endocrine and metabolic Flashcards
(152 cards)
1
Q
Define Addison’s disease
A
primary adrenal insufficiency caused by adrenal cortex destruction
- low cortisol + elevated ACTH in response
- low aldosterone
- low adrenal androgens (DHEAP - dehydroepiandrosterone)
2
Q
Causes of Addison’s disease
A
- TB
- autoimmune addison’s
3
Q
Presenting symptoms of Addison’s
A
- fatigue
- hyperpigmentation (high ACTH+ high MSH => high )
- GI (weight loss, loss of appetite, vomiting + nausea, abdominal pain)
- dizziness
- muscle weakness + cramps (electrolyte imbalance)
- fever, headache
4
Q
Examination findings for Addison’s disease
A
- postural hypotension (bp 20mmHg lower standing)
- other autoimmune (vitiligo, pernicious anaemia, coeliac disease)
- hyperpigmentation
- loss of body hair on women (less androgens)
- skin changes - darkening of elbows, under palms, gums
5
Q
Investigations + findings for Addison’s disease
A
- 9am serum cortisol (<100nmmol/L = likely adrenal insufficiency
*cortisol= diurnal - Bloods:
- U&Es (low Na+, high K+)
- FBC (anaemia)
- Hypercalcemia
- low glucose
- TFTs (exclude hyperthyroidism)
- short Synacthen test (should in normals increase cortisol) - cortisol <500mmol/L in 30 mins = likely adrenal insufficiency
- plasma renin/ aldosterone levels
- serum DHEA-s (low)
- autoantibodies
6
Q
What factors can affect serum cortisol levels (other than addison’s disease)?
A
- people working shifts (disrupts diurnal variation of cortisol)
- pregnancy
- oestrogen based medication (OCP/hormone replacement) - increases cortisol binding globulins increasing cortisol
- people on long term corticosteroids
7
Q
Management for Addison’s disease
A
- 3mg daily prednisilone OR 15-25mg 3/daily hydrocortisone (replace cortisol)
- fludrocortisone (replace aldosterone)
- DHEA replacement (unlicensed)
8
Q
What advice should be given to patients with Addison’s disease?
A
- have a steroid warning card
- carry emergency hydrocortisone
- wear a medic-alert bracelet (take double steroid dosage when ill)
9
Q
Features of Addison’s crisis
A
- Hypotension
- Hypovolemic shock (dehydration)- tachycardia
- altered consciousness
- seizures/convulsions
- cardiac arrest (hyperkalemia)
- severe vomiting/diarrhoea
10
Q
Management of Addison’s crisis
A
- IV fluid rehydration (replace Na+)
- IV bolus hydrocortisone
- dextrose to treat hypoglycaemia
- treat cause (ABs for infection)
- monitor (electrolyte levels/ vitals)
11
Q
What is cushing syndrome ?
A
high levels of cortisol
12
Q
Causes of Cushings syndrome
A
ACTH dependant
- cushings disease (adrenal hyperplasia due to pituitary adenoma)- trea
- ectopic ACTH production -small cell lung cancer)
ACTH- independant
- ORAL STEROIDS
- adrenal adenoma
- adrenal nodular hyperplasia
13
Q
Presenting symptoms of Cushing’s syndrome
A
- increased weight
- mood change (depression)
- proximal weakness
- erectile dysfunction/ irregular menses
14
Q
Examination findings of cushing’s syndrome
A
- central obesity
- moon face, red cheeks
- buffallo hump
- purple abdominal striae
- poor wound healing
- thin skin - bruises
- osteoporosis (thin bones)
15
Q
Investigations for cushing’s syndrome
A
- Bloods- U&Es, high glucose
2, High-sensitivity tests:
- urinary free-cortisol
- late-night cortisol (usually only high in morning unless cushings)
- overnight dexamethasone suppression test
- low dose dexamethasone suppression tests
- CT/MRI of adrenals, measure ACTH => ACTH dependant
Pituitary MRI => ACTH independant
lung cancer? => CXR, bronchoscopy
16
Q
Management of cushing’s syndrome
A
- stop steroids
- pre-surgery/ unfit
- metyrapone (11b-hydroxylase inhbitor)
- ketoconazole (17a-hydroxylase inhibitor => inhibitis cortisol/ aldosterone + sex-steroids)
- drugs for osteoporosis - surgery
- pituitary adenoma => trans-sphenoidal adenoma resection
- adrenal adenoma => surgical removal of tumour
17
Q
Mechanism + Side effects of metyrapone
A
Inhibits 11 hydroxylase enzyme and inhibits cortisol production
- nausea, vomiting
- hypoadrenalism (low mineralcorticoids)
18
Q
Mechanism + Side effects of ketoconazole
A
Inhibits 17a hydroxylase enzyme and inhibits cortisol (+ sex steroids) production
- nausea, vomiting
- alopecia
- liver damage
19
Q
complications of cushing’s syndrome
A
- diabetes (high cortisol => high glucose)
- osteoporosis
- hypertension
- increased infection risk
20
Q
prognosis for patients with cushing’s syndrome
A
untreated 5 yr survival - = 50%
21
Q
Define thyrotoxicosis
A
abnormally high levels of thyroid hormones in blood due to problem with HPT axis (hypothalamus-pituitary-thyroid)
=> Hyperthyroidisim (subset of thyrotoxicosis)
- increased thyroid production from thyroid gland
22
Q
Causes of thyrotoxicosis
A
- Graves disease
- Toxic multinodular goitre (from Plummer’s)
- Early phase Thyroiditis - de Quervains/ post-partum/ hashimoto’s (most common in elderly)
Thyroiditis causes stored thyroxine to be released from thyroid gland=> causing brief early hyperthyroidism but as stores get used up => hypothyroidism
23
Q
Define Graves disease
A
autoimmune condition where anti-TSH antibodies bind to TSH receptors on thyroid gland and activate thyroid gland => increased T3/T4 production
24
Q
Symptoms of Grave’s disease
A
- weight loss + increased appetite
- heat intolerance (hot)
- diarrhoea
- sweating
- tremor
- anxiety/ irritability
- oligo/amenorrhoea
- libido loss
- weakness
25
Examination signs of Grave's
* palmar erythema
* sweaty hands
* thyroid acropachy (severe + painful finger/toe clubbing)
* fine tremor
* hair thinning
* exopthalmos
* opthalmoplegia (CN III,IV,VI palsy)
* lid lag
* goitre
* gynaecomastia
* tachycardia (AF most common arrythmia with thyrotoxicosis)
* pre-tibial myxoedema
26
Investigations of Grave's
Bedside
* ECG
* glucose
Bloods
* TFTs (raised T3/T4, low TSH)
* FBC
* U&Es
* LFTs
* autoantibodies (anti-TPO, anti-TSH receptor, anti-thyroglobulin)
Imaging
* neck ultrasound
* radioiodine uptake scan
27
Management of acute thyroid storm
* IV fluids
* beta-blockers (for tachycardia)
* anti-thyroid drugs (propylthiouracil/ carbimazole)
* IV steroids (hydrocortisone)
* iodine/ pottassium iodide
28
Management of Grave's (subacute)
First line:
1. beta-blockers for tachycardia/anxiety/tremor/ palpitations + steroids-prednisilone
* anti-thyroid drugs (carbimazole/ propylthiouracil) =\> 1yr
* radioactive iodine
Surgery (usually in planning to get pregnant/ severe Graves/ ineffective first line/ suspect malignancy)
* Thyroidectomy
29
Mechanism of antithyroid drugs (thionamides =\> propylthiouracil, carbimazole)
1. inhibit thyroid peroxidase enzyme
2. inhibit iodination of iodine
3. inhibit iodination of thyroglobulin =\> no thyroxine synthesis
Side effects= rashes, agranulocytes (SEVERE)
30
Complications of Grave's
* AF =\> strokes/ heart attacks
* Congestive heart failure (elderly)
* Untreated =\> osteroporosis
* Elephantessis (RARE)
* Orbitopathy (RARE)
31
Define Plummer's =\> toxic multinodular goitre
* benign tumour of thyroid gland =\> increased thyroxine production
* Unilateral lump on one side
* Radioactive iodine uptake on one side
32
Define thyrotoxic storm
Extreme and sudden thyrotoxicosis
33
Symptoms of thyrotoxic storm
* hyperpyrexia (fever)
* hypertension
* severe tachycardia (\>140bpm)
* confusion/ delerium
* fainting
* jaundice, nausea, abdominal pain
34
Management of thyrotoxic storm
* IV fluids
* beta-blockers (for tachycardia)
* anti-thyroid drugs (propylthiouracil/ carbimazole)
* IV hydrocortisone
* URGENT endocrinology review
35
What can trigger thyrotoxic storm?
* INFECTION
* trauma
* thyroid surgery
* stroke
* diabetic ketoacidosis
* MI/ congestive heart failure
* radioactive iodine replacement
36
define hypothyroidism
syndrome caused by low levels of thyroid hormones (T3/T4)
37
Causes of primary hypothyroidism (low T3/T4 + high TSH)
* iodine deficiency (or XS)
* Hashimoto's thyroiditis (AUTOIMMUNE)
* Post-surgery damage to thyroid gland (neck/thyroid)
* iatrogenic (anti-thyroid drugs, iodine, amiodarone)
* Transcient thyroiditis (de Quervains/viral, Post-partum)
38
causes of secondary hypothyroidism (low T3/T4 + low TSH)
pituitary dysfunction due to:
- tumours
- surgery/ trauma
- pituitary infarction
- infiltration (amyloidosis, sarcoidosis, haemachromotosis, TB)
- Sheehan's syndrome (pituitary necrosis due to post-partum haemorrhage)
- drugs (cocaine, dopamine, glucocorticoids, metformin)
39
presenting symptoms of hypothyroidism
\*everything slows down
- slower metabolism=\> weight gain
- bradycardia
- cold intolerance
- fatigue
- constipation
- dry skin/ hair loss
- weakness
- depression, impaired concentration
- menstrual irregularities
+ for secondary hypothyroidism
- recurrent headaches/ vision changes
- changes to other pituitary hormone levels- skin depigmentation (ACTH), galactorrhea (prolactin), erectile dysfunction/amennorrhea (LH/FSH), acromegaly (GH)
40
examination findings of hypothyroidism
* hands (cold, bradycardia)
* head/neck/ arms (puffy face, goitre, oedema, hair loss, dry skin, vitiligo, Thyroid pain (subacute thyroiditis)
* chest (pericardial effusion, pleural effusion)
* abdominal (ascites)
* neurological (reduced deep tendon reflexes, signs of carpal tunnel)
41
What is myxoedema coma + symptoms:
severe hypothyroidism seen in the elderly
* hypothermia
* hypoventilation
* hyponatremia
* heart failure
* confusion
* coma
42
investigations + findings for hypothyroidism
Bloods
* Thyroid function tests (low T3/T4 +/- low TSH)
* FBC + serum b12 ( check for associated normacytic anaemia)
* U&Es- may have low sodium
* high cholesterol (check for associated dyslipidaemia)
* glycated HbA1c (check for associated diabetes)
* check for coeliac disease (anti-transglutaminase antibody)
* serum thyroid peroxidase antibodies (for autoimmune disease)
* ultrasound of neck (look at goitre)
43
Management of hypothyroidism
1. hypothyroidism =\> 50-100ug levothyroxine daily before food + **monitor TSH** (to normalise) every 3 months and adjust dose
\*in secondary hypothyroidism monitor using free T4 levels
2. hypothyroidism during pregnancy- need higher levothyroxine dose to prevent neonatal complications (monitor TFTs more frequently)
44
why can the thyroid function tests still be abnormal in (suspected) hypothyroidism after adequate levothyroxine treatment
* poor drug compliance (side effects)
* interacting with other drugs
* malabsorption of levothyroxine in gut (coeliac, pernicious anaemia, H. pylori gastritis, atrophic gastritis, IBD)
* increased LT4 demands (weight gain/ pregnancy)
* foods that reduce LT4 absorption (grapefruit, coffee, milk, soya)
45
Why does adrenal insufficiency need to be ruled out before prescribing levothyroxine?
as it can precipitate Addison's crisis
46
Management of myxoedema coma
* oxygen
* rewarming
* rehydration
* IV T3 (faster action onset than T4)
* IV hydrocortisone (for adrenocortical insufficiency)
* treat underlying cause (e.g. infection)
47
complications of hypothyroidism
- myxoedema coma (80% mortality rate)
- myxoedema madness (+ delusions/ psychosis)
48
Define hyperparathyroidism
XS production of PTH (by chief cells of parathyroid gland)
* Primary - high PTH regardless of calcium levels (high Ca2+)
* Secondary - high PTH in response to hypocalcemia (low Ca2+)
* Tertiary- increased PTH in response to inital hypocalcemia, then autonomous secretion of PTH
49
Causes of hyperparathyroidism
Primary (high PTH)
* parathyroid adenoma (80%)
* parathyroid hyperplasia
* parathyroid carcinoma
* MEN syndromes
Secondary (low Ca2+ =\> high PTH)
* chronic renal failure
* Vit. D deficiency
50
Presenting symptoms of hyperparathyroidism (hypercalcemia)
Primary
* bone pain
* renal calculi
* abdominal pain, nausea, constipation, dyspepsia, anorexia
* pscyhcic groans (depression, fatigue, impaired concentration)
* polyuria, polydypsia
* lethargy
* pancreatitis, duodenal ulcers??
Secondary
* could present with hypocalcemia signs (Convulsions, arrhytmias, tetany, parasthesia)
51
Investigations for hyperparathyroidism
Bloods
* U&Es- albumin
* PTH (high)
* serum calcium
* serum phosphate (low)
* LFTs- ALP
* Vit D
* calcium: creatinine ratio- differentiates primary hyperparathyroidism with familial hypercalciuric hypercalcemia (FHH)
*
Imaging
* renal USS - check for stones
52
Management of hyperparathyroidism
Primary
* IV fluids
* moderate calcium/ vit D intake
* avoid thiazide diuretics (worsens hypercalcemia)
* Surgery - partial/total parathyroidectomy
Secondary
* treat cause- renal failure (dialysis?) / vit D deficiency (Ca2+/ Vit D supplements)
53
Complications of hyperparathyroidism
* Primary =\> increased bone resporption, increased calcium reabsorption =\> HYPERCALCEMIA
* Secondary =\> stimulates osteoclasts =\> osteitis fibrosa cystitis
* Post-surgery =\> hypoPTH, hypoCa2+, hoarse voice (reccurent laryngeal nerve damage),
54
Define hypoparathyroidism
low pTH production
* Primary - Low pTH =\> low Ca2+
* Secondary - high Ca2+ =\> low PTH
55
Causes of hypoparathyroidism
Primary (low PTH, low Ca2+)
* trauma
* parathyroidectomy
* thyroidectomy
* hypomagnesium- chronic alcohol intake, XS diarrhoea, poor nutrition/ malabsoprtion
* genetic mutations in CASR, GATA3
Secondary (high Ca2+ =\> low PTH)
* malignancy (bone metastasis, multiple myeloma, lung Squamous CC)
* thiazide diuretics
* XS vit D (high calcitriol)
* sarcoidosis
*
56
Presenting symptoms of hypoparathyroidism
Primary -hypocalcemia
Secondary - hypercalcemia
Primary (low PTH =\> low Ca2+)
* Convulsions
* Arrhytmias
* Tetany
* Parasthesia
57
Examination findings of primary hypoparathyroidism (hypocalcemia)
* Chovostek's sign (ipsilateral facial twitch when cheek touched)
* Trousseau's sign (blood pressure cuff inflates, cause carpopedal spasm)
58
Investigations for hypoparathyroidism
Bedside
* ECG- prolonged QT interval (arrythmias)
Bloods
* U&Es- albumin, creatinine (normal- unless renal failure)
* serum calcium (low)
* serum phosphorous
* serum magnesium (low)
* serum PTH (low)
* Vit D (low)
* LFTs- ALP
* FBC
IMaging
* renal imaging
59
Management of hypoparathyroidism
Primary (low PTH =\> low Ca2+)
* Ca2+ / Mg2+ supplements
* recombinant PTH
* calcitirol supplements
* thiazide diuretics (reduce the rate of urinary calcium excretion )
* reduce PPI/Corticosteroids (reduce Ca2+ absorption), loop diuretics (increase Ca2+ excretion)
Secondary (high Ca2+ =\> low PTH)
* treat cause
* moderate Ca2+/ Vit D
* reduce thiazide diuretics (worsen hypercalcemia)
60
Complications of hypoparathyroidism
* hypocalcemia (CATs NUMB)
* increased phosphate reabsorption
* cataracts
* renal stones/ insufficiency (hypercalcemia?)
*
61
define hypercalcemia of malignancy
malignancy =\> hypercalcemia
62
Differentials for hypercalcemia of malignancy
* primary hyperparathyroidism (high PTH =\> high Ca2+)
* hyperthyroidism
* adrenal insufficiency
63
Presenting symptoms of hypercalcemia of malignancy
* risk factors (malignancy)
* can have no signs of hypercalcemia
* medication worsening hypercalcemia
* polydypsia
* polyuria
* bone pain
* nausea
* constipation
* confusion
* fatigue
64
Risk factors for hypercalcemia of malignancy
* non-metastatic disease **(_humoral hypercalcemia_**) =\> releases PTH related peptide ***r**enal, ovarian, endometrial, squamous cell, breast*
* metastatic skeletal involvement (**_osteolytic hypercalcemia_**) =\> *breast cancer, muliple myelom****a***
* **_lymphoma_** (calcitriol- mediated hypercalcemia)
65
What medications worsen hypercalcemia?
* thiazide diuretics (reduce calcium excretion)
* lithium
* Ca2+ supplements
* antacids
* XS Vit D supplements
66
Investigations for hypercalcemia of malignancy
Bedside
* ECG- arrythmias (prolonged QT interval)
Bloods
* U&Es - elevated creatinine (renal failure), albumin
* serum calcium (high)
* serum phosphorous (low)
* serum intact PTH (high hyperparathyroidism)
* serum PTH-related peptide (high in humoral hypercalcemia)
* serum calcitriol (high in calcitriol-mediated hypercalcemia)
* metabolic panel - elevated bicarbonate (malignancy)
Imaging
* Skeletal screen- osteolytic lesions, pathological fractures, osteopenia
* CXR- TB/sarcoidosis/lung cancer signs
67
Management for hypercalcemia
Mild hypercalcemia/ asymptomatic
* Treat malignancy
* stop hypercalcemia exacerbating medication
Severe hypercalcemia/ symptomatic without AKI
* IV fluids
* **BISPHOSPHONATES** (stimulates osteoblasts) + calcitonin (reduces Ca2+)
* Furosemide (loop diuretic)
* Stop hypercalcemia exacerbating medication
* Treat underlying malignancy
+ corticosteroid (if calcitriol-mediated hypercalcemia)
Symptomatic Hypercalcemia + AKI
* renal dialysis
* denusomab
68
define Type 1 diabetes
* autoimmune destruction of pancreatic-beta cells =\> no insulin production
* prone to diabetic ketoacidosis (no background insulin so glucose converted to ketone bodies)
* LADA - latent autoimmune diabetes of adults (slower progression to insulin dependance)
69
cause of T1DM
* genetic susceptibility + environmental trigger
* **genes (HLA DR3/4)**
* Autoantigens associated with T1DM (glutamic acid decarboxylase, insulin, insulinoma-associated protein 2)
70
Presenting symptoms of T1DM
* younger onset (\<30)
* **_osmotic diuresis_** (polyuria, polydypsia,nocturia)
* **_tiredness_**
* **_weight loss_**
Associated autoimmune conditions
* vitiligo (skin condition)
* addison's (tan)
* autoimmune thyroid disease
71
Investigations for T1DM
Bedside
* **Urinalysis** - glucose, ketones
* **Blood glucos**e (random/ fasting)
* **blood pressure** (can repeat with ABPM/HBPM)
Bloods:
* **HbA1c** (42- pre-diabetes, 48-diabetes)
* FBC
* U&Es
* Lipid profile
* **anti-GAD/ islet cell autoantibodies**
* Urine albumin: creatinine ratio
* Investigate DKA =\> capillary blood glucose, urine dipstick, ABG, FBC
72
Management of T1DM
Glycaemic control
* adjust insulin doses to exercise/meals (DAFNE-dose adjusted for normal eating)
* calorie counting
* illness increases insulin requirements
**_Basal-bolus regime_**
1. Short acting insulin x3daily before meals (**Lispro**, Aspart)
2. Long acting insulin x1daily (**Glargine**, Isophane)
Insulin pumps
Monitor/ screen for complications/ CVD risk factor management
Treat for hypoglycaemia =\> if reduced consiousness (50ml of 50% glucose IV) if conscious 50g of oral glucose
73
define Type 2 diabetes mellitus
* insidious onset (won't know for many years)
* **_resisitance to insulin + eventually impaired insulin secretion_**
* hyperglycaemia but no acidosis (as there's background insulin to suppress ketone body formation)
* intermittent polyuria + polydypsia - assume they have prostate problems/UTIs
74
pathophysiology of type 2 diabetes
* months to years of hyperglycaemia
* slow damage to endothelium
* microvascular complications (retinopathy/nephropathy/neuropathy)
* macrovascular damage (IHD/ CVA/paeriperal gangrene)
75
risk factors for type 2 diabetes
* **_obesity, inactivity (_**NEFAs =\> post-receptor defects)
* **_hypertension_**
* **_south-east asians_**
* genetics- mutations in insulin receptors (MODY, mitochondrial diabetes)
* chronic pancreatitis
* endocrine disorders (Cushing, acromegaly, phaechromocytoma)
* drugs (corticosteroids, atypical antipsychotics, TB drugs, SSRIs
* autoimmune
* renal failure
* cystic fibrosis
* PCOS
* Werner's syndrome
* metabolic syndrome
76
presenting symptoms of Type 2 diabetes
* usually **_asymptomatic_**
* **osmotic diuresis** (polyuria, polydypsia)
* lethargy
* can present with hyperglycaemic hyperosmolar state (HHS)
* infections (infected diabetic foot, candidiasis)
77
examination signs of type 2 diabetes
acanthosis nigricans
78
investigations for type 2 diabetes
Bedside:
* **Urine dipstick**- proteinurea/ albuminurea
* **blood glucose** - random (\>11) / fasting (\>7) / 75g oral glucose tolerance (\>11)
* **blood pressure**
Bloods
* **HbA1c** (42- pre-diabetes, 48-diabetes)
* **U&Es**- urea/creatinine
* lipid profile
* eGFR (check renal function as complication)
* urine albumin: creatinine ratio (microalbuminurea)
79
How to measure osmotic pressure/ hyperosmolar state
osmolality= cations (Na + K) + anions (Cl + bicarb) + glucose + urea
= 2(cations/ Na + K) + glucose + urea
\*as cations = anions
Normally = 295mM
80
management for type 2 diabetes
* Lifestyle modification - diet, exercise
* Glycaemic control
1. metformin (HbA1c \>48)
2. + sulphonylurea (gliclazide)/ SGLT-2 inhibitor (flozin)/ DPP-4 inhibitor (pioglitazone)
3. + add another drug or INSULIN
* BP control- ACE/ARB or CCB =\> A+C/D
* Lipid management - atorvastatin 20mg (Q-risk \>10%) or 80mg (IHD/CAD/PAD)
* Antiplatelets - aspirin 75mg (if IHD/CVD/PAD)
81
different medications for glycaemic control + side effects
* metformin increases insulin sensitivity + weight loss (side effects = diarrhoea)
* Sulphonylureas (gliclazide) - inhibit K+/ATPase in beta cells =\> Ca2+ influx =\> increase insulin release (side effects =weight gain)
* Insulin/ insulin analogues
* SGLT-2 inhibtors (flozin) =\> reduces glucose reabsorption + HF (side effects= UTIs/ thrush/ hypoglycaemia)
* GLP-1 analogues (increase insulin release)
* Gliptins/DPP4 inhibitors-stop GLP-1 breakdown =\> increased insulin release (side effects= flu/runny nose, allergy, joint pain)
82
Complications of diabetes mellitus
Acute:
* **Diabetic ketoacidosis (T1DM)**
* **Hyperosmotic osmolar state (T2DM)**
* **hypoglycaemia -**due to insulin treatment
Long-term:
* Microvascular complications - glycosylation of basement membranes =\> leaky capillaries (retinopathy, neuropathy, nephropathy)
* Macrovascular complication - atheroma development (peripheral vascular disease, IHD, Stroke/TIA)
* Increased infection risk
83
Define diabetic ketoacidosis
* Increased ketone body production as there insufficient insulin to suppress it (e.g. in T1DM)
* Diagnosed = metabolic acidosis (pH \<7.3) + hyperglycaemia (\>11mmol/L) + ketonaemia (\>3mmol/L)
84
Why does body increase ketone body production in T1DM?
1. XS glucose but insufficent insulin to cause glucose uptake into cells
2. body is starved
3. so ketoacidosis is only mechanism of energy production
85
symptoms + signs of DKA
Symptoms:
* **nausea/vomiting**
* **abdo pain**
* **drowsiness/ confusion**/ coma
* polyuria/polydypsia
Signs:
* **kussmaul breathing** (deep, rapid breathing)
* ketotic breath
* signs of dehydration (dry mucous membranes)
86
Investigations for DKA
Bedside
* Capillary blood glucose (diabetes- glucose \>11mmol/L)
* **_Urinalysis_** (check ketonuria (\>3mmol/L), glycosuria)
Bloods
* FBC- raised WCC without infection =DKA
* **_ABG-_** metabolic acidosis (pH \<7.3)
87
Management of DKA
1. **_IV fluids (saline)_**
* SBP \<90 =\> 500ml bolus saline
* SBP \>90 =\> 0.9% saline IV fluids
1. **_Fixed rate IV insulin infusion_**
2. If K is low =\> KCL
3. Include dextrose in saline if gluocse is \<14mmol/L
4. Monitor blood glucose, capillary ketones, urine ouput HOURLY
5. Treat underlying cause- infection=\> broad spectrum antibiotics
88
What can trigger DKA/HSS other than diabetes?
* surgery
* **_infection_**- UTI
* medication: **_wrong insulin dose/non-compliance_**, drugs that reduce insulin dose- chemotherapy, psychotics
* MI/ STROKES
* pancreatitis
89
define Hyperosmolar hyperglycaemic state (HSS)
* **severe hyperglycaemia** (\>30mmol/L) without ketonemia/acidosis as some backrgound insulin present to suppress ketone body formation
* more common in T2DM
90
symptoms + signs of HSS
Symptoms:
* nausea, vomiting
* confusion/drowsy
* coma
* polyuria
* severe dehydration (thirst)
Signs:
* kussmaul breathing (deep, heavy breathing)
* dry mucous membranes
* dehydration signs (increased HR/RR, low bp)
91
Investigations for HSS
* urinalysis - no ketonuria (\<3mmol/L)
* blood glucose- HIGH GLUCOSE (\>30mmol/L)
* ABG - normal pH
92
Management of HSS
* IV fluids
* Fixed rate IV insulin infusion
* If K+ is low =\> KCL
* Treat underlying cause
93
complications of HSS
* clots
* SHOCK, coma
* Stroke/ MI
* brain swelling
94
Risk factors for microvascular complications
* poorly controlled hyperglycaemia
* prolonged diabetes
* hypertension
* \>70
* CVD risk factors (type 2 diabetes)
* dyslipidemia
95
define diabetic nephropathy and it's pathophysiology
* microvascular complication of DM that leads to reduced renal function =\> **chronic kidney disease**
* with albuminurea and reduced eGFR
* progressive worsening of proteinurea
Pathophysiology:
* hypertension =\> progressive proteinurea =\>kidney failure
96
symptoms of diabetic nephropathy
* usually asymptomatic and present in later stage
* swelling of extremeties (oedema)
* lethargy
* anorexia
* fever
97
Examination findings of diabetic nephropathy
* hypertension
* oedema
* other microvascular complications (retinopathy/ neuropathy)
98
Investigations for diabetic nephropathy
Bedside
* urine dipstick- proteinurea
* **_urinalysis_**: albumin:creatinine ratio (microalbuminuria) FIRST LINE
Bloods
* FBC
* U&Es - urea/creatinine
* eGFR- reduced in later stage renal failure
Imaging:
* kidney ultrasound (larger in diabetes =\> normal in nephropathy)
* CT abdomen - rule out hydronephresis/ renal carcinoma/ renal stones
* Magnetic resonance angiography - rule out renal artery stenosis
Other
* **kidney biopsy**- GOLD-STANDARD but rarely done
glomerular changes (**Kimmelstiel Wilson nodules**, mesangial expansion, basement mebrane thickening)
99
Management of diabetic nephropathy
* **ACE-inhibitor** (inhibit RAAS system) =\> worsen creatinine immediately
* **Angiotensin receptor blocker** (ARB- lorsartan)
* **diabetic control** (control blood glucose)
* Nutrition- low fat/cholesterol diet
* Statins
* Stop smoking
If bp not controlled with ACE-inhibitor/ARB =\> CCB/ thiazide diuretics
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Mechanism of ACE inhibitors/ Angiotensin 2 receptor blockers in diabetes
* inhibit ACE (less angiotensin 1=\> 2 conversion)
* small fall in bp =\> reduces eGFR
* reduction in microalbuminurea=\> prevent end-stage renal failure
ACE inhibitor side effects= hyperkalemia
\*worsens creatinine (increases) immediately (as GFR falls) if too much worsening stop ACE-inhibitor
101
Why are ACE inhibitors not given in renal artery stenosis?
* renal artery narrowed means flow is already low
* With ACE inhibitor =\> fall in AT2
* bp falls a lot =\> GFR falls a lot (0) =\> **stops weeing**
\*STOP ACE INHIBITOR ASAP
102
define diabetic neuropathy
microvascular complication of diabetes (type 1/2) that leads to peripheral nerve/ autonomic nerve dysfunction
* affects vaso nervovum (vessels supplying nerves)
103
Types of diabetic neuropathy
1. diffuse neuropathy (**peripheral polyneuropathy / autonomic neuropathy**)
2. Mononeuropathy
3. Radiculopathy/ polyradiculopathy
104
Pathogenesis of diabetic neuropathy
hypertension + hyperglycaemia
=\>
1. oxidative stress
2. produce AGE (advanced glycated end products)
3. hypoxia
=\> activates pro-inflammatory cytokines
=\> inflammation
=\> neuropathy (inflammation of vaso nervovum= vessels supplying nerves)
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symptoms + signs of of diabetic neuropathy
peripheral nerve lesion (polyneuropathy)
* **glove-stocking sensory loss**
* **reduced/ absent ankle reflex**
* **painless injuries (foot ulcers)**
* pain (burning - worse at night)
* burnining/tingling/numbness
* **loss of sensation** (vibration, proprioception, temp)
autonomic neuropathy
* tachycardia
* **bladder dysfunction**- urinary frequency, urgency, nocturia, retention, incontinence
* **GI disturbance-** difficulty swallowing, nausea/vomiting, constipation
* **postural hypotension** =\> SUDDEN CARDIAC DEATH
* erectile dysfunction + reduced libido + painful sex
radiculopathy
* numbness/ tingling over dermatomal patterns (resolves in 4-6 months)
mononeuropathy (RARE)
* motor loss (wrist drop, foot drop)
* cranial nerve palsy (III =\> abducted, depressed eyes, droopy eyelid)
106
Examination findings of diabetic neuropathy (foot)
* absent/ reduced ankle jek reflexes = peripheral neuropathy
* Monofilament used to investigate light touch (when it bends applying 10g of pressure) = peripheral sensory neuropathy
* inspect foot - Clawed toes – increased pressure on metatarsal head, flexed toes, Greater risk of ulcers on big toe, Charcot foot = peripheral MOTOR neuropathy
* Tachycardia/ hypotension - autonomic neuropathy
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investigations for diabetic neuropathy
Bedside:
* blood glucose + HbA1c (check for undiagnosed diabetes)
Bloods:
* HbA1c
* FBC- Hb,WCC (exclude anaemia/inflammation)
* LFTs (exclude hepatic disease)
* U&Es (exclude renal disease)
* lipid profile
* TFTs (TSH) -exclude thyroid dysfunction
* serum B12 - exclude deficiency
Imaging
* corneal confocal microscopy - exclude severe disease
Other
* **Nerve conduction studie**s - reduced nerve conduction
* **Elecromyography** (in asymmetry/ muscle weakness) - worse in severe disease
* immunoelectrophoresis - exclude multiple myeloma
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management for diabetic neuropathy
_polyneuropathy_
* without pain = **glycaeminc control**
* with pain = 1. **pregabalin/ gabapentin** (treats nerve pain) + glycaemic control 2. antidepressant + glycaemic control 3. opioid analgesia + glycaemic control 4. Transcutaneous electrical nerve stimulation (TENS) or acupuncture
*
_cranial neuropathies / Limb mononeuropathy_
* glycaemic control + supportive measures
_autonomic neuropathy (t**reat symptoms**)_
* with orthostatic hypotension =\> miodirine (antihypotensive) + glycaemic control + lifestyle (small,frequent meals, low salt, avoid abrupt body position changes)
* gastroparesis (poor stomach emptying) =\> erythromycin/metoclopramide (ABs) + glycaemic control + low fat/fibre meals
* diarrhoea =\> broad-spectrum ABs + glycaemic control
* bladder dysfunction =\> bethanechol (parasympathetic stimulator) + glycamic control
* erectile dysfunction =\> sildenafil(viagra- increases blood flow to penis) + glycaemic control
*
* Diabetic foot= inspect foot, good footwear, avoid barefoot walking
* ulcers =\> foot clinic (offload pressure, infected = antibiotics, revascularise, amputate)
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complications of diabetic neuropathy
* foot ulcers
* wound infection/ gangrene
* silent MI (autonomic neuropathy)
* death
* charcot's foot (abnormal pressure loading - as bones in foot are in the wrong place (+ fused together) =\> loss of joint space =\> **CHANGE IN FOOT SHAPE** + No pain) untreated =\> OSTEOLMYELITIS
110
define hypoglycaemia
low levels of blood glucose (\<3.6mmol/L)
* impaired cognition when \<3mmol/L
111
causes of hypoglycaemia
* Diabetics on insulin therapy
Recurrent hypoglycaemia
* medication (anabolic steroids, ACE inhibitors, beta-blockers-mask tremor)
* **XS ALCOHOL**
* check diet (missed meals, reduced meals)
* exercise routine (too intense)
* incorrect dosing/ type of insulin
* changes in insulin sensitivity
* medical conditions (anorexia, hepatitis/cirrhosis, kidney disorders, Addison's)
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presenting symptoms of hypoglycaemia
mild
* **palpitations**
* **tremors**
* **sweating**
moderate
* **headaches**
* **drowsiness**
* **impaired vision**
* **difficulty concentrating**
* **confusion**
* behaviour change (children)
severe (3Cs)
* convulsions
* consciousness (loss of)
* coma
113
How to manage mild/moderate hypoglycaemia? (conscious/can swallow)
1. **oral glucose (short acting)-** 200ml juice, 7 jelly beans, 4tsp sugar, 5 glucose tablets
2. long acting complex carbohydrates
114
How to manage severe hypoglycaemia (unconscious)
* IM glucagon (1mg adults, 500ug children)
* monitor blood glucose
115
When to call 999 for patient with severe hypoglycaemia?
* doesn't respond to glucagon \<10mins
* IM glucagon not available
* family/carers not trained in glucagon injection
* taken alcohol =\> need **IV glucagon**
116
How to manage nocturnal hypoglycaemia? (fatigue, hangover, headache)
* monitor blood glucose at 2-3am (most likely to get hypoglycaemia)
* have a snack before bed and keep short acting carbohydrate by bed
117
How to prevent hypoglycaemia?
* educate patient/family on symptoms + emergency treatment of hypoglycaemia
* regularly monitor blood glucose
118
Define Diabetes Insipidus
disorder of no AVP production/ insensitivity to AVP
=\> large amounts of dilute urine (\>3L/day)
119
Types of Diabetes Insipidus
Cranial - no AVP production
Nephrogenic - insensitivity of collecting duct to AVP
120
Causes of cranial DI
- idiopathic
- congenital (defects in AVP gene)
- tumours (pituitary, craniopharyngioma, metastasis)
- sarcoidosis
- meningitis
- vascular
- trauma
- hypophysectomy
- autoimmune hypophysitis (pituitary gland inflammation)
121
Causes of nephrogenic DI
- idiopathic
- inherited
- metabolic (low K+, high Ca2+)
- lithium
- pyelonephritis
- chronic renal disease
- pregnancy
- amyloidosis
- hypercalciuria
122
presenting symptoms of DI
- polyuria
- nocturia
- polydipsia
- children (enuresis/ bed-wetting ,sleep disturbance)
123
signs of DI on examination
urine output \<3L/day
if fluid intake \< fluid output = dehydration (tachycardia, reduced tissue turgor, postural hypotension, dry mucous membranes)
- cause related (pituitary tumour = visual defect)
124
Investigations for DI
- Water deprivation test
1. fluid deprive for 8hrs + measure urine + plasma osmolality + weigh patient hourly to monitor dehydration
2. At 8 hours, stop test if urine osmolality \>600mOsmol/kg
or
Results= low urine osmolality
- bloods (U&Es, Ca2+, increased plasma osmolality, decreased urine osmolality)
125
When to stop water deprivation test?
- fall in body weight \>3%
126
how to differentiate between cranial and nephrogenic DI with investigations
- give desmopressin (ddAVP) after water deprivation test
Results:
- cranial =\> urine osmolality increases \>50%
- nephrogenic =\> urine osmolality rises \<45%
127
management for cranial DI
- find cause (MRI)
- give desmopressin
for mild give carbamazepine (reduces effects of residual AVP)
128
management of nephrogenic DI
- sodium/ K+ restrictions help with polyuria
- thiazide diuretics inhibits Na/Cl- transporters in DCT, causes compensatory increase in Na+ reabsorption from PCT
- NSAIDs (lower urine volume and plasma Na+ by inhibiting prostaglandin synthesis)
129
lesion in the optic chasm causes which visual field defect
bitemporal hemianopia
130
lesion in the optic tract causes which visual field defect
homonymous hemianopia
131
define pituitary tumours
tumours of the pituitary gland that can compress the pituitary gland and sometimes the optic chiasm =\> bitemporal hemianopia
* non-functional
* functional
132
types of functional pituitary adenomas
* acromegaly (high GH)
* prolactinomas (high prolactin)
* cushing's disease (ACTH secreting tumour)
133
symptoms of prolactinomas
Men
* **erectile dysfunction**
* loss of libido
* **infertility**
* galactorrhoea (rare)
Female
* **galactorrhoea**
* **secondary amennorrhoea/** oligomennorrhea
* infertility
* loss of libido
General:
* headaches
* visual field defects (bitemporal hemianopia)
134
Investigations for prolactinomas/ hyperprolactinemia
* Pregnancy test
* TFTs
* basal prolactin level (if \>6,000mU/L =\> prolactinoma)
* MRI to check for prolactinoma
135
Management for prolactinoma
1. dopamine agonists (cabergoline, bromocriptine) FIRST-LINE
2. Trans-sphenoidal surgery
136
Other causes of hyperprolactinemia
Physiolgical:
* pregnancy/ breast feeding (NORMAL)
Pathological:
* Prolactinoma
* Primary hypothyroidism
* Pituitary stalk compression (other pituitary adenoma)
137
signs + symptoms of acromegaly (ABCDEF)
* A-arthritis
* B- raised bp
* C- carpal tunnel (due to nerve compression)
* D- diabetes (insulin resistance)
* E- **enlarged hands, feet, face, TONGUE**
* F- visual field defect (compression of optic chiasm), **prominent FOREHEAD**
* Sweating, thick,oily skin
\*most GH-producing tumours also secrete prolacting =\> galactorrhoea, amenorrhoea
138
Investigations for acromegaly
* blood glucose
* bloods: Ca2+, phosphate, lipid profile
* **IGF-1** levels (GH unreliable measurement)
* MRI of pituitary/hypothalamus
* check other pituitary hormone levels (prolactin, LH/FSH, ACTH)
139
Management for acromegaly
Medical
* **somatastain analogues** (inhibit GH) - ocreotide
* dopamine agonists (bromocriptine, cabergoline)
Surgical:
* trans-sphenoidal surgery
140
Symptoms + signs of Cushings disease (ACTH secreting tumour)
* moon face
* centripetal obesity, buffalo hump
* poor wound healing, easy bruising
* striae
* diabetes - osmotic symptoms (polyuria, polydypsia)
* proximal muscle weakness + wasting
other pituitary adenoma associated symptoms:
* headaches, visal field defects
* prolactin =\> galactorrhea/ amennorrhea
141
Investigations for Cushing's disease (pituitary adenoma)
* 9am serum cortisol
* SynACTHen test
* insulin induced hypoglycaemia (should increase cortisol)
142
Management of Cushing's disease (pituitary adenoma)
* drugs: metyrapone, ketoconazaole
* MRI
* visual field assessment
143
define obesity
XS fat usually due to energy intake \> energy expenditure
* Obesity I - BMI 30-35
* Obesity II- BMI 35-40
* Obesity III- BMI 40+
Higher waist circumference increases complications of obesity
144
causes of obesity
* Lifestyle - inactivity + poor diet (MOST COMMON)
* Genetic - leptin deficiency
* medication - insulin, sulphonylureas
* Medical conditions (weight gain)
1. hypothyroidism
2. Cushing's syndrome
3. GH deficiency
4. PCOS
5. genetic=\> hypogonadism (Prader-willis syndrome)
6. hypothalamic dysfunction (tumour/trauma/surgery)
145
Management of obesity
1. Lifestyle interventions - structured activity/ diet
2. Drugs - orlistat (reduces fat reabsorption) V expensive
3. Refer Weight management services (cormorbidites)
4. Bariatric surgery (first line for BMI \>50, with significant cormorbidities)
146
complications of obesity
* diabetes
* CVD
* hypertension/ stroke
* hyperlipidemia
* asthma
* depression
* lower life expectancy
147
Define thyroid nodules
* abnormal growths of thyroid gland =\> single/ multi-nodular
* usually benign
* single nodules more likely to become malignant
* more common in WOMEN
148
types of thyroid cancer
* papillary carcinoma (most common)- childhood radiation exposure
* follicular carcinoma- low iodine intake
* medullary carcinoma (MEN 2A/2B)
* Anaplastic carcinoma
* Lymphoma (RARE)
149
Symptoms and signs of benign thyroid nodules
* usually asymptomatic
* can sometimes be painful (rarely =\> trachea compression =\> dyspnoea)
* moves when water is swallowed
* regional lymphadenopathy (if malignant)
* sometimes causes hyperthyroidism symptoms
150
Symptoms + signs of thyroid cancer (malignant nodule)
Signs:
* single, irregular shape, hard and fixed nodule
* painless, rapidly growing
* cervical lymphadenopathy
Symptoms:
* hoarse voice (compression of recurrent laryngeal nerve)
* dysphagia (compression of trachea)
* haemoptysis
* airway obstruction
151
Investigations for thyroid nodules
Bloods
* TFTs (usually normal)
Imaging
* Thyroid US
* Radioiodine uptake scan
* CT/MRI - check for spread if cancer
Other
* Fine needle aspiration =\> check cytology (CANCER?)
152
management of thyroid cancer
1. thyroidectomy
2. radioiodine to kill remaining thyroid gland
3. levothyroxine treatment + monitor thyroglobulin
