Endocrinology Flashcards
Hormones from posterior pituitary and target tissue
Vasopressin - renal tubules
Oxytocin - breast and uterus
Hormones from anterior pituitary and target tissue
LH/FSH - ovaries and testis Growth hormone - lots of tissues TSH - thyroid Prolactin - breasts and gonads ACTH - adrenals to make steroids.
What is the function of the adrenal cortex
Make mineralocorticoids e.g. aldosterone, glucocorticoids e.g. cortisol and androgens e.g. DHEA
Difference between Cushing’s syndrome and Cushing’s disease
Syndrome = any cause of chronic excessive glucocorticoids. Disease = cause of excessive glucocorticoids is due to a pituitary adenoma
Causes of Cushing’s syndrome
STEROIDS USE (low ACTH) Other low ACTH, loss of negative feedback loop and hence 'ACTH-indpendent' causes = Adrenal carcinoma, adrenal nodular hyperplasia.
ACTH-dependent/high ACTH levels = Cushing’s disease/Pituitary adenoma, small cell lung cancer paraneoplastic syndrome/ectopic ACTH production.
S+S of Cushing’s syndrome
Weight gain Central obesity and moon face Proximal muscle weakness Bruises Acne Irregular menses, erectile dysfunction Mental change e.g. depression, irritability
O/E: Facial plethora, buffalo hump, supraclavicular fat pads. Hirsutism Purple striae on abdo Osteoporosis or unexplained fractures High BP Glucose intolerance/high BM.
Investigating for Cushing’s syndrome
Bloods = HbA1c, plasma ACTH levels, pregnancy test in females.
Other Lab = ∆ overnight dexamethasone suppression test (Failure to suppress cortisol <50nmol/L = +ve for Cushing’s) or 3x24hr urinary free cortisol (high). In secondary care can do a 48hr suppression test or higher-dose.
Imaging = pituitary MRI.
Mx of Cushing’s syndrome
If Cushing’s disease = transsphenoidal pituitary adenomectomy.
Stop steroids.
Metyrapone for symptomatic relief for ectopic ACTH.
Name 4 skin changes in Cushing’s
Purple striae
Easy bruising
Hirsutism
Acne
Normal cortisol level fluctuation
Diurnal - highest in morning and lowest at midnight.
Adrenal insufficiency causes
Primary adrenal insufficiency = Addison’s disease. Autoimmune destruction of adrenal cortex leading to glucocorticoids and mineralocorticoid deficiency. Primary insufficiency also caused by TB (globally most common cause!), lymphoma, adrenal mets from kidneys, breast, lung.
Secondary adrenal insufficiency = long-term steroid therapy (on withdrawal of steroids only)
S+S of Addison’s/Adrenal insufficiency
In adrenal crisis. Chronic symptoms: so vague 🤕 Fatigue Weight loss, anorexia, premature satiety. Nausea, vomiting, abdo pain, salt cravings. Muscle cramps and arthralgia Headache Polyuria and polydipsia
O/E:
Hyperpigmentation at scars, pressure points, palmar creases, mucus membranes.
Muscle weakness
Females loose pubic hair
Differentials for adrenal insufficiency
Anorexia - will have a potassium but in Addison’s its raised.
Investigating adrenal insufficiency
Primary care = MORNING serum cortisol (refer if less than 500nonomol/L, admit ASAP if less than 100), U+E (low Na, high K), BM low.
Secondary care = adrenocorticotrophic hormone stimulation test (Synacthen) which involves injection of an ACTH synthetic analogue and measuring serum cortisol. serology for 21-hydroxylase autoantibody, plasma renin (high) and aldosterone (low).
Exclusion = HbA1c.
Antibody common in Addison’s disease
21-hydroxylase autoantibody.
Management of confirmed adrenal insufficiency
Glucocorticoid replacement = hydrocortisone, prednisolone, dexamethasone. Resemble physiological release so higher dose in morning and then smaller doses at lunch and evening.
Mineralocorticoid replacement = Fludrocortisone
Safety net advise for features of an adrenal crisis. Increase steroids on sick days.
Who get Addison’s
Females on steroids
2 drugs for Addison’s
Hydrocortisone and fludrocortisone.
S+S of Addisonian crisis
Abdo pain Tachycardia Hypotensive Low grade fever Oliguria Altered mental state/confused Hx of steroid use.
Precipitated by infection, trauma, surgery, missed replacement therapy.
Ix and Mx for Addisonian crisis
A to E resuscitation. Urgent Ix = serum cortisol, serum ACTH, U+E, BM, ECG IV Hydrocortisone IV fluid bolus Monitor and ween IV to oral steroids.
Adrenal cortex haemorrhage in a meningococcal septicaemia patient
Waterhouse-Friderichsen syndrome. Rx = Ceftriaxone + IV hydrocortisone.
Diabetes Mellitus Type 1 and Type 2 pathophysiology
T1 = Deficient insulin secretion due to destruction of beta-cells in pancreatic Islets of Langerhans, majority is autoimmune destruction. T2 = Insulin resistance/insensitivity as body is unable to respond to serum insulin and relative insulin deficiency as pancreas is unable to secrete enough insulin to compensate for resistance.
RFx for Type 2 DM
Obesity Inactivity FHx Asian, African or black ethnicity. Hx of gestational diabetes. PCOS Drugs = second generation antipsychotics, corticosteroids.
Micro and Macro - vascular complications of DM and other random complications.
Macro: CVD e.g. MI, stroke/TIA, peripheral arterial disease (intermittent claudication).
Micro: retinopathy, nephropathy (hyperfiltration), neuropathy (glove and stocking).
Other: depression, infections esp UTI, increased risk of dementia.
Genetic link in T1DM
HLA D3 and HLA D4.
Clinical features of diabetes (not hypo or DKA).
Rapid weight loss Lethargy Polyuria Polydipsia FHx Poor wound healing Recurrent thrush.
How could a T1DM present acutely
DKA!!
Investigating DM
- Random plasma glucose of ≥ 11.1mmol/L.
- Fasting plasma glucose concentration ≥7.0mmol/L.
- OGTT 2hr plasma glucose concentration ≥11.1mmol/L
- HbA1c ≥48mmol/mol (6.5%).
∆ if symptomatic + either random or fasting is +ve or is asymptomatic + both random and fasting are +ve.
Other Ix = urine dipstick (+ve protein in nephrotpathy), BP, fasting lipids
When not to use HbA1c
Children and suspected type 1 DM. Pregnancy Haemolytic anaemias Haemaglobinopathies Splenectomy patients Antiretroviral drug patients. quite a few others actually
Pre-diabetes
- HbA1c 42-47mmol/mol
- Fasting glucose 6.1 – 6.9 mmol/L
- OGTT 7.8 – 11.0 mmol/L.
Lifestyle advice and monitor annually for progression to diagnostic DM.
Non-drug treatment of DM
Lifestyle advice - healthy eating (low saturated fats, low sugar, higher starchy-carbohydrates), physical exercise.
Avoid alcohol on an empty stomach, have a carbohydrate snack pre drinking.
Annual influenza vaccine.
Group eduction e.g. DESMOND, DAPHNE
Screen for complications, foot care advice.
Treatment algorithm for T2 DM
Group eduction e.g. DESMOND, DAPHNE
- Metformin - monitor renal function.
- add a sulfonylurea/DPP4 inhibitor/SGLT-2 inhibitor/ thiazolidinedione,.
- triple therapy with a combo of metformin and 2 of above.
- Insulin.
Example of a
- Sulfonylurea
- DPP4 inhibitor
- SGLT 2 inhibiro
- Thiazolidinedione
- Gliclazide.
- Sitagliptin.
- Canagliflozin.
- Pioglitazone. Risk of HF and bladder cancer.
Target HbA1c in T2DM
48mmol/mol / 6.5%.
If on sulfonyurea or combo therapy aim for 53mmol/mol / 7.0%.
How does metformin work
Biguanide. Increase insulin sensitivity and helps control weight.
SE = GI upset (titrate dose up) and renal-toxic from lactic acidosis.
Target HbA1c in T1DM
48mmol/mol or 6.5%
Management of T1DM
Safety net advice for DKA/hypo
Basal-bolus insulin regimen - long-acting insulin (detemir) at night with short-acting insulin (Novorapid) to cover meals.
Sick day rules for DM
When pt is feeling unwell may need to adjust insulin = ‘sick days rules’.
- monitor BM more frequently (3-4hrs) and titrate insulin dose accordingly.
- consider ketone monitoring.
- try and maintain normal meal pattern even if appetite is reduced.
- Well hydrated.
Diabetic retinopathy
- Non-proliferative retinopathy = microaneurysm formation, leaky capillaries, macular oedema, cotton-wool spots.
- Preproliferaive retinopathy = increased as vascular tortuosity and haemorrhages.
- Proliferative retinopathy = retinal ischaemia, neovascularisation. Can lead to glaucoma, vitreous haemorrhage, retinal detachment and blindness.
Diabetic nephropathy
- Leading cause of CKD in developed world!! 🌎
- Thickening of basement membrane, increased gaps between podocytes, hyperfiltration.
- Proteinuria, albuminuria.
- Annual early morning urine sample for albumin:creatinine ratio. If raised Rx with ACE inhibitor (ramipril).
- Monitor eGFR, esp as Metformin increases risk of lactic acidosis.
Diabetic neuropathy
- Glove and stocking distribution. test sensation with monofilament fibre, lower limb reflexes and ‘Charcot’s foot’/rocker-bottom foot.
- Nocturnal diarrhoea = autonomic neuropathy.
Diabetic foot
Peripheral artery disease + neuropathy (no pain sensation to increased mechanical stress) +/- infection.
S+S = painless punched-out ulcers in area of thick callus/infection. Rocker-bottom feet, claw toes.
May need amputation.
Main cause of death in DM
Vascular disease e.g. MI. Prophylaxis statin (QRISK score).
DKA
Excess glucose, lack of insulin to take it up into cells and be metabolised. Body turns to starvation-like state of ketoacidosis to produce energy.
= Acidosis and hyperglycaemia.
S+S = drowsy/altered mental state, vomiting, abdo pain, coma, dehydration.
Ix = ABG pH <7.3, BM >11.0mmol/L or known DM patient, ketonaemia >3mmol/L or significant ketonuria.
Mx =
1. A to E resuscitation.
2. 500ml 0.9% saline STAT.
3. Order investigations e.g. ECG, ABG, urine dipstick, BM, serum ketones, U+E, FBC, CRP, CXR.
4. Mix soluble insulin with 0.9% saline to create a solution of 1unit/mol (e.g. 50 units in 50mls) and administer to patient at 0.1units/kg/hr.
5. Continue any sub-cut insulin the patient may be prescribed.
6. Monitor BM and ketones hourly.
7. Once BM is <14mmol/L administer Glucose 10% alongside 0.9% saline to avoid hypoglycaemia.
What is also needed in DKA fluids and why
0.9% saline may need potassium adding because hyperglycaemia can lead to hypokalaemia.
What is the ‘equivalent’ of DKA for T2DM
- Hyperosmolar hyperglycaemic state.
- Less acute prevention, develops over 1 week.
- Hypovolaemia, marked hyperglycaemia, high serum osmolality (>320mosmol/kg).
- S+S = Polyuria, polydipsia, weak, weight loss, TC, dry mucous membranes, poor skin turgor, hypotensive, dehydration, hypovolaemic shock.
- Ix = Urine dipstick +++glucose and +ketones, BM high, serum osmolarity >320mmol/L, ABG normal.
- Mx = IV 0.9% saline, only give insulin if failure to respond to fluids or signs of ketoacidosis, anticoagulation as increased risk of arterial or venous embolism (LMWH)
Complication of DKA/high BM
Cerebral oedema
Hypoglycaemia
- S+S = sweating, tachycardia, seizures, aggressive.
- 10g glucose oral = 2 teaspoons of sugar, 110ml if Lucozade + carbohydrate snack e.g biscuit.
- 1mg Glucagon either sub-cut or IM
- 20% glucose infusion + good flush.
