Endocrinology Flashcards
WHO definitions of DM
reduction in insulin action sufficient to cause level of hyperglycaemia which will result in microvascular pathology:
plasma glucose concentration (mmol/L): -fasting >7.0 (x2 or + symptoms) OR -2h post glucose load (or random glucose) >11.1 \+ -HbA1c > 48 mmol/mol
WHO definitions of impaired glucose tolerance (non diabetic hyperglycaemia)
blood glucose is raised above normal but not enough to cause microvascular damage:
plasma glucose concentration (mmol/L): -fasting <7.0 OR -2h post glucose load 7.8-11.1 \+ -HbA1c 42-47 mmol/mol
what does HbA1c represent
glycosylated haemoglobin (over a period of 3 months)
which kind of fat drives insulin resistance
abdominal obesity (visceral fat)
risk factors in insulin resistance diabetes
family history ethnicity (black african, south asian) age social deprivation diet composition lack of exercise overweight and obesity (visceral)
what is the twin cycle hypothesis in DMT2
pre existing insulin resistance: positive calori balance leads to:
liver cycle: increase liver fat –> resistance to insulin suppression of hepatic glucose production –> increase plasma glucose/ increase insulin secretion
pancreas cycle: increase liver fat –> increase VLDV triglyceride –> taken up by beta cells in pancreas: increase islet triglyceride–> decrease acute insulin response to food –> increase in plasma glucose
def polyphagia
excessive hunger or increased appetite
clinical presentation of diabetes
- symptoms of hyperglycaemia (thirst, polyuria, polyphagia, tiredness, weight loss + subacute Candida infection )
- hyperglycaemic emergency (diabetic ketoacidsis or HHS)
- diabetic complications (neuropathy, retinopathy, nephropathy, ACS, Stoke, PVD, erectile dysfunction)
- asymptomatic (present at cardiovascular disease review, NDH or gestational diabetes annual review, age related health check, other acute illness
different types of insulin
quick acting: route: subcutaneous injection/infusion, IV infusion
slow acting: route: subcutaneous injection only
(can have added chemical compounds added to slow the absorption i.e. isoprene, lente, soluble)
bi-phasic (mixes of QA and SA, ratio of 25/75 or 30/70)
(basal analogues)
what increases insulin sensitivity
reduced calorie intake increased islet function
weight loss
exercise
what are the different drugs for type 2 diabetes
- reduce insulin resistance (biguanides i.e. metformin and thiazolidenediones i.e. pioglitazone)
- increase beta cell activity (sulphonylureas i.e. gliclazide and meglitinides i.e. nateglinide)
- increase GLP1 activity (DPP4 inhibitors i.e. sitagliptin and ingrains, GLP1 agonists i.e. exenatide)
- slow glucose absorption (acarbose: alpha-glucosidase inhibitor)
- enhance glucose excretion (SGL2 inhibitors ie dapagliflozin)
- insulin supplementation
main side effects of diabetes drugs
- weight gain (all drugs that increase beta cell activity: sulphonylureas, meglitinides and insulin)
- hypoglycaemia (all drugs that increase beta cell activity: sulphonylureas, meglitinides and insulin)
- GI symptoms ie diarrhoea, nausea, abdo discomfort (metformin, incretins, acarbose)
- weight loss (metformin, incretins, SGLT2 inhibitors)
- random i.e. osteoporosis (pioglitazone), UTI (SGLT2 inhibitors)
what you check in your annual tests for diabetes
lipids UACR (urine albumin:creatinine ratio) eGFR foot exam refer to diabetic eye screening program
risk factors for microvascular diabetic complications
insulin resistance
genes
proportional to hyperglycaemia and hypertension
how does visual loss occur in diabetic eye disease
- capillary leakage
- capillary occlusion
stages of chronic kidney disease (CKD)
stage 1: microproteinuria: kidney damage with normal/increased GFR (GFR>90)
stage 2: mic/macroproteinuria: kidney damage with mid reduction GFR (GFR 60-90)
stage 3: macroproteinuria: moderate reduction GFR (GFR 30-59)
stage 4: macroproteineuria: severe reduction GFR (GFR 15-29)
stage 5: macroprotinuria: kidney failure ESRF (GFR<15)
minimising blindness in diabetes (primary, secondary prevention and salvage therapy)
primary prevention: BM control, BP control
secondary prevention: early detection of sight threatening retinopathy (retinal screening), ALLC (anti VEGF), BM and BP control
salvage therapy: vitrectomy
minimising end stage kidney disease in diabetes (primary, secondary prevention and salvage therapy)
primary prevention: BM control
secondary prevention: early detection of minimal nephropathy (UACR, eGFR), intensive BP control (<120/75, ACEi, A2RB), BM and vascular risk factor control
salvage therapy: diet, epo, ca, vitD, bicarbonate, early AVF, early transplantation, dialysis
minimising amputation in diabetes (primary, secondary prevention and salvage therapy)
primary prevention: BM control, lifestyle (smoking, exercise, alcohol)
secondary prevention (early identification of ‘at risk’ feet, footwear protection programme, BM and vascular risk factor control
salvage therapy: prompt multidisciplinary high risk foot team, revascularisation, local amputation
minimising adverse pregnancy outcomes in diabetes (primary, secondary prevention and salvage therapy)
primary prevention: pre-pregnancy BM control/folate
secondary prevention: intense retinal and renal screening/management
salage therapy: anomaly screening, foeti-placental monitoring
What is the link between between diabetes an cardiovascular disease?
Metabolic syndrome
Lifestyles
Subclinical inflammation (raised CRP, TNF-alpha, IL6)
Lipid excess and hyperglycaemia are toxic to beta cells
More?
Abnormalities of insulin secretion and action DMT2
Insulin resistance: associated with central obesity and intracellular triglyceride accumulation in muscle and liver (often NAFLD)
Pathophysiology: Decreased beta cell mass and islet amyloid deposition (it is cosecreted with insulin)
Hypersécrétion of insulin (blood insulin levels are higher than normal)
Insulin insufficiency: Increase gluconeogenesis and reduced glucose uptake by peripheral tissues
More
where does the parathyroid hormone act upon?
- kidneys (simulates tubules for increased reabsorption)
- bones (stimulates osteoblasts to release RANKL which stimulates osteoclasts to reproduce)
- gut (increase absorption of calcium)
what are the effects of hypercalcaemia?
NS:
- anxiety
- depresion
- cognitive change
- mantal changes
- lethargy
- coma
muscles (mainly gut smooth muscles)
- weakness
- cramping
- nausea, vomiting
- anorexia
heart: arrhythmias
treatment of hypercalcaemia
fluids and Lasix + treat underlying cause
bisphosphonates +/- calcitonin
pathophysiology of T1DM
beta cell destruction (early viral trigger)
pathophysiology of T2DM
insulin resistance and beta cell dysfunction
diabetic treatment goals
- minimise treatment side effects (hypo, weight gain)
- as near normal glucose as possible
- cardiovascular risk management
def acromegaly
excess growth hormone
DKA clinical features
- hyperventilation (metabolic acidosis)
- vomiting (ketosis + hyperglycaemic gastric statis)
- dehydration (osmosis diuresis + vomiting)
- hypotension w/ warm peripheries (dehydration and vasodilation)
- decreased conscious level (hypotension - CV shock)
DKA + HHS - metabolic characteristics
- H20 deficiency
- Na+, K+ deficiency
- hyperglycaemia
- metabolic acidosis (only in DKA)
DKA presenting test results
- hyperglycaemia, glycosuria
- ketoanaemia, ketonuria
- highish Na+ and K+
- raised urea and creatinine (muscle breakdown + hypotensive AKI)
- lipid rated
- leucocytosis
how to treat DKA/HHS
(prevention: never stop basal insulin)
- fluid resuscitation (for hypovolaemic shock)
- airway protection if comatose GCS<9 (aspiration pneumonitis)
- careful IV fluids (cerebral oedema: once BP is fine, don’t replace all fluids)
- monitor/replace K+ (for fatal arrhythmias)
- prophylaxis LMWH (for PE)
symptoms/signs of severe hypoglycaemia
- adrenergic symptoms (sweating, trembling, hunger)
- neuroglycopenia (parasthesia, blurred vision, confusion)
treatment of severe hypoglycaemia
- able to cooperate: lucozade
- conscious but unable to cooperate: glucogel (buccal)
- comatose: glucagon (sc, im, iv), IV glucose AVOID (venotoxic)
clinical diagnosis of T1DM
- hyperglycaemia (random glucose > 11mmol/L)
- polyuria
- polydipsia
- weight loss
- excessive tiredness
causes of thyrotoxicosis
- Grave’s disease
- multi nodular goitre
- solitary toxic nodules
- drugs (interferon, amiodorone)
what is Graves disease
pathophysiology
autoimmune process resulting in a stimulating ab to TSH receptor
symptoms and signs of thyrotoxicosis
- weight loss
- good appetite
- tachycardia
- AF
- sweating
- heat intolerance
- irritability
- mood swings
- frequent bowel action
- increase goitre
- lid retraction, lid lag
- exothalamus of the eye/proptosis
- peri orbital oedema
what are the clinical features only found in Grave’s disease
- thyroid acropachy
- exopthalmos
- pretibial myxoedema
- ophthalmoplegia
what is the treatment for thyrooxicosis
- beta adrenergic blockers
- antithyroid drugs (carbimazole, propylthiouracil)
- radioactive iodine
- surgery
side effects of antithyroid drugs?
rash, itching arthralgia nausea, vomiting mild leucopenia agranulocytosis
clinical difference between euthyroid state and mild hypothyroidism
- hoarse or deep voice
- myalgia and muscle weakness
- cold intolerance
- constipation
what is the pathophysiology of Hashimoto’s thyrotoiditis
T cell infiltration and thyroid tissue destruction : ab to TPO and thyroglobulin
clinical features of hypothyroidism
weight gain lethargy cold intolerance cool dry skin dry brittle hair, nail changes constipation, heavy periods muscle cramps
test of sub-clinical hypothyroidism
raised TSH, still maintained T3/T4
treatment of hypothyroidism in elderly patients
if IHD: should be started on low dose (25microg) and then increased every 4 weeks
red flag symptoms for thyroid cancer
- nodule
- dysphagia
- neck pain
- hoarseness
- personal history of radiation to neck
- FH of thyroid cancer
main histological types of thyroid carcinomas
papillary carcinoma follicular carcinoma anaplastic carcinoma lymphoma medullary cell carcinoma
(papillary and follicular carcinoma derived from follicular epithelial and good prognosis)
thyroid cancer treatment
- surgery (total thyroidectomy or lobectomy)
- post-operative radioactive iodine treatment
- thyroid hormone suppression (to suppress TSH so tumour growth is not stimulated)
what is a goitre?
enlarged thyroid
diffuse goitre: sign of what conditions?
Grave’s disease
Hypothyroidism (Hashimoto’s)
Colloid goitre (euthyroid)
Iodine deficiency; drugs (lithium)
nodular goitre: sign of what conditions?
multi nodular goitre
solidary nodular
cysts
FNA and cytology- diagnostic grading
Thy1: non diagnostic (inadequate cellularity): do test again
Thy2: benign (usually colloid nodules)
Thy3: indeterminate (“follicular lesion”: could be adenoma or carcinoma)
Thy4: suspicion of malignancy
Thy5: diagnostic of malignancy
what is postpartum thyroiditis
transient following pregnancy
can cause hyper, hypo or both
up to 12 months post birth BUT usually between 3-4 months post birth
associated with T1DM and TPO ab
pathophysiology of sheehan syndrome
pituitary infarction following postpartum haemorrhage leading to hypothyroidism
which drug can induce both hypo and hyperthyroidism
amiodorone
low T4
high TSH
primary hypothyroidism
high T4
low TSH
primary hyperthyroidism
low TSH
low T4
TSH deficiency (secondary hypo)
high TSH
normal T4
subclinical hypothyroidism
OR poor compliance with thyroxine
what treatment for hypertension in diabetes
- ACEi/ARB
- Ca channel blocker/diuretic
- ca channel blocker/diuretic
BMI weight classes
heathy weigh: 18.5-24.9 overweight: 25-29.9 obesity I: 30-34.9 obesity II: 35-39.9 obesity III: 40+
when do you consider referring an obese patient to specialist series (for their obesity)
- underlying causes of obesity needs assessing
- complex disease states and/or needs that can’t be managed in tier 2
- conventional treatment unsuccessful
- drug treatment being considered for BMI>50
- specialist intervention may be needed (i.e. low calorie diet)
- surgery being considered
what drug treatment for obesity, and at what point should you consider it? How long should you use it for?
orlistat, only if:
- BMI>28 w/ risk factors
- BMI>30
- continue therapy beyond 3 months only if person has lost >5% of initial body weight
- naltrexone-buproprion
when can you consider bariatric surgery for obesity treatment?
- BMI>40, or 35>BMI>40 + other significant disease that could be improved if they lost weight
- all non surgical measures have been tried and not achieved
- will/has received intensive management in tier 3 services
- fit for anaesthesia and surged
- commits to long term follow up
what are the main actions of stimulated glucocorticoids
gluconeogenesis glycogen deposits protein catabolism fat deposits sodium retention potassium loss free water clearance uric acid production circulating neutrophils
what are the main effects when glucocorticoids are inhibited
protein synthesis host respond to infection lymphocyte transformation delayed hypersensitivity circulating lymphocytes and neutrophils
causes of cushing syndrome
- pituitary dependent (Cushing’s disease)
- ectopic ACTH producing tumours
- adrenal carcinoma/adenoma
- exogenous steroids
symptoms of cushion’s syndrome?
- change of appearance
- weight gain (central)
- hair growth/acne
- think skin/easy bruising
- depression
- psychosis
- insomnia
- muscular weakness
- back pain
- amenorrhoae/gomenorrhoea
- poor libido
- growth arrest in children
- polyuria/polydipsia
signs in Cushing’s syndrome?
- moon face
- hypertension
- buffalo hump
- central obesity
- depression/psychosis
- glycosuria
- oedema
- hirsutism
- acne
- bruising
- poor wound healing
- skin infection
- striae
- pigmentation
- osteoporosis
- proximal muscle wasting
diagnosis of cushion’s syndrome
- 48h low dose dexamethasone tests (suppress cortisol production normally but no in Cushing’s disease or tumours)
- 24h urinary free cortisol measurement
adrenal gland blood supply
- superior suprarenal artery (from inferior phrenic)
- middle suprarenal artery (abdominal aorta)
- inferior suprarenal artery (renal artery)
venous drainage of adrenal gland
right suprarenal vein –> inf vena cava
left suprarenal vein –> left renal vein
when is serum cortisol the lowest
evenings
how do you define adrenal crisis
adrenal insufficient (low levels of cortisol) sick patient, hypotension, hyponatraemia
Causes of primary hypoadrenalism
Autoimmune disease TB Surgical removal Haemorrhage/ infarction Infiltration (malignant destruction/amyloid) Schilder’s disease
Symptômes of Addison’s disease
Weight loss Malaise Weakness Fever Anorexia Nausea/vomiting Diarrhoea/constipation Dépression Confusion Myalgia Syncope (postural hypotension)
Signs of Addison’s disease
Loss of weight General wasting Pigmentation Postural hypotension Loss of body hair Dehydration hyponatraemia, hyperkalaemia and azotaemia
what is addison’s disease?
destruction of entire adrenal cortex (corticosteroids, mineralicorticoids and sex steroids are reduced)
how does aldosterone affect potassium, sodium, bicarb, H20 and BP
promotes sodium reabsorption and potassium excretion in the kidney
promotes regeneration of bicarb
H20: increase reabsorption
BP: increase BP
what are the hormones produced by the pituitary?
anterior: GnRH, GHRH, somatostatin, dopamine, TRH, CRH
posterior: vasopressin, oxytocin
what conditions result from pituitary deficiencies/excess
prolactinoma acromegaly cushion's disease Nelson syndrome non functional tumours craniopharngioma
types of diabetes insipidus
- cranial DI: too little vasopressin produced by the kidney
- nephrotic DI: kidney become insensitive to vasopressin and does not make aquaporin channels to reabsorb H20 from collecting duct
how do you diagnose diabetes insipidus
water restriction test and measure Na (would be hypernatraemic)
embryological layers of the medulla
cortex: mesoderm
medulla: neuroectoderm
treatment of Cushing’s syndrome
surgery
drugs: metyrapone, ketoconazole
