Endo Flashcards
T1DM is an autoimmune disease caused by
- Destruction of pancreatic beta cells (Islets of Langerhans) by autoantibodies
- Complete insulin deficiency
- Reduced glucose uptake by cells (raised blood sugars)
4 key sx of T1DM
- Polyuria / glycosuria
- Polydipsia
- Weight loss
- Fatigue
Complications of T1DM:
* Microvascular (3)
* Macrovascular (4)
* Infective/immunosuppressed (3)
* Emergencies (3)
* Ischemic/poor wound healing (2)
- Retinopathy, Peripheral neuropathy, Nephropathy
- Stroke, PVD, CAD
- Pneumonia, UTIs, oral/vaginal candidiasis
- Hypo, DKA, HHS
- Ulceration, diabetic foot
Diagnosis for T1DM (5)
- note difference for sx and asx patients
- OGTT
- Fasting glucose test
- Autoantibody screen
- Urine dip (increased ketones & glucose)
- Serum C-peptide (reduced)
For symptomatic = OGT or GFT.
For asx = Evidence of raised OGT or FGT on 2 occasions
Cut offs for OGTT and FGT
> =7 mmol/l
=11.1mmol/l
What autoantibodies could be present in T1DM?
1. in 80%
2. In 70%
3. In younger kids
4. Rare
- Anti-GAD (glutamic acid carboxylase)
- Anti-islet cell (ICA)
- Anti-insulin (IAA)
- Insulinoma-associated 2 (IA-2A)
Normal physiology: GAD (in beta cells) produces GABA which produces insulin. In diabetes: anti-GAD –> reduced GABA, reduced insulin release.
Two main insulin regimes for T1DM are basal-bolus and pre-mixed. Explain the difference.
Basal-bolus = 4 inj/day
* One long acting in AM
* + 3 short/rapid acting, 30 mins prior to meals
Pre-mixed/biphasic = 2 inj/day, e.g. 70/30
* 70% intermediate acting
* 30% short/rapid acting
* Each given before breakfast & dinner
Insulin therapy
Rapid acting
Short-acting (soluble)
Intermediate
Long
- Aspart, lispro
- Actrapid, Humulin.S
- Isophane
- determir, glargine
Duration of action: 3-5, 5-8, 12-18, up to 24
How does the insulin pump work?
- Continuous S/C Insulin Infusion - rapid acting
- Delivered at an adjustable constant basal rate
- boosts at meal times
What sx do these cause in DKA?
* Increased blood glucose
* Increased ketones
* Electrolyte imbalance
* Hypovolaemia/dehydration
- Polyuria and polydipsia
- Nause and vomiting
- Abdominal pain and muscle cramps
- Shock –> seizure/coma
DKA - diagnosis
Considerations to investigate (2)
Blood glucose >11mmol/l
Ketonaemia >3 or >2 ketonuria
Acidosis pH <7.3
Bicarb <15mmol
- Consider ECG/CXR for arrythmias/pneumonia as underlying cause
most dangerous aspects of DKA that require correcting by fluid resus are (3)
- K+ imbalance
- Dehydration
- Acidosis
Insulin normally drives potassium into cells - in DKA (lack of insulin) K+ can start off high
Management of DKA (4 key points)
FIGP –> ICK
* IV fluids - 0.9% normal saline - most impotant to do first
* IV insulin infusion- e.g. Actarapiad 0.1unit/kg/hr
* Add Glucose infusion to insulin infusion- once glucose levels have e.g. <14mmol/l
* Potassium? - correct low K+ as a result of insulin treatment to prevent arrythmia, normal =3.5-5.5
* Infection? Manage underlying cause
* Chart - fluid chart
* Ketones - monitoring, 1hr then 2hrly
Insulin - long acting; stop short acting temporarily
What if the ketonaemia and acidosis haven’t returned to normal within 24hr?
Reqs senior review from endocrinologist
normally should have resolved by then –> pt back to subcut
Pre-diabetes Hba1c mmol/mol
42-47
Targets for HbA1c in T2DM:
* Lifestyle, or Lifestyle + Metformin
* On an antidiabetic causing hypo / already on drug but HbA1c has risen to 58
- <48
- <53
1st line treatment T1DM:
Exception to rule: If cardiovascular risk factors (Q-risk >10, risk of CVD or existing chronic heart failure):
Metformin 500mg OD –> titrate
Metformin + SGLT2 inhibitors
Stepwise treatment T2DM
1. If target 48
2. If target 53
3. “
4. “
- Lifestyle only
1. Metformin
2. + AD
3. +1AD or + Insulin
4. Swap 1AD for GLP-1 mimetic
1st line treatment if Metformin contra-indicated
SGLT2 inhib
Metformin
Class
MOA
Side effects
Note - metformin is what % renally excreted?
- Biguanide
- Insulin sensitiser (increases cell sensitivity to insulin)
- Reduced glucose outpout from liver (reduced gluconeogenesis, glycogenolysis)
- GI upset & lactic acidosis
- 100% renal excretion - CI in AKI/alcohol abuse
Sulfonylureas (Gliclazide/Glimepiride)
- Stimulates insulin release form the pancreas (blocks ATP dependent K+ channels on beta cells)
- Risk of Hypo and weight gain
Click, GIMME
Similar drug to Sulphonylurea useful for patients with renal insufficiency
Repaglinide
DPP4 Inhibitors (Sita/Lina-gliptins)
- Increase levels of GLP-1 (inhibiting DPP4 prevents its breakdown)
- incretin effect - enhanced effect of insulin in response to food
* hypoglycaemia
pancreatitis
Thiazolidinedione (Pioglitazone)
- PPAR-y agonist (on adipose tissue)
- Promotes genetic transcription –> insulin senitisation (& glucose metabolism)
- SEs; weight gain, fluid retention- heart failure, #s, bladder cancer
- CI liver disease
- Low risk of hypo
PARTY –> Fatty food (adipose tissue), wearing jeans (alters gene transcription) and taking drugs (steroid type SEs; weight gain, fluid retention), long term partying –> #s, bladder cancer. People with liver disease shouldn;t be drinking at parties. Low risk of hypo —>hyper at parties.
SGLT2 inhb (Empagiflozin)
- Increased urinary excretion of glucose
- Blocks SGLT2 on proximal tubule
- UTI, candidiasis. DKA & gangrene
- Must check renal function before initiating, avoid if eGFR <60
GLP-1 Analogues (Sub-cut) (Liraglutide)
Mimics GLP-1 (incretin)
INhibits glucagon release,
Reduced appetite (reduces greediness)
Gastric SE: Pancreatitis
**
HHS (emergency for T2 diabetics) - describe the diagnostic features
- Hyperglycaemia >30mmol
- Hyperosmolarity >320mOsm/kg
- Absence of ketones/ no significant ketonaemia (<3)
- Absence of acidosis
Causes osmotic diuresis and severe Gdehydration
HHS treatment
- IV Fluids
- VTE prophylaxis
- insulin if glucose remains high with iV fluids*
Addison’s disease (primary adrenal insufficiency): investigations
- Morning cortisol
- Short synacthen test
(positive test if less than 2x rise of cortisol from baseline)
General sx of adrenal sufficiency
Fatigue & weakness
N&V
Weight loss
Cramps & abdo pain
Secondary and tertiary - no skin pigmentation, no salt craving, no hyponatraemie due normal ACTH levels.
Effect of long-term steroids
Adrenal atrophy
- shrinking of the adrenal gland due to presence of exogenous steroids
- patients must be weaned off steroids gradually
Specific sx and signs: Addison’s (4)
Addison’s - hyperpigmentation (increased production of melanin due to increased levels of ACTH/mimic of MCH), salt craving (aldosterone deficiency), hyperkalaemia/metabolic acidosis (reduced urinary excreion of potassium due to decreased aldosterone) and hyponatreamia - reduced aldosterone
Hypoglycaemia - due to reduced cortisol
RAAS increases BP through salt & fluid retention, and increased excretion of K+ - due to action of Na+/K+ ATPase pump in the nephron.
In Addison’s: Impaired RAAS; therefore = Loss of salt (hyponatreamia) and reduced excretion of K+ (hyperkalaemia).
Investigating adrenal insufficiency - if there is a rise in cortisol in response to the ACTH stimulation test then rule out Addion’s/primary AI.
What test distinguishes between secondary and tertiary AI?
What other blood test and imaging could you do? - autoantibodies for addison’s
CRH stimulation test:
* Secondary AI (anterior pituitary) - no ACTH
* Tertiary (pituitary) - increased ACTH
Other
* Bloods - adrenal autoantibodies (adrenal cortex & 2I-hydroxylase antibodies)
* CT/MRI adrenals/ MRI pituitary
Managment: Addison’s
- lifelong hormone replacement (Hydrocortisone, Fludrocortisone +/- DHEA)
- what are thesick day rules?
Double dose steroid during infection
aka 2 x hydrocortisone but keep fludrocortisone the same
Addisonian crisis can occur when (2)?
- main sx and management
Pt with Addison’s + infection; or secondary AI with sudden withdrawl of exogenous steroids.
* Reduced GCS (confusion,LOC)
* Systemic - fever, vomiting
* Hypotension & dehydration
* Electrolyte imbalance - Hypoglycaemia, hyponatraemia, Hyperkalaemia
Majority of patients: lethargy and W/L
mx
Plasma cortisol and ACTH
Start treatment before results
IV steroids
Distinguish Cushing’s disease from Cushing’s syndrome
What would the U&Es show for cushins syndrome?
Cushing’s syndrome - sx and symptoms due to prolonged abnormal elevation of cortisol.
Cushing’s disease - ACTH secreting pituitary adenoma
U&E - hypokalaemic metabolic aklalosis (cortisol - enhanced mineralcorticoid effect - salt and water retention) and impaired glucose tolerance
Cushing’s syndrome:
First line test is the low dose dexamethasone suppression test. What other 2 investigationsa re available?
What test can be used to distinguish causes of Cushing’s?
Both steroids are given in PM and cortiso/ACTH tested in the morning.
Other tests: 24hr urinary cortisol (x2 measurements) or bedtime salivary cortisol.
Low dose= ? Cushing’s syndrome or disease. Abnormal response is no suppression of endogenous cortisol release, aka high cortisol.
High dose = Underlying cause of Cushing’s syndrome (pituitary adenoma, ectopic ACTH, Adrenal adenoma).
The high dose of Dexamethasone is enough to suppress the excess cortisol caused by pituitary adenoma (aka HPA axis returns to normal), but not by ectopic ACTH or adrenal adenoma.
High dose Dexamethasone supression test = effective at the highest level (causes cortisol suppression in pituitary adenoma)
ATCH/Cortisol Results for high dose Dexamethasone test:
- Ectopic ACTH (e.g. pareneoplastic)
- Adrenal adenoma
- Pituitary adenoma (Cushing’s disease)
- Cortisol not suppressed, ACTH high (ATCH production is independent of ACTH axis)
- Cortisol not suppressed, ACTH low (-ve feedback)
- Cortisol low (suppressed), ACTH high
Management - Cushing’s syndrome
- surgery
- weaning off..
- + medication to reduce production of cortisol?
- Wean off steroids/remove tumour (trans-phenoidal removal of pituitary adenoma) or adrenelectomy + life-long steroid replacement therapy
- Metyaprone
Thyroiditis
Which causes of hypothyroidisim have an initial thyrotoxicosis stage (2)?
- De Quervain’s (sub acute thyroiditis)
- Pregnancy (post partum thyroiditis)
- Drug induced
- (Hashimoto’s)
Main causes of hyperthyroid (3) and hypothyroid (3)
Which drug is thyrotoxic?
Hyper - Grave’s, TMN, malignancy, autonomous adenoma
Hypo - Hashimoto’s, Iodide deficiency, Riedel’s (painless goitre), De Quervain’s, pregnancy. Secondary causes - pituitary pathology
Drugs - Amiodarone, Lithium
Grave’s disease (4 clinical features) and auto-antibodies
Eye disease, pretibial myxoedema, oncholysis & acropachy (rare).
Anti-TSH (90%) and anti-TPO
Acropachy - “thick edge/extremity” finger soft tissue swelling and clubbing, periosteal new bone formation
Thyroid eye disease: complications
affects up to 1/2 of grave’s patients: name condition and presenting features
- most common complication due to eyelid retraction/proptosis
- most serious complication, enlarged extrocular muscles compress the optic nerve
- fibrosis and enlargement of extrocular muscles result in misalignment of the eyes:
- Exposure keratopathy (corneal exposed causing dryness, irritation –> pain, photophobia,vision impairment)
- Otpic neuropathy: reduction in visual acuity, colour vision defects (e.g. red desats) and visual field defect - urgent intervention
- Strabismus (laxy eye) and diplopia (doube vision)
Hashimoto’s autoantibodies
Anti-TPO
Anti-thyroglobulin
Function of
* TSH
* Thyroid peroxidase (TPO)
* Thyroxine binding globulin (TBG)
* Deiodinase enzymes
- Uptake of iodine into colloid
- Conversion of iodine to iodide
- bind to thyroid hormones (not bioactive until un-bound)
- conversion of T4 (thyroxine) to T3 (tri-idothyronine) at the periphery
Management: Grave’s
Medical = Block & replace - initial treatment of anti-thyroid dose –> maintenance dose + top up of Levothyroixine
Interventional = Radio-iodine
Surgical = Throidectomy + life long Levothyroxine treatment
1st line & 2nd line management for Grave’s
+ MOA
- Carbimazole (TPO inhb);
- Propylthiouracil (inhb T4 to T3)
Both - risk of agranulocytosis (note sore throat)
Thyrotoxic crisis features (3) and treatment (3)
- Tachycardia, fever & delirium
- IV fluids, beta-blockers and anti-thyroid drugs
- Sx treatment e.g. paracetamol
Hashimoto’s monitoring
TFTs initially after 6 weeks
3 monthly TFTs until stable
Annual TFTs
6 hormones impacted in hypopituitarism (anterior).
What 2 hormones are from the posterior pituitary?
- ACTH
- TSH
- LH
- FSH
- Prolactin
- Growth hromone
Posterior: ADH (Vasopressin) & Oxytocin
Causes of hypopituitarism include trauma, toxins, tumour (benign pituitary adenoma/malignant), radiation, drug-realted.
Name 3 other specific causes:
Dx (2) and mx (2):
- Sheehan’s (pregnancy assciated pituitary necrosis)
- Haemochromatosis (iron deposition in pituitary)
- Sarcoidosis (granulomas in pituitary gland)
Dx - hormone profile testing & imaging (MRI).
Mx - hormoe repalcement & treat underlying cuase
what is the only anterior pituitary hormone that cannot be replaced synthetically?
Prolactin
Sx of pituitary adenoma caused by:
1. Hypertrophy of glands
2. Compression on specific gland
3. Stretching of dura
4. Optic chiasm compression
Ix:
1. Pituitary blood profile (includes ….)
2. Imaging (?)
3. Formal (?)
General principles of mx
- Can be function or non functional, micro or macroadenoma
- Can cause sx if excess hormone production (hypertrophy) or deficiency of hormone production (due to compression of specific gland), stretching of dura (headache) or optic chiasm compression (bitemporal hemianopia)
Ix
* Pituitary blood profile (LH, FSH, TSH, ACTH, GH, Prolactin)
* MRI Brain with contrast
* Formal visual fields
Mx
* Hormone therapy, surgery (transphenoidal surgery) and radiotherapy (residual.recurrent)
Acromegaly is excess GH caused by a pituitary adenoma in 95% of cases. Other causes - ectopic GnRH/GH production by tumours.
Sx/signs are due to tissue overgrowth, SoL compression and organ dysfunction.
what conditions are patients at risk of (4)?
what causes galactorrhoea - nipple discharge?
what genetic syndrome is it associated with, in the minority of cases?
- Cardiomyopathy
- HTN
- T2DM
- Colorectal cancer
Excess prolactin (in 1/3)
MEN1
Acromegaly: 1 screening test –> 1 further test, imaging & referral.
- IGF-1 (initial screening) - raised in acromegly
- Oral glucose tolerance test - GH levels raised (normally glucose would suppress GH)
- MRI Pituitary
- Refer to opthalmlolgy
Mx for acromegaly
Medical: Somatostatin analogues to block GH release (Ocretotide)
Dopamine agonists to block GH release (Bromocriptine)
GHr antagonists: Pegvisomant SC injections
Surgical: transphenoidal surgery (1st line in majority)
Distinguish cranial diabetes insipidus (central) and nephrogenic DI (peripheral)
Cranial - reduced production of ADH from hypothalamus; caused by tumours, trauma & surgery - or haemachromatosis (note tanned skin)
**Nephrogenic **- reduced response of nephrons to ADH - caused by renal disease, nephrotoxic drugs, electrolyte imbalance
Explain the results of the water deprivation test: how does the urineosmolarity change after addition of synthetic ADH (Desmopressin)?
* For central DI
* For nephogenic DI
8hrs water deprivation –> measure urine osmolarity –> add Desmopressin –> remeasure.
* Central: urine osmolarity low –> high (Desmopressin acts as asynthetic ADH, makes urine less dilute)
* Nephrogenic: urine osmolarity low –> stays low (sufficient Desmopressin but kidneys not susceptible to ADH).
Hyperparathyroidism
Cause:
Primary
Secondary
Tertiary
How can causes of secondary parathyroidism be distinguished?
- Parathyroid solitary adenoma (or multifocal or cancer)
- Compensatory due to decreased Ca2+ (e.g. CKD or Vitamin D Deficiency - ostemalacia)
- Prolonged secondary hyperparathyroidism causing parathyroid hyperplasia ( - e.g. spinal metastasis, bone #, nephrolithiasis, pancreatitis)
Secondary hyperpth is a response to decreased Ca2+, either because of CKD or reduced Vitamin D (needed to absorb Ca2+). Bloods for serum 25-OH cholecalciferol will show low levels in osteomalacia
pth is phosphaturic - excess –> low blood levels. but in kidney disease (2nd or tertiary hyperparathyroidism) the excretion is impaired = normal/high levels
Hyperparathyroidism: Blood findings
Primary
Secondary
Tertiary
- Primary: raised PTH, raised Ca2+ , low PO4
- Secondary: raised PTH, in response to low/normal Ca2+
If CKD: high PO4 (unable to excrete)
If Osteomalacia: decreased PO4 (low bone mineral content) - Tertiary: raised PTH, normal/high Ca2+, low PO4, raised ALP
First line test for diabetic nephropathy
Urine ACR
(quantity of albumin too low to be detected by urine dip)
PCOS
* Diagnosis (Rotterdam criteria)
* Insulin resistance can result in….
* Mx (Aims = to induce periods, to help with symptoms, to prevent infertility)
* complications
2 out of:
- clinical/biochemical signs of hypogonadism (amenorrhoea/olgiomenorrhoea, hirsutism, acne; raised LH:FSH, normal/low sex hormone binding globulin - SHBG)
- evidence of polycystic ovaries (US)
- anovulation/oligo-ovulation
Acanthosis nigrans (dark patches in skin folds e.g. under armpit)
Mx
- Address omorbidities (DM, HTN)
- monthly bleed - COCP
- hirstuism - Eflornithene. Acne - COCP
- infertility - weight reduction, Clomifene
Cx
- inferility (most common cause in young women)
- pregnancy complications
- endometrial cancer
-
SIADH: euvolemic/hypervolaemic hyponatraemia - can present with confusion/decreased GCS, nausea, vomiting, seizures, if severe - brain stem herniation
1. Blood findings
2. Urine findings
3. Management
- Hyponatraemia, low urine osmolality (water reabsorbed –> dilute blood)
- Raised urine Na+ (water reabsorbed but solutes not –> concentrated urine)
- Fluid restriction, find underlying cause
Hyponatraemia
- classes of hypovolemic based on urine Na+
- Can be hypovolemic (dehydrated, loss of sodium with water), euvolemic or hypervolemic (overloaded, dilutional effect of sodium)
**Hypovolemic hyponatraemia: **
Urine Na >20 mmol/l = renal cause (renal failure, diuretics) or Addison’s (low Na+, hyperkalaemia, hypoglycaemia)
Urine Na <20mmol/l = water losses from other (non-kidney) sources - diarrhoea, vomiting, sweating, burns
Hypervolemic - Cardiac failure, liver failure, renal failure, nephrotic syndrome
Euvolemic - SIADH
- Primary polydipsia, or severe hypothyroid/steroid insufficiency
Underlying causes of SIADH (no negative feedback on ADH production)
- Primary brain injury (SAH, meningitis)
- Hypothyroidism
- Malignancy (SCLC)
- Infectious (atypical pneumonia, cerebral abscess)
- Drugs - SSRI, Carba, Amitrypt
Hyperaldosteronism
- Causes of primary hyperaldosteronism (2)
- Presentation (3)
- Causes of secondary (3)
- Investigation (first line)
- Further ix -
- Mx - for both causes of primary hyperaldost
- comparison to adrenal gland tumour
Primary: excess aldosterone
1. Bilateral adrenal hyperplasia
2. Adrenal adenoma (Conn’s)
Secondary: excess aldosterone due to excess renin; caused by low BP (reduced perfusion) in kidneys
1. Renal artery stenosis
2. Liver failure
3. Heart failure
Px
- Headache
- HTN
- Fatigue
Ix
1. Plasma aldosterone:renin ratio
- high ratio if primary cause: aldosterone due to excess from adrenals, low renin due to negative feedback
- both high aldosterone and high renin in secondary hyperaldosteronism (low BP stimulates exagerated RAAS)
2. Imaging: CT Abdomen; Adrenal vein sampling (AVS)
Mx
1. Adrenal adenoma (Conn’s): adrenalectomy
2. Adrenal hyperplasia: antagonist (Spironalactone)
Difference to phaechromocytoma is the presentation - phaeo causes increased adrenalineso presents with exaggerated fight or flight (tachycardia, sweating) whereas hyperaldosteronism (hyperplasia or adenoma) causes symptoms related to RAAS (high BP, headache)
Phaeochromocytoma
- what is it
- underlying cause
- % cancerous
- ix (bloods and imaging)
- mx
- adrenal gland tumour
- secretes multiple catecholamines (adenaline) - exaggerated fight or flight response
- linked to genetics (MEN1, NF type 1,von HLD)
- 10% are cancerous
ix
* plasma free metanephrines and 24hr urine catecholamines
* CT/MRI adrenals
mx
- alpha blockers
- beta blockers
- surgical management
Prior to surgery what do additional supplement do patients taking steroids require? and why?
- Hydrocortisone
- During surgery the body normally produces more cortisol (under stress); but for patients on long term steroids the adrenals are suppressed and unable to meet the cortisol requirement
- risk of Addisonian crisis
