Endo Flashcards
1
Q
What is congenital adrenal hyperplasia (CAH)?
A
A group of autosomal recessive disorders caused by deficiencies in adrenal steroid synthesis enzymes.
Produce too little cortisol and/or aldosterone
2
Q
What are the causes of congenital adrenal hyperplasia?
A
21-hydroxylase deficiency (90%)
Also = 11-b hydroxylase and 17-hydroxylase deficiency
3
Q
What is the pathophysiology of congenital adrenal hyperplasia?
A
Low corticosteroids > anterior pituitary secretes high levels of ACTH > adrenal hyperplasia > increased production of adrenal androgens
- LOW corticosteroids, HIGH androgens
4
Q
What are the S/S of congenital adrenal hyperplasia?
A
> More obvious in girls
> Severity of sx depends on gene affected
Virilisation:
- Female infants = clitoromegaly, fusion of labia
- Male infants = enlarged penis, scrotum pigmented (much harder to see)
- Tall stature
- Muscular build
- Deepened voice
- Adult body odour
- Early puberty / pubic hair / increased body hair
- Acne
- Irregular periods
5
Q
What are the investigations for congenital adrenal hyperplasia?
A
Initial (ambiguous genitalia, no external gonads)
- USS > examine internal genitalia
Confirmatory
- Raised plasma 17a-hydroxyprogesterone
- ACTH stimulation test - significant increase in 17-OHP
FBC, U&Es, BM, BG
- Salt-losing crisis > low Na, high K
- Metabolic acidosis > low bicarb
- Hypoglycaemia > from low cortisol
Other
- Karyotyping
- Genetic testing
- Antenatal testing - CVS/AC
- High urea (dehydrated)
6
Q
What is the management for congenital adrenal hyperplasia?
A
Medical
- Life-long glucocorticoids (hydrocortisone)
- Growth hormone
- +/- mineralocorticoids
- +/- NaCl supplementation prn
- Additional hormone replacement at times of illness or surgery
Surgical
- Genital surgery if required (delayed until after puberty)
Monitoring
- Growth
- Skeletal maturity
- Plasma androgens and 17a-hydroxyprogesterone levels
7
Q
What is diabetes?
A
Chronic metabolic disorder characterised by hyperglycaemia secondary to absolute or relative deficiency of insulin secretion
8
Q
What are the RFs for diabetes?
A
- Strong genetic influence
- Autoimmune (80% have islet cell antibodies)
- Environmental (mumps, rubella, coxsackie B4)
- Associations = HLA DR-3, HLA-DR4, other autoimmune conditions, viral infections in pregnancy
9
Q
What are the types of diabetes?
A
Type 1
- Destruction of pancreatic beta-1 cells
- 96% of DM children
Type 2
- Insulin resistance
- Usually in older children and obesity-related
10
Q
What are the investigations for diabetes?
A
Urine dip = Glucose, nitrites, leucocytes, protein, ketones
Bloods = Glucose (fasting or OGTT)
11
Q
What is the diagnostic criteria for diabetes?
A
Symptomatic + fasting glucose >=7
or
Symptomatic + random glucose >=11 (after 75g OGTT)
or
Asymptomatic + ^^ on 2 separate occasions
(HbA1c >6.5% / 48)
12
Q
What are the RFs for neonatal hypoglycaemia?
A
· IUGR
· Maternal DM
· Premature
· Hypothermia
· Neonatal sepsis
· Inborn errors of metabolism
· Labetalol (pre-eclampsia)
13
Q
What are the early S/S of DM?
A
‘Classical triad’
- Polydipsia
- Polyuria
- WL
Less common:
- Secondary enuresis
- Skin sepsis
- Candida (+other recurrent infections)
Type-2 specific:
- Acanthosis nigricans
- Skin tags
- PCOS
14
Q
What are the S/S of DKA?
A
LATE SIGNS / DKA
- Abdominal pain
- Vomiting
- Dehydration
- Acetone breath
- Kussmaul breathing (rapid deep breathing)
- Drowsiness progressing to coma
- Hypovolaemic shock
15
Q
What are the S/S of neonatal hypoglycaemia?
A
May be asymptomatic
- Jittery
- Irritable
- Tachypnoea
- Pallor
- Poor feeding/sucking
- Weak cry
- Drowsy
- Hypotonia
- Seizures
- Apnoea
- Hypothermia
16
Q
What is the management of T1D?
A
Insulin therapy:
1st line = multiple daily injection basal-bolus
- Injections of short-acting insulin before meals, with 1 or more separate daily injections of intermediate acting or long-acting insulin analogue
2nd line = continuous SC insulin infusion (insulin pump)
- Programmable pump / insulin storage device that gives regular or continuous amounts of insulin (usually rapid acting or short acting)
Blood glucose monitoring:
- At least 5 capillary blood glucose per day
- Fasting = 4-7, after meals = 5-9, driving = >5
Ongoing real-time continuous monitoring with alarms for children with:
- Frequent severe hypoglycaemia
- Impaired hypoglycaemic awareness
- Inability to recognise / relay sx of hypoglycaemia (i.e. cognitive disability)
Healthy diet and exercise
- Carbohydrate counting education (DAFNE)
- 5 fruit and veg per day
- Regular exercise (with insulin adjustment)
Psychological and Social Issues
- Offer ongoing access to mental health services
17
Q
What advice would you give regarding the management of diabetes?
A
Educational programme:
- Long-acting = Glargine, Detemir
- Short-acting = Lispro, Glulisine, Aspart
- Method = gently pinch skin, inject at 45-degree angle
- Rotate sites frequently to avoid lipohypertrophy (antero-lateral thigh, buttocks, abdomen)
‘Sick-day rules’
- Explain the symptoms of DKA: N/V, abdominal pain, hyperventilation, dehydration, reduced consciousness
- Change insulin dose
- Offer blood ketone testing strips and a meter and advise testing for ketonaemia if they are ill or hyperglycaemic
Also
- Recognition and tx of hypoglycaemia
- Advise always carrying an immediate source of fast-acting glucose and blood glucose monitoring equipment (include parents + school nurses)
- NOTE: alcohol is a risk factor for hypoglycaemia (they should eat carbohydrates before and after drinking)
18
Q
What must be monitored in patients with diabetes?
A
- Annual monitoring from 12yrs for diabetic retinopathy, nephropathy, HTN
- HbA1c checked >4x per year
19
Q
What is the management of neonatal hypoglycaemia?
A
Asymptomatic:
- Encourage normal feeding (breast or bottle)
- Monitor blood glucose
Symptomatic or very low blood glucose:
- Admit to the neonatal unit
- intravenous infusion of 10% dextrose
20
Q
What is the management of hypoglycaemia in an older child?
A
Mild/moderate:
- Give fast-acting glucose by mouth (usually liquid carbohydrate e.g. Lucozade)
- May need to be given in small amounts if vomiting
- Recheck blood glucose within 15 mins and repeat fast-acting glucose if hypoglycaemia persists
- As symptoms improve, give oral complex long-acting carbohydrate to maintain blood glucose levels
Severe:
- Treat in hospital
- IV 10% glucose
- Once symptoms improve, give oral complex long-acting carbohydrate
If NOT in hospital
- IM glucagon or concentrated oral glucose solution (e.g. glucogel)
- Seek medical help if blood glucose remains low after 10 mins
21
Q
What is the management of T2D?
A
(1) Diet and exercise
(2) Oral monotherapy
1st line = Metformin
(3) Oral combination therapy
2nd line = sulphonylurea (Increases insulin secretion)
- For non-obese
- Glipalamide, Chlorpropamide, Tolbutamide
3rd line = glucosidase inhibitor > post-prandial hyperglycaemia
- Acarbose
(4) Oral and injectable incretin mimetics
(5) Oral and insulin
(6) Insulin
22
Q
What are the S/S of HHS?
A
- Weakness
- Leg cramps
- Visual disturbances
- N&V (less than in DKA)
- Massive dehydration e.g. dry mucus membranes, confusion, lethargy
- Focal neurological sx (seizures, coma)
23
Q
What are the investigations for HHS?
A
Bloods = no hyperketonaemia, no acidosis
Serum osmolarity will be >320
24
Q
What is DKA?
A
Hyperglycaemia, ketonuria, acidosis
BM > 11.1
Ketones > 3
pH < 7.3
25
What is the classification for DKA?
**Mild DKA:**
- pH<7.3
- 5% fluid deficit
**Moderate DKA:**
- pH<7.2
- 7% fluid deficit
**Severe DKA:**
- pH<7.1
- 10% fluid deficit
26
What are the causes of DKA?
> Anything that raises bodies need for insulin (lack of insulin = DKA)
- Discontinuation / not enough insulin (i.e. anorexic T1DM that wants to lose weight)
- Drugs (steroids, thiazides, SGLT-2 inhibitors)
- Physiological stress (pregnancy, trauma, surgery)
27
What are the investigations for DKA?
- Basic obs and full examination (check hydration status)
- Urine dip - glucose, ketones
- Blood gas - acidotic
- Blood glucose - high
- Blood ketones - high
28
What is the management of DKA?
**EMERGENCY, ABCDE approach**
- IV 0.9% saline bolus for fluid resuscitation (10mk/kg - lower rate due to risk of cerebral oedema)
- Maintenance fluids with 40mmol/L KCl (unless renal failure)
- IV insulin (1hr after fluids)
- Once glucose <14, switch to IV saline and 5% dextrose
>Monitor blood glucose, vital signs, fluid balance, and LOC every 1hr or every 30 mins if severe DKA / <2yrs
>Continuous ECG to monitor for hypokalaemia
>Oral fluids and SC insulin can be used if the child is ALERT, not nauseated or vomiting, and not clinically dehydrated
29
What are the complications of DKA treatment?
**Cerebral oedema:**
- S/S > headache, agitation, irritability, Cushing’s triad, high ICP signs
- Mx > mannitol or hypertonic saline, restrict fluid intake
**Hypokalaemia (<3mm/L):**
- Mx > stop insulin temporarily
**Also:**
- Aspiration pneumonia
- Inadequate resuscitation
30
What is delayed puberty?
Lack of any pubertal signs (secondary sexual characteristics, accelerated linear growth, increase in secretion of sex hormones, maturation of gonads, potential for reproduction)
- **13yrs in girls**
- **14yrs in boys**
31
When do you refer for faltering growth?
If >=75th centile, refer once centile drops >=3
If 25-75th centile, refer once centile drops >=2
If <25th centile, refer once centile drops >=1
32
What are the causes of delayed puberty?
**Functional (most commonly):**
- Constitutional delay of growth and puberty (CDGP): Low bone age, no puberty signs, no organic causes, FHx - most common cause in boys
- Chronic disease / malnutrition
- Psychiatric: Excessive exercise, depression, AN
**Hypogonadotropic (low LH/FSH) hypogonadism**
- Hypothalamo-pituitary disorders: Panhypopituitarism, intercranial tumours
- Kallmann’s syndrome (LHRH deficiency and anosmia)
- Prader-Willi
- Hypothyroidism
**Hypergonadotropic (high LH/FSH) hypogonadism**
- Congenital: Cryptorchidism, Klinefelter’s, Turner’s
- Acquired: Testicular torsion, chemo, infection, trauma, autoimmune
33
What are the investigations for delayed puberty?
**Initial examination:**
- Charting (height, weight, mid-parental height)
- Note dysmorphic features
- Prader’s orchidometer for boys / Tanner staging for girls
**Bloods:**
- Gonadotrophin-dependant vs independent > LH and FSH levels
- TSH, prolactin, testosterone
**Imaging:**
- Bone age (from wrist XR)
- MRI brain
**+Karyotyping**
34
What is the management for delayed puberty?
**CDGP > most don’t need tx, great prognosis:**
- 1st line = reassure and offer observation
- 2nd line = short course of sex hormone therapy
- Boys > IM testosterone (every 6wks for 6m)
- Girls > transdermal oestrogen (6m) then cyclical progesterone once established
**Primary testicular / ovarian failure:**
- Pubertal induction > regular hormone replacement
- Boys > regular testosterone injections
- Girls > oestrogen replacement (gradual)
**+Address psychological concerns**
35
What is precocious puberty?
**Early normal puberty:**
- Girls = 8< age >=10
- Boys = 9< age >=12
**Precocious puberty:**
- Girls = age <8
- Boys = age <9
36
How is puberty determined?
**GIRLS = Tanner’s 5 breast development stages:**
- Stage 1 = flat
- Stage 2 = buds appear, breast and nipple raised, fat forms, areola enlarged
- Stage 3 = breasts grow larger (conical > rounder shape)
- Stage 4 = nipple and areola raise above the mound, menstruation within 2yrs of this stage
- Stage 5 = mature adult breast is rounded, and only nipple is raised
**BOYS = Prader’s orchidometer (testicular development)**
37
What are the causes of precocious puberty?
**Gonadotropin-Dependant Precocious Puberty (GDPP)**
*Due to premature activation of HPG axis - LH/FSH raised*
- Idiopathic
- CNS abnormalities (tumours, trauma, infection, cyst)
**Gonadotrophin-Independent Precocious Puberty (GIPP)**
*Due to excess sex hormones - LH/FSH low*
- Ovarian / testicular / adrenal cyst or tumour
- Dysfunction of other glands: Adrenal (CAH, Cushing’s), thyroid
- b-hCG-secreting tumour of liver
- McCune-Albright syndrome (multiple endocrinopathy of thyrotoxicosis, Crushing’s, acromegaly)
- Exogenous hormones: COCP, testosterone gels
**Benign isolated precocious puberty (self-limiting)**
*Premature thelarche (isolated breast development before 8yrs, usually 6m-2yrs)*
- Spontaneously regresses
- Absence of other pubertal signs
- Normal USS of uterus
- Normal growth
*Premature pubarche/adrenarche (isolated pubic hair development before 8yrs (F) or 9yrs (M))*
- Due to early adrenal androgen secretion in middle childhood
- More common in Asian or Afro-Caribbean
*Premature menarche (isolated vaginal bleeding before 8yrs)*
38
What are the investigations for precocious puberty?
**GOLD STANDARD = GnRH stimulation test**
- FSH, LH low = GIPP
- FSH, LH high = GDPP
**Also:**
- Tanner Staging / Prader orchidometer
- Wrist XR (non-dominant) for skeletal age
- General hormone profile (basal LH/FSH, serum testosterone and oestrogen)
- Urinary 17-OH progesterone if CAH suspected
- Pelvic USS (rule out gonadal tumours/cysts)
- MRI (intracranial tumours)
39
What does testicular size suggest about the cause of precocious puberty?
- Bilateral enlargement = Gonadotropin release from intracranial lesion (i.e. optical glioma in NF1)
- Unilateral enlargement = gonadal tumour
- Small testes = adrenal cause (tumour or CAH)
40
What is the management of precocious puberty?
*>Refer to paediatric endocrinologist*
**GDPP with no underlying pathology:**
- NO treatment
**GDPP:**
- Referral and treatment of underlying cause
- +GnRH agonist e.g. leuprorelin
- Consider GH
**GIPP:**
- McCune Albright or Testotoxicosis: 1st = ketoconazole
- CAH: Hydrocortisone + GnRH agonist
- Tumours = refer to specialist
- Exogenous oestrogen or androgens = identify and discontinue agent
41
What is skeletal dysplasia?
A group of over 350 disorders leading to various degrees of dwarfism (height < 2 S.D. below the mean)
42
What is Achondroplasia?
Most common skeletal dysplasia / form of dwarfism
- Short stature
- Disproportionally short arms and legs
- Large head, frontal bossing
- Torso is normal length
- +/- hydrocephalus
- Depression of nasal bridge
- Marked lumbar lordosis
- Short, broad hands
- ‘Trident hands’
43
What is Hypochondroplasia?
Milder form of achondroplasia
44
What is osteogenesis imperfecta?
Genetic disorder that affects bone development and causes bones to be brittle and fragile (break easily)
- Short stature
- Blue sclera
- Muscle weakness
- Joint laxity
- Hearing loss
- Breathing problems
7 types.
45
What genetic mutations can cause skeletal dysplasia?
**Mutated FGFR3 (fibroblast growth factor receptor 3):**
- Achondroplasia / hypochondroplasia
- Autosomal dominant
- Causes severe bone shortening through constitutively active receptors
**SHOX (short stature homeobox) gene defects:**
- Turner’s = 1 less SHOX, Klinefelter’s = >2 SHOX genes
- X-linked
- Idiopathic short stature thought to be due to polymorphisms in this gene
46
What is a RF for skeletal dysplasia?
Advancing parental age at conception
47
What must be excluded if there is isolated short stature in a girl?
Must exclude Turner’s (karyotype)
48
What are the investigations for Achondroplasia?
- Usually based on physical characteristics and measurements
- Prenatal: Scans (not apparent until >22wks so may be missed), CVS/AC for mutation
- XR = metaphyseal irregularity (inverted V metaphysis = ‘chevron deformity’), flaring in long bones, late-appearing irregular epiphyses
- Genetic testing for confirmation
49
What is the management of Achondroplasia?
**Condition specific centile charts (final height = 80-150cm), prone to weight gain**
**Regular follow-up (complications)**
- Gross motor skill delay
- Risks from hydrocephalus
- Kyphosis
- Obesity
- Early osteoarthritis
- ENT issues
50
What is the management of osteogenesis imperfecta?
Bisphosphonates
51
What are the causes of congenital hypothyroidism?
**Thyroid gland defects (75%)**
- Missing, ectopic/poorly developed
- Not inherited
**Disorder of thyroid hormone metabolism (10%)**
- TSH unresponsive / defects in TG structure
- Inherited
**Hypothalamic or pituitary dysfunction (5%)**
- Tumours, ischaemic damage, congenital defects
**Transient hypothyroidism (10%)**
- Maternal medication (carbimazole), maternal Abs (e.g. Hashimoto’s)
52
What are the S/S of congenital hypothyroidism?
- Feeding difficulties
- Lethargy
- Constipation
- Large fontanelle
- Myxoedema
- Nasal obstruction
- Low temperature
- Jaundice
- Hypotonia
- Pleural effusion
- Short stature
- Oedema
- +/- goitre, +/- congenital defects
Unique sx > coarse features, macroglossia, umbilical hernia
53
What are the investigations for congenital hypothyroidism?
- High TSH
- Low T4
- Measure thyroid autoantibodies +/- US or radionucleotide scan
54
What is the management of congenital hypothyroidism?
- Levothyroxine OD > titrate dose to TFTs + regular monitoring
- Monitor growth, milestones, development
55
What is the main cause of acquired hypothyroidism?
Hashimoto’s autoimmune thyroiditis
56
What syndromes are associated with Hashimoto's?
Down’s Syndrome, Turner’s
57
What are the S/S for Hashimoto's?
Growth failure, excess weight gain, short stature
58
What are the investigations for Hashimoto's?
anti-TPO and anti-Tg antibodies
59
What is the main complication of Hashimoto's?
Associated with the development of MALT lymphoma
60
What are the S/S of hyperthyroidism?
**Foetus** > high CTG trace and foetal goitre on USS
**Newborn (<2wks)** > irritability, WL, tachycardia, HF, diarrhoea, exophthalmos
61
What is the management of hyperthyroidism?
**Carbimazole or propylthiouracil**
- Both associated with neutropenia
- Safety net to seek medical attention / blood count if sore throat or fever while on tx
**Also:**
- Beta-blockers may be considered for symptomatic relief
- Medical treatment is usually given for around 2 years
- Other options = radioiodine tx, surgery
NOTE: neonatal hyperthyroidism may occur due to the transplacental transfer of TSIs
62
What is the management of hypocalcaemia?
**MANAGEMENT of Acute Symptomatic Hypocalcaemia**
- IV calcium gluconate
**MANAGEMENT of Chronic Hypocalcaemia**
- Oral calcium + high dose vitamin D analogues
IMPORTANT: avoid hypercalciuria because it can lead to nephrocalcinosis so urinary excretion should be monitored
63
What is the management of severe hypercalcaemia?
Rehydration
Diuretics
Bisphosphonates
64
How is obesity classified?
Severely obese = 99th centile
Obese = >95th centile
Overweight = 85-94th centile
65
What are RFs for obesity?
Low socioeconomic status
Poor diet
Genetics
Little exercise
66
What are the investigations for obesity?
- Growth chart plotting > BMI percentile chart, adjusted to age and gender
- Nutritional assessment > BMI, triceps skinfold thickness
- Bloods > cholesterol, triglyceride levels, endocrine assays for conditions e.g. adrenal disease
- Urine > glucosuria (T2DM)
- Radiology > USS/CT/MRI head for specific conditions / syndromes
67
What is the management for obesity?
*>Exclude underlying medical condition*
**Conservative:**
- Self-esteem and confidence building (early intervention is key)
- Address lifestyle (food diary > address where they eat too much)
**Therapeutic aims:**
- Reduce excess weight whilst not compromising growth needs
- Dietary counselling with vitamin and micronutrient supplementation
- Behaviour modification
- Stepwise physical activity programme
- Strong support from child and family
- Fat intake <30% of total calories
**Surgical:** Not recommended in young people
68
What are the complications of obesity?
- Psychosocial > bullying, discrimination, isolation
- Growth > advanced bone age, increased height, early menarche
- Resp > sleep apnoea, Pickwickian syndrome
- Ortho > slipped capital femoral epiphysis, Blount disease
- Metabolic > insulin resistance
- Hepatobiliary > hepatis steatosis, gallstones
69
What is rickets?
Impaired skeletal growth through inadequate mineralisation of bone laid down at the epiphyseal growth plates
70
What are the causes of rickets?
**Calcium deficiency:**
- Dietary
- Malabsorption
**Vitamin D defects:**
- Deficiency > diet, malabsorption, lack of sunlight, iatrogenic (drug induced > phenytoin therapy)
- Metabolic > 1-alpha hydroxylase deficiency, liver disease, renal disease
- Defect in action > HVDRR (hereditary vitamin D receptor resistant) rickets
**Phosphate deficiency:**
- Reduced intake
- Renal tubular phosphate loss > hypophosphatemic rickets (X-linked, AR, AD)
- Acquired hypophosphatemic rickets > Fanconi syndrome, renal tubular acidosis, nephrotoxic drugs
71
What are the S/S of rickets?
- Growth delay or arrest
- Bone pain, fracture
- Swelling wrists/costochondral junctions (rickets rosary)
- Bowed long bones
- Frontal bossing
72
What are the investigations for rickets?
**X-ray**
- Thickened and widened epiphysis / joint widening
- Cupping metaphysis
- Bowing diaphysis
**Biochemical:**
- Reduced Ca and phosphate
- Raised ALP
73
What is the management of rickets?
**Prevention:**
- Infants receive daily Vit D in formula / multivitamin, pregnant/lactating women receive 400iu/day
**Dietary sources:**
- Fatty fish (herring, mackerel, salmon, tuna), egg yolk, fortified foods, shop bought milk, cereals
**Correct low vit D levels with increased intake:**
- Ca supplements
- Oral vit D2 (ergocalciferol) or oral vit D3 (cholecalciferol)
Periodic measurement of serum Ca, phosphate, ALP, urine Ca : creatinine ratio
74
What is a salt losing crisis ?
**Life-threatening condition that occurs when the adrenals do not produce enough aldosterone**
- Often first sign in boys > 1-3wks of age
- Can cause dangerous drop in BP and electrolyte imbalances
- Vomiting, WL, hypotonia, dehydration, low BP, irregular HR
75
What is the management of an acute salt losing crisis?
- IV saline
- IV hydrocortisone
- IV dextrose
