Endocrinology and metabolism Flashcards
Type 1 Diabetes
T1DM, 0.6% UK population
- autoimmune destruction of pancreatic Beta cells, so insulin not produced, ‘starving in the midst of plenty’ - glucose levels are high but the body cannot use or store it
Presentation (typically age 5-15) - polyuria - polydipsia - weight loss (or in DKA) \+ long term retinopathy, nephropathy, neuropathy, macrovascular complications
- see autoantibodies GAD, IA-2, Tyrosine-phosphatase like molecule, ZnT8
- fasting plasma glucose of >6.9mmol/L
- random plasma glucose of >11.1mmol/L
- HbA1c >48mmol/L
- risk from genetics, geography, childhood infection
Mx
- education! LIFELONG AND RISKY
- diet - weight loss, low bp, low lipid profile
- SC insulin to maintain blood glucose 3.9-6mmol/L and HbA1c <53
- ACEi to control bp
- statins to control lipids
Type 2 Diabetes
T2DM, 5% of the UK population and rising fast
- obesity -> insulin insensitivity -> exhausted pancreas -> insulin deficiency
Presentation
- often asymptomatic, through screening
- but can get polyuria, polydipsia, weight loss in hyperglycaemia
+ candida infections, cellulitis, UTIs
(or present in HHS)
+ long term retinopathy, nephropathy, neuropathy, macrovascular complications
- fasting plasma glucose of >6.9mmol/L
- random plasma glucose of >11.1mmol/L
- HbA1c >48mmol/L
- risk from age, obesity, gestational diabetes, fhx, ethnicity, HTN, PCOS
Mx
- conservative - education, diet and exercise, smoking cessation
- medical - ACEi bp control, statins, metformin (biguanides) to increase insulin sensitivity, insulin in late stage
Thyrotoxicosis presentation, causes and risk factors
= condition when excess thyroid hormone
- usually caused by Grave’s - diarrhoea, exopthalmos, fatigue, fine tremor, goitre, heat intolerance, non-pitting oedema, palpitations, unintentional weight loss
Beware thyroid storm presenting as above but in severe emergency!
Caused by
- Grave’s disease 10x more in females, more in smokers and if autoimmune history (autoimmune activation of TSH receptor)
- Toxic multinodular goitre more in iodine deficiency, older age, head and neck irradiation (autonomously functioning (hot) nodules independent of TSH control, + cold nodules with potential for cancer)
- Toxic thyroid adenoma more in iodine deficiency, young adulthood (single large thyroid nodule)
- Post partum thyroiditis - don’t give thyroid blocking meds!
Investigations and management of thyrotoxicosis
Ix
- low TSH
- high free T4 and T3
- elevative radioactive iodine uptake
- TSH receptor antibodies +ve in Grave’s
- TPO antibody suggests autoimmune
- thyroid USS (enlarged diffuse vascular in Grave’s, nodules if not)
Mx
- Grave’s - anti-thyroid drug therapy carbimazole (beware bone marrow supression) or symptomatic therapy (eg propanolol, prednisolone)
- toxic multinodular goitre - radioactive iodine therapy
- for all - surgery if retrosternal and compressing trachea or oesophagus
Hypothyroidism presentation, investigations and management
Presentation - weakness, lethargy, depression, weight gain, constipation, cold intolerance, menstrual irregularity, dry skin/eyes, bradycardia, outer eyebrow loss
- 8x more in females, peak age 30-50
Investigations
- low serum T4
- serum TSH raised in primary, lowered in secondary hypothyroidism
- TPO (antithyroid peroxidase antibody) raised suggests autoimmune
Management
- daily levothyroxine (don’t over-treat)
Causes of hypothyroidism
Primary (95%)
- thyroid not making enough T3/4, raised TSH to try and stimulate it
- primary atrophic
- Hashimoto’s (with goitre, often other autoimmune problems also)
- post-thyroidectomy or radio-iodine treatment
- drug induced - antithyroid drugs, amiodarone, lithium, iodine
Secondary (5%)
- not enough TSH
Risk factors
- female, middle aged, fhx of autoimmune disorders, radiotherapy to head and neck, Turner’s/Down’s syndromes, MS, iodine deficiency, drugs
Primary hyperparathyroidism
- too much PTH -> hypercalcaemia
Presentation
- osteoporosis, bone pain
- kidney stones
- paraesthesia, muscle cramps
- poor sleep, fatigue, anxiety, depression
Caused by
- parathyroid adenomas (85%)
- inherited - multiple endocrine neoplasia, HPT-jaw tumour syndrome
- rarely malignancy
Risk factors - female, age 50-60, fhx, lithium treatment
Investigations
- raised serum calcium
- raised PTH
Treatment
- parathyroidectomy if symptomatic, monitor if not
Secondary hyperparathyroidism
- hypocalcaemia -> reactive raise in PTH
Presentation
- bone pain
- paraesthesia, muscle cramps
- Chvostek’s and Trousseau’s sign
Caused by
- CKD (almost all dialysis dependent patients get)
- vitamin D deficiency
- malabsorption diseases
Investigations
- low serum calcium
- raised serum PTH
- check eGFR
Management
- treat cause (sunlight, active vit D/calcium supplementation)
- if untreated, will lead to tertiary hyperPTH where even if you resolve cause the parathyroid will continue to be overactive
Cushing’s syndrome
= clinical manifestation of pathological hypercorticolism (from any cause)
Signs
- weight gain (central obesity, moon face
- proximal muscle weakenss
- thinned skin, bruising
- striae
- HTN
- glucose intolerance/DM
- osteopenia
Causes
- usually exogenous steroid use
- endogenous - Cushing’s disease (ACTH-secreting pituitary tumour), ectopic ACTH tumour, adrenal adenoma, adrenal carcinoma
Ix
- elevated glucose
- late night salivary cortisol
- low dose dexamethasone suppression test (remains elevated)
- 24hr urinary free cortisol
Mx
- remove cause if tumour/drugs
Addison’s disease
= primary adrenal insufficiency
RARE (12x more in F>M)
Presentation - fatigue - anorexia + weight loss - hyperpigmentation (gums) \+ nausea, vomiting, hypotension
90% due to autoimmune, or sometimes TB or other infections
- primary = adrenal gland dysfunction
- secondary = inadequate ACTH
- tertiary = inadequate CRH
Ix
- electrolytes - low Na, high K (lack of aldosterone)
- low morning serum cortisol
- low ACTH stimulation test
Mx
- hormone replacement - glucocorticoid (hydrocortisone), mineralocorticoid (fludrocortisone), androgen replacement (DHEA)
Hyperprolactinaemia
= abnormally high levels prolactin >20 men, >18 women
Women - galactorrhoea, disrupted menstrual cycle (infertility)
Men - hypogonadism (infertility), erectile dysfunction
Due to excess TRH (from hypothalamus), too little dopamine, excess prolactin
- caused by breastfeeding, stress, pituitary prolactinoma, drugs, hypothyroidism
(this then inhibits GnRH)
Investigations - blood prolactin, thyroid function, MRI for pituitary tumour
Management - dopamine agonists
Diabetic ketoacidosis
In T1DM - hyperglycaemia, acidaemia, ketonaemia
Presentation
- polyuria, polydipsia, weakness
- nausea + vomiting, abdo pain, Kussmaul respiration, acetone breath, reduced GCS
+ volume depletion signs - dry, tachycardia, hypotension, coma
Triggers
- lifestyle - skipping meals/alcohol
- infection
- stressors eg MI/stroke/trauma
- first presentation diabetes
- drugs eg steroids, thiazides, sympathomimetics
Ix
- ABG and bloods - high glucose, low pH, low bicarb, raised ketones, raised K+?, raised anion gap
- urinalysis
Management
- REHYDRATE
- REPLACE INSULIN ( 0.1 units/kg/hour, + dextrose alongside saline)
- POTASSIUM (will drop as give insulin so may need to replace OR reduce)
- TREAT CAUSE
- stop short acting insulin, continue long acting dose
- MONITOR (hourly potassium and VBG and cap ketones)
Hyperosmotic Hyperglycaemic Syndrome
= HHS, = hyperosmolar non-ketotic coma
- in T2DM, where profound hyperglycaemia and volume depletion (NO ketoacidosis)
- slower onset than DKA, over days-weeks
- polyuria, polydipsia, weight loss, weakness, altered mental state
- rare, but high mortality (occurs in older comorbid T2DM)
- usually precipitated by infection, acute illness, inadequate diabetic therapy, dehydration
Ix
- plasma glucose >33.3
- urea rise
- Na+ reduce, K+ rise
- osmolality rise
- anion gap normal (no ketoacidosis)
- ECG (potassium)
- creatinine rise (AKI from dehydration)
Mx
- rehydration (IV fluid)
- IV insulin
- treat and monitor potassium
- treat underlying cause
- stop nephrotoxic meds
Hypoglycaemia
<3.3mmol/L
Can be non-diabetic!
Presentation
- sweating, shaking, palpitations, anxiety
- confusion, aggression, seizures, coma
- Whipple’s triad = hypo symptoms + low plasma glucose + resolution of symptoms after raising glucose
Causes
- iatrogenic (excess insulin or sulphonylurea)
- GH (pituitary) deficiency/adrenal insufiency
- insulinoma
- simple reactive hypoglycaemia
Mx
- oral glucose (eg lucozade/glucogel) if conscious, if unconscious then IM glucagon or IV 20% dextrose
- review meds/treat cause
Diabetic foot
Due to
- reduced recognition of damage - visual impairment, sensory neuropathy
- reduced protective mechanisms - dry skin, PAD
- abnormal plantar pressurs - bunions, Charcot’s deformity
Ix
- FBC (infection)
- blood glucose
- Xray of foot
- ABPI
Mx
- dressings for moist environment
- podiatrist
- address nutrition
- abx
- surgery to debride/amputate if needed
Hyponatraemia
<135mmol/L
- nausea, headache, confusion, seizures, lethargy, muscle weakness/cramps
+ maybe signs of volume expansion or depletion
Risk factors
- old age, hospitalisation, SSRIs, thiazides, comorbidities, ecstasy
Diagnosis
- Exclude pseudohyponatraemia (if lipaemia/hyperproteinaemia) and compensatory hypoNa (if hyperglycaemia)
- Determine if volume expanded, depleted or euvolaemic
- Measure urine sodium
Volume depleted hyponatraemia
If urinary Na >30
= renal loss
- diuretics (esp thiazides)
- Addison’s disease (low aldosterone)
If urinary Na<30
= extra-renal loss
- vomiting / diarrhoea (when severe, RAAS can’t cope so ADH system is switched on)
Treat both with normal saline
Euvolaemic hyponatraemia
Urinary Na >30
- SIADH (syndrome of inappropriate ADH) - diagnosis of exclusion only
- hypothyroidism
Fluid restrict
