
Congenital Adrenal Hyperplasia (ADH)
```
33
What can cause secondary adrenal underactivity in children?
Pituitary disease
| Suppression secondary to high dose steroids
34
What is the pathological process behind congenital adrenal hyperplasia?
1) 21-hydroxylase deficiency
2) Reduced cortisol production
3) Increased ACTH production
4) Adrenal hyperplasia
5) Increased steroid precursors
6) Increased testosterone production
7) Foetal virilisation
35
What can result in the absence of cortisol and aldosterone?
Addisonian crisis:
- Hyponatraemia
- Hyperkalaemia
- Hypotension
36
What are the downsides to using the FRAX assessment of osteoporotic fracture risk?
```
Underestimates vertebral fracture risk
Dichotomised variables (Only yes/no):
- Smoking
- Alcohol
Lack of clarity
```
37
How does virilisation present in girls and boys?
Girls:
- Ambiguous genitalia
Boys:
- Precocious puberty
38
How can ambiguous genitalia be diagnosed?
CAH/Steroid abnormalities
Gene/Chromosomal defects
Congenital defects
39
What is osteoporosis characterised by?
Low bone mass
| Microarchitectual deterioration of bone
40
What can osteoporosis result in?
Increased bone fragility
| Susceptibility to fracture
41
How common is osteoporosis in people over 50 years of age?
1 in 2 women
| 1 in 6 men
42
True or false; Osteoporosis is symptomatic regardless of whether or not a fracture has occurred?
False:
| - Only symptomatic if there is a fracture
43
Where are osteoporotic fractures common?
Neck of femur
Vertebral body
Distal radius
Humeral neck
44
Where does bone remodelling occur?
Bone remodelling units
45
What does bone remodelling contribute to?
Calcium homeostasis
| Skeletal repair
46
What are the steps in bone remodelling?
1. Osteoclasts appear at inactive surfaces
- > Resorb bone
2. Osteoblasts fill cavity by putting down osteoid
- > Mineralised to new bone
3. Normally the cavity is totally filled
47
What happens to bone remodelling in osteoporosis?
Relative/Absolute increase in resorption over formation:
| -> Bone loss
48
Which of the following is not a negative risk factor for osteoporotic fractures:
- Smoking
- Alcohol
- Obesity
- Bone mineral density
- Older people
- Females
- Previous fracture
- Family history
Obesity:
| - Underweight people are at a greater risk of #
49
How should a patient, who is at risk of an osteoporotic fracture, alter their diet?
Make sure they are eating:
- 700mg calcium daily
- If post-menopausal -> 1000mg calcium daily
50
What is the main downside to the use of the QFracture tool?
Doesn't allow an input of BMD
51
Who should be assessed with either FRAX or QFracture?
People aged >50 with risk factors
| People aged
52
When should a patient be referred for a DEXA scan?
If >10% risk of osteoporotic fracture in the neck 10 years
53
What is a normal DEXA result?
BMD within one standard deviation of young adult mean
54
What is osteopenia defined as?
BMD >1 standard deviation below the young adult mean
| BUT
55
What is osteoporosis defined as?
BMD >2.5 standard deviations below the young adult mean
56
What is severe osteoporosis defined as?
Osteoporosis with a fragility fracture
57
What should be measured if the patient is younger than 20?
Only the Z score
58
What are some secondary endocrine causes of osteoporosis?
Hyperthyroidism
Hyperparathyroidism
Cushing's
59
What are some secondary GI causes of osteoporosis?
Coeliac disease
IBD
Chronic liver disease/Pancreatitis
60
What is a potential side effect of Zoledronic acid use?
1 in 3 have an acute phase reaction:
| - Give paracetamol
61
What lifestyle management can help prevent osteoporotic fractures?
```
Strength training
Weight bearing:
- Low impact
Avoidance of:
- Smoking
- Alcohol
```
62
How should a patient, who is at risk of an osteoporotic fracture, alter their diet?
Make sure they are eating:
- 700mg calcium daily
- If post-menopausal -> 1000mg calcium daily
63
What is the first line treatment for osteoporosis?
Bisphosphonates (Alendronic Acid):
| - With calcium and Vit. D supplements
64
What is the second line treatment for osteoporosis and when is it used?
Zolendronic Acid IV
OR
Denosumab (Monoclonal Ab):
- With calcium and Vit. D supplements
- Used when:
> Intolerant to bisphosphonates
> Contraindications to bisphosphonates
65
What is the third line treatment for osteoporosis?
Strontium ranelate:
| - With calcium and Vit. D supplements
66
What is the fourth line treatment for osteoporosis?
Teriparatide (Recombinant PTH)
67
How do bisphosphonates work?
Antiresorptive:
| - Reduce osteoclast activity
68
How does teriparatide work?
Increases bone growth (Anabolic)
69
What are bisphosphonates?
Pyrophosphate analogues:
- Adsorb onto bone within matrix
- Lead to osteoclast death
70
When should antiresorptive treatment be commenced?
When T score 7.5mg prednisolone for >3 months
| - If vertebral fracture
71
What are some long term side effects of bisphosphonates?
Jaw osteonecrosis
Oesophageal cancer
Atypical fractures
72
How is Zoledronic acid administered to patients?
Once yearly IV infusion for 3 years:
| - 5mg in 100ml NaCl over 15 minutes
73
What is a potential side effect of Zoledronic acid use?
1 in 3 have an acute phase reaction:
| - Give paracetamol
74
How does Denosumab work?
Targets and binds to the Receptor Activator of Nuclear Factor - kB Ligand (RANKL) with high affinity:
- Prevents RANK activation
> Inhibits osteoclast development + activity
75
How is Denosumab administered?
S/C injection every 6 months
76
What are side effects of Denosumab?
Hypocalcaemia
Eczema
Cellulitis
77
What osteoporosis treatment is contraindicated in severe renal disease?
Strontium ranelate
78
How does strontium ranelate work?
Antiresorptive
79
What are most cases of osteogenesis imperfecta secondary to?
Mutations in type 1 collagen genes:
- COL1A1
- COL1A2
80
Which of the following is not a contraindication of strontium ranelate use:
- Thromboembolic disease
- IHD
- PAD
- CHF
- Uncontrolled hypertension
CHF
81
How does teriparatide work?
Increases bone growth (Anabolic)
82
What criteria must be met before teriparatide can be prescribed?
```
>65 years old with T score 65 years old with T score -3.5:
- With 2 fractures
55-64 years old with T score -4:
- >2 fractures
- Intolerance to oral agents
```
83
When should antiresorptive treatment be commenced?
When T score 7.5mg prednisolone for >3 months
| - If vertebral fracture
84
What direct effects do corticosteroids have on bones?
Decrease osteoblast activit + lifespan
Reduce replication of osteoblast precursors
Reduce calcium absorption
85
What happens in Paget's Disease?
Abnormal osteoclast activity and increased osteoblast activity:
- Reduced bone strength
- Increased fracture risk
86
What bones does Paget's Disease affect?
Long bones
Pelvis
Lumbar spine
Skull
87
How does Paget's disease present?
Bone pain and deformity
Deafness (Conductive)
Compression neuropathy -> Vision loss
88
What role does UVB have on vitamin D metabolism?
Converts Dehydro-cholesterol to Cholecalciferol (D3)
89
How is Paget's disease diagnosed?
X-Ray
Isotope bone scan
Raised ALP (Normal FLTs)
90
What levels of the following are seen in Paget's disease:
- Calcium
- Phosphate
- ALP
- PTH
All normal except ALP which is elevated
91
How is Paget's disease treated?
Analgesia
| Bisphosphonates if analgesia doesn't reduce pain
92
What are some signs of hypocalcaemia?
```
Chovstek's sign:
- Tap over CN vii
Trousseau sign:
- Carpopedal spasm
ECG:
- QT prolongation
```
93
What is the mode of inheritance of most cases of osteogensis imperfecta?
Autosomal dominant
94
What is the most mild type of osteogenesis imperfecta and when does it present?
Type i
| Presents in adults
95
What are the two very severe types of osteogenesis imperfecta and how do they present?
Types iii and iv
| Present as multiple fractures in childhood
96
How does type ii osteogenesis imperfecta present?
It is neonatally lethal
97
What is osteogenesis imperfecta associated with?
Blue sclerae
| Dentinogenesis imperfecta
98
How is osteogenesis imperfecta treated?
Fracture fixation
Correction of deformities
Bisphosphonates
99
How is hypoparathyroidism managed long term?
```
Calcium supplements:
- >1-2g/day
Vitamin D tablets:
- 1α calcidol 0.5-1μg
Vitamin D injection:
- Cholecalciferol 300,000 units every 6 months
```
100
How can hypomagnesaemia cause hypoparathyroidism?
Calcium release from cells depends on magnesium
Magnesium deficiency:
- Increased intracellular calcium concentration
> PTH release inhibited
101
What role does UVB have on vitamin D metabolism?
Converts Dehydro-cholesterol to Cholecalciferol (D3)
102
What role does the liver play in vitamin D metabolism?
Converts cholecalciferol to 25-OH Vitamin D
103
What role does the kidney play in Vitamin D metabolism?
Converts 25-OH Vitamin D to 1,25-OH Vitamin D
104
What are some symptoms of hypocalcaemia?
```
Paraesthesia:
- Fingers
- Toes
- Perioral
Tetany and cramps
Muscle weakness
Fatigue
Broncho-/Laryngospasm
Fits
```
105
What are some signs of hypocalcaemia?
```
Chovstek's sign:
- Tap over CN vii
Trousseau sign:
- Carpopedal spasm
ECG:
- QT prolongation
```
106
What are the common causes of hypocalcaemia?
```
Hypoparathyroidism
Vitamin D deficiency:
- Osteomalacia
- Rickets
Chronic renal failure
```
107
What drugs can cause rickets and osteomalacia?
Anticonvulsants
108
How is acute hypocalcaemia treated?
IV calcium gluconate:
- 10ml, 10% over 10 minutes
- In 50ml saline or dextrose
109
What is the congenital absence of hypoparathyroidism associated with?
DiGeorge Syndrome
110
How can the parathyroid gland be destroyed?
Surgery
Radiotherapy
Malignancy
111
What are some other causes of hypoparathyroidism (apart from destruction and congenital absence)?
Autoimmune
Hypomagnesaemia
Idiopathic
112
How is hypoparathyroidism managed long term?
```
Calcium supplements:
- >1-2g/day
Vitamin D tablets:
- 1α calcidol 0.5-1μg
Vitamin D injection:
- Cholecalciferol 300,000 units every 6 months
```
113
How can hypomagnesaemia cause hypoparathyroidism?
Calcium release from cells depends on magnesium
Magnesium deficiency:
- Increased intracellular calcium concentration
> PTH release inhibited
114
What can cause hypomagnesaemia?
```
Alcohol
Drugs:
- Thiazides
- PPIs
GI Illness
Pancreatitis
Malabsorption
```
115
What causes pseudohypoparathyroidism?
Genetic defect:
- GS-α subunit dysfunction
- GNAS1 gene
116
What biochemistry is seen in pseudohypoparathyroidism?
Low calcium
| High PTH
117
What happens in pseudohypoparathyroidism?
There is PTH resistance
118
What are some long-term effects of pseudohypoparathyroidism?
```
Bone abnormalities:
- McCune-Albright Syndrome
Obesity
S/C calcification
Leaning disability
Brachdactyly:
- Short 4th metacarpal
```
119
What is pseudopseudohypoparathyroidism?
All features of pseudohypoparathyroidism
| BUT normal calcium
120
What drugs can cause rickets and osteomalacia?
Anticonvulsants
121
What are the biochemical findings in osteomalacia?
```
Reduced:
- Calcium
- Phosphate
- 25-OH Vitamin D
Increased:
- ALP
- PTH
```
122
What are some clinical signs of osteomalacia?
```
Muscle wasting -> Proximal myopathy (waddling gait)
Dental defects:
- Caries
- Enamel
Bone:
- Tenderness
- Fractures
- Rib and limb deformities
- Looser's zones
> Pseudofractures -> Transverse lucencies
```
123
What are the consequences of vitamin D deficiency?
```
Bone disease:
- Demineralisation -> Fractures
- Osteomalacia/Rickets
Malignancy -> Espeically colon
Heart disease
DM
```
124
How is vitamin D deficiency treated?
```
Vitamin D:
- D3 tablets (400-800IU/day)
> Load with 3200IU/day for 12 weeks
- Calcitriol
- Alfacalcidol
Combined Calcium + Vitamin D -> Adcal D3
```
125
What cause Vitamin D-Resistant Rickets?
An X-linked hypophosphataemia:
| - PHEX gene mutation
126
How is Vitamin D-Resistant Rickets treated?
Phosphate and Vitamin D supplements
| +/- Surgery
127
What is the biochemistry likely to be in Familial Hypocalciuric Hypercalcaemia?
Raised Calcium
Raised/Normal PTH
Normal ALP
Normal Phosphate
