Endocrinology Flashcards
T1DM - what is it? Epidemiology?
- autoimmune destruction of pancreatic beta cells → complete insulin deficiency
- usually presents aged 5-15
- 10% of all diabetes
Risk Factors of T1DM
- family history of HLA DR3-DQ2 or HLA DR4-DQ8
- Northern European
- other autoimmune diseases eg autoimmune thyroid, coeliac, Addison’s
Pathophysiology of T1DM
- autoantibodies attack beta cells in the islets of Langerhans
- causes insulin deficiency → hyperglycaemia
- continuous breakdown of glycogen from liver (glucogenesis) → glycosuria
Signs and Symptoms of T1DM
- classic triad = polydipsia, polyuria, weight loss (BMI <25)
- usually short history of severe symptoms
- may present with ketosis
Diagnostic Criteria of T1DM
random plasma glucose >11
Treatment of T1DM
- insulin
- short-acting insulin/insulin analogues → 4-6hrs
- longer-acting insulin → 12-24hrs
What is T2DM?
- non-insulin dependent
- patients gradually become insulin resistant AND/OR
- pancreatic beta cells fail to secrete enough insulin
- progresses from impaired glucose tolerance
Causes of T2DM
- gestational diabetes
- steroids
- Cushing’s
- chronic pancreatitis
Risk Factors of T2DM
- lifestyle factors
- Asian men
- > 40yrs
- HTN
Signs and Symptoms of T2DM
- polydipsia
- polyuria
- glycosuria
- central obesity
- blurred vision
Investigations for T2DM
- fasting plasma glucose >7
- random plasma glucose >11
- HbA1c >48
1st Line Management for T2DM
LIFESTYLE
- dietary advice
- smoking cessation
- decrease alcohol intake
- encourage exercise
- regular blood glucose and HbA1c monitoring
2nd Line Management for T2DM
MEDICATIONS
1. metformin → increased insulin sensitivity → 1st choice if overweight
2. add either DPP4 inhibitor, sulphonylurea (increased insulin secretion) or pioglitazone
3. triple therapy
4. then add insulin
use HbA1c levels to monitor
What is DKA
- diabetes ketoacidosis
- complete lack of insulin → high ketone production
- medical emergency
- serious complication of T1DM
Causes of DKA
- untreated/undiagnosed T1DM
- infection
- illness
Pathophysiology of DKA
- absence of insulin → hyperglycaemia
- hyperglycaemia → osmotic diuresis → dehydration
- peripheral lipolysis for energy → increased circulating free fatty acids → oxidised to acetyl CoA → ketone bodies (acidic) → acidosis
Symptoms of DKA
- extreme diabetes symptoms plus
- N&V
- weight loss
- confusion and reduced mental state
- lethargy
- abdominal pain
Signs of DKA
- Kussmaul’s breathing
- ‘pear drop’ breath
- hypotension
- tachycardia
Investigations of DKA
- random plasma glucose >11
- plasma ketones >3
- blood pH <7.35
- bicarb >15
- urine dipstick → glycosuria, ketonuria
- raised urea and creatinine
- decreased total K+ and increased serum K+
Treatment of DKA
- ABCDE management
- replace fluid → 0.9% saline IV
- IV insulin
- restore electrolytes → K+
What is ABCDE management?
- Airway
- Breathing
- Circulation
- Disability
- Exposure
What is HHS?
- hyperosmolar hyperglycaemic state
- marked hyperglycaemia, hyperosmolality, mild/no ketosis
- medical emergency
- serious complication of T2DM
Pathophysiology of HHS
- low insulin → increased glucogenesis
- hyperglycaemia but enough insulin to inhibit ketogenesis
- hyperglycaemia → dehydration
Signs and Symptoms of HHS
- extreme diabetes symptoms plus
- confusion and reduced mental state
- lethargy
- severe dehydration
Investigations for HHS
- random plasma glucose >11
- urine dipstick = glycosuria
- plasma osmolality = high
- decreased total K+ and increased serum K+
Treatment of HHS
- replace fluids → 0.9% saline IV
- low rate infusion of insulin
- restore electrolytes → K+
- LMW heparin
What is Hyperthyroidism
- clinical effect of thyroid hormone
- primary = abnormal increased thyroid function
- secondary = abnormal increased TSH production
Causes of Hyperthyroidism
- Graves disease
- toxic multinodular goitre
- toxic adenoma
- metastatic follicular thyroid cancer
- iodine excess eg IV contrast
- secondary causes = TSH secreting pituitary tumour
Epidemiology of Hyperthyroidism
- mainly young women → 20-40yrs
- Graves disease
Risk Factors of Hyperthyroidism
- smoking
- stress
- HLA-DR3
- other autoimmune diseases eg T1DM, Addison’s, vitiligo
Pathophysiology of Hyperthyroidism
- increased T3
- increased metabolic rate, CO, bone resorption
- also activates sympathetic NS
Signs and Symptoms of Hyperthyroidism (9)
- hot and sweaty
- diarrhoea
- hyperphagia
- weight loss
- palpitations
- tremor
- irritability/anxiety/restlessness
- oligomenorrhoea
- goitre
Investigations for Hyperthyroidism
- TFTs → increased T4/T3
- primary = decreased TSH
- secondary = increased TSH
- thyroid autoantibodies → anti-TSHR
- US/CT head
Treatment for Hyperthyroidism
- carbimazole → blocks synthesis of T4
- propylthiouracil → prevents conversion of T4 to T3
- beta-blockers for symptom relief
- radioiodine
- thyroidectomy
Pathophysiology of Graves
- IgG autoantibodies (anti-TSHR-Ab) bind to TSH receptors
- increased T3/T4 production
- also react with orbital autoantigens
Symptoms of Graves
- hyperthyroid symptoms
- thyroid eye disease → eyelid retraction, periorbital swelling, proptosis
- pretibial myxoedema
- thyroid acropachy → clubbing, painful finger and toe swelling
What is Hypothyroidism
- clinical effect of lack of thyroid hormone
- primary = abnormal decreased thyroid function
- secondary = abnormal decreased TSH production
- not enough T3 to increase metabolic rate for normal body functions
Epidemiology of Hypothyroidism
- mainly >40yrs
- female > male
Causes of Hypothyroidism
- autoimmune diseases eg hashimotos, primary atrophic hypothyroidism
- primary iodine deficiency
- drugs eg antithyroid, lithium
- secondary cause = hypopituitarism
Signs and Symptoms of Hypothyroidism (9)
- fatigue
- weight gain
- loss of appetite
- cold
- lethargy
- constipation
- low mood
- menorrhagia
- goitre
Investigations for Hypothyroidism
- TFTs → decreased T3 and T4
- primary = increased TSH
- secondary = decreased TSH
- autoantibodies → anti-TPO
Treatment for Hypothyroidism
levothyroxine T4
What is Hashimoto’s thyroiditis
- most common cause of hypothyroidism
- cause = autoimmune inflammation of thyroid gland
- associated with anti-TPO and antithyroglobulin antibodies
- goitre then atrophy of gland
What is Cushing’s
long term exposure cortisol → released by adrenal glands
Causes of Cushing’s
- ACTH secreting from pituitary adenoma (Cushing’s disease)
- ectopic ACTH production from small cell lung cancer
- iatrogenic → steroids
- adrenal adenoma
Signs and Symptoms of Cushing’s (8)
- moon face
- central obesity
- buffalo hump
- acne
- HTN
- striae
- hirsutism
- weight gain
Investigations for Cushing’s
- raised random plasma cortisol
- overnight dexamethasone suppression test → cortisol will not be suppressed
- urinary free cortisol
- plasma ACTH
Treatment for Cushing’s
- depends on underlying cause
- Cushing’s disease → remove pituitary adenoma → transsphenoidal surgery
- adrenal adenoma → adrenalectomy
- cortisol synthesis inhibition → metyrapone, ketoconazole
What is Acromegaly?
- release of excess GH causing overgrowth of all systems
- GH acts directly on tissues eg liver, muscle, bone, fat
- GH acts indirectly through induction of insulin-like GF
Causes of Acromegaly
- pituitary adenoma
- secondary to malignancy that secretes ectopic GH eg lung cancer
Complications of Acromegaly
- erectile dysfunction
- DM
Signs and Symptoms of Acromegaly (7)
- prominent forehead and brow
- increased jaw size
- large hands, nose, tongue, feet
- visual field defect
- profuse sweating
- lower pitch of voice
- obstructive sleep apnoea
Investigations for Acromegaly
- insulin-like GF 1 test = raised
GOLD STANDARD = oral glucose tolerance test
- random serum GH = raised
- MRI pituitary fossa
Treatment for Acromegaly
- transshpenoidal resection surgery (for adenoma)
- somatostatin analogue eg octreotide
- GH receptor antagonist eg pegvisomant
- dopamine agonist eg cabergoline
What is Prolactinoma?
- benign adenoma of pituitary gland producing excess prolactin
- thought to have a genetic association
Causes of Hyperprolactinaemia
- non-functioning pituitary tumour → compresses pituitary stalk → no inhibition of prolactin release
- prolactinoma
- antidopaminergic/antipsychotic drugs
Pathophysiology of prolactinoma
- two types of tumour → micro and macro
- increased release of prolactin = galactorrhea (stimulates milk) and inhibits FSH and LH
Signs and Symptoms of Prolactinoma (6)
- visual field defect
- headache
- menstrual irregularity
- infertility
- galactorrhoea
- secondary hypogonadism (rediced libido, sexual dysfunction)
Investigations for Prolactinoma
- prolactin levels
- CT head
Treatment for Prolactinoma
- dopamine agonists → bromocriptine/cabergoline
GOLD STANDARD = transsphenoidal resection surgery of pituitary gland
What is Conn’s?
primary hyperaldosteronism due to an aldosterone producing adenoma
Pathophysiology of Conn’s
- excess production of aldosterone, independent of RAAS
- high Na+ and H2O retention
- increased K+ excretion in kidneys
- low renin release
Signs and Symptoms of Conn’s (5)
- HTN
- hypokalaemia
- nocturia, polyuria
- mood disturbance
- difficulty concentrating
Investigations for Conn’s
- aldosterone-renin ratio blood test = increased
- plasma K+ = reduced
- U&E
Treatment for Conn’s
- spironolactone → if hyperplasia
GOLD STANDARD = laporascopic adrenalectomy → if adenoma
aim = lower BP, decrease aldosterone, resolve electrolyte imbalance
What is Addison’s
- primary adrenal insufficiency
- destruction of adrenal cortex → decreased production of glucocorticoid (cortisol) and mineralocorticoid (aldosterone)
Causes of Addison’s
- autoimmune destruction = most common in UK
- TB → most common cause worldwide
- adrenal metastases
Signs and symptoms of Addison’s
Signs
- 4T’s = thin, teary, tired, tanned
- pigmented palmar creases
- postural hypotension
Symptoms
- diarrhoea
- dizziness
- nausea
- lethargy
Investigations for Addison’s
- U&E → hyponatraemia, hyperkalaemia, blood glucose (high)
GOLD STANDARD = short synACTHen test = ACTH stimulation test
- presents with low cortisol, high ACTH
- plasma renin high, aldosterone low
Treatment for Addison’s
- glucocorticoids → oral hydrocortisone/prednisolone to replace cortisol
- mineralocorticoids → fludrocortisone to replace aldosterone
- double dose of steroid when there is infection, trauma, surgery, nightshift work
What is SIADH?
- syndrome of inappropriate ADH
- large amounts of ADH secretion → water reabsorption in CD
Causes of SIADH
- post-op from major surgery
- infection → atypical pneumonia, lung abscess
- head injury
- medications → thiazide diuretics = most common
Signs and Symptoms of SIADH
- headache
- nausea
- fatigue
- muscle cramps
- confusion
- severe hyponatraemia
Investigations for SIADH
- diagnosis of exclusion
- U&E = hyponatraemia
- urine Na+ and osmolality = high
exclude causes of hyponatraemia
- -ve short synACTHen test
- no D&V
- no history of diuretic use
- no AKI/CKD
What is Hyperkalaemia?
high K+
>5.5
Causes of Hyperkalaemia
impaired excretion
- AKI/CKD
- drugs eg ACEi, NSAIDs, beta blockers
- renal tubular acidosis
- addisons → decreased aldosterone
increased intake
- IV K+ therapy
- increased dietary intake
shift to EC
- metabolic acidosis
- rhabdomyolysis
- decreased insulin
- tumour lysis syndrome
Symptoms of Hyperkalaemia
- fatigue
- lightheadedness
- weakness
- chest pain
- palpitations
Signs of Hyperkalaemia
- arrhythmias → potential cardiac arrest
- reduced power and reflexes
- flaccid paralysis
Investigations for Hyperkalaemia
- ECG
- bloods
- urine osmolality and electrolytes
Treatment for Hyperkalaemia
- cardiac monitoring
- calcium gluconate → protects myocardium
- insulin/dextrose/nebulised salbutamol → drive K+ IC
What is Hypokalaemia?
low K+
<3.5
Causes of Hypokalaemia
increased excretion
- renal disease
- drugs eg thiazide/loop diuretics, laxatives
- GI loss → D&V
- Conns → increased aldosterone
decreased intake
- dietary deficiency/fasting
- liquorice abuse
shift to IC
- metabolic alkalosis
- drugs eg insulin, SABA/LABAs
Investigations for Hypokalaemia
- ECG
- bloods
- urine osmolality and electrolytes
Treatment for Hypokalaemia
- K+ → PO/IV
- other electrolytes as required
What are the two types of DI?
cranial and nephrogenic
Pathophysiology of DI
- impaired water resorption from kidneys
- large volumes of dilute urine due to reduced ADH
- impaired ADH secretion from posterior pituitary = cranial
- impaired response of the kidney to ADH = nephrogenic
Symptoms of DI
- polyuria
- polydipsia
- dehydration
Causes of Cranial DI
- idiopathic
- congenital
- tumour
- trauma
- infection
Causes of Nephrogenic DI
- inherited
- metabolic → low K, high Ca
- drugs → Li
- chronic renal disease
Diagnosis of DI
GOLD STANDARD = 8hr water deprivation test
- then desmopressin test → establish cranial or nephrogenic
- cranial MRI
Treatment of DI
- mild = manage conservatively → rehydration
- cranial = desmopressin (synthetic ADH)
- nephrogenic = if cause persists → bendroflumethazide
What is Primary Hyperparathyroidism?
- excessive secretion of PTH
- 1 PTH gland produces excess PTH
What is Secondary Hyperparathyroidism?
- excessive secretion of PTH
- increased secretion of PTH to compensate for hypocalcaemia
What is Tertiary Hyperparathyroidism?
- excessive secretion of PTH
- autonomous secretion of PTH even after corrrect of Ca2+ deficiency due to CKD
How does PTH raise Ca2+ levels?
- bone resorption
- gut/renal absorption
- activates vitamin D
- when blood Ca2+ levels are too high, PTH glands produce less PTH
Causes of Hyperparathyroidism
- adenomas = main, hyperplasia of all glands
- CKD, low vitamin D
- develops from prolonged secondary hyperPTH
Signs and Symptoms of Hyperparathyroidism
- bones = bone pain
- stones = renal calculi
- moans = psychic moans
- groans = abdominal groans
- hypercalcaemia
Investigations for Hyperparathyroidism
- PTH/bone profile → high PTH/Ca2+, low phosphates
1. raised Ca2+
2. low serum Ca2+, high PTH
3. raised Ca2+ and PTH - DEXA scan
- xray → salt and pepper degradation
- US for stones
Management of Hyperparathyroidism
- watchful waiting
1. surgical removal of adenoma, bisphosphonates
2. Ca2+ correction, treat underlying cause
3. Cinacalet (Ca2+ mimetic), total/part parathyroidectomy
What is Primary Hypoparathyroidism? Causes?
- reduced pTH production due to gland failure
- autoimmune destruction
- congenital = DiGeorge syndrome → 22q11 del
What causes Secondary Hypoparathyroidism?
- surgical removal
- decreased Mg+ → required for PTH secretion
Risk Factors for Hypoparathyroidism
- other autoimmune disorders
Pathophysiology of Hypoparathyroidism
- low PTH - hypocalcaemia and hyperphosphataemia
- neurons become more excitable
Symptoms of Hypoparathyroidism
CATS go numb
- convulsions
- arrhythmias
- tetany
- spasm
- numbness
Signs of Hypoparathyroidism
- Chvostek’s sign → facial nerve induces spasm
Trousseau’s → BP cuff causes wrist flexion and fingers to pull together → carpopedal spasm
Investigations for Hypoparathyroidism
- bloods → bone profile = decreased Ca2+/PTH, increased/normal phosphate
- ECG = prolonged QT and ST segments
Treatment for Hypoparathyroidism
- IV Ca2+
- AdCal D3 = calcitriol
- synthetic PTH is required
What is pheochromocytoma?
- adrenal medullary tumour that secretes catecholamines (adrenaline)
- very rare
Causes of pheochromocytoma
occur in certain familial syndromes
- multiple endocrine neoplasia (MEN) syndrome
- neurofibromatosis
- von-Hippel Lindau disease
Symptoms of pheochromocytoma
- headaches
- profuse sweating
- palpitations
- tremor
- pallor
Signs of pheochromocytoma
- HTN
- postural hypotension
- hypertensive retinopathy
Investigations for pheochromocytoma
- plasma metanephrines and normetanephrines
- 24hr urinary total catecholamines
- CT → look for tumour
Treatment for pheochromocytoma
without HTN crisis:
- alpha blockers → phenoxybenzamine
- most patients eventually get tumour removed then managed medically
with HTN crisis
1. antihypertensive agents → phentolamine
Signs of hypocalcaemia
- paraesthesia
- tetany
- seizures
- basal ganglia calcification
- cataracts
- Chvostek’s and Trousseau’s
ECG abnormalities in hypocalcaemia
long QTc interval
Causes of hypocalcaemia
- hypoparathyroidism
- acute pancreatitis
- hypophosphataemia
- hypomagnesaemia
- diuretics
Signs of hypercalcaemia
- BONES
- renal STONES
- psychiatric GROANS
- abdominal MOANS
typical presentation = thirst, polyuria, constipation
ECG abnormalities in hypercalcaemia
short QTc interval
Causes of hypercalcaemia
- malignancies → myeloma, bone metastases, lymphoma
- hyperparathyroidism → primary and tertiary
ECG abnormalities in hypokalaemia
- flat T waves
- ST depression
- long QT interval
- prolonged PR interval
- ST depression
- flat T waves
- prominent U waves
ECG abnormalities in hyperkalaemia
- tall tented T waves
- ST elevation
- short QT interval
- small/absent P waves
- prolonged PR interval
- wide QRS interval
- tall tented T waves
