Endocrine Flashcards
1
Q
What are the phases of normal growth
A
Fetal Phase
Infantile Phase
Childhood phase
Pubertal growth spurt
2
Q
What drives Fetal growth, height velocity
A
Uterine environment
E.g. maternal diet, placental insufficiency, Size of mother
Fastest phase of growth
3
Q
What drives infantile phase of growth, height velocity
A
Growth hormone - IGF axis
Slow, prolonged
4
Q
What drives childhood phase of growth, height velocity
A
Nutrition
Rapid rate, decelerating
5
Q
What drives pubertal growth spurt
A
Testosterone and oestrogen
Growth hormone
6
Q
What do you measure for growth?
A
Weight Height Head circumference BMI Bone age
7
Q
How to measure height
A
> 2: standing height
<2: lying length
Sitting height
8
Q
What are signs of significant abnormalities of height
A
Measurements below 0.4th of above 99.6th centiles, or outside midparental height range
Markedly discrepancy from weight
Serial measurements which cross growth centile lines after 1st year of life
9
Q
How to calculate mid-parental height and target height
A
Mid parental height = parents height/2 + 7 for boys, - 7 for girls
Target height = MPH +-8.5 cm
10
Q
How to plot growth parameters
A
UK WHO chart
Different charts for age and gender
They are constructed to ethnicity, socioeconomic status, overall standards of health and nutrition, changes over time
11
Q
Define growth deceleration
A
Growth velocity below 5th percentile
Height drops across two or more percentiles on growth chart
12
Q
How can you identify growth failure
A
- Height centile
- Parental height
- Height velocity - subjective to phases of growth
- Height trajectory - height falling across centile lines, detect abnormal growth before height centile falls below second centile
13
Q
Define short stature
A
Height below second centile (2SDs below mean)
Height below 0.4th centile - extreme short statue
14
Q
How to measure height velocity?
A
Two accurate measurements at least 6 months apart
15
Q
Causes of short stature
A
Normal variant Idiopathic Endocrine Genetic Chronic illness MSK Psychosocial
16
Q
What are normal variant causes of short stature
A
Familial short stature
Constitutional delay of growth and development: short stature in adolescence due to delay in onset of puberty, but final height reaches target height. There is delayed bone age and delayed pubertal development
17
Q
What are idiopathic causes of short stature
A
Idiopathic short stature
Small for gestational age without catch-up: patients who are born SGA but have not caught up in height by 4 years, requires GH treatment
18
Q
What are endocrine causes of short stature
A
Hypothyroidism Hypopituitarism Cushing’s syndrome Untreated CAH - accelerated bone growth Hyperthyroidism - accelerated bone growth
19
Q
What are genetic causes of short stature
A
Turners Syndrome Noonan Syndrome Down’s syndrome Prader-Willi syndrome DiGeorge Syndrome (CATCH-22) Russel-silver Syndrome
20
Q
What are common chronic illnesses that cause short stature
A
Present with faltering growth (underweight) Coeliac disease - first 2 years Crohn’s disease CKD Cystic fibrosis TB - measles, vitamin D infection Bronchiectasis CHD Malnutrition
21
Q
Causes of disproportionate short stature
A
Skeletal dysplasia (abnormal bone formation): achondroplasia - autosomal dominant hypochondoplasia, osteogenesis imperfecta - Group of disorders of collagen metabolism leading to bone fragility, bowing and fractures; T1 present with #s, blue scleral hearing loss; T2 more severe, stillborn
Rickets
Spinal disorders: scoliosis, irradiation
22
Q
What are psychosocial causes of short stature
A
Psychosocial deprivation: physical/emotional abuse, neglect; resumes normal growth once removed from adverse enviro
Eating disorders
Fetal alcohol syndrome
23
Q
Growth chart for familial short stature
A
Following growth centile within predicted range for parental height
24
Q
Growth chart for SGA without catch up
A
Short stature from birth
25
Growth chart for constitutional delay of growth and puberty
Short stature in adolescence due to delayed puberty
| Delayed bone age
26
Growth chart for endocrine cause of short stature
Falling off height centiles
Weight centile > height centile
Delayed bone age
27
Growth chart for short stature caused by psychosocial/chronic illness
Falling off height centiles
Weight centile > height centile
Delayed bone age
28
How do you measure bone age?
Left wrist x Ray - skeletal maturity
29
What factors affect growth
Genetics
General health - nutrition, thyroid function
Timing of pubertal growth spurt
Psychosocial environment
30
Assessment of short stature
Pathological short stature —>
Dysmorphic features present
—> proportionate = genetic
—> disproportionate = MSK
Dysmorphic features absent
—> increased weight for height = endocrine
—> decreased weight for height = chronic illness, nutritional, emotional
31
Investigations for short stature
```
Growth chart
Target height
Height velocity
Bone age - left wrist and hand x Ray
FBC
Metabolic profile: U+E, calcium, glucose, LFT
Urinalysis
TFT
Karyotyping
IGF-1
Anti-tissue transglutaminase
ESR
```
32
Further investigations for short stature
GH stimulation test
Diurnal cortisol Levels, urinalysis cortisol Levels, dexamethasone suppression test
Skeletal survey
33
Indications for growth hormone treatment
```
GH deficiency
Turner syndrome
Prader-Willi syndrome
CKD
SHOX deficiency
IUGR/SGA with failure of catch-up growth
```
34
Prevalence of diabetes mellitus in children
2 in 1000
35
Classification of diabetes in children
Type 1 - 98% cases
Type 2 - older children w obesity, FHx
Maturity onset diabetes of the young - strong FHx, group of autosomal dominant genetic disorders that cause non-insulin dependent diabetes of <25 year old
Drugs
Pancreatic insufficiency - CF, iron overload in thalassaemia
Endocrine - Cushing’s
Genetic - Turners, Down’s
Neonatal Diabetes - due to defective B cell function
Gestational Diabetes
36
Aetiology of T1 DM
Genetic predisposition
Environmental precipitants - viral infection, diet, cows milk proteins
Autoimmune destruction of pancreatic Beta islet cells
37
Clinical features of diabetes
```
Presentation peaks at spring and autumn
Early:
Polyuria, polydipsia, weight loss
Secondary enuresis
Intercurrent illness: Skin sepsis, Candida, other infections
```
```
Late - diabetic ketoacidosis:
Smell of acetone on breath
Vomiting
Dehydration
Abdominal pain
Hyperventilation (Kussmaul breathing from acidosis)
Hypovoaemic shock
Drowsiness
Coma
```
38
Diagnosis of T1 DM in children
In symptomatic child:
Raised random blood glucose >11.1 mmol/L
Glycosuria
Ketosis
39
what are the components of Initial management of T1DM
```
Parent and child education
Insulin
Diet
Blood glucose monitoring
Management of acute complications - acute hypoglycaemia, DKA
```
40
What is covered in educational programme for child and family
```
Understanding of diabetes
Injection of insulin
Blood glucose monitoring
Diet
Exercise
Sick day rules
Recognition and treatment of hypoglycaemia
Voluntary groups
Psychological impact of life long condition
```
41
Types of insulin used in T1DM in children
Human insulin in concentrations of 100 units:
Rapid acting insulin analogues: insulin lispro (Humalog), insulin aspart (Novorapid)
Very long acting insulin analogues: insulin detemir (Levemir), glargine (Lantus)
Short-acting human insulin: Actrapid, Humulin S
Intermediate acting insulin: Insulatard, Humulin I
42
How should insulin be administered
Subcutaneous injection
Method - at anterolateral thighs, abdomen, buttocks; rotation of injection sites, skin pinched and injected at 45 degrees
Complications - lipohypertrophy, lipoatrophy, intramuscular injection (painful)
43
Insulin regimen for children and why is it recommended
Basal-bolus regimen:
By Continuous subcutaneous insulin pump or multiple daily injection
Rapid acting insulin + long acting insulin
Allows greater flexibility
Achieves best glycaemic control
Reduce risk of long term complications
44
What is ‘honeymoon’ period
Reduced insulin requirements and good glycaemic control that occurs shortly after presentation/diagnosis
Requirement subsequently increases during puberty
45
Blood glucose targets in children
4 - 7 mmol/L before meals
| HbA1C <48 mmol/mol (6.5%)
46
Methods of blood glucose monitoring
Blood glucose diary
Continuous glucose monitoring sensors
Blood ketone testing
HbA1C
47
Benefits of continuous glucose monitoring sensors
Control insulin delivered from pump
| Allows detection of asymptomatic episodes of nocturnal hypoglycaemia, times of poor control during the day
48
when do you need to do blood ketone testing
Mandatory during illness or poor control
49
Diet changes in T1DM
High complex carbohydrate and modest fat content
High fibre intake - sustained release of glucose
Avoid refined carbohydrates - rapid swings of glucose
Carbohydrate counting - to calculate insulin requirements for meal
50
Clinical features of hypoglycaemia in T1DM
```
Hunger
Tummy ache
Sweating
Feeling faint, dizzy, wobbling of legs
Pallor
Irritability
Seizures
Coma
```
Loss of awareness of symptoms with frequent hypoglycaemia
51
Management of hypoglycaemic episode in T1DM
Glucose tablets / sugary drink
Oral glucose gels - If uncooperative
Glucagon injection - if severe w reduced level of consciousness
Give carbohydrate rich foods after treatment
52
Investigations for DKA
```
Blood glucose - >11
Blood ketones - >3
U+E, creatinine - dehydration
Blood gas - pH <7.3 or bicarbonate <15
Blood and urine culture - precipitating event
Cardiac monitor - Hypokalaemia
Weight
```
53
Management of DKA
1. Fluids:
- initial resuscitation
- gradual fluid replacement over 48hrs (risk of cerebral oedema)
- 0.9% NaCl w 40mmol KCl for first 12hrs + 5% glucose once <14mmol, 0.45% NaCl W 40mmol KCl for next 12hrs
- monitor blood glucose hourly, blood ketones 2 hrly, U+E and ABG 4 hrly
2. Insulin:
- IV infusion 0.1u/kg/Hr
3. Potassium:
- falls w insulin treatment and rehydration
- Start K+ replacement w start of maintenance fluids
- continuous cardiac monitoring, 4 hrly plasma K+ measurements
4. Acidosis: avoid bicarbonate replacement, tx w fluid and insulin
5. Re-establish oral fluids, SC insulin, normal diet
6. Identify and treat underlying cause
54
Aims of long term management for DM
Normal growth and development
Maintaining normal home and school life
Good diabetes control
Encouraging children to become self-reliant with adult supervision until they can take responsibility
Anticipating and minimising hypoglycaemia
Maintain HbA1c <48 mmol
55
Why is it important to monitor HbA1C
Levels above 48mmol/L increases risk of long term complications exponentially
56
Assessment of diabetes
Episodes of hypoglycaemia, DKA, hospital admission
Is there still Awareness of hypoglycaemia
Absence from school
Interference with normal life
HbA1c
Blood glucose diary
Insulin regimen
Injection sites for lipohypertrophy or lipoatrophy
Diet
57
How to monitor for development of complications in DM
Height, weight and BMI - at each visit
BP - HTN
Microalbuminuria - annually from 12 years
Pulses and sensation - circulation
Retinal photography - annually from 12 years
Feet - annually
Coeliac and thyroid disease - screen at diagnosis, screen for thyroid annually and coeliac if symptomatic
Annual flu vaccination
58
What are problems with long term diabetes control
Eating too many sugary foods without insulin
Infrequent unreliable glucose testing - ‘perfect’ results
Illnesses - variable required dose of insulin
Exercise
Eating disorders
Family disruption
Inadequate family support, understanding, motivation
59
Influence of puberty on diabetes
Biological - In pubertal growth spurt, oestrogen, testosterone, growth hormone and insulin-like growth factors cause insulin resistance
Thus increase in insulin requirement
Psychological - concrete and abstract thinking about long term effects of diabetic control —> focus on immediate effects of good diabetes control
60
Influence of diabetes on adolescents
Biological - grow and pubertal delay, obesity if insulin not reduced towards end of puberty
Psychological - reduced self esteem
Social - increased risk from smoking, alcohol, drugs
61
Measures to manage diabetes in adolescents
Focus on immediate benefits of good diabetes control - short term goals suggested by themselves
Communicate enthusiastically their efforts to improve diabetes control
United team approach
Peer group support
62
What are causes of SGA without catch up
```
First trimester:
TORCH infections
Maternal PKU
Fetal alcohol syndrome
Recreational drug abuse
```
Second trimester:
Pre eclampsia
Diabetes Mellitus
Neonatal:
Cows milk allergy
GORD
63
Causes of tall stature
Familial - most common
Secondary endocrine:
Congenital adrenal hyperplasia - excess steroids
Precocious puberty - excess sex hormones
Hyperthyroidism
True gigantism - excess GH
Syndromes:
Long legged - Klinefelter, Marfan, Homocystinuria
Sotos Syndrome
Excessive growth at birth:
Maternal diabetes
Primary hyperinsulinism
Beckwith Syndrome
64
What age do fontanelles close
Posterior - 8 weeks
| Anterior - 12-18 months
65
When do most head growth occur
First two years
| 80% head growth by 5 years
66
What does increase in head circumference across centile lines mean
Normal in first few months
| Rise in ICP
67
Define microcephaly
Head circumference below 2nd centile
68
Causes of microcephaly
Familial
Congenital infection
Autosomal recessive condition
Acquired after insult to developing brain - perinatal hypoxia, hypoglycaemia, meningitis
69
Define microcephaly
Head circumference above 98th centile
70
Define macrocephaly
Head circumference above 98th centile
71
Causes of macrocephaly
Tall stature
Familial
Raised ICP - subdural haematoma, tumour, neurofibromatosis
Sotos Syndrome (cerebral gigantism)
CNS storage disorders - Mucopolysaccharidosis
72
Investigations for increase in head circumference across centile lines
Cranial uss - If anterior fontanelle open
| CT/MRI
73
Causes of skull asymmetry
Plagiocephaly - positional moulding
| Craniosyntosis
74
What causes plagiocephaly
Infants lying on their back
Hypotonia
Preterm infants
75
How to differentiate plagiocephaly from craniosyntosis
Both: paralellogram shaped head, frontal protuberance
Plagiocephaly: all sutures open, ear displaced anteriorly, flattening at back of skull
Craniosyntosis: fusion of cranial sutures, ear displaced posteriorlyn
76
What is craniosyntosis
Premature fusion of cranial sutures, leading to distortion of head shape
77
Types of craniosyntosis
Localised:
Sagittal - long narrow skull
Coronal - asymmetrical skull
Lambdoid - flattening of skull
Generalised - microcephaly
78
Causes of generalised craniosyntosis
Genetic syndromes:
Crouzon Syndrome - exophtalmos
Apert Syndrome - syndactyly
79
Investigations for asymmetrical head
Palpable ridge
Skull x Ray
Cranial ct
(For fused sutures)
80
What are female stages of puberty
Breast development - starts bw 8.5-12.5
Pubic hair growth, Rapid height growth - occurs after breast development
Menarche - occurs 2.5 years after start of puberty, signals growth coming to an end with 5cm height gain remaining
81
What are Male stages of puberty
Testicular enlargement - measured using orchidometer, first sign of puberty
Pubic hair growth - follows testicular enlargement, 10-14 years
Rapid height growth - 18 months after first sign of puberty, occurs much later and greater magnitude than females
82
Age for premature sexual development
Girls - 8
| Males - 9
83
Types of premature sexual development
Precocious puberty
Premature breast development
Premature pubic hair development
Isolated premature menarche
84
Types of precocious puberty
Gonadotrophin dependent - central/true; due to premature activation of HPG axis, with normal sequence of pubertal development and high LH/FSH Levels
Gonadotrophin independent - pseudo/false; due to excess sex steroids, with abnormal sequence of pubertal development and low LH/FSH Levels
85
Causes of precocious puberty in females
Gonadotrophin dependent:
Idiopathic/familial - most common
Pituitary adenoma
Gonadotrophin independent:
Congenital adrenal hyperplasia
Adrenal tumours
—> pubic hair/adult body odour/acne/virilization of genitalia before breast development
86
Why is gonadotrophin dependent PP commonly familial/idiopathic in females but likely pathological in males
Ovaries sensitive to secretions of gonadotrophins from pituitary gland
87
How can you distinguish clinically bw different causes of precocious puberty in males
Bilateral enlargement of testes - gonadotrophin dependent (volume >4ml)
Prepubertal testes - gonadotrophin independent
Unilateral enlarged testes - gonadal tumour
88
Causes of precocious puberty
Gonadotrophin dependent:
Idiopathic/familial
CNS abnormalities - congenital (hydrocephalus), acquired (infection, post irradiation, brain injury), tumours
Hypothyroidism
```
gonadotrophin independent:
Adrenal - tumour, congenital adrenal hyperplasia
Ovarian tumour (granulosa cell)
Testicular tumour (Leydig cell)
Exogenous steroids
```
89
Management of precocious puberty
Gonadotrophin-releasing hormone analogue - to delay onset of menarche
Medroxyprogesterone acetate, ketoconazole - for gonadotrophin independent pp to inhibit sex steroids
90
Clinical features of premature breast development (thelarche)
6 month - 2 year old
Asymmetrical, not beyond stage 3 (juvenile smooth contour)
Absence of pubic hair and significant growth spurt
Self-limiting
91
What is premature pubarche
Development of pubic hair before <8 in female and <9 with no other signs of sexual development
92
Pathophysiology of premature pubarche
Accentuation of normal maturation of androgen production by adrenal gland
93
Clinical features of premature pubarche and pathological pubarche
In Asian/black
Slight increase in growth rate and bone age
Self limiting
Pathological - aggressive virilisation
94
Investigations for premature pubarche
Urinalysis steroid profile
Androgens in blood
X Ray left hand and wrist - Bone age
95
Define delayed puberty
Absence of pubertal development by 14 in girls and 15 in boys
96
Causes of delayed puberty
Constitutional delay of growth and puberty/familial
Hypogonadotrophic hypogonadism:
Systemic disease - CF, severe asthma, Crohn’s, organ failure, starvation, excess physical training, anorexia nervosa
HP distorder - pituitary dysfunction, isolated gonadotrophin deficiency, intracranial tumour, Kallmann Syndrome (LH deficiency)
Acquired hypothyroidism
Hypergonadotrophic hypogonadism:
Chromosomal abnormalities - Klinefelter, Turner
Steroid hormone enzyme deficiencies
Acquired gonadal damage - surgery, chemotherapy, trauma, torsion, autoimmune
97
Why is delayed puberty more common in boys
Relative insensitivity of testes to gonadotrophin
Thus more common in boys
But more likely pathological in girls
98
Management of delayed puberty in boys
Assessment - Pubertal staging (testicular volume)
Reassurance
Oxandrolone - androgenic steroid
IM testosterone
99
Investigations for delayed puberty in girls
Karyotyping
TFT
Sex steroid hormones
100
Clinical value of hypoglycaemia
Plasma glucose <2.6mmol/L
101
Why is hypoglycaemia common in infants
High energy requirements and poor glucose reserves (from gluconeogenesis + glycogenolysis)
Thus should not be fasted for >4 hours
102
What are the neurological consequences of hypoglycaemia in childhood
Epilepsy
Severe learning difficulties
Microcephaly
- period of most rapid brain growth
103
Causes of hypoglycaemia in childhood
Fasting:
1. Insulin excess
- insulin therapy in DM
- persistent hypoglycaemic hyperinsulinism If infancy
- autoimmune
2. Without insulin excess
- ketotic hypoglycaemia of childhood
- hormonal deficiency: GH, ACTH, Addisons
- liver disease
Non fasting
- maternal diabetes
- fructose intolerance
- galactosaemia
104
What is ketotic hypoglycaemia
When children readily become hypoglycaemic after short period of starvation due to limited reserves for gluconeogenesis
105
What is persistent hypoglycaemic hyperinsulinism of infancy
Genetic mutations leading to dysregulation of insulin release by beta islet cells
Causes persistent neonatal hypoglycaemia
107
Investigations for hypoglycaemia
If cause unknown, collect blood + first available urine
Laboratory blood glucose
GH, IGF1, cortisol, insulin, C-peptide, fatty acids, ketones, glycerol, lactate, amino acids
First urine after hypoglycaemia - organic acids
108
Physiological changes in thyroid hormone levels after birth
Fetal period: synthesis of reverse T3 - inactive
| After birth: surge in TSH, rise in T3 + T4
109
Causes of congenital hypothyroidism
Thyroid aplasia
Ectopic thyroid gland
Dysmorphogenesis
110
What is the screening test for congenital hypothyroidism and why is it needed
Day 5 Serum TSH (Guthrie test)
Common
Preventable cause of severe learning difficulties
111
Clinical features of congenital hypothyroidism
Prolonged jaundice - thyroxine for bilirubin metabolism
Neonatal hypoglycaemia
Signs of hypothyroidism - Constipation, Cold intolerance, dry skin, Delayed development, Coarse facies, Large tongue, Hoarse cry, Goitre
112
Management of congenital hypothyroidism
Thyroxine
| Started before 2 weeks of life - prevent cretinism
116
When should you check blood glucose in children
Becomes septic/seriously ill - ABC DEFG
Prolonged seizure
Altered state of consciousness
117
Cause of acquired hypothyroidism
Autoimmune thyroiditis
- presence of antithyroid peroxidase antibodies (TPO)
- Hashimoto’s disease
- initial transient hyperthyroid phase: lymphocytic destruction and release of preformed hormones
118
Clinical features of acquired hypothyroidism
```
Females
Short stature
Delayed puberty/amenorrhoea
Learning difficulties
Deterioration in school work
Initial thyrotoxic phase - tremulous
Hypothyroidism - cold intolerance, dry skin, constipation, obesity, bradycardia, thin dry hair, slow reflexes, poor concentration
```
119
Investigations for autoimmune hypothyroidism
TSH
Serum free T3 t4
TPO - positive (confirm autoimmunity)
TRAb - negative (TSH receptor antibodies, rule out Graves’ disease)
120
Causes of hypopituitarism
Congenital:
pituitary hypoplasia, aplasia
midline defects
Acquired:
Tumours - craniopharyngioma
Irradiation
Infection - meningitis
121
Clinical features of congenital hypopituitarism
Short stature
Prolonged neonatal jaundice - hypothyroidism
Neonatal hypoglycaemia - hypothyroidism
Undervirilisation of boys - micropenis
122
Why do you get undervirilisation in boys from hypopituitarism
Virilisation of external genitalia requires hormones thus functioning pituitary
123
Indications for growth hormone therapy
```
Growth hormone deficiency
Turner syndrome
Prader Willi Syndrome
Chronic renal insufficiency
SGA without catch up at 4 years old
Short stature homebox-containing gene (SHOX) deficiency
```
