Endo Flashcards
Mx of Addison’s Disease?
Hydrocortisone + fludrocortisone
Management of intercurrent illness in addisons:
in simple terms the glucocorticoid dose should be doubled
common precipitating factors of DKA?
infection, missed insulin doses and myocardial infarction
features of DKA?
abdominal pain
polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
Acetone-smelling breath (‘pear drops’ smell)
diagnostic criteria of DKA?
glucose > 11 mmol/l or known diabetes mellitus
pH < 7.3
bicarbonate < 15 mmol/l
ketones > 3 mmol/l or urine ketones ++ on dipstick
mx of DKA?
fluid replacement: most patients with DKA are deplete around 5-8 litres. Isotonic saline is used initially.
insulin: an intravenous infusion should be started at 0.1 unit/kg/hour. Once blood glucose is < 14 mmol/l an infusion of 5% dextrose should be started
correction of hypokalaemia (add KCl if K+<5.5)
MOA Sulfonylureas?
Sulfonylureas are oral hypoglycaemic drugs used in the management of type 2 diabetes mellitus. They work by increasing pancreatic insulin secretion and hence are only effective if functional B-cells are present. On a molecular level they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells.
Common adverse effects
hypoglycaemic episodes (more common with long-acting preparations such as chlorpropamide)
weight gain
Rarer adverse effects
syndrome of inappropriate ADH secretion
bone marrow suppression
liver damage (cholestatic)
peripheral neuropathy
diagnosis of phaeochromo?
Urine analysis of vanillymandelic acid (VMA) is often used (false positives may occur e.g. in patients eating vanilla ice cream!)
Blood testing for plasma metanephrine levels.
CT and MRI scanning are both used to localise the lesion.
mx of phaeo?
- alpha blockade
- +? beta blockade
Once medically optimised the phaeochromocytoma should be removed.
factors suggesting benign adrenal disease on CT?
Size less than 3cm
Homogeneous texture
Lipid rich tissue
Thin wall to lesion
Thyroid acropachy
seen in Graves disease
due to autoimmune reactions of the thyroid antibodies causing soft tissue swelling under the nail bed.
causes of primary hyperPTH?
80%: solitary adenoma
15%: hyperplasia
4%: multiple adenoma
1%: carcinoma
features of primary HyperPTH?
bones, stones, abdominal groans and psychic moans’
polydipsia, polyuria
peptic ulceration/constipation/pancreatitis
bone pain/fracture
renal stones
depression
hypertension
ix of primary hyperPTH?
raised calcium, low phosphate
PTH may be raised or normal (inappropriately normal)
technetium-MIBI subtraction scan
pepperpot skull is a characteristic X-ray finding of hyperparathyroidism
tx of hyperPTH in pts not fit for surgery?
calcimimetic agents such as cinacalcet are sometimes used in patients who are unsuitable for surgery
Impt adverse effects of Carbimazole?
carbimazole used in mx of hyperthyroidism
agranulocytosis:
If the patient develops any symptoms of an infection, particularly sore throat or fever then must seek urgent medical review and a FBC must be performed to check the neutrophil count.
what can be used as ‘rescue therapy’ for exacerbations of neuropathic pain
tramadol
mx of addisonian crisis?
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
meningococcal septicaemia -> hypoadrenalism
Waterhouse-Friderichsen syndrome
- adrenal haemorrhage
Pt with hypothyroidism being treated.
What is the single most important blood test to assess her response to treatment?
TSH
As the majority of unaffected people have a TSH value 0.5-2.5 mU/l it is now thought preferable to aim for a TSH in this range
diagnosis of T2DM?
If the patient is symptomatic:
- fasting glucose greater than or equal to 7.0 mmol/l
- random glucose greater than or equal to 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.
definition of pre diabetes?
HbA1c 42-47
or fasting glucose 6.1-6.9
when is HbA1c not reliable?
misleading HbA1c results can be caused by increased red cell turnover (see below)
Conditions where HbA1c may not be used for diagnosis:
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)
impaired fasting glucose?
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)
impaired glucose tolerance?
Impaired glucose tolerance (IGT) is 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
diabetic complications?
macrovascular (ischaemic heart disease, stroke) and microvascular (eye, nerve and kidney damage) complications.
pathophysiology of T1DM?
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
pathophysiology of T2DM?
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.
other causes of diabetes?
chronic pancreatitis
haemochromatosis.
principles of managing diabetes?
drug therapy to normalise blood glucose levels
monitoring for and treating any complications related to diabetes
modifying any other risk factors for other conditions such as cardiovascular disease
main side effects of metformin?
Gastrointestinal upset
Lactic acidosis*
metformin and eGFR?
Cannot be used in patients with an eGFR of < 30 ml/min
what may reduce risk of developing thyroid eye disease in graves disease pts?
stop smoking
prednisolone
acute illness, a normal TSH and low T3 and T4 levels
sick euthyroid syndrome
blood pressure targets in T2DM?
no organ damage: < 140 / 80
end-organ damage: < 130 / 80
risk factor modification in T2DM?
Blood pressure
target is < 140/80 mmHg (or < 130/80 mmHg if end-organ damage is present)
ACE inhibitors are first-line
Lipids
following the 2014 NICE lipid modification guidelines only patients with a 10-year cardiovascular risk > 10% (using QRISK2) should be offered a statin. The first-line statin of choice is atorvastatin 20mg on
features of hyperaldosteronism?
hypertension
hypokalaemia (e.g. muscle weakness). This is a classical feature in exams but studies suggest this is seen in only 10-40% of patients
alkalosis
ix of hyperaldosteronism?
high aldosterone: renin ratio
high-resolution CT abdomen and adrenal vein sampling : to differentiate between unil and bilat sources of aldosterone excess
mx of bilateral adrenocortical hyperplasia?
spironolactone
- aldosterone antagonist
mx of adrenal adenoma causing hyperaldosteronism?
surgery
most common type of congenital adrenal hyperplasia?
21-hydroxylase deficiency (90%)
(responsible for biosynthesis of aldosterone + cortisol)
-> Increased plasma 17-hydroxyprogesterone levels
pathophysiology of hyperosmolar hyperglycaemic state (HHS)?
- ) Severe hyperglycaemia
- ) Dehydration and renal failure
- ) Mild/absent ketonuria
Hyperglycaemia -> osmotic diuresis with associated loss of Na and K
Severe volume depletion results in a significant raised serum osmolarity (typically > than 320 mosmol/kg)-> 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 HHS?
General: fatigue, lethargy, nausea and vomiting
Neurological: altered level of consciousness, headaches, papilloedema, weakness
Haematological: hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis)
Cardiovascular: dehydration, hypotension, tachycardia
diagnosis of HHS?
- Hypovolaemia
- Marked Hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis
- Significantly raised serum osmolarity (> 320 mosmol/kg)
Note: A precise definition of HHS does not exist
Goals of mx of HHS?
- Normalise the osmolality (gradually)
- Replace fluid and electrolyte losses
- Normalise blood glucose (gradually)
1st line mx of HHS?
Fluid replacement
(IV 0.9% NaCl)
*If serum osmolarity is not declining despite positive balance with 0.9% NaCl, then the fluid should be switched to 0.45% NaCl solution which is more hypotonic relative to the HHS patients serum osmolarity
aim of treatment should be to replace approx 50% of estimated fluid loss within the first 12h and the remainder in the following 12h
key parameter to monitor while treating HHS?
osmolality (+Na and glucose)
Guidelines suggest that serum osmolarity, sodium and glucose levels should be plotted on a graph to permit appreciation of the rate of change. They should be plotted hourly initially.
A safe rate of fall of plasma glucose of 4-6 mmol/hr is recommended.
rate of fall of plasma Na should not > 10 mmol/L in 24h.
is insulin required in HHS?
NO
unless
significant ketonaemia is present (3β-hydroxy butyrate is more than 1 mmol/L)
ie. mixed DKA/HHS picture
diagnostic ix of addisons?
short synACTHen test
1st line tx of acromegaly?
trans-sphenoidal hypophysectomy is 1st line for majority
dopamine agonist (bromocriptine) and somatostatin analogue (octreotide) used as medical adjuncts
or radiotx
in mx of DKA, what rate should insulin be set up at?
started at 0.1 unit/kg/hr.
what may cause HbA1c levels to be higher than expected?
due to increased red blood cell lifespan
e.g
Vitamin B12/folic acid deficiency
Iron-deficiency anaemia
Splenectomy
what medication is best to add to metformin in pt who is obese T2DM?
DPP-4 inhibitors are useful in T2DM patients who are obese
e.g. sitagliptin
Sitagliptin works by essentially increasing satiety and the insulin response to high-glucose content foods and so is more helpful in patients who overeat.
best choice for 2nd drug to add to metformin in T2DM pt who is non-obese?
sulfonylurea such as gliclazide or glibenclamide
- most effective at reducing blood glucose
drug causes of gynaecomastia?
spironolactone (most common drug cause)
cimetidine
digoxin
cannabis
finasteride
gonadorelin analogues e.g. Goserelin, buserelin
oestrogens, anabolic steroids
ix of suspected pituitary adenoma?
a pituitary blood profile (including: GH, prolactin, ACTH, FH, LSH and TFTs)
formal visual field testing
MRI brain with contrast
diagnostic ix of acromegaly?
oral glucose tolerance (OGTT) with serial GH measurements.
in normal patients GH is suppressed to < 2 mu/L with hyperglycaemia
in acromegaly there is no suppression of GH
may also demonstrate impaired glucose tolerance which is associated with acromegaly
what ix is used to differentiate T1DM from other types of diabetes?
C-peptide
when do u decide to add another drug to metformin or a third drug?
HbA1c>58
tx of choice for toxic multinodular goitre?
radioiodine
what is the first line insulin regimen for T1DM pts?
first-line insulin regime should be a basal–bolus using twice‑daily insulin detemir
MEN1?
3 Ps
Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia
Pituitary (70%)
Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration)
MEN1 gene
auto dom
MEN2a?
2 Ps 1 M
Parathyroid (60%)
Phaeochromocytoma
Medullary thyroid ca
RET oncogene
auto dom
MEN 2b?
1 P, 3 Ms
Phaeochromocytoma
Medullary thyroid cancer
Marfanoid
Multiple neuromas
RET oncogene
diabetic foot disease occurs due to?
neuropathy: resulting in loss of protective sensation (e.g. not noticing a stone in the shoe), Charcot’s arthropathy, dry skin
peripheral arterial disease: diabetes is a risk factor for both macro and microvascular ischaemia
how are diabetics screened for diabetic foot disease?
screening for ischaemia: done by palpating for both the dorsalis pedis pulse and posterial tibial artery pulse
screening for neuropathy: a 10 g monofilament is used on various parts of the sole of the foot
tertiary hyperPTH?
Ca high, PTH high
occurs following a prolonged period of secondary hyperparathyroidism, which is a high PTH with a low calcium - the parathyroid glands begin to function autonomously having undergone hyperplastic/adenomatous change.
how to differentiate primary from secondary adrenal insufficiency?
skin hyperpigmentation
primary: problem in the adrenal. decreased feedback -> high ACTH from pit.
POMC -> ACTH + MSH (melanocyte stimulating hormone)
Tests to confirm Cushing’s syndrome?
overnight dexamethasone suppression test (most sensitive)
24 hr urinary free cortisol
endocrine parameters reduced in stress response?
Insulin
Testosterone
Oestrogen
definition of diabetes mellitus?
multisystem disorder due to absolute or relative lack of endogenous insulin -> high blood glucose levels -> metabolic and vascular complications
T1DM vs T2DM?
T1DM: autoimmune destruction of B cells -> absolute insulin deficiency
usually starts in adolescents
presents w polyuria/ dipsia, weight loss, DKA
anti-islet, anti-glutamic acid decarboxylase Abs
T2DM: insulin resistance and B-cell dysfunction -> relative insulin deficiency
usually older pts
presents w polyuria, dipsia, complications, weight gain
high genetic concordance: 80% in Monozygotic twins
assoc w obesity, high caloric intake, alcohol excess
secondary causes of diabetes mellitus?
drugs: steroids, atypical neuroleptics, anti-HIV
pancreatic: chronic pancreatitis, panc ca, CF, haemochromatosis
Endo: Phaeo, cushings, Acromegaly
Other: glycogen storage diseases
what is metabolic syndrome?
central obesity (increased waist circumference) and 2 of:
high triglycerides,
low HDL
HTN
Hyperglycaemia: DM, IGT, IFG
Mx of diabetes mellitus?
MDT: GP, endocrinologist, surgeons, specialist nurses, dieticians, chiropodists
Monitoring: 4Cs glycaemic control, Complications, competency, coping
Lifestyle modification:
diet, exercise, smoking cessation, reduce alcohol
Medications: Statins (regardless of lipids), Anti-hypertensives (e.g. ACEi), aspirin (primary prevention due to raised CVD risk)
Glycaemic Control medications: oral hypoglycaemics/ insulin
what to monitor in DM patients?
glucose Control:
- record of complications: DKA, HONK, hypos
- Cap blood glucose
- HbA1c
- BP, lipids
Complications:
macrovascular- pulses, BP, cardiac auscultation
Micro: fundoscopy, Albumin:Cr, U+Es, sensory testing + foot exam
competency:
- w insulin injections
- check injection sites
- BM monitoring
coping:
- psychosocial: depression
- occupation
- home life
statins in diabetics?
give all DM pts statins if >40 regardless of lipids level for primary prevention
BP target for DM pts?
<130/80
what anti-hypertensive class is best for DM?
ACEi
(BB may mask hypos, thiazides may increase [glucose])
Aspirin in diabetics?
aspirin is used for pirmary prevention if >50 or <50 w other CV RFs
1st line oral hypoglycaemic medication for DM?
Metformin
(if HbA1c> target after lifestyle changes)
SE: nausea, diarrhoea, abdo pain, lcatic acidosis
CI: eGFR<30, tissue hypoxia (sepsis, MI), morning before GA and iodinated contrast media
principles w insulin administration?
ensure pt education about
- self adjustment w exercise and calories
- titrate dose
- family member can abort hypos w sugary drinks of Glucogel
finger prick BM after meal informs re short-acting insulin dose (for that last meal)
insulin requirements in illness?
generally increase even if food intake decreases
maintain calories e.g. milk
check BMs >4hrly and test for ketonuria
increase insulin dose if glucose rising
side effects of insulin?
hypoglycaemia
lipohypertrophy
- rotate injection sites
weight gain in T2DM
Diabetic complications?
Hyperglycaemia: DKA, HONK
hypoglycaemia
infection
Macrovascular: MI, CVA
Microvascular
what macrovascular complications are assoc w DM?
MI: may be silent due to autonomic neuropathy
CVA
PVD: claudication, foot ulcers
tx: manage CV risk factors.
anti-hypertensives to reduce BP, statins for lipids,
stop smoking, HbA1c control
prevention of macrovascular complications in DM?
Good glycaemic control (HbA1c <6%) prevents both macro and microvasc complications
what are the microvascular complications assoc w DM?
kidney failure
retinopathy
Peripheral + autonomic neuropathy -> diabetic feet
what are diabetic feet due to?
- Ischaemia
Peripheral arterial disease
critical toes, absent pulses
ulcers: painful, punched out, foot margins
2. Peripheral neuropathy
- > loss of protective sensation
- > Charcot’s joints, pes cavus, claw toes
injury or infection over pressure points
ulcers: painless, punched out, pressure points e.g. metatarsal heads, calcaneum
arterial vs neuropathic ulcers?
arterial:
painful, punched out, foot margins, deep
neuropathic:
pressure points (Metatarsal heads, calcaneum), painless, punched out
Mx of diabetic feet?
conservative:
daily foot inspection w mirror
comfortable/ therapeutic shoes
regular chiropody
medical:
tx infection: benpen+ fluclox +/- metronidazole
surgical:
abscess or deep infection/ spreading cellulitis, gangrene, suppurative arthritis
features of diabetic nephropathy?
hyperglycaemia -> nephron loss and glomerulosclerosis (Kimmelstiel-Wilson lesions)
features:
microalbuminuria: urine albumin:Cr ratio >30mg/mM
if present -> ACEi/ ARB
what kind of diabetic nephropathy does one see?
nephron loss
glomerulosclerosis (kimmelstiel-wilson lesions)
pathogenesis of diabetic retinopathy?
microvascular disease -> retinal ischaemia -> raised VEGF -> new vessel formation
-> intra ocular haemorrhage and possible vessel detachment w profound global sight loss
and
localised damage to the macula/ fovea of the eye w loss of central visual acuity
presentation of diabetic retinopathy?
retinopathy and maculopathy
cataracts
new vessels on iris -> glaucoma
CN palsies
classification of diabetic retinopathy?
Background retinopathy:
- dots: microaneurysms
- blot haemorrhages
- hard exudates
Pre-proliferative retinopathy:
- cotton wool spots (retinal infarcts)
- venous bleeding
- haemorrhages
Proliferative Retinopathy:
- new vessels
- pre-retinal or vitreous haemorrhage
Diabetic maculopathy?
decreased visual acuity
hard excudates within one disc width of macula
mx of diabetic retinopathy?
laser photocoagulation
Ix of diabetic retinopathy?
fluorescein angiography
what types of neuropathies are seen in DM?
ischaemia: loss of vasa nervorum
metabolic: glycosylation, Reactive O2 species
symmetric sensory polyneuropathy
- glove and stocking -> loss of all modalities
- absent ankle jerks
- numbness, tingling, pain
mononeuropathy/ mononeuritis multiplex
e.g. CN3/6 palsies
Femoral Neuropathy
- painful asymmetric weakness and wasting of quads w loss of knee jerks
autonomic neuropathy
- postural hypotension
- urinary retention
- gastroparesis -> early satiety, bloating
- erectile dysfunction
- diarrhoea
diabetic amyotrophy:
- weakness + excruciating pain in thigh, hip, butt
- absent reflexes
- usually unilateral
mx of peripheral neuropathy due to DM?
paracetamol for pain
or Neuropathic pain meds: gabapentin, amitriptyliine
diagnosis of femoral neuropathy/ amyotrophy from DM?
nerve conduction and EMG
mx of autonomic dysfunction in DM?
postural hypotension: fludrocortisone
diarrhoea: codeine phosphate
pathogenesis of DKA?
ketogenesis: low insulin -> decreased glucose utilisation + increased fat B-oxidation
increased generation of ketone bodies (acidic)
dehydration: severe hyperglycaemia (osmotic diuresis) + high ketones -> vomiting
Acidosis
diagnosis of DKA?
cap ketones: ≥ 3mM (≥ 2+ on dipstick)
Acidosis: pH <7.3 (Severe if pH<7.1)
Hyperglycaemia: ≥11.1 mM or known DM
IX of DKA?
capillary blood glucose and ketones
Urine: ketones and glucose, MCS
VBG: acidosis + high K
Bloods: FBC, U+E, Glucose, cultures
CXR: evidence of infeciton
what is Klinefelter’s Syndrome?
47 XXY
- often taller than average
- lack of secondary sexual characteristics
- small firm testes
- infertile
- gynaecomastia (increased incidence of breast CA)
- elevated gonadotrophin levels
diagnosis by chromosomal analysis
complications of DKA?
cerebral oedema: excess fluid administration
-> commonest cause of mortality
aspiration pneumonia
hypoK
HypoPO4 -> resp and skeletal muscle weakness
thromboembolism
arrhythmias
mx of DKA v simply?
GRIP
gastric aspiration
Rehydration
Insulin infusion (+ dextrose later)
Potassium replacement
electrolyte abnormalities u may also see in DKA?
hypoNa
- osmolar compensation for hyperglycaemia
amylase often raised (up to 10x)
excretion of ketones -> loss of potential bicarb-> hyperchloraemia metabolic acidosis after tx
once glucose is normalised in DKA, why still administer insulin?
glucose decreases faster than ketones and iinsulin is necessary to get rid of the ketones
Mx of DKA?
A-> E approach
**CALL FOR SENIOR HELP (Always)
Fluids: 0.9% NS via large bore cannula 1L stat if SBP<90, 1L over 1h if SBP>90
then 1L over next 2h/2h/4h/4h/6h
switch to 10% dex 1L /8h when glucose <14mM
K+ replacement: <5.5
3.5-5.5 -> 40mmol/L
<3.5mM -> consult senior for review
Insulin infusion:
Actrapid 0.1u/kg/h IVI (6u if no weight, max 15u)
mx of DKA after acute mx of fluids/ insulin/ K+?
urinary catheter: aim 0.5ml/kg/h
NGT if vomiting or reduced GCS
thromboprophylaxis w LMWH
refer to specialist Diabetes team
find and treat precipitating factors
what to monitor during DKA tx?
hourly cap glucose and ketones
VBG @ 60 min, 2h and then 2 hrly
plasma electrolytes 4hrly
complications of hyperosmolar non-ketotic coma?
occlusive events are common: DVT, stroke
- give LMWH
Mx of hyperosmolar non-ketotic coma?
rehydrate w 0.9% NS over 48h
- may need ~9L
wait 1h before starting insulin
- may not be needed
- start low to avoid rapid changes in osmolality (ie 1-3 u/hr)
look for precipitant: MI, infection, bowel infarct
what is Whipples Triad for defining Hypoglycaemia?
Low plasma glucose <3mM
symptoms consistent w hypoglycaemia
relief of symptoms by glucose administration
symptoms of hypoglycaemia?
autonomic: 2.5-3
sweating, anxiety, hunger, tremor, palpitations
neuroglycopaenic: <2.5
confusion, drowsiness, seizures, personality change, coma
causes of hypoglycaemia?
exogenous drugs: insulin, gliclazide
pituitary insufficiency
liver failure
addisons
islet cell tumour (insulinomas)
Hypoglycaemia + high insulin?
drugs: high C-peptide -> sulfonylurea
normal c-peptide -> Insulin
insulinoma
hypoglycaemia + low insulin + no ketones?
cause
non-pancreatic neoplasms e.g. fibrosarcomas
insulin receptor Abs e.g. Hodgkins
hypoglycaemia + low insulin + high ketones?
Alcohol binge w no food
pituitary insufficiency
addisons
what is Nelson’s syndrome?
following bilateral adrenalectomy -> rapid enlargement of a pituitary corticotroph adenoma (ATH producing adenoma)
due to lack of cortison’s negative feedback
presents as: bitemporal hemianopia (mass effect), hyperpigmentation
what is an insulinoma?
benign B-cell tumour usually seen w MEN1
presents w fasting/ exercise-induced hypoglycaemia
Ix of insulinoma?
hypoglycaemia + high insulin
exogenous insulin does not suppress c peptide
MRI, EUS pancreas
mx of insulinoma?
excision
Mx of hypoglycaemia if pt is alert and orientated?
oral carbohydrates
rapid acting: lucozade
long acting: sandwich, next meal
mx of hypoglycaemia in pt drowsy/ confused but swallow intact?
Glucogel/ hypostop
(buccal carb)
consider IV access
mx of hypoglycaemia in pt if unconscious or concerned about swallow?
IV dextrose 100ml 20%
or IM Glucagon (esp if no access)
problems with IM glucagon?
wont work in drunks + short duration of effect (20 min)
insulin release may -> rebound hypoglycaemia
symptoms of thyrotoxicosis?
hot, sweating
weight loss
diarrhoea
tremor
palpitations
oligomenorrhoea +/- infertility
signs of hyperthyroidism/
hands:
fast irregular pulse, fine tremor, warm/ moist skin, palmar erythema
face:
thin hair
lid lag
lid retraction
neck:
goitre
Graves specific:
- Exophthalmos, ophthalmoplegia
- pretibial myxoedema
- thyroid acropachy
Ix of hyperthyroidism?
TFTs: low TSH, high T4/3
Abs: TSH receptor, Thyroid Peroxidase
High Ca, LFTs
Radionuclide isotope scan
Visual fields, acuity, movements
features of Graves disease?
diffuse goitre w increased iodine uptake
ophthalmopathy
pretibial myxoedema
triggers: stress, infection, childbirth
Assoc w T1DM, vitiligo, Addisons
What is Plummer’s Disease?
toxic multinodular goitre
iodine scan shows hot nodules
causes of hyperthyroidism?
Graves
Toxic multinodular goitre
thyroid adenoma
toxic phase of de Quervains thyroiditis
drugs: thyroxine, amiodarone
mx of thyrotoxicosis?
medical:
symptomatic - BB e.g. propranolol
anti-thyroid - carbimazole (inhibits TPO) or propylthiouracil
radiological: radio iodine
surgical: thyroidectomy
in Graves disease, how long do you tx pts with carbimazole?
for 12-18 mos then withdraw
50% relapse -> surgery or radioI
contraindications to radioiodine mx of hyperthyroidism?
pregnancy
lactation
complications of thyroidectomy?
recurrent laryngeal n damage -> hoarseness
hypoPTH
hypothyroidism
features of thyroid storm?
high temp
agitation, confusion, coma
tachycardia, AF
acute abdomen
HF
precipitants of a thyroid storm?
recent thyroid sx or radioI
infection
MI
trauma
Mx of thyroid storm?
Resus, A->E, call senior help
- fluid resus + NGT
- Bloods: TFTs + cultures if infection suspected
- Propranolol PO/IV
- Digoxin may be needed
- Carbimazole then Lugol’s Iodine 4h later to inhibit thyroid
- Hydrocortisone
- tx cause
symptoms of hypothyroidism?
cold intolerance
weight gain
lethargy
constipation
menorrhagia
low mood
signs of hypothyroidism?
cold hands
bradycardic
slow relaxing reflexes
dry hair and skin
puffy face
goitre
myopathy, neuropathy
ascites
myxoedema -> subcut tissue swelling in severe hypothyroidism, typically around eyes and dorsum of hand
causes of hypothyroidism?
primary: atrophic thyroiditis, Hashimotos thyroiditis, post-partum, post-deQuervains, iodine deficiency (commonest worldwide), drugs- carbimazole, amiodarone, lithium
congenital: thyroid agenesis
post surgical: thyroidectomy, radioiodine
Atrophic thyroiditis vs Hashimoto’s thyroiditis?
Atrophic:
thyroid abs +ve: anti-TPO, anti-TSH
lymphocytic infiltrate -> atrophy (no goitre)
Hashimotos:
TPO +ve, anti thyroglobulin +ve
atrophy + regen -> goitre
mx of hypothyroidism?
levothyroxine
- titrate to normalise TSH
check for other autoimmune disease e.g. Addisons
features of Acromegaly?
Symptoms: amenorrhoea, headache, snoring, sweating, arthralgia, carpal tunnel
Face: coarse facial appearance, large tongue, prognathism (jaw protrudes), interdental spaces, prominent supraorbital ridges, big ears
Hands: spade-like hands, thenar wasting (carpal tunnel)
Other: increase in shoe size, excessive sweating and oily skin
features of pituitary tumour: hypopituitarism, headaches, bitemporal hemianopia
raised prolactin in 1/3 of cases → galactorrhoea
6% of patients have MEN-1
complications of acromegaly?
hypertension
diabetes (>10%) or impaired glucose tolerance
cardiomyopathy, LVH, increased risk IHD/ stroke
colorectal cancer
features of myxoedema coma?
hypothyroid +
hypothermia
hypoglycaemia
heart failure: bradycardia + low BP
coma and seizures
Mx of myxoedema coma?
Correct any hypoglycaemia
T3/T4 IV slowly
Hydrocortisone 100mg IV
tx hypothermia and HF
mx of thyroid cyst?
aspiration or excision
mx of de quervains thyroiditis?
pain relief -> nsaids
Self limiting: conservative approach
what is Riedel’s thyroiditis?
dense fibrosis that replaces normalthyroid parenchyma
mass effects
hard fixed thyroid mass
assoc w retroperitoneal fibrosis
mx: conservative
ix of cerebral oedema if suspected?
CT head
indications for thyroid surgery?
pressure symptoms
relapse hyperthyroidism
cosmetic
carcinoma
what to do pre-op in thyroid surgery?
render euthyroid w antithyroid drugs
- start 10d prior to surgery as they increase vascularity
check for phaeo preop in medullary carcinoma
laryngoscopy: check vocal cords pre and post op
complications of thyroid surgery?
Early
- reactionary haemorrhage -> haematoma -> can cause airway obstruction
- laryngeal oedema can -> airway obstruction
recurrent laryngeal n palsy -> hoarse voice (R more common due to oblique ascent)
- hypoPTH -> low Ca
- thyroid storm
late:
hypothyroidism
recurrent hyperthyroidism
Keloid scar
mx of haematoma from thyroid surgery?
call anaesthetist and remove wound clips
evacuate haematoma and re explore wound
which laryngeal n is most likely damaged in thyroid surgery?
R due to oblique ascent
damage to one -> hoarse voice
damage to both -> obstruciton needing trache
features of primary hyperaldosteronism?
excess aldosterone
HTN
HypoK: muscle weakness, hypotonia, hyporeflexia, cramps
alkalosis
causes of primary hyperaldosteronism?
Bilateral adrenal hyperplasia (70%)
Adrenocortical adenoma: conns (30%)
Ix of primary hyperaldosteronism?
1st line: Aldosterone/ renin ratio (high)
High resolution CT abdomen and adrenal vein sampling used to differentiate between unilateral and bilateral sources
U+Es, high Na, low K, alkalosis
ECG: signs of hypoK (flat inverted T waves)
mx of primary hyperaldosteronism?
adrenal adenoma: surgery
bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone or eplerenone
CT Abdo showing right sided adrenal adenoma
seen below liver
what is secondary hyperaldosteronism?
high aldosterone due to high renin from decreased renal perfusion
causes:
Renal artery stenosis
diuretics
CCF
hepatic failure
nephrotic syndrome
(Aldosterone; renin ratio is normal)
what is Bartter’s syndrome?
auto recess
blockage of NaCl reabsorption in loop of Henle (as if taking frusemide)
congenital salt wasting -> RAS activation -> hypoK and metabolic alkalosis
normal BP
What does PTH do?
secreted in response to low Calcium
- increases osteoclast activity
- increases Ca and decreases PO4 reabsorption in kidney
increases 1a-hydroxylation in 25OH-VitD3
features of high Calcium?
stones; renal stones, polyuria and dipsia (nephrogenic DI), nephrocalcinosis
Bones: bone pain, pathological #s
moans: depression
groans; abo pain, constipation, pancreatitis
causes of primary hyperPTH?
80%: solitary adenoma
15%: hyperplasia
4%: multiple adenoma
1%: carcinoma
Primary HyperPTH is assoc w?
high Ca
HTN
MEN 1 and II
Ix of Primary HyperPTH?
raised calcium, low phosphate
PTH may be raised or normal (inappropriately), Alk phos raised
technetium-MIBI subtraction scan
Xray: osteitis fibrosa cystica, pepperpot skull, phalangeal erosions
DEXA: osteoporosis
ECG: shortened QT interval, bradycardia, 1st degree block
Mx of primary HyperPTH?
General: increase fluid intake, avoid dietary calcium and thiazides (increase serum Ca)
definitive tx: total parathyroidectomy / excision of adenoma
conservative management may be offered if the calcium level is less than 0.25 mmol/L above the upper limit of normal AND the patient is > 50 years AND there is no evidence of end-organ damage
calcimimetic agents such as cinacalcet are sometimes used in patients who are unsuitable for surgery
what is secondary hyperPTH?
Caused: chronic renal failure, Vit D deficiency
Low Ca-> secondary hyper PTH
Low, Ca, high PTH, high PO4, high Alk phos, low Vit D
Mx of secondary hyperPTH?
tx cause
phosphate binders: e.g. calcichew (w ca)
Vit D: alfacalcidol
Cinacalcet: increases PTH Ca sensitivity
what is tertiary hyperPTH?
prolonged secondary hyperPTH -> autonomous PTH secretion
high Ca, high PTH, low PO4, high alk phos
Causes of hypoPTH?
Autoimmune
Congenital: DiGeorge’s
- CATCH 22 (cardiac abnormality Fallots, abnormal facies, thymic aplasia, cleft palate, hypoCa, chr22)
iatrogenic: surgery, radiation
Mx of hypoPTH
Ca supplements
calcitriol (alcalcidol)
What is pseudohypoPTH?
failure of target organ response to PTH
symptoms of hypoca
short 4 and 5th metacarpals, short stature
IX: low Ca, high PTH
Tx: Ca, calcitriol
phaeochromocytoma rules of 10s?
bilateral in 10%
malignant in 10%
extra-adrenal in 10% (most common site = organ of Zuckerkandl, adjacent to the bifurcation of the aorta)
10% familial and assoc w MEN II, neurofibromatosis and von Hippel Lindau
features of phaeochromocytoma?
typically episodic
hypertension (around 90% of cases, may be sustained)
headaches
palpitations
sweating
anxiety
Ix of phaeochromocytoma?
24h Urinary collection of metanephrines
(also vanillylmandelic acid)
Abdo CT/MRI
Mx of phaeo?
Medical:
if malignant
chemo or radiolabelled MIBG (mete-iodobenzylguanide)
Surgery:
adrenalectomy is definitive
use Alpha blocker (phenoxybenzamine) first, then BB (propranolol) preop
-monitor BP post op
features of hypertensive crisis?
pallor
pulsating headache
feeling of impending doom
V high BP
Tachycardic and cardiogenic shock
mx of hypertensive crisis?
Phentolamine 2-5mg IV (a blocker) or labetalol 50mg IV
- repeat to safe BP
phenoxybenzamine 10mg/d PO when BP controlled
elective surgery after 4-6 wks to allow full alpha blockade and volume expansion
features of cushings syndrome?
catabolic effects:
proximal myopathy
striae
bruising
osteoporosis
glucocorticoid effects:
obesity
DM
mineralocorticoid effects:
HTN
hypoK
appearance:
moon face
thin skin
centripetal obesity, thin limbs
acne and hirsutism
interscapular and supraclaviciular fat pads
Causes of high ACTH causing CUshings?
Cushings disease:
- bilateral adrenal hyperplasia due to ACTH- secreting pituitary tumour
- cortisol suppression w high dose dex
Ectopic ACTH:
- SCLC
- carcinoid tumour
- skin pigmentation, metabolic alkalosis, weight loss, hyperglycaemia
- no suppression w any dose of dex
causes of ACTH independent Cushings?
ie. no suppression w any dose of dexamethasone
iatrogenic steroids: commonest cause
adrenal adenoma/ ca
Carney complex: LAME syndrome
McCune Albright
Ix of Cushings?
1st line: 24h urinary free cortisol
Dexamethasone suppression test
- High dose dexamethasone suppresses Cushings Disease
- CT/MRI brain/ adrenals
- DEXA scan: osteoporosis
Mx of Cushings’ Syndrome?
treat underlying cause
Cushings disease: transsphenoidal excision
Adrenal Adenoma/Ca: adrenalectomy
Ectopic ACTH: tumour excision, metyrapone (inhibits cortisol synthesis)
Symptoms of Diabetes Insipidus?
polyuria
polydipsia
dehydration
hyperNa: lethargy, thirst, confusion, coma
causes of Diabetes Insipidus?
Cranial:
idiopathic 50%
congenital
tumours
trauma
vascular - sheehans syndrome
infection - meningoencephalitis
infiltration: sarcoidosis
nephrogenic:
- congenital
metabolic: low K, high Ca
drugs: lithium, vaptans, demecleocycline
post obstructive uropathy
Ix of Diabetes Insipidus?
Bloods: U+E, Ca, glucose
Urine and plasma osmolality: urine fails to concentrate w water deprivation
Diagnosis via water deprivation test w desmopressin trial
Mx of cranial DI?
Find cause: MRI brain
Desmopressin PO
Mx of nephrogenic DI?
treat cause
causes of erectile dysfunction?
Smoking
Alcohol
DM
endo: hypogonadism, hyperthyroid, high prolactin
neuro: MS, autonomic neuropathy, cord lesion
Pelvic surgery: bladder, prostate
penile abnormalities: peyronies disease
How do thiazolidinediones work in DM?
agonists to PPAR-gamma receptor and REDUCE peripheral insulin resistance
e.g. pioglitazone
adverse effects: weight gain, liver impairment, fluid retention, increased risk of #s and bladder Ca
Pioglitazone SE profile?
weight gain
liver impairment (monitor LFTs)
fluid retention - contraindicated in HF
Increased risk of #s and bladder cancer
causes of hirsutism?
familial
idiopathic
increased androgens: PCOS, Cushings, Adrenal Ca, drugs- steroids
features of PCOS?
secondary oligo/amenorrhoea -> infertility
obesity
acne, hirsutism
Ix of PCOS?
US ovaries: bilateral polycystic ovaries
Hormones: high testosterone, low SHBG, high LH:FSH ratio
Mx of PCOS?
metformin
COCP
clomifene for infertility
causes of gynaecomastia?
liver cirrhosis
hypogonadism
hyperthyroidism
oestrogen producing tumours
drugs: spironolactone, cimetidine, digoxin, oestrogen
symptoms of hyperprolactinaemia?
amenorrhoea
infertility
galactorrhoea
decreased libido
Erectile dysfunction
mass effects from prolactinoma
Ix of Acromegaly?
raised IGF-1
high glucose, Ca, PO4
glucose tolerance test: GH not suppressed
visual fields and acuity
MRI brain
Causes of hyperprolactinoma?
Dopamine antagonists (commonest cause):
antiemetics: metoclopramide
antipsychotics: haloperidol, risperidone
disinhibition by compression of pituitary stalk:
pituitary adenoma
craniopharyngioma
excess pituitary production:
pregnancy, breastfeeding
prolactinoma (PRL >5000)
hypothyroidism (high TRH-> increased prolactin)
Ix of prolactinoma?
basal prolactin (>5000 - prolactinoma)
pregnancy test
TFTs
MRI brain
Mx of hyperprolactinoma?
1st line: dopamine agonists
cabergoline, bromocriptine
- to decrease prolactin secretion and tumour size
2nd line; transsphenoidal excision
- if visual or pressure symptoms not managed by medical tx
what rate should insulin be given at initially in DKA?
0.1 u/kg/ hour
micro vs macroadenoma?
micro <1 cm
macro >1 cm
most common hormone secreted by a pituitary tumour
prolactin 50%
features of pituitary adenoma?
headache
visual field defect: bitemporal hemianopia (superior)
CN palsies: 3, 4, 5, 6 (pressure on cavernous sinus)
Diabetes insipidus
CSF rhinorrhoea
Ix of pituitary adenoma?
MRI pituitary
Visual field testing
hormones: Prolactin, IGF (GH), ACTH, cortisol, TFTs, LH/FSH
suppression tests
Craniopharyngioma features?
superior to optic chiasm -> inferior bitemporal hemianopia
commonest childhood intracranial tumour -> Growth failure
Calcification seen on CT/MRI
What is pituitary apoplexy?
rapid pituitary enlargement due to bleed into a tumour
mass effects: headache, meningism, low GCS, bitemporal hemianopia
cardiovascular collapse due to acute hypopituitarism
mx of pituitary apoplexy?
urgent hydrocortisone 100mg IV
Mx of pituitary adenoma?
medical:
replace hormones
treat hormone excess
surgery: trans sphenoidal excision
- pre op hydrocortisone
- post op dynamic pituitary tests
radiotherapy
what drug is given pre op to trans sphenoidal excision of pituitary?
Hydrocortisone
Causes of hypopituitarism?
Hypothalamic:
Kallmann’s (anosmia + GnRH deficiency)
Tumour
Inflam, infection, ischaemia
Pituitary stalk:
trauma, surgery, craniopharyngioma
Pituitary:
irradiation
ischaemia- apoplexy, sheehans
tumour
infiltration: hereditary haemochromatosis, amyloid
commnest causes of panhypopituitarism?
surgery
tumour
irradiation
features of hypopituitarism?
Hormone deficiency:
GH = central obesity, atherosclerosis, decreased strength/ CO
LH/FSH: low libido, erectile dysfunction, amenorrhoea, breast atrophy
TSH; hypothyroidism
ACTH: secondary adrenal failure
Ix of hypopituitarism?
basal hormone tests
dynamic pituitary function test:
insulin -> should raise cortisol + GH
GnRH -> LH/FSH
TRH -> T4 + prolactin
MRI brain
Tx of hypopituitarism?
hormone replacement
tx underlying cause
What is MEN1?
auto dom
3 Ps
Pituitary adenoma: prolactin or GH
Pancreatic tumour: insulinoma/ gastrinoma
Parathyroid adenoma/ hyperplasia
What is MEN 2a?
auto dom
functioning hormone tumours in multiple organs
2 Ps 1M
Phaeochromocytoma
Parathyroid hyperplasia/ adenoma
Medullary thyroid Ca
What is MEN 2b?
auto dom
functioning hormone tumours in multiple organs
3Ms + 1 P
phaeochromocytoma
marfanoid habitus
Medullary thyroid Ca
Multiple mucosal neuromas
What is Carney Complex/ LAME syndrome?
LAME Syndrome
auto dom
Lentigenes: spotty skin pigmentation
Atrial Myxoma
Endocrine tumours: pituitary, adrenal hyperplasia
Schwannomas
what is Von Hippel Lindau?
Renal cysts
bilat RCC
haemangioblastomas - often in cerebellum
phaeochromocytoma
pancreatic endocrine tumours
what is the most severe of Grave’s eye disease?
from most severe:
sight loss due to optic n involvement
corneal involvement
extra ocular muscle involvement
proptosis
Autoimmune polyendocrine syndrome type 1 consists of?
Auto recessive
Addisons
Candidiasis
HypoPTH
Autoimmune polyendocrine Syndrome Type 2 consists of?
polygenic
addisons
thyroid disease: Graves, hypothyroid
T1DM
Causes of Addison’s disease?
destruction of adrenal cortex -> glucocorticoid and mineralocorticoid deficiency
Autoimmune destruction 80% in UK
TB: commonest worldwide
Mets: lung
Haemorrhage; waterhouse-friedrichson
congenital: CAH
features of addisons?
hyperpigmentation: buccal mucosa, palmar creases
vitiligo
weight loss
lethargy
postural hypotension-> dizziness, faints
hypoglycaemia
addisonian crisis
Ix of addisons disease?
Bloods: low Na, high K, low glucose, Ca, anaemia
Short SynACTHen test to diagnose
21-hydroxylase Abs: +ve in 80% of autoimmune disease
plasma renin and aldosterone
CXR: TB?
AXR: adrenal calcification
Mx of Addisons?
Replace: Hydrocotrisone, fludrocortisone
Advice:
dont stop steroids suddenly, increase steroid dose during illness, injury
wear medic alert bracelet
Causes of secondary adrenal insufficiency?
ie. hypothalamic or pituitary failure
chronic steroid use -> suppression of HPA axis
pituitary apoplexy/ Sheehans
pituitary microadenoma
features: no pigmentation (ACTH low)
Addisonian crisis features?
shocked: confused, low BP, high HR, oliguria
hypoglycaemia
precipitated by:
infection, trauma, surgery, stopping long term steroids,
adrenal haemorrhage (Waterhouse-Friedrichson)
Mx of Addisonian Crisis?
hydrocortisone 100 mg im or iv 6hrly until pt stable
1L normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
Tx underlying cause
oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
Mx of Addisons disease pt w intercurrent illness?
what to change for doses of hydrocortisone and fludrocortisone
double dose of hydrocort
keep same dose fludrocort
which mx has the lowest glucocorticoid activity and highest mineralocorticoid?
fludrocortisone
which mx has the highest glucocorticoid activity and lowest mineralocorticoid?
dexamethasone
betamethasone
what mx has high glucocorticoid and mineralocorticoid activity?
Hydrocortisone
features of neuroblastoma?
tumour arises from neural crest tissue of the adrenal medulla (the most common site) and sympathetic nervous system.
abdominal mass
pallor, weight loss
bone pain, limp
hepatomegaly
paraplegia
proptosis
Ix of neuroblastoma?
raised urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels
calcification may be seen on abdominal x-ray
biopsy
Mx of subclinical hypothyroidism in < 65 years with symptoms suggestive of hypothyroidism?
trial of levothyroxine
If there is no improvement in symptoms, stop levothyroxine
Mx of subclinical hypothyroidism in asymptomatic ppl?
observe and repeat thyroid fn in 6mo
mx of subclinical hypothyroidism in older ppl?
follow a ‘watch and wait’ strategy, generally avoiding hormonal treatment’
esp if over 80
what electrolyte is extremely important for Calcium levels in the body?
Magnesium
required for both PTH secretion and its action on target tissues. Hypomagnesaemia may both cause hypocalcaemia and render patients unresponsive to treatment with calcium and vitamin D supplementation.
Magnesium and calcium interact at a cellular level also and as a result decreased magnesium will tend to affect the permeability of cellular membranes to calcium, resulting in hyperexcitability.
