Paediatrics- Genetics + Endo Flashcards
Presentation of Type 1 DM
The remaining paediatric patients present with the classic triad of symptoms of hyperglycaemia:
- Polyuria (excessive urine)
- Polydipsia (excessive thirst)
- Weight loss (mostly through dehydration)
Type 1 DM
When a new diagnosis is established the following bloods should be taken to exclude other associated pathology and get a baseline idea of the child’s overall health
- Baseline bloods including FBC, renal profile (U&E) and a formal laboratory glucose
- Blood cultures should be performed in patients with suspected infection (i.e. with fever)
- HbA1c can be used to get a picture of the blood sugar over the previous 3 months. This gives an idea of how long they have been diabetic prior to presenting.
- Thyroid function tests and thyroid peroxidase antibodies (TPO) to test for associated autoimmune thyroid disease
- Tissue transglutaminase (anti-TTG) antibodies for associated coeliac disease
- Insulin antibodies, anti-GAD antibodies and islet cell antibodies to test for antibodies associated with destruction of the pancreas and the development of type 1 diabetes
Long term management of Type 1 DM
Management involves the following components:
- Subcutaneous insulin regimes
- Monitoring dietary carbohydrate intake
- Monitoring blood sugar levels on waking, at each meal and before bed
- Monitoring for and managing complications, both short and long term
Insulin is usually prescribed as a combination of a background, _____ acting insulin given once a day, and a ____ acting insulin injected 30 minutes before the intake of carbohydrates (i.e. at meals).
Alternatively, insulin can be administered by an _____ ____ Insulin regimes are initiated by a diabetic specialist.
Insulin is usually prescribed as a combination of a background, long acting insulin given once a day, and a short acting insulin injected 30 minutes before the intake of carbohydrates (i.e. at meals).
Alternatively, insulin can be administered by an insulin pump. Insulin regimes are initiated by a diabetic specialist.
Injecting into the same spot repeatedly can cause a condition called _________, where the _________ ____ hardens and prevents normal absorption of insulin when further doses are injected into this area. For this reason patients should cycle their injection sites. If a patient is not responding to insulin as expected, ask where they inject and check for lipodystrophy.
Injecting into the same spot repeatedly can cause a condition called lipodystrophy, where the subcutaneous fat hardens and prevents normal absorption of insulin when further doses are injected into this area. For this reason patients should cycle their injection sites. If a patient is not responding to insulin as expected, ask where they inject and check for lipodystrophy.
Explain the Basal Bolus Regimes
Insulin regimes are initiated by a specialist in diabetes. Patients are usually initiated on a basal-bolus regime.
The basal part refers to an injection of a long acting insulin, such as “Lantus”, typically in the evening. This gives a constant background insulin throughout the day.
The bolus part refers to an injection of a short acting insulin, such as “Actrapid”, usually three times a day before meals. This is also injected according to the number of carbohydrates consumed every time the patient has a snack.
Advantages and disadvantages of insulin pump
The advantages of an insulin pump are better blood sugar control, more flexibility with eating and less injections. The disadvantages are difficulties learning to use the pump, having it attached at all times, blockages in the infusion set and a small risk of infection.
There are two types of insulin pump:
- Tethered pump
- Patch pump
Explain the difference
Tethered pumps are devices with replaceable infusion sets and insulin. They are usually attached to the patients belt or around the waist with a tube that connects from the pump to the insertion site. The controls for the infusion are usually on the pump itself.
Patch pumps sit directly on the skin without any visible tubes. When they run out of insulin the entire patch pump is disposed of and a new pump is attached. Patch pumps are usually controlled by a separate remote.
Type 1 DM
Short term complications relate to immediate insulin and blood glucose management:
- Hypoglycaemia
- Hyperglycaemia (and DKA)
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Hypoglycaemia needs to be treated with a combination of r_____ acting glucose such as _______ and _____ acting carbohydrates such as biscuits or toast to maintain the blood sugar level when the rapid acting glucose is used up.
Hypoglycaemia needs to be treated with a combination of rapid acting glucose such as lucozade and slower acting carbohydrates such as biscuits or toast to maintain the blood sugar level when the rapid acting glucose is used up.
Options for treating severe hypoglycaemia where there is impairment of consciousness, seizures or coma, and oral glucose would not be safe, are __ ______ and _____ ________. IM glucagon does not require a cannula. If a cannula is sited then ____ dextrose solution can be given according to local protocols, for example 2mg/kg bolus followed by a 5mg/kg/hour infusion.
Options for treating severe hypoglycaemia where there is impairment of consciousness, seizures or coma, and oral glucose would not be safe, are IV dextrose and intramuscular glucagon. IM glucagon does not require a cannula. If a cannula is sited then 10% dextrose solution can be given according to local protocols, for example 2mg/kg bolus followed by a 5mg/kg/hour infusion.
Causes of hypoglycaemia?
too much insulin, not enough carbohydrates
hypothyroidism, glycogen storage disorders, growth hormone deficiency, liver cirrhosis, alcohol and fatty acid oxidation defects
What is Nocturnal hypoglycaemia
Nocturnal hypoglycaemia is a common complication. The child may be sweaty overnight. Morning blood glucose levels may be raised. Diagnosis of nocturnal hypoglycaemia can be made by continuous glucose monitoring. It can be treated by altering the bolus insulin regimes and snacks at bedtime.
Macrovascular Complications of DM
Coronary artery disease is a major cause of death in diabetics
Peripheral ischaemia causes poor healing, ulcers and “diabetic foot”
Stroke
Hypertension
Microvascular Complications of DM
Peripheral neuropathy
Retinopathy
Kidney disease, particularly glomerulosclerosis
Infection Related Complications of DM
Urinary tract infections
Pneumonia
Skin and soft tissue infections, particularly in the feet
Fungal infections, particularly oral and vaginal candidiasis
How does DKA cause potassium imbalance
Insulin normally drives potassium into cells. Without insulin, potassium is not added to and stored in cells. Serum potassium can be high or normal in diabetic ketoacidosis, as the kidneys continue to balance blood potassium with the potassium excreted in the urine, however total body potassium is low because no potassium is stored in the cells. When treatment with insulin starts, patients can develop severe hypokalaemia (low serum potassium) very quickly, and this can lead to fatal arrhythmias.
The most dangerous aspects of DKA are _________ _________ _______ ________ These are what will kill the patient. Therefore the priority is fluid resuscitation to correct the dehydration, electrolyte disturbance and acidosis. This is followed by an insulin infusion to allow the cells to start taking up and using glucose and stop producing ketones.
The most dangerous aspects of DKA are dehydration, potassium imbalance and acidosis. These are what will kill the patient. Therefore the priority is fluid resuscitation to correct the dehydration, electrolyte disturbance and acidosis. This is followed by an insulin infusion to allow the cells to start taking up and using glucose and stop producing ketones.
Presentation of DKA
The patient will present with symptoms of the underlying hyperglycaemia, dehydration and acidosis:
- Polyuria
- Polydipsia
- Nausea and vomiting
- Weight loss
- Acetone smell to their breath
- Dehydration and subsequent hypotension
- Altered consciousness
- Symptoms of an underlying trigger (i.e. sepsis)
Diagnosing DKA
Check the local DKA diagnostic criteria for your hospital. To diagnose DKA you require:
- Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
- Ketosis (i.e. blood ketones > 3 mmol/l)
- Acidosis (i.e. pH < 7.3)
Principles of DKA Management in Children
Follow local treatment protocols and involve senior paediatricians. The two pillars of correcting DKA are:
- Correct dehydration evenly over 48 hours. This will correct the dehydration and dilute the hyperglycaemia and the ketones. Correcting it faster increases the risk of cerebral oedema.
- Give a fixed rate insulin infusion. This allows cells to start using glucose again. This in turn switches off the production of ketones.
Other important principles:
- Avoid fluid boluses to minimise the risk of cerebral oedema, unless required for resuscitation.
- Treat underlying triggers, for example with antibiotics for septic patients.
- Prevent hypoglycaemia with IV dextrose once blood glucose falls below 14mmol/l.
- Add potassium to IV fluids and monitor serum potassium closely.
- Monitor for signs of cerebral oedema.
- Monitor glucose, ketones and pH to assess their progress and determine when to switch to subcutaneous insulin.
What is Addisons disease
Addison’s disease refers a the specific condition where the adrenal glands have been damaged, resulting in reduced secretion of cortisol and aldosterone. This is also called primary adrenal insufficiency. The most common cause is autoimmune.
What is Secondary adrenal insufficiency
Secondary adrenal insufficiency is a caused by inadequate ACTH stimulating the adrenal glands, resulting in low levels of cortisol being released. This is the result of loss or damage to the pituitary gland. This can be due to congenital underdevelopment (hypoplasia) of the pituitary gland, surgery, infection, loss of blood flow or radiotherapy.
What is Tertiary adrenal insufficiency
Tertiary adrenal insufficiency is the result of inadequate CRH release by the hypothalamus. This is usually the result of patients being on long term oral steroids (for more than 3 weeks) causing suppression of the hypothalamus. When the exogenous steroids are suddenly withdrawn the hypothalamus does not “wake up” fast enough and endogenous steroids are not adequately produced. Therefore, long term steroids should be tapered slowly to allow time for the adrenal axis to regain normal function.
Adrenal Insufficiency of Features in Babies
Lethargy
Vomiting
Poor feeding
Hypoglycaemia
Jaundice
Failure to thrive
Adrenal Insufficiency Features in Older Children
- Nausea and vomiting
- Poor weight gain or weight loss
- Reduced appetite (anorexia)
- Abdominal pain
- Muscle weakness or cramps
- Developmental delay or poor academic performance
- Bronze hyperpigmentation to skin in Addison’s caused by high ACTH levels. ACTH stimulates melanocytes.
Investigations of adrenal insufficency
- All children with suspected adrenal insufficiency should have U&Es (hyponatraemia and hyperkalaemia) and blood glucose (hypoglycaemia) levels checked.
- Test for the diagnosis with cortisol, ACTH, aldosterone and renin levels, prior to administering steroids if possible.
- Short Synacthen Test (ACTH Stimulation Test)
Low cortisol
High ACTH
Low aldosterone
High renin
Does this suggest?
Addisons Disease (Primary Adrenal Failure)
Low cortisol
Low ACTH
Normal aldosterone
Normal renin
What does this suggest?
Secondary Adrenal Insufficiency
What is Short Synacthen Test (ACTH Stimulation Test)
The short synacthen test can be used to confirm adrenal insufficiency. It is ideally performed in the morning when the adrenal glands are the most “fresh”. The test involves giving synacthen, which is synthetic ACTH. The blood cortisol is measured at baseline, 30 and 60 minutes after administration. The synthetic ACTH will stimulate healthy adrenal glands to produce cortisol. The cortisol level should at least double in response to synacthen. A failure of cortisol to rise (less than double the baseline) indicates primary adrenal insufficiency (Addison’s disease).
Treatment of adrenal insufficiency
Treatment of adrenal insufficiency is with replacement steroids titrated to signs, symptoms and electrolytes.
Hydrocortisone is a glucocorticoid hormone used to replace cortisol. Fludrocortisone is a mineralocorticoid hormone used to replace aldosterone if aldosterone is also insufficien
Patients are given a steroid card and an emergency ID tag to inform emergency services they are dependent on steroids for lifet.
Patients should be followed up by a specialist paediatric endocrinologist and have an individual care plan. They are monitored closely for:
Growth and development
Blood pressure
U&Es
Glucose
Bone profile
Vitamin D
What is Addisonian Crisis (AKA Adrenal Crisis)
Addisonian crisis is the term used to describe an acute presentation of severe Addisons, where the absence of steroid hormones result in a life threatening presentation. Patients can be very unwell. They present with:
- Reduced consciousness
- Hypotension
- Hypoglycaemia, hyponatraemia and hyperkalaemia
Do not wait to perform investigations and establish a definitive diagnosis before initiating treatment for someone with suspected Addisonian crisis, as the condition is life threatening and immediate treatment is required.
Management of Addisonian Crisis
- Intensive monitoring if they are acutely unwell
- Parenteral steroids (i.e. IV hydrocortisone)
- IV fluid resuscitation
- Correct hypoglycaemia
- Careful monitoring of electrolytes and fluid balance
WHat is congential adrenal hyperplasia
Congenital adrenal hyperplasia is caused by a congenital deficiency of the 21-hydroxylase enzyme. This causes underproduction of cortisol and aldosterone and overproduction of androgens from birth. It is a genetic condition that is inherited in an autosomal recessive pattern.
In a small number of cases it is caused by a deficiency of 11-beta-hydroxylase rather than 21-hydroxylase.
Testosterone is an androgen hormone. It is found in high levels in men and low levels in women. It acts to promote….
male sexual characteristics.
Function of Glucocorticoid hormones
Glucocorticoid hormones act to help the body deal with stress, raise blood glucose, reduce inflammation and suppress the immune system. Cortisol is the main glucocorticoid hormone. The level of cortisol fluctuates during the day, with higher levels in the morning and during times of stress
Function of Mineralocorticoid hormones
Mineralocorticoid hormones act on the kidneys to control the balance of salt and water in the blood. Aldosterone is the main mineralocorticoid hormone. It is released by the adrenal gland in response to renin. Aldosterone acts on the kidneys to increase sodium reabsorption into the blood and increase potassium secretion into the urine. Therefore, aldosterone acts to increase sodium and decrease potassium in the blood.
21-hydroxylase is the enzyme responsible for converting ________ into aldosterone and cortisol. Progesterone is also used to create testosterone, but this conversion does not rely on the 21-hydroxylase enzyme.
In CAH, there is a defect in the __ ________ enzyme. Therefore, because there is extra progesterone floating about that cannot be converted to aldosterone or cortisol, it gets converted to ________ instead. The result is a patient with ___ aldosterone, ___ cortisol and abnormally ___ testosterone.
21-hydroxylase is the enzyme responsible for converting progesterone into aldosterone and cortisol. Progesterone is also used to create testosterone, but this conversion does not rely on the 21-hydroxylase enzyme.
In CAH, there is a defect in the 21-hydroxylase enzyme. Therefore, because there is extra progesterone floating about that cannot be converted to aldosterone or cortisol, it gets converted to testosterone instead. The result is a patient with low aldosterone, low cortisol and abnormally high testosterone.
Female patients with CAH usually presents at birth with virilised genitalia, known as “______ ______” and an enlarged clitoris due to the ____ testosterone levels.
Female patients with CAH usually presents at birth with virilised genitalia, known as “ambiguous genitalia” and an enlarged clitoris due to the high testosterone levels.
Patients with more severe CAH present shortly after birth with _________, __________, and __________
Patients with more severe CAH present shortly after birth with hyponatraemia, hyperkalaemia and hypoglycaemia.
CAH
This leads to signs and symptoms:
Poor feeding
Vomiting
Dehydration
Arrhythmias
CAH
Patients who are less severely affected present during childhood or after puberty. Their symptoms tend to be related to
high androgen levels.
Presentation in Mild Cases
Female patients:
Tall for their age
Facial hair
Absent periods
Deep voice
Early puberty
Presentation in Mild Cases
Male patients:
Tall for their age
Deep voice
Large penis
Small testicles
Early puberty
: A textbook and exam clue that a patient has CAH is ____ ____________
: A textbook and exam clue that a patient has CAH is skin hyperpigmentation.
CAH
Management will be coordinated by specialist paediatric endocrinologists. They will be followed up closely for their growth and development. Treatment involves:
- Cortisol replacement, usually with hydrocortisone, similar to treatment for adrenal insufficiency
- Aldosterone replacement, usually with fludrocortisone
- Female patients with “virilised” genitals may require corrective surgery
Growth hormone stimulates the release of
insulin-like growth factor 1 (IGF-1) by the liver, which is also important in promoting growth in children and adolescents.
Congenital growth hormone deficiency results from a disruption to the growth hormone axis at the hypothalamus or pituitary gland. It can be due to a known genetic mutation such as the GH1 (growth hormone 1) or GHRHR (growth hormone releasing hormone receptor) genes, or due to another condition such as _______ ___ ______ the pituitary gland is under-developed or damaged.
Congenital growth hormone deficiency results from a disruption to the growth hormone axis at the hypothalamus or pituitary gland. It can be due to a known genetic mutation such as the GH1 (growth hormone 1) or GHRHR (growth hormone releasing hormone receptor) genes, or due to another condition such as empty sella syndrome where the pituitary gland is under-developed or damaged.
Acquired growth hormone deficiency can be secondary to
infection, trauma or interventions such as surgery.
Growth hormone deficiency may present at birth or in neonates with:
Micropenis (in males)
Hypoglycaemia
Severe jaundice
Presentation
Growth hormone deficiency
Older infants and children can present with:
Poor growth, usually stopping or severely slowing from age 2-3
Short stature
Slow development of movement and strength
Delayed puberty
Growth hormone deficiency Ix
Investigation, diagnosis and management will be made by specialists in paediatric endocrinology.
Growth hormone stimulation test:
Growth hormone levels are monitored regularly for 2-4 hours after administering the medication to assess the hormonal response. In growth hormone deficiency there will be a poor response to stimulation.
Other investigations:
- Test for other associated hormone deficiencies, for example thyroid and adrenal deficiency
- MRI brain for structural pituitary or hypothalamus abnormalities
- Genetic testing for associated genetic conditions such as Turner syndrome and Prader–Willi syndrome
- Xray (usually of the wrist) or a DEXA scan can determine bone age and help predict final height
Children with growth hormone deficiency will be managed and followed up by a paediatric endocrinologist with
Daily subcutaneous injections of growth hormone (somatropin)
Treatment of other associated hormone deficiencies
Close monitoring of height and development
Hypothyroidism in children can be ______or acquired.
Hypothyroidism in children can be congenital or acquired.
Congenital hypothyroidism is screened for on the newborn blood spot screening test. Where it is not picked up a birth, patients can present with:
- Prolonged neonatal jaundice
- Poor feeding
- Constipation
- Increased sleeping
- Reduced activity
- Slow growth and development
What is Acquired Hypothyroidism
Acquired hypothyroidism is where a child or adolescent develops an underactive thyroid gland when previously it was functioning normally.
The most common cause of acquired hypothyroidism is
autoimmune thyroiditis, also known as Hashimoto’s thyroiditis.
What antibodies and diseases are associated with Hashimoto’s thyroiditis.
antithyroid peroxidase (anti-TPO) antibodies and antithyroglobulin antibodies.
There is an association with other autoimmune conditions, particularly type 1 diabetes and coeliac disease.
Acquired Hypothyroidism
symptoms
Fatigue and low energy
Poor growth
Weight gain
Poor school performance
Constipation
Dry skin and hair loss
Management of hypothyroidism
Children will be managed and followed up by a paediatric endocrinologist. Investigations include full thyroid function blood tests (TSH, T3 and T4), thyroid ultrasound and thyroid antibodies.
Levothyroxine orally once a day is used to replace the normal thyroid hormones. Doses are titrated based on thyroid function tests and symptoms.
Common causes of Hearing loss
COngenital
perinatal
after birth
Congenital
- Maternal rubella or cytomegalovirus infection during pregnancy
- Genetic deafness can be autosomal recessive or autosomal dominant
- Associated syndromes, for example Down’s syndrome
Perinatal
- Prematurity
- Hypoxia during or after birth
After birth
- Jaundice
- Meningitis and encephalitis
- Otitis media or glue ear
- Chemotherapy
The UK newborn hearing screening programme (NHSP) tests hearing in all neonates. This involves special equipment that delivers sound to each eardrum individually and checks for a response. This can identify congenital hearing problems early.
Children with hearing difficulties may present with parental concerns about hearing or with behavioural changes associated with not being able to hear:
Ignoring calls or sounds
Frustration or bad behaviour
Poor speech and language development
Poor school performance
What is audiometry
Younger children (under 3 years) are tested by looking for a basic response to sound (i.e. turning towards a sound). Older children can be tested properly with headphones and specific tones and volumes. The results of audiometry testing are recorded on an audiogram, which can help identify and differentiate conductive and sensorineural hearing loss.
What is a Audiogram
Audiograms are charts that document the volume at which patients can hear different tones. The frequency in hertz (Hz) is plotted on the x-axis, from low to high pitched. The volume in decibels (dB) is plotted on the y-axis, from loud at the bottom to quiet at the top. It is worth noting that the lower down the chart, the higher the decibels and the louder the volume.
What is Otitis Media
Otitis media is the name given to an infection in the middle ear. The middle ear is the space that sits between the tympanic membrane (ear drum) and the inner ear. This is where the cochlea, vestibular apparatus and nerves are found. It is a very common site of infection in children. The bacteria enter from the back of the throat through the eustachian tube. Bacterial infection of the inner ear is often preceded by a viral upper respiratory tract infection.
The most common bacterial causes of otitis media, as well as other ENT infections such as ________ ________ and tonsillitis is _____________ ____
The most common bacterial causes of otitis media, as well as other ENT infections such as rhino-sinusitis and tonsillitis is streptococcus pneumoniae.
Other causes of otitis media
- Haemophilus influenzae
- Moraxella catarrhalis
- Staphylococcus aureus
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Presentation
Otitis media
Otitis media typically presents with ear pain, reduced hearing in the affected ear and general symptoms of upper airway infection such as fever, cough, coryzal symptoms, sore throat and feeling generally unwell.
When the infection affects the vestibular system it can cause balance issues and vertigo. When the tympanic membrane has perforated there may be discharge from the ear.
It is worth noting that symptoms can be very non-specific, particularly in young children and infants. They may present with symptoms of fever, vomiting, irritability, lethargy or poor feeding. It is always worth examining the ears in unwell children.
What does otitis media look like on examination
In a normal child the tympanic membrane should be “pearly-grey”, translucent and slightly shiny. You should be able to visualise the malleus through the membrane and a cone of light reflecting the light of the otoscope.
Otitis media will give a bulging, red, inflamed looking membrane. When there is a perforation, you may see discharge in the ear canal and a hole in the tympanic membrane.
Management of otitis media
Most cases of otitis media will resolve without antibiotics,
The first line choice of antibiotic is amoxicillin for 5 days. Alternatives are erythromycin and clarithromycin.
otitis media complications
- Otitis medial with effusion
- Hearing loss (usually temporary)
- Perforated eardrum
- Recurrent infection
- Mastoiditis (rare)
- Abscess (rare)
What is Glue ear also known as
Glue ear is also known as otitis media with effusion. The middle ear becomes full of fluid, causing a loss of hearing in that ear.
The__________ ____ connects the middle ear to the back of the throat. It helps drain secretions from the middle ear. When it becomes blocked, this causes middle ear secretions (fluid) to build up in the middle ear spac
The Eustachian tube connects the middle ear to the back of the throat. It helps drain secretions from the middle ear. When it becomes blocked, this causes middle ear secretions (fluid) to build up in the middle ear spac
Symptoms and Presentation of GLue ear
The main symptom of glue ear is a reduction in hearing in that ear. The main complication of glue ear is infection (otitis media).
Otoscopy can show a dull tympanic membrane with air bubbles or a visible fluid level, although it can look normal.
Management of glue ear
Referral for audiometry to help establish the diagnosis and extent of hearing loss. Glue ear is usually treated conservatively, and resolves without treatment within 3 months. Children with co-morbidities affecting the structure of the ear, such as Down’s syndrome or cleft palate may require hearing aids or grommets
