Endo Flashcards
1
Q
Signs / Symptoms of DMT2
A
Polyuria
Polydipsia
Polyphagia
Glycosuria
Usually picked up on routine blood tests
2
Q
Pathology of DMT2
A
Repeated, prolonged exposure to glucose results in insulin resistance
+
Pancreatic B cells become damaged from hyperglycaemia and produce less insulin
=
Chronic hyperglycaemia
3
Q
Ix DMT2
A
-
HbA1C - GS !!
tells us avg. blood glucose levels for past 3 months
HbA1C > 48 mmol/L = DIABETES
HbA1C between 42 - 47 mmol/L = PRE-DIABETES
- Blood tests
Random plasma glucose > 11.1 mmol/L
Fasting plasma glucose > 7 mmol/L - Oral glucose tolerance test
Fasting > 7 mmol/L
then test 2 hours after glucose
//
If asymptomatic, at least 2 of above
If symptomatic, 1 of above
4
Q
Tx T2DM
A
1st line - Lifestyle management
2nd line - Metformin
3rd line - if HbA1C rises to 58, depends on drug tolerance/individual factors
Metformin + sulphonylurea e.g. glicazide
Metformin + DPP4-inhibitor e.g. sitagliptin
Metformin + SGLT-2i e.g. glifazon
4th line - Insulin
5
Q
Mechanism of Sulphonylurea
A
Stimulates pancreatic B cells to secrete insulin
6
Q
S/E of sulphonylurea
A
Weight gain
Hyponatraemia
Hypoglycaemia
7
Q
Examples of sulphonylurea
A
Glicazide
Glimepiride
8
Q
Describe the mechanism of Metformin
A
Increases insulin sensitivity
Decreases hepatic gluconeogenesis
9
Q
Side effects of Metformin
When is it CI?
A
GI upset
Lactic acidosis
CANNOT be used in Px with eGFR < 30ml/min AKA renal failure!!
10
Q
Describe the mechanism of DPP4-inhibitors
A
Increase incretin levels
∴ ↓ Glucagon secretion
11
Q
Side effects of DPP4-i
A
Usually not many side effects
But does increase risk of pancreatitis
12
Q
Describe the mechanism of SGLT-2 inhibitors
A
Inhibits reabsorption of glucose in the kidney
13
Q
Side effects of SGLT-2 inhibitors
A
UTI !!
& Weight loss
14
Q
Example of SGLT-2 inhibitors
A
Glifazone
15
Q
Example of DPP4-i
A
Sitagliptin
16
Q
Signs / Symptoms of Cushing’s
A
Round, moon face
Truncal obesity
Abdominal striae
Buffalo hump
Acne
Hirsutism
Mood changes - depression, anxiety
Irregular periods - Amennorhoea
Proximal limb wasting
17
Q
Define Cushing’s
A
Chronic, abnormal elevation of cortisol
18
Q
Causes of Cushing’s
A
ACTH-Independent -
> Iatrogenic !! - most common!
usually prednisolone (or other steroids)
> Adrenal adenoma - benign tumour, secretes XS cortisol
ACTH-Dependent
> Cushing’s disease - Ant. pituitary adenoma causes ↑ ACTH ∴ ↑ cortisol
(most common dependent cause)
> Ectopic ACTH production - neoplasm somewhere in body, esp small cell lung cancer!! also carcinoid tumours - produce XS ACTH
19
Q
Investigations for Cushing’s
A
1st Line - Raised plasma cortisol
(don’t do randomly! bc cortisol levels fluctuate throughout the day)
GS!! DEXAMETHASONE SUPPRESSION TEST - low dose (1mg)
Other -
24hr urinary free cortisol (can be used instead of ^DST but doesn’t indicate cause)
MRI brain - to find pituitary adenoma
Chest CT - SCLC
Abdo CT - adrenal tumours
20
Q
Describe how you can identify the cause of Cushing’s disease using the dexamethasone suppression test
A
Low dose (1mg) should be suppressed to < 50 nmol after 2 hours if normal
If NOT suppressed = Cushing’s syndrome
THEN high dose,
If Cushing’s disease, Px should suppress within 48 hours.
If NOT, it suggests an ectopic source (high ACTH) or adrenal tumour (low ACTH).
21
Q
Treatment for Cushing’s
A
If iatrogenic, STOP STEROIDS !!
If adrenal adenoma, adrenalectomy
If Cushing’s disease, transsphenoidal surgery to remove pituitary adenoma
If ectopic ACTH production and hasn’t metastasised, surgery to remove neoplasm
If can’t do surgery, could remove both adrenal glands and give replacement steroid hormones for life
22
Q
CUSHING
(acronym)
A
Cataracts
Ulcers
Striae
Hyperglycaemia or HTN
Increased risk of infection
Necrosis
Glycosuria
23
Q
RF Acromegaly
A
MEN-1
24
Q
Why are plasma GH levels not used as a diagnostic factor in Acromegaly?
A
Bc secretion is pulsatile
increases due to stress, pregnancy, puberty and during sleep
25
Signs / Symptoms Acromegaly
Bitemporal hemianopia
Large, spade-like hands and feet
Frontal bossing
Large ears, tongue, nose
Spacing between teeth
Large protruding jaw
Back ache
Arthralgia
XS sweating
Sleep apnoea
Amenorrhoea
Oily skin
Mood disturbances
Headache
Acroparaesthesia / Carpal tunnel signs
"My rings don't fit anymore, I've gone up a couple of shoe sizes recently and my teeth have become more separated"
26
Pathophysiology of Acromegaly
Hypothalamus secretes GHRH ∴ Ant. pit secretes GH
XS GH causes XS production of IGF-1
∴ inappropriate growth of soft tissue and bone
27
RF Acromegaly
MEN-1
28
Ix Acromegaly
1st Line - Raised IGF-1 (bloods)
**GS** !! - Oral glucose tolerance test !
Give Px glucose
Serum GH should fall if normal
In acromegaly, serum GH release is not suppressed
29
Tx Acromegaly
If Acromegaly secondary to pit. adenoma, do **transsphenoidal surgery** to remove
If secondary to cancer, surgically remove tumour
--
If can't do above, can be treated w/ mediation :
1. Somatostatin analogues e.g. octreotide - blocks GH release
2. Pegvisomant - GH antagonist given via SC daily
3. Dopamine agonist e.g. cabergoline, bromocriptine - blocks GH release
30
S/E of Somatostatin analogues
Pain at injection site
Loose stool
Abdo cramps
↑ Gallstones
Impaired glucose tolerance
31
When would you use pegvisomant instead of somatostain analogues (SSA) ?
If intolerant or resistant to SSA
32
Monitoring Acromegaly
Yearly follow up - vascular assessment, visual fields, GH levels, BMI
33
Complications / Co-morbidities Acromegaly
HTN / Heart disease - due to ↑ GH ∴ hypertrophy of the heart
Sleep apnoea
Arthritis - due to overgrowth of cartilage
T2 Diabetes - bc constantly high blood glucose
Carpal tunnel - muscle growth compresses nerve
Visual field defects - bitemporal hemianopia
Cerebrovascular events + headaches
34
RF Prolactinoma
Female
Peak incidence @ 20 - 40 years
35
Signs / Symptoms Prolactinoma
GENERAL : Headache, visual defect (bitemporal hemianopia), CSF leak (rareee)
FEMALES : Amennorrhoea, oligomenorrhoea, infertility, low libido, galactorrhoea
MALES : Erectile dysfunction, low testosterone, ↓ facial hair, low libido
--
Males can have galactorrhoea too but rarer
36
Pathophysiology Prolactinoma
Tumour of lactotroph cells
∴ hypersecretion of prolactin
∴ inhibits release of GnRH from hypothalamus
∴ ↓ LH, FSH from ant. pituitary
↓ release oestrogen and progesterone in females / in males ↓ release of testosterone
--
2° hypogonadism
37
Ix Prolactinoma
1st Line - Serum prolactin levels (ALSO GS!!! If high = prolactinoma)
2nd Line - Pituitary MRI (to detect adenoma)
38
Tx Prolactinoma
Medication is preferred over surgery!
**1st Line - Dopamine agonists**
e.g. ORAL cabergoline, bromocriptine
(bc dopamine inhibits prolactin secretion ∴ shrinks the prolactinoma)
Usually see big reduction of macroadenoma, can be sight saving
Microadenoma - responds to small doses, 1 or 2 a week
**2nd Line - Hormone replacement therapy** e.g. oestrogen
(if galactorrhoea/fertility isn't an issue)
39
Complications Prolactinoma
Infertility
Sight loss
↑ Intracranial pressure - bc adenoma growth
40
Quick! What is Addison's?
Too little cortisol and too little aldosterone
41
What is the fun key phrase to remember for Addison's?
Tanned, Toned (fit and ready), Tired, Tearful
42
Causes of Adrenal Insufficiency
1° - **Addison's** aka autoimmune adrenalitis (most common! 90%!)
Adrenal TB
Surgical removal of adrenal glands
Adrenal infarction/haemorrhage (meningococcal septicaemia)
Malignancy
2° - Steroids
CRH deficiency
Trauma
Radiotherapy
43
Signs / Symptoms Adrenal insufficiency
N + V
Fatigue
Postural hypotension
**Hyperpigmentation** esp in palmar creases for Addison's
Pallor
Headaches
Depression
Impotence
Amennorrhoea
Weight loss
REMEMBER : Tanned, Toned, Tired, Tearful
44
Ix Adrenal Insufficiency
> **GS!!** Short synACTHen
If Px healthy, cortisol levels should double
If doesn't, indicates Addison's (1°) (or doesn't indicate between 1° and 2° confused)
> Plasma ACTH levels
If high with low/normal cortisol = 1° (Addison's)
If low with low cortisol, indicates 2° or 3°
> U&E
Low Na+ and High K+ (bc low aldosterone)
Low aldosterone, high renin
45
Tx Adrenal Insufficiency / Addison's
**STEROIDS!!** - double dose if trauma, nightshift work, infection or surgery
Oral Hydrocortisone/Prednisolone - to replace cortisol
Fludrocortisone - to replace aldosterone
46
Which medication used to treat adrenal insufficiency corrects postural hypotension?
Fludrocortisone
Bc by replacing aldosterone, it ↑ Na+ and ↓ K+
47
What is an Addisonian crisis?
Medical emergency!! Sudden drop in aldosterone and cortisol
48
How does an Addisonian crisis present?
Hypotension and cardiovascular collapse
Fever
Hypoglycaemia
Hyponatraemia and hyperkalaemia
Hypovolaemic shock
Confusion
Fatigue
N+V
Abdo and back pain
Muscle cramps
49
How to treat an Addisonian crisis?
Fluid and **IV** Hydrocortisone
50
Describe the differences between 1°, 2° and 3° adrenal insufficiency
**1° - adrenal gland is damaged** (Addison's)
∴ ↓ cortisol and ↓ aldosterone
Most common cause worldwide = TB, in UK = autoimmune adrenalitis
**2° - loss/damage of pituitary gland**
∴ inadequate ACTH (∴ less stimulation of adrenal gland)
**3° - suppression of hypothalamus**
∴ inadequate CRH release
Usually bc patients on long term oral steroids (more than 3 weeks)
51
When treating adrenal insufficiency, what is important to remember?
Double dose of steroids if infection, trauma, surgery or nightshift work
52
Causes Hyperthyroidism
GRAVES' DISEASE (80%!!)
Toxic multinodular goitre
XS iodine consumption
De Quervain's thyroiditis/Thyroiditis
Drug induced (iodine, amiodarone)
Pregnancy
53
Signs / Symptoms Hyperthyroidism
**General :**
Weight loss
Heat intolerance
Palpitations
Anxiety
Tremors
Tachycardia
**Graves' Specific :**
EYE SIGNS! - Exopthalmos, lid retraction, lid lag, lacrimation, diplopia
Pretibial myxoedema
Thyroid acropachy
Diffuse goitre
54
Ix Hyperthyroidism
1. THYROID FUNCTION TEST
If 1° - ↓ TSH, ↑ T3/T4
If 2° - ↑ TSH, ↑ T3/T4
2. THYROID AUTO-ANTIBODIES
Thyroid peroxidase Abs - more in hypothyroidism
Thyroglobulin Abs
TSH receptor Abs (TRAb) - ONLY Graves
3. THYROID ULTRASOUND
4. RADIOACTIVE ISOTOPE UPTAKE SCAN
Much higher in Graves'
**Important !**
If drug induced, everything is normal except ↑Thyroid hormones
--
_Might_ be mild normocytic anaemia and mild neutropenia
55
Tx Hyperthyroidism
Depends on cause !
> Beta blockers - rapid system control in attacks
> Anti-thyroid drugs e.g. **Carbimazole** - blocks thyroid hormone synthesis
> **Radioiodine treatment**
nb. can do thyroidectomy but leave a small bit behind so thyroid function can still happen
56
What is a common S/E of Carbimazole when treating Hyperthyroidism?
Agranulocytosis
57
Contraindications of Radioiodine treatment in Hyperthyroidism
Pregnancy
Breast-feeding
58
Mechanisms for Hyperthyroidism
1. Overproduction of thyroid hormone
2. Leakage of pre-formed hormone from thyroid
3. Ingestion of XS thyroid hormone
59
What are the 2 strategies when giving Carbimazole for hyperthyroidism?
1. **Titration** - oral carbimazole for 4 weeks then reduce according to TFTs
2. **Block & Replace** - oral Carbimazole and thyroxine (has a less risk of going hypo)
60
Complications of Hyperthyroidism
Congestive HF
Atrial Fibrillation
Osteoporosis
Graves' opthalmopathy complications
Graves' dermopathy - elephantitis
THYROID STORM
61
Comp of Radioiodine therapy when treating Hyperthyroidism
Could lead to HYPOthyroidism
62
Mechanism of Radioiodine therapy when treating Hyperthyroidism
Iodine taken up and local irradiation and tissue damage causes return to normal
function
63
What drugs must be adjusted alongside a thyroidectomy when treating hyperthyroidism?
Anti-thyroid drugs are stopped 10-14 days prior and replaced w/ oral potassium iodide
64
Complications of Thyroidectomy
Bleeding
Post-op infection
Hypocalcaemia
Hypothyroidism
Hypoparathyroidism
Recurrent laryngeal palsy - due to laceration
Recurrent hyperthyroidism
65
What is Thyroid Storm / Thyroid Crisis?
Rare, life-threatening condition
Rapid deterioration of thyrotoxicosis
66
Signs / Symptoms Thyroid Storm
Hyperpyrexia
Tachycardia
Extreme restlessness
Potentially delirium, coma and death
67
What is Thyroid Storm usually precipitated by?
Infection
Stress
Surgery
Radioactive Iodine therapy
68
How do you treat Thyroid Crisis/Thyroid Storm?
Large doses of Carbimazole
Propanolol
Potassium iodide - to acutely block release of thyroid hormone from gland
Hydrocortisone - inhibits peripheral conversion of T4 to T3
69
Causes Hypothyroidism
Post-partum
Autoimmune thyroiditis (Hashimoto;s)
Iodine deficiency
Drug-induced (Carbimazole, Lithium, interferon Amiodarone)
Iatrogenic (thyroidectomy or radioactive iodine therapy)
Congenital hypothyroidism
70
Signs / Symptoms Hypothyroidism
**Symptoms :**
Goitre
Weight Gain
Constipation
Lethargy
Poor memory
Puffy eyes
Arthralgia
Hoarse voice
Cold intolerance
Menorrhagia
Tiredness
**Signs : BRADYCARDIC**
**B**radycardic
**R**eflexes relax slowly
**A**taxia
**D**ry thin hair/skin
**Y**awning
**C**old hands
**A**scites
**R**ound puffy face
**D**efeated demeanour
**I**mmobile - ileus
**C**ongestive HF
--
nB . Women w/ period problems should always have hypothyroidism excluded !!
71
Ix Hypothyroidism
**Thyroid Function Tests**
1° - ↑ TSH, ↓ T3/4
2° - ↓↓ TSH (inappropriately low for what T3/4 are), ↓ T3/T4
**Thyroid Antibodies**
Anti-thyroid Peroxidase Abs in Hashimoto's!!!!
**Other Hypo**
> FBC - normocytic, normochromic anaemia. Could be macrocytic (menorrhagia) or microcytic (pernicous anaemia)
> Hyperlipidaemia
> Hyponatraemia (bc ↑ ADH)
> ↑ Serum creatinine kinase w/ associated myopathy
72
Tx Hypothyroidism
Lifelong, oral **Levothyroxine** (T4)
Start w/ 25 mcg, increase incrementally every 3-6 weeks
**AIM is to get TSH = 0.5**
w/ 1° - titrate dose until TSH normal
w/ 2° - TSH will always be low, monitor T4
73
Monitoring Hypothyroidism Tx
T4 half-life is ~7 days
∴ wait ~ 4 weeks to see new TSH levels after dose adjustment
74
Hashimoto's Thyroiditis pathophysiology
Cell and antibody mediated autoimmune disease
Causes formation of anti-thyroid antibodies
∴ forming progressive fibrosis
75
What is Hashimoto's thyroiditis associated with?
DMT1, Addison's, Pernicious anaemia
76
RF Hashimoto's Thyroiditis
Down's syndrome
Turner's
HLA-DR3
Graves'
77
Ix Hashimoto's thyroiditis
**1st Line = Thyroid Function Tests**
↑ TSH, ↓T4
**GS = Anti-Thyroid Peroxidase Antibodies**
78
Tx Hashimoto's thyroiditis
Levothyroxine
79
What is Diabetic ketoacidosis?
A life-threatening, medical emergency
80
Signs / Symptoms of DKA
N+V
Severe dehydration - can cause hypotension
**PEAR DROP BREATH**
Abdo pain
↓ Consciousness
Hyperventilation - Kussmaul's
Confused
Confusion - could lead to coma
Potassium imbalance
Also, signs of DM - i.e. polyuria, polydipsia etc
81
What is the associated between DKA and DMT1?
Most common way children w/ DMT1 present is with DKA
82
Is DKA preventable?
YES, so preventable
Usually occurs when people w/ DMT1 stop insulin (bc of illness/vomiting)
Pxs SHOULD NEVER STOP INSULIN !!!!!!!!!!!
83
Causes DKA
Untreated DMT1 / Interruption of insulin therapy
Undiagnosed DM
Infection/Illness
Myocardial infection
84
What is Kussmaul's breathing?
Deep, laboured breathing pattern at consistent pace
Often associated with severe metabolic acidosis
85
Ix DKA
Need 3 of the following for diagnosis !! :
1. **Hyperglycaemia** - BG > 11mmol/L
2. **Ketosis** - blood ketones > 3mmol/L
3. **Acidosis** - ABG, pH < 7.3 and/or bicarbonate < 15mmol/L
Clinical features
+ BG measurement
+ Blood gas
86
DKA Pathology
↓↓↓ Insulin
∴ _unrestrained_ glucose production (hepatic gluconeogenesis)
∴ ↓ peripheral glucose uptake
High levels of circulating glucose
-> Osmotic diuresis by kidneys
∴ DEHYDRATION
Peripheral lipolysis = ↑ FFAs
FFAs oxidised to Acetyl CoA -> ketones
∴ ACIDOSIS
87
Tx DKA
**IMMEDIATE ABC management if unconsciousness**
**Replace fluid loss w/ 0.9% saline**
**Replace deficient insulin** - give insulin AND glucose (will prevent hypoglycaemia, will both inhibit gluconeogenesis and ∴ ketone production)
**Treat underlying triggers** - e.g. illness w/ Abx
88
Why can insulin Tx for DKA cause hypokalaemia?
Why is this dangerous?
Bc insulin decreases K+ levels
K+ goes into cells bc ↑ Na+ pump activity
∴ Hypokalaemia
∴ can lead to arrhythmias etc
89
Monitoring DKA
Monitor BG closely
Bc therapy can lead to shift of K+ into cells
∴ hypokalaemia
90
Complications DKA
Cerebral oedema
91
Cell types of Thyroid Cancers
Papillary
Follicular
Medullary
Lymphoma
Anaplastic
92
Behaviour
Spread
Prognosis
for Papillary cell Thyroid Cancer
Affects young people
Local spread, followed by pulmonary/skeletal
Good prognosis
93
Behaviour
Spread
Prognosis
for Follicular Cell Thyroid Cancer
Affects middle aged people, 3x more common in Females
Pulmonary & skeletal (lung/bone)
Usually good prognosis if early but poorer than papillary
94
Behaviour
Spread
Prognosis
for Medullary Cell Thyroid Cancer
Often familial
Local and metastases (liver, lung, skeletal)
Poor prognosis - depends on age/stage
95
Behaviour
Spread
Prognosis
for Lymphoma Cell Thyroid Cancer
Variable
/
Usually poor prognosis
96
Behaviour
Spread
Prognosis
for Anaplastic Cell Thyroid Cancer
Aggressive, mean onset = 65years
Local spread
Very very poor prognosis (avg. survival = 3-8 months)
97
RFs Thyroid Cancer
Head & neck irradiation
Females
98
Signs / Symptoms Thyroid Cancer
**Palpable thyroid nodule** - increased size, hardness and irregularity
Dysphagia
Hoarseness of voice - if tumour presses on recurrent laryngeal nerve
99
DDx Thyroid Cancer
Goitre
100
Ix Thyroid Cancer
**1st Line** = Ultrasound of neck (thyroid)
Fine needle biopsy cytology (to distinguish between benign and malignant)
Laryngoscopy
TFTs - hypo/hyperthyrodism needs to be treated before surgery
101
Tx Thyroid Cancer
**Follicular & Papillary Cancers -**
Total _thyroidectomy_
_Ablative radioiodine_ given after - this is taken up by remaining thyroid tissue or metastatic lesions
**Anaplastic & Lymphoma -**
Tx is largely palliative :(
But external radiotherapy might provide some respite
102
Complications Thyroid Cancer
↑ Risk of recurrent laryngeal nerve damage OR hypoparathyroidism
103
Phases of De Quervain's Thyroiditis
**4 Phases**
**Phase 1** - Lasts 3 to 6 weeks. Hyperthyroidism, painful goitre, ↑ ESR
**Phase 2** - Lasts 1 to 3 weeks, Euthyroid
**Phase 3** - Weeks to months, Hypothyroidism
**Phase 4** - Thyroid structure, function goes back to normal
104
What is De Quervain's Thyroiditis ?
Transient, self-limited inflammation of thyroid gland
Subacute granulomatous thyroiditis
Presents w/ hyperthyroidism
Probs viral
105
Ix De Quervain's Thyroiditis
**1st Line =**
Total T4/T3
T3 resin uptake
Free thyroxine index
(all of above is elevated)
CRP = elevated
106
Tx De Quervain's Thyroiditis
In HYPERthyroidism phase, NSAIDs and corticosteroids
(Usually only give steroids if v severe)
In HYPOthyrodism phase, no treatment usually. If severe, give small dose of Levothyroxine
107
Complications De Quervain's
Thyroid storm
Long term hypothyroidism
108
DDx De Quervain's
Thyroid cancer!
Toxic multinodular goitre
Hashimoto's
Graves'
109
How can you clinically detect recurrence with medullary thyroid cancer?
Calcitonin !
Medullary thyroid cancer often secretes calcitonin!
110
Causes Hyperparathyroidism
**1° - XS PTH**
Tumour - solitary adenoma
**2° - Compensatory hypertrophy of glands in response to HYPOcalcaemia**
Vitamin D deficiency!!
Chronic renal disease
**3° - After prolonged 2°, causes glands to act autonomously ∴ hyperplastic OR adenomatous change**
(∴ ↑ Ca2+ bc no neg feedback bc ↑↑PTH)
Usually seen in CKD!
**Malignant** - Parathyroid-related protein (PTHrP) is produced by squamous cell lung cancer, breast & renal cell carcinomas
Mimics PTH
111
Describe the Ca2+, PTH and phosphate levels in 1°, 2°, 3° & Malignant Hyperparathyroidism
**1°** - ↑Ca2+, ↑PTH, ↓Phosphate
**2°** - ↓Ca2+, ↑PTH, ↑Phosphate
**3°** - ↑Ca2+, ↑↑PTH, ↑Phosphate
Malignant - ↑Ca2+, ↓PTH (bc PTHrP isn't in assay)
112
Signs / Symptoms Hyperparathyroidism
**Renal STONES, painful BONES, abdo GROANS, psychiatric MOANS**
--
**STONES** - renal colic from renal stones (can lead to renal failure)
Biliary stones
**BONES** - painful bones, fractures & osteoporosis
Usually osteotitis fibrosa cystitis
**GROANS** - GI symptoms
N+V, constipation, indigestion
**MOANS** - lethargy, fatigue, depression, memory loss, psychosis, insomnia
--
ALSO, thirst, polyuria, HTN
Often asymptomatic at first w/ ↑ Ca2+
In retrospect, it's not !
113
Describe the 3 reasons that Hyperparathyroidism presents the way it does
**1.** ↑Ca2+
**2.** Bone resorption effects of PTH
**3.** ↑BP ( ∴ check Ca2+ in EVERYONE with HTN)
114
Ix Hyperparathyroidism
STONES - Ultrasound KUB
BONES - DEXA bone scan for osteoporosis
GROANS - Abdo XR, renal calculi or nephrocalcinosis
ADENOMAS - Radioisotope scanning
--
BLOODS -
**1°** - ↑Ca2+, ↑PTH, ↓Phosphate
**2°** - ↓Ca2+, ↑PTH, ↑Phosphate
**3°** - ↑Ca2+, ↑↑PTH, ↑Phosphate
Malignant - ↑Ca2+, ↓PTH (bc PTHrP isn't in assay), ? Phosphate (depends on the exact underlying cause)
--
& 24 hour calcium excretion
115
Tx Hyperparathyroidism
**1°**
Parathyroid adenoma - surgical removal
Parathyroid hyperplasia - ALL 4 glands removed
Give calcimetic (e.g. Cinacalcet) - ↑Sensitivity of parathyroid cells to Ca2+ ∴ ↓ PTH secretion
--
**2° & 3°**
Treat the cause
--
**If emergency :**
> Rehydrate w/ 0.9% saline (to prevent STONES)
> Bisphosphonates _after_ rehydration (prevents bone resorption - prevents painful BONES) e.g. IV Pamidronate
116
What should a Patient with 1° Hyperparathyroidism avoid?
Thiazide diuretics
High Ca2+
Vitamin D intake
117
Monitoring Hyperparathyroidism
Measure serum U&Es daily
?
118
S/E of Cinacalcet
Myalgia
↓ Testosterone
119
Associations with Hyperparathyroidism
MEN-1
120
What should you check in ALL patients with HTN?
Ca2+
Bc could be hyperparathyroidism
121
What are the complications of removing the adenoma or of ALL 4 hyperplastic glands to treat Hyperparathyroidism?
HYPOparathyroidism
Recurrent laryngeal nerve damage (∴ hoarse voice)
122
Hyperparathyroidism :
Phosphate levels ↓ EXCEPT
In cases of renal failure
123
What is the most likely cause of increased Ca2+?
Hyperparathyroidism
124
What is Phaechromocytoma and where are they found?
RARE, catecholamine-producing tumours
Usually found in adrenal medulla, arise from paraganglia cells (which is a type of chromaffin cells)
Extra-adrenal tumours are even rarer - if found, usually at aortic bifurcation
125
Signs / Symptoms Phaechromocytoma
Often all vague and episodic
**CLASSIC TRIAD :**
1. Episodic headache
2. Tachycardia
3. Sweating
↑ BP and ↑ glucose sometimes
Sx may be precipated by exercise, stress etc
Skin pallor
Cold peripheries
_Suspect if BP is hard to control, accelerating or episodic !_
126
Ix Phaechromocytoma
↑Plasma/Urinary metanephines
(Should do 3 x 24 hour urine test for free metanephrine)
127
Tx Phaechromocytoma
Phentolamine - alpha receptor blocker
**SURGERY** - remove tumour
If malignant, can also use chemo or radiotherapy
128
Pathophysiology Phaechromocytoma
Neoplasia of adrenal medulla
Which secretes catecholamines
129
Monitoring Phaechromocytoma
Monitor BP
Lifelong followup (bc malignant recurrence may present late!)
130
Causes Hypoparathyroidism
1° - Gland failure
Congenital, auto-immune (Di George's)
2° - Radiation, surgery (parathyroidectomy), magnesium def
131
Causes Pseudoparathyroidism
Failure of target cells to respond to PTH
132
Signs / Symptoms Hypoparathyroidism
**SPASMODIC**
**S**pasm - carpopdeal spasm, Trousseau's sign, larynx spasm - obstructing airway, premature labour (uterus contractions)
**P**erioral/peripheral paraesthesia
**A**nxious, irritable
**S**eizures
**M**uscle tone ↑
**O**rientation impaired & confusion
**D**ermatitis
**I**mpetigo herpetiformis
**C**hvostek's sign / **C**ardiomyopathy / **C**ataracts
--
**CATS go NUMB**
**C**onvulsions
**A**rrhythmias
**T**etany
**S**pasms
**NUMB** fingers/hands
133
Signs / Symptoms Pseudoparathyroidism
Short metacarpals (esp 4th & 5th)
Round face
Short stature
Calcified basal ganglia
Intellectual impairment
134
Tx Hypoparathyroidism
Calcium supplements + Calcitriol (active vit D)
OR Synthetic PTH (SC, every 12 hours)
135
Tx Hypercalcaemia
Rehydration w 0.9% saline
Then, bisphosphonates
Sometimes - loop diuretics e.g. furosemide
136
Define hypercalcaemia
> 2.66 mmol/L Ca2+ in blood
137
Causes Hypercalcaemia
Check if it actually is - could just be tourniquet being on for too long, falsely elevates Ca2+ levels
--
**MOST** (90%) of cases are due to hyperparathyroidism OR malignancy (NHL, Myeloma, Bone mets, PTHrP)
--
**CHIMPANZEES**
**C**alcium supplements
**H**yperparathyrodism
**I**atrogenic drugs
**M**ilk alkali syndrome
**P**aget's disease of the bone
**A**ddison's & **A**cromegaly
**N**eoplasms
**Z**ollinger-Ellison's - MEN type 1
**E**xcess Vit D
**E**xcess Vit A
**S**arcoidosis
138
What is PTHrP?
Parathyroid Hormone relating peptide - mimics PTH, released in some kidney & lung cancer
139
What is Milk Alkali syndrome?
TRIAD OF :
1. Hypercalcaemia
2. Metabolic alkalosis
3. AKI
140
Why can cancer cause hypercalcaemia?
Unregulated bone breakdown
∴ ↑ Ca2+ in blood
141
Signs / Symptoms Hypercalcaemia
**Renal STONES, painful BONES, abdo GROANS, psychiatric MOANS**
--
**STONES** - renal colic from renal stones (can lead to renal failure)
Biliary stones
**BONES** - painful bones
Usually osteotitis fibrosa cystitis
**GROANS** - GI symptoms
N+V, constipation, indigestion
**MOANS** - lethargy, fatigue, depression, memory loss, psychosis, insomnia, confusion
--
ALSO, thirst, polyuria, HTN, fractures & osteoporosis
142
RF Hypercalcaemia
Typically affects older women
143
Ix Hypercalcaemia
> **ECG** - Short QT, tented T waves
> **24 Urinary Calcium** - check in young patients or if family history to test if familial hypocalcuric hypercalcaemia
> **Bloods** - Ca2+ & PTH
If PTH undetectable and Ca2+ is high, means NOT hyperparathyroidism ∴ reqs further investigation (could be tumour secreting PTHrP)
> Rule out possible causes - CXR (Myeloma, NHL), SynACTHen (Addison's), US (1° hyperparathyroidism) etc
> DEXA
144
Tx Hypercalcaemia
If Hyperparathyroidism, treat accordingly
**IV saline** - helps dilute Ca2+ in blood
**Bisphosphonates** - encourages osteoclasts to apoptosise so ↓bone breakdown
145
Causes Hypocalcaemia
State whether they present with low or high phosphate
> Vit D def (low)
> Hypoparathyroidism (high)
> Pseudohypoparathyroidism -
> Acute pancreatitis (low)
> Osteomalacia (low)
> CKD (high)
> Drugs - Calcitonin, bisphosphonates
146
Describe the mechanism of Vitamin D deficiency as a cause for Hypocalcaemia
Vit D = ↑ Ca2+ uptake
∴
Vitamin D deficiency causes ↓ Ca2+ uptake at GI tract & ↓ absorption in kidneys
147
Describe the mechanism of Osteomalacia as a cause of Hypocalcaemia
Serum calcium low bc Ca2+ can't be absorbed from blood
Parathyroid gland recognises this and produces PTH to suck calcium from kidneys and resorb bone ∴ low Phosphate
148
Describe the mechanism of CKD as a cause of Hypocalcaemia
What might you find in tissues?
Poor uptake of Calcium in kidneys
Bc insufficient production of active vitamin D & renal phosphate retention
∴ might find microprecipitations of calcium phosphate in tissues
149
Describe the mechanism of drugs as a cause of Hypocalcaemia
Calcitonin - ↓ Ca2+ and phosphate
Bisphosphonates - ↓ Osteoclast activity ∴ ↓ Ca2+
150
Signs / Symptoms of Hypocalcaemia
**SPASMODIC**
**S**pasm - carpopdeal spasm, Trousseau's sign, larynx spasm - obstructing airway, premature labour (uterus contractions)
**P**erioral/peripheral paraesthesia
**A**nxious, irritable
**S**eizures
**M**uscle tone ↑
**O**rientation impaired & confusion
**D**ermatitis
**I**mpetigo herpetiformis
**C**hvostek's sign / **C**ardiomyopathy / **C**ataracts
--
**CATS go NUMB**
**C**onvulsions
**A**rrhythmias
**T**etany
**S**pasms
**NUMB** fingers/hands
151
What is Trousseau's sign?
Carpopdeal spasm when BP cuff is inflated to 20mmHg above systolic blood pressure
Usually indicative of hypocalcaemia
152
Ix Hypocalcaemia
ECG - long QT
Bloods - Ca2+ < 8.5mg/dL
Test PTH, Vit D, Albumin, Phosphorus and Mg levels
153
Tx Hypocalcaemia
If mild, Adcal supplements (Calcium carbonate) OR cholecalciferol
If severe/acute, IV Calcium Gluconate
10ml of 10% solution over 10 mins
**OR**
IV Calcium chloride (but more likely to cause local irritation)
If persistent, Vitamin D supplements (50000 IU orally once a week for 8 weeks)
154
Complications Hypocalcaemia
Seizure
Cardiac arrest
Long QT syndrome
155
Define Hypokalaemia
**< 3.5 mmol/L serum potassium level**
If <2.5 mmol/L = Severe & medical emergency !!
156
Explain the pathophysiology of Hypokaelaemia
If ↓ K+ in serum (ECF), creates a water conc gradient out of cells (ICF)
∴ ↑ Leakage from ICF
Causes hyper-polarisation of myocyte membrane
∴ ↓ Myocyte excitability
157
Causes of Hypokalaemia
Essentially :
↓ Potassium intake
↑ Potassium entry into cells
↑ Potassium excretion (sweat, urine, GI etc)
Magnesium depletion
Hyperaldosteronism
--
If with **ALKALOSIS**, causes might include : Vomiting, Thiazide & Loop diuretics, Cushing's, Conn's
If with **ACIDOSIS**, causes might include : Diarrhoea, Renal tubular acidosis, Acetazolamide, Partially treated DKA
158
Why does hyperaldosteronism cause Hypokalaemia?
Aldosteronism stimulates K+ excretion
159
Signs / Symptoms Hypokalaemia
Usually asymptomatic !!
Muscle weakness
Cramps
Tetany
Palpitations
Light headedness
Constipation
Arrhythmias
160
Ix Hypokalaemia
**ECG**
**U** have **no pot** (K+) and **no tea** but you have a **long PR** and a **long QT**
> Prominent U waves
> Inverted/Small T waves
> Long PR interval
> Long QT
> Depressed ST
--
Metabolic panel
Urine electrolytes - helps to differentiate between renal/non-renal causes
161
What is a U wave?
> 0.5mm deflection after the T wave
162
Tx Hypokalaemia
If mild (3-3.4 mmol/L), Oral replacement -> Sando-K
Consider IV
If severe (<2.5 mmol/L), IV replacement KCL
40 mmol KCL in IL 0.9% NaCl
163
Complications Hypokalaemia
CVS - Chronic HF, acute MI, arrhythmias
Muscle - weakness, depression of deep tendon reflexes, rhabdomyolysis
164
What is rabdomyolysis?
How does it present?
When damaged skeletal muscle breaks down rapidly
Tea-coloured urine & irregular heartbeat
165
Define Hyperkalaemia
Serum K+ > 5.5 mmol/L
166
Pathophysiology of Hyperkalaemia
When ↑ K+ :
↓ Difference in electrical potential between cardiac myocytes and outside cell
∴ ↓ Threshold for action potential
∴ Abnormal action potentials
∴ Arrhythmias
∴ Cardiac arrest
167
Causes Hyperkalaemia
Essentially :
↑ Intake
↑ Production
Redistribution
↓ Excretion
--
XS consumption very quickly e.g. IV fluids
↓ Aldosterone in kidneys - adrenal insufficiency
AKI
DRUGS - ACE-i, Spironolactone, Heparin, NSAIDs, Ciclosporin
168
Why does low aldosterone (e.g. adrenal insuffiency) cause Hyperkalaemia?
Aldosterone stimulates K+ excretion
169
How do ACE-i cause hyperkalaemia?
Blocks aldosterone binding to receptors
170
How does spironolactone cause hyperkalaemia?
Potassium-sparing diuretics
171
How does AKI cause hyperkalaemia?
Decreased filtration rate
∴ more K+ maintained in blood
172
Signs / Symptoms Hyperkalaemia
Usually asymptomatic until cardiac arrest
--
Muscle weakness
Rapid, irregular pulse
Impaired neuromuscular transmission
Flaccid paralysis
Chest pain
Light-headedness
Tachycardia
KUSSMAUL'S SIGN
173
Ix Hyperkalaemia
**ECG** - small P waves, tall tented T waves, wide QRS complex, sine wave, ventricular fibrillations
U&E (>5.5mmol/L = HYPERkalaemia)
If ≥ 6.5 mmol/L = medical emergency!
Urine analysis
Metabolic panel
174
Describe the gradual ECG changes in Hyperkalaemia
175
Tx Hyperkalaemia
**CIGS**
**C**alcium gluconate - stabilise myocardial cells
**I**nsulin
**G**lucose - Dextrose
**S**ABA - as alternative to I+G
176
How do loop diuretics e.g. furosemide help treat Hyperkalaemia?
↑ K+ excretion
177
How does insulin & dextrose help treat Hyperkalaemia?
Drives K+ into cells
Short-term shift of potassium from ECF to ICF
178
How does Polystyrene sylphonate resin help treat Hyperkalaemia?
Binds K+ in gut
∴ ↓ Uptake
179
How does Calcium gluconate stabilise the myocardium?
↓ Excitability of cardiac myocytes
&& ↓ VF risk !
180
Further management Hyperkalaemia
Stop exacerbating drugs - ACEi
Treat underlying cause - AKI
Lower body K+ - loop diuretics etc
181
What is Carcinoid Syndrome?
When carcinoid tumour (made of enterochromaffin cells) is present and producing serotonin (5-hydroxytrytamine) (**5HT**)
182
Where do carcinoid tumours most commonly arise?
GI TRACT
then liver, lungs, ovaries, thymus
MC GI site = appendix
then ileum, rectum
80% of tumours mets - usually from ileum to LIVER
(treat all as malignant)
183
Signs / Symptoms Carcinoid Syndrome
Initially very few symptoms
But when liver mets, hormone released into circulation & liver dysfunction
--
Bronchoconstriction (asthma/wheezing)
Paroxysmal flushing - upper body
Diarrhoea
HF - pulmonary stenosis, triscupid incompentence bc _5HT fibrosis_
Abdo cramps
184
Ix Carcinoid Syndrome
1st line - 24 hour urine 5-hydroxyindoleacetic acid ↑
If liver mets not found/to find 1° tumour : CXR and chest/pelvic MRI & CT
185
Tx Carcinoid Syndrome
**SURGERY !!!** - resection of tumour is only cure !! ∴ VITAL to find 1° tumour
**Somatostatin analogues** - Octreotide!
To ↓ Sx - debulking, embolisation, radiofrequency ablation
186
How does octreotide help treat Carcinoid Syndrome ?
Blocks release of tumour mediators
Counters peripheral effects
187
Median survival of Carcinoid syndrome?
5-8 years
BUT can survive ~20 years!
so don't give up
188
Complications Carcinoid Syndrome
**CARCINOID CRISIS**
If tumour outgrows blood supply/tumour handled too much in surgery, tumour mediators flood out into circulation
Sx - Vasodilation, HYPOtension, tachycardia, bronchoconstriction, hyperglycaemia
Tx - HIGH dose Octreotide, careful management of fluid balance
189
Epidemiology T1DM
Young < 30 years, usually juvenile but can be any age
Lean
North European - e.g. Finland
190
RF T1DM
FHx of autoimmune disease (HLA-DR3/DR4)
Personal Hx of autoimmune disease
191
Signs / Symptoms T1DM
2-6 week history
Weight loss
Polyuria
Polydipsia
Glycosuria
MIGHT PRESENT W DKA
192
Why do T1DM patients present with weight loss?
Fluid depletion & breakdown of fat/muscle bc of insulin deficiency
193
Why do T1DM patients present with polyuria?
Osmotic diuresis, occurs when BG is higher than renal tubular absorptive capacity (/renal threshold)
194
Pathophysiology of T1DM
Autoimmune destruction of pancreatic B cells
Autoantibodies directed against insulin & islet cell antigens
195
Ix T1DM
Fasting plasma glucose ≥ 7.0 mmol/L
Random plasma glucose ≥ 11.1 mmol/L
If symptomatic, 1 abnormal value
If asymptomatic, at least 2 abnormal values
--
Can also explore :
> Ketosis
> Rapid weight loss
> Age of onset < 5 years old
> BMI < 25 kg/m2
> Personal/FHx of autoimmune disease
196
Tx T1DM
**BASAL BOLUS INSULIN**
--
Basal - Long acting insulin
SC insulin
Once a day usually
Bolus - Short acting insulin
Soluble or analogues
Faster onset, shorter duration
Given ~30 mins before meals
--
Patient education is vital !!!!
--
Lifelong insulin
197
Name the macrovascular complications of DM
Why do these occur?
Usually occur bc DM is a RF for atherosclerosis
Cerebrovascular events - MI/Stroke
Peripheral vascular disease
198
How much more common is MI in a DM Px?
4 times
199
How much more common is stroke in a DM Px?
2 times
200
Name some microvascular complications of DM
Neuropathy - Diabetic foot
Nephropathy - Renal failure
Retinopathy - glaucoma, blindness
201
Why does diabetic neuropathy occur?
Occlusion of vasa nervosum & accumulation of fructose/sorbitol in vessels supplying peripheral nerves
∴ impaired function of peripheral nerves
202
Signs / Symptoms Diabetic Neuropathy
> Numbness or ↓Ability to feel pain and/or temperature - usually in fingers/toes or glove/stocking distribution
> Tingling/burning sensation
> Sharp cramps/pains
> Hypersensitivity - even a bedsheet can ouch
> Muscle weakness
> Hyporeflexia
> Loss of balance/coordination
> DIABETIC FOOT
203
How might diabetic foot first present?
↓ Sensation to vibration, temp, pin-prick
Signs of vascular disease in lower leg i.e. thin skin, no hair, blue discolouration
204
How might neuropathy result in diabetic foot and amputation?
Neuropathy causes a traume
∴ Ulcer forms
If ulcer fails to heal, causes severe infection
∴ Amputation is required
205
Can you prevent diabetic foot?
If so, how?
YES !!!
Regular chiropody, daily inspection of feet
If trauma, seek early advice/Tx
206
Management foot ulcers
Swab ulcers for culture & ∴ early Abx Tx
Good local wound care/surgical debridement
Reconstructive vascular surgery if artery occlusions
207
Describe the pathophysiology of diabetic retinopathy
XS glucose in blood causes glucose uptake into lens
∴ blockage of retinal blood vessels
∴ eye tries to grow new vessels but don't develop properly
∴ will leak !
208
What are the 2 types of diabetic retinopathy?
&& QUICK! What are the differences?
1. Proliferative - forms NEW blood vessels
2. Non-proliferative - doesn't
209
What 3 big boi things happens in proliferative diabetic retinopathy?
Describe the pathophysiology behind them
1. Damaged blood vessels close off
∴ new, abnormal vessels form
∴ **leakage into vitreous humour**
2. Scar tissue forms bc of new vessels forming
Can cause **retina to detach from back of eye**
3. If new blood vessels interfere w/ normal fluid outflow, will ↑ pressure
∴ affects optic nerve
∴ **Glaucoma**
210
Describe the pathophysiology of non-proliferative diabetic retinopathy
Walls of retinal vessels weaken
∴ leakage of microaneurysms into retina
Larger vessels dilate, become irregular in diameter
Retinal nerve fibre may swell
∴ Macular oedema
211
Signs / Symptoms Diabetic Retinopathy
Spots/Floaters in vision
Blurred vision
Impaired colour vision
Dark/empty areas in vision
Vision loss (blindness)
212
What might prevent blindness in retinopathy?
Aspirin
213
Ix Diabetic Retinopathy
Fundoscopy - cotton wool spots & flare haemorrhages
(Will see if pre-proliferative)
214
What is the earliest indicator of diabetic nephropathy?
Microalbuminuria
-> Can progress to intermittent albuminuria & persistent proteinuria
(Creatinine is normal! But once this stage has been reached, Px is usually 5-10 years away from end stage renal failure)
215
What is microalbuminuria?
What does this indicate when put into context of Diabetic nephropathy?
When urine is -ve for protein but urine albumin:creatinine ratio (UCR) > 3mg/mmol
Indicates early renal risk & ↑ Vascular risk
If UCR > 3, should inhibit RAAS to protect kidneys even if BP isn't high
216
Tx Diabetic Nephropathy
Aggressive BP control
ACEi
If CI, Angiotension II antagonistis
217
Other types of Diabetes
**MODY** - Mature onset diabetes of the young (rare autosomal dominant T2DM)
**LADA** - Latent autoimmune diabetes of adults (T1DM w/ slower progression)
**1° Neonatal diabetes**
**Gestational diabetes** - pregnancy, 3rd trimester
218
What does SIADH stand for?
Syndrome of inappropriate secretion of ADH
219
Causes SIADH
Bc of disordered pituitary secretion OR ectopic production of ADH
--
> Idiopathic
> Malignancy - **SCLC**, pancreas, prostate, thymus, lymphoma
> Major surgery!
> Drugs - Opiates, chlorpropamide, carbamazepine, vincristine, SSRIs
> Lung - pneumonia, TB, abscess, asthma, CF
> Brain issues - head injury!, meningitis, tumour, stroke, haemorrhage, GB
> Metabolic - Porphyria, alcohol withdrawal
220
Signs / Symptoms SIADH
Presentation mostly bc of hyponatraemia
--
↓ GCS, confusion w/ drowsiness
Irritability
Headaches
Anorexia
Nausea
Concentrated urine
Muscle aches/cramps
If severe, seizures/loss of consciousness
221
Ix SIADH
Usually diagnosis of exclusion
Must be distinguished from hyponatraemia
--
Clinical exam - euvolaemia
U&E - hyponatraemia
Serum osmolality - low
Urine Na+ & osmolality - high
Absence of hypokalaemia, hypovolaemia, hypotension
Normal renal, adrenal & thyroid function
--
Hyponatraemia is v common in elderly
∴ hard to distinguish
So test with 1-2L of 0.9% saline
If hyponatraemia, will respond. If SIADH, will not respond
--
Any type of imaging to find cause
222
Pathophysiology of SIADH
XS ADH causes ↑ aquaporin 2 insertion
In turn, this causes :
**1.** ↑ Water retention
∴ dilution of blood plasma
∴ HYPONATRAEMIA
**2.** ↓ RAAS (↓aldosterone)
∴ ↑ secretion of Na+
The XS water is being secreted with Na+
i.e. body is removing Na+ from low Na+ concentrated blood
∴ **NORMOVOLAEMIC & HYPONATRAEMIC**
223
Tx SIADH
1. **Treat cause & restrict fluid**
Might not need further treatment after this
2. Demeclocycline
-
IF SEVERE : Loop diuretic (furosemide) +/- salts
IF CHRONIC (?) : Vasopressin receptor antagonist (vaptans) e.g. Tolvaptan
224
How dose Demeclocycline work to treat SIADH?
Inhibits vasopressin action of kidneys
essentially causes nephrogenic DI
225
Essentially, what is Diabetes insipidus?
Not enough ADH
226
Pathophysiology DI
Cranial DI - Hypothalamus doesn't produce ADH
Nephrogenic DI - Collecting duct of kidneys don't respond to ADH
227
Causes DI
**CRANIAL** or **NEPHROGENIC**
--
**CRANIAL :**
Idiopathic
Congenital - defect in ADH gene
Tumour - craniopharyngioma, mets, pit tumour (might present as DI & hypopituitarism
Head trauma
Infiltrative disease - sarcoidosis, histiocytes
Surgery
Haemorrhage
Meningoencephilitis
--
**NEPHROGENIC :**
Drugs - Lithium, demeclocycline
↓ K+
↑ Ca2+
Sickle cell disease
CKD
Inherited (MC) - ADH receptor defect
Post-obstructive uropathy
--
NB. damage to hypothalamus-neurohyphysisial tract or post. pit does NOT cause ADH deficiency bc ADH can leak
228
Signs / Symptoms DI
**Polydipsia** - uncontrollable & all-consuming!
Polyuria
Sx of hypernatraemia
229
Ix DI
**GS!! - Water Deprivation Test**
Aim : to determine whether kidneys continue to produce dilute urine even when dehydrated
1. Restrict fluid
2. Measure urine osmolarity (if low = DI)
3. Desmopressin
(If osmolarity stays same = Nephrogenic, If increases = Cranial)
--
MRI Hypothalamus
Plasma biochemistry
Urine volume - to confirm polyuria
BG, Serum K+ & Ca2+ should be measured to exclude other causes of polyuria (DM)
230
Tx DI
Cranial - desmopressin
Nephrogenic - Oral bendroflumethiazide & NSAIDs
231
Describe how bendroflumethiazide & NSAIDs helps to treat nephrogenic DI
**Bendroflumethiazide**
Causes ↑ Na+ secretion in DCT
The increased water lost causes the body to ↓GFR
∴ diuretics are required
**NSAIDs**
↑GFR by inhibiting prostaglandin synthesis
Prostaglandins inhibit ADH action
232
Complications DI
Severe hypernatraemia
(When treating, careful not to ↓ Na+ too quickly!!!)
233
Pathophysiology Graves'
TSH-R autoantibodies formed
∴ Autostimulation of thyroid gland
234
What is Hyperosmolar Hyperglycaemic State?
Life-Threatening emergency!!!!!!
Hyperglycaemia
Hyperosmolality
Usually no ketosis
235
Signs / Symptoms Hyperosmolar Hyperglycaemic State
Fatigue, lethargy, N+V
Altered level of concious
Headaches
Papilloedema
Hyperviscosity
Dehydration
Hypotension
Tachycardia
236
Ix Hyperosmolar Hyperglycaemic State
**Severe Hyperglycaemia** > 33mmol/L
**Hypotension**
**Hyperosmolality** > 320 mosmol/kg
No signif acidosis or ketosis
237
Tx Hyperosmolar Hyperglycaemic State
Fluid replacement w 0.9% saline
VTE prophylaxis (high risk of dehydration) - LMWH e.g. enoxaparin
Insulin - *only* if ketones/glucose don't decrease after fluid replacement
238
Comps Hyperosmolar Hyperglycaemic State
Stroke
MI
PE
Insulin-related hypoglycaemia
Tx related Hypokalaemia
239
Pathophysiology Hyperosmolar Hyperglycaemic State
↓ Insulin is enough to cause hepatic ketogenesis
BUT not enough to stop hepatic gluconeogenesis ∴ ↑glucose
Hyperglycaemia causes osmotic diuresis !! w assoc ↓Na+ and ↓K+
Severe vol depletion results in hyperviscosity of blood
240
Typical Px for Hyperosmolar Hyperglycaemic State?
Elderly with T2DM
241
Conn's Types
1º - adrenal glands produce XS aldosterone
2º - XS renin stimulates adrenal glands to produce aldosterone
242
Causes of 1º Conn's
Bilateral adrenal hyperplasia - MC
Adrenal adenoma = Conn's
243
Signs / Symptoms Conn's
Often ASx
HTN
Headaches
↓K+
Weakness, cramps, paraesthesia
Polyuria, nocturia, polydipsia!
No change in HR, glucose or skin colour
244
Ix Conn's
1. FBC/U&E/LFT
Plasma K+ might be low
**If aldosterone:renin is high = 1º**
CT/MRI - locate adrenal lesion
**GS** = Selective adrenal venous sampling
245
Tx Conn's
Aldosterone antagonist - Eplerenone, Spironolactone
Tx underlying cause - surgery
e.g. Percutaneous renal artery angioplasty - via femoral artery to Tx renal artery stenosis
246
Familial cause of phaeochromocytoma
Men 2a
247
How to avoid hypertensive crisis in surgery with phaeochromocytoma?
Give Phentolamine - alpha receptor blocker
248
Triad of DKA
1. Polydipsia
2. Polyuria
3. Weight loss
249
Where is aldosterone formed?
Zona glonerulosa in adrenal medulla
250
Hypokalaemia ECG readings
Prominent U waves
Flattened T waves
Long PR
Long QT
251
