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Paediatrics STG > Paediatric Endocrinology > Flashcards

Paediatric Endocrinology Flashcards

1
Q

T1DM

A

Destruction of pancreatic B-cells by Autoimmune process

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2
Q

T2DM

A

Insulin resistance followed by B-cell failure; Usually older children, associated with Obesity and FMHx; More common Afro-Caribbean and Asian populations

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3
Q

Other forms of diabetes

A

MODY (Genetic defects in B-cell function; Strong FMHx), Drugs (Corticosteroids), Pancreatic Insufficiency (CF, Haemochromatosis), Endocrine Disorders (Cushing’s), Genetic Disorders (Down, Turner Syndromes), Neonatal and Gestational Diabetes

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4
Q

Pathophysiology of T1DM

A

Believed to be interplay of Genetics, Environment and Trigger (e.g. Molecular mimicry with B-cell antigen) leading to destruction
o Auto-Ig against Glutamic Acid Decarboxylase, Islet Cell, Insulin
o Associated with Hypothyroidism, Addisons Disease, Coeliac Disease, RA

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5
Q

Presentation of T1DM

A

Peaks in presentation in Spring and Autumn months (? Enteroviral trigger); Children only present with few weeks of Polyuria, Polydipsia and Weight Loss; Secondary Nocturnal Enuresis in younger children

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6
Q

Diagnosing T1DM

A

Diagnosis crucial to prevent DKA; Referral to specialist once diagnosis suspected
o Diagnosis in Symptomatic (Glycosuria, Ketosis) child by marked, raised Random Blood Glucose (>11.1mmol/L)
▪ If in doubt, Fasting Glucose >7mmol/L or HbA1c
o Should be suspected if FMHx, Severely Obese children with signs of Insulin Resistance (Acanthosis Nigricans, Skin Tags, Polycystic Ovarian phenotype)

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7
Q

Management of T1DM

A

DKA requires urgent admission and treatment
• Education – Basic understanding of Diabetes, Injection Technique and Sites, Blood glucose testing for Glucose and Ketones, Health diet (Fruit and Vegetables, Carb counting), Exercise, ‘Sick day rules’ for Insulin, Recognition of Complications

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8
Q

Insulin in T1DM

A

Insulin – In the UK, all Human Insulin; In 100 units/ml concentration
o Human Analogues (Rapid acting e.g. NovoRapid, Humalog, or Long acting e.g. Levemir, Lantus), Short acting Regular Insulin e.g. Actrapid, Intermediate acting e.g. Insulatard, Humulin
o Injection to anterior/lateral thigh, buttocks and abdomen subcutaneously at 45 deg
▪ Rotation of sites to prevent Lipohypertrophy and Lipoatrophy
o Most children either continuous pump, or multiple daily regimen (basal bolus) of rapid before every meal, and long-lasting insulin in late evening or before breakfast
▪ Basal Bolus has better flexibility to relate more closely to intake and exercise
▪ Aim blood glucose 4 – 7 mmol/L before meals; Extra rapid acting insulin at mealtimes; Best glycaemic outcomes and lowers complications

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9
Q

Dietary Control

A

Healthy diet and Matched-insulin doses to Carbohydrates
• High complex carbohydrates, modest fat content (<30% total calories)
• Rich in fibre (sustained release of glucose) rather than refined carbohydrates

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10
Q

Monitoring glycaemic control: Purpose

A

Regular glucose measurement to adjust insulin regimen, understand how lifestyle, food, exercise affects glycaemic control

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11
Q

Monitoring glycaemic control: Target

A

Aim for 4 – 7mmol/L before meals; If change in routine or illness, more testing

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12
Q

Monitoring glycaemic control: Continuous glucose monitoring sensors

A

Useful for unexpected, asymptomatic nocturnal hypoglycaemia, or poor control

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13
Q

Monitoring glycaemic control: Ketone Testing

A

Blood ketone testing mandatory during illness or poor control to detect DKA

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14
Q

Monitoring glycaemic control: HbA1c

A

Overall Diabetes control over previous 6-12/52; Checked four times a year
o Target <48 mmol/mol (6.5%); Related to risk of complications disproportionately
o Misleading if RBC lifespan reduced (Sickle-Cell) or abnormal HbA (e.g. Thalassaemia)

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15
Q

Long term management of Diabetes

A

Aims for normal growth and development, normalcy at home and school, good diabetic control through knowledge and good technique, encouraging self-reliance, minimising hypoglycaemia and maintaining glycaemic control
• Avoid long term complications – Macrovascular (Coronary, CVA, HTN) and Microvascular (Retinopathy, Nephropathy, Neuropathy); Good control delays onset and progression

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16
Q

How is diabetes complicated in children

A

Sugary food intake, Unreliable blood glucose testing and fabricated glycaemic diaries, Illness (raised insulin requirements, partially due to reduced food intake), exercise, eating disorders, family disruption or motivation et

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17
Q

Long term management of Diabetes:School

A

Individualised care plan covers dietary needs, hypoglycaemic management or loss of consciousness; Operation of diabetic control appliances

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18
Q

Diabetes in Puberty

A

Influenced by Biological, Psychological and Social factors; Rapid growth governed by complex hormonal changes, many involving Insulin and Insulin-like Growth Factors
• GH, Oestrogen and Testosterone antagonise Insulin – Increase requirement to 1 unit/kg/day in early childhood, up to 2 units/kg/day
o Especially crucial in morning – Peak of GH secretion overnight
o Insulin dose needs to be reduced during end of puberty; can lead to weight gain
• Glycosuric anorexia – Omission of insulin

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19
Q

Hypoglycaemia Symptoms

A

Most develop symptoms when below 4mmol/L; Highly individual, changes with age
o Hunger, tummy ache, sweatiness, feeling faint/dizzy, wobbly feeling in legs
o Can progress to Seizures and Coma if unmanaged; Can be identified sometimes by pallor, irritability (e.g. change in behaviour)
• Frequent episodes of Hypoglycaemia can lead to loss of awareness

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20
Q

Management of Hypo in Children

A

Early stage management – Easily absorbed glucose (tablets, drinks, buccal gels)
o IM Glucagon injection kit for Severe Hypoglycaemia when child has reduced LOC
• Food should be given subsequently to prevent further Hypos

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21
Q

What can precipitate DKA

A

Infection or other stressors, or neglected Insulin

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22
Q

How does DKA present

A

Presents with Fruity-breath, Vomiting, Dehydration, Abdominal Pain, Acidosis-driven Hyperventilation (Kussmaul), Hypovolaemia Shock, Coma

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23
Q

What will investigation show in DKA presentation

A

Hyperglycaemia, Ketosis, Dehydration (U/Es, Creatinine), Severe Metabolic Acidosis

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24
Q

Management of DKA: Dehydration, Hypovolemia

A

10ml/kg 0.9% saline if in shock;
o Gradual correction over 48hrs after stabilisation to prevent Cerebral Oedema; Replace KCl with saline; monitor fluid balance, blood glucose (hrly), ketones (1-2hrly), U/Es, Acid-base status (2-4hrly) and Neurological state

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25
Q

Management of DKA: Insulin

A

0.1u/kg/hr after IV fluids running for 1hr (Not bolus); Change fluids to 5% glucose when blood glucose falls to 14mmol/L to prevent hypoglycaemia

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26
Q

Management of DKA: Potassium

A

Initial Hyperkalaemia (due to H/K exchange) will fall following Insulin and Rehydration; Potassium replacement once maintenance fluids started; Cardiac monitoring

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27
Q

Management of DKA: Acidosis

A

Avoid bicarbonate unless shock; Acidosis corrects with DKA management

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28
Q

Management of DKA: Other

A
  • IV Insulin infusion should not be stopped until after 1hr after Subcut insulin
  • Identify any underlying infection (DKA can cause neutrophilia but typically afebrile
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29
Q

Importance of thyroxine in foetal development

A

Only small amounts of maternal thyroxine reach foetus; Severe maternal hypothyroidism can affect foetal brain development
o Foetal thyroid produces a largely inactive T3 derivative; After birth, surge in TSH leads to increase in thyroid hormones; Declines to normal adult ranges within week
o Preterm infants may have very low T4 for first few weeks of life; TSH typically normal, additional thyroxine not required

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30
Q

How common is congenital hypothyroidism

A

• Relatively common (1 in 4000); Preventable cause of severe learning disabilities

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31
Q

How is congenital hypothyroidism detected?

A

• Detection as part of Neonatal screening (by Guthrie test detecting raised TSH);

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32
Q

Cause of congenital hypothyroidism

A

Common causes include Thyroid maldescent or Athyrosis, Dyshormonogenesis (Inborn error of Thyroid Hormone synthesis), Iodine Deficiency (Most common cause worldwide, rare in the UK), TSH deficiency (Rare; usually associated with Pituitary Dysfunction; GH, GnRH and ACTH deficiencies accompany)

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33
Q

How is congenital hypothyroidism treated?

A

Treatment with Thyroxine within 2-3/52 age to reduce risk to neurodevelopment; Lifelong oral replacement of Thyroxine titrated to normal growth, TSH and T4 levels

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34
Q

Causes of Acquired Hypothyroidism

A

• Most commonly Autoimmune; Increased risk in Down or Turner Syndrome; Associated with other Autoimmune disorders (Vitiligo, RA, DM, Addison’s)

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35
Q

How does acquired hypothyroidism present?

A

• More common in females; Can present as Growth Failure accompanied with delayed bone age; Goitre is often present; Treat with Thyroxine

36
Q

How often are babies weighed?

A

• Babies weighed at week 1 to assess feeding, then again at 8, 12, 16 and 52 weeks

37
Q

Which babies should be evaluated?

A

• Any child whose weight crosses two centile-spaces, or is below 0.4th centile, or has BMI less than 2nd centile should be evaluated
o If preterm, allow for time during first 1-2yrs of age; some severe IUGR infants remain small but most will exhibit catch-up growth

38
Q

Most common causes of weight faltering

A

• Inadequate Intake of Food is most common cause; often Multifactorial

39
Q

Causes of inadequate food intake

A 
o Feeding problems, Unsuitable feed, Behavioural, Impaired suck/swallow
Inadequate retention 
Malabsorption
Failure to utilise nutrients
Increase requirements
40
Q

Causes of inadequate retention

A

Vomiting, Severe GOR

41
Q

Causes of malabsorption

A

Coeliac, CF, Allergy, Bile issues

42
Q

Causes of failure to utilise nutrients

A

IUGR, Prematurity, Metabolic disorders

43
Q

Causes of increased requirements

A

Thyrotoxicosis, CF, Infection, Congenital Heart Disease

44
Q

Management of Weight Faltering: Dietary History

A

History of milk feeding, Age of weaning, Food now taken, Meal time routine and Behaviour, 3-day Food Diary
o Prematurity, IUGR, Current child behaviour, FMHx, Development, Psychosocial issues

45
Q

Management of Weight Faltering: Signs of Organic Disease

A

Dysmorphic features, Malabsorption (Distention, Thin buttocks, Misery), Chronic Respiratory Disease, Heart Failure, Evidence of Nutritional Deficiencies (Koilonychia, Angular Stomatitis)

46
Q

Management of Weight Faltering: Investigations

A

o FBC and Serum Ferritin to identify IDA; Correcting might lead to improved appetite
o U/Es, LFTs, TFTs, Inflammatory markers, Ferritin, Ig, IgA tTG or EMA, MC+S
o Sweat test, CXR for Cystic Fibrosis

47
Q

Management of Weight Faltering: Health Visitors

A

Mealtime Observation, Food Diary to assess and support feeding and caloric intake; Paediatric Dietitian and SALT if required

48
Q

Management of Weight Faltering: Nursery and Progression

A
  • Nursery placement can relieve stress at home and assist feeding
  • Rise in weight centiles typically occurs 4-8/52 after intervention
49
Q

Management of Weight Faltering: When to admit

A

• If <6/12 age with Severe Growth Faltering, admission for active refeeding and MDT

50
Q

Foetal Growth

A

Fastest period, accounting for 30% of eventual height; Size at birth determined by Maternal size and Placental supply, modulating IGF-2, HPL and Insulin

51
Q

Infantile Phase

A

Characterised by rapid but
decelerating growth rate; 15% of eventual height
o Growth during infancy to 18/12 largely dependent on adequate nutrition and towards genetic height growth pattern
o Good health, normal Thyroid function is necessary

52
Q

Childhood Phase

A

Slow, steady but prolonged period of growth contributing 40% of height
o Pituitary GH secretion to produce IGF-1 at Epiphysis; main determinant of height
o Thyroid hormone, Vit D and steroids affect cartilage cell division and bone growth

53
Q

Puberty Growth

A

Sex hormones, mainly Testosterone and Oestradiol, cause back to lengthen and boost GH secretion
o Adds 15% to final height; Sex steroids also cause Epiphyseal plate fusion, ceasing growth; Early puberty leads to reduction in final height

54
Q

Adrenarche

A

(around 7yrs) – Development of Zona Reticularis; Adrenal Androgens produced

55
Q

Gonadarche

A

(around 8yrs) – Earliest development of Genitals; Sex steroids produced

56
Q

Pubarche

A

(around 12yrs) – First appearance of Pubic hair; Linked to Androgen production

57
Q

Which stage of maturation follows pubarche

A

Menarche and Spermarche

58
Q

Laron Syndrome

A

Defect GH receptors leading to GH insensitivity; High GH but low IGF-1 produced by the Epiphyseal plates and Liver

59
Q

Female Puberty

A

Breast development (Thelarche = Palpable breast disc starting 8.5-12.5yrs), Pubic Hair Growth and Rapid Height Growth (Almost immediately after breast development), Menarche (2.5yrs after the start of puberty; Signals around 5cm of height gain remaining)

60
Q

Male Puberty

A

Testicular enlargement (>4ml volume), Pubic Hair Growth (Usually between 10-14yrs), Rapid Height Growth (About 18/12 after testicular growth to 12-15ml)

61
Q

How can abnormally early or late puberty be assessed?

A

Bone Age (Head and Wrist XR) and Pelvic Ultrasound in females for Uterine size and Endometrial Thickness

62
Q

Precocious Puberty: Categorisation

A

Categorised as Gonadotrophin Dependent (True; Consonant Stage s) or Independent, due to Excess Sex Steroids outside Pituitary gland (False; Dissonant Stages

63
Q

Precocious puberty in females

A

Ovaries are very sensitive to GnRH; Precocious puberty common in girls
o Can be pathological and secondary to Excess Androgens (e.g. CAH, Adrenal tumours); presents as Pubic hair and virilisation before Thelarche
o Gonadotrophic dependent causes such as Pituitary Adenoma
o Ultrasound Ovaries and Uterus

64
Q

Precocious Puberty in males

A

Testes relatively insensitive to GnRH; Gonadotrophin-dependent Precocious Puberty is rare; Important to exclude pathological cause
o Bilateral Testicular enlargement suggests Gonadotrophin dependent; Intracranial tumours or rarely Beta-HCG secretion from Liver Tumours
o No testicular development suggests Gonadotrophin independent causes e.g. Adrenal Tumour, CAH
o Unilateral enlarged testis suggests Testicular tumour

65
Q

Management of Precocious Puberty

A
  • Detection and treatment of underlying pathology – Intracranial MRI, particularly in males
  • Reducing the rate of skeletal maturation and Addressing psychological and behavioural issues
  • GnRH analogues can delay onset of Menarche in Gonadotrophin-dependent PP
  • Sources of Excess Sex Steroids identified; Inhibition of Androgen or Oestrogen production or action can be used (e.g. Cyproterone, Testolactone, Ketoconazole)
66
Q

Delayed Puberty

A

• Absence of Pubertal Development by 14yrs in females, 15yrs in males; More common in males, due to relatively GnRH-insensitive Testes

67
Q

Commonest cause of delayed puberty

A

By far most commonly due to Constitutional delay; Variation of normal timing rather than pathological, due to dieting or excessive physical training
▪ Bone age would also show moderate delay
▪ Eventually, target height will be reached

68
Q

Hypogonadotropic Hypogonadism

A

Systemic disease, Hypothalamo-pituitary

69
Q

Hypergonadotrophic Hypogonadism

A

Klinefelter, Turner, Steroid Hormone enzyme deficiencies, Acquired damage (Postoperative, Chemotherapy, Radiotherapy, Trauma, Testicular torsion, Autoimmune disease

70
Q

How can delayed puberty be assessed in boys?

A

Oral Oxandrolone can be used (weakly androgenic anabolic steroid induces catch-up growth, or low-dose IM Testosterone (induces growth plus secondary sexual characteristics)

71
Q

Delayed puberty in girls

A

Delayed Puberty far less common; need to exclude organic causes
o Turner’s syndrome – Karyotype to diagnose
o Thyroid and Sex steroid deficiencies, Pituitary disorders
o Eating disorders
• Oestradiol can be used to induced puberty in girls

72
Q

Inborn Errors of Metabolism

A

Inborn Errors of Metabolism are disorders of Enzymatic reactions; They are generally separated into disorders of Intoxication, Energy Metabolism, and Complex Organelles

73
Q

Intoxication Disorders

A

Amino-acidopathies (e.g. Homocystinuria), Urea cycle disorders (e.g. Citrullinaemia), Carbohydrate disorders (e.g. Galactosaemia) and Neurotransmitter disorders (e.g. Pyridoxine-dependent seizures)

74
Q

Energy Metabolism Disorders

A

Mitochondrial (e.g. MELAS, MERRF), Fatty acid oxidation disorders (e.g. Carnitine transporter deficiency), Glycogen storage disorders (e.g. McArdle disease)

75
Q

Complex Organelles Disorders

A

Lysosomal Storage Disorders (e.g. Mucopolysaccharidosis), Peroxisomal (Zellweger syndrome)

76
Q

How do inborn errors of metabolism present?

A

Can present variably and many in early childhood; Considering in all children with unexpectedly severe presentation of otherwise common illness, significant Metabolic Acidosis, unexplained Respiratory Alkalosis, Hypoglycaemia, HF or Cardiomegaly, Hepatomegaly, Splenomegaly or Liver Dysfunction, Altered Mental Status, Early Onset Seizures, Dysmorphic features, Developmental Regression or Sudden Unexplained Death

77
Q

What is important to know in history with inborn errors or metabolism

A
  • FHx is crucial; FHx of IEMs, Sudden Death, Epilepsy, Learning Disabilities, Consanguinity
  • IEMs are Inherited and display specific Inheritance pattern; Most commonly AR (although Mitochondrial inheritance, and de novo for few)
  • Infection is a common trigger for IEM presentation; Might confound Metabolic acidosis
78
Q

Investigation of Inborn Errors of Metabolism

A

• Early discussion with specialist centre is vital; If Metabolic Disease not within differential, unlikely to identify through standard investigations
• First line investigations depend on suspected clinical pictures
o E.g. Amino acids and acyl-carnitines for suspected Urea Cycle Disorders, Amino-acidopathies or Organic Acidaemia; Ammonia for Urea Cycle Disorders, Beutler screening test for Galactosaemia, etc

79
Q

Management of Inborn Errors of Metabolism: Medical Intervention

A

Symptom management, Specific therapies, Enzyme replacement therapy; Bone marrow transplantation for a specific few disorders

80
Q

Management of Inborn Errors of Metabolism: Dietary Manipulation

A

Supplying a deficient product, Prevention of Accumulation of toxic substrate (e.g. by dietary restrictions), Prevention of Catabolism (e.g. through replacing diet with Glucose in times of increased Catabolism) or Ketogenic Diet

81
Q

Newborn Screening

A

Aims to detect treatable conditions prior to presentation to improve outcome; Offered to newborns at day 5-7, heel-prick
• Tests CF, Congenital Hypothyroidism, Haemoglobinopathies, and six IEMs (Phenylketonuria, MCAD Deficiency, Glutaric Aciduria type 1, Isovaleric Acidaemia, Homocystinuria, MSUD)

82
Q

Phenylketonuria (PKU)

A

• Decreased metabolism of Phenylalanine (Classically, Phenylalanine Hydroxylase mutation)
• 1 in 10,000; Can present with Learning difficulties, Seizures and Microcephaly
• Management is with Phenylalanine restricted diet
o Tyrosine is conditionally essential in patients with PKU

83
Q

Medium-chain Acyl CoA Dehydrogenase (MCAD) Deficiency

A

• Impaired ability to break down Medium-chain fatty acids into Acetyl-CoA
o Fatty acid oxidation is crucial for providing energy when Glucose and Glycogen stores depleted in fasting
• 1 in 10,000; Can present with Rapidly Progressive Encephalopathy and Collapse after prolonged fast; Non-Ketotic hypoglycaemia
• Management is avoiding fasting/hypoglycaemia, and provision of emergency regimen in times of increased catabolism

84
Q

Glutaric aciduria type 1 (GA1)

A

• Unable to break down Lysine, Hydroxylysine and Tryptophan, resulting in accumulation of intermediates (Glutaric acid, Glutaryl CoA, 3-Hydroxyglutaric acid and Glutaconic acid
o Particularly damaging to Basal Ganglia and other areas of brain
o Secondary Carnitine deficiency (Excessive Glutaric acid is detoxified by Carnitine)
• 1 in 30,000; Macrocephaly with Encephalic crisis around 1yr resulting in Dystonic-Dyskinetic Movement disorder
• Specialist Diet, Avoidance of Fasting and Daily Carnitine

85
Q

Homocystinuria

A

Cystathionine-Beta-Synthase deficiency classically (=Homocystinuria I); leading to abnormal accumulation of Homocysteine and metabolites;
• 1 in 65,000 in Irish ancestry; Marfanoid appearance, Learning Disability, Lens dislocation, Osteoporosis and Thromboembolism
• Management with Low Protein Diet, Pyridoxine and Folic Acid Supplementation
o Homocysteinaemia associated with higher risk of cerebrovascular events (Increased carotid plaque thickness; vit B supplementation slows progression)

86
Q
  • Galactosaemia
A

o This presents when lactose containing milk feeds are given with vomiting, jaundice, hepatomegaly, chronic liver disease, cataracts and developmental delay
o Treatment is lactose free diet

87
Q

Glycogen storage disorders

A

Glycogen storage disorders come in nine forms, but all prevent mobilisation of glucose from glycogen
o Treatment is to give frequent feeds to maintain blood glucose, this may need to be via NG. High protein may be recommended to prevent muscle wasting
o Enzyme replacement is important where available

Paediatrics STG (17 decks)

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