Endocrinology Flashcards
When a child has been newly diagnosed with T1 diabetes what antibodies are looked for on the blood tests?
Diabetic antibodies, Coeliac antibodies and TPO
What are some triggers which may lead to the development of T1 diabetes?
Infection (enteroviral) - usually more common in the spring and autumn
What are the most common early signs symptoms that patients with T1 diabetes may present with?
What are some other early symptoms they may present with?
Polyuria, Polydipsia, Weight loss
Lethargy Candida and other infections Skin sepsis Enuresis (bet wetting) - Secondary (Secondary eneuresis is when bed wetting develops at least 6 months (or even several years) after a person has learned to control his or her bladder)
What are the late (‘DKA’) symptoms T1 diabetic patients may present with?
Abdominal pain Vomiting Dehydration Smell of acetone breath Hyperventilation due to acidosis (Kussmaul breathing) Hypovolaemic shock Drowsiness Coma and death
What are the 3 things, according to NICE criteria, which diagnose DKA?
HAK
Hyperglycaemia - blood glucose >11mmol/L
Acidaemia - pH <7.3
Ketones >3 (blood) or ++ or more on urine
What are some signs of insulin resistance that may be seen in children with T2 diabetes?
What factors may be present in the history?
Acanthosis nigricans
Severe obesity
Skin tags
Polycystic ovary phenotype in teenage girls
What are some examples of rapid acting insulin analogues?
Novorapid (insulin lispro), Humalog (insulin glulisine), Apidra (insuling aspart)
What are some examples of long acting insulin analogues?
Levemir (insulin detemir) and Lantus (insulin glargine)
What are some examples of short acting human regular insulin?
Actrapid and Humulin S
Onset of action = 30-60 minutes. Peak = 2-4 hours
Where can insulin be injected?
Why is it important to rotate the sites?
Anterior and lateral aspects of the thigh, abdomen, buttocks
It is important to rotate the location with the aim to avoid lipohypertrophy
What level blood glucose are patients with T1 DM told to aim for? At what time in the day?
4-7mmol/L
Before meal times
What are the 2 types of regimes children may be started on for their insulin when diagnosed?
Why are these recommended?
- Started on a continuous subcutaneous insulin pump
- Started on a long acting insulin (e.g Levemir) and a rapid acting insulin (e.g Novorapid) given before meals and snack times
This is recommended because they ar eshown to achieve the best glycaemic control and reduce risks of long term complications
A measurement of a patients HbA1c is good for telling patients their diabetic control over how many weeks?
How often should it be checked?
What is the target HbA1c?
It what situations can it be misleading?
Over the past 6-12 weeks
It should be checked at least 4 times a year
Target HbA1c < 48mmol/L (6.5%)
If patient’s blood cells have a shorted life span e.g sickle cell trait or if the HbA molecule is abnormal (thalassaemia)
What are the positives of insulin pumps?
The can detect if a hypo is anticipated and withhold the administration of insulin
They also can detect nocturnal hypoglycaemias that the patient may be otherwise unaware of
What symptoms may a patient get during a hypoglycaemic episode?
How is a hypo treated?
What rate IVI may be given?
Hunger, tummy ache, dizziness, clamminess, feeling faint or dizzy or a ‘wobbly feeling’ in their legs
Treatment is dependent on level of consciousness/orientation:
If c&o and able to swallow: 15-20g of quick acting carbohydrate snack e.g 200ml orange juice and recheck blood glucose 10-15 mins after. Repeat snack up to 3 times.
If c but unco-operative: glucose gel can be squirted between teeth and gums.
In unconscious patients or tthose not responding to above measures: Start glucose IVI - 10% at 200ml/h is conscious - 10% at 200ml/15mins if unconscious - Glucagon 1mg IV/IM
Once blood glucose >4.0mmol/L and patient has recovered give long acting carbohydrate e.g slice of toast
When a child is newly diagnosed with diabetes they must undergo an education programme. What does this programme cover?
- Pathophysiology of diabetes
- Injection of insulin - technique and sites
- Blood glucose monitoring
- Healthy diet and carb counting
- Regular exercise and how to adjust for it
- Sick day rules
- Recognition and stages treatment of hypos
- Where to get advice 24hrs a day
- Voluntary groups available to help
- Psychological impact of the long term condition
Why should rapid rehydration in DKA be avoided?
Due to the risk of cerebral oedema
How is cerebral oedema treated?
Mannitol
Hypertonic saline
In the treatment of DKA when should IV insulin be started?
1 hour after administration of fluids
What are some signs of cerebral oedema?
Early manifestations include: Irritability or agitation Headache Unexpected fall in heart rate Increased blood pressure
During the treatment of DKA what is monitored in a child?
BP, RR, HR, Neuro status, U&E 2-4 hourly, Blood ketones (1-2hrly), Blood glucose (1hrly) , Fluid balance, ECG, 2xdaily weights
At what rate is insulin infused at in the treatment of DKA?
0.1unit/kg/hour
What conditions are T1 diabetics monitored for? How often and from what age?
They are screened for thyroid disease and coeliac disease on diagnosis
Blood pressure check for HTN annually
Peripheral neuropathy - foot checks annually
Annual reminder of flu vaccinations
Nephropathy - screening for microalbuminuria annually from age 12
Retinopathy/Cataracts - annually screening from age 12. Ideally should include retinal photography
What if the definition of hypoglycaemia?
Blood glucose <2.6mmol/L
Don’t get this confused with the <2.2 that is required for the insulin tolerance test
What age of children is hypoglycaemia common in?
What factors make hypoglycaemia more common in infants?
In neonates during the first few days of life
Infants have high energy requirements and they also have poor reserves of glucose from gluconeogenesis and glycogenesis so they are at risk of hypoglycaemia on fasting
What clinical features are common with hypoglycaemia?
Headache Dizziness Stomach ache Sweating Pallor
Over what time periods should infants NOT be starved for longer than?
Should not be started for >4 hours
What is ketotic hypoglycaemia of childhood?
How is it generally managed?
How does it progress in the long term
It is when children readily become hypoglycaemic following a short period of starvation. It is probably due to limited reserves for gluconeogenesis
It is usually managed by making sure that the child has regular snacks so that they do not enter levels of hypoglycaemia. Also glucose drinks when ill.
The condition usually resolves spontaneously in later life
If hypoglycaemia occurs with hepatomegaly what may this be suggestive of?
The possibility of an inherited glycogen storage disorder
What are some cause of fasting hypoglycaemia with insulin excess?
Insulinoma Excess administration of endogenous insulin Drug induced (e.g sulphonylurea) Autoimmune (insulin receptor antibodies) Beckwith syndrome
What are some causes of fasting hypoglycaemia without hyperinsulinaemia?
Ketotic hypoglycaemia of childhood
Liver disease
Glycogen storage disease
Hormonal deficiency e.g decreased GH, ACTH, Addison’s disease, congenital adrenal hyperplasia
What are some causes of reactive/non-fasting hypoglycaemia?
Maternal diabetes (child is used to a high level of blood glucose in the body so produce a high level of insulin, however, when they are born the intake of glucose in not as high as the circulating levels whilst in the womb so the enter hypoglycaemia as they are over producing insulin)
What is glycogen storage disease?
A metabolic disorder affecting the enzymes involved in glycogen synthesis, glycogen breakdown or glycolysis, typically within muscles and/or liver cells
What precautions should be taken during treatment of hypoglycaemia?
Care must be taken to avoid giving XS volume as the IV solution is hypertonic and could cause cerebral oedema
What is the aim of newborn screening?
When is it carried out?
What is it also known as?
To detect diseases early so they can be treated before they have irreversible effects
Carried out between days 5-7
Guthrie test
What conditions are screened for on newborn screening?
CF
Congenital hypothyroidism
Hemoglobinopathies
6 inborn errors of metabolism
What are the complications of untreated congenital hypothyroidism?
Learning difficulties, faltering growth, feeding problems, prolonged jaundice, constipation, cold, mottled dry skin, coarse facies, large tongue, hoarse cry, umbilical hernia, delayed development
What are some causes of congenital hypothyroidism?
- Maldescent of the thyroid and athyrosis
- Dyshormonogenesis
- Iodine deficiency
- TSH deficiency
Congenital hypothyroidism is one of the conditions looks for on the new-born screening. What is tested for?
A certain type of thyroid dysfunction is not picked up - why?
How does this condition usually manifest?
TSH levels
Hypothyroidism due to TSH deficiency as they have a low TSH and this is not picked up
It is usually associated with pituitary dysfunction which manifests with GH, LH/FSH and ACTH deficiency - leading to hypoglycaemia, micropenis, undescended testes - thesie are evident before hypothyroidism becomes evident
How is congenital hypothyroidism treated? When is it given?
Administration of thyroxine
Should be started before week 2/3 to reduce the risk of impaired neurodevelopment
What gene is present in all males but not in females?
What is the role of this gene?
SRY gene
It has a role in the development of the testes
How does gonadotroph deficiency present in boys?
Micropenis and undescended testes
Which cells produce testosterone?
What is it’s role in gonad development?
-
Which cells produced anti-Mullerian hormone?
What is it’s role in gonad development?
-
What is meant by the term virilisation?
In the prenatal period is refers to closure of the perineum, thinning and wrinkling (rogation) of the scrotum, growth of the phallus and closure of the urethral groove to the tip of the penis
Masculinisations is synonymous with virilisation
Prenatal virilisation of genetic females and undervirilisation of genetic males are both common causes of ambiguous genitalia and intersex conditions
What is the first feature of puberty in girls?
-
What is the first feature of puberty in boys?
-
How much longer after breast development does menarche usually occur?
-
If puberty is abnormally late in either males/females what further assessments can be carried out?
-
What age is delayed puberty usually stated to be in a)females b)males?
-
What is the definition of premature puberty in males and females?
-
What are the secondary sexual characteristics a)in males b)in females
-
What is the difference between true and false precocious puberty?
-
Which type of precocious puberty is fairly common in girls? Why?
-
Pathological causes of precocious puberty are very rare in females. What are some causes?
-
How does congenital adrenal hyperplasia lead to precocious puberty?
-
Which type of precocious puberty is rare in males? Why?
-
How may gonadotrophin dependent precocious puberty present in males?
What may be the cause of this?
-
What does a unilateral precocious enlarged testis suggest?
-
What are most pre-pubertal testes suggestive of?
-
How are tumours in the hypothalamic region best investigated?
-
If precocious puberty is gonadotrophin dependent how may it be treated?
-
What is the normal circadian rhythm of cortisol secretion?
It is usually highest on waking
What are the main causes of cushings syndrome?
The MAIN cause is oral steroids
Endogenous causes are rare but the main cause is pituitary adenoma (cushing’s disease)
What is cushing’s disease?
A bilateral adrenal hyperplasia from and ACTH secreting pituitary adenoma
What investigation is used to investigation cushings syndrome? How does this work? What are the findings in cushings disease?
Overnight dexamthosone suppression test
Patient is given dexamethasone 1mg PO at midnight and the serum cortisol is checked at 8am.
In normal patients the cortisol level will be suppressed by low dose dexamethasone because of negative feedback however in cushings syndrome the cortisol level is not suppressed.
What are the symptoms of cushings syndrome?
CUSHINGOID Cataracts Ulcers Striae/Skin thinning HTN Infections Necrosis of the femoral head Glucose raised Osteoporosis Impaired wound healing Depression
ALSO gonadal dysfunction - e.g irregular menses, hirsutism, erectile dysfunction)
What are common conditions that may be treated with steroids in children?
Nephrotic syndrome
Asthma
As well as many other side effects of steroids what side effect can be particularly seen in children as a result of steroids?
How can side effects be reduced?
Growth suppressors
Prolonged use in high dosage will lead to reduced adult height and osteopenia
Take steroids in the morning and on alternate days
What is an alternative to overnight dexamethasone suppression test for the diagnosis of cushings syndrome?
24 hours urinary free cortisol
What is the difference between primary and secondary adrenal insufficiency?
Primary adrenal insufficiency is addison’s disease and occurs when there is destruction of the adrenal cortex, resulting in reduced levels of glucocorticoids (cortisol) and mineralocorticoids (aldosterone)
Secondary adrenal insufficiency, however, is usually iatrogenic and occurs when a patient has long term steroid therapy which results in suppression of the pituitary-adrenal axis. It only becomes apparent on withdrawal of the steroids.
Why can patients with addisons disease present with hyperpigmentation?
Because the raised ACTH cross reacts with melanin receptors.
How is addisons disease diagnosed?
Describe the test
Short synacthen test
Plasma cortisol is measured before and 30 minutes after administration of synacthen.
Addisons is excluded if at 30 minutes cortisol is greater than 550nmol/L
In the treatment of addisons disease when are the steroids given and why?
Highest dose is given on waking and another dose is given at lunchtime. Doses should avoid being given late because they can cause insomnia.
If there is a poor response to treatment of addisons disease what should be suspected?
An autoimmune disease (therefore thyroid should be checked and coeliac serology)
What is congenital adrenal hyperplasia?
Insufficient cortisol and (in 80%) mineralocorticoid secretion
There is a deficiency in the enzyme required for cortisol synthesis
In the fetus the deficiency in cortisol stimulates the pituitary to produce ACTH, which drives overproduction of adrenal androgens
How does congenital adrenal hyperplasia present most commonly in males/females?
In female infants virilisation (masculinisation) of the external genitalia is seen with clitoral hypertrophy and variable fusion of the labia
In males a salt losing adrenal crisis in the 80% of males who are salt losers; weeks 1-3 - presenting with vomiting, weight loss, hypotonic and circulatory collapse. The reason why this is a rare presentation in females is because the virilisations is noted early and treatment started before salt loss is significant
Finally, tall stature can be seen in the 20% of non-salt losers/precocious pubarche (adult body odour, pubic hair, acne from the XS androgen production).
What is Addison’s disease also known as?
Primary adrenal insufficiency
What is the approach in the management of addisons during illness?
The dos eof hydrocortisone should be doubled for a fever of greater than 37.5 or for infection sepsis requiring antibiotics
What should be the approach of addisons disease if the child vomits?
IM hydrocortisone - emergency
Where may hyperpigmentation be seen in Addison’s disease?
Palms
Buccal mucosa
What are the actions of parathyroid hormone?
Where is it produced?
PTH is produced in the parathyroid glands (4 glands situated posterior to the thyroid)
Actions:
1. Stimulates the conversion of activated vitamin D (which then promotes gut absorption of calcium)
2. Increases osteoclast activity releasing Ca2+ and PO4- from bones
3. Increases Ca2+ and decreases PO4- reabsorption in the kidneys
When calcium levels are normal in the body what is the role of parathyroid hormone?
It promotes bone formation via osteoblasts
What is the difference between primary hyperparathyroidism and secondary hyperparathyroidism?
PRIMARY = Raised PTH, Raised Ca2+ SECONDARY = Raised PTH, Low Ca2+
What symptoms may a child with primary hyperparathyroidism present with?
Constipation Anorexia Lethargy Behavioural effects Polyuria Polydypsia
What may be the underlying cause of hyperparathyroidism in:
a) neonates and young children?
b) Later childhood?
Neonates and young children - associated with some rare genetic abnormalities (e.g William syndrome)
Later childhood is can be secondary to adenomas (which have occurred spontaneously) or then can occur as part of the MEN syndromes
What symptoms may an ADULT with primary hyperparathyroidism present with?
“Stones, moans, groans, psychic overtones”
Weak, tired, depressed, thirsty, dehydrated but polyuric, renal stones, abdominal pain, pancreatitis, and ulcers
Raised BP
Symptoms related to the bone- pain, fractures, osteopenia/osteoporosis
What is hypoparathyroidism in infants usually due to?
Usually due to a congenital deficiency (DiGeorge syndrome)
How can severe hypoparathyroidism present in children?
Muscle spasm
Fits
Stridor
Diarrhoea
Patient with diabetes are told to monitor what when they are ill?
Blood ketones (rather than urine ketones)
What general rules should be followed for managing diabetes during illness?
Never stop or omit insulin - dose may be changed according to basal glucose levels
Check blood glucose more frequently e.g every 2 hours through the night
Check for blood ketone levels whenever a child is ill, regardless of blood glucose level
Give additional fast acting insulin every 2 hours if blood glucose is bove target
Keep well hydrated
If ketones are positive and blood glucose low respond by drinking extra fluids containing sugar
What are the medications used in a carb counting regime for type 1 diabetes?
insuilin glargine before bed and act rapid before meals
