Endocrine Flashcards
Name 6 complications diabetes
Acute
- hypoglycaemic
- DKA
- HHS (hyperglycaemic hyperosmolar state)
Chronic
→ Microvascular
- retinopathy, cataract
- nephropathy
- neuropathy: peripheral and autonomic (gastroparesis, altered bowel habit, postural hypotension )
- foot disease
→ Macrovascular
- cardiovascular: coronary artery disease, mi
- Cerebrovascular: stroke
- peripheral vascular disease: claudication, ischaemia, decreased pulses
Name 7 symptoms diabetes
- Polyphagia (hunger)
- glycosuria
- polyuria
- polydipsia (thirst)
- unexplained weight loss
- visual blurring
- genital thrush
- lethargy
Name 10 causes insulin resistance
Non-modifiable
- Asians, especially Indians
- cystic fibrosis
- acromegaly
Modifiable
- obesity
- Tb drugs
- pregnancy
- Cushing’s
- renal failure
- PCOS
- metabolic syndrome: central obesity, hyperglycaemia, ht, dyslipidaemia
Treatment hypoglycemia?
- Stat 20ml vile of 50% dextrose
- another 20ml vile added to 10% dextrose drip
Management DKA? (6)
- Blood gas
- check potassium
- controversial: correct acidosis with bicarb if ph < 7
- Fluid
- iv 0,9% sodium chloride (prefer) or ringers 1l over 1h then 250 - 500ml per hour
- goal: replace 50% of fluid deficit in first 12 hours, rest in next 12 hours (about 5-10 L average loss)
- once glucose <14, use 5% dextrose to prevent hypoglycaemia
- Insulin
- first check serum potassium
- 0,15 units /kg/hour of iv short/rapid acting insulin if K not low
- or 10 units regular insulin IM or iv hourly
- then continuous infusion 0,1 u/kg/h until glucose < 14, then half infusion rate.
- monitor glucose hourly and adjust accordingly
- switch to subcutaneous insulin when: fully concious and eating, AGAP normal and acidosis resolved, glucose < 15, bohb<1
- Electrolytes
- potassium: first check levels. If < 3,5, give before insulin 40 mmol. 20 mmol KCI per L iv fluid if 3.5-5.5. Don’t give if 5.5 or more
Name the 3 types of insulin and doses
• Short acting subcutaneous injections (Sc) 3x daily 30 min before meals
• intermediate acting sc once or twice daily usually at night at bedtime, approx 8
hours before breakfast
• biphasic sc once or twice daily
Name and describe the 2 insulin regimens for dm 1
- Basal bolus regimen: combined intermediate acting (basal) and short acting (bolus).
Pre-meal short acting and bedtime intermediate acting not later than 22h00. Preferred in dm 1 - Pre-mixed twice daily insulin: twice daily mixture of intermediate or short acting insulin and used with at least daily glucose monitoring - practical solution for those that can’t monitor blood glucose frequently
Dose Of basal bolus insulin regimen?
Initial total daily insulin dose: 0,6 units/kg/ body weight
Total dose divided into
• 40-50% basal insulin
• rest as bolus insulin, split equally before each meal
Adjust according to individual needs
For dm 1
Add on insulin therapy (intermediate to long acting) starting dose and increments for dm 2?
Starting: 10 units in evening before bedtime but not after 22h00
Increments: increase gradually to 20 units, 2-4 units increase each week.
Substitution insulin therapy (biphasic) starting dose and increments for dm 2?
Starting: twice daily. total daily dose 0,3 units /kg/day divided as 213 30 minutes before breakfast and 1/3 30 minutes before supper
Increment: 4 units weekly. First increment added to dose before breakfast, second added to dose before supper.
Which 2 tests screen for diabetic peripheral neuropathy
- Ipswich touch test
- monofilament testing
- tuning fork 128 Hz
Name 10 clinical features hyperthyroidism
Like hyper metabolism.
- General: fatigue, heat intolerance,
- CNS: fine tremor! Proximal muscle weakness! Hypo K periodic paralysis , irritable
- skin: Palmar erythema! Fine hair! Vitiligo! Pruritis, clubbing + pretibial myxoedema in graves
- eye: lid lag! Lid retraction, exophthalmos, diplopia, periorbital oedema,
- neck: goiter.in graves, goitre with bruit!
- chest: tachycardia! Palpitations! Afib! Increase sbp, breast enlargement
- git: weight loss + increased appetite! Diarrhoea! Thirst
- gynae: oligomenorrhea/amenorrhoea, loss fertility
- musculoskeletal: proximal muscle weakness! loss bone mass
- haematology: graves - leukopenia, lymphocytosis, splenomegaly, lymphadenopathy
Which is the only disease that causes exophthalmos
Graves’ disease: tsh receptors on orbital muscles. Biopsy shows lymphocyte infiltration
Name 3 manifestations of Graves’ disease
- Eye disease!: exophthalmos! Ophthalmoplegia (if see eye involvement, think graves)
- pretibial myxoedema
- thyroid acropachy: extreme manifestation - clubbing, painful finger and toe swelling, periosteal reaction in limb bones
Name 8 causes hyperthyroidism/ thyrotoxicosis
- Graves’ disease (76 % )
- toxic multi nodular goitre (14%)
- toxic nodule (adenoma) (5%)
- thyroiditis eg de Quervain’s (viral) (3%); postpartum
- iodide induced: drugs eg amioderone!, radiographic contrast media, iodine supplement
- extra thyroidal source thyroid hormone: factitious thyrotoxicosis, struma ovarii (ovarian teratoma containing thyroid tissue)
- TSH induced: tsh- secreting pituitary aclenoma, choriocarcinoma + hydatiform mole ( HCG stimulates thyroid)
- follicular carcinoma with or without metastases
Name 4 causes hypothyroidism
- Hashimoto’s! (Other autoimmune = spontaneous atrophic hypothyroidism, graves with TSH r blocking antibodies)
- congenital (dyshormonogenesis, thyroid aplasia)
- iatrogenic !: thionamides, radioactive iodine, surgery, amiodarone, lithium
- hypothyroid phase of thyroiditis (transient thyroiditis)
- iodine deficiency
- infitrative: amyloidosis, sarcoidosis, Riedel’s thyroiditis
- secondary hypothyroid: TSH deficiency
Test for dm 1?
Anti-gad (islet cell ab against glutamic acid)
Name 6 oral agents used in diabetes
DIE GAMES
- DPP 4 inhibitors (dipeptidyl peptidase): vildagliptin (block inactivation of incretin. Don’t use with GLP 1)
- incretins: glp-1 (glucagon like peptic 1 inject) eg exenetide ( stimulate B cells + slow gastric empty,significant weight loss. don’t use with DPP4)
- sulphonylurias: glimepiride (stimulate insulin release from B cells )
- alpha glucosidase inhibitors: acarbose (slows digestion)
- biguanides: metformin (increase peripheral glucose uptake)
- meglitinides: repaglinide (post prandial glucose regulator)
- SGLT2 inhibitors eg canagliflozin
Name types of insulins and examples
- Short acting regular human insulin (actrapid)
- rapid acting analogue insulin (aspart / novorapid ; lispro )
- intermediate acting basal human insulin ( NPH /protaphane)
- long acting basal analogue insulin (glargine / optisulin)
- pre-mixed human biphasic insulin = 30% regular + 70% intermediate human / NPH (actraphane humulin 30/70)
- pre-mixed analogue insulins
(For bolus, analogue preferred if can afford. For basal, human preferred)
Insulin regimen for diabetes 2?
Metformin + basal intermediate insulin ( nph protaphane) at night.
- start 10 u protaphane at night and titrate up based on morning fasting glucose
- if > 20 - 30 u needed, change to biphasic mixed insulin (actraphane/ humulin 30/70): 2/3 in morning, 1/3 at night at 0,3u/kg (start this immediately if hba1c > 10%)
Insulin regimen for diabetes 1?
Basal bolus regimen at 0,7 - 0,9 u/kg
- 40% basal at night of intermediate (nph protaphane) or long ( glargine) acting
- 60% bolus divided by 3 meals of rapid (aspart) or short (actrapid) acting
Approach to treating hyperlipidaemia?
- Simvastatin 10mg (25% reduction)
- SimVa 20mg
- Change to Atorvastatin 40 mg if LDL > 3,5 (45% reduction)
- Atorva 80 mg
- Ezetemibe ( further 25% reductions )
6% statin rule: double dose only reduces by 6%
Targets in diabetes? (6)
ABCDES
- a1c target < 7%, FBG 4 - 7, PPG <10
- blood pressure < 140/90, < 130/80 if renal disease ( enalapril, amlodipine unless kidney / liver damage, hctz)
- cholesterol: LDL < 1,8
- drugs for CVD risk reduction
- exercise + diet
- smoking cessation, screen for complications
Clinical clue to DM 2?
Obese, older
Metabolic phenotype
Acanthoses nigricans !
Define exophthalmos
Hertel exophthalmometer reading ( measure distance lat orbital rims to apex of cornea) > 21 mm
Antibodies in hashimoto? (3)
- Thyroglobulin antibodies
- anti thyroid peroxidase antibodies (tpo ab)
- tsh receptor antibodies
Antibodies in graves?
Tsh receptor antibodies
Also thyroid peroxidase and thyroglobulin antibodies
Name 4 autoimmune conditions associated with DM 1
- Hyper+ hypo thyroid
- celiac sprue
- pernicious anaemia
- adrenal insufficiency
Normal waist circumference?
Men < 94 cm
Women < 80cm
Define impaired glucose tolerance
OGTT 2 h glucose 7,8 - 11,1
But fasting < 7
Define impaired fasting glucose
Fasting 6,1 - 7
Define gestational diabetes
From 24 weeks of pregnancy
Treatment neuropathic pain in diabetic foot?
- Tricyclics eg amitryptilline
- pregabalin
- duloxetine (SSNRI)
- anti-epileptics eg carbamazepine, gabapentin
- capsaicin
Treatment diabetic infected foot ulcer as outpatient?
- Flucloxacillin 500mg 6 hourly po
- amoxicillin - clavulanate 1g 12 hourly po
7-14 days
Treatment diabetic infected foot ulcer as inpatient with limb threatening infection? (2)
- Amoxicillin-clavulanate 1,2g 8 hourly iv
- piperacillin-tazobactam 4,5 g 8 hourly iv for pseudomonas
1-4 weeks
Treatment hyperthyroidism?
Carbimazole + bb
Rai (radioactive iodine) / surgery
Treatment thyroid storm? (5)
- resuscitate: cooling blankets , fluid, electrolytes, vasopressors
- carbimazole 40 - 60 mg 6 hourly until crisis controlled (inhibit synthesis thyroid hormone)
- 30 mins after firSt dose: Lugol’s iodine 10 drops in milk 8 hourly (inhibits thyroid hormone)
- beta blocker atenolol 50mg daily (decrease periph conversion T4 → T3 )
- if life threatening: add iv hydrocortisone 100 mg 8 hourly
What is myxedema coma?
Medical emergency.
Severe hypothyroid complicated by trauma, sepsis, cold exposure, mi, inadvertent admin of hypnotics or narcotics, stress
Treatment myxedema coma (4)
- Resuscitate+ admit to ICU
- corticosteroids (hydrocortisone 100mg 8 h iv) for risk concomitant adrenal insufficiency
- levothyroxine 0,2 - 0,5 mg iv loading dose, then 0,1 mg iv daily until oral therapy tolerated. Consider T3
- monitor for arrhythmia!
How and when screen for dm nephropathy?
- Urine dipstick at every visit for gross proteinuria, min 4/ year
- microalbuminuria albumin: creatinine ratio annually
- start screening for microalbuminuria for type 1 5 years after diagnosis
- screen for type 2 from diagnosis
Name 5 neuropathies in diabetes
- Distal symmetrical polyneuropathy
- proximal symmetrical polyneuropathy
- mononeuritis multiplex: 2 separate nerve areas asymmetrical
- mononeuropathy eg carpal tunnel
- Autonomic neuropathy
Define Charcot’s foot
Neuropathic arthropathy
Collapse of arch of midfoot and bony prominences → deformities
Fundoscopy findings in diabetic retinopathy? (3)
- Non-proliferative: asymptomatic, microaneurysms, dot and blot flame haemorrhages, hard exudates
- pre-proliferative: soft exudates, macular edema, cotton wool spots, venous beading
- proliferative: neovascularisation, increased risk of vitreous haemorrhage + retinal detach
Which 2 hormones are secreted by adrenal cortex
- Cortisol
- aldosterone
Which 2 hormones are secreted by adrenal medulla
- Dopamine
- metanephrines
Define adrenal insufficiency
Inadequate secretion adrenal cortex hormones
Lab findings in primary adrenocortical insufficiency? (7)
= Addison’s disease
- High ACTH
- low cortisol → hypoglycaemic
- low mineralocorticoid (aldosterone) → low sodium, high potassium
Also:
- uraemia
- high calcium (cortisol normally antagonises Vit D, so also high vit d. )
- eosinophilia
- Anaemia
- plasma renin high
- DHEA low in females ( → loss libido, hair loss)
Define Addison’s disease
Primary adrenocortical insufficiency. Cortisol and aldosterone deficiency.
Name 5 causes Addison’s disease
- Autoimmune 80%! - poly glandular syndromes
- infection: tb!, HIV + its opportunistic infections eg CMV, MAC.
- malignancy: metastases or lymphoma
- adrenal haemorrhage: Waterhouse - friederichsen syndrome, antiphospholipid syndrome
- congenital: congenital adrenal hyperplasia
Causes secondary adrenocortical insufficiency?
- iatrogenic: long-term steroid then withdrawal. Most common
- hypothalamic disease
- pituitary disease
Lab findings secondary adrenocortical insufficiency?
- Low ACTH
- low cortisol, aldosterone
Symptoms adrenal insufficiency? (5)
- Chronic fatigue, depression, weakness, psychosis
- anorexia, weight loss (due to hypoglycaemia)
- dizzy, fainting
- myalgias, arthralgia
- gi!: nausea vomiting, abdominal pain, diarrhea/constipation (think of Addisons in unexplained abdominal symptoms)
Signs Addison’s? (8)
- Hyperpigmentation (due to increased ACTH - cross-reacts with melanin receptors) at palmar creases + buccal mucosa
- postural hypotension
- androgens: loss libido, alopecia
- dehydration: loss sodium and water from low aldosterone
- Excess potassium
- weight loss, mental changes, muscle weakness, vomiting
- arrhythmia
- hypoglycaemia
May have vitiligo
Presentation addisonian crisis?
Precipitated by infection/trauma/ surgery
- Shock: tachy, peripheral vasoconstriction, postural hypotension, oliguria, weak, confused, coma
- hypoglycaemic
- electrolytes: low na, high K and Ca
Management adrenal crisis? (3)
Don’t delay treatment for lab results. Treat if suspected.
- hydrocortisone 100 mg iv stat every 6 hours. Change to oral after 72h of improved
- fluids: 5% dextrose in normal saline
- antibiotics if suspect sepsis. Treat precipitant.
Treatment adrenal insufficiency? (3)
- 15 - 25 mg hydrocortisone daily in 2-3 divided doses. Avoid giving late in day (insomnia). Increase dose temporarily in stress situations
- mineralocorticoid replacement if postural hypotension, low sodium, high potassium or high renin: fludrosortisone 0,05 - 0,2 mg daily.
- adjust based on clinical response, not lab findings
- consider androgen replacement for symptomatic female: DHEA 50 mg/day
If poor response to treatment, suspect associated autoimmune disease.
Cushing syndrome vs disease?
Syndrome: chronic glucocorticoid excess, origin adrenal.
Disease: Bilateral adrenal hyperplasia due to ACTH secreting pituitary Adenoma
Clinical triad of phaeochromocytoma?
- Episodic headache
- Diaphoresis (sweating)
- tachycardia
With or without ht. (If all 4, > 90% probability)
Other symptoms: anxiety, tremor, pallor, visual changes (papilloedema, blurred vision), weight loss, polyuria, polydipsia, hyperglycaemia, arrhythmia, cardiomyopathy
Rule of 10 for phaeochromocytoma?
10% extra-adrenal
10% Bilateral
10% familial
10% malignant
Diagnosis phaeochromocytoma? (3)
- 24 hour urine catecholamines and metanephrines and chromogranin A
- clonidine suppression test: measures plasma catecholamines before and 3 hours after oral administration of 0,3 mg clonidine. Clonidine will fail to suppress in positive.
- plasma free adrenaline and noradrenaline: if >2 -4 X ULN, do abdominal Ct or MRI to localise tumour (can also localise with mibg scan)
Treatment phaeochromocytoma? (3)
- Pre-op alpha blocker: phenoxybenzamine
- then only beta blocker (atenolol) to avoid peripheral vasoconstriction and ht exacerbation with only beta blocker
- to avoid crisis from unopposed alpha adrenergic stimulation during surgery ( HT crisis)
- then surgery.
Signs and symptoms acromegaly? (10)
Excessive soft tissue growth!
Symptoms
- headache
- excess sweating
- arthralgia, oa, carpal tunnel syndrome
- proximal muscle weakness
Signs
- growth hands and feet: increase ring size, large shoe size, spade -like hands, thick heel pads
- course facial features: prominent supraorbital ridge (frontal bossing), prognathism, wide spaced teeth, macroglosia
- hoarse voice
- obstructive sleep apnoea
- organomegaly, including cardiomegaly with CCF
- hyperprotectinaemia: gynaecomastia, galactorrhoea
- hypogonadism
- signs pituitary tumour: hypopituitarism.
Diagnosis acromegaly? (3)
- Screen: serum IGF - 1 (levels correlate with gh secretion in last 24h)
- definitive: OGTT with serum growth hormone. Gh is usually suppressed by glucose so should be undetectable. += not suppressed
- MRI pituitary
- pituitary function: hyper prolactinaemia, hypogonad
Treatment acromegaly? (4)
Surgical
- trans-sphenoïdal resection first choice.
Medical (needed post-op to keep suppressed)
- somatostatin analogues: ocreotice monthly IM, lanreotide
- gh receptor antagonist: pegVisomant
- Dopamine agonists eg bromocriptine but not as effective
Radiotherapy if failed treatment or contraindications.
Diagnosis and investigation Cushing’s syndrome? (8)
First line screening
- overnight dexamethasone suppression test: give dexamethasone 1 mg po at midnight. Check serum cortisol before and at 8 am. Failure to suppress cortisol =+
- 24h urinary cortisol (normal < 280 nmol /24h)
Second line screening tests of one of above abnormal
- 48 hour dexamethasone suppression test: give 0,6 mg/6h po, measure cortisol at 0 and 48h.
- midnight cortisol: normal circadian rhythm (cortisol lowest at midnight, highest early morning) lost.
If above positive, do localisation tests
- plasma ACTH
→ if undetectable, likely adrenal tumour → do Ct adrenal
> if no mass on Ct: adrenal vein sampling or adrenal scintigraphy (radiolabelled cholesterol ),
→ if detectable, do one of following to distinguish pituitary vs ectopic ACTH production
> high dose 48h dexamethasone suppression test: 2mg/6h. Suppression = pituitary cause. None = ectopic ; or
> corticotrophin releasing hormone test: 100 microgram CRH iv. Measure cortisol at 2h. Cortisol rise= pituitary. None = ectopic.
Approach to cushings syndrome causes? (7)
ACTH dependent (increased ACTH) (85%)
- Cushing’s disease: pituitary adenoma
- ectopic ACTH production: small cell lung carcinoma, carcinoid tumours.
- ectopic CRF (corticotrophin releasing factor): medullary thyroid carcinoma, prostate ca
- iatrogenic: ACTH administration
ACTH independent (low ACTH )
- iatrogenic: steroids
- adrenal adenoma / carcinoma
- adrenal modular hyperplasia
- rare: mccune Albright syndrome, carney complex
Treatment cushings? (6)
Depends on cause.
- iatrogenic: stop medications
- Cushing’s disease: trans-sphenoidal resection of pituitary adenoma. Bilateral adrenalectomy if source can’t be located or recurrence post-op. Pituitary radiotherapy is effective in children + used in adults to prevent Nelson’s syndrome (post- adrenalectomy development of locally aggressive pituitary tumour - corticotrophinoma - due to lack of -ve feedback)
- adrenal adenoma: adrenalectomy
- adrenal carcinoma: adrenalectomy followed by radiotherapy, adrenolytic drugs eg mitotane
- ectopic ACTH: surgery if tumour can be located and hasn’t spread.
Medical treatment with ketoconazole or metyrapone (adrenal enzyme inhibitors) reduce cortisol secretion pre-op or while waiting for radiotherapy to become effective.
Cause acromegaly?
- 99% pituitary tumour → increased gh
- rarely ectopic eg carcinoid syndrome
Name 3 complications acromegaly
- Gh suppress insulin → impaired glucose tolerance, dm
- vascular: ht, lvh, cardiomyopathy, IHD, stroke (main cause death)
- malignancy: colon polyps → colon ca.
Which drugs should not be taken with levothyroxine
Preferably empty stomach 30 min before meals
Avoid taking with ppl + antacids, otherwise won’t absorb. Need acidic environment to absorb
At what tsh level should subclinical hypothyroidism he treated
> 10
Define conn’s syndrome
Hyperaldosteronism due to solitary aldosterone producing adenoma
Most common cause of hyperaldosteronism (then bilateral adrenocortical hyperplasia).
Name 3 symptoms/signs conn’s syndrome.
Main cause of hyperaldosteronism.
- Usually asymptomatic
- hypokalaemia → weakness, cramps, paraesthesiae, polyuria, polydipsia
- weight gain
- hypertension
When start patient with subclinical hypothyroidism on levothyroxine?
TSH > 10 mu/l
Describe which eye symptoms all thyrotoxicosis vs only graves produces (6)
All cause: (due to potentiation of sympathetic innervation of levator palpebrae muscles)
- lid retraction
- lid lag
Only graves:
- periorbital oedema
- conjunctival irritation
- exophthalmos
- diploma
Function aldosterone
- Kidney reabsorb Na
- excrete K
Name 2 causes low uptake thyrotoxicosis
- Transient thyroiditis!
- extrathyroidal T4 source
Name cause thyrotoxicosis with scintigraphy uptake in only 1 area
Toxic adenoma
Name cause thyrotoxicosis with patchy, low scintigraphy uptake
Toxic multinodular yoitue
Name cause thyrotoxicosis with diffuse scintigraphy uptake
Graves’ disease
Which scoring system can be used for thyrotoxic crisis?
Burch - wartofsky
Differential anterior neck swelling? (5)
- goitre (moves with swallowing!)
- lymphadenopathy
- brAnchial cyst
- dermoid cyst
- thyroglossal duct cyst (move on protrusion of tongue)
What will goitre ultrasound show in graves
- Diffuse hypoechogenic (dark)
- Doppler: increased thyroid blood flow
Differential diffuse goitre? (9)
Hypothyroid
- Hashimoto’s thyroiditis
- iodine deficiency (endemic goitre)
- Suppurative thyroïditis
- transient thyroïditis
- infiltrative: amyloidosis, sarcoidosis, Riedel’s thyroïditis
Hyperthyroid
- graves
Other
- drugs: iodine, amiodarone, lithium
- simple goitre (no biochemical abnormality)
- dyshormonogenesis
Differential solitary thyroid nodule? (8)
- Colloid cyst
- hyperplastic nodule
- follicular adenoma/ carcinoma
- papillary carcinoma, (most common malignant tumour! )
- medullary cell carcinoma
- anaplastic carcinoma
- lymphoma
- metastasis
Causes subacute (de Quervain’s) transient thyroiditis
After infection with coxsackie, mumps or adenovirus
Treatment subacute (de Quervain’s) transient thyroiditis
NSAIDs
Temporary levothyroxone
How does amiodarone affect thyroid
Hypothyroidism ( anti-arrythmic amiodarone contains lot of iodine + structurally similar to T 4)
OR
Hyperthyroid
Usual treatment toxic multi nodular goitre?
Radioactive iodine
Most common malignant thyroid tumour?
papillary carcinoma
Diagnosis HHS (2)
- Severe hyperglycaemia > 30
- hyperosmolality >320
