Endocrinology Flashcards
1
Q
T1 and T2 diabetes pathophys
A
T1 = Autoimmune destruction of pancreatic islet cells cause reduced insulin
T2 = Insulin resistance and hyper secretion of insulin which fails to keep up with inc demand leading to failure of beta cells
2
Q
C-peptide in diabetes
A
low in T1
high in T2
3
Q
Assoc features of diabetes
A
Retinopathy (cotton wool spots, haemorrhage)
Neuropathy (glove stocking)
Nephropathy
Skin infection/UTI
4
Q
Pancreatic Islet cell and function
A
Alpha cells = Glucagon
Beta cells = Insulin
5
Q
Mechanism of insulin release
A
Glucose enters beta cells via GLUT2, increased ATP, this closes K+ channels to depolarise cell, opens Ca channels and cellular release of Insulin
6
Q
Role of insulin
A
Increase live and muscle uptake of glucose
Suppress: Gluconeogenesis, Lipolysis, Proteolysis, Ketogenesis
7
Q
T1DM
- Aetiology,
- Presentation,
- Complications
A
- Genetic predisposition, autoimmune process (env trigger??)
- FH of autoimmune disease (HLA DR3/4)
Polyuria, polydipsia, weight loss, lethargy, DKA (dehydration, ketones, abdominal pain) - DKA
8
Q
T2DM
- RF
- Presentation
A
- BMI over 30, low activity, PCOS, metabolic syndrome, FH, South Asian, Gestational diabetes
- Polyuria, polydipsia, lethargy, prolonged/frequent infections (e.g. thrush)
9
Q
Investigating DM
A
Urine dip, Oral Glucose tolerance test, Fasting glucose (over 7 is diagnostic)
HbA1c (over 48mmol.mol or 6.5%)
Ix for complications - urine dip (protein), fundoscopy, BP for HTN, fasting lipids (hyperlipidaemia)
10
Q
when might HbA1c not be accurate?
A
In anaemic patients, esp haemolytic anaemia
11
Q
HbA1c treatment goal
A
below 58mmol/mol of 7.5%
12
Q
Diabetic Neuropathy
A
Hyperglycaemia causes oxidative stress and destruction of myelin sheath. Glove and stocking distribution
13
Q
Diabetic Nephropathy
A
Hyperglycaemia thickens glomerular BM (sclerosis)
Narrowing efferent artery inc pressure in glomerulus.
The above cause inc gaps between podocytes (more permeable)
Proteinuria and decreased GFR occur due to kidney damage
14
Q
Diabetic Retinopathy
A
microvascular occlusion - retinal ischaemia, can see neovascularisation
Pericyte loss - diffuse haemorrhage and oedema
Microaneurysms and haemorrhages
Cotton wool spots from axonal debris build up
number of microaneurysms and quadrants involved determine severity
15
Q
CVS risks in DM
A
MI/Stroke
16
Q
Autonomic dysfunction in DM
A
Erectile dysfunction, Bladder retention, postural hypotension, tachycardia, diarrhoea
17
Q
infection in diabetes
A
due to hyperglycaemia causing reduced phagocytosis
Give pneumococcal vaccine and annual influenza
18
Q
Diabetic foot
- Incidence
- importance
- Presentation
- Mech
- Chronic features
A
- 10% diabetics
- most common cause of amputation
- Hot, swollen foot, painless punched out (neuropathic) ulcers
- loss of sensation during damage, ulcer development, bone degeneration, poor healing
- Rockerbottom sole, Charcot foot
19
Q
Diabetic eye probs presentation and treatment
A
- Painless reduction in central vision, Haemorrhage (sudden onset dark painless floater)
- optimise BP/glycaemic control/lipid control, Anti-VEGF, Intravitreal steroids (laser photocoagulation)
20
Q
Emergency referral of diabetic eye
A
Sudden loss of vision
Red eye
Retinal detachment
21
Q
Diabetes Tx
A
lifestyle and diet (6weeks) inform DVLA
- low glucose, dairy, control fats, limit sugar and lose weight.
HbA1c 3-6monthly and then 6 monthly aim for 48mmol/mol or 6.5%
single drug therapy - Metformin (unless not tolerated) - 6.5% target
dual therapy - metformin + gliptin/sulfonylurea/pioglitazone - target 7% (53mmol/mol
Triple therapy - if still not 58mmolmol/7.5% add third drug or consider insulin
if can’t give metformin then on of the above, add another if not control and then third line is insulin
22
Q
Diabetes annual review checks
A
BMI
Complications: Hypos, Hyperosmolar hypoglycaemic state, DKA
CVS assess: BP, pulses, bruits
inspect injection sites (lipodystrophy)
Foot check (neuropathy and pulses)
Urine: protein, nitrites, ketones
Eyes: acuity and ophthalmoscopy
Erectile dysfunction
Bloods: HbA1c
23
Q
Metformin
- mech
- CI
- SE
A
Increases sensitivity to insulin
CKD
GI upset: nausea and diarrhoea (20% don’t tolerate)
24
Q
Gliptin
- mech
- SE
A
Raised incretin produce more insulin when needed
GI upset, flu-like symptoms
25
Sulfonylurea
- mech
- CI
- SE
increase pancreatic insulin secretion (S for secretion and Sulfonylurea)
Pregnancy CI
Can cause Hypo (affecting insulin release), weight gain
26
Pioglitazone
- mech
- CI
- SE
increases insulin sensitivity
osteoporosis, heart failure (due to fluid retention SE)
weight gain, fluid retention, osteoporosis
27
Insulin Regimes
Once daily
- Long/intermediate acting at bedtime
- only for T2DM
Twice daily
- Pre-breakfast/evening meal
Basal-bolus
- Long/intermediate acting at bedtime with short acting to cover meals
Continuous subcut or insulin pump
- in those with v poor control
28
NICE Tx T1DM
Basal Bolus regimen
- twice daily insulin deter (long acting)
- Rapid acting insulin analogue (humalog, novorapid) before meals
29
Nice Tx T2DM
Intermediate acting insulin twice per day: Humulin N or Novolin N
30
SE of insulin Tx
Hypoglycaemia
- Sweating, confused, aggression, blurred vision
Lipodystrophy
31
Tx for a Hypo
Conscious:
- 10-20g short acting carb (glass of lucozade, glucogel)
Unconscious:
- IM Glucagon
Inform DVLA
32
What to do if Diabetic is unwell
4 hourly BG monitoring, monitor ketones
3L fluid every 24 hours
continue oral med, continue insulin with inc monitoring
Stress response = inc cortisol this increases blood sugars and decreases insulin so may need more control
seek help: glucose more than 13mmol/L, DKA signs, BG over 25 and giving more insulin.
33
DKA precipitants
- Missed insulin
- Infection (corticosteroid risk hyperglycaemia)
- Intoxication (live impairment)
- Ischaemia
- Infarction
34
Presentation of DKA
Abdominal Pain + Vomiting
Polyuria, polydipsia, dehydration
Kussmaul breathing (deep hyperventilation to correct acidosis)
Acetone breath
35
Pathophysiology DKA
- Decreased insulin
- Inc protein and fat metabolism
- Ketogenesis from lipolysis
- Acidosis(ketones), hyperglycaemia, Osmotic diuresis, Hypokalaemia (Due to acidosis)
- Dehydration, Acidosis, Coma, Death
36
ECG Hypokalaemia
PRSTTU
PR prolonged
ST depression
T flat/inverted
Prominent U wave after T
37
DKA investigation findings
Plasma glucose: over 11
Plasma Ketones: over 3mmol/l
ABG: pH over 7.3
Urine dip: Ketones and glucose high
38
DKA management
- Fluids
- Hyperglycaemia
- What to watch out for
- Acidaemia
- IV NaCl: 1L in 1st hour, 1L in 2nd hour, 1L in following 2hrs and 1L every 4 hours. When BG below 180mg/mol use 5-10% dextrose
- IV Insulin
- Hypokalaemia (insulin causes K+ to enter cells)
- IV Bicarbonate
39
Hyperosmolar hyperglycaemic state
- Who gets
- What can be seen on blood tests
T2DM (no DKA as enough insulin to suppress ketogenesis)
| Very high blood glucose (over 40) V. high serum osmolality.
over 320mosmol/kg- normal is 285-290
Hypovolaemia
40
What is osmolality
Osmolarity
concentration expressed as number of solute particles per Kg fluid
Osmolarity is per L fluid
41
Precipitants to Hyperosmolar hyperglycaemic state
Infection, MI, Dehydration, Thiazides and loop diuretics, poor glucose control.
42
Hyperosmolar hyperglycaemic state Pathogenesis
Hyperglycaemia, osmotic diuresis, hyperosmolarity gives fluid shift into intravascular compartment = severe dehydration
No ketogenesis as some residual pancreatic function surpasses ketogenesis
43
Hyperosmolar hyperglycaemic state Presentation
Extreme dehydration and altered mental state
± seizures
± delirium
44
Investigation findings Hyperosmolar hyperglycaemic state
Urinalysis - glycosuria and sometimes ketonuria (mild)
Blood glucose - over 30
Serum osmolality - over 320mmol/L
U&E - shows AKI (high creatinine+urea)
ABG - normal
45
Hyperosmolar hyperglycaemic state Tx
Treat cause (e.g. infection, dehydration)
replace fluid and electrolytes to normalise osmolality (NaCl, positive balance of 3-6 L by 12 hours)
Insulin if glucose not falling with other medications.
46
Hyperosmolar hyperglycaemic state complications
Seizures
Cerebral oedema (if glucose drop too quick)
Pontine myelinosis
47
Pathogenesis of Cerebral Oedema in DKA and Hyperosmolar hyperglycaemic state
Sudden drop in blood glucose and decrease in osmolality
Brain traps osmotially active particles
Conc gradient means fluid moves from intravasc to brain parenchyma
48
Metabolic syndrome criteria for Dx
```
Truncal obesity or BMI over 30
BP systolic over 130 or prev HTN
High triglycerides
Reduced HDL
fasting glucose over 6.1mmol/l (prediabetes)
```
49
Metabolic Syndrome complications
Atherosclerosis (CVD), Diabetes, PCOS, NAFLD
50
Cause of metabolic syndrome
Obesity epidemic - Overnutrition, atherogenic diet, sedentary lifestyle
51
BMI Levels
```
under 18.5 = under
18.5 - 24.9 = Optimal
25-29.9 = Over
30-34.9 = Obese I
35-39.9 = Obese II
Over 40 = Obese III
```
52
Medication causes of Obesity
```
Glitazone, Sulfonylurea
Anticonvulsants
Antidepressants: tricyclics, mirtazapine
Lithium
Progesterone only contraception
BB
Corticosteroids
```
53
Conditions that cause obesity
```
PCOS
Hypothyroidism
Cushing's
Hypogonadism
Prader-Willi
```
54
When to consider surgery in Obesity
```
Obese II (BMI 35-39.9)
Always try lifestyle (diet & exercise) and drug (e.g. Orlistat)
```
55
How does Orlistat work
Inhibits lipase
56
Gynaecomastia pathophysiology
balance between oestrogen (stimulate) and androgens (inhibit).
Conditions raising oestrogen, dropping testosterone or increase in conversation androgen to oestrogen (aromatisation by inc fats)
57
Physiological causes of gynaecomastia
in early teenage assoc with delayed testosterone.
Unilateral and tender
Also seen with ageing (dec in testosterone)
58
Pathological causes gynaecomastia
Low testosterone:
- Androgen resistance, Klinefeltners, Viral Orchitis (mumps), renal disease
High Oestrogen
- HCG secreting neoplasms (seminoma), ectopic BCG (lung, renal, adrenal tumours), CAH, Liver disease, Obesity, Hyperthyroid, Prolactinoma
59
Medications causing Gynaecomastia
DISCO:
- Digoxin
- Isoniazid
- Spironalactone
- Cimetide
- Oestrogen
```
Anabolic steroids
(inc androgens = inc conversion to oestrogen)
```
Prolactin - antipsychotics, TCA, Metoclopramide
60
LH and testosterone in gynaecomastia
LH high Testosterone low = testicular failure
LH low Testosterone low = inc oestrogen
LH high Testo high = Androgen resistance or neoplasm
61
Investigations in Gynaecomastia
Hormones: Estradiol, testosterone, Prolactin, bHCG, AFP, LH,
LFT, TFT
Imaging - USS/mammography or needle core biopsy if suspicious.
62
Thyroid-Hypothalamic-Pituitary axis
TRH from Hypothalamus to Pituitary
TSH from pituitary to Thyroid follicular cella
Thyroid secrets Active T3 and also T4
(peripheral conversion to T3 also occurs). T3 both free (active) and also bound to TBG/Albumin.
Negative feedback of T3/4 to Pituitary and Hypothalamus
63
How is Thyroid hormone excreted
Liver conjugation/Excretion
Renal excretion
64
Which is active form of thyroxine.
Function of Thyroid hormones
T3 (Tri-iodothyronine)
Must be unbound (free
Control metabolic rate of tissues
65
Target for Thyroxine
THRa and THRb
66
What is
TRH
TSH
Thyrotropin releasing hormone
Thyroid stimulating hormone
67
Where does T4 get converted to T3
80% Liver
| 20% Thyroid
68
Cause of goitre:
- Diffuse goitre
- Nodular goitre
- Painful goitre
- Physiological, Graves, Hashimoto's (autoimmune)
- Mulitnodular goitre, Adenoma, adenocarcinoma
- De Quervain's (sub-acute hypothyroiditis)
69
Hypothyroidism
| - Most common cause and what other assoc diseases
Hashimoto's Thyroiditis
Other autoimmune conditions: T1DM, Addisons, pernicious anaemia
70
Causes of Hypothyroidism
```
Atrophic hypothyroidism
Subacute hypothyroidism (De Quervain's - painful and raised ESR)
Riedels
Post partum
Iatrogenic - surgery and radio iodine Tx
```
71
Secondary causes of hypothyroidism
```
TSH deficiency, Hypopituitary disorders (Neoplasm, Radiotherapy, infection)
Hypothalamic disorders (Neoplasm, Trauma)
```
72
Hypothyroidism Signs
```
Bradycardia
Delayed tendon reflex
Ataxia (cerebellar)
Dry thin skin/hair
Puffy face/hands/feet (myxoedema)
Obesity
Carpal tunnel
Megacolon
```
73
Hypothyroidism symptoms
```
Tired & Lethargic
Cold intolerance
Slow intellectually (poor memory, difficult concentrate)
Constipation
Weight gain + low appetite
Deep/Hoarse voice
Monorrhagia
Reduced libido
Depression
```
74
Acute presentation of severe Hypothyroid & Tx
Features of hypothyroidism + seizures + decreased consciousness + hypoventilation
Tx- IV levothyroxine + IV hydrocortisones + Resp support
75
Hashimotos:
- Goitre
- Autoimmune Ab's
Painless, diffuse, varying size, rubbery, irregular surface
Anti-thyroid peroxidase
Antithyroglobulin (90-95%)
76
De Quervains
- pathophysiology
- Tx
viral infection then local symptoms of pain and nodularity
Initially thyrotoxic and then hypothyroid
Aspirin and prednisolone can be given although most cases self resolving
77
Investigation of hypothyroidism
- TFTs (TSH, T3 and T4) shows primary or secondary
- Antibodies: antiTPO, anti Tg
if worry neoplasm - USS
is secondary cause - MRI pituitary and check visual fields
78
Diagnosis of primary or secondary thyroid disease
high TSH and low T3/4 = primary
low TSH, low T3/4 = secondary
79
Clinical management of hypothyroidism
- What
- Follow up
- Risks of medication
T4 - Levothyroxine for life
check TFT every 3-4 weeks. Annual TFT once stable
Osteoporosis, Arrhythmia
for subacute treat if TSH below 10
80
Hyperthyroidism Causes
Grave's disease (75%)
Toxic mutinodular goitre (high iodine diet or amiodarone)
Toxic nodule/ adenoma
Subacute/De Quervain's (transient toxicosis, pain, raised ESR)
Drugs: amiodarone, exogenous thyroids hormone treatment excess
Ectopic thyroid tissue: metastatic follicular carcinoma, ovarian teratoma
Secondary - pituitary adenoma
81
Hyperthyroidism symptoms
```
weight loss, inc appetite
irritable and weak
sweating
tremor
Diarrhoea
Anxiety and psychosis
Heat intolerance
loss of libido
Oligomenorrhea
```
82
Hyperthyroidism signs
```
Sweaty/Warm palms
Fine tremor
Tachycardia ± AF
Hair thinning
Goitre
Proximal myopathy (wasting and weakness)
Gynaecomastia
Brisk reflexes
Pruritus
Pretibial myxoedema
Eye disease (lid lag, ophthalmoplegia, exophthalmos)
```
83
Graves disease
- Pathology
- AAb
Anti-TSH receptor Abs
(may also react with orbital antigens to give thyroid eye disease)
Hyperplasia of follicular cells = diffuse goitre
anti TSHR (99%), anti-thyroglobulin, anti-TPO
84
Thyroid eye disease
lid lag, lid retraction, ophthalmoplegia, exophthalmos, gritty eyes, diplopia, loss of colour vision, conjunctival oedema, papilloedema.
85
Investigations hyperthyroidism
TFT: TSH low, T3/4 high in primary
Imaging: USS to look for cancer/adenoma
Radioisotope uptake scale hot = overactivity. (if not hot then could be De Quervain's)
ESR raised in De Quervain's
Of suspect secondary (pituitary adenoma) then MRI head + check visual fields
86
Hyperthyroidism management
Betablockers (propranolol)
Lubricating eye drops
Antithyroid drugs
- Carbimazole start 10-20mg daily, monthly titration based on TFTs (enzyme inhibitor of T3/4 production)
- Propylthiouracil - causes liver failure (reserve for pregnancy or thyroid storm)
Warning - anti-thyroid drugs can cause myelosuppression and agranulocytosis/neutropaenic sepsis.
In those who relapse after 18mnths Carbimazole, Radioactive iodine (note - worsens eye disease)
Surgery = Subtotal thyroidectomy (risk or hypothyroidism and damage recurrent laryngeal nerve.
87
Thyroid storm:
- Who gets it
- Presentation
- Precipitation
- Investigations
- Tx
- Graves or getting levothyroxine
- Hyperpyrexia (over 41), HR over 140, hypotension, GI (nausea, jaundice, vomiting, diarrhoea, abdominal pain), Neuro (confusion, delirium)
- Infection
- Sepsis screen, TFTm ECG, CXR, ABG
Treatment:
- Resus: O2 fluids
- Antithyroid: oral carbimazole/propylthiouracil
- IV propanolol
- Lugols solution (aqueous iodine) after 4 hours.
- Keep cool with tepid sponging.
88
Thyroid cancer:
- Types
- Presentation
- Management
- 70% papillary carcinoma (good prognosis)
- 20% follicular carcinoma
- 5% medullary (parafollicular C cells which secrete calcitonin
- Nodules and effects of secretions
- Total thyroidectomy, radioiodine to kill residual cells
89
When is PTH secreted
Response to low Calcium
90
PTH actions
Bone: inc osteoclast activity (release Ca and PO4)
Kidney: 25-OH-D to 1,25 OH2-D increases calcium absorption in the gut and from urine, Inc potassium excretion
91
Effect of hyperparathyroid
increased Ca and decreased PO4
92
Calcitonin
- From what cells
- Effect
- Parafollicular C cells in the thyroid
| - Reduce osteoclasts activity
93
Reasons for PTH secretion
- primary: solitary adenoma (85%) - assoc with MEN1/2 and postmenopausal women
- secondary: result of low calcium. gives PT gland hyperplasia
almost always assoc with kidney/liver or bowel disease
94
Presentation and signs of high PTH
80% asymptomatic and diagnosis with hyper Ca found
Excess Ca absorption from bone = Osteopenia, osteoporosis and in extreme osteitis fibrous cystica (pepper pot skull, subperiosteal resorption phalanges
Excess renal Ca excretion: calculi
95
Symptoms of hypercalcaemia
Bones, stones, abdominal moans, psychic groans
96
Parathyroid investigations
Most freq cause of hypercalcaemia
U&E
measure PTH, Ca, PO4, hydroxyvitamin D (25-OH-D)
X-ray: skill and hands
Annual DEXA for those with hyperparathyroid
97
Complications of hyperparathyroidism
Osteoporosis and peptic ulcers
98
Management of hyperparathyroidism
Correct Vitamin D deficiency - suppresses PTH, inc calcium from GI and urine
Avoid drug precipitants (thiazides)
Curative - Surgery (if developed kidney stone or if symptomatic) either of single adenoma or subtotal
- complications of common laryngeal damage, hypocalcaemia
Medical - Bisphosphonates (alendronate)
99
Drug causes of hypercalcaemia
Thiazide, Lithium
100
What disease is assoc with hypoparathyroid
DiGeorge - disease with abnormal tissue formation during development
- immunodeficient
- congenital heart disease
- hypocalcaemia (Hypo PTH)
101
Hypercalcaemia
- Normal range
- how does it circulate
- most common cause of hypercalcaemia
- important causes
- 2.25-2.5mmol/L
- bound (albumin) and unbound ( this is physiologically important form)
- hyper PTH in post-menopausal women
- malignancy (ectopic PTH in Squamous lung cancer, breast Ca, osteolytic activity of emts)
- Granulomatous: TB, Sarcoid
- Endocrine: thyrotoxicosis, Phaeo, Addison's
- Drugs Thiazide, Lithium
102
Hypercalcemia symptoms
Abdo groans L pain, nausea and vomiting, acute pancreatitis
Thrones: polyuria, polydipsia
Stones: renal colic
Psychic Moans: depression, dementia, confusion
Muscle and CVS: weakness, proximal myopathy, fatigue, short QT
103
Treating hypercalcemia
0.9% saline to inc urinary excretion
Loop diuretic for fluid overload (furosemide)
IV bisphosphonates
104
Hypocalcaemia symptoms
CATS - emergency hypocalcaemia symptoms
Convulsions, Arrhythmias (long QT), Tetany, Stridor/Spasms
Parasthesia: fingers, toes, mouth
105
Hypocalcaemia Tx
Give calcium , vit D
If acute presentation: CATS
give calcium gluconate IV infusion
correct hypomagnesia
106
What other electrolyte abnormality may be a reason for hypocalcaemia
Hypomagnesia
must be corrected as part of Tx otherwise calcium levels will not respond
107
What is produced by anterior pituitary (Adenohypophysis)
GH - stim liver to prod IGF-1, also counteracts insulin
Prolactin - mammary gland growth. inhibited by dopamine
FSH - stimulates Sex steroid release
LH - stimulates Sex steroid release
ACTH - Adenocorticotropic hormone stimulates adrenal cortex to release glucocorticoids and androgens
TSH - Thyroid stim
108
What is produced by posterior pituitary (Neurohypophysis)
Vasopressin: ADH
Oxytocin: uterine contractions
109
Pituitary Tumours: effects
- Excessice hormone
- Local effects: compress surrounding
- inadequate production by rest of gland
110
Most common pituitary tumour
Benign non-functioning adenoma.
111
Pituitary tumours:
- Eosinophilic
- Basophilic
- GH/Prolactin
| - ACTH: Presents as Cushings
112
Mass effect of pituitary tumours
Optic chasm - bitemporal hemianopia (more affecting upper quadrants)
Occular nerve palsy - squint
Headache - retroorbital
113
Hypopituitarism
Order of functional loss
Presentation
order: LH, GH, TSH, ACTH, FSH
Presentation: infertility/oligomenorrhea, erectile dysfunction, loss of libido
114
Differential for pituitary tumour
Caniopharyhgioma
- benign and cystic growth from Rathke's pouch
- Headache, visual field defect (bottom half vision as it grows from above) hypopituitarism
115
Surgical route to pituitary
Transsphenoidal
116
Drug therapy for pituitary lesions
Prolactinoma: Bromocriptine
GH: somatostatin analogue (somatostatin = GH limiting hormone)
117
Complication of pituitary lesions
Pituitary apoplexy: this is worrying
Rapid enlargement due to bleed int tumour/infarction
Mass effect, CV collapse, acute hypopituitarism
118
Prolactinaemia Cause
Commonly hormone secreting adenoma, physiological in pregnancy, can be caused by drugs such as antipsychotics which block dopamine receptors, seen following head injury
MEN1 - Proactinoma
Hypothyroidism
- raises TSH, raises Prolactin
119
Prolactinaemia presentation
Women
Men
Children
- Oligomenorrhoea, amenorrhoea, galactorrhea (milky nipple discharge), infertility, hirtuism
- reduced libido, erectile dysfunction, may get milky discharge
- Growth failure, delayed puberty
If due to prolactinoma then mass effects of lesion (headache/upper temporal quadrantanopia) may be seen
120
Prolactinaemia Investigations
Prolactin levees, TFTs, exclude pregnancy, MRI pituitary
121
Symptoms of Pituitary apoplexy
Sudden onset headache
| Sudden onset visual disturbance
122
Treating prolactinaemia
Mass effect if prolactinoma = transsphenoidal surgery
Effects: Dopamine agonist e.g. Bromocriptine
123
Long term effects of hyperprolactinaemia
```
Hypogonadism
Osteoporosis
Reduced fertility
Erectile dysfunction
Apoplexy
```
124
Acromegaly hormone
Growth Hormone (GHRH from hypothalamus)
125
Negative feedback for GH
GH to hypothalamus des GHRH
Dietary Carbs
Adrenal output
126
End product of GH
Liver: IGF-1 (insulin like GF)
Adipose tissue: FFA (free fatty acids)
127
Acromegaly pathophys
Micro/Macrodenoma (depends on if causes visual disturb etc)
excess GH and IGF1 before closure of epiphyseal plates = gigantism. inc brow/hands after plate closure
128
Acromegaly associated diseases
Prolactinoma
MEN1
McCune-Albright
Complications of acromegaly:
T2DM
Colon cancer
129
Presentation of acromegaly
enlargement of hands/feet, frontal bossing, thick nose, large jaw, macroglossia
skin: thick, oily, sweating
nerve compression: bilateral carpal tunnel
Cardio/hepatomegaly
130
Investigating acromegaly
serum IGF-1 raised with high GH, OGTT glucose inhibition of GH lost in acromeg
MRI pituitary, visual field testing
131
Normal GH secretion
Pulsatile in peaks, inhibited by glucose this inhibition is lost in acromegaly --> OGTT therefore used to test
132
Acromegaly management
1st line - Transsphenoidal surgery
2nd line - somatostatin analogies
133
Acromegaly complications
Carpal tunnel
impaired glucose tolerance and diabetes (insulin resistance due to GH excess)
HTN
LVH - ECG to monitor for arrhythmias
Risk colon cancer
134
Adrenal axis
ACTH stimulates adrenal cortex
135
Layers of adrenal cortex and secretions
GFR - deeper you go, sweeter it gets
Zona Glomerulosa - Mineralocorticoids (aldosterone)
Zona Fasciculata - Glucocorticoids (cortisol)
Zona Reticularis - Androgens (DHEA)
136
Effects of cortisol
RIDGE suppression
- Reproduction
- Immunity
- Digestion
- Growth
- Mobilises Energy: increases sugar
137
Cortisol cycle
Diurnal variation (highest in morning)
138
Cushing's syndrome
| - Pathophysiology
loss of negative feedback for cortisol (prolonged exposure to exogenous or endogenous glucocorticoids)
ACTH dependant disease - inc ACTH secretion from pituitary
139
Causes of high ACTH
- ACTH dependant: disease due to inc ACTH secretion/ectopic ACTH secreting tumours (e.g. lung Ca)
- ACTH independant: due to adrenal adenoma/carcinoma/excessive glucocorticoids
140
Cushings presentation
```
Truncal obesity
Buffalo hump
Moon face
Proximal muscle wasting
Diabetes
Hypertension
Osteoporosis
Infection prone/poor healing
mood change (depression, lethargy, irritable, psychosis)
```
skin: atrophy, hirtuism, acne
if adenoma: headache, visual disturbance
141
Cushings investigations
1st line = over night dexamethasone suppression test. If cortisol not suppressed on morning testing then +ve
serum glucose: elevated (blocked effect of insulin)
Plasma ACTH (if high distinguish pituitary, from ectopic e.g. SCLC, carcinoid) IV contrast CT
142
Cushings Tx
Transphenoidal pituitary adenomectomy, if this fails the radiation of pituitary
143
Complications of Cushings
Metabolic syndrome: HTN, T2DM
Impaired immunity
Osteoporosis
144
Pathophysiology of Addison's
Autoimmune destruction of adrenal cortex and reduction of adrenal steroid hormone output (cortisol, aldosterone)
145
Types of Adrenal insufficiency
Primary - inability of adrenal glands to produce steroid (Addison's)
Secondary - inadequate pituitary stimulation
146
Causes of Adrenal insufficiency
Addisons
Surgical
CAH - 21-hydroxylase deficiency
Exogenous steroids (chronic steroids suppress axis)
147
Antibodies seen in Addison's
Anti-21 hydroxylase in 85% of cases (enzyme involved in converting Cholesterol to Aldosterone and Cortisol)
148
Why is Cortisol and Aldosterone more affected than DHEA in Addisons
As Anti-21 hydroxylase AAb affects conversion of cholesterol to Cortisol and Aldosterone not DHEA
149
Addisons Presentation
Chronic: Thin, Tired, Tearful and Tumbling
- fatigue, weakness
- GI: anorexia, WL, vomiting
- Craving salty food
- Muscle cramps
- Faintness due to hypotension
- confusion, personality change
150
Signs of Addisons
Pigmented palmar crease/buccal mucosa,
| hypotension, low sodium/high potassium (low aldosterone)
151
Investigations Addisons
Blood levels of:
- sodium: low
- potassium: high
- glucose: low (low cortisol)
- cortisol low
- ACTH (high in primary/Addisons, low in secondary/hypopituitary)
Short synacthen test
- take cortisol, give synacthen IM
- retake cortisol in 30 min, a rise will exclude Addisons
CT adrenals
152
Difference in Addisons and CAH 21-hydroxylase levels
in Addison's there is autoimmune destruction ( anti-21-hyroxylase) in CAH there is deficiency
153
Typical electrolytes in Addisons
Hyponatraemia
Hyperkalaemia
Hypoglycaemia
Metabolic acidosis (due to hyperkalaemia)
154
Management of Addison's
Glucocorticoid: hydrocortisone (3Xday) - increase if ill
Mineralocorticoid: fludrocortisone: 50-300mcg/day to correct postural hypotension and electrolyte imbalance.
Educate: importance of not missing steroids
155
SE of too many corticosteroids
- skin thinning
- osteoporosis
- weight gain/obesity
- raised BP
156
Addisonian crisis
- Def
- Precipitation
- Pres + complication
Acute deficiency of glucocorticoids and mineralocorticoids
major/minor infection, commonly due to com/diarrhoea. Injury, surgery, pregame's also
malaise, fatigue, vomiting, muscle cramps, confusion
can progress to dehydration hypotension and hypovolaemic shock
157
Addisonian crisis
- Investigation
- Management
Bloods:
- low sodium, high K+, raised creatinine, hypoglycaemia
- low cortisol, high ACTH
Management:
- IV/IM hydrocortisone(not at high dose ALSO has a mineralocorticoid effect)
- Rehydration w fluids
- Glucose
- Tx underlying infection/cause
- ECG and reg U&E
158
Whats is Conn's
Primary hyperaldosteronism (independant of RAAS due to adrenal adenoma)
- Water retention
- Hypokalaemia
- Hypernatraemia
159
Action of Aldosterone
Insertion of ENaC (Sodium ion channel) in the luminal side (i.e. side of collecting duct) causing inc in sodium
160
Causes for high Aldosterone
Conn's (Adrenal adenoma 80%, bilateral hyperplasia 20%)
Secondary due to high RAAS (e.g. due to decreased renal perfusion following renal artery stenosis --> atherosclerosis)
161
Conn's Presentation
Oedema (salt and water retention)
Hypertension
Hypokalaemia (weak, cramps, parasthesia)
Metabolic alkalosis (due to low K+, K+ swapped for H+ in serum&kidney)
162
Conns Investigations
U&E high
BP high
Aldosterone:Renin ratio high (if Renin also high then consider diuretics, renal artery stenosis)
CT/MRI for adrenal adenoma
163
Conns management
Medical management prior to surgery
- Spironolactone (aldosterone antagonist)
Surgical - laparoscopic adrenalectomy (for unilateral disease)
Bilateral adrenal hyperplasia - Spironolactone
164
Spironolactone SE
Block Testosterone
- Gynaecomastia
- Erectile dysfunction
- Mestrual problems
165
Conn's complications
HTN may persist
166
Hyperkalaemia Causes
Renal: AKI, CKD, Mineralocorticoid deficiency (Addison's)
Medicines: interfere with excretion (Spironolactone, Amiloride), interfere with RAAS (ACEi, ARB, NSAID, heparin --> block of RAAS blocks Aldosterone)
Inc circulation: Tissue damage (burns, rhabdo, trauma), shift intracell to extra cell (acidosis e.g. DKA, medications: Digoxin tox, beta blockers - remember salbutamol used to push into cell)
167
Hyperkalaemia presentation
Weakness, fatigue, flaccid paralysis, depressed tendon reflexes
Palpitations, chest pain
168
Investigating hyperkalaemia
```
U&E
ABG - check acidosis
Check medications (e.g. Dogixin toxicity)
```
ECG: P loss, PR prolong, QRS wide, Peak T
PPRQRST
169
Treatment for hyperkalaemia
ABCDE + 12 lead ECG
If ECG changes:
Reduce Potassium: stop supplemental K+ and any drugs causing
Protect cardiac membrane - IV calcium gluconate (repeat every 10 min if no improv)
Shift K+ into cells - insulin infusion with glucose with nebuliser salbutamol
- Recheck U&E at 2 hours
Remove K+ from body - Calcium resonium + Lactulose (GI removal)
- Haemodialysis
170
Hypokalaemia Causes
Mostly due to diuretic consumption or GI fluid loss (laxative abuse, chronic diarrhoea, persistent vomiting)
Hyperaldosteronism/high RAAS
Transcellular shift - alkalosis, insulin & glucose
171
Hypokalaemia presentation
Weakness, muscle pain, constipation
Serious: neuromuscular problems, ascending paralysis and weakness, tetany
172
Hypokalaemia ECG
Long PR, ST depression, flat T, U
173
Investigations for hypokalaemia
U&E, bicarb, glucose,
Serum Mg - this is important accompaniment with low K+ and must be corrected to allow K+ correction
ECG
174
Tx Hypokalaemia
K+ replacement (always slow IV, too fast can cause fatal arrhythmia)
Cardiac monitoring & 1-3 hourly bloods
175
Phaeochromocytoma definition
Catecholamine producing adrenal tumour in adrenal medulla
adrenaline secreted autonomously from SNS
176
Phaeochromocytoma 10% rule
10% are bilateral / malignant / extra-adrenal / familial (MEN2)
177
Phaeo familial syndromes
MEN (bilateral)
Neurofibromatosis
Von-Hippel Lindau
178
Phaeochromocytoma Classic Quartet of symptoms
1) Headache
2) Sweating
3) Palpitations
4) Tremor
Other: sense of doom, anxiety
179
Phaeochromocytoma examination findings
Hypertension
Tremor
Flushing
Tachycardia
180
Phaeochromocytoma Investigations
24 hour urine catecholamines
VMA / Metanephrine (metabolites of epinephrine raised in serum with phase)
Abdominal CT/MRI to visual adrenal mass
Genetic testing: VHL. MEN2
181
Phaeochromocytoma Tx
Surgery is definitive
Pre surgery alpha blocker
Monitor 24 hour catecholamines and VMA 2 weeks post op
182
Pheao complications and tx
Hypertensive crisis = hypertension with multiple organ failure
Phentolamine - alpha blocker
IV Nitroprusside - powerful vasodilator
183
Adrenergic A1 blockade
action on smooth muscle in blood vessels = reduce BP
relaxes smooth muscle of bladder neck to inc peeing
184
Adrenergic A2 blockade
Stimulates insulin release
185
Adrenergic B1 blockade
Decrease HR + CO
| Decreased Renin
186
Adrenergic B2 blockade
Bronchoconstriction
187
Carcinoid syndrome cause
Tumour of enterochromaffin cell
188
Carcinoid syndrome presentation
Flushing and diarrhoea
Wheeze, palpitations, telangiectasia, abdo pain
189
Carcinoid syndrome what released?
What is detectable in urine
Serotonin and other vasoactive peptides
5HIAA detected in urine
190
Location of carcinoid tumours
30% gut
| 5% Bronchail
191
Genetic association carcinoid
MEN 1
192
Carcinoid syndrome investigations and findings
Urinary 5-HR/5-HIAA raised
Serum Chromogranin A/B raised
CT chest abdo pelvis (find tumour and check for liver mets)
193
Carcinoid syndrome Tx
Surgical resection and preoperative ocreotide infusion (prevent carcinoid crisis)
194
Carcinoid crisis, precipitating and Tx
Flushing, Tachy, hypertension, diarrhoea
Can lead to altered mental state, coma and death
Precip by stress, anaesthetic, chemo
Ocreotide (somatostatin analogue inhibits release of serotonin and gastric vasoactive mediators)
195
MEN:
- Inheritance
- Cancers
Autosomal dominant
Parathyroid, pituitary, Phaeo, pancreas, Thyroid etc
196
Types of Diabetes insipidus
Nephrogenic and cranial
197
What is Diabetes insipidus
Excretion of large amounts of dilute urine
| due to hyposecretio/resistance to ADH (Vasopressin)
198
ADH synthesis and excretion
Synthesised in the hypothalamus and transported to posterior pituitary
excreted in response to dehydration
199
Mechanism of ADH
Inserts Aquaporin 2 to luminary's membrane of Distal convoluted tubule and collecting duct
200
Diabetes insipidus causes (Cranial)
Acquired: tumours (e.g. craaniopharygioma), surgery, head injury, Granulomatous tissue (Sarcoid, TB, GPA), infection (meningitis, encephalitis)
Inherited: autosomal dominant vasopressin gene
201
Diabetes insipidus causes (nephrogenic)
Hypokalaemia, CKD, Lithium, hypercalcaemia
202
Diabetes insipidus presentation
Polyuria (over 3L 24hr) polydipsia and chronic thirst
Nocturia
Symptoms of hyponatraemia - lethargy, weakness, confusion
Distended bladder
203
Diabetes insipidus Investigations
Urine Osmolality less than 300
Serum osmolality normal
MRI pituitary/hypothalamus
204
Treatment:
Cranial
Nephrogenic
- Desmopressin replacement (overdose = hyponatraemia)
- stop causative drug/underlying cause, drink in response to thirst
- inc sodium with thiazide + NSAID
205
SIADH
Hypotonic hyponatraemia with concentrated urine
206
SIADH pathology
impaired water excretion due to high ADH secretion
207
Aetiology of SIADH
Pulmonary: pneumonia, lung cancer (small cell)
CNS: infection, trauma, MS, haemorrhage, malignancy
Malignancy: lung, GI, GU, Lymphoma
Drugs: SSRIs, NSAIDs, chemo
208
Normal AVP ADH response
ADH is released following decrease in osmolality by 1%
209
SIADH presentation
Euvolaemic, nausea, confusion, irritability vomiting.
210
SIADH investigations
Serum osmolality - low (below 280)
Hyponatraemia (dilutional)
Urine osmolality higher than plasma and high urine Na
Normal renal and adrenal function
211
SIADH management
IV hypertonic saline
Treat cause
Furosemide if risk fluid overload
in chronic/severe: tolvaptan (vasopressin receptor antagonist)
212
Sodium and Cerebral oedema
Acute/chronic hyponatraemia: Low serum osmolality means water moves into brain where higher Na/K/Cl
Rapid correction of dehydration:rapid movement of water our of brain = osmotic demyelination.
213
Serotonin syndrome Features and Tx
```
Altered mental state
Hypertension
Hyperthermia
Muscle rigidity
Tachycardia
```
Give Benzodiazepines 1st line
