Endocrinology Flashcards
Type 1 Diabetes Mellitus (T1DM)
a metabolic disorder characterised by hyperglycaemia due to absolute insulin deficiency secondary to the autoimmune destruction of pancreatic beta cells
Most pts have genetic predisposition e.g. HLA-DR3 & HLA-DR4
Epidemiology of Type 1 Diabetes Mellitus (T1DM)
accounts for ~15% of diabetic pts (but ~85% of cases of diabetes in <20 y/o)
presents at age <20yrs in majority of pts (but can occur at any age)
associated with HLA-DR3 & HLA-DR4 and other autoimmune conditions
Presentation of Type 1 Diabetes Mellitus (T1DM)
often sudden onset
generally polyuria, lethargy, weight loss, blurred vision, abdo pain
~1/3 pts present with diabetic ketoacidosis (DKA) as first manifestation
-dehydration, polyuria, polydipsia, Kussmaul respiration
Investigations for Type 1 Diabetes Mellitus (T1DM)
Random plasma glucose
-≥11.1 mmol/l
Fasting plasma glucose
-≥7.0 mmol/l
Plasma glucose 2h post 75g of glucose
-≥11.1 mmol/l
HbA1c
- ≥48 mmol/l
- NB less useful in T1DM due to rapid ↑ of glucose
C-peptide
-↓ / undetectable
Urine dip
-ketones +ve in DKA
Diabetes specific antibodies (+ve in ~80% of pts)
- Islet cell antibodies
- insulin autoantibodies
- anti-GAD
TFTs, lipid profile, U&Es
NB C-peptide & diabetes specific antibodies are generally used in T1DM suspected but pt has atypical features e.g. age >50yrs / BMI ≥25, slow development of hyperglycaemia
Management of Type 1 Diabetes Mellitus (T1DM)
pt education with diet & lifestyle advice
Monitor HbA1c every 3-6months (target ≤48mmol/L)
Glucose monitoring
- at least 4x per day (before every meal & before bed)
- more frequently if unwell
- target 5-7mmol/L on waking
- target 4-7mmol/L before meals / random
Insulin
- 1st line: offer multiple daily injection basal bolus insulin regime e.g. twice daily insulin determir
- 2nd line: once daily insulin glargine
Metformin
-consider adding if BMI ≥25
Statins
-most pts offered 20mg statin at some point
Diagnostic criteria for Type 1 Diabetes Mellitus (T1DM)
If the patient is symptomatic:
- fasting glucose ≥7.0 mmol/l
- random glucose ≥11.1 mmol/l
- or after 75g oral glucose tolerance test)
If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.
Atypical features of Type 1 Diabetes Mellitus (T1DM)
age >50yrs
BMI ≥25
slow development of hyperglycaemia
C-peptide & diabetes specific antibodies are generally used if T1DM suspected but pt has atypical features
Monitoring in Type 1 Diabetes Mellitus (T1DM)
HbA1c
- monitor every 3-6months
- target ≤48mmol/L
Glucose monitoring
- at least 4x per day
- before every meal & before bed
- more frequently if unwell
- target 5-7mmol/L on waking
- target 4-7mmol/L before meals / random
Annual reviews:
- TFTs
- U&Es
- Lipid profile
- eye screening
- foot checks
Type 2 Diabetes Mellitus (T2DM)
a disorder characterised by progressive deficiency in insulin secretion and ↑ insulin resistance leading to abnormal glucose metabolism
accounts for ~85% of all cases of diabetes
usually presents at age >40yrs
-the incidence in children/adolescents is rising
more common in people of south asian / african / afro-carribbean / middle eastern ancestry
Epidemiology of Type 2 Diabetes Mellitus (T2DM)
accounts for ~85% of all cases of diabetes
usually presents at age >40yrs
-the incidence in children/adolescents is rising
more common in people of south asian / african / afro-carribbean / middle eastern ancestry
Risk factors for Type 2 Diabetes Mellitus (T2DM)
- obesity (especially central / truncal)
- lack of physical activity
- south asian/african/afro-carribbean/middle eastern ancestry
- history of gestational diabetes
- impaired fasting glucose
- PCOS
- Family history
- Dislipidaemia
Presentation of Type 2 Diabetes Mellitus (T2DM)
onset typically gradual & majority of pts are asymptomatic
elderly pts present in HHS
symptoms of complications may be first presentation
polyuria, polydipsia
candidal/skin/urinary tract infections
acanthosis nigricans
Investigations for Type 2 Diabetes Mellitus (T2DM)
Fasting glucose
-≥7.0 mmol/L
Random glucose / post OGTT
-≥11.1 mmol/L
HbA1c
-≥48 mmol/L
NB needs to by on 2 occasions if asymptomatic
Lipid profile, U&Es (GFR), LFTs
Pre-diabetes
HbA1c:
-42-47 mmol/mol
Impaired fasting glucose:
-≥6.1 but <7.0 mmol/L (i.e. 6.1-6.9)
Glucose tolerance impaired:
- fasting glucose <7.0
- 2h post OGTT glucose = 7.8-11.1
Management of Type 2 Diabetes Mellitus (T2DM)
Patient education
Dietary advice
weight loss
exercise
Pharmacological
- 1st line: Metformin
- give if HbA1c >48 on lifestyle intervention
- give max dose before adding a further drug
- if HbA1c >58 on metformin = add 2nd drug
- e.g. sulfonylurea / gliptin / pioglitazone / SGLT-2 inhibitors
- if HbA1c >58 on metformin + other drug = add 3rd drug
- metformin + gliptin + sulfonylurea
- metformin + pioglitazone + sulfonylurea
- metformin + sulfonylurea + SGLT-2 inhibitor
- metformin + pioglitazone + SGLT-2 inhibitor
- Or consider Insulin therapy
- if triple therapy not tolerated / effective & BMI >35
- metformin + sulfonylurea + GLP-1 mimetic
- If metformin contraindicated / not tolerated
- 1st line = sulfonylurea / gliptin / pioglitazone
- add 2nd drug if HbA1c >58
- gliptin + pioglitazone
- gliptin + sulfonylurea
- pioglitazone + sulfonylurea - if HbA1c >58 on 2 drugs
- consider insulin therapy
NB see the NICE T2DM treatment diagram for a clearer picture
HbA1c targets for Type 2 Diabetes Mellitus (T2DM)
Lifestyle = 48mmol/mol
-if >48 on lifestyle then offer drug
Lifestyle + metformin = 48mmol/mol
Lifestyle + other drug e.g. sulfoylurea =53mmol/mol
NB if HbA1c ≥ 58mmol/mol on drug therapy then add another agent
Pharmacological management of Type 2 Diabetes Mellitus (T2DM)
1st line: Metformin
- give if HbA1c >48 on lifestyle intervention
- give max dose before adding a further drug
If HbA1c >58 on metformin = add 2nd drug
-e.g. sulfonylurea / gliptin / pioglitazone / SGLT-2 inhibitors
If HbA1c >58 on metformin + other drug = add 3rd drug
- metformin + gliptin + sulfonylurea
- metformin + pioglitazone + sulfonylurea
- metformin + sulfonylurea + SGLT-2 inhibitor
- metformin + pioglitazone + SGLT-2 inhibitor
- Or consider Insulin therapy
If triple therapy not tolerated / effective & BMI >35
-metformin + sulfonylurea + GLP-1 mimetic
If metformin contraindicated / not tolerated
- 1st line = sulfonylurea / gliptin / pioglitazone
- add 2nd drug if HbA1c >58
- gliptin + pioglitazone
- gliptin + sulfonylurea
- pioglitazone + sulfonylurea - if HbA1c >58 on 2 drugs
- consider insulin therapy
Metformin
A biguanide that helps ↑insulin sensitivity & ↓insulin resistance
Contra-indications:
- eGFR <30 (causes
- NB ↓ dose if eGFR <45
Side effects:
- GI upset (nausea, anorexia, diarrhoea)
- try modified release to combat these
Does not cause hypoglycaemia
NB stop 48h before procedure using iodine enhanced contrast media due to ↑ risk of nephropathy
Sulfonylureas
Examples:
-gliclazide, glimipramide, glipizide
MOA:
-↑ pancreatic insulin secretion by enhancing pancreatic islet cell function
Side effects:
- hypoglycaemia**
- weight gain
NB beta blockers can ↓ hypoglycaemic awareness and should therefore be used with caution
Thiazolidinediones (Glitazones)
Examples:
-Pioglitazone
MOA:
-↓ peripheral insulin resistance
Side effects:
- weight gain
- ↑ risk of fractures
- liver impairments
- fluid retention
Contraindicated in HF due to fluid retention
Gliptins (DPP-4 inhibitors)
Examples:
-linagliptin, sitagliptin
MOA:
-inhibit DPP-4 = ↑GLP-1 = ↑ insulin secretion & ↓glucagon secretion
Side effects:
- ↑risk of pancreatitis
- GI sumptoms
- ↑ feeling satiety
NB no weight gain
SGLT-2 inhibitors (glifozins)
Examples:
-dapagliflozin, canagliflozin
MOA:
-↓glucose absorption in proximal convoluted tubule = ↑glucose excretion in urine
Side effects:
- urinary & genital infections (due to glycosuria)
- dehydration
- often ↓ weight
- ↑ risk of limb amputation
Contraindicated in ↓ renal function
SGLT-2 inhibitors (glifozins)
Examples:
-dapagliflozin, canagliflozin
MOA:
-↓glucose absorption in proximal convoluted tubule = ↑glucose excretion in urine
Side effects:
- urinary & genital infections (due to glycosuria)
- dehydration
- often ↓ weight
- ↑ risk of limb amputation
Contraindicated in ↓ renal function
GLP-1 agonists
Examples:
-exenatide, liraglutide (both S/c)
MOA:
-↓ glucagon secretion, ↑insulin secretion
Side effects:
- nausea & vomiting
- ↑ risk pf pancreatitis
NB consider in pts with BMI ≥35 or pts who hold LGV/PCV drivers license who may lose these if taking insulin
Diabetic ketoacidosis (DKA)
a metabolic complication of diabetes characterised by absolute/relative insulin deficiency leading to hyperglycaemia, ketoanaemia and acidosis
its a medical emergency
Most common acute hyperglycaemic complications of T1Dm
Precipitating factors for Diabetic ketoacidosis (DKA)
Infection discontinuation of insulin inadequate insulin stress (e.g. MI/trauma/surgery) Medications (e.g. corticosteroids, diuretics, alpha/beta blockers) alcohol abuse
Presentation of Diabetic ketoacidosis (DKA)
polyuria, polydipsia
vomiting, dehydration
abdo pain, weakness, lethargy
altered mental state / coma
Kussmaul respiration (deep hyperventilation)
acetone smelling breath (‘pear drop’ smell)
Investigations for Diabetic ketoacidosis (DKA)
ABG/VBG
- metabolic acidosis
- ↑ anion gap (>16 indicates severe DKA)
Blood ketones
->3.0mmol/L
Blood glucose
->11.0mmol/L
U&Es
- ↑ K+
- ↓ Na+
- NB ↓ K+ indicates severe DKA as indicated intracellular K+ depletion
FBC
-↑ WCC
Urinalysis
- ketones ++
- glucose ++
ECG, CXR
NB despite ↑ K+ total body K+ is depleted and K+ should be replaced
Diagnostic criteria for Diabetic ketoacidosis (DKA)
Key points
- glucose > 11 mmol/l or known diabetes mellitus
- pH < 7.30
- bicarbonate < 15 mmol/l or anion gap > 10
- ketones > 3 mmol/l or urine ketones ++ on dipstick
Management of Diabetic ketoacidosis (DKA)
Fluid replacement
- usually NaCl 0.9%
- deficit ~100ml/kg
- K+ supplementation should be given early (due to cellular depletion of K+)
- rate shouldn’t exceed 10mmol/h
Insulin
- fixed rate IV insulin at 0.1 units/kg/h
- once blood glucose < 15mmol/L starts 5% dextrose infusion
- long-acting insulin should be continued
- short-acting insulin should be stopped
- restart normal insulin if pt eating & drinking normally
Hyperosmolar hyperglycaemic state (HHS)
an acute hyperglycaemic state characterised by profound hyperglycaemia (often >30mmol/L), hyperosmolarity and volume depletion in the absence of significant ketoacidosis
typically presents in pts with T2DM especially elderly pts (may be the initial prevention)
NB ketosis does not occur due to the presence of basal levels of insulin secretion in T2Dm
precipitants include stress e.g. MI, infection, stroke, trauma, PE, surgery
Presentation of Hyperosmolar hyperglycaemic state (HHS)
fatigue, lethargy, nausea & vomiting
weakness,, polyuria, polydipsia
altered level of consciousness, headache, papilloedema
dehydration (hypotension, tachycardia, ↓ skin turgor)
focal neurological deficits, seizures
Investigations for Hyperosmolar hyperglycaemic state (HHS)
Blood glucose
-often >30mmol/L
Blood ketones
-<3mmol/L
ABG/VBG
- mild acidosis
- usually lactic acidosis
Serum osmolarity
->320mOsm/kg
U&Es
- dehydration (↑ urea)
- pre-renal AKI
- Na+ / K+ deranged
FBC
-↑ WCC
Urinalysis
-ketones -ve
ECG, CXR, cardiac enzymes, CRP
Management of Hyperosmolar hyperglycaemic state (HHS)
Fluid replacement
- IV NaCl 0.9% is 1st line
- NB if osmolarity not ↓ with 0.9% NaCl consider 0.45%
- aim to replace ~50% by 12h & 100% by 24h
- deficit ~100-220ml/kg
- add K+ as required
Insulin
- only give if ketoanaemia as it indicates hypoinsulinaemia
- recommendation is 0.05units/kg/h
NB using insulin in HHS can cause adverse outcomes due to ↑ insulin sensitivity
Diagnostic criteria for Hyperosmolar hyperglycaemic state (HHS)
Diagnosis
- Hypovolaemia
- Marked Hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis
- Significantly raised serum osmolarity (> 320 mosmol/kg)
NB: A precise definition of HHS does not exist, however the above 3 criteria are helpful in distinguishing between HHS and DKA. It is also important to remember that a mixed HHS / DKA picture can occur.
Hypoglycaemia
a syndrome present when blood glucose concentrations falls below the normal fasting glucose range (glucose <3.3mmol/L)
Whipples Triad
Used for diagnosis of Hypoglycaemia
- plasma hypoglycaemia (glucose <3.3mmol/L)
- symptoms attributable to hypoglycaemia
- resolution of symptoms with correction of hypoglycaemia
Aetiology of Hypoglycaemia
insulinoma self administration of insulin / sulfonylureas liver failure Addisons disease chronic alcohol use
Presentation of Hypoglycaemia
Neurogenic/autonomic symptoms (<3.3 mmol/L )
- sweating, shaking, trembling, hunger
- anxiety, nausear, palpitations
- tingling, paraesthesia, pins & needles
Neurglycopenic symptoms (<2.8 mmol/L)
- agitation, confusion, behavioural change
- seizures, focal neurological signs
- ↓ GCS
Investigations for Hypoglycaemia
Blood glucose
-<3.3 mmol/L
HbA1c, LFTs, TFTs, U&Es
Management of Hypoglycaemia
If pt alert / able to swallow
- glucose 10-20g PO e.g. as liquid form like lucozade or granulated sugar
- glucogel (buccal)
If pt unconscious / unable to swallow
- at home / no IV access
- IM glucagon 1mg
- if ineffective after 10min give IV glucose
- If IV access
- IV glucose 10% / 20% (15-20g) over 15min
NB once pt recovered somewhat ensure they are given long acting glucose source e.g. bread
NB generally treatment is repeated every 15min if no response
Management of Hypoglycaemia in a conscious pt
- glucose 10-20g PO e.g. as liquid form like lucozade or granulated sugar
- glucogel (buccal)
Management of Hypoglycaemia in an unconscious pt
at home / no IV access
- IM glucagon 1mg
- if ineffective after 10min give IV glucose
If IV access
-IV glucose 10% / 20% (15-20g) over 15min
Diabetic nephropathy
one of the most common causes of CKD (NB one of the causes where kidneys do not shrink in CKD)
characterised by albuminuria & progressive ↓eGFR in the context of long standing diabetes (>10yrs especially T1DM, but may be present early in T2DM)
generally asymptomatic
Screening & Investigations for Diabetic nephropathy
Screening
- annual screening using urine ACR (albumin:creatinine ratio) using first morning urine sample
- also annual U&Es with eGFR
Investigations
- urinalysis (proteinuria)
- ACR (microalbuminuria >2.5 / albuminuria ≥30)
- U&Es (↓eGFR)
Management of Diabetic nephropathy
Tight glycaemic control
BP control (aim for <130/80)
Control dyslipadaemia with statin
ACE-Is/ARBs
-start if ACR ≥3
Diabetic retinopathy
most common caused of blindness in adults aged 35-65yrs
essentially the retinal consequence of chronic progressive diabetic microvascular leakage & occlusion
Diabetic retinopathy presentation
often minimal symptoms until late stages
↓ visual acuity
retinal haemorrhages
-sudden onset of dark, painless floaters that resolve over several days
Investigations & Screening for Diabetic retinopathy
Screening:
- annual eye screening
- refer to ophthalmology when diagnosed with T2DM or if sudden unexplained ↓ visual acuity
Investigations:
- Fundoscopy
- dilated retinal photography (gold standard)
- optical coherence tomography screening
- fluorescein angiography
Non proliferative diabetic retinopathy (NPDR)
Mild:
-≥ 1 microaneurysm
Moderate:
-microaneurysms, blot haemorrhages, hard exudates, cotton wool spots (soft exudates i.e. areas of retinal infarction), venous bleed
Severe:
-blot haemorrhages & microaneurysms in all 4 quadrants, venous bleeding, intraretinal microvascular abnormalities
Proliferative diabetic retinopathy
retinal neovascularisation, may lead to vitreous haemorrhages, fibrovascular proliferation, traction retinal haemorrhages, and features of NPDR
Diabetic Maculopathy
- any macular involvement, including macular oedema, macular ischaemia etc
- more based on location than other features
Classification of Diabetic retinopathy
Non proliferative diabetic retinopathy (NPDR):
- Mild = ≥ 1 microaneurysm
- Moderate = microaneurysms, blot haemorrhages, hard exudates, cotton wool spots (soft exudates i.e. areas of retinal infarction), venous bleed
- Severe = blot haemorrhages & microaneurysms in all 4 quadrants, venous bleeding, intraretinal microvascular abnormalities
Proliferative diabetic retinopathy:
-retinal neovascularisation, may lead to vitreous haemorrhages, fibrovascular proliferation, traction retinal haemorrhages, and features of NPDR
Maculopathy
- any macular involvement, including macular oedema, macular ischaemia etc
- more based on location than above features
Management of Diabetic retinopathy
Optimise BP / glycemic / lipid control
Non proliferative diabetic retinopathy (NPDR)
- generally observed
- may be teated with laser photocoagulation if severe
Proliferative diabetic retinopathy
- intravitreal anti-VEGF injections
- laser photocoagulation
Maculopathy
–intravitreal anti-VEGF injections
Diabetic neuropathy
hyperglycaemia leads to glycation of axons leading to progressive sensorimotor neuropathy
- sensori-neuropathy is most common
- affects up to 70% of diabetics
Presentation
- peripheral neuropathy with glove & stocking distribution & proximal progression
- dyesthesia (burning feet) worse at night
- NB autonomic neuropathy with erectile dysfunction, bladder dysfunction etc can also occur
Usually a clinical diagnosis
Management includes amitriptyline / duloxetine / gabapentin / pregabalin as 1st line (if one drug doesn’t work then try other 1st line drugs, always as mono therpay)
NB tramadol may be used as rescue therapy for acute exacerbations of neuropathic pain
Diabetic foot disease
Diabetes is the most common cause on non traumatic limb amputation
Contributing factors:
- neuropathy (loss of protective sensation)
- PAD can be diabetes induced
Presents with recurrent foot infections e.g. cellulitis or athletes foot, Malum performs (painless neuropathic ulcers on plantar pressure points) & charcot arthropathy
screening for foot tease is done annually
Management includes BP & glycemic control as well as pt education & foot care
Diabetes and hypertension
For T2DM pts BP goal is <140/90
For T1DM pts BP goal is <135/85
-if albuminuria BP goal <130/80
First line antihypertensive for diabetics = ACE-Is/ARBs
NB avoid routine use of beta blockers due to altered autonomic response to hypoglycaemia (↓ hypoglycaemic awareness)
Diabetes and the DVLA
drivers should contact the DVLA especially if taking insulin
usually no issues unless ↓ hypoglycaemic awareness or >1 episode of hypoglycaemia requiring assistance from another person in preceding 12 months
NB if well controlled diabetes then don’t need to contact DVLA
Maturity onset diabetes of the young (MoDY)
characterised by onset of T2DM at age <25yrs
typically inherited in autosomal dominant fashion
often misdiagnosed
Diabetes and sick day rules
↑ frequency of glucose monitoring while unwell
encourage oral fluid intake (take sugary drinks if unable to eat)
if on oral hypoglycaemic
- continue as normal even if not eating much
- stop metformin if dehydrated
if on insulin
- must not stop it due to risk of DKA
- if ↑ ketones/↑ glucose = give corrective dose (total daily dose divided by 6, max 15 units)
go to hospital if unable to keep down fluids or significant ketosis in insulin dependent diabetic despite additional insulin or if glucose >20 despite additional insulin
Adrenal insufficiency
adrenal insufficiency is a condition in which there is a ↓ adrenal hormone output i.e. glucocorticoids e.g. cortisol and/or mineral corticoids e.g. aldosterone
Autoimmune destruction of the adrenal glands is the commonest cause of primary hypoadrenalism in the UK, accounting for 80% of cases.
Addisons disease
Primary adrenal insufficiency
usually due to autoimmune destruction of the adrenal glands, often associated with other autoimmune conditions (accounts for ~90% of cases)
other causes include Waterhouse-Friedrichsen syndrome, TB (~10%)
Adrenal insufficiency & Addisons disease aetiology
Primary (Addisons)
- autoimmune destruction of the adrenal
- TB
- Waterhouse-Friedrichsen syndrome
Secondary
- impaired HPA axis e.g. exogenous steroid use, radiation
- pituitary / hypothalamic tumours
NB secondary adrenal insufficiency is more common
Presentation of Adrenal insufficiency
General adrenal insufficiency:
- lethargy, weakness, anorexia, nausea & vomiting
- weight loss
- diarrhoea/constipation
- loss of axillary & pubic hair
- hypotension
- hypoglycaemia
- irritability
- ↓ libido
Specific to Addisons:
- hyperpigmentation (due to ↑ACTH)
- salt cravings
NB symptoms are generally subclinical until ↑ stress e.g.in infection
Investigations for Adrenal insufficiency
Morning Cortisol
-↓ in primary & secondary
Morning ACTH
- ↑ in primary (Addisons)
- ↓ in secondary
ACTH stimulation / synacthen test
- no change in primary (Addison’s)
- ↑ cortisol after test in secondary
U&Es
-Na+ ↓, K+↑ in Primary (Addisons)
Ca2+
-↑ in Primary (Addisons)
FBC
-anaemia
Glucose
-↓ in primary & secondary
Renin & aldosterone
-Renin ↑, Aldosterone ↓ in primary in Primary (Addisons)
Anti-21-hydroxylase antibodies
-+ve in Primary (Addisons)
CT/MRI adrenals
Management of Adrenal insufficiency
Glucocorticoid replacement
- for both primary & secondary causes
- hydrocortisone (1st line)
- usually 3 divided doses, with ~1/2 of total daily dose given in the morning (when natural levels are highest)
Mineralocorticoid replacement
- only for Primary (Addisons)
- fludrocortisone (1st line)
In Illness
- 2x hydrocortisone dose
- no change to fludrocortisone dose
Differentiating primary (addisons) & secondary Adrenal insufficiency
Morning Cortisol
-↓ in primary & secondary
Morning ACTH
- ↑ in primary (Addisons)
- ↓ in secondary
ACTH stimulation / synacthen test
- no change in primary (Addison’s)
- ↑ cortisol after test in secondary
U&Es
-Na+ ↓, K+↑ in Primary (Addisons)
Ca2+
-↑ in Primary (Addisons)
Differentiating primary (Addisons) & secondary Adrenal insufficiency
Morning Cortisol
-↓ in primary & secondary
Morning ACTH*
- ↑ in primary (Addisons)
- ↓ in secondary
ACTH stimulation / synacthen test*
- no change in primary (Addison’s)
- ↑ cortisol after test in secondary
U&Es
-Na+ ↓, K+↑ in Primary (Addisons)
Ca2+
-↑ in Primary (Addisons)
Renin & aldosterone
-Renin ↑, Aldosterone ↓ in primary in Primary (Addisons)
Anti-21-hydroxylase antibodies
-+ve in Primary (Addisons)
Addisonian crisis (Adrenal crisis)
an acute severe glucocorticoid deficiency & to a lesser a mineralocorticoid deficiency
a medical emergency commonly occurring in pts with longstanding adrenal insufficiency
Precipitating factors for Addisonian crisis (Adrenal crisis)
stress in pts with underlying adrenal insufficiency
- GI illness (Most common)
- infection
- injury
- surgery
- pregnancy
- psychological stress
- dehydration
abrupt withdrawal of steroid treatment
bilateral adrenal haemorrhage (Waterhouse-Friedrichsen syndrome)
- usually seen as complication of septicaemia
- leads to adrenal necrosis
pituitary apoplexy
Presentation of Addisonian crisis (Adrenal crisis)
hypotension & hypovolaemic shock due to dehydration impaired consciousness coma malaise low grade fever nausea & vomiting severe abdo pain (may resemble peritonitis) confusion LOC
Investigations for Addisonian crisis (Adrenal crisis)
Clinical diagnosis generally i.e. investigations should not delay treatment
U&Es
-Na+ ↓, K+ ↑, Ca2+ ↑
ABG
- Glucose ↓
- normal anion gap metabolic acidosis
Cortisol
ACTh
Management of Addisonian crisis (Adrenal crisis)
IM / IV Hydrocortisone
- 100mg in adults
- can be repeated 6 hourly till stabilised
1L NaCl 0.9% ± dextrose over 30-60min
NB no fludrocortisone is required as high dose glucocorticoids have mineralocorticoid action
Cushing’s syndrome (hypercortisolism)
the clinical manifestation of pathological hypercortisolism from any cause
peak incidence is age 25-40yrs
Aetiology of Cushing’s syndrome (hypercortisolism)
ACTH dependent
- Cushings disease
- most common cause
- pituaitray adenoma secreting ACTH
- ectopic ACTH production e.g. from SCLC
ACTh independent
- iatrogenic e.g. long term steroid use
- adrenal adenoma / carcinoma
NB prolonged alcohol misuse may cause pseudo-cuhsings
Presentation of Cushing’s syndrome (hypercortisolism)
truncal obesity, supraclavicular fat pads, buffalo hump, weight gain moon facies & facial plethora facial fullness hyperglycaemia (insulin resistance) skin atrophy, purple striae easy bruising hirsutism, acne proximal muscle weakness depression, cognitive dysfunction, emotional liability recurrent infections irregular menses slow wound healing hypertension osteoporosis unexplained fractures
NB if ACTH dependent e.g. Cushings disease
- hyperpigmentation (due to ↑ ACTH)
- headaches
- galactorrhea
- visual disturbances
Management of Cushing’s syndrome (hypercortisolism)
surgical resection of tumour where possible
cortisol suppression
- metyrapone, ketoconazole
- if tumour inoperable mitotane
NB cortisol suppression is generally used temporarily pre surgery / radiation to control cortisol levels
Investigations for Cushing’s syndrome (hypercortisolism)
24h urine free cortisol
- ↑ levels
- usually >3x upper limit of normal
overnight dexamethasone suppression test
- no suppression of morning cortisol
- levels >50
Morning / midnight ACTH
- ↑ in ACTH dependent disease e.g. Cushings disease
- ↓ in ACTH independent disease
High dose dexamethasone suppression test
-if cortisol suppressed = pituitary cause
Late night salivary / serum cortisol (↑)
Glucose (↑)
MRI/CT pituitary
NB insulin stress test can be used to differentiate pseudo-bushings
Differentiating ACTH dependent & ACTH independent Cushing’s syndrome (hypercortisolism)
Morning / midnight ACTH
- ↑ in ACTH dependent disease e.g. Cushings disease
- ↓ in ACTH independent disease
High dose dexamethasone suppression test
-if cortisol suppressed = pituitary cause
Hyperaldosteronism
defined as excessive levels of aldosterone which can be independent of the renin-angiotensin axis (primary) or due to high renin levels (secondary)
Most common causes are adrenal adenomas (Conn’s syndrome)
NB this is the most common curable cause of secondary HTN
Aetiology of Hyperaldosteronism
Primary
- Adrenal adenoma (Conns syndrome)*
- ~80% of all cases of hyperaldosteronism - Bilateral adrenal hyperplasia (BAH)
- adrenal carcinoma
- familial hyperaldosteronism
Secondary
- diuretics
- congestive HF
- hepatic failure
- renal artery stenosis
Presentation of Hyperaldosteronism
Hypertension
- often >150/100
- may be >140/90 and resistant to 3 drug therapy
Features of hypokalaemia
- fatigue
- muscle weakness
- cramps
- headaches
- polyuria
- polydipsia
- constipation
- palpatations
- paraesthesia
Presentation of Hyperaldosteronism
Hypertension
- often >150/100
- may be >140/90 and resistant to 3 drug therapy
Features of hypokalaemia
- fatigue
- muscle weakness
- cramps
- headaches
- polyuria
- polydipsia
- constipation
- palpitations
- paraesthesia
Investigations for Hyperaldosteronism
U&Es
- K+ ↓
- Na+ ↑/normal
Aldosterone / renin ratio
- Renin ↓
- Aldosterone↑
Adrenal venous smapling
- to localise aldosterone production
- if bilateral = bilateral adrenal hyperplasia
High resolution abdominal CT
NB if unclear results consider oral sodium loading test / saline infusion test
Management of Hyperaldosteronism
Dietary Na+ restriction
Conn’s syndrome
- srugical adrenalectomy
- life long aldosterone antagonists e.g. spironolactone if unfit for surgery
Bilateral adrenal hyperplasia (BAH)
-spironolactone / epleronone
Phaeochromocytoma
a rare catecholamine secreting tumour typically developing in the adrian medulla
-if outside of adrenal medulla then its called a paraganglioma
~10% are familial associated with MEN-III (bilateral), neurofibromatosis, von Hippel-Lindau
usually presents 3rd-5th decade of life
Phaeochromocytoma presentation
episodic / persistent hypertension headache profuse sweating palpitations & tachycardia nausea, weakness, anxiety pallor weight loss tremor abdo pain
NB hypertensive crisis can be triggered by palpation of tumour on abdo examination
Investigations for Phaeochromocytoma
24h urine metanephrines (↑)
- 1st line investigation
- collect immediately after crisis
Plasma catecholamines (↑) Plasma metanephrines (↑)
adrenal CT/MRI
24h urine catecholamines (↑)
-no longer first line
Precipitants of Phaeochromocytoma hypertensive crisis
anaesthetics opiates decongestants TCAs cocaine X-ray contrast media childbirth
Hyperthyroidism (thyrotoxicosis)
The overactivity of the thyroid gland
most commonly due to Graves disease, an autoimmune disease leading to overstimulation of thyroid due to TSH-receptor autoantibodies
Hyperthyroidism (thyrotoxicosis) aetiology
Graves disease (most common)
- autoimmune disease
- TSH-receptor autoantibodies
Toxic multi-nodular goitre
-autonomously functioning thyroid nodules
Thyroid adenoma
Thyroiditis
-e.g. DeQuervains causes transient Hyperthyroidism
Drugs
- amiodarone
- lithium
Graves disease
autoimmune disease causing thyroid overstimulation due to TSH receptor stimulating antibodies
most common cause of thyrotoxicosis, typically seen in women aged 30-50yrs
presents with features of hyperthyroidism + classic triad of pretibial myxoedema, exophthalmos/opthalmoplegia and thyroid acropachy (digital clubbing, soft tissue swelling of the hands and feet, periosteal new bone formation)
Graves disease
autoimmune disease causing thyroid overstimulation due to TSH receptor stimulating antibodies
most common cause of thyrotoxicosis, typically seen in women aged 30-50yrs
presents with features of hyperthyroidism + classic triad of pretibial myxoedema, exophthalmos/opthalmoplegia and thyroid acropachy (digital clubbing, soft tissue swelling of the hands and feet, periosteal new bone formation)
Toxic multi nodular goitre
describes a thyroid gland that contains a number of autonomously functioning thyroid nodules resulting in hyperthyroidism.
Nuclear scintigraphy reveals patchy uptake.
The treatment of choice is radioiodine therapy.
Presentation of Hyperthyroidism (thyrotoxicosis)
Heat intolerance weight loss ↑ appetite manic restlessness weakness/fatigue ↑ sweating tachycardia fine tremor lid lag brisk reflexes goitre oligomenorrhoea diarrhoea / frequent bowel movements proximal myopathy hynaecomastia hair thinning
Investigations for Hyperthyroidism (thyrotoxicosis)
TFTs
- TSH ↓
- free T3/T4 ↑
Autoantibodies
- TSH receptor antibodies (+ve in Graves)
- anti-thyroid peroxidase antibodies (may be seen in Graves)
Thyroid isotope scan
- single hot nodule in thyroid adenoma
- diffuse uptake in Graves
- several hot nodules in multi nodular goitre
Management of Hyperthyroidism (thyrotoxicosis)
Anti-thyroid drugs
- Carbimazole (1st line)
- propylthiouracil (reserved for pregnancy & thyroid storm)
- may be given as block & replace along with thyroxine
- or as dose titration to achieve euthyroid
Radio-iodine
- treatment of choice for multi nodular goitre & relapsed Graves
- contraindicated if breast feeding
- can get pregnant for minimum 6months after treatment
- avoid close contact with children & pregnant women for 3 weeks
NB TFTs should be monitored at least annually
Hyperthyroid crisis / Thyrotoxic storm
an extreme manifestation of thyrotoxicosis, may rarely be the first presentation of hyperthyroidism
generally rare, but usually seen in pts with established thyrotoxicosis
NB iatrogenic thyroxine excess does not usually result in thyroid storm
Precipitating events for Hyperthyroid crisis / Thyrotoxic storm
withdrawal / non compliance with anti-thyroid medication recent trauma / surgery infection acute iodine load e.g. CT contrast media thyroid surgery
Investigations for Hyperthyroid crisis / Thyrotoxic storm
Clinical diagnosis
investigate underlying cause
FBC, U&Es, TFTs, LFTs, ABG, ECG
NB the degree of thyroid hormone elevation does not determine the presence / absence of thyrotoxic storm
Presentation of Hyperthyroid crisis / Thyrotoxic storm
Hyperpyrexia (temp >38.5°C but often >41°C) profuse sweating tachycardia (>140bpm) confusion & agitation Delirium Nausea & vomiting Hypertension Heart failure arrhythmia e.g. AF seizures jaundice
Investigations for Hyperthyroid crisis / Thyrotoxic storm
Clinical diagnosis
investigate underlying cause
FBC, U&Es, TFTs, LFTs, ABG, ECG
NB the degree of thyroid hormone elevation does not determine the presence / absence of thyrotoxic storm
Hypothyroidism
a clinical state resulting from the under production of thyroid hormone
most commonly caused by Hashimotos thyroiditis
generally more common in women
Hypothyroidism
a clinical state resulting from the under production of thyroid hormone
most commonly caused by Hashimotos thyroiditis
generally more common in women
Aetiology of Hypothyroidism
Hashimotos thyroiditis
- most common cause
- autoimmune condition
- due to anti-thyroid peroxidase (TPO) and also anti-thyroglobulin (Tg) antibodies
de Quervains thyroiditis
- subacute granulomatous thyroiditis
- usually self limiting
Iodine deficiency
-most common cause in developing world
Medication
- lithium
- amiodarone
Postpartum thyroiditis
Hashimotos thyroiditis
Most common cause of hypothyroidism
an autoimmune thyroiditis due to anti-thyroid peroxidase (TPO) and also anti-thyroglobulin (Tg) antibodies
10x more common in women, usually aged 30-50yrs
associated with other autoimmune conditions & MALT lymphoma
de Quervains thyroiditis
Subacute thyroiditis, usually presenting after viral infection with hypothyroidism
NB the characteristic feature is the painful goitre
There are typically 4 phases;
- phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR
- phase 2 (1-3 weeks): euthyroid
- phase 3 (weeks - months): hypothyroidism
- phase 4: thyroid structure and function goes back to normal
generally self limiting, thyroid pain may be treated with NSAIDs & aspirin
Presentation of Hypothyroidism
weight gain ↓ appetite cold intolerance lethargy constipation hoarse voice menorrhagia hyporeflexia bradycardia myalgia / stiffness / cramps hair loss brittle nails cold / dry skin poor memory & difficulty concentrating puffy hands / face / feet (myxoedema) carpal tunnel syndrome goitre
Investigations for Hypothyroidism
TFTs
- TSH ↑
- free T3/T4 ↓
Anti thyroid peroxidase (TPO) antibodies
-+ve in Hashimotos
Anti-thyroglobulin antibodies
-+ve in Hashimotos
FBC
-anaemia
Creatine kinase (↑) Cholesterol (↑)
Thyroid USS
Management of Hypothyroidism
Levothyroxine
- start with lower dose in IHD & elderly its
- side effects: AF, worsening angina, ↓ bone mineral density
- ↑ dose in women who become pregnant
NB TFTs should be monitored annually, and more frequently until correct dose established
Myxoedema coma
A rare decompensation of established thyroid hormone deficiency generally seen in elderly pts
mortality rate is up to 50%
main precipitants include infection & discontinuation of thyroxine
presents with ↓ level of consciousness, seizures, hypothermia, concurrent myxoedema, hypoventilation & hypercapnia, hypotension, bradycardia and hypoglycaemia
management
- IV thyroxine
- IV corticosteroids
- IV fluids
Sick euthyroid syndrome
occurs in severe illness or physical stress (usually in ITU pts)
pts have normal thyroid function i.e. no symptoms of hypo/hyperthyroidism
TFTs show ↓T3, ↓T4, ↓/low normal TSH
if underlying illness is treated then TFTs normalise without further treatment
Subclinical hypothyroidism
defined by ↑TSH but normal T3/T4 levels
usually seen in pts on the way to developing hypothyroidism
NB this is as TSH is a more sensitive & early marker of thyroid problems
Poor compliance with thyroxine
TSH ↑ but normal T3/T4
usually as pt takes thyroxine the days before their blood test normalising T3/T4 levels but the TSH lags behind so remains ↑
Thyroid cancer
A carcinoma of the thyroid gland, usually presenting age 30-50yrs
generally uncommon cancer but most common cancer of the endocrine system
Most common type is papillary thyroid cancer
Types of thyroid cancer
Papillary (~70%)
- most common type
- more common in women
Follicular (~20%)
-usually presents as solitary thyroid nodule
medullary (~5%)
- arises from parafollicular cells (C-Cells)
- Part of MEN-2
- secretes calcitonin (i.e. ↑ calcitonin levels)
Anaplastic (~1%)
- most common in elderly females
- rapid progression & growth
- often presents with symptoms of compression
- very poor prognosis
NB papillary & follicular are well differentiated & carry good prognosis
Presentation of thyroid cancer
Thyroid nodule
- hard, fixed nodules more suggestive of cancer
- usually painless
Features of local infiltration / compression
- hoarseness
- dysphagia
- dyspnoea
- Horners syndrome (miosis (small pupil), ptosis, enophthalmos, unilateral anhidrosis)
Painless cervical lymphadenopathy
Investigations for thyroid cancer
TFTs thyroid USS fine needle aspiration cytology radionucleotide scan CT/MRI scan serum calcitonin (↑ in medullary cancer) thyroglobulin antibodies (used to follow up thyroid cancers)
Management of thyroid cancer
Total thyroidectomy if cancer >4cm / bilateral disease
radioiodine remnant ablation after surgery
consider radiotherapy
NB there is no effective treatment for anaplastic thyroid cancer
Hypoparathyroidism
a disorder caused by reactive / absolute deficiency of parathyroid hormone (PTH) leading to ↑phosphate, ↓Ca2+, ↓PTH
generally a rare disorder but most commonly a post-op complication of thyroid surgery causing damage to parathyroid glands
NB in pseudo-hypoparathyroidism ↑phosphate, ↓Ca2+, ↑PTH* due to PTH resistance
Aetiology of Hypoparathyroidism
Post-op complication of thyroid surgery
- damage to parathyroids
- most common cause
Wilsons disease
Haemochromatosis
Radiation damage
DiGeorge syndrome (parathyroid aplasia)
Presentation of Hypoparathyroidism
Mainly symptoms due to hypocalcaemia
tetany (muscle twitching/cramping/spasm) perioral paraesthesia Bone pain convulsions brittle nails / nail dystrophy memory impairment facial twitching
Chvostek sign
-tapping over parotid = facial muscle twitch
Troussea sign
-carpal spasm if occluding brachial artery using BP cuff
Investigations for Hypoparathyroidism
Phosphate (↑) Ca2+(↓) PTH (↓) Vit D levels (normal) ECG (prolonged QT interval) U&Es
Management of Hypoparathyroidism
Calcium & Vit D supplements
PTH replacement
-helps ↓ dose of Ca2+ replacement
Pseudo-hypoparathyroidism
results from resistance to actions of PTH produced by a loss of G-protein mediated signalling
characterised by ↑ phosphate, ↓ Ca2+ but ↑ PTH*
associated with ↓ IQ, short stature and shortened 4th & 5th digits
treated with Vit D & Calcium supplements
Hyperparathyroidism
abnormally high PTH levels due to overactivity the parathyroid glands
May be
- Primary (usually due to thyroid gland adenoma)
- Secondary (usually due to CKD or Vit D defiency)
- Tertiary (occurs after long standing Secondary Hyperparathyroidism)
Primary Hyperparathyroidism
Usually due to parathyroid gland adenoma causing ↑ PTH secretion
most frequently seen in postmenopausal woman
presents with features of hypercalcaemia e.g. bone bone, pathological fractures, polydipsia, polyuria, depression, constipation, muscle weakness
characterised by PTH (↑), Ca2+ (↑), Phosphate (↓), ALP (↑), urine cAMP (↑)
managed with total parathyroidectomy
NB if unstable for surgery use calcimimetic e.g. cinacalcet
Secondary Hyperparathyroidism
usually due to CKD or Vit D deficiency causing parathyroid gland to become hyper plastic due to chronic hypocalcaemia
presents with symptoms of CKD, bone pain & pathological fractures
NB there is no features of hypercalcaemia
characterised by PTH (↑), Ca2+ (↓), Phosphate (↑), Vit D (↓), ALP (↑)
Managed with Calcium & Vit D supplements and phosphate restriction ± phosphate binders
Tertiary Hyperparathyroidism
Occurs after long standing secondary Hyperparathyroidism as parathyroid glands become autonomous and secrete PTH despite Ca2+ being corrected
presents with features of hypercalcaemia (i.e. similar to primary hyperparathyroidism)
characterised by PTH (↑↑), Ca2+ (↑), Phosphate (↑), ALP (↑)
treated with total / subtotal parathyroidectomy or with cinacalcet
Differentiating Primary, Secondary and Tertiary Hyperparathyroidism
Primary
- PTH ↑
- Ca2+ ↑
- Phosphate ↓
- presents with features of Hyercalcaemia
Secondary
- PTH ↑
- Ca2+ ↓
- Phosphate ↑
- No features of hypercalcaemia
Tertiary
- PTH ↑↑
- Ca2+ ↑
- Phosphate ↑
- presents similar to primary hyperparathyroidism
Acromegaly
a condition where benign pituitary adenomas lead to excess secretion of growth hormone (GH) & insulin like growth factor 1 (IGF-1)
insidious onset with slow progression, associated with MEN-1 & McCune-Albright syndrome
usually diagnosed in middle age adults ~40y/o
-NB if condition occurs in children before closure of growth plates it is known as gigantism
Management of Acromegaly
Trans-sphenoidal pituitary adenoma resection (1st line)
if inoperable / unsuccessful surgery
- 1st line = somatostatin analogues e.g. ocreotide (directly inhibit GH secretion)
- pegvisomant (GH receptor antagonist)
Presentation of Acromegaly
Tumour symptoms
- headaches
- visual field defects (bitemporal hemianopia)
Gradual change in appearance
- coarse facial features
- spade like hands
- ↑ ring & shoe size
- large tongue, frontal bossing
- hyperhidrosis, doughy & oily skin
- deepening of voice
- painful arthropathy (ankles, knees, hips, spine)
Hyperprolactinaemia (seen in 1/3 pts)
- galactorrhoea
- amenorrhoea
- erectile dysfunction
- ↓ libido
Investigations for Acromegaly
Serum IGF-1
- levels ↑
- gold standard investigation
Serum Growth hormone (GH)
- Levels ↑
- bit as grid as IGF-1 due to short T1/2
Oral glucose tolerance test (OGTT)
- no suppression of GH in acromegaly
- normally pts GH is suppressed <2
pituitary CT/MRI prolactin (often ↑) visual field testing ECG Echo (for cardiomyopathy)
Diabetes insipidus (DI)
A metabolic disorder characterised by an absolute or relative inability to concentrate urine either due to ↓ secretion or insensitivity to anti-diuretic hormone (ADH)
May be Cranial or Nephrogenic
Presentation of Diabetes insipidus (DI)
Polyuria -urine volume >3L/24h Polydipsia Nocturia chronic thirst dehydration if water not available
Diabetes insipidus (DI)
A metabolic disorder characterised by an absolute or relative inability to concentrate urine either due to ↓ secretion or insensitivity to anti-diuretic hormone (ADH)
May be Cranial or Nephrogenic
NB Cranial DI is most common kind
Water deprivation test results
Normal
Psychogenic polydipsia
Cranial Diabetes insipidus
Nephrogenic diabetes insipidus
Investigations for Diabetes insipidus (DI)
Urine osmolality (↓) -NB urine osmolality >700mOsm/kg excludes DI
Serum osmolality (↑) 24h urine volume (>3L)
Water deprivation test
- deprive to 5% loss of body weight / for 8h then give Desmopressin (DDVAP)
- Cranial DI = low urine osmolality post deprivation, but normalised urine osmolality post DDVAP
- Nephrogenic DI = low urine osmolality post deprivation & DDAVP
Cranial Diabetes insipidus (DI)
Most common form of DI
due to insufficent / absent ADH synthesis / secretion
may be idiopathic, post head injury or due to craniopharyngioma, intracranial surgery or inherited (Wolframs syndrome)
Still sensitive to ADH
Water deprivation test:
- Starting plasma osmolality: ↑
- Urine osmolality post deprivation: <300
- Urine osmolality post DDVAP: >600
Nephrogenic Diabetes insipidus (DI)
due to insensitivity / resistance of kidney to ADH
may be inherited (often ADH receptor mutation) or medication induced e.g. Lithium (common side effect)
Water deprivation test
- Starting plasma osmolality: ↑
- Urine osmolality post deprivation: <300
- Urine osmolality post DDVAP: <300
Water deprivation test results
Deprive pt to 5% loss of body weight / for 8h then give Desmopressin (DDVAP)
Normal
- Starting plasma osmolality:
- Urine osmolality psot deprivation:
- Urine osmolality post DDVAP:
Psychogenic polydipsia
- Starting plasma osmolality:
- Urine osmolality psot deprivation:
- Urine osmolality post DDVAP:
Cranial Diabetes insipidus
- Starting plasma osmolality:
- Urine osmolality psot deprivation:
- Urine osmolality post DDVAP:
Nephrogenic diabetes insipidus
- Starting plasma osmolality:
- Urine osmolality psot deprivation:
- Urine osmolality post DDVAP:
Water deprivation test results
Deprive pt to 5% loss of body weight / for 8h then give Desmopressin (DDVAP)
Normal
- Starting plasma osmolality: Normal
- Urine osmolality post deprivation: >600
- Urine osmolality post DDVAP: >600
Psychogenic polydipsia
- Starting plasma osmolality: ↓
- Urine osmolality post deprivation: >400
- Urine osmolality post DDVAP: >400
Cranial Diabetes insipidus
- Starting plasma osmolality: ↑
- Urine osmolality post deprivation: <300
- Urine osmolality post DDVAP: >600
Nephrogenic diabetes insipidus
- Starting plasma osmolality: ↑
- Urine osmolality post deprivation: <300
- Urine osmolality post DDVAP: <300
Primary polydipsia / Psychogenic polydipsia
Characterised by excessive volitional water intake often seen in pts with severe mental illness and/or developmental disability
associated with schizophrenia, OCD, autism
generally a diagnosis of exclusion that is managed with fluid restriction & behavioural therapy
Presentation fo Primary polydipsia / Psychogenic polydipsia
Polyuria Nausea Headache water seeking excessive water intake
Investigations for Primary polydipsia / Psychogenic polydipsia
Na+ (↓) ADH levels (normal) Plasma osmolality (slightly ↓) urine osmolality (↓↓)
Water deprivation test
- Starting plasma osmolality: ↓
- Urine osmolality post deprivation: >400
- Urine osmolality post DDVAP: >400
Hyperprolactinaemia
a condition defined by ↑ serum prolactin levels due to ↑ prolactin secretion by the anterior pituitary
can be physiological e.g. in pregnancy, lactation of in response to stress
most common pathological cause are Prolactinomas (prolactin secreting pituitary adenoma)
overall more common in women
Aetiology of Hyperprolactinaemia
Physiological
- pregnancy
- lactation
- stress
Pathological
- Prolactinomas (most common cause)
- severe hypothyroidism
- Acromegaly
- PCOS
Medication / Drugs (usually those agains as dopamine antagonists)
- metoclopramide
- domperidone
- haloperidol
- risperidone
Presentation of Hyperprolactinaemia
Men
- ↓ libido, erectile dysfunction
- ↓ beard growth
- gynaecomastia
- osteoporosis
Females
- galactorrhoea
- amenorrhoea / oligomenorrhoea
- hirsutism
- ↓ libido
- atrophic endometrium & vaginal atrophy
NB if prolactinoma may have bitemporal hemianopia, headaches, cranial nerve palsy
Investigations for Hyperprolactinaemia
Prolactin levels
- ↑
- > 5000mU/L indicates prolactinoma
TFTs
pregnancy test
pituitary MRI
Management of Hyperprolactinaemia
Dopamine agonists
- e.g. bromocriptine, cabergoline, quinagolide
- inhibit prolactin secretion via stalls effect
Consider transsphenoidal resection of tumour if medical therapy fails in prolactinoma
Hypopituitarism
a partial or complete deficiency of one or more pituitary hormones due to damage to the pituitary gland and/or hypothalamus
most common cause is compression of pituitary by non secretory pituitary macroadenoma
Aetiology of Hypopituitarism
Compression of pituitary by non-secretory pituitary macroadenoma (most common)
pituitary apoplexy Sheehans syndrome trauma iatrogenic irradiation hypothalamic tumours e.g. craniopharyngioma sarcoidosis infection e.g. neurosyphilis, meningitis
Presentation of Hypopituitarism
Symptoms depend on deficient hormone
GH ↓ = short stature if in childhood, otherwise subtle
ACTH ↓ = tiredness, postural hypotension, weight loss
FSH/LH ↓ = amenorrhoea, loss of libido, testicular atrophy, ↓ body hair in men
TSH ↓ = cold intolerance, constipation, tiredness,, bradycardia, weight gain
ADH ↓ = polyuria, polydipsia, inability to concentrate urine
NB if due to pituitary apoplexy = sudden onset symptoms
with severe headache, sudden hypotension
NB if tumour may have mass effect = headache, bitemporal hemianopia
Investigations for Hypopituitarism
U&Es Serum & urine osmolality Hormonal assay -TFTs -prolactin -gonadotrophins -testosterone -cortisol -GH
Management of Hypopituitarism
treat underlying cause e.g. remove pituitary macro adenoma with surgery
hormone replacement of deficient hormones
Pituitary adenoma
a common benign tumour of the pituitary gland, account for ~10% of all adult brain tumours
often asymptomatic
classified as micro adenoma <1cm or macro adenoma >1cm, may be secretory or non secretory
Prolactinomas are the most common types followed by none secretory tumours and then GH secreting adenomas (Acromegaly)
Presentation of Pituitary adenoma
Local effects due to mass effect
- headache (retro-orbital / bitemporal)
- visual field defects (bitemproal hemianopia)
- occular nerve palsy
hypopituitarism
hyperpituitarism (if secretory e.g. acromegaly if secreting GH)
NB sudden severe headache may indicate pituitary apoplexy
Investigations for Pituitary adenoma
pituitary function tests for hormone hyper/hyposecretion MRI pituitary (contrast enhanced)
Management of Pituitary adenoma
trans-sphenoidal surgical resection
-1st line
Radiotherapy
-usually after incomplete resection
Bromocriptine if prolactinoma
Pituitary apoplexy
sudden onset hypopituitarism caused by acute infarction / haemorrhage into pituitary adenoma
presents with sudden onset severe headache, vomiting, neck stiffness, hypotension
require urgent steroid replacement & fluid balancing
Hypernatraemia
An electrolyte imbalance consisting of a rise in Sodium (Na+) defined as serum Na+ concentration >145mmol/L (normal range 135-145)
Risk factors include elderly pts, infants, altered mental status, AKI, reliance on IV fluids
Aetiology of Hypernatraemia
Essentially 3 types:
- Hypovolaemic e.g. dehydration
- Euvolaemic e.g. renal loss
- hypervolaemic e.g. excess fluids
dehydration, fluid loss e.g. burns / excessive sweating / GI loss, diabetes insipidus, osmotic diuresis (e.g. HHS/DKA), excessive IV saline, renal loss e.g. loop diuretics
Investigations for Hypernatraemia
U&Es (Na+ ↑) urine & serum osmolality Ca2+ glucose FBC lithium levels (↑Na+ causes ↓lithium excretion so increased chance of toxicity)
Investigations for Hypernatraemia
U&Es (Na+ ↑) urine & serum osmolality Ca2+ glucose FBC lithium levels (↑Na+ causes ↓lithium excretion so increased chance of toxicity)
Management of Hypernatraemia
Address underlying cause where possible
-may be sufficient to address ↑ Na+
Determine fluid requirements
Correct hypernatraemia carefully
- rate no greater than 0.5mmol/h or 10-12mmol/day
- correction to rapidly predisposes to cerebral oedema as lowering of other osmolytes other than Na+ / K+ occurs at slower rate especially water
NB acute hypernatraemia (<24h duration) may be corrected quicker
Hyponatraemia
An electrolyte imbalance consisting of a fall in Sodium (Na+) defined as serum Na+ concentration <135mmol/L (normal range 135-145)
most common electorate abnormality encountered in clinical practice
infants & elderly pts are most at risk
Aetiology of Hyponatraemia
Sodium depletion (pts often hypovolaemic)
- renal loss (↑ urine Na+) e.g. loop diuretics
- Addisons
- diuretic stage of renal failure
- extra renal losses (normal urine Na+) e.g. burns, diarrhoea
Euvolaemic
- SIADH (e.g. in SCLC, storke, SSRIS, SAH, carbamazepine)
- hypothyroidism
Hypervolaemic
- HF / liver cirrhosis (secondary hyperaldosteronism)
- IV dextrose
- psychogenic polydipsia
Presentation of Hyponatraemia
symptoms are dictated by absolute Na+ levels & rate of fall of Na+
If rapid ↓
- confusion, coma, seizures, ataxia, respiratory failure, headaches, N&V, brain stem herniation
- due to cerebral oedema
if slow ↓
-forgetfulness, gait disturbance, headache, dizziness, fatigue, lethargy
NB sudden drop even if midl can cause significant symptoms
Investigations for Hyponatraemia
U&Es
- Na+ ↓
- NB if K+ ↑ consider addisons
Serum osmolality
- most commonly ↓,
- if ↓ = true hyponatraemia e.g. renal loss / SIADH
urine Na+
->20mmol/L indicates renal cause
Management of Hyponatraemia
If hypovolaemic
-give NaCl 0.9%
If euvolaemic
- fluid restriction to 500-1000ml / day
- consider demeclocycline or vaptans
If hypervolaemic
- fluid restriction to 500-1000ml / day
- consider loop diuretics & vaptans
If severe i.e. Na+ <120mmol/L
- monitor in HDU
- giver hypertonic saline (i.e. NaCl 3%)
NB if untreated hyponatraemia can cause cerebral oedema so prompt treatment is vital
Complications of Hyponatraemia
Osmotic demyelination syndrome (central pontine myelosis)
- irreversible
- can be due to overcorrection of hyponatraemia
- avoid replacing by >4-6mmol/L per 24h
- presents with dysarthria, paresis, dysphagia & Locked in syndrome
Hypercalcaemia
An electrolyte imbalance consisting of a rise in Calcium (Ca2+) defined as serum Ca2+ concentration >2.6mmol/L (normal range 2.1-2.6)
uncommon issue generally but often seen in pts with malignancy
Aetiology of Hypercalcaemia
Primary hyperparathyroidism & malignancy account for ~90% of cases)
Others:
sarcoidosis, TB, Pagets disease, familial hypocalciuric hypercalcaemia, Vit D intoxication, dehydration
Presentation of Hypercalcaemia
Stone, Bones, Groan, Psychiatric moans
polyuria, polydipsia depression muscle weakness constipation, abdo pain fatigue bone pain kidney stone pancreatitis dehydration cardiac arrhythmias, palpitations
Investigations for Hypercalcaemia
Ca2+ (↑) ECG (short QTc) phosphate ALP urine Ca2+ album level calcitonin PTH X-rays
Management of Hypercalcaemia
rehydration with NaCL 0.9%
after rehydration give bisphosphonates
- IV pamidronate or zolendronic acid
- NB consider calcitonin if quicker action needed
Use furosemide it pt cannot tolerate fluid therapy
- use with caution
- may worsen other electrolyte abnormalities
Steroids
-if sarcoidosis or Vit D toxicity are cause
Common blood pictures in hypercalcaemia
Primary hyperparathyroidism
- Ca2+ ↑
- Phosphate ↓
- ALP ↑
- PTH ↑
- urine calcium ↑
Malignancy
- Ca2+ ↑
- Phosphate ↓
- ALP ↑
- PTH normal/↓
Hypocalcaemia
An electrolyte imbalance consisting of a fall in Calcium (Ca2+) defined as serum Ca2+ concentration <2.1mmol/L (normal range 2.1-2.6)
NB factitious hypocalcaemia = asymptomatic ↓ total Ca2+ but normal ionised Ca2+ which is usually due to ↓ serum protein levels
Aetiology of Hypocalcaemia
Hypoparathyroidism (↓PTH) Secondary Hyperparathyroidism (↑PTH) Pseudohypoparathyroidism Others -acute pancreatitis -acute rhabdomyolysis -massive blood transfusion (citrate in blood products chelates calcium) -hyperventilation -medication e.g. citrate, bisphosphonates
NB contamination of blood samples with EDTA may give falsely low Ca2+ readings
Presentation of Hypocalcaemia
Paraesthesia (perioral, fingers/toes) Tetany, muscle cramps / twitching carpopedal spasm seizures papilloedema sub capsular cataracts
Trousseau sign
-carpal spasm if brachial artery occluded by BP cuff i.e. wrist flexion & fingers drawn together)
Chvostek sign
-tapping over parotid leads to facial muscle twitching
Investigations for Hypocalcaemia
Ca2+ (↓) U&Es amylase PTH creatine kinase Mg2+ phosphate Vit D studies ECG (↑ QT interval) urine Ca2+ & Mg2+ fundoscopy
Management for Hypocalcaemia
Acute:
- treat if symptomatic or Ca2+ <1.90mmol/L
- 10ml of 10% calcium gluconate IV over 10min
- calcium chloride is an alternative but causes local irritation
- if Mg2+ ↓ then correct this
- ECG monitoring recommended
Chronic
-Calcium & Vit D supplementation
ECG findings in different electrolyte abnormalities
Hypocalcaemia
-↑ QT interval
Hypercalcaemia
-↓ QT interval
Hypokalaemia
- U waves
- small or absent T waves
- prolonged PR interval
- ST depression
Hyperkalaemia
- Peaked or ‘tall-tented’ T waves (occurs first)
- Loss of P waves
- Broad QRS complexes
- Sinusoidal wave pattern
- Ventricular fibrillation
Hypomagnasaemia
- ECG features similar to those of hypokalaemia
- Wide QRS
- prolonged QT
- flat T waves
- U waves
- Torsades des pointes
Hyperkalaemia
An electrolyte imbalance consisting of a rise in Potassium (K+) defined as serum K+ concentration >5.5mmol/L (normal range 3.5-5.0)
Mild = 5.5-5.9 mmol/L Moderate = 6.0-6.4 mmol/L Severe = ≥6.5 mmol/L
NB K+ & H+ are competitors, ↑K+ is associated with acidosis as fewer H+ particles can enter cells
Aetiology of Hyperkalaemia
AKI Medication e.g. ACE-Is/ARBs, amiloride, spironolactone, NSAIDs, tacrlimus Addisons disease Rhabdomyolysis massive blood transfusion metabolic acidosis
NB errors in blood drawing e.g. prolonged tourniquet time or haemolysed samples may lead to ↑K+
Presentation of Hyperkalaemia
Cardiac arrhythmias e.g. VF (i.e. pt may present in cardiac arrest) muscle weakness paralysis paraesthesia ↓ reflexes nausea & vomiting diarrhoea flaccid paralysis palpitations
NB cardiac conduction abnormalities are more likely if rapidly ↑ K+
Investigations for Hyperkalaemia
ECG
- peaked/tall tented T waves
- loss of P waves
- broad QRS complex
- sinusoidal wave pattern
U&Es (↑ K+)
FBC
ABG
Glucose
NB cardiac conduction abnormalities are more likely if rapidly ↑ K+
Management of Hyperkalaemia
K+ ≥6.5 or ECG changes require emergency treatment
- 10ml of 10% calcium gluconate IV
- helps stabilise cardiac membranes - Insulin + dextrose infusion
- shifts K+ into cells
- short term ↓ in K+ - Nebulised salbutamol
- shifts K+ into cells
Stop exacerbation drugs & treat underlying cause
↑ K+ excretion
- calcium resonium (PO or enemas*)
- loop diuretics
- dialysis (for AKI & persistently ↑K+)
ECG features of Hypokalaemia
Peaked or 'tall-tented' T waves (occurs first) Loss of P waves Broad QRS complexes Sinusoidal wave pattern Ventricular fibrillation
Hypokalaemia
An electrolyte imbalance consisting of a fall in Potassium (K+) defined as serum K+ concentration <3.5mmol/L (normal range 3.5-5.0)
probably the most common electrolyte disturbance seen in hospitalised pt
Aetiology of Hypokalaemia
Vomiting thiazide & loop diuretics Cushing's Conns syndrome diarrhoea renal tubular necrosis acetazolamide laxatives (especially laxative abuse) hypomagnesaemia RAS DKA excessive liquorice ingestion chronic alcoholism
NB if ↓Mg2+ it can be hard to correct K+ if Mg2+ isn’t normalised
Investigations for Hypokalaemia
ECG
- U waves
- small/absent T waves
- prolonged PR interval
- ST depression
- pseudo QT prolongation
U&Es (↓K+) Glucose Mg2+ ABG serum digoxin
Nb if K+ ↓ it predisposes to digoxin toxicity so if pt on digoxin then should check digoxin levels
Management of Hypokalaemia
If mild / low risk pts
- oral K+ supplementation(40-120mmol/day)
- regular monitoring
If severe / high risk pts
- IV KCl in NaCl 0.9%
- rate of K+ not to exceed 10mmol/h
- NB ITU may be able to supplement at higher rate
NB if ↓Mg2+ it can be hard to correct K+ if Mg2+ isn’t normalised
NB if hypokalaemia along with hypertension should consider Conn’s syndrome, Cushings syndrome or Liddles syndrome
Presentation of Hypokalaemia
Mild forms are generally asymptomatic, symptoms generally arise if rapid fall or levels <3.0 mmol/L
muscle weakness, hypotonia, tetany hypotension cardiac arrhythmias, palpitations irregular pulse constipation respiratory failure ileus
Hypermagnesaemia
Mg2+ levels >1.05 mmol/L (normal range 0.70-1.05), much less common than ↓Mg2+
commonly seen in renal failure, rhabdomyolysis or trauma
presents with facial flushing, N&V, paralytic ileus, hypotension, flaccid muscle paralysis, absent reflexes, bradycardia, respiratory depression, complete heart block or cardiac arrest
investigations show ↑Mg2+, ↓Ca2+
Management includes IV calcium gluconate, IV fluids, Loop diuretics and dialysis (especially if severe i.e. >4mmol/L, renal insufficiency or CVS / neuromuscular symptoms)
Hypomagnesaemia
Mg2+ levels <0.7mmol/L (normal range 0.70-1.05)
aetiology includes PPIs (especially long running), diuretics, digoxin, theophylline, total parenteral nutrition, malabsorption, acute pancreatitis, refeeding syndrome
presents with paraesthesia, tetany, seizures, arrhythmias, fasciculations, tremor & confusion
Management & Investigations for Hypomagnesaemia
Investigations
- Mg2+
- U&Es
- Ca2+
- ECG (Wide QRS, prolonged QT, flat T waves, U waves, Torsades des pointes)
Management
- Mg2+ <0.4mmol/L or tetany/arrhythmias/seizures
- IV Magnesium e.g. Magnesium sulphate - Mg2+ >0.4mmol/L
- PO Magnesium salts (NB may cause diarrhoea)
offending medications e.g. PPIs should be stopped
