Paediatric - Endocrinology Flashcards
What is adrenal insufficiency and what are the causes of each of the three types?
Pathognomic presentation of addisons?
Adrenal insufficiency is where the adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone. Steroids are essential for life. Therefore, the condition is life threatening unless the hormones are replaced.
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.
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.
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 When the exogenous steroids are suddenly withdrawn the hypothalamus does not “wake up” fast enough and endogenous steroids are not adequately produced.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.
In babies it presents with:
- Features in Babies
Lethargy
Vomiting
Poor feeding
Hypoglycaemia
Jaundice
Failure to thrive
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.
Fairly non specific basically, apart from the hyperpigmentation in children - wuldnt bother memorising too much but just be aware of it
What are the investigations for adrenal insufficiency?
Management?
Ix:
- U+E and blood glucose to check for hyponatreamia and hypocalaemia (aldosterone stimulates Na reabsorbtion)
- Test cortisol, ACTH, aldosterone and renin levels
- Addisons: low cortisol, high ACTH
- Secondary adrenal - low cortisol, low ACTH
Short Synacthen Test - Synathetic ACTH = Synacten
Confrims adrenal insufficiency. Giving synacthen stimulates healthy adrenal glands to produce cortisol (levels should double). Failure to double indicates primary adrenal insufficiency
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Hydrocortisone to replace cortisol
Fludrocortisone to replace aldosterone
Titrated to symptoms and electrolyte levels
Sick day rules - double if have fever, diarhoea of vomitting
What is an addisonian crisis?
How is it managed?
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
Adrenal crisis can be the first presentation of Addison’s disease or triggered by infection, trauma or other acute illness in someone with established Addison’s. It can also occur in patients on long term steroids that have suppressed their natural steroid production, if that patient stops taking the steroids abruptly.
Management
- IV HYDROCORTISONE
- IV fluids
- correct hypoglycemia
- monitor electrolytes
Type 1 diabetes mellitus (T1DM) is a disease where the pancreas stops being able to produce insulin
About 25 – 50% of new type 1 diabetic children present in diabetic ketoacidosis (DKA)
The remaining paediatric patients present with the classic triad of symptoms of hyperglycaemia:
Polyuria (excessive urine)
Polydipsia (excessive thirst)
Weight loss (mostly through dehydration)
When a new diagnosis of T1DM is established what Ix should be taken? - 5
What does management involve - 4 things?
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 testsand 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
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Management involves the following components:
Subcutaneous insulin regimes - Insulin is usually prescribed as a combination of a background, long acting (basal) insulin given once a day, and a short acting (bolus) insulin injected 30 minutes before the intake of carbohydrates (i.e. at meals). Cycle injection sites to prevent lipodystrophy.
Insulin pumps are small devices that continuously infuse insulin at different rates to control blood sugar levels. They are an alternative to basal blous regimes. To be eligible for a pump the child must be over 12 and have difficulty controlling their HbA1c
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 - Short term are Hypoglyceamia and DKA
DKA
Ketone acids (ketones) are buffered in normal patients so the blood does not become acidotic. When underlying pathology (i.e. type 1 diabetes) causes extreme hyperglycaemic ketosis, this results in a metabolic acidosis that is life threatening. This is called diabetic ketoacidosis.
criteria?
How does DKA present?
2 steps to management?
Big risk in management?
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)
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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.
REMEMBER FIG PICK
Fluids
Insulin
Glucose (keep above 14)
Add potassium to IV fluids.
Treat underlying infection.
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Children with DKA are at high risk of developing cerebral oedema. Dehydration and high blood sugar concentration cause water to move from the intracellular space in the brain to the extracellular space. This causes the brain cells to shrink and become dehydrated. Rapid correction of dehydration and hyperglycaemia (with fluids and insulin) causes a rapid shift in water from the extracellular space to the intracellular space in the brain cells. This causes the brain to swell and become oedematous, which can lead to brain cell destruction and death.
Neurological observations (i.e. GCS) should be monitored very closely (e.g. hourly) to look for signs of cerebral oedema. Be concerned when patients being treated for diabetic ketoacidosis develop headaches, altered behaviour, bradycardia or changes to consciousness.
Management options for cerebral oedema are slowing IV fluids, IV mannitol and IV hypertonic saline. These should be guided by an experienced paediatrician.
Other than DKA, what is the other short term complication of T1DM?
Sx?
Management?
Hypoglycaemia
Hypoglycaemia is a low blood sugar level. In diabetes this is caused by:
- too much insulin
- not enough carbohydrates
- too much exercise
- malabsortion in gastroenteritis
Typical symptoms are hunger, tremor, sweating, irritability, dizziness and pallor. More severe hypoglycaemia will lead to reduced consciousness, coma and death unless treated.
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 - IV dextrose or intramuscular glucagon.
How does Congenital adrenal hyperplasia present - both severe and mild cases for male and female?
Unique presenting feature?
Management?
Severe cases:
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 hyponatraemia, hyperkalaemia and hypoglycaemia -> similar to adrenal insufficiency (essentially its is addisons + the high testosterone)
This leads to signs and symptoms:
- Poor feeding
- Vomiting
- Dehydration
- Arrhythmias
Presentation in Mild Cases:
Patients who are less severely affected present during childhood or after puberty. Their symptoms tend to be related to high androgen levels.
Female patients:
- Tall for their age
- Facial hair
- Absent periods
- Deep voice
- Early puberty
Male patients:
- Tall for their age
- Deep voice
- Large penis
- Small testicles
- Early puberty
TOM TIP: A textbook and exam clue that a patient has CAH is skin hyperpigmentation. Hyperpigmentation occurs because the anterior pituitary gland responds to the low levels of cortisol by producing increasing amounts of ACTH. A byproduct of the production of ACTH is melanocyte simulating hormone. This hormone stimulates the production of melanin (pigment) within skin cells.
Manament:
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
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Background notes on steroids
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.
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. It is released in response to adrenocorticotropic hormone (ACTH) from the anterior pituitary.
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.
What is congenital adrenal hyperplasia?
How does it affect 3 hormones?
Cause?
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.
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.
What is androgen insensitivity syndrome?
Management
Androgen insensitivity syndrome is a condition where cells are unable to respond to androgen hormones due to a lack of androgen receptors. It is an X-linked recessive genetic condition, caused by a mutation in the androgen receptor gene on the X chromosome. Extra androgens are converted into oestrogen, resulting in female secondary sexual characteristics. It was previously known as testicular feminisation syndrome.
Patients with androgen insensitivity syndrome are genetically male, with XY sex chromosome. However, the absent response to testosterone and the conversion of additional androgens to oestrogen result in a female phenotype externally. Typical male sexual characteristics do not develop, and patients have normal female external genitalia and breast tissue.
Patients have testes in the abdomen or inguinal canal, and absence of a uterus, upper vagina, cervix, fallopian tubes and ovaries. The female internal organs do not develop because the testes produce anti-Müllerian hormone, which prevents males from developing an upper vagina, uterus, cervix and fallopian tubes.
The insensitivity to androgens also results in a lack of pubic hair, facial hair and male type muscle development. Patients tend to be slightly taller than the female average. Patients are infertile, and there is an increased risk of testicular cancer unless the testes are removed.
This section mainly covers complete androgen insensitivity syndrome. There is also a condition called partial androgen insensitivity syndrome, where there the cells have a partial response to androgens. This presents with more ambiguous signs and symptoms, such as a micropenis or clitoromegaly, bifid scrotum, hypospadias and diminished male characteristics.
Androgen insensitivity syndrome often presents in infancy with inguinal hernias containing testes. Alternatively, it presents at puberty with primary amenorrhoea.
Management:
Bilateral Orchidectomy
Oestrogen therapy
Vaginal Dilators or vaginal surgery
What are the two types of hypothyroidism in children?
How does each present?
Investigations and management?
Hypothyroidism in children can be congenital or acquired. Thyroid hormone is essential for the development and functioning of the brain and body. Undiagnosed hypothyroidism can lead to significant problems with neurodevelopment and intellectual disability.
Congenital Hypothyroidism
Congenital hypothyroidism is where the child is born with an underactive thyroid gland. This occurs in around 1 in 3000 newborns. I**t can be the result of an underdeveloped thyroid gland (dysgenesis) or a fully developed gland that does not produce enough hormone (dyshormonogenesis). **Very rarely it can be the result of a problem with the pituitary or hypothalamus. This usually occurs without any other problems and the cause is not clear.
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
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. This causes autoimmune inflammation of the thyroid gland and subsequent under activity of the gland. It is associated with antithyroid peroxidase (anti-TPO) antibodies and antithyroglobulin antibodies. There is an association with other autoimmune conditions, particularly type 1 diabetes and coeliac disease.
This can lead to symptoms of:
Fatigue and low energy
Poor growth
Weight gain
Poor school performance
Constipation
Dry skin and hair loss
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.
Delay in puberty can be due to hypogonadism. What are the two types of hypogonodism?
Causes of Each?
Investigations?
Hypogonadotrophic hypogonadism: a deficiency of LH and FSH. Leads to deficiency of the sex hormones because there are no gonadotrophins stimulating the gonads.
Caused by:
- damage to the hypothalamus or pituraty from radiotherapy, surgery or cancer
- GH deficiency
- hypothyrodism
- hyperprolactinaemia
- Cystic fibrosis or IBD
- anorexia in girls
- constiutational delay in growth (look at the growth plates)
- Kallman syndrome
Hypergonadotrophic hypogonadism: a lack of response to LH and FSH by the gonads (the testes and ovaries). It is the result of abnormal funtion of the gonads due to:
- damage to the gonads - tosion, cancer, infections
- congeintal obsence of hte gonads
- kleinfelter’s syndrome
- turner’s syndrome - CAME UP
Both have hypogonaidsm - low oestrogen and testosterone
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Ix:
Initated at 13 or 14 for girls and boys respectively when there is no evidence of puberty
Initial investigations can be used to look for underlying medical conditions:
- Full blood count and ferritin for anaemia
- U&E for chronic kidney disease
- Anti-TTG or anti-EMA antibodies for coeliac disease
Hormonal blood tests can be used to look for hormonal abnormalities:
- Early morning serum FSH and LH (the gonadotropins). These will be low in hypogonadotrophic hypogonadism and high in hypergonadotrophic hypogonadism.
- Thyroid function tests
- Growth hormone testing. Insulin-like growth factor I is often used as a screening test for GH deficiency.
- Serum prolactin
- Genetic testing with a microarray test can be used to look for underlying genetic conditions: Kleinfelter’s syndrome (XXY) Turner’s syndrome (XO)
Imaging can be useful:
- Xray of the wrist to assess bone age and inform a diagnosis of constitutional delay
- Pelvic ultrasound in girls to assess the ovaries and other pelvic organs
- MRI of the brain to look for pituitary pathology and assess the olfactory bulbs in possible Kallman syndrome
What is precautios puberty?
Two types?
Ix?
Rx?
Early puberty:
- before 8 in girls (development of breast buds is 2 years before menarche)
- before 9 in boys (enlargement of the testicles then the penis)
Two forms exist: gonadotrophin-dependent precocious puberty (known as central precocious puberty [CPP]; due to premature activation of the hypothalamo-pituitary-gonadal axis) and gonadotrophin-independent precocious puberty (GIPP; due to autonomous secretion of sex steroids)
Cases:
Central PP:
- idiopathic - most common in females
- brain neoplasm
- pituiatry damage form radiotherapy/head injury
- Others…
GIPP:
- ovarian or testicular tumours
- congenital adrenal hyperplasia in males
- McCune-Albright syndrome - random genetic disease
Ix:
- tanner staging
- gondaotrophin levels - FSH and LH concentrations helps differentiate patients with central precocious puberty (CPP), with elevated levels, from those with gonadotrophin-independent precocious puberty (GIPP), with low levels.
- US gonads/MRI brain
- GnRH stimulation test- specialist
Rx: GnRH analogues
What is Kallman Syndrome?
Ix
Kallman syndrome is a genetic condition causing hypogonadotrophic hypogonadism, resulting in failure to start puberty. It is associated with a reduced or absent sense of smell (anosmia).
Ix:
once more common causes have been excluded i assume…
MRI of the brain to look for pituitary pathology and assess the olfactory bulbs in possible Kallman syndrome
