Endocrine Flashcards
What is adrenal cortical ca?
cancer cells form in outer layer (cortex) of adrenal gland
Rare, usually functional, XS hormone secretion
GC: Cushing’s
Androgens: virilisation/ feminisation
Aldosterone: ↑K
RF: F, 0-5, 40-50, more aggressive in adults, MEN1, Li-Fraumeni, CAH,
Sx of adrenal cortical ca?
Rapidly progressing hypercortisolism: ↑weight, muscle wasting, fat redistribution, skin atrophy
Hyperaldosterone - raised blood pressure, thirst, passing urine frequently, muscle cramps
Hyperandrogenism: female (hirsutism, male pattern baldness, oligomenorrhoea), male (gynecomastia, testicular atrophy, ED).
Mass effect: abdo/ flank pain, N/V
Complications:
Mets
DM
Diagnosis and Tx of adrenal cortical ca?
CT: unilat, irregular shape, heterogenous, necrosis, calcification
Fasting BG, K, basal cortisol, corticotropin, 24 hr urinary free cortisol, sex hormones
Chemo
Surgery
Radiation
Symptoms of pituitary adenoma?
excess of a hormone (e.g. Cushing’s disease due to excess ACTH, acromegaly due to excess GH or amenorrhea and galactorrhea due to excess prolactin)
depletion of a hormone(s) (due to compression of the normal functioning pituitary gland)
non-functioning tumours, therefore, present with generalised hypopituitarism
stretching of the dura within/around pituitary fossa (causing headaches)
compression of the optic chiasm (causing a bitemporal hemianopia due to crossing nasal fibers)
Go look for that adenoma please: G: GH, L: LH, F: FSH, T: TSH, A: ACTH, P: prolactin function. Order of loss of hormones due to mass effect.
Symptoms of pituitary adenoma?
excess of a hormone (e.g. Cushing’s disease due to excess ACTH, acromegaly due to excess GH or amenorrhea and galactorrhea due to excess prolactin)
depletion of a hormone(s) (due to compression of the normal functioning pituitary gland)
non-functioning tumours, therefore, present with generalised hypopituitarism
stretching of the dura within/around pituitary fossa (causing headaches)
compression of the optic chiasm (causing a bitemporal hemianopia due to crossing nasal fibers)
Pressure: CN 3, 4, 5 palsy (pressure/ invasion of cavernous sinus), DI, disturbance of temp, sleep, appetite
Go look for that adenoma please: G: GH, L: LH, F: FSH, T: TSH, A: ACTH, P: prolactin function. Order of loss of hormones due to mass effect.
Investigations for pituitary adenoma?
a pituitary blood profile (including: GH, prolactin, ACTH, FH, LSH and TFTs)
formal visual field testing
MRI brain with contrast (Gadolinium)
Treatment of pituitary adenoma?
hormonal therapy (e.g. bromocriptine is the first line treatment for prolactinomas)
surgery (e.g. transsphenoidal transnasal hypophysectomy)
e.g. if progression in size
radiotherapy
Treatment of pituitary adenoma?
hormonal therapy (e.g. bromocriptine is the first line treatment for prolactinomas)
Replacement hormones eg hydrocortisone for hypopit
Hormone suppression: somatostatin analogue for GH, bromocriptine/ cabergoline for prolactinomas.
Steroids given before levothyroxine as may precipitate adrenal crisis.
surgery (e.g. transsphenoidal transnasal hypophysectomy)
e.g. if progression in size
radiotherapy
Complications of pituitary adenoma?
Mass effect
Pit apoplexy > haem into pit
Sella turcica erosion
Panhypopituitarism
What is pituitary apoplexy?
Sudden enlargement of a pituitary tumour (usually non-functioning macroadenoma) secondary to haemorrhage or infarction.
Precipitating factors:
HTN, pregnancy, trauma, anticoagulation
Features:
- sudden onset headache similar to SAH
- vomiting
- neck stiffness
- visual field defects - classically bitemporal superior quadrantic defect
- extraocular nerve palsies
- features of pituitary insufficiency
e. g. hypotension/hyponatraemia secondary to hypoadrenalism
Investigation
- MRI is diagnostic
Management
- urgent steroid replacement due to loss of ACTH
- careful fluid balance
- surgery
Types of thyroid cancer?
Papillary: differentiated, 60%. Least aggressive. RET/BRAF mutations, ionising radiation as kid. Cowden/ Gardner syndrome. Multiple small projections from follicular cells, growing towards BVs, lymphatic. Seldon encapsulated. LN mets predominate
Follicular: <25%, differentiated. Adenocarcinoma. Grows until breaks through fibrous capsule, invade nearby BV + spread. Well circumscribed single nodules, with colloid filled follicles, may be calcified/ central necrosis. Low dietary iodine, RAS, PTEN vascular invasion.
Medullary: 5%, parafollicular C cells, upper 1/3 or gland/ medulla. C cells make XS calcitonin, deposits between C cells. Release serotonin + VIP ↑GI motility. 1/3 familial, 1/3 sporadic 1/3 MEN 2A, 2B. RET mutation (single Ca in 1 lobe), familial multiple across both lobes.
Symptoms of thyroid cancer?
Large, solitary, painless, thyroid nodule, hard consistency, fixed
Hypothyroid
Mass effect: hoarseness, dysphagia, tracheal deviation
Cervical lymphadenopathy: neck mets
Medullary: release of VIP, diarrhoea, ↑serotonin, flushing of skin.
Complications of thyroid cancer?
Lymphoma, rare, associated with Hashimoto’s thyroiditis
Anaplastic: rare, most aggressive, undiff, grow beyond fibrous capsule, invade nearby structures, may derive from existing papillary/ follicular Ca where cells mutate more. Elderly females.
Investigation of thyroid cancer?
Papillary: cells with empty nuclei, Orphan Annie eyes. Psammoma bodies (Ca deposit in papillae)
Follicular: eosinophilic cells, granula cytoplasm > Hurthle cells stains pink.
Medullary: spindle shaped cells, amyloid deposits
Anaplastic: spindle shaped, pleomorphic giant cells.
USS thyroid
TFTs
Fine needle aspiration
Calcitonin levels
Radioiodine scan: usually thyroid tumours don’t make thyroid hormones so cold nodules.
Treatment of thyroid cancer?
Surgical resection
Levothyroxine
Radioactive iodine ablation
Yearly thyroglobulin levels to detect early recurrent disease.
Metastatic: sorafenib, Lenvatinib, vandetanib
Papillary: excellent prognosis
Anaplastic: not responsive to Tx/ chemo , can cause pressure Sx
What is hyperaldosteronism?
condition in which one or both adrenal glands produce too much of the hormone aldosterone
can lower K+ levels > weakness and muscle spasms
XS reabsorption of Na within distal nephron, HTN, RAAS suppression. Urinary loss of H + K.
RF: F, 20-60, FH
Causes of primary hyperaldosteronism?
genetic
random
benign cortical adenoma (Conn’s synd)
bilat idiopathic adrenal hyperplasia (70%)
familial hyperaldosteronism
Causes of primary hyperaldosteronism?
genetic
random
benign cortical adenoma (Conn’s synd)
bilat idiopathic adrenal hyperplasia (70%)
familial hyperaldosteronism
adrenal carcinoma - rare cause
Features of hyperaldosteronism?
Headache, facial flushing (HTN)
Constipation, muscle weakness, arrhythmias (↓K)
HTN unresponsive to Tx
Cramps, paraesthesia, polyuria, polydipsia, nocturia, lethargy, mood disturbance, difficulty concentrating, muscle cramps, palpitations.
Alkalosis
Complications of hyperaldosteronism?
↓K, HCO3, ↑Na, met alkalosis.
Heart disease, vascular disease, renal disease, stroke
Investigations for hyperaldosteronism?
1st Plasma aldosterone: renin, >20. 1° ↑aldosterone, ↓ renin. (-ve feedback due to Na retention form aldosterone)
CT abdo: tumour or idiopathic hyperaldosteronism
Adrenal vein sampling: if Ct normal, CT doesn’t detect lesions <1cm, aldosterone production lateralises to 1 adrenal in unilat, bilat in bilat forms. Distinguish between unilat adenoma + bilat hyperplasia.
No suppression of aldosterone to fludrocortisone or salt loading.
2°: ↑renin, ↑aldosterone
Management of hyperaldosteronism?
Adenoma: surgery
Bilat hyperplasia: aldosterone antagonist, spironolactone
Control HTN: thiazide, ACEi, CCB, Ang II blockers
What is Cushing’s syndrome?
too much cortisol
Causes of Cushing’s syndrome?
1°: adenoma/ adenocarcinoma in zona fasciculata of adrenal secretes cortisol, hyperplastic adrenal gland/ nodular adrenal hyperplasia.
2°: iatrogenic (GCs) pit adenoma (Cushing’s disease), ectopic ACTH (benign bronchial carcinoid, malig oat cell Ca/ small cell lung ca.
Carney complex: syndrome incl cardiac myxoma.
Pseudo Cushing’s: oestrogen contraceptives ↑ cortisol binding globulin ↑cortisol. Alcohol XS or severe depression.
Causes of Cushing’s syndrome?
1°: adenoma/ adenocarcinoma in zona fasciculata of adrenal secretes cortisol, hyperplastic adrenal gland/ nodular adrenal hyperplasia.
2°: iatrogenic (GCs) pit adenoma (Cushing’s disease), ectopic ACTH (benign bronchial carcinoid, malig oat cell Ca/ small cell lung ca.
Carney complex: syndrome incl cardiac myxoma.
Pseudo Cushing’s: mimics Cushing’s, often due to alcohol excess or severe depression, cause false positive dexamethasone suppression test or 24hr urinary free cortisol, oestrogen contraceptives ↑ cortisol binding globulin ↑cortisol.
ACTH dependent
- Cushing’s disease - pituitary tumour secreting ACTH producing adrenal hyperplasia
- ectopic ACTH production - SCLC
ACTH independent
- iatrogenic - steroids
- adrenal adenoma
- adrenal carcinoma
- Carney complex
- micro nodular adrenal dysplasia (rare)
Complications of Cushing’s syndrome?
Metabolic syndrome
DM
Infection due to IS
Fragility # due to osteoporosis
Renal stones
Venothrombolic event: hypercoag
Necrosis of femoral head
Glaucoma
Poor libido, ED
Amenorrhoea
Hypokalaemia metabolic alkalosis
↓K common with ectopic ACTH
Investigations for Cushing’s syndrome?
Overnight dexa suppression test: ↑ cortisol
High dose dexa: ↓cortisol Cushing’s disease,
↑cortisol ↓ACTH adrenal cushing
↑cortisol ↑ACTH ectopic ACTH
↑24hr urinary free cortisol
9am + midnight ACTH if ACTH supressed then non-ACTH dependent cause likely: adrenal adenoma. If >4 ACTH dependend eg Cushing’s disease/ ectopic ACTH.
CRH stimulation: if pit source, cortisol ↑, ectopic/adrenal, no change in cortisol.
Psuedo: false pos dexamethasone suppression test or 24 urinary cortisol. Insulin test to differentiate
Management of Cushing’s syndrome?
Wean steroid meds for iatrogenic Cushing;s
Surgery: for adenoma or ectopic ACTH
Pasierotide (somatostatin analogue), cabergoline (dopamine agonist), osilodrostat, ketoconazole, metyrapone, mitotane, etomidate (steroidogenesis inhibitor), mifepristone (glucocorticoid antagonist)
Pituitary radiotherapy
What is Addison’s disease?
hypoadrenalism
reduced cortisol and aldosterone
AI destruction of adrenal glands is commonest cause
What is Addison’s disease?
hypoadrenalism
reduced cortisol and aldosterone
AI destruction of adrenal glands is commonest cause
RF: F>M, adrenocortical IG, use of anticoags.
Causes of hypoadrenalism?
Primary causes
- Addison’s
- tuberculosis
- metastases (e.g. bronchial carcinoma)
- meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
- HIV
- antiphospholipid syndrome
- Drugs that inhibit cortisol synthesis eg ketoconazole, suramin.
Secondary causes
- pituitary disorders (e.g. tumours, irradiation, infiltration)
Exogenous glucocorticoid therapy
Features hypoadrenalism/ Addison’s?
Lean, tanned, tired + tearful, weakness.
lethargy, weakness, anorexia, nausea & vomiting, weight loss, ‘salt-craving’
hyperpigmentation (especially palmar creases)*, vitiligo, loss of pubic hair in women, hypotension, hypoglycaemia
GI: abdo pain, anorexia, N/V, weight loss
Vitiligo: AI destruction of melanocytes.
hyponatraemia and hyperkalaemia may be seen
crisis: collapse, shock, pyrexia
* Primary Addison’s is associated with hyperpigmentation whereas secondary adrenal insufficiency is not
Investigations for Addison’s disease?
ACTH stimulation test (short Synacthen test). Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. insuff/ no cortisol produced. Addison’s excluded if 30 min cortisol >550nmol/L.
Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated.
9am serum cortisol:
> 500 nmol/l makes Addison’s very unlikely
< 100 nmol/l is definitely abnormal
100-500 nmol/l should prompt a ACTH stimulation test to be performed
Electrolyte abnormalities: hyperkalaemia hyponatraemia hypoglycaemia metabolic hyperchloraemic acidosis
↑renin compensatory to ↓aldosterone
Plasma dehydroepiandrosterone + DHEA sulphate suppressed.
Abdo CT: enlarged adrenal glands with TB/malig, small if AI/ advanced TB. If infectious > calcifications
Management of Addison’s disease?
GC and MC replacement therapy
> hydrocortisone: usually given in 2 or 3 divided doses. Patients typically require 20-30 mg per day, with the majority given in the first half of the day
fludrocortisone
Pt. education
- emphasise the importance of not missing glucocorticoid doses
- consider MedicAlert bracelets and steroid cards
- patients should be provided with hydrocortisone for injection with needles and syringes to treat an adrenal crisis
- discuss how to adjust the glucocorticoid dose during an intercurrent illness
Management of intercurrent illness?
- in simple terms the glucocorticoid dose should be doubled, with the fludrocortisone dose staying the same
What is Addisonian crisis?
life-threatening situation that results in low blood pressure, low blood levels of sugar and high blood levels of potassium, precipitated by physiological stress where sudden need for aldosterone + cortisol but body can’t deliver
Features = hypoglycaemia, circ collapse, shock fatal. Pain in back, abdo legs, severe N/V, pyrexia
Causes
- sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison’s, Hypopituitarism)
- adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
- steroid withdrawal
Management
- hydrocortisone 100 mg im or iv
- 1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
- continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
- oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
What is Waterhouse-Friderichsen syndrome?
Severe, adrenal failure due to overwhelming infection, adrenal gland haem. Necrosis, adrenal crisis.
Sx:
Initial: fever, malaise, chills, headache, vomiting
Shock: ↓BP ↑HR, tachypnoea
Cyanosis
Ix:
CT: blood in adrenals
Blood culture
DIC: ↑fibrinogen degradation products, d dimer, prolonged PT, aPTT ↓plts, fibrinogen.
Tx:
IV GC
Abx
IV fluids, vasopressors
What is diabetes mellitus?
defined as a chronic condition characterised by abnormally raised levels of blood glucose
What is type 1 diabetes mellitus?
Autoimmune disorder where the insulin-producing beta cells of the islets of Langerhans in the pancreas are destroyed by the immune system
This results in an absolute deficiency of insulin resulting in raised glucose levels
Patients tend to develop T1DM in childhood/early adult life and typically present unwell, possibly in diabetic ketoacidosis
Genes (HLA-DR3/4, PTPN22, CD25) + environmental trigger (childhood enterovirus, bystander activation, molecular mimcry)
What is type 2 diabetes mellitus?
the most common cause of diabetes in the developed world.
It is caused by a relative deficiency of insulin due to an excess of adipose tissue. In simple terms there isn’t enough insulin to ‘go around’ all the excess fatty tissue, leading to blood glucose creeping up.
What is prediabetes?
This term is used for patients who don’t yet meet the criteria for a formal diagnosis of T2DM to be made but are likely to develop the condition over the next few years. They, therefore, require closer monitoring and lifestyle interventions such as weight loss
What is Gestational diabetes?
Some pregnant develop raised glucose levels during pregnancy. This is important to detect as untreated it may lead to adverse outcomes for the mother and baby
What is Maturity onset diabetes of the young (MODY)?
A group of inherited genetic disorders affecting the production of insulin.
Results in younger patients developing symptoms similar to those with T2DM, i.e. asymptomatic hyperglycaemia with progression to more severe complications such as diabetic ketoacidosis
What is Latent autoimmune diabetes of adults (LADA)?
The majority of patients with autoimmune-related diabetes present younger in life. There are however a small group of patients who develop such problems later in life. These patients are often misdiagnosed as having T2DM
Other causes of DM?
Any pathological process which damages the insulin-producing cells of the pancreas may cause diabetes to develop. Examples include chronic pancreatitis and haemochromatosis.
Drugs may also cause raised glucose levels. A common example is glucocorticoids which commonly result in raised blood glucose levels
Sx of DM?
Polyuria, polydipsia, polyphagia.
Glycosuria
Dehydration
Hypotension
Blurred vision
Gastroparesis
Paraesthesia
Unexplained weight loss
↓sensation, glove + stocking distribution
Autonomic NS malfunction: sweating, passing gas
Complications of T1DM?
DKA: abdo pain, vomiting, ↓consciousness
Infection
Delayed wound healing
Amputations
Microvascular: retinopathy, nephropathy, ED
Macrovascular: CV, cerebrovascular, peripheral vascular disease
Hypoglycaemia
Lipodystrophy
Investigations for T1DM?
Random glucose/ 2hr GTT >11
Fasting: >7
HbA1c: >48. Not as useful in T1, as not accurately reflect rapid ↑
Urinalysis: albuminemia, glycosuria, ketones
C peptide: byproduct of insulin production, if ↓ pancreas no longer producing enough insulin
Autoantibodies against β cells: glutamic acid decarboxylase (GAD), insulinoma-associated-2 autoantibodies (IA-2A), islet cell autoantibodies, insulin autoantibodies (IAA), zinc transporter 8 (ZnT8Ab), tyrosine-phosphate like molecule – islet auto-antigen-2.
Consider C-peptide and/or diabetes-specific autoantibodiesif T1DM suspected but clinical presentation includes atypical features (>50, BMI >25m slow evolution of hypoglycaemia or long prodrome)
Management of T1DM?
Life long insulin
Illness: maintain calorie intake, monitor glucose, ↑insulin if glucose rising.
HbA1c: monitor 3-6 mnths, target 48
Self-monitoring - at least 4 times a day (before meals and bed), more frequent monitoring if frequent hypoglycaemic episodes, periods of illness, before, during and after sport, planning pregnancy and during, and while breastfeeding
BG targets: 5-7 on waking, 4-7 before meals + other times.
Metformin: BMI>25
Basal bolus: basal glargine + degludec, determir, bolus lispro (humalog), aspart (novorapid)
Bipashic: Humalog mix 25: 25% quick acting, 75% intermediate acting.
Insulin pumps
Summary of ultra-short acting insulin analogues?
Lispro, aspart, glulisine
12-30 min onset
Take prior to meal
Peak 0.5-3 hours
Duration 3-5 hours
Summary of short-acting soluble/ neutral insulin?
Humulin S, Hypurin Porcine, Neutral
Humulin S - 30mins
Hypurin Porcine - 60 mins
Taken 30 mins prior to eating a meal
Humulin S - 2-3 hrs onset
Hypurin Porcine - 2-5 hrs onset
6-8 hours duration
Summary of intermediate acting insulin?
Insulin NPH
1.5-4 hour onset
Taken twice daily in combination with rapid acting insulin
Peak 4-12 hours
Duration 14-24 hours
Summary of long-acting insulin?
glargine/Lantus, detemir/Levemir
3-4 hour onset
Used when rapid-acting insulin stops working
Peak minimal, non-defined peak
Duration >24 hours
RFs for T2DM?
FH
physical inactivity
poor diet
obesity
HTN
hypertriglyceridemia
> 45
gestational DM
prediabetes
PCOS
↑BG level (GC, atypical antipsychotics, thiazide diuretics)
LBW
Sx of T2DM?
Polyuria, polydipsia, polyphagia
Glycosuria
Weakness
Blurred vision
Acanthosis nigricans: hyperpigmented
Candida infections
Skin abscesses: cellulitis/ abscess
UTIs
Fatigue
Complications of T2DM?
↑risk CV, PAD.
Hyperosmolar hyperglycaemic state.
HTN: <80 clinic 140/90, HBPM 135/85. >80 150/90, HBPM 145/85
Neuropathy
Diabetic food
Retinopathy
How does metformin work?
↑insulin sensitivity, ↓hepatic gluconeogenesis, GI upsets, ↓B12 absorption, lactic acidosis (liver/ renal failure, MI, sepsis, dehydration), CI GFR <30
SE - Gastrointestinal side-effects
Lactic acidosis
How do sulfonylureas work?
stimulate pancreatic β cells to secrete insulin, gliclazide, hypoglycaemia, hypersensitivity, ↓Na, weight gain. ↑appetite, weight gain, SiADH, liver dysfunction (cholestatic)
SE - Hypoglycaemic episodes
Increased appetite and weight gain
Syndrome of inappropriate ADH secretion
Liver dysfunction (cholestatic)
How do thiazolinediones work?
pioglitazone. Activate PPAR gamma receptor in adiopocytes, promote adipogenesis + fatty acid uptake. Weight gain, fluid retention, liver dysfunction, #. CI in HF.
SE - Weight gain
Fluid retention
Liver dysfunction
Fractures
How to DDP-4 inhibitors work?
gliptin, ↑incretin by ↓periph breakdown, inhibit glucagon secretion. Well tolerated, ↑ risk of pancreatitis. Don’t cause WL.
SE - pancreatitis
How do SGLT-2 inhibitors work?
gliflozins, inhib reabsorption of glucose in PCT. SE: UTIs. Gangrenous infection of peritoneum. DKA.
How do GLP-1 inhibitors work?
exenatide. Injection. Inhibits glucagon secretion. SE: N/V, pancreatitis
Diagnosis of T2DM?
Non-fasting: >11.1, impaired gluc tol if >7.8
Fasting: prediabetes 6-7, DM >7
If asymptomatic above must be demonstrated on 2 occasions.
HbA1c: >48. ↓than normal sickle cell, GP6D def, hereditary spherocytosis ↑than normal: vit B12/ folic acid def, Fe def anaemia, splenectomy.
Features of DKA?
abdominal pain
polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
acetone-smelling breath (‘pear drops’ smell)
Main differences between T1DM and T2DM?
T1 - typically <20, more acute (hours-days), recent weight loss typical, features of DKA how present, ketonuria is common
T2 - typically >40, slower onset of weeks to months, obesity strong RF (WL rare), milder Sx (polydipsia/polyuria), ketonuria is rare
When can HbA1c not be used for diagnosis of T2DM?
haemoglobinopathies
haemolytic anaemia
untreated iron deficiency
anaemia
suspected gestational diabetes
children
HIV
chronic kidney disease
people taking medication that may cause hyperglycaemia (for example corticosteroids)
What is impaired fasting glucose?
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l
People with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn’t have diabetes but does have IGT.
What is impaired glucose tolerance?
defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
Management of T2DM?
Lifestyle - high fibre, low glycemic index source of carbs, low-fat airy and oily fish, control sat fats and trans fatty acids, initial target weight loss in overweight person is 5-10%
Metformin: titrated up slowly. If SE modified release
Target HbA1c 48. If on gliclazide (or any drug causing hypoglycaemia, eg sulfonylurea) aim for 53.
If HbA1c 58 add: sulfonylurea (gliclazide), gliptin (DDP-4), pioglitazone, SGLT-2 inhib (empagliflozin)
If stays 58: metformin + gliptin + SU OR, metformin + SU + pioglitazone, OR metformin + SU + SGLT-2 inhib OR metformin, pioglitazone, SGLT-2.
Insulin
GLP-1 mimetic: exenatide, after triple therapy. Metformin + SU + GLP-1.
RF modification - BP targets same as person without T2D
Diabetes sick day rules?
Increase frequency of blood glucose monitoring to four hourly or more frequently
Encourage fluid intake aiming for at least 3 litres in 24hrs
If unable to take struggling to eat may need sugary drinks to maintain carbohydrate intake
It is useful to educate patients so that they have a box of ‘sick day supplies’ that they can access if they become unwell
Access to a mobile phone has been shown to reduce progression of ketosis to diabetic ketoacidosis
If a patient is taking oral hypoglycaemic medication, they should be advised to continue taking their medication even if they are not eating much
If a patient is on insulin, they must not stop it due to the risk of diabetic ketoacidosis.
Hosp admission - underlying illness needing hospital, inability to keep fluids down, persistent diarrhoea, significant ketosis, BG persistently >20 despite additional insulin, unable to manage adjusts to DM management, lack of support
What is DKA?
may be a complication of existing type 1 diabetes mellitus or be the first presentation, accounting for around 6% of cases. Rarely, under conditions of extreme stress, patients with type 2 diabetes mellitus may also develop DKA.
stress, body releases epinephrine, glucagon release, ↑glucose, loss of glucose in urine, loss of water, dehydration, need alternative energy
DKA is caused by uncontrolled lipolysis (not proteolysis) which results in an excess of free fatty acids that are ultimately converted to ketone bodies, increases blood acidity
most common precipitating factors of DKA are infection, missed insulin doses and myocardial infarction.
anion gap metabolic acidosis
Diagnostic criteria for DKA?
Key points
glucose > 11 mmol/l or known diabetes mellitus
pH < 7.3
bicarbonate < 15 mmol/l
ketones > 3 mmol/l or urine ketones ++ on dipstick
ECG: abnormal T/1 waves, K changes.
Management of DKA?
fluid replacement = isotonic saline is used initially, even if the patient is severely acidotic
insulin = an intravenous infusion should be started at 0.1 unit/kg/hour
once blood glucose is < 15 mmol/l an infusion of 5% dextrose should be started
correction of electrolyte disturbance = following Tx with insulin high serum potassium falls to hypokalaemia, so potassium may be needed to be added to replacement fluids, if the rate of potassium infusion is greater than 20 mmol/hour then cardiac monitoring may be required
potassium level 3.5-5.5 = give 40mmol/L replacement in solution
long-acting insulin should be continued, short-acting insulin should be stopped
Definition of DKA resolution?
pH >7.3 and
blood ketones < 0.6 mmol/L and
bicarbonate > 15.0mmol/L
both the ketonaemia and acidosis should have been resolved within 24 hours. If this hasn’t happened the patient requires senior review from an endocrinologist
if the above criteria are met and the patient is eating and drinking switch to subcutaneous insulin
the patient should be reviewed by the diabetes specialist nurse prior to discharge
Complications of DKA? (or Tx)
gastric stasis
thromboembolism
arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia
iatrogenic due to incorrect fluid therapy: cerebral oedema*, hypokalaemia, hypoglycaemia
acute respiratory distress syndrome
acute kidney injury
What is hyperosmolar hyperglycaemic state?
medical emergency which is extremely difficult to manage and has a significant associated mortality
SE of T2DM (typically elderly with T2DM)
results in osmotic diuresis, severe dehydration, and electrolyte deficiencies
Systemic cellular dehydration as water leaves cell into blood following glucose
Pathophysiology of hyperosmolar hyperglycaemic state?
Hyperglycaemia results in osmotic diuresis with associated loss of sodium and potassium
Severe volume depletion results in a significant raised serum osmolarity (typically > than 320 mosmol/kg), resulting in hyperviscosity of blood.
Despite these severe electrolyte losses and total body volume depletion, the typical patient with HHS, may not look as dehydrated as they are, because hypertonicity leads to preservation of intravascular volume.
Features of hyperosmolar hyperglycaemic state?
General: fatigue, lethargy, nausea and vomiting, confusion
Neurological: altered level of consciousness, headaches, papilloedema, weakness, LOC
Haematological: hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis)
Cardiovascular: dehydration, dry mucous membranes, poor skin turgor, hypotension, tachycardia, warm skin w/o sweat
Hallucinations
Polyuria
Diagnosis of hyperosmolar hyperglycaemic state?
- Hypovolaemia
- Marked Hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis (Ketones <3mmol/L, pH >7.3)
- Significantly raised serum osmolarity (> 320 mosmol/kg)
Low Na + K
