Endocrinology

Question 1

What is thought to cause T1DM?

Answer 1

There may be a genetic component. It may be triggered by certain viruses, such as the Coxsackie B virus and enterovirus.

Question 2

Which cells produce insulin?

Answer 2

Insulin is produced by the beta cells in the Islets of Langerhans in the pancreas.

Question 3

What type of hormone is insulin?

Answer 3

Anabolic

Question 4

How does insulin act to lower blood sugars?

Answer 4

Firstly, it causes cells to absorb glucose from the blood and use it as fuel.

Secondly, it causes muscle and liver cells to absorb glucose from the blood and store it as glycogen.

Insulin is essential in letting cells take glucose out of the blood and use it as fuel. Without insulin, cells cannot take up and use glucose, leading to hyperglycemia

Question 5

What does glucagon do?

Answer 5

Glucagon is a hormone that increases blood sugar levels. It tells the liver to break down stored glycogen into glucose. This process is called glycogenolysis. It also tells the liver to convert proteins and fats into glucose. This process is called gluconeogenesis.

Question 6

Where if glucagon produced?

Answer 6

It is produced by the alpha cells in the Islets of Langerhans in the pancreas.

Question 7

What type of hormone is glucagon?

Answer 7

It is a catabolic hormone (a breakdown hormone).

Question 8

When is glucagon released?

Answer 8

It is released in response to low blood sugar levels and stress.

Question 9

When is insulin released?

Answer 9

It is always present in small amounts, but increases when blood sugar levels rise.

Question 10

When and why does ketogenesis occur?

Answer 10

Ketogenesis occurs when there is insufficient supply of glucose, and glycogens stores are exhausted, such as in prolonged fasting.

The liver takes fatty acids and converts them to ketones.

Ketones are water soluble fatty acids that can be used as fuel.

They can cross the blood brain barrier and be used by the brain.

Producing ketones is normal and not harmful in healthy patients when under fasting conditions or on a very low carbohydrate, high fat diet.

People in ketosis have a characteristic acetone smell to their breath.

Question 11

What presentation do 25-50% of children with T1DM initially present with?

Answer 11

Diabetic ketoacidosis

This is the result of a situation where the pancreas can no longer produce enough insulin to maintain basic blood glucose regulation.

Question 12

T1DM symptoms?

Answer 12

Polydipsia
Polyuria
Weight loss

Question 13

In what ways might T1DM present?

Answer 13

About 25 – 50% of new type 1 diabetic children present in diabetic ketoacidosis (DKA). This is the result of a situation where the pancreas can no longer produce enough insulin to maintain basic blood glucose regulation.

The remaining paediatric patients present with the classic triad of symptoms of hyperglycaemia:

Polyuria (excessive urine)
Polydipsia (excessive thirst)
Weight loss (mostly through dehydration)

Other less typical presentations include secondary enuresis (bedwetting in a previously dry child) and recurrent infections. Symptoms are usually present from 1 to 6 weeks prior to developing DKA, however this can vary significantly.

Question 14

When a new diagnosis is established what bloods should be taken to exclude other associated pathology and get a baseline idea of the child’s overall health?

Answer 14

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

Question 15

Long term management of T1DM?

Answer 15

Patient and family education is essential. Monitoring and treatment is relatively complex. The condition is life-long and requires the patient to fully understand and engage with their condition. Patients need to take responsibility for their diabetes and become “expert patients” as they mature and become independent from their family.

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

Question 16

Insulin regimes?

Answer 16

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 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.

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.

Question 17

Insulin pumps

Answer 17

Insulin pumps are small devices that continuously infuse insulin at different rates to control blood sugar levels. They are an alternative to the basal bolus regimes. The pump pushes insulin through a small plastic tube (cannula) that is inserted under the skin. The cannula is replaced every 2 – 3 days and the insertion sites are rotated to prevent lipodystrophy and absorption issues.

To qualify for an insulin pump funded by the NHS the child needs to be over 12 and have difficulty controlling their HbA1c. Local criteria may vary.

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
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.

Question 18

Short term complications T1DM?

Answer 18

Short term complications relate to immediate insulin and blood glucose management:

Hypoglycaemia
Hyperglycaemia (and DKA)

Question 19

Treating Hypoglycemia

Answer 19

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 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.

Question 20

What is hypoglycemia and what presentations may occur?

Answer 20

Hypoglycaemia is a low blood sugar level. In diabetes this is caused by too much insulin, not enough carbohydrates or not processing the carbohydrates properly, for example in malabsorption, diarrhoea and vomiting and sepsis.

Most patients are aware when they are hypoglycaemic by their symptoms, however some patients can be unaware until severely hypoglycaemic.

Typical symptoms are hunger, tremor, sweating, irritability, dizziness and pallor.

More severe hypoglycaemia will lead to reduced consciousness, coma and death unless treated.

Question 21

Causes of hypoglycemia in patients not on insulin therapy?

Answer 21

Other causes of hypoglycaemia include hypothyroidism, glycogen storage disorders, growth hormone deficiency, liver cirrhosis, alcohol and fatty acid oxidation defects (such as MCADD).

Question 22

What is nocturnal hypoglycaemia?

Answer 22

Nocturnal hypoglycaemia is a common complication of insulin therapy

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.

Question 23

Management of hypergylcemia

Answer 23

Patients that are hyperglycaemic, but not in DKA, may require their insulin dose to be increased.

Patients will get to know their own individual response to insulin and be able to administer a dose to correct the hyperglycaemia.

For example, they may learn that 1 unit of novorapid reduces their sugar level by around 4 mmol/l.

Be conscious that it can take several hours to take effect and repeated doses could lead to hypoglycaemia.

When they meet the criteria for DKA they need admission for inpatient management.

Question 24

T1DM - long term complications

Answer 24

Chronic exposure to hyperglycaemia causes damage to the endothelial cells of blood vessels. This leads to leaky, malfunctioning vessels that are unable to regenerate. High levels of sugar in the blood also causes suppression of the immune system, and creates an optimal environment for infectious organisms to thrive.

Macrovascular Complications

Coronary artery disease is a major cause of death in diabetics
Peripheral ischaemia causes poor healing, ulcers and “diabetic foot”
Stroke
Hypertension

Microvascular Complications

Peripheral neuropathy
Retinopathy
Kidney disease, particularly glomerulosclerosis

Infection Related Complications

Urinary tract infections
Pneumonia
Skin and soft tissue infections, particularly in the feet
Fungal infections, particularly oral and vaginal candidiasis

Question 25

T1DM blood sugar monitoring

Answer 25

HbA1c When we check HbA1c we are counting glycated haemoglobin, which is how much glucose is attached to the haemoglobin molecules inside red blood cells. This is considered to reflect the average blood glucose level over the last 3 months, because red blood cells have a lifespan of around 3 to 4 months. We measure it every 3 to 6 months to track the average blood sugar over time and determine how effective our interventions are and how well controlled the diabetes is. It requires a blood sample sent to the lab, usually red top EDTA bottle. Capillary Blood Glucose Capillary blood glucose is measured using a little machine called a glucose meter. It gives an immediate result. Patients with type 1 and type 2 diabetes rely on these machines to self-monitor their sugar levels. Flash Glucose Monitoring (e.g. FreeStyle Libre) This uses a sensor on the skin that measures the glucose level of the interstitial fluid in the subcutaneous tissue. There is a 5 minute lag behind blood glucose. The sensor records the glucose readings at short intervals so you get a really good impression of what the glucose levels are doing over time. The user needs to use a “reader” to swipe over the sensor. The reader shows the blood sugar readings. Sensors need replacing every 2 weeks for the FreeStyle Libre system. It is quite expensive and NHS funding is only available in certain areas at present. The 5 minute delay also means it is necessary to do capillary blood glucose (finger prick testing) checks if hypoglycaemia is suspected.

Question 26

Pathophysiology of DKA?

Answer 26

Diabetic ketoacidosis occurs in type 1 diabetes, where the person is not producing adequate insulin themselves and is not injecting adequate insulin to compensate for this. It occurs when they body does not have enough insulin to use and process glucose. The main problems are ketoacidosis, dehydration and potassium imbalance. Ketoacidosis When the cells in the body have no fuel and think they are starving, they initiate the process of ketogenesis so they have a usable fuel. Ketogenesis normally occurs when there is an insufficient supply of glucose and glycogens stores are exhausted. This may happen during prolonged fasting or very low carbohydrate diets. The liver takes fatty acids and converts them to ketones. Ketones are water soluble fatty acids that can be used as fuel. They can cross the blood brain barrier and be used by the brain. Over time the glucose and ketone levels get higher and higher. Initially the kidneys produce bicarbonate to buffer the ketone acids in the blood and maintain a normal pH. Over time the ketone acids use up the bicarbonate and the blood starts to become acidic. This is called ketoacidosis. Dehydration Hyperglycaemia overwhelms the kidneys and glucose starts being filtered into the urine. The glucose in the urine draws water out with it in a process called osmotic diuresis. This causes the patient to urinate a lot (polyuria). This results in severe dehydration. The dehydration stimulates the thirst centre to tell the patient to drink lots of water. This excessive thirst is called polydipsia. 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.

Question 27

Management of DKA

Answer 27

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. Follow local treatment protocols and involve senior paediatricians. The two pillars of correcting DKA are: 1. 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. 2. 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.

Question 28

Diagnosing DKA

Answer 28

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) Ketone levels can be measured in the urine using a urine dipstick and in the blood using a ketone meter.

Question 29

When is ketogenesis normal?

Answer 29

Producing ketones is normal and not harmful in healthy patients when under fasting conditions or on a very low carbohydrate, high fat diet.

Question 30

Children with DKA are at high risk of developing cerebral oedema - why might this occur and how might this be managed?

Answer 30

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.Wh

Question 31

Presentation of DKA?

Answer 31

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)

Question 32

What is adrenal insufficiency?

Answer 32

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.

Question 33

What is Addison's disease?

Answer 33

Addison’s disease refers a the specific condition of adrenal insufficiency, 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.

Question 34

What is secondary adrenal insufficiency?

Answer 34

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.

Question 35

What is tertiary adrenal insufficiency?

Answer 35

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.

Question 36

Features of adrenal insufficiency in babies?

Answer 36

Lethargy Vomiting Poor feeding Hypoglycaemia Jaundice Failure to thrive

Question 37

Features of adrenal insufficiency in older children?

Answer 37

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.

Question 38

What does bronze hyperpigmentation to skin in Addison’s occur?

Answer 38

ACTH stimulates melanocytes.

Question 39

How is ?adrenal insufficiency investigated:

Answer 39

All children with suspected adrenal insufficiency should have: U&Es (hyponatraemia and hyperkalaemia) Blood glucose (hypoglycaemia) levels Test for the diagnosis with cortisol, ACTH, aldosterone and renin levels, prior to administering steroids if possible.

Question 40

Primary adrenal failure: investigation results

Answer 40

Low cortisol High ACTH Low aldosterone High renin Hyponatremia, hyperkalaemia and hypoglycaemia as per secondary and tertiary adrenal failure

Question 41

Secondary adrenal failure: investigation results

Answer 41

Low cortisol Low ACTH Normal aldosterone Normal renin Hyponatremia, hyperkalaemia and hypoglycaemia as per primary and tertiary adrenal failure

Question 42

Low cortisol, high ACTH, low aldosterone, high renin

Answer 42

Primary adrenal insufficiency

Question 43

Low cortisol, low ACTH, normal aldosterone, normal renin

Answer 43

Secondary adrenal insufficiency

Question 44

The short synacthen test can be used to confirm what?

Answer 44

Adrenal insufficiency

Question 45

Which test can be used to confirm adrenal insufficiency?

Answer 45

The short synacthen test

Question 46

How is the short synacthen test performed and what do the results suggest?

Answer 46

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).

Question 47

Management of adrenal insufficiency?

Answer 47

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 insufficient. Patients are given a steroid card and an emergency ID tag to inform emergency services they are dependent on steroids for life. Steroid doses are increased during an acute illness to match the normal steroid response to illness. 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

Question 48

Sick day rules - adrenal insufficiency

Answer 48

Usually minor coughs or colds without fever not not require a change in medications. If they are more unwell, for example with a temperature over 38ºC or vomiting and diarrhoea, there is an increased demand on the body for steroids to deal with the illness. There is also an increased risk of hypoglycaemia. They need to have an individual care plan documenting exactly how to manage acute illnesses: The dose of steroid needs to be increased and given more regularly until the illness has completely resolved. Blood sugar needs to be monitored closely and they need to eat foods containing carbohydrates regularly. With diarrhoea or vomiting, they need an IM injection of steroid at home and likely required admission for IV steroids.

Question 49

Why might adrenal crisis occur?

Answer 49

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.

Question 50

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. How might they present?

Answer 50

Reduced consciousness Hypotension Hypoglycaemia, hyponatraemia and hyperkalaemia

Question 51

Management of Addison's crisis?

Answer 51

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

Question 52

What is congenital adrenal hyperplasia?

Answer 52

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.

Question 53

What enzyme is (usually) deficient in congenital adrenal hyperplasia?

Answer 53

21 hydroxylase

Question 54

What type of hormone is testosterone and what is its action?

Answer 54

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.

Question 55

What are glucocorticoid hormones?

Answer 55

Glucocorticoid hormones act to help the body deal with stress, raise blood glucose, reduce inflammation and suppress the immune system.

Question 56

What is the main glucocorticoid hormone?

Answer 56

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.

Question 57

From where is cortisol released and what is it released in response to?

Answer 57

It is released in response to adrenocorticotropic hormone (ACTH) from the anterior pituitary.

Question 58

When are cortisol levels higher?

Answer 58

The level of cortisol fluctuates during the day, with higher levels in the morning and during times of stress.

Question 59

What is the role of mineralocorticoid hormones?

Answer 59

Mineralocorticoid hormones act on the kidneys to control the balance of salt and water in the blood.

Question 60

What is the main mineralocorticoid hormone?

Answer 60

Aldosterone

Question 61

What is the action of aldosterone?

Answer 61

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.

Question 62

Congenital Adrenal Hyperplasia Pathophysiology

Answer 62

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.

Question 63

21-hydroxylase is the enzyme responsible for converting progesterone into aldosterone and cortisol. Why does congenital adrenal hyperplasia not cause low testosterone?

Answer 63

Progesterone is also used to create testosterone, but this conversion does not rely on the 21-hydroxylase enzyme. Because there is extra progesterone floating about that cannot be converted to aldosterone or cortisol, it gets converted to testosterone instead.

Question 64

Presentation of congenital adrenal hyperplasia - severe cases?

Answer 64

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. This leads to signs and symptoms: Poor feeding Vomiting Dehydration Arrhythmias

Question 65

Presentation of congenital adrenal hyperplasia - mild cases?

Answer 65

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

Question 66

Why does CAH cause hyperpigmentation?

Answer 66

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.

Question 67

Management of congenital adrenal hyperplasia?

Answer 67

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

Question 68

Where is growth hormone produced?

Answer 68

Anterior pituitary gland

Question 69

Role of growth hormone

Answer 69

It is responsible for stimulating cell reproduction and the growth of organs, muscles, bones and height. It 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.

Question 70

Why does congenital growth hormone deficiency occur?

Answer 70

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.

Question 71

Why might acquired growth hormone deficiency occur?

Answer 71

Acquired growth hormone deficiency can be secondary to infection, trauma or interventions such as surgery.

Question 72

What might growth hormone deficiency occur alongside?

Answer 72

Growth hormone deficiency can occur in isolation or in combination with other pituitary hormone deficiencies like hypothyroidism, adrenal insufficiency and deficiencies of the gonadotrophins (LH and FSH). When the pituitary does not produce a number of pituitary hormones this is called hypopituitarism or multiple pituitary hormone deficiency.

Question 73

Presentation of growth hormone deficiency at birth or in neonates?

Answer 73

Micropenis (in males) Hypoglycaemia Severe jaundice

Question 74

How might growth hormone deficiency present in older infants and children?

Answer 74

Poor growth, usually stopping or severely slowing from age 2-3 Short stature Slow development of movement and strength Delayed puberty

Question 75

Growth hormone stimulation test?

Answer 75

Growth hormone stimulation tests involve measuring the response to medications that normally stimulate the release of growth hormone. Examples of these medications include glucagon, insulin, arginine and clonidine. 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.

Question 76

Investigating ?GH deficiency

Answer 76

Growth hormone stimulation test 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

Question 77

Management of growth hormone deficiency?

Answer 77

Children with growth hormone deficiency will be managed and followed up by a paediatric endocrinologist. Daily subcutaneous injections of growth hormone (somatropin) Treatment of other associated hormone deficiencies Close monitoring of height and development

Question 78

Why is hypothyroidism significant in children?

Answer 78

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.

Question 79

Presentation of congenital hypothyroidism?

Answer 79

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

Question 80

Why does congenital hypothyroidism occur?

Answer 80

DYSGENESIS - the result of an underdeveloped thyroid gland (dysgenesis) DYSHORMONOGENESIS - fully developed gland that does not produce enough hormone Very rarely it can be the result of a problem with the pituitary or hypothalamus.

Question 81

What is meant by acquired hypothyroidism and what may cause it?

Answer 81

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.

Question 82

Symptoms of acquired hypothyroidism?

Answer 82

Fatigue and low energy Poor growth Weight gain Poor school performance Constipation Dry skin and hair loss

Question 83

Management of hypothyroidism

Answer 83

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.

Question 84

What is the most common cause of childhood hypothyroidism in the United Kingdom?

Answer 84

Autoimmune thyroiditis