Metabolic/endocrine

Question 1

Discuss pathogenic mechanisms of inborn errors of metabolism

Answer 1

1) Accumulation of substrate A which was meant to be convereted to B
2) Lack of product B which was meant to be convered from A
3) Excess subtrate A is convereted to another compound C via an alternative pathway
4) If reactions earlier reaction are reversible than accumulation of substrate A can lead to accumulation of an earlier metabolirte
5) Excess A is remoeved by reacting with or conjugating compound D which results in deficiency of D

Question 2

Discuss clinical presentation of fatty acid oxidation disorders

Answer 2

Caused by inability to produce ketone bodies as a an alternative fuel for brain heart muscle and kidney

Can present at any age with the most severe forms such as the long chain fatty acid oxidation disorders presenting within the first few days of life
MCAD usually presents in early childhood

The most common presenting signs include hypoglycaemia, hyperammonemia, liver disease and failure cardiac and skeletal mypathy, rhabdo and retinal dengeration.

Life threatening presentation can occur with minimal fasting in infants but may require 24 to 48 hours of fasting in older individuals.

Question 3

Discuss IX of LCAD and MCAD

Answer 3

Hypoketotic hypoglycaemic with low or absent serum beta hydroxybutyrate leves and urine ketones

Metabolic acidosis and dehydration
LFT derangement
Hyperammonemia

Question 4

Discuss management of Fatty acid oxidation disorders

Answer 4

1) Prevention of metabolic decompensation
- avoid prologed fasting and maintenance of a constatn energy supply during times of catbabolism
- IV glucose for those who can tolerate orally
- - Should have emergency protocol/letter for presentation to ED and signs and symptoms to watch for
- - Safe fasting times discussion, changes with age and illness
- - Avoid use of propofol as contains long chain fatty acids and can cause deteriation of patients

2) Dietary mangement
- fat restirction is not strictly necessary except to accomodate the addition of medium chain triglyceriede oil into the deite

Question 5

Discuss glycogen storage disorders

Answer 5

There are number of inborn erros of glucose and glycogen metabolism (GSD 1-15)

Glycogen is the stored form of flucose and serves as a buffer for glucose needs.

The liver and the skeletal muscle are the most commonly affected by disorders of glucose and glycogen metabolism

The major manifestations of disorder of glycogen metabolism affecting th liver are hypogycaemia and hepatomegaly, for those affecting the muscle are cramping, exercise intolerance and easy fatigability, progressive weakness and variable cardiac invovlemtn with cardiomyopathy

Hypoglycemia – patient with glycogen storage disorders present with hypoglycaemia, ketosis with or wihtout hepatomegaly

Question 6

Discuss maple syrup urine disease

Answer 6

Bracnhed chain ketoaciduria caused by defieincy in brainched chain alphketoacid dehydrogenase complex

Newborns develop ketonuria 48 hours from birth and present with irritbaility poor feeding vomiting lethargy and dystonia, by age four neurological abnormailities including alternating lethargy and irritabilty dystonea apnoea, seizurea and sings of cerbral oedema.

Other protein metabolism defects include

• phenylketonuria
• tyrosinaemia

Question 7

Discuss management of inherited disorders of metabolism

Answer 7

In general three main tenatns

1) correction of altered homeostasis
- hypoglycaemia corrected with 2-5mls of 10% dextrose followed by infusion if required.
- if nil IV acess can be obtained buccal glucose gel or honey can be used initialy
- glucagon can be trialled however is unlikley to be useful due to glycogen depletion (0.5 mg children >8 otherwise 1 mg)

2) Reduction of toxic compound production
- generally achieved thorugh dietary means and vaires with the metabolic condition.
- feature common to all dietary intervention in the acutely unwell paitent with an IEM is the provision of calories.

3) Removal/ehanced excretion of toxic compounds

Question 8

Discuss categories of hypoglycaemic disorders

Answer 8

1) Insulin mediated
- hyperinsulinism
- insyulinoma
- factitious hypoglycemia
- disorders of glycosylation

2) fatty acid oxidation disorders

3) ketotic hypoglycaemic disorders
- disorders of glycogen metabolism
- hormones deficiencies (adrenal insufficiency, GH and combined pituiraty hormone deficiency)
- ketone utilaitzation defect
- idiopathic ketotic hypoglycaemia

4) disorders of gluconeogenesis
- GCSD

5)other causes including tox and acute critical illness

Question 9

Discuss hyperinsulinsims

Answer 9

The most common cause of pesistent hypoglycaemia in infants and children
Dysregulated secretion by the beta cells of the pancrease causes severe recurrent hypoglycaemia

Can be congenitial, perinatal stress induced and syndromic (Beckwith-Wiedemann syndrome or Kabuki)

Due to the lack of alternative fuels ie ketones HI caries high risk of neurological damage and developmental delays

Question 10

Discuss insulinomas

Answer 10

Insulin secreting islet cell tumors which are typically benign. They sometimes occur in the setting of multiple endocrine neoplasia type 1 - rare but should be considered with persistant hypoglycaemic epidodes in children and adolecents

Question 11

Discuss factitious hypoglycaemia

Answer 11

Induced hypoglycemia refers to intentional administration of insulin or an oral hypoglycaemic medication

NAI, Medical child abuse

Question 12

Define DKA

Answer 12

presence of all of the following

1) hyperglycaemia BGL <11
2) ketonaemia or ketoruria
3) metabolic acidosis pH <7.3 or hco3 <15

Question 13

Define HHS

Answer 13

1) Marked hyperglycaemia – >33.3mmol/L
2) minimal acidosis venous ph >7.25 and arterial >7.3 or hco3 >15
3) Absent to mild ketosis
4) marked elevation in serum osmolality - >320mOsm/Kg

Question 14

Discuss assessment of severity of DKA

Answer 14

Severity is measured using acid base status
Mild Ph 7.2-7.3
Moderate 7.1-7.2
Severe <7.1

Question 15

Discuss fluid management in DKA

Answer 15

Average water losses in children with DKA are approximately 70ml/kg due to urinary loss from osmotic diuresis and GI losses from vomiting and insensible losses from hyperventilation

Clinical signs of dehydration tend to be inaccurate so mild DKA is assumed to have dehydration of 5-7% for mild to moderate and 10% for severe

Initial volume expansions should eb 10-20mls of isotnoic slaine or hartmans, subsequent if HD instability. If well child tend not to benefit from initial boluses.

Once the child is HD stable additional fluids should be administered to replace the remaining fluid deficit over 24-48 hours with 0.9% saline .

A range of IV flyuid protocols can be used to safely rehydrate children as shown with the large randmoised clinical trial (FLUID). FLUID showed nil difference between rapid and slow fluid rehydration or with the use of 0.9 or 0.45% saline

Question 16

Discuss Insulin therapy in DKA

Answer 16

Should be administered at a rate of 0.05-0.1 units/kg (small studies showing nil difference in rate of BGL decrease with smaller dose)

In most cases insulin and iV fluids resolve the hyperglyceamia prior to the ketosis being corrected. When BGL >14 dextrose should be added to the IV fluid infusion.

Question 17

Discuss electrolyte balance in the setting of DKA treatment

Answer 17

NA unlikley to be major issue – correct for hyperglycaemia

K: Patient with DKA have a total potassium defecit although presenting K levels may be normal or increased.
Insulin treatment will cause intracellular transport of K as well as the correction of acidosis reducing the accumulation. Almost all DKA patient will need K replacement
-If hyperK dont given initially with insuling treatment
-If normal K give alongside insulin therapy
-If hypoK replace and delay insuling therapy until within normal limits

Phosphate- often low in DKA , controversial if replacement causes and difference in outcomes.

Question 18

Discuss discontinuation of insulin

Answer 18

Insulin infusion should continue at 0.05-0.1 units/kg/hour until all the following are met

1) serum anion gap reduced to normal or Serum BOHB <1
2) Venous Ph >7.3 or hco3 >15
3) BSL <11.1
4) patient is tolerating oral intake

Question 19

Discuss Complications of DKA

Answer 19

Cerebral injury : occurs in 0.3-0.9% of children with DKA with a high mortality rate of 21-25%. Severe dehydration or acidosis are at greatest risk.

• usually develops in the first 12 hours of treatment but can also occur prior to treatment beginning
• Signs change in mental status, urinary incontinence, new headache or recurrence of vomiting.
• if suspected mannitol or hypertonic saline are management of choice

Cognitive impairment

VTE: increased risk of DVT particularly in associated with femoral CVC placement

AKI

Question 20

Disk risk factors and diagnosis of cerebral odema in children with DKA

Answer 20

Risk factors

• severe acidosis at presentation
• substantially elevated BUN at presentation
• Severe hypocapnia
• Young children

Minor criteria

• Headache
• Vomiting
• Irritability, lethargy or not easily roused from sleep
• Elevated BP

Major

• Abnormal or deteriating mental status after initiation of therapy, agitated behavior or fluctuating level of conciouness
• incontinence inappropriate for age
• Inappropriate slowing of heart rate – more than 20 beats that is not attributable to improved intravascular volume

Diagnositc

• abnormal motor or verbal response to pain
• decorticate or decerebrate posture
• abnormal pupillary repsonse or other CN pals
• abnormal neurogenic respiratory pattern (grunting, tachypnoea, CHyene stokes repsiration, apnoea

Treat if:
1 diagnostic 
2 major 
1 major + 2 minor 
1 major + 1 minor if under 5 years of age

Question 21

Discuss DDX of adrenal insufficiency in children

Answer 21

Primary

• congenitial adrenal hyperplasia
• Addisons
• adrenal aplasia or hypoplasia
• adrenal infarction secondary to haemorrahge or sepsis
• other: trauma, tumour post surgical

Secondary

• CNS tumor or trauma
• idiopathic
• exogenous steroid therapy

Question 22

Discuss clinical finding assocaited with primary adrenal insuffiency in children

Answer 22

Glucocorticoid defiency:

• Hypotensoins –> shock (absolute or postural) – due to permissive affects on catecholamines
• fatigue
• nasuea
• fasting hypoglycaemia secondary to icnreased insulin sensitivity
• muscle weakness
• morning headache
• Increased melanin syntyhesis leading to hyperpigmentation (elbows and kness, palmar creases, axillae, palate and gingival borders)

Mineralocorticoid

• Sodium loss
• potassium retention
• metabolic acidosis

Adrenal androgen defeiency
- lack of secondary sex characteristics

Question 23

Discuss treatment of adrenalin insufficiency in general

Answer 23

Replacement of hormone

• hydrocortosone is the steroid of choice for glucocorticoid replacement
• fludrocortisone is the steroid of choice if requried (primary will require, central or secondary will not)

Stress dose steroids will often have to be used
0-3 years old 25mg IV
3-12 years old 50mg IV
12 years and older 100mg IV

Question 24

Discuss adrenal crisis

Answer 24

Predominant manifestations of adrenal crisis are hypotension and shock usually with hyponatremia and hyperkalemia

Usually will have other non specific symptoms including anorexia, nasuea, vomiting abdominla pina, wekaness, feer confusion or coma

Usually seen in primary adrenal insuffiency as there is cocommitant loss of mineralcorticoids as apposed to central

Management tenants

1) fluids managment – 10-20ml/kg – may need to progress to inotropic support will need steroids replacement as will not work well wihtou
2) hypoglcaemia initial boluse than added to maintanence fluid
3) stress dose steroids as above
4) electrolyte management (hyper K)

Question 25

Discuss Cushing disease in infants

Answer 25

Rare life threatening disorder caused by prolonged exposure to excess glucocorticoid hormone concentration

CS can be divided into ACTH dependant and indepedant aetiology

5 key features for diagnosis

1) change in facial appearance
2) weight gain
3) growth failure
4) weight gain
5) genital virilisation