Endocrine Flashcards
What is the pathogenesis of type 1 diabetes ?
AutoimmuneDestruction of pancreatic beta cells (which normally secrete insulin) - absolute insulin deficiency
What are the causes of diabetes type 1?
- genetic susceptibility
- HLA gene system - DR3 and DR4 genes in chromosome 6 modulate autoimmune disease
- environmental triggers e.g. Viruses, diet, toxins, emotional/physical stress
- idiopathic
What symptoms do all types of diabetes present with ?
- polyuria
- polydipsia
- lethargy
- boils
- pruritis vulvae
- freq, recurrent or prolonged infections
Which symptoms are more specific to the presentation of type 1 diabetes ?
- weight loss
- dehydration
- ketonuria
- hyperventilation
How is the diagnosis of diabetes made (investigations etc)?
- one abnormal plasma glucose with diabetic symptoms
OR - Two abnormal fasting venous plasma glucose readings
What readings suggests diabetes ?
Fasting plasma glucose > 7 mmol/L
Random plasma glucose > 11.1
Glucose tolerance test > 11.1
HbA1c > 48
When would you reconsider whether apparent diabetes type 1 in a younger person was actually type 2?
- obese
- family history (esp. If non-white)
What can be tested to distinguish between type 1 and type 2 diabetes ?
Specific autoantibodies and C-peptide (present in type 1)
Management plan for type 1 diabetes ?
- insulin
- education
- smoking cessation
- monitoring feet, eyes, kidneys
In what situation would you reconsider a diagnosis of type 2 diabetes to be type 1?
- ketonuria
- marked weight loss
- do not have features of metabolic syndrome
What are the 4 main determinants for type 2 diabetes ?
- increasing age
- obesity
- ethnicity
- family history
What is the pathogenesis of type 2 diabetes ?
Body is no longer able to secrete enough insulin to meet its requirements due to less insulin secretion and increased insulin resistance -> relative insulin deficiency
- insulin less able to bind to receptor due to resistance, higher circulating levels of insulin but increased glucose production from liver and decreased uptake of glucose by cells
- hyperglycaemia and lipid excess toxic to beta cells - may advance disease
Which drugs may cause type 2 diabetes ?
- thiazide diuretic
- b blockers
Which medical syndromes are linked to a higher risk of type 2 diabetes ?
- polycystic ovary syndrome
- metabolic syndrome
What is the main difference Presentation between type 1 and type 2 diabetes ?
Type 2 tend to be subacute and longer duration of symptoms
What surgical procedure can reverse diabetes ?
Bariatric surgery - gastric bypass
What complication may diabetic patient present with ? (5)
- staphylococcal skin infections
- retinopathy
- neuropathy
- macro vascular disease e.g. Stroke, MI, PVD
- erectile dysfunction
What is the first line treatment for type 2 diabetes ?
Diet and exercise changes
When would you start drug treatment for type 2 diabetes ?
If diet and exercise has achieved unsatisfactory metabolic control within 4-6 weeks
First line drug treatment for type 2 diabetes ?
How does it work ?
Metformin
- reduces rate of gluconeogenesis (and so hepatic glucose output) and increases insulin sensitivity
- doesn’t affect insulin output or predispose to hypoglycaemia or weight gain
- reduces CV risk
What must be monitored while on Metformin ?
Serum creatinine/ e GFR - eliminated via kidneys
What is the second line treatment for type 2 diabetes ?
How does it work?
Sulfonylureas e.g. Gliclazide
- promotes insulin release
- ineffective in those with decreased beta cells
- may cause Weight gain it hypoglycaemia
What is the third line treatment for type 2 diabetes ?
How does it work ?
Thiazolidinediones aka glitazones
- reduce insulin resistance
- fat redistribution, reducing truncal obesity
-
When is insulin therapy required for type 2 diabetes ?
When all other therapies have been tried and can’t keep hba1c
What is Cushing’s syndrome ?
Chronic excess of free glucocorticoids due to prolonged exposure of elevated levels of endogenous or exogenous glucocorticoids
What is the most common cause of Cushing’s syndrome ?
Therapeutic administration of synthetic steroids or ACTH
What are the ACTH dependant causes of Cushing’s syndrome ?
- pituitary producing excess ACTH (Cushing’s disease)
- ectopic ACTH producing tumours e.g. From small cell lung carcinoma
- ACTH administration
What are the ACTH independent causes of Cushing’s syndrome ?
Primary endogenous cortisol:
- adrenal Adenoma
- adrenal carcinoma
- glucocorticoid administration
What may present on the skin in Cushing’s syndrome ?
- striae
- bruising
- pigmentation
- hirsutism
Classical signs in Cushing’s syndrome ?
- moon face
- buffalo hump
- truncal obesity
- proximal muscle wasting and weakness
What does the dexamethosone suppression test measure ?
Measures whether ACTH secretion by the pituitary can be suppressed (taking dexamethosone should reduce ACTH production and therefore cortisol)
- diagnostic for Cushing’s
Which specialist tests can be done for Cushing’s ?
- insulin stress test
- Desmopressin stimulation test
- corticotrophin releasing hormone test
What is the treatment for Cushing’s syndrome ?
Surgical removal of tumours
Pharm: metyrapone and ketoconaole
What are the complication of Cushing’s syndrome if left untreated ?
- hypertension
- stroke
- heart attack
- infections
Who is hypothyroidism most likely to present in ?
- women
- peak age of onset 60 years
What is the most common cause of hypothyroidism world wide ?
Iodine deficiency
In areas where iodine deficiency is not a problem, what are the most common causes of hypothyroidism ?
- autoimmune
- iatrogenic
What is Hashimoto’s thyroiditis and what is the pathogenesis ?
- autoimmune disease producing atrophic changes with regeneration leading to goitre formation
What are the primary causes of hypothyroidism ? (Caiiid)
- autoimmune - Hashimoto’s thyroiditis
- iatrogenic e.g. Radio-iodine therapy
- iodine deficiency
- drugs e.g. Amiodarone
- congenital - dysmorphogenesis, absence of thyroid gland
- infiltration e.g. Amyloidosis, sarcoidosis
What are the secondary causes of hypothyroidism ?
- isolated TSH deficiency
- hypopituitarism - neoplasm, infiltration, infection, radiotherapy
- hypothalamic disorders - neoplasms and trauma
What types of hypothyroidism are transient ?
- postpartum
- withdrawal of thyroid suppressive therapy
Symptoms of hypothyroidism
- tiredness, lethargy, intolerance to cold
- dry skin, hair loss
- slowing of intellectual activity - memory, concentration
- decreased appetite, weight gain, constipation
- menorrhagia and later oligomenorrhoea/amenorrhoea
- Reduced libido
Signs of hypothyroidism
- dry, coarse skin, hair
- cold peripheries
- puffy face, hands, feet (myxoedema)
- bradycardia
- delayed tendon reflex
- ## carpel tunnel syndrome
In autoimmune hypothyroiditis, patients may have features of which other conditions ?
- vitiligo
- pernicious anaemia
- Addison’s disease
- diabetes mellitus
What are the more atypical presentations of hypothyroidism ?
- acute renal failure
- female sexual dysfunction
- Hyoercholesterolaemia
What are the signs and symptoms of myxoedema ?
- expressionless, dull face with periorbital puffiness, tongue swelling, sparse hair
- pale cool skin with rough, doughy texture
- enlarged heart
- psychosis
- cerebellar ataxia, encephalopathy
patients can develop in to myxoedema coma
Which investigations should be carried out for hypothyroidism ?
- Serum TSH (if high confirms primary hypothyroidism)
- T4 - low free serum level = hypothyroidism
How would the thyroid gland feel on palpation in Hashimoto’s thyroiditis ?
Painless goitre, varying in size, rubber consistency and irregular surface e
What is the thyroid stimulates and controlled by ?
TSH from anterior pituitary gland , which is released by TRH from the hypothalamus
Where is T4 converted to T3?
Peripherally e.g. In liver and kidneys
Who is hyperthyroidism most likely to present in ?
Women aged 20-50
What are the risk factors for hyperthyroidism ?
- family history
- high iodine intake
- smoking (esp. For associated eye problems)
- trauma to thyroid
What is the pathogenesis in Graves’ disease ?
Autoimmune process where IgG antibodies bind to TSH receptors, acting like TSH and stimulate thyroid hormones
What is de Quervains thyroiditis ?
Transient form of hyperthyroidism from acute inflammatory process, usually viral in origin,.
- also present with fever, neck pain, malaise, tachycardia, local thyroid tenderness
- TFTs show initial hyperthyroidism, then transient hypothyroidism follows
What signs may be seen in the hands in hyperthyroidism ?
- palmar erythema
- sweaty warm palms
- fine tremor
- thyroid acropathy - clubbing, painful swellings of digits
What happens to the reflexes in hyperthyroidism ?
Brisk reflexes
What signs may be seen in the eyes in hyperthyroidism ?
- exophthalmos
- opthalmoplegia
- lid lag
- lid retraction
What dermopathy is seen in hyperthyroidism ?
Pre tibial myxoedema - non pitting plaques with pink/purple colour just above lateral malleolus
What symptoms may be described in thyroid in hyperthyroidism ?
- weight loss despite increased appetite
- fine tremor, usually in hands
- heat intolerance
- irritability
- mental health - anxiety -> psychosis
- sweating
- diarrhoea
What may precipitate a thyrotoxic crisis/storm ?
- infections
- poor compliance with meds
- radio iodine therapy
How would thyrotoxic crisis present ?
- fever > 38.5
- tachycardia
- delirium or coma
- seizures
- vomiting
- diarrhoea and jaundice
What is first line antithyroid drug and how does it work ?
Carbimazole: inhibits formation of thyroid hormone
* careful of bone marrow suppression, patient must report signs of infection especially sore throat*
Conditions presenting similarly to hyperthyroidism ?
- mild hyperthyroidism may be confused for anxiety
- phaeochromocytoma
- any cause of weight loss
What is the pathogenesis of goitre formation ?
Low T3/T4 means the negative feedback loop is inactive, causing increased TSH secretion which In turn causes follicular hyper trophy and hyperplasia -> goitre
What is meant by a nontoxic thyroid nodule ?
Thyroid nodule with no hyperthyroidism
What is a multinodular goitre?
Irregular enlargement of thyroid gland due to repeated episodes of hyperplasia and involution (degeneration) of simple goitre
In what age groups are thyroid nodules most likely to be malignant ?
Under 20 or over 70
What are the red flag signs for goitre ? (5)
- stridor
- child with thyroid nodule
- unexplained hoarseness of voice associated with goitre
- painless mass enlarging rapidly
- palpable cervical lymphadenopathy
What investigations should be carried out in patients with thyroid nodules or goitre ?
- TFTs
- ultrasound
- FNA
What sized thyroid nodule is likely to be cancerous ?
> 4cm
Who is type 1 diabetes most likely to present in ?
Juveniles of Northern European ancestry
Peak age of onset around puberty
What blood results would suggest hypothyroidism ?
Raised TSH, low T4
Raised TSH and raised T4 would suggest which diagnosis ?
- TSH secreting tumour
- thyroid hormone resistance
Low TSH and raised T3/T4 suggests which diagnosis?
Hyperthyroidism
Which patients should be screened for thyroid dysfunction ?
- AF
- hyperlipidaemia
- diabetes annual review
- women with type 1 DM, in 1st trimester and post delivery
- those on amiodarone and lithium
- those with downs or turners syndrome and Addison’s disease
When is parathyroid hormone (PTH) usually secreted
..
In response to low levels of ionised Ca
What are the actions of parathyroid hormone ?
- increased osteoblast activity - releasing Ca and PO4(3-) from bones
- increased calcium and decreased phosphate reabsorption at kidneys
- vit D production increased
Symptoms and signs of primary hyperparathyroidism ?
- weak, tired, depressed
- dehydrated but polyuric
- renal stones
- abdo pain
- pancreatitis and peptic ulcers
- osteopenia/osteoporosis
- hypertension
What is Conns syndrome
Primary aldosteronism - increased sodium and water retention
- hypertension
- hypokalaemia
- alkalosis (retain sodium is in exchange for potassium or proton so overall alkalosis)
