1
Q
hyperthyroidism definition
A
over-production of the thyroid hormones, triiodothyronine (T3) and thyroxine (T4), by the thyroid gland
2
Q
thyrotoxicosis definition
A
refers to effects of an abnormal and excessive quantity of thyroid hormones in the body
3
Q
primary hyperthyroidism
A
due to thyroid pathology
thyroid is behaving abnormally and producing excessive thyroid hormone
4
Q
secondary hyperthyroidism
A
- pathology in the hypothalamus or pituitary
- pituitary gland produces too much thyroid-stimulating hormone, stimulating the thyroid gland to produce excessive thyroid hormones.
5
Q
subclinical hyperthyroidism
A
- thyroid hormones (T3 and T4) are normal and thyroid-stimulating hormone (TSH) is suppressed (low)
6
Q
what is grave’s disease?
A
- an autoimmune condition where TSH receptor antibodies cause primary hyperthyroidism
- These TSH receptor antibodies stimulate TSH receptors on the thyroid
- most common cause of hyperthyroidism
7
Q
what is Toxic multinodular goitre?
A
- a condition where nodules develop on the thyroid gland, which are unregulated by the thyroid axis and continuously produce excessive thyroid hormones
- It is most common in patients over 50 years.
8
Q
which hormones are released by anterior pituitary
A
FLAT PEG
- FSH
- LH
- Adrenocorticotropic hormone (ACTH)
- Thyroid-stimulating hormone (TSH)
- Prolactin
- Growth hormone (GH)
9
Q
briefly outline the thyroid axis?
A
- hypothalamus releases thyrotropin-releasing hormone (TRH)
- TRH stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH)
- TSH stimulates the thyroid gland to release triiodothyronine (T3) and thyroxine (T4)
NB hypothalamus and anterior pituitary respond to T3 and T4 by suppressing the release of TRH and TSH = negative feedback
10
Q
which hormones are release by posterior pituitary?
A
Oxytocin
Antidiuretic hormone (ADH)
11
Q
briefly summarise the growth hormone axis
A
- hypothalamus produces growth hormone-releasing hormone (GHRH)
- GHRH stimulates the anterior pituitary to release growth hormone (GH)
- Growth hormone stimulates the release of insulin-like growth factor 1 (IGF-1) from the liver
12
Q
what hormone inhibits growth hormone release from anterior pituitary?
A
somatostatin
13
Q
what does insulin-like growth factor do?
A
- stimulates fat breakdown
- releases glucose from liver
- cell division
- protein synthesis
- increased bone density
14
Q
causes of hyperthyroidism?
A
G – Graves’ disease
I – Inflammation (thyroiditis)
S – Solitary toxic thyroid nodule - usually benign adenoma
T – Toxic multinodular goitre
15
Q
causes of thyroiditis (gland inflammation that causes hyperthyroid then hypothyroid) ?
A
- DeQuervain’s - transient inflammation of thyroid after viral infection
- Hashimoto’s
- Post-partum
- Drug-induced - amiodarone, iodine, lithium
16
Q
Hyperthyroidism Px
A
Anxiety and irritability
Sweating and heat intolerance
Tachycardia
Weight loss
Fatigue
Insomnia
Frequent loose stools
Sexual dysfunction
Brisk reflexes on examination
17
Q
Graves specific Px ?
A
Diffuse goitre (without nodules)
Graves’ eye disease, including exophthalmos (eye bulging)
Pretibial myxoedema
Thyroid acropachy (hand swelling and finger clubbing)
18
Q
Hyperthyroidism Ix
A
- TFTs - high T3/4, TSH low (high in 2ndary)
- Thyroid ABs - TSHR-Ab, TPO-Ab, TgAb
- CRP / ESR - thyroiditis
- baseline FBC, U/E
- US thyroid - if lump
- thyroid isotope scan
19
Q
Hyperthyroidism Mx
A
1st line = carbimazole (start high, titrate down, block and replace by adding lego)
2nd line = propylthiouracil
- radioactive iodine
- subtotal / total thyroidectomy
beta blockers can be used for symptom control
20
Q
possible side effects of carbimazole?
A
risk of:
- neutropenia
- agranulocytosis
- congenital malformations
21
Q
What is a thyrotoxic crisis (aka thyroid storm) and how do you manage it?
A
- rapid T4 increase / release
- eg stress, infection, surgery, stopping anti-thyroid drugs
Px
- high temp, tachy, restless, delirium, coma, death
Mx
- IV fluids, corticosteroids, BBs, carbimazole / propylthiouracil
- potassium iodide
22
Q
what is hypothyroidism? define primary and secondary?
A
Low TH - T3/4
Primary - thyroid gland disease - T3/4 low, TSH high
Secondary - disease of hypothalamus / pituitary - T3/4 low, TSH low
23
Q
Causes of primary hypothyroidism
A
Primary:
1. Hashimoto’s - autoimmune inflammation
2. iodine deficiency
3. hyperthyroidism Tx
4. lithium
24
Q
Causes of secondary hypothyroidism
A
Secondary:
1. Tumours (e.g., pituitary adenomas)
2. Surgery to the pituitary
3. Radiotherapy
4. Sheehan’s syndrome (where major post-partum haemorrhage causes avascular necrosis of the pituitary gland)
5. Trauma
25
what antibodies are associated with Hashimoto's?
- anti-thyroid peroxidase (anti-TPO) antibodies
- anti-thyroglobulin (anti-Tg) antibodies
26
what is Sheehan's syndrome?
major post-partum haemorrhage causes avascular necrosis of the pituitary gland leading to hypopituitarism
27
Hypothyroidism Px
Weight gain
Fatigue
Dry skin
Coarse hair and hair loss
Fluid retention (including oedema, pleural effusions and ascites)
Heavy or irregular periods
Constipation
28
Hypothyroidism Ix
- TFTs
- thyroid ABs - anti-TPO, anti-Tg
- FBC - anaemia
29
Hypothyroidism Mx
- levothyroxine
30
Myoxedema coma
- severe hypothyroidism
Px
- confusion, coma, hypothermia, hypoglycaemia, hyponatraemia
Mx
- T3/4 replacement (T3 causes arrhythmias)
- IV glucose
- hydrocortisone if needed
- fluids / supportive care
31
describe the renin-angiotensin aldosterone system
1) low bp sensed by juxtaglomerular cells in afferent arterioles of kidneys stimulating renin secretion
2) renin converts angiotensinogen (from liver) to angiotensin 1
3) angiotensin 1 converted to angiotensin 2 by ACE (released by lungs)
4) angiotensin 2 stimlates aldosterone secretion from adrenals
32
what are the actions of aldosterone?
- increase Na reabsorption
- increased K secretion from distal tubules
33
adrenal axis: mechanism of glucocorticoid release?
stress and time of day (AM) stimulate hypothalamus to secrete corticotropin-releasing hormone (CRH)
CRH stimulates anterior pituitary to secrete adrenocorticotrophic hormone (ACTH)
ACTH stimulates adrenals to secrete glucocorticoids (cortisol, cortisone, corticosterone)
34
6 actions of cortisol?
1 - stimulates metabolic rate
2 - increases alertness
3- increases sodium and water reabsorption
4 - increases blood sugar levels
5 - inhibits immune system
6 - inhibits protein synthesis / bone formation
35
What is cushing’s syndrome ?
refers to signs and symptoms of prolonged high levels of glucocorticoids in the body.
36
Cushing's disease?
refers to a pituitary adenoma secreting excessive adrenocorticotropic hormone (ACTH), which stimulates excessive cortisol release from the adrenal glands
37
Causes of cushing’s syndrome ?
C – Cushing’s disease (a pituitary adenoma releasing excessive ACTH)
A – Adrenal adenoma (an adrenal tumour secreting excess cortisol)
P – Paraneoplastic syndrome
E – Exogenous steroids (patients taking long-term corticosteroids)
38
Cushing’s features?
- Round face (known as a “moon face”)
- Central obesity
- Abdominal striae (stretch marks)
- Enlarged fat pad on the upper back (known as a “buffalo hump”)
- Proximal limb muscle wasting (with difficulty standing from a sitting position without using their arms)
- Male pattern facial hair in women (hirsutism)
- Easy bruising and poor skin healing
- Hyperpigmentation of the skin in patients with Cushing’s disease (due to high ACTH levels)
may also see: HTN, T2DM, osteoporosis, dyslipidaemia, mental health problems
39
Cushing’s Ix
1. low dose dexamethasone suppression test to confirm cushing's
2. high dose dexamethasone suppression test to determine cause of Cushing's
3. FBCs and U&Es
4. MRI/ CT TAP
40
what are the low/high dose dexamethasone suppresion tests?
low dose
- give 1mg dex at night and measure ACTH and cortisol in the AM. dex will normally suppress cortisol so failure to suppress suggests Cushing's
high dose
- give 8mg dex at night and measure ACTH and cortisol in the AM. high dos is enough to suppress cortisol caused by pituitary adenoma (cushing's disease) but not if due to adrenal adenoma / ectopic ACTH
41
Cushing’s Mx
- stop steroids
- Cushing's - transsphenoidal resection of adenoma
- Adrenal adenoma - adrenalectomy
- adrenal carcinoma - surgery / radio / mitotane
- ectopic ACTH - surgery / metyrapone / ketoconazole
42
Nelson’s syndrome
development of an ACTH-producing pituitary tumour after the surgical removal of both adrenal glands due to a lack of cortisol and negative feedback. It causes skin pigmentation (high ACTH), bitemporal hemianopia and a lack of other pituitary hormones
43
Hyperaldosteronism: primary versus secondary
excess aldosterone
Primary
- adrenals producing too much aldosterone, renin low due to high BP
Secondary
- high renin levels leading to high aldosterone
44
Causes of hyperaldosteronism: primary and secondary
Primary
- Adrenal adenoma - Conn's syndrome
- bl adrenocortical hyperplasia (more common)
Secondary
- reduced renal perfusion e:g
- renal artery stenosis
- HF
- liver cirrhosis / ascites
45
Hyperaldosteronism Px
- asym
- HTN, headaches, flushing
- metabolic alkalosis - H secretion
- hypokalaemia - weakness, cramps, paraesthesia, polyuria, polydipsia, constipation, arrhythmias
46
Hyperaldosteronism Ix
1) aldosterone-to-renin ratio (ARR)
2) Raised blood pressure (hypertension)
3) Low potassium (hypokalaemia)
4) Blood gas analysis (alkalosis)
5) CT / MRI
6) renal artery imaging - eg doppler, angiography
7) adrenal vein sampling - which adrenal gland is producing more aldosterone
47
aldosterone-to-renin ratio (ARR) results in primary versus secondary hyperaldosteronism
High aldosterone and low renin indicate primary hyperaldosteronism
High aldosterone and high renin indicate secondary hyperaldosteronism
48
Hyperaldosteronism Mx
- oral spironolactone or eplerenone
Surgical removal of the adrenal adenoma
Percutaneous renal artery angioplasty via the femoral artery to treat renal artery stenosis
49
adrenal insufficiency defintion
underproduction of adrenal cortex hormones - mineralocorticoids (aldosterone) and glucocorticoids (cortisol)
50
primary adrenal insufficiency: pathology site and causes?
damage to adrenal glands means not enough hormones are produced
causes: Addison's, infection, surgery, malignancy
51
secondary adrenal insufficiency: pathology site and causes?
damage to pituitary (so not enough ACTH)
causes: pituitary adenoma, Sheehan's syndrome, pituitary injury (infection/surgery/malignancy)
52
tertiary adrenal insufficiency: pathology site and causes
inadequate CRH release from hypothalamus
causes:
cessation of long term steroid use (>3m)
53
what is Sheehan's?
major post-partum haemorrhage causes avascular necrosis of the pituitary gland
54
Adrenal insufficiency presentation?
- tanned, toned, tired, tearful
- fatigue, muscle weakness, cramps, dizziness, fainting, thirst, wt loss, abdo pain, N+V, depression, reduced libido, vitiligo, bronze hyperpigmentation, postural hypotension
55
what do you see bronze pigmentation in adrenal insufficiency?
ACTH stimulates melanocytes to produce melanin
56
Adrenal insufficiency Ix
1) bloods
2) short synacthan test
3) ACTH test
4) adrenal autoantibodies
5) CT/MRI of adrenals or MRI pituitary
57
autoantibodies that may be present in autoimmune adrenal insufficiency?
Adrenal cortex antibodies
21-hydroxylase antibodies
58
biochemical findings you might see in someone with adrenal insufficiency?
Hyponatraemia (low sodium)
Hyperkalaemia (high potassium)
Hypoglycaemia (low glucose)
Raised creatinine and urea due to dehydration
Hypercalcaemia (high calcium)
59
what is the short synacthan test?
- give dose of synthetic ACTH
- check blood cortisol before and 30 mins after dose
- cortisol level should double
failure to double suggests Addison's or significant adrenal atrophy due to secondary insufficiency
60
Adrenal insufficiency Mx
- hydrocortisone (double when ill) = glucocorticoid replacing cortisol
- fludrocortisone = mineralocorticoid replacing aldosterone
- steroid card, ID tag, IM hydrocortisone
61
Adrenal crisis
- acute severe adrenal insufficiency - eg infection, trauma
Px
- low GCS, hypotension, low BMs, low Na, high K
Mx
- IM/IV hydrocortisone (100mg stat), IV fluids, IV dextrose
62
Acromegaly
- excess GH in adults due to pituitary adenoma (most common) or ectopic production of hormones involved in growth hormone axis (GH/ GHRH) (usually cancer e.g. lung/pancreas)
63
what visual field defect might be seen with a pituitary tumour?
bitemporal hemianopia
64
Acromegaly Px
Excess growth hormone causes tissue growth:
- Prominent forehead and brow (frontal bossing)
- Coarse, sweaty skin
- Large nose
- Large tongue (macroglossia)
- Large hands and feet
- Large protruding jaw (prognathism)
Additional features include:
- headaches
- Hypertrophic heart
- Hypertension
- Type 2 diabetes
- Carpal tunnel syndrome
- Arthritis
- Colorectal cancer
65
Acromegaly Ix
- IGF-1 = raised
- growth hormone suppression test = 75g glucose drink with growth hormone tested at baseline and 2 hours following the drink.Glucose should suppress GH level. Failure to suppress GH suggest acromegaly.
- MRI pituitary
66
Acromegaly Mx
1. surgical = transsphenoidal resection of adenoma
2. medical = IM octreotide (somatostatin analogue)
- oral cabergoline, bromocriptine (dopamine agonist)
- SC pegvisomant (GH receptor antagonist)
67
growth hormone deficiency: Px, Ix and Mx
Px = small physical features, low energy levels, short stature
Ix = low IGF-1
Mx = daily injections of recombinant human growth hormone
68
T1DM
Autoimmune destruction of beta cells in pancreas leading to lack of insulin production and a high blood glucose
69
T1DM Px
- DKA
- polyuria
- polydipsia
- wt loss
70
ideal blood glucose ?
4.4 – 6.1 mmol/L.
71
where is insulin produced?
beta cells in the Islets of Langerhans in the pancreas
72
how does insulin work?
insulin causes:
- cells to take up glucose from blood
- prompt muscle/liver cells to absorb glucose and store it a glycogen (glycogenesis)
73
where is glucagon produced?
alpha cells in the Islets of Langerhans in the pancreas
74
how does glucagon work?
- released in response to low blood glucose / stress
- prompts liver to breakdown glycogen to release as glucose = glycogenolysis
- prompts liver to convert fat/protein into glucose = gluconeogenesis
75
T1DM Ix
- usually clinical
- urine dip for glucose and ketones
- fasting glucose and random glucose
- ? c-peptides - not routine
- ? autoantibodies to distinguish T1 and T2
76
fasting and random blood glucose thresholds in T1DM
if symptomatic:
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test
asymptomatic? as above but on 2 separate occasions
77
T1DM Mx
1. Subcutaneous insulin
2. Monitoring dietary carbohydrate intake
3. Monitoring blood sugar levels upon waking, at each meal and before bed
4. Monitoring for and managing complications, both short and long term
S/C insulin
- ideal is basal-bolus regime
78
T1DM: what is a basal bolus regimen
- Background, long-acting insulin injected once a day
- Short-acting insulin injected 30 minutes before consuming carbohydrates (e.g., at meals)
79
T1DM: what is an insulin pump?
pumps that continuously infuse insulin at different rates to control blood sugar levels. They are an alternative to basal-bolus regimes
80
T1DM sick day rules
- Don't stop insulin
- Check BMs more frequently
- Consider checking ketones
- Maintain normal meal pattern if possible - carb drinks if necessary
- Drink plenty fluids
81
T1DM complications: macrovascular + acute complications
- atherosclerosis
- stroke
- IHD
- PVD
Acute
- DKA, HHS, hypos
82
T1DM complications: microvascular
- diabetic retinopathy
- nephropathy
- neuropathy
- infections (UTI, pneumonia, skin)
83
insulin adverse effects?
- hypos
- lipodystrophy
- weight gain
84
T2DM - pathophysiology
increased insulin resistance and decreased production, leading to persistent hyperglycaemia
85
T2DM risk factors
- non-modifiable - older age, Black / South Asian, FHx
- modifiable - obesity, sedentary lifestyle, high sugar die
86
T2DM Px
- asym
- fatigue
- polyuria, polydipsia
- wt loss
- opportunistic infections - eg oral thrush
- slow wound healing
- acanthosis nigricans
87
what HbA1C suggests pre-diabetes?
HbA1c of 42 – 47 mmol/mol indicates pre-diabetes
88
T2DM diagnosis
HbA1C >48 mmol (6.5%)
[asymptomatic? need two positive tests. symptomatic? 1 positive test]
89
glucose cut of values for diabetes mellitus Dx [fasting, random, OGTT]
Serum blood glucose
- fasting >7, IGT 6.1-6.9
- random >11.1, IGT 7.8-11
OGTT
- >11.1 2hrs after 75g glucose - diagnostic
90
T2DM: HbA1C treatment targets
48 mmol/mol for new type 2 diabetics
53 mmol/mol for patients requiring more than one antidiabetic medication
91
T2DM Mx - lifestyle
lifestyle:
- Low-glycaemic-index, high-fibre diet
- exercise
- weight loss
- manage complications e.g. HTN
92
T2DM Mx - medical - 4 stages
1st line = metformin [ + SGLT-2 if cardiovascular disease or HF ]
2nd line = add sulfonylurea / pioglitazone / DPP4 inhibitor / SGLT-2 inhibitor
3rd line = triple therapy [metformin + 2 of the 2nd line drugs] or insulin therapy
4th line (triple therapy failure and patient BMI >35) = GLP-1
93
T2DM sick day rules
- Some OHAs may be stopped, restart once feeling better
- Metformin - stop if risk of dehydration
- Sulfonylureas - increase hypo risk
- SGLT-2 - check ketones
- GLP-1 - stop if dehydrated
- Monitor BMs more
94
DVLA diabetes rules
Group 1
- insulin - can drive if has hypo awareness, <1 bad hypo in last 12mo, no visual impairment
- tablets - no need to notify DVLA
- diet controlled - no need to notify
Group 2 must meet
- no severe hypos <12mo
- control of condition, monitoring etc
- understand hypo risks
- no cx of DM
95
Diabetic neuropathy?
- Glove + stocking sensory loss
- If painful - neuropathic pain meds, pain clinic
Also GI autonomic neuropathy
- Gastroparesis - erratic blood control, bloating, vomiting, Mx with metoclopramide, domperidone, erythromycin
- Chronic diarrhoea
- GORD
96
Diabetic foot
- from neuropathy / PAD
- loss of sensation, absent foot pulses, reduced ABPI
- calluses, ulcers, Charcot's arthropathy, cellulitis, osteomyelitis,
- screen annually - palpate pulses, 10g monofilament
97
Biguanides - metformin
Mechanism and S/E
- increases insulin sensitivity and decreases glucose production by the liver
S/Es
- GI Sx: including pain, nausea and diarrhoea (depending on the dose)
- Lactic acidosis (e.g., secondary to acute kidney injury)
NB does not cause weight gain or hypoglycaemia
98
SGLT-2 inhibitors - cana/empa/dapa-gliflozin
Mechanism and S/E
- block action of sodium-glucose co-transporter 2 protein in kidneys, inhibiting glucose resorption and increasing urinary glucose loss
S/Es
- increased frequency of UTI and genital thrush
- DKA
- Fournier's gangrene
- inreased urine output
99
Thiazolidinediones / glitazones - pioglitazone, rosiglitazone
Mechanism and S/E
- increase insulin sensitivity, decrease liver glucose production
S/Es
- Weight gain
- Heart failure
- Increased risk of bone fractures
- small increase in bladder Ca risk
100
Sulfonylureas - gliclazide, tolbutamide
Mechanism and s/e
- stimulate insulin secretion from pancreas
S/Es
- Weight gain
- Hypoglycaemia
101
DPP4 inhibitors - sita/lina/saxa-gliptin
Mechanism and S/E
- enhance incretin effect (increased insulin response to oral glucose) - increase insulin, lower glucagon
S/Es
- nausea, headaches
- pancreatitis
102
GLP-1 agonists - exanatide, liraglutide
Mechanism and S/E
- injectable S/C - increase incretin effect
S/Es
-Reduced appetite
- Weight loss
- GI sx including discomfort, nausea and diarrhoea
103
What is DKA?
- diabetic emergency usually due to inadequate insulin
- 3 key features: ketoacidosis, dehydration, potassium imbalance
104
DKA: why does ketoacidosis happen?
- liver starts producing ketones to use as fuel
- this builds up and kidneys start producing bicarb to counteract ketone acids
- over time ketone acids use up bicarb and blood becomes acidotic
105
DKA: when can insulin infusion continue til?
- Ketosis and acidosis should have resolved
- They should be eating and drinking
- They should have started their regular subcutaneous insulin
106
DKA Px
- pear drop breath
- Kussmaul's respiration
- reduced LOC
- vomiting
- abdo pain
- dehydration - dry mucous membranes, slow CRT, tachycardia, hypotension
107
DKA Ix
- CBG - hyperglycaemia
- ketone - blood ketones > 3
- VBG - acidosis
- investigate precipitant e.g. infection (CXR)
108
criteria for DKA dx
all 3 of:
1. Hyperglycaemia (e.g., blood glucose above 11 mmol/L)
2. Ketosis (e.g., blood ketones above 3 mmol/L)
3. Acidosis (e.g., pH below 7.3)
109
DKA Mx
F – Fluids – IV fluid resuscitation with normal saline (e.g., 1 litre in the first hour, followed by 1 litre every 2 hours)
I – Insulin – fixed rate insulin infusion (e.g., Actrapid at 0.1 units/kg/hour)
G – Glucose – closely monitor blood glucose and add a glucose infusion when it is less than 14 mmol/L
P – Potassium – add potassium to IV fluids and monitor closely (e.g., every hour initially)
I – Infection – treat underlying triggers such as infection
C – Chart fluid balance
K – Ketones – monitor blood ketones, pH and bicarbonate
110
DKA Cx
- Hypoglycaemia
- Hypokalaemia
- Cerebral oedema, particularly in children
- Pulmonary oedema secondary to fluid overload or acute respiratory distress syndrome
111
HHS
- rare but potentially fatal complication of type 2 diabetes.
- characterised by hyperosmolality (water loss leads to very concentrated blood), high sugar levels (hyperglycaemia) and the absence of ketones, distinguishing it from ketoacidosis
112
HHS Px
- polyuria
- polydipsia
- weight loss
- dehydration
- tachycardia
- hypotension
- confusion
113
HhS Ix
- CBG - usually hyperglycaemia
- serum osmolarity - >320 mOsm/kg
- ketones - no ketones
- VBG - no sig. acidosis
- U+Es - hypo/hypernatraemia, hypo/hyperkalaemia, dehydration
- investigate precipitant e.g. septic screen, MI etc
114
HHS Mx
- 0.9% NaCl - 0.5-1l/hr
- correct electrolytes
- insulin - give if BM stops falling with fluids
- LMWH for VTE prophylaxis
115
Hypoglycaemia
BM <4
116
Causes of hypoglycaemia
EXogenous drugs - insulin, OHAs, alcohol, quinine, quinolones
Pituitary insufficiency - no GH/cortisol
Liver failure - no glycogen stores
Adrenal failure - no cortisol
Insulinomas / immune hypoglycaemia
Non-pancreatic neoplasms
117
Hypoglycaemia Px
Adrenergic
- sweating, palpitations, tremor, anxiety/irritable, hunger, feel cold
Neuroglycopenic
- confusion, dizziness, tingling, blurred vision, slurred speech, headache, N+V, seizure, coma
- fatigue, weakness
118
Hypoglycaemia Ix
- CBG
- ix for cause
119
Hypoglycaemia Mx
- conscious, orientated - oral glucose
- conscious, confused, IV access - 100mls 20% / 200mls 10% glucose
- conscious, confused, no IV access - 1mg IM glucagon
- unconscious / fitting - as above
- give long-acting carb on recovery
- review meds etc
120
Hyperglycaemia
- high BMs
Causes
- decompensated / undiagnosed DM
- stress - acute illness
- Cushing's, pheochromocytoma, acromegaly, hyperthyroidism
- meds - eg steroids, BBs
121
Hyperglycaemia Px
- weakness, headache, blurred vision, polyuria, polydipsia, palpitations, N+V, abdo pain, drowsiness, seizure, coma
122
Hyperglycaemia Ix
- CBG, VBG, bloods, HbA1c
123
Hyperglycaemia Mx
- Novarapid if need to bring down BM
- diabetic team review
- meds review
- tx cause
124
describe the parathyroid axis?
PTH released from chief cells in 4 parathyroid glands in response to low calcium
125
3 key actions of PTH?
1) increases activity and number of osteoclasts in bone causing bone resorption
2) stimulates calcium reabsorption in the kidneys
3) stimulates the kidneys to convert vitamin D3 into calcitriol, the active form of vitamin D - vitamin D promotes calcium absorption from food in intestine
net effect = serum calcium increases and serum phosphate decreases
126
Hyperparathyroidism
high PTH
127
symptoms of hypercalcaemia ?
Kidney stones
Painful bones
Abdominal groans (constipation, nausea and vomiting)
Psychiatric moans (fatigue, depression and psychosis)
128
Primary hyperparathyroidism
- excess PTH production from parathyroid tumour -> hypercalcaemia
- mostly solitary adenoma, also hyperplasia, multiple adenoma, carcinoma
129
Primary hyperparathyroidism: blood results (PTH, Ca, phosphate
high PTH
high Ca
low Phosphate
130
hyperparathyroidism Ix
1. bloods - PTH, calcium, phosphate, ALP
2. urine calcium
131
Primary hyperparathyroidism Mx
- total parathyroidectomy - risk of low Ca / recurrent laryngeal nerve injury
- calcimimetic (cinacalcet)
- bisphosphonate - alendronate
132
Secondary hyperparathyroidism
- insufficient vitamin D or CKD reduces calcium absorption from the intestines, kidneys and bones.
- results in low blood calcium
- parathyroid glands react to the low serum calcium by excreting more parathyroid hormone
133
Secondary hyperparathyroidism: blood results (PTH, Ca, phosphate
- PTH high
- Ca normal (or low)
- phosphate high
134
Secondary hyperparathyroidism Mx
- Tx cause - vit D replacement, renal transplant
- maybe cinacalcet
135
Tertiary hyperparathyroidism? blood results (PTH, Ca, phosphate
- occurs after long period of secondary hyperparathyroidism resulting in hyperplasia of PTH glands -> autonomously produce high PTH
- high PTH leads to inappropriately high Ca absorption
bloods
- PTH very high
- Ca very high
- phosphate high
136
Hypoparathyroidism
Low PTH, leading to low Ca
137
Primary hypoparathyroidism
Low PTH due to PT gland failure
Causes - acquired / congenital
- DiGeorge syndrome
- Autoimmune cause
- Lack of PT gland at birth
- Genetic mutations
138
Secondary hypoparathyroidism
- low PTH after damage
Causes - physiological
- Parathyroidectomy / thyroidectomy (most common)
- Radiation
- Hypomagnesaemia - Mg required for PTH secretion
139
Pseudohypoparathyroidism
- PTH present but body unable to respond to it due to genetic mutations in PTH receptors
140
Pseudopseudohypoparathyroidism
- Same phenotypic defects as pseudo- without abnormalities of Ca metabolism
141
Hypoparathyroidism Px
hypocalcaemia signs :
trousseau's sign - carpopedal spasm caused by BP cuff
chvostek's sign - facial contraction caused by tapping facial nerve
hypocalcaemia symptoms:
- muscle cramps / pain
- fatigue
- twitching
- paraesthesia
- confusion
142
Hypoparathyroidism Ix
- bloods - PTH, calcium, phosphate, ALP
- test for underlying causes (genetics, auto-antibodies, infection)
- test for complications (ECG - see long QT with hypocalcaemia)
143
Hypoparathyroidism blood results: hypo, pseudo and pseudo pseudo
Hypo - normal appearance, low PTH, low Ca, high phosph
Pseudo - skeletal defects, high PTH, low Ca, high phosph
Pseudopseudo - skeletal defects, normal PTH, normal Ca, normal phosph
144
Hypoparathyroidism Mx
- IV calcium if severely low
- Ca supplements
- calcitriol - active vit D
145
where is ADH secreted from and what does it do?
Antidiuretic hormone (ADH) is produced in the hypothalamus and secreted by the posterior pituitary gland aka vasopressin
ADH stimulates water reabsorption from the collecting ducts in the kidneys
146
2 key sources of excess ADH?
- Increased secretion by the posterior pituitary
- Ectopic ADH, most commonly by small cell lung cancer
147
what happens if a person has too much ADH?
- Excessive ADH results in increased water reabsorption in the collecting ducts, diluting the blood
- excess water reduces the sodium concentration (hyponatraemia)
- extra water is not usually significant enough to cause fluid overload
- SIADH results in euvolaemic hyponatraemia
148
what happens to the urine if a person has excess ADH?
- urine becomes more concentrated as kidneys excrete less water
- SO patients with SIADH have high urine osmolality and high urine sodium
149
top 3 causes of SIADH?
- post-operative
- SSRIs
- small cell lung cancer
150
SIADH Px
- symptoms related to hyponatraemia:
- Headache
- Fatigue
- Muscle aches and cramps
- Confusion
severe? seizures, low gcs
151
Primary polydipsia (a DDx of SIADH)
- excessive water consumption, no cause
- euvolaemic hyponatraemia, but low urine Na/osmolality also
152
SIADH Ix
- euvolaemic
- FBC, U/E - low Na, low serum osmolality
- urine studies - high Na, high osmolality >100
- Ix for cause - CXR, CT TAP, short synacthen test, TFTs, serum cortisol
153
SIADH Mx
1. Admission if symptomatic or severe (e.g., sodium under 125 mmol/L)
2. Treating the underlying cause (e.g., stopping causative medications or treating the infection)
3. Fluid restriction
4. Vasopressin receptor antagonists (e.g., tolvaptan)
154
why is it essential to raise sodium slowly?
risk of osmotic demyelination syndrome
155
Diabetes insipidus (DI) definition (+ detail on types!)
- lack or production or loss of sensitivity to ADH
Cranial DI ' low ADH' = reduced ADH secretion from post pituitary
Nephrogenic DI 'insensitivity to ADH' = impaired response of kidney to ADH
156
causes of cranial DI
- Brain tumours
- Brain injury
- Brain surgery
- Brain infections (e.g., meningitis or encephalitis)
- Genetic mutations in the ADH gene (autosomal dominant inheritance)
- Wolfram syndrome (a genetic condition also causing optic atrophy, deafness and diabetes mellitus)
157
causes of nephrogenic DI?
- Medications, particularly lithium (used in bipolar affective disorder)
- Genetic mutations in the ADH receptor gene (X-linked recessive inheritance)
- Hypercalcaemia
- Hypokalaemia
- Kidney diseases (e.g., polycystic kidney disease)
158
DI Px
- polyuria
- polydipsia, chronic thirst
- nocturia
- dehydration
- postural hypotension
159
DI Ix
- urine collection - >3L/24hrs
- high/normal serum osmolality
- low urine osmolality
water deprivation test
160
what is the water deprivation test?
used in DI
- no water for 8 hours
- given desmopressin and measure urine osmolality before and after
cranial DI? urine osmolality high
nephrogenic DI? urine osmolality low
161
DI Mx
Cranial DI
- oral desmopressin
Nephrogenic DI
- tx cause
- low salt / protein diet
- thiazide diuretics
- NSAIDs - ibuprofen
162
Pheochromocytoma: definiton and risk factors
- tumour of the adrenal glands that secretes unregulated and excessive amounts of catecholamines (adrenaline)
- secrete adrenaline in bursts -> intermittent sx
RFx: MEN II, NFT1, von-Hippel-Lindau
163
Pheochromocytoma Px
- periodic sx
- anxiety, sweating, headache, tremor, palpitations, HTN, tachycardia
164
Pheochromocytoma Ix
- plasma free metanephrines
- 24hr urine catecholamines
- CT / MRI
- genetic testing
165
Pheochromocytoma Mx
- alpha blockers - phenoxybenzamine, doxazosin
- BBs
- partial adrenalectomy
166
Thyroid cancer (&RFx)
- cancer of thyroid gland
- papillary, follicular, anaplastic, lymphoma, medullary cell
RFs
- radiation exposure
- hx of goitre, nodule, thyroiditis, FHx, female, Asian
167
Thyroid cancer Px
- thyroid nodule
- hard / irregular thyroid
- cervical lymphadenopathy
- mets to lungs, brain, hepatic, bone
- hoarse voice
168
Thyroid cancer Ix
- fine needle aspiration biopsy / cytology
- Bloods - TFTs
- US thyroid
- thyroglobulin
169
Thyroid cancer Mx
- papillary / follicular - total thyroidectomy / radioactive iodine
- anaplastic / lymphomas - external radiotherapy
- medullary - thyroidectomy, lymph node removal
- levothyroxine - keep TSH reduced
- chemotherapy
170
what hormone is released from hypothalamus that acts on anterior pituitary to inhibit prolactin release?
dopamine
continuously secreted in absence of pregnancy
171
important hormonal S/E of dopamine inhibiting medications?
prolactin will be secreted
172
what does prolactin do?
1. stimulates milk production
2. inhibits GnRH secretion so inhibits FSh and LH release (they regulate menstruation) --> so during lactation, a period of amenorrhoea will occur
NB oxytocin inhibits dopamine so promotes prolactin production
173
what is a prolactinoma?
pituitary adenoma secreting prolactin
174
signs of prolactinoma in males?
gynacomastia
erectile dysfunction
loss of libido
galactorrhea
NB generic pituitary adenoma too - headaches / bitemporal hemianopia
175
signs of prolactinoma in females?
amenorrhoea
galactorrhea
infertility
NB generic pituitary adenoma too - headaches / bitemporal hemianopia
176
prolactinoma ix?
bloods - GH, prolactin, ACTH, FSH, LH, TFTs
MRI head
177
Prolactinoma Mx
Medical = dopamine agonist - cabergoline, bromocriptine
Surgical = transsphenoidal pituitary resection
178
Hyperkalaemia
- high serum K
Classification
- Mild - 5.5-5.9
- Moderate - 6.0-6.4
- Severe - >6.5
179
Causes of hyperkalaemia
Renal
- AKI, CKD, Addison's,
- drugs - spironolactone, ACEi, ARBs, NSAIDs, ciclosporin, heparin
Increased circulation of K
- exogenous - foods, blood transfusion
- endogenous - rhabdo, crush, burns, tumour lysis syndrome
IC->EC
- DKA, metabolic acidosis
- digoxin toxicity, BBs, sux, theophylline
Pseudo
- haemolysed sample
180
Hyperkalaemia Px
- asym
- Palpitations
- Chest pain
- Dizzy
- Muscle weakness
- Stiffness
- Fatigue
181
Hyperkalaemia Ix
- VBG, U/E, FBC, LFTs, BMs
- serum cortisol / aldosterone if adrenal insufficiency suspected
ECG
- tall tented T waves
- flattened P waves
- PR prolongation
- broad QRS
- sine wave pattern
- then VF
182
Hyperkalaemia Mx
- ABCDE
- remove cause
- calcium gluconate / chloride (if >6.5 / ECG changes)
- insulin + dextrose - 10-20 units in 500mls of 10% glucose
- salbutamol
- furosemide, calcium resonium (GI binder), sodium bicarb, dialysis
183
hypokalaemia
serum K<3.5
184
Hypokalaemia causes
- not enough K in fluids
- GI losses - D+V, malabsorption, laxatives, high output stoma, poor oral intake / inadequate feed
- Renal losses - genetic syndromes, Conn's, Cushing's, renal tubular acidosis, furosemide, thiazides
- Intracellular shift - alkalosis, insulin, adrenaline, salbutamol
185
Hypokalaemia Px
- asym
- Muscle weakness
- Hypotonia
- Hyporeflexia
- Tetany
- Constipation
- Palpitations
- Light-headed
186
Hypokalaemia Ix
- U/E
ECG
- small / inverted T waves
- Long PR
- prominent U waves
- ST depression
- long QT, Torsades de Pointes
187
Hypokalaemia Mx
- tx cause
Mild >3.1
- oral sando-K
Severe <3.1
- IV KCl - no quicker than 10mmol/hr
- lower - ITU discussion
188
Hypercalacaemia
- normal serum Ca 2.1-2.6
Classification
- mild 2.65-3 - asym
- moderate - 3.01-3.40 - asym/sx
- severe >3.40 - arrhythmias, coma
189
Causes of hypercalcaemia
High/normal PTH
- hyperparathyroidism
Low PTH
- malignancy - SCLC, bone mets, myeloma, ectopic
- sarcoidosis, TB
- Drugs - Ca/vit D, antacids, thiazides, lithium, theophylline
- rhabdo
- adrenal insufficiency, thyrotoxicosis, phaeo
190
Hypercalcaemia Px
Bones
- bone pain, fractures, osteopenia, osteomalacia, osteoporosis
Stones
- renal / biliary stones
Groans
- abdo pain, pancreatitis, malaise, nausea, constipation, polydipsia, dehydration, confusion
Moans
- depression, anxiety, cognitive dysfunction, insomnia, coma
- sx of malignancy etc
191
Hypercalcaemia Ix
- hydration
- Bloods - bone profile, vit D, ALP, U/E
- ECG - short QT, brady, 1st HB
- CXR, isotope bone scan, CT / MRI
- serum ACE (sarcoidosis)
192
Hypercalcaemia Mx
- 0.9% NaCl 4-6l/24hrs
- IV bisphosphonates - zolendronate
- dialysis
- cinacalcet, denosumab, calcitonin, prednisolone
193
Hypocalcaemia
Ca <2.1
194
Causes of hypocalcaemia
- total thyroidectomy / parathyroidectomy / hypoparathyroid
- vit D deficiency
- CKD
- low Mg (PPIs)
- pancreatitis
- rhabdo, tumour lysis syndrome
- Loop diuretics, steroids, gent, phosphates, theophylline
- massive transfusion
195
Hypocalcaemia Px
SPASMODIC
- Spasms - Trousseau's
- Perioral paraesthesia
- Anxious, irritable, irrational
- Seizures
- Muscle tone increase in smooth muscle - wheeze
- Orientation impaired and confused
- Dermatitis
- Impetigo herpetiformis - reduced Ca and pustules in pregnancy
- Chvostek's sign, cataracts, cardiomyopathy (long QT)
196
Hypocalcaemia Ix
- Bloods - bone profile, U/E, Mg, vit D, PTH, amylase, CK
- ECG - prolonged QT
197
Hypocalcaemia Mx
Mild >1.9
- oral sandocal / adcal
- vit D - colecalciferol
- IV Mg if low
- may need calcitriol in para/thyroidectomy
Severe <1.9 / sx
- cardiac monitor
- calcium gluconate bolus / infusion
- tx cause
198
Hypophosphataemia
low serum phosph <0.8 (normal 0.8-1.5)
199
Hypophosphataemia causes
- redistribution into cells - resp alkalosis, insulin, adrenaline
- increased urinary excretion - acidosis, DKA, hyperparathyroid
- decreased intestinal absorption - antacids, vit D deficiency, D+V, malabsorption
- refeeding syndrome
- chronic alcohol
- acute liver failure
200
Hypophosphataemia Px
- Asymptomatic
- Myopathy, rhabdomyolysis, weakness
- Resp failure
- Arrhythmias, cardiomyopathy
- Irritable, confused, hallucinations, lethargy, seizure, coma
- Rickets / osteomalacia if chronic
201
Hypophosphataemia Ix
- bloods - bone profile, Ca, phosph, U/E
202
Hypophosphataemia Mx
- oral phosphate sandoz
- IV phosphates polyfusor / sodium glycerophosphate
203
Hypomagnesaemia
- low serum Mg (normal 0.7-1.05)
204
Hypomagnesaemia causes
- refeeding syndrome
- D+V, high output stoma
- alcoholism
- hypercalcaemia
- SIADH, DKA, aldosteronism
- renal losses
- post-parathyroidectomy
- drugs - diuretics, gent, PPIs
205
Hypomagnesaemia Px
- asym
- irritable, lethargy
- N+V
- confusion, depression, psychosis
- tremors, cramps, tetany, weakness, seizures
206
Hypomagnesaemia Ix
- ECG - PR prolongation, ST depression, altered T waves, ventricular arrhythmias, eg VF
- Bloods - U/E, Ca, Mg
- urinary Mg
207
Hypomagnesaemia Mx
0.4-0.7
- oral Mg salts
<0.4 / tetany, arrhythmias, seizures
- IV Mg
208
Hypernatraemia
- serum Na >145
209
Causes of hypernatraemia
Hypovolaemic hypernatraemia - salt + water lost, but more water
- D+V, sweating, burns, loop diuretics, osmotic diuresis
Normovolaemic hypernatraemia - loss of purely water
- impaired thirst / water intake -> dehydration - dementia, decreased access to water
- diabetes insipidus
Hypervolaemic hypernatraemia - rare, iatrogenic
- hypertonic saline
- hypertonic dialysis
- hyperaldosteronism
210
Hypernatraemia Px
- Thirst, lethargy, weakness, nausea, loss of appetite
- Severe - myoclonic jerks, intracranial haemorrhage, coma, death
211
Hypernatraemia Ix
- assess fluid status
- bloods - U/E, glucose, Mg, Ca
- urine / serum osmolalities
212
Hypernatraemia Mx
- tx cause
- oral fluids
- 0.9% NaCl (unless hypervolaemic)
- correct <0.5mmol/L/hr (cerebral oedema risk)
213
Hyponatraemia
- low serum Na <135
Severity
- Mild – 130-134
- Moderate – 120-129
- Severe – <120
214
Hyponatraemia causes
Hypovolaemic hyponatraemia - loss of Na and water
- diuretics, Addisonian crisis, D+V, MDMA, pancreatitis
- exercise induced hyponatraemia (EAH)
Euvolaemic hyponatraemia - volume expansion, no oedema
- SIADH
- hypothyroidism
- beer potomania
- adrenal insufficiency
Hypervolaemic hyponatraemia - Na and water increase, more water
- HF, liver failure, nephrotic syndrome, excessive water consumption
215
False hyponatraemia?
- lab results show low Na, but no hypotonicity
- eg glucose - draws water into blood - appears like Na low
216
Hyponatraemia Px
- asym
early
- Headache
- Lethargy
- N+V
- Dizziness
- Confusion
- Muscle cramps
late
- seizures
- coma
- cardio-respiratory arrest
217
Hyponatraemia Ix
- fluid status
- U/E
- serum / urine osmolality
- urinary sodium
- if fluid overloaded - BNP, LFTs, urine dip, protein:creatinine ratio
- TFTs, 9am cortisol
218
Hyponatraemia Mx
Severe sx, Na <120
- HDU / ITU
- hypertonic saline - 3% NaCl
Hypovolaemic
- 0.9% NaCl
Euvolaemic
- fluid restrict 500-1000ml/d
- tolvaptan / demeclocycline
Hypervolaemic
- fluid restrict 500-1000ml/d
- furosemide / tolvaptan
219
Osmotic demyelination syndrome
- from rapid over-correction of hyponatraemia
- astrocyte/oligodendrocyte apoptosis -> demyelination
Px
- irreversible sx
- dysarthria, dysphagia, paralysis, seizures, confusion
- coma - locked-in-syndrome
Mx
- avoid - Na levels raised by 8mmol/L/24hrs
220
Bartter's syndrome
- autosomal recessive disease of severe hypokalaemia
- defective NKCC2 transporter - like lots of furosemide
Px
- childhood - failure to thrive
- polyuria, polydipsia
- hypokalaemia
- normotension
- weakness
221
Insulinoma
- NE tumour derived from pancreatic Islets of Langerhans cells
Px
- hypoglycaemia - early morning, just after meal
- rapid weight gain
Ix
- high insulin, raised proinsulin:insulin ratio
- high c-peptide
- supervised prolonged fasting
- CT pancreas
Mx
- surgery
- diazoxide / somatostatin
222
Liddle's syndrome
- autosomal dominant - disordered Na channels in distal tubules -> increased Na reabsorption
- HTN, hypokalaemic alkalosis
Mx
amiloride / triamterene
223
Maturity-Onset Diabetes of the Young (MODY)
- monogenic diabetes, autosomal dominant inheritance
- impaired insulin secretion
Px
- mild, non-ketotic hyperglycaemia
Ix
- genetic testing
Mx
- Sulfonylurea / insulin / nothing depending on type
224
what is Multiple endocrine neoplasia
- autosomal dominant disorders causing different endocrine glands to grow benign, malignant or non cancerous growths
225
what are the 3 types of MEN?
MEN-1
- parathyroid, pituitary, pancreas, adrenal, thyroid
- commonly px with hypercalcaemia
MEN-2a
- medullary thyroid cancer, parathyroid, phaeo
MEN-2b
- medullary thyroid cancer, phaeo, marfanoid body habitus, neuromas
226
Gynaecomastia
- abnormal breast tissue in males - increase in oestrogen:androgen ratio
Causes
- Physiological: normal in puberty
- Syndromes with androgen deficiency: Kallman's, Klinefelter's
- Testicular failure: e.g. mumps
- Liver disease
- Testicular cancer e.g. seminoma secreting hCG
- Ectopic tumour secretion
- Hyperthyroidism
- Haemodialysis
- Drugs - spironolactone, cimetidine, digoxin, cannabis, finasteride, GnRH agonists, oestrogens, anabolic steroids
227
Thyroid eye disease Px
- affects 25-50% pts with graves
- May be eu/hypo/hyperthyroid
- Exophthalmos
- Conjunctival oedema
- Optic disc swelling
- Ophthalmoplegia
- Eyelid retraction
- Inability to close eyelids -> sore, dry eyes
228
Thyroid eye disease Mx
- stop smoking
- topical lubricants
- steroids
- radiotherapy
- surgery
Urgent ophthal review if
- Unexplained deterioration in vision
- Change in colour vision
- Hx of eye popping out – globe subluxation
- Corneal opacity
- Cornea visible when eyelids closed
- Disc swelling
229
BMI ranges for overweight and obesity
Overweight 25 - 30
Obese class 1 30 - 35
Obese class 2 35 - 40
Obese class 3 > 40
230
obesity management options
conservative: diet, exercise
medical
- orlistat
- liraglutide
surgical
231
Orlistat
a pancreatic lipase inhibitor used in the management of obesity
only prescribed for adults as part of a plan who have:
- BMI of 28 kg/m^2 or more with associated risk factors, or
- BMI of 30 kg/m^2 or more
- continued weight loss e.g. 5% at 3 months
- orlistat is normally used for < 1 year
232
current NICE criteria for Liraglutide use?
- person has a BMI of at least 35 kg/m²
- prediabetic hyperglycaemia (e.g. HbA1c 42 - 47 mmol/mol)
finals
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