Endocrinological Disorders

Question 1

Describe thyroxine production in-utero.

Answer 1

• A small amount of thyroxine is transferred from mother to foetus
• The foetal thyroid predominantly produces reverse T3 which is a largely inactive derivative of T3
• After birth, there is a surge of TSH which is accompanied by a marked increase in T4 and T3 levels
• TSH levels then decline to normal adult levels within a week

Question 2

How common is congenital hypothyroidism?

Answer 2

1 in 3000 births

Question 3

What is a preventable complication of congenital hypothyroidism?

Answer 3

Severe learning difficulties

Question 4

What causes of congenital hypothyroidism?

Answer 4

• thyroid agenesis – the thyroid gland is absent – the most common cause of sporadic congenital hypothyroidism
• maldescent of the thyroid – where the thyroid remains as a lingual mass or a unilobular small gland, instead of migrating in early fetal life from a position at the base of the tongue (sublingual) to its normal site below the larynx
• dyshormonogenesis – an inborn error of thyroid hormone synthesis, with autosomal recessive inheritance, in about 10% of cases
• maternal iodine deficiency – a common cause of congenital hypothyroidism worldwide but rare in the UK; it can be prevented by iodination of salt in the diet
• hypothyroidism due to TSH deficiency – isolated TSH deficiency is rare (<1% of cases) and is usually associated with other features of pituitary dysfunction.

Question 5

Whats are the features of hypothyroidism?

Answer 5

Question 6

What are the investigations of congenital hypothyroidism?

Answer 6

Most infants are detected during routine neonatal biochemical screening (Guthrie test) which identifies raised TSH in the blood at 5 days of age
o Hypothyroidism secondary to pituitary abnormalities will not be picked up during screening as they have a low TSH - rare

Question 7

What is the management of congenital hypothyroidism?

Answer 7

Thyroxine treatment should be started within 2-3 weeks of age to reduce the risk of impairedneurodevelopment

Treatment is life-long with oral replacement of thyroxine

With adequate and early intervention, intelligence and development should be normal

Question 8

What is acquired hypothyroidism usually caused by?

Answer 8

Autoimmune thyroiditis

Question 9

What individuals are at higher risk of having acquired hypothyroidism?

Answer 9

• Individuals with
  
  • Down syndrome
  • Turner syndrome
  • other AI disorders such as vitiligo, rheumatoid arthritis, Diabetes mellitus

Question 10

What is the tx of acquired hypothyroidism?

Answer 10

Thyroxine

Question 11

What is the most common cause of hyperthyroidism?

Answer 11

Usually results from autoimmune thyroiditis (Graves disease) secondary to the production of thyroid-stimulating antibodies

Question 12

What are the clinical features of hyperthyroidism?

Answer 12

Similar to those in adults, most often seen in teenage girls.

Question 13

What are the investigations for hyperthyroidism?

Answer 13

TFTs

o High T3 and T4

o Low TSH

Antithyroid peroxisomal antibodies → may result in spontaneous resolution of hyperthyroidism but may cause hypothyroidism

Question 14

What is the management of hyperthyroidism?

Answer 14

• 1st Line: Carbimazole or propylthiouracil
  
  • Carbimazole: converted to active form, methimazole, which inhibits thyroid peroxidase to inhibit T3/T4 production
  • Propylthiouracil: inhibits thyroid peroxidase, also inhibits 5’-tetradeiodinase which normally converts T4 to T3
    
    • IMPORTANT: Both associated with a risk of neutropaenia
      o Families should be safe-netted about seeking urgent medical attention and a blood count if a sore throat or fever occur whilst on treatment
• Beta-blockers may be considered for symptomatic relief of anxiety, tremor, and tachycardia.
• Medical treatment is usually given for around 2 years, which should control the thyroid hormone excess, but eye signs may not resolve.
• When medical treatment is stopped, two thirds of patients relapse.
• A second course of drugs may be given or permanent remission considered with radioiodine treatment or surgery (thyroidectomy).
• Follow-up is always required as thyroxine replacement is needed for subsequent hypothyroidism.
• Other options: radioiodine treatment, surgery
• NOTE: neonatal hyperthyroidism may occur due to the transplacental transfer of TSIs

Question 15

What is the risk of of neonatal hyperthyroidism? How is it managed?

Answer 15

Neonatal hyperthyroidism may occur in infants of mothers with hyperthyroidism from the transplacental transfer of thyroid-stimulating hormone receptor antibodies.

Treatment of the neonate is required as it is potentially fatal, but it resolves with the regression of maternal antibodies.

Question 16

Define T1DM

Answer 16

Characterised by absolute insulin deficiency, usually from autoimmune pancreatic beta-cell destruction in genetically susceptible individuals

Question 17

Define T2DM

Answer 17

▪ Insulin resistance followed later by beta cell failure

▪ Usually older children, obesity-related, positive family history, not as prone to ketosis, more common in Black and Asian ethnicity

▪ Commonly associated with acanthosis nigricans: velvety dark skin on neck or armpits (~90%)

Question 18

What are the other types of diabetes?

Answer 18

▪ Maturity onset diabetes of the young: strong family history

▪ Drugs e.g. corticosteroids

▪ Pancreatic insufficiency e.g. cystic fibrosis, iron overload in thalassemia

▪ Endocrine disorders e.g. Cushing syndrome

▪ Genetic/chromosomal syndromes e.g. Down and Turner

▪ Neonatal diabetes: transient and permanent secondary to defective B cell function

▪ Gestational diabetes

Question 19

Describe the aetiology of T1DM

Answer 19

• Genetic predisposition
• Immune activation → pancreatic B cell damage → increased insulin deficiency
• Recognised auto-antibodies - identification of >1 of these → potential to develop diabetes
  
  • glutamic acid decarboxylase
  • zinc transporter 8
  • islet antigen 2

Question 20

What is T1DM associated with?

Answer 20

Associated with HLA DR3/DR4

Associated with other autoimmune conditions e.g. coeliac, Addison’s

Also associated with Down + Turner syndrome

Question 21

Describe the presentation of T1DM.

Answer 21

Presentation peaks in spring and autumn months

Most common early symptoms: referral should be done as soon as dx is suspected

o Polyuria
o Polydipsia

o Weight loss

Less common early symptoms

o Enuresis (secondary)

o Skin sepsis
o Candida and other infections

o Excessive tiredness

• Late: can present with diabetic ketoacidosis - URGENT

o Smell of acetone on breath

o Vomiting
o Dehydration
o Abdominalpain
o Hyperventilation due to acidosis (Kussmaul breathing)

o Hypovolaemic shock
o Drowsiness
o Coma and death

Question 22

What are the investigations of T1DM?

Answer 22

• Diagnostic criteria

o plasma glucose ≥ 11.1 mmol/L in a symptomatic child + Urine dipstick: glycosuria, ketonuria

When in doubt Fasting plasma glucose ≥ 7.0 mmol/L OR High HbA1c

OGTT is rarely required

Consider T2DM if family history of obesity with signs of insulin resistance

C-peptide

o Not measured at initial presentation to distinguish T1 and T2DM
o Consider measuring after initial presentation if difficulty distinguishing T1DM from other types

Question 23

How should we be thinking of managing T1DM?

Answer 23

1. MDT Involvement
2. Admission? DKA?
3. Intensive educational programme for parents and children
4. Lifestyle changes
5. Blood glucose targets and monitoring
6. Insulin therapy
7. Sick day rules
8. DKA
9. Complications explanation

Question 24

Who is the MDT involved in T1DM care?

Answer 24

• Consultant paediatrician with a specialist interest in diabetes
• Paediatric diabetes specialist nurse
• paediatric dietician
• clinical psychologist
• social worker, youth worker, play specialist
• adult diabetes team for transition clinics
• parent-patient support groups

Question 25

What does the intensive educational programme for parents and children provide?

Answer 25

Basic understanding of pathophysiology of diabetes.

Injection of insulin technique and sites.

Blood glucose monitoring to allow insulin adjustment.

Blood ketone monitoring when on well.

Healthy diet: minimum five fruit and veggies per day, carbohydrate counting.

Encouragement to exercise regularly.

Sick day rules to prevent ketoacidosis.

Recognition and treatment of hypoglycaemia.

Where to get advice 24 hours per day.

Help available from voluntary groups for example diabetes UK.

Psychological impact of lifelong with potentially serious complications.

Question 26

What are the blood glucose targets and HbA1c Targets and Monitoring?

Answer 26

o Routinely perform at least 5 capillary glucose tests per day

Fasting plasma glucose and at other times in the day: 4-7 mmol/L

After meals: 5-9 mmol/L
If driving: > 5 mmol/L

o Offer ongoing real-time continuous glucose monitoring with alarms for children with:

• Frequent severe hypoglycaemia
• Impairment awareness of hypoglycaemia with adverse consequences (e.g. seizures, anxiety)
• Inability to recognise or communicate symptoms of hypoglycaemia (e.g. cognitive disability)

o HbA1c target < 48 mmol/L (6.5%)

Blood Ketone Monitoring
o Offer blood ketone testing strips and a meter and advise testing for ketonaemia if they are ill or hyperglycaemic

Question 27

What are the types of insulin therapy for T1DM?

Answer 27

• Insulin Therapy for T1DM
o Three Types of Insulin Therapy

1. Multiple Daily Injection Basal-Bolus: injections of short-acting insulin or rapid-acting insulin analogue before meals, with 1 or more separate daily injections of intermediate acting insulin or long-acting insulin analogue
2. Continuous Subcutaneous Insulin Infusion (insulin pump therapy): programmable pump and insulin storage device that gives regular or continuous amounts of insulin (usually rapid-acting insulin or short-acting insulin) by a subcutaneous cannula
3. One, Two or Three Insulin Injections Per Day: injections of short-acting insulin or rapid-acting insulin analogue mixed with intermediate-acting insulin

o Offer multiple daily injection basal-bolus insulin regimens from diagnosis
o If this is inappropriate, consider continuous subcutaneous insulin infusion (CSII or pump therapy)

Question 28

What are the sick day rules?

Answer 28

o During illness, body releases stress hormones such as cortisol which can cause a rise

in blood glucose hence may need more insulin to control this. If you do not get enough insulin, body starts to break down fat and ketones are produced.

▪ Note: DKA occurs when there is insufficient insulin to allow glucose to enter cells

o Provide clear individualised oral and written advice regarding sick days inc

▪ Continue insulin regimen

▪ More frequent blood glucose monitoring

▪ Check ketone levels

▪ Encourage fluid intake

▪ If unable to eat, may need sugary drinks

o Offer blood ketone testing strips to test for ketonaemia if they are ill

o Diagram is an example of sick day rules that are given to patient

Question 29

What are the complications of T1DM?

Answer 29

Complications

o Diabetic retinopathy, nephropathy, and hypertension – monitor annually from 12 years

o Thyroid disease at diagnosis and annually until transfer to adult services

• Long-Term Complications
o MACROvascular: hypertension, coronary heart disease, cerebrovascular disease

o MICROvascular: retinopathy, nephropathy, neuropathy

• DKA

o Explain the symptoms of DKA: nausea/vomiting, abdominal pain, hyperventilation, dehydration, reduced consciousness

Question 30

Define hypoglycaemia

Answer 30

plasma glucose < 4 mmol/L

Question 31

What are the clinical features of hypoglycaemia?

Answer 31

Depends on whether other substrates can be utilised

Sweating

Pallor

Central nervous system signs of irritability, headache, seizures and coma

Question 32

How should you treat hypoglycaemia?

Answer 32

Advise always carrying an immediate source of fast-acting glucose and blood glucose monitoring equipment (include parents and school nurses)

Mild-to-Moderate Hypoglycaemia

o Give fast-acting glucose by mouth (usually liquid carbohydrate (e.g.Lucozade))
o May need to be given in small amounts if vomiting
o Recheck blood glucose within 15 mins and repeat fast-acting glucose if hypoglycaemia persists
o As symptoms improve, give oral complex long-acting carbohydrate to maintain blood glucose levels

SEVERE Hypoglycaemia

o Treat in hospital

Give IV 10% glucose (maximum dose of 500 mg/kg of bodyweight (5 ml/kg))

o If NOT in hospital: unresponsive or PO route cannot be used

IM glucagon or concentrated oral glucose solution (e.g. glucogel)

• IM glucagon:500μg for < 8 years; 1mg for > 8 years

Seek medical help if blood glucose remains low after 10 mins

Once symptoms improve, give oral complex long-acting carbohydrate

NOTE: alcohol is a risk factor for hypoglycaemia (they should eat carbohydrates before and

after drinking)

Question 33

How should you counsel for a diagnosis of T1DM?

Answer 33

Question 34

Define DKA.

Answer 34

An acute metabolic complication of diabetes characterised by absolute insulin deficiency leading to extremely high blood glucose and ketone levels – MEDICAL EMERGENCY

Question 35

What are the triggers of DKA?

Answer 35

o Stress
o Infection
o Insufficientinsulin

Question 36

Describe the pathophysiology of DKA?

Answer 36

• There is reduced insulin concentration along with increased insulin counter-regulatory hormones (e.g. glucagon, catecholeamines, cortisol, GH)
• This leads to hyperglycaemia, volume depletion and electrolyte imbalance
• Although there is high circulating glucose, the insulin deficiency means tissues such as muscle, fat and liver are unable to take up glucose
• The starvation of cells leads to release of counter-regulatory hormones such as glucagon
• These hormones promote break down of triglycerides into free fatty acids (lipolysis) and initiate gluconeogenesis which further increases blood glucose
• Free fatty acids are in abundance and are metabolised into ketone bodies in liver
• The increase in circulating ketones causes metabolic acidosis (ketoacidosis) as well at ketonuria
• The high circulating glucose will eventually cause glycosuria → glucose produces an osmotic effect so will also draw water out into urine (osmotic diuresis)→this leads to volume depletion and dehydration
• Causes: e .g. if someone is ill→stress hormones are produced e.g. glucagon→can cause rise in blood glucose

Question 37

What are the clinical features of DKA?

Answer 37

Polyuria

Polydipsia

Weight loss

Smell of acetone on breath (fruity scent)

V omiting or nausea

Dehydration

Abdominal pain

Lack of appetite

Weakness/fatigue

Kussmaul breathing

Hypovolaemic shock

Confusion

Drowsiness/reduced level of consciousness

Blurred vision

Coma and death

Question 38

What are the investigations for a DKA?

Answer 38

o Blood glucose

o Blood ketones

o U&Es
o Creatinine

o Blood gas
o Cardiac monitor

o Weight

If plasma glucose is > 11 mmol/L in a child without known diabetes but with symptoms of DKA, suspect DKA and send immediately to hospital

NOTE: blood glucose can be normal in DKA

When a child with suspected or known DKA arrives at hospital measure:

o Capillary blood glucose
o Capillary blood ketones (beta-hydroxy butyrate) if possible (otherwise test urine ketones)
o Capillary or venous pH and bicarbonate

• Diagnose DKA in children with diabetes who have:
o Acidosis (pH \< 7.3 or plasma bicarbonate \< 15 mmol/L)
o Ketonaemia (blood beta-hydroxybutyrate \> 3 mmol/L) or ketonuria (++)

Question 39

How should we manage a DKA?

Answer 39

• A-E Approach
• Call Senior
• Record parameters
• Transfer to ward
• Assess severity
• Emergency measures
• Fluid Therapy
• Insulin therapy
• Monitor
• Normalise
• Think of complications

Question 40

What is the A-E approach in DKA?

Answer 40

Ensure airway patent
100% oxygen by face mask
Insert IV cannula and take bloods
Assess for signs of cerebral oedema (headache, irritability, slowing pulse, rising BP, reducing conscious levels, late sign = papilloedema)
Weigh child if possible

Question 41

What should you be measures initially in DKA?

Answer 41

When DKA is diagnosed, record their:
▪ Level of consciousness
▪ Vital signs (HR, BP, Temp, RR)

▪ History of nausea or vomiting
▪ Clinical evidence of dehydration

▪ Body weight

When DKA is diagnosed, measure their:
▪ pH and pCO2
▪ Plasma sodium, potassium, urea and creatinine

▪ Plasma bicarbonate

Question 42

When should the child be admitted?

Answer 42

o Children should be cared for with one-to-one nursing either in an HDU or a general paediatric ward if:

• < 2 years old
• Severe DKA

NB: consider PICU transfer if one-one nursing not available in the above settings

Question 43

How can you assess severity?

Answer 43

Question 44

What are the emergency measures?

Answer 44

Question 45

Describe fluid maintenance in DKA?

Answer 45

o Oral fluids can be used if the child is ALERT, not nauseated or vomiting, and not clinically dehydrated
o Treat with IV fluids and IV insulin in children who are not alert, are nauseated or vomiting or is clinically dehydrated
o Calculate total fluid requirement by adding the estimated fluid deficit to the maintenance requirement

• Initial fluid bolus
  
  • If presenting with SHOCK (tachycardia, prolonged CRT etc)→20 ml/kg 0.9% saline over 15 mins
  • Reassess
  • If needed, further bolus of 10 ml/kg
  • Maximum of 40 ml/kg→after this consider inotropes
  • Boluses given to treat shock are NOT subtracted from fluid deficit
• Everyone else in whom IV fluids felt to be indicated (and not in shock)
  
  • Give initial 10 ml/kg 0.9% NaCl over 60 minutes
  • Shocked patients do not need this extra bolus
  • This is subtracted from fluid deficit

o Total fluid requirement: estimated fluid deficit + maintenance requirement

Fluid Deficit

• 5% fluid deficit in mild-moderate DKA (pH >7.1)
• 10% fluid deficit in severe DKA (pH < 7.1)

• Subtract non-shock 10ml/kg bolus from fluid deficit

IMPORTANT: fluid deficit should be replaced over 48 hours

• Maintenance Requirement
  
  • 100ml/kg/day for first 10kg
  • 50ml/kg/day for next 10kg
  • 20ml/kg/day for each additional kilogram above 20kg

Hourly rate: ((Deficit – Initial bolus)/48 hr) + maintenance per hour

o Which Fluids?

• 0.9% saline without added glucose should be used for rehydration and maintenance until plasma glucose is < 14 mmol/L
• Change to 0.9% saline + 5% glucose after plasma glucose drops below 14 mmol/L
• IMPORTANT: Ensure all fluids (except boluses) administered to children with DKA contain 40mmol/L potassium chloride (unless they have renal failure)

o Once blood glucose <14 mmol/L, add 5% glucose to the fluid.
o Only consider stopping IV fluids if ketosis is resolving, the child is alert, and can take oral fluids without nausea or vomiting

Question 46

A 20 kg 6 year old boy who has a pH of 7.15 (Moderate DKA => 5% Dehydrated) will receive a 10ml/kg bolus (200mls fluid) over 30 minutes as part of his initial management

Answer 46

Question 47

A 60 kg 15 year old girl with a pH of 6.9 who was shocked at presentation has received 30ml/kg of 0.9% Saline for resuscitation

Answer 47

Question 48

Describe insulin therapy in DKA.

Answer 48

o Start IV insulin infusion 1-2 hours after beginning IV fluid therapy in children with DKA

Use a soluble insulin infusion at a dose 0.05-0.1 units/kg/hour (0.1 in severe DKA)

Do NOT give bolus doses of insulin

If the child is using an insulin pump, disconnect it before starting IV insulin

Continue any long-acting insulin that a child is already on

o If the blood ketone level is NOT falling after 6-8 hours, think about increasing the insulin dosage to 0.1 units/kg/hour or more AND seek senior help

o Do NOT change from IV insulin to SC insulin until ketosis is resolving (<1 mmol/L), the child is alert, and can take oral fluids without nausea or vomiting

o Start SC insulin in the child at least 30 mins BEFORE stopping IV insulin
o If using an insulin pump, start the pump at least 60 mins BEFORE stopping the IV insulin
• NOTE: remember to change the insulin cartridge and infusion set, and insert the cannula into a new SC site

Question 49

What other thinks should we consider in DKA?

Answer 49

o Consider inserting urinary catheter if it is difficult to monitor urine output
o Consider inserting an NG tube if a child with DKA has a reduced level of consciousness and is vomiting (due to risk of aspiration)
o Consider the use of inotropes in a patient with DKA who is in hypovolaemic shock

o Consider sepsis in a patient with DKA who has any of:

• Fever or hypothermia
• Hypotension
• Refractory acidosis
• Lactic acidosis

Question 50

Describe the monitoring in DKA.

Answer 50

o Monitor and record at least HOURLY

• Capillary blood glucose
• Vital signs (HR, BP, Temp, RR)
• Fluid balance with fluid input and output charts
• Level of consciousness (using modified GCS)

o NOTE: level of consciousness and heart rate (to detect bradycardia) should be recorded every 30 mins in:

• Children < 2 years
• Children with severe DKA
• This is because they have an increased risk of cerebral oedema

o Monitor children receiving IV therapy for DKA using a continuous ECG to detect HYPOKALAEMIA (ST depression, prominent U waves, flattened P waves)

o At 2 hours after starting treatment, and then at least every 4 hours afterwards, measure and record:

• Glucose (laboratory measurement)
• Blood pH and pCO2
• U&E
• Beta-hydroxybutyrate

o The patient should be reviewed at least every 4 hours looking at:

• Clinical status (including vital signs and neurological status)
• Results of blood investigations
• ECG trace
• Cumulative fluid balance record

Question 51

What are the complication of DKA management?

Answer 51

o Cerebral Oedema

• Suspect cerebral oedema if:

• Headache
• Agitation or irritability
• Unexpected fall in heart rate
• Increased blood pressure

• If cerebral oedema is suspected, treat with mannitol or hypertonic sodium chloride

Immediately treat if any of these serious signs of cerebral oedema are present:

• Deterioration in level of consciousness
• Abnormalities of breathing pattern
• Oculomotor palsies
• Pupillary inequality or dilatation

o Hypokalaemia (< 3 mmol/L)

• Consider temporarily stopping the insulin infusion
• Discuss management with paediatric critical care specialist (central venous catheter is needed for IV administration of potassium solutions > 40 mmol/L)

o Venous thromboembolism - there is an increased risk of VTE in children with DKA, especially if they have a central venous catheter

Question 52

How would you counsel about DKA?

Answer 52