Endocrinology Flashcards
(215 cards)
1
Q
Describe pathophysiology of T2DM?
A
In T2DM, the response to insulin is diminished, and this is defined as insulin resistance. During this state, insulin is ineffective and is initially countered by an increase in insulin production to maintain glucose homeostasis, but over time, insulin production decreases, resulting in T2DM.
2
Q
What criteria is used to diagnose T2DM?
A
HbA1c > 48mmol
Fasting glucose > 7mmol
Random glucose > 11.1mmol
Usually these are monitored over several repeat readings, to ensure the diagnosis is correct - need to repeat the reading.
3
Q
In which patient groups is HbA1c not reliable to use?
A
Under 18 years
Pregnancy or 2 months post-partum
Recent pancreatic injury or surgery
On certain medications causing hyperglycaemia (i.e. steroids)
ESRD
T2DM patients who have had acute illness
4
Q
What lifestyle advice should be given for T2DM?
A
Diet - high fibre, low-glycaemic-index sources of carbohydrate (such as fruit, vegetables, wholegrains, and pulses), low-fat dairy products, and oily fish. Low sugar intake, regular meal times.
Weight loss - if obese, aim for 5-10% body weight loss.
Regular exercise
Alcohol advice - risk of hypoglycaemia due to interaction with medications
Smoking cessation
Risk of periodontitis - regular review
5
Q
How often should HbA1c be measured in T2DM?
A
3–6 monthly intervals initially until stable on unchanging antidiabetic treatment, and then every 6 months to ensure adequate blood glucose control.
6
Q
What is the first line medication for T2DM?
A
Metformin monotherapy
OR
Metformin with SGLT-2 inhibitor if high risk for CVD
When starting an adult with type 2 diabetes on dual therapy with metformin and an SGLT-2 inhibitor as first-line therapy, introduce the drugs sequentially, starting with metformin and checking tolerability. Start the SGLT-2 inhibitor as soon as metformin tolerability is confirmed.
ALSO
ensure you calculate Qrisk - if risk > 10% over 10 years, start statin
7
Q
What is the MOA of metformin?
A
Inhibiting hepatic gluconeogenesis and opposing the action of glucagon (released from the alpha cells of islets of langerhans in pancreas in response to hypoglycaemia, in order to stimulate glucose production) - overall lowering the levels of glucose in the bloodstream.
Increases peripheral insulin sensitivity
8
Q
What are some contraindications to metformin?
A
Renal dysfunction (eGFR < 30mmol) - due to risk of lactic acidosis
alcohol excess - risk of lactic acidosis
severe hepatic impairement
Hypersensitivity to metformin.
Acute or chronic metabolic acidosis.
9
Q
What are some side effects of metformin?
A
Abdominal pain; appetite decreased; diarrhoea; gastrointestinal disorder; nausea; taste altered; vitamin B12 deficiency; vomiting - the GI effects are common, and usually improve with length of treatment
10
Q
When would you consider first line metformin PLUS SGLT-2 inhibitor for T2DM?
A
If the patient already has chronic heart failure,
established atherosclerotic cardiovascular disease, or
at high risk of developing cardiovascular disease.
11
Q
How does an SGLT-2 inhibitor work?
A
Blocking SGLT2 protein located in the proximal convoluted tubule of the nephron.
The SGLT2 protein is responsible for the resorption of approximately 90% of filtered glucose while the remainder is reabsorbed by SGLT1 proteins found on the distal part of the proximal convoluted tubule.
SGLT2 inhibition results in glycosuria (and natriuresis as the protein is a co-transporter), thereby lowering plasma glucose concentrations.
12
Q
How does pioglitazone work for T2DM?
A
Thiazolidinediones, such as pioglitazone, activate peroxisome proliferator-activated receptor gamma (PPAR gamma) to improve insulin sensitivity. However, they also cause increased sodium and fluid retention, thereby leading to a 42% increased risk of incident heart failure.
13
Q
What is the second line management of T2DM (also what should be offered if metformin is not tolerated or contraindicated)?
A
Offer an SGLT-2 inhibitor to people with chronic heart failure or established atherosclerotic cardiovascular disease, and consider offering an SGLT-2 inhibitor to people at high risk of developing cardiovascular disease.
For other people, consider one of the following as first-line treatment:
A dipeptidyl peptidase-4 inhibitor (DPP-4 inhibitor).
Pioglitazone.
A sulfonylurea.
A sodium-glucose cotransporter-2 inhibitor (SGLT-2 inhibitor) — this may be considered instead of a DPP-4 inhibitor if a sulfonylurea or pioglitazone is not appropriate.
14
Q
How does a DPP-4 inhibitor work?
A
DDP-4 inhibitors work by blocking the action of the enzyme DPP-4, which destroys incretins – hormones - that the body makes. Incretins are naturally produced by the stomach when we eat. They help the body produce more insulin when it’s needed and lowers blood sugar levels
15
Q
What are some examples of SGLT-2 inhibitors?
A
Dapagliflozin
Canagliflozin
Empagliflozin
16
Q
What are some examples of DPP-4 inhibitors?
A
Sitagliptin
Vildagliptin
17
Q
What are contraindications to SGLT-2 inhibitors?
A
CKD - eGFR < 30 - however if already established on SGLT2 inhibitor can continue
T1DM - risk of DKA
liver disease
increasing age - avoid in over 85 years (risk of volume depletion)
active foot disease
18
Q
What are contrainidications to DDP-4 inhibitors?
A
Ketoacidosis.
Hepatic impairment — avoid vildagliptin; avoid saxagliptin and alogliptin if severe hepatic impairment.
Heart failure — avoid vildagliptin if severe heart failure; avoid alogliptin if moderate-to-severe heart failure.
19
Q
what are the different treatment steps for T2DM?
A
first line - metformin / metformin + SGLT-2 inhibitor if indicated
second line - dual agent therapy - usually metformin + one of the other medications
third line - triple agent therapy
fourth line - insulin
20
Q
what are some complications of T2DM?
A
Macrovascular -
Atherosclerotic cardiovascular disease (CVD)
Microvascular -
chronic kidney disease
diabetic retinopathy
peripheral neuropathy
foot complications
21
Q
what is the role of urine albumin:creatinine ratio?
A
Performed first thing in the morning
Indicative of level of kidney disease in the context of HTN or T2DM - if urine albumin: creatinine ratio high, this indicates worsening renal disease
22
Q
what screening is associated with T2DM management?
A
Diabetic eye screening will be offered at diagnosis and:
Every 2 years for people at low risk of sight loss (no identified diabetic retinopathy on two successive screening tests).
At least annually for all other people with diabetes.
Yearly diabetic foot review
Yearly diabetes review
Yearly screening for diabetic nephropathy - U+E monitoring, urine albumin:creatinine ratio
23
Q
what are some side effects of SGLT-1 inhibitors?
A
Urinary and genital infections
Fournier’s gangrene
Normoglycaemic ketoacidosis
Increased risk of lower limb amputation so need to monitor feet carefully
24
Q
what type of drug is gliclazide?
A
SULFONYLUREA
25
examples of sulfonylureas?
Gliclazide
Tolbutamide
26
Effect of SGLT-2 inhibitors on weight
weight loss
27
Mechanism of action of sulfonylureas
Increased pancreatic excretion of insulin
28
Where in the pancreas do sulfonylureas work?
ATP dependent K+ channels on the cell membrane of pancreatic beta cells
to increase pancreatic insulin secretion
29
Side effects of sulfonylureas
Hypoglycaemia
Weight gain
SIADH
Bone marrow suppression
Cholestatic liver damage
Peripheral neuropathy
30
Effect of sulfonylureas on weight
weight gain
31
Which T2DM medication can cause liver damage?
Sulfonylureas cause cholestatic liver damage
Pioglitazone causes liver impairment, need to monitor LFTs
32
Example of thiazolidinediones
Pioglitazone
33
Mechanism of action of pioglitazone
Reduces peripheral insulin resistance
by agonising the PPAR-gamma receptor
34
Which T2DM medication reduces peripheral insulin resistance?
Pioglitazone
35
Side effects of pioglitazone
Weight gain
Liver impairment
Fluid retention so C/I in heart failure
Increased risk of fractures
Increased risk of bladder ca
36
Effect of pioglitazone on weight
weight gain
37
what are the causes of hypothyroidism?
primary:
- hashimotos
- iodine deficiency
- thyroidectomy
- radiation damage to the thyroid
- subacute thyroiditis (de quervains)
- medications (such as amiodarone)
secondary:
- hypopituitrisim
- i.e. tumours
- Sheehans syndrome
38
what is the pathophysiology of hashimotos hypothyroidism?
autoimmune condition where anti-TPO antibodies and anti-thyroglobulin antibodies are produce which attack the thyroid gland.
39
what are the symptoms of hypothyroidism?
weight gain
fatigue
cool peripheries
hair loss
goitre
dry skin
oedema
constipation
menorrhagia
decreased reflexes
carpal tunnel syndrome
40
what are the clinical features of hashimotos?
signs of hypothyroidism + painless goitre
41
what is de quervains thyroiditis?
Although the precise cause is not known, De Quervain's thyroiditis is believed to be caused by a viral infection and the inflammatory process associated with such infections.
42
what are the clinical features of de quervains thyroiditis
signs of hypothyroidism + associated with a painful goitre and raised ESR
43
what is the de quervains thyroiditis characterised by?
Triphasic course of transient thyrotoxicosis, followed by hypothyroidism, followed by a return to euthyroidism.
44
what is riedel thyroiditis?
Fibrous tissue replacing the normal thyroid parenchyma
45
what are the clinical symptoms of riedel thyroiditis?
hypothyroidism symptoms + painless goitre - fixed and hard
46
what drugs cause hypothyroidism?
amiodarone
lithium
47
TFT in primary hypothyroidism?
TSH high
T3 and T4 low
48
TFT in secondary hypothyroidism?
T3 and T4 low
TSH low
49
management of primary hypothyroidism?
commence levothyroxine
50
how should levothyroxine be commenced in the elderly or those with ischaemic heart disease?
initial starting dose of levothyroxine should be lower in elderly patients and those with ischaemic heart disease.
The BNF recommends that for patients with cardiac disease, severe hypothyroidism or patients over 50 years the initial starting dose should be 25mcg od with dose slowly titrated. Other patients should be started on a dose of 50-100mcg od
51
how often should TFT be checked when commencing levothyroxine?
8- 12 weeks after a dose change
once TSH stable (2 readings, 3 months apart) then check annually
52
how should levothyroxine be taken?
Advise the person to take LT4 medication on an empty stomach in the morning before other food or medication.
53
what are some side effects of levothyroxine therapy?
hyperthyroidism: due to over treatment
reduced bone mineral density
worsening of angina
atrial fibrillation
54
what dose change should occur for women who have become pregnant and are taking levothyroxine?
women with established hypothyroidism who become pregnant should have their dose increased 'by at least 25-50 micrograms levothyroxine'* due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value
55
what is subclinical hypothyroidism?
TSH raised but T3, T4 normal
no obvious symptoms
56
management of subclinical hypothyroidism if TSH > 10?
consider offering levothyroxine if the TSH level is > 10 mU/L on 2 separate occasions 3 months apart
57
management of subclinical hypothyroidism if TSH < 10, and patient is symptomatic?
consider 6 month trial of levothyroxine
58
management of subclinical hypothyroidism if asymptomatic or elderly?
watch and wait
repeat TFT in 6 months
59
causes of hyperthyroidism?
graves disease
toxic nodular goitre
60
TFT in hyperthyroidism?
T3 and T4 high
TSH low
61
what are signs of thyrotoxicosis?
weight loss with a normal or increased appetite
heat intolerance with increased sweating
palpitations
tremor
anxiety
proximal muscle weakness
alopecia
increased fatigability
62
what are specific signs of graves disease?
eye signs (30% of patients)
- exophthalmos
- ophthalmoplegia
- pretibial myxoedema
thyroid acropachy, a triad of:
- digital clubbing
- soft tissue swelling of the hands and feet
periosteal new bone formation
63
what is the pathophysiology of graves disease?
autoimmune condition where antibodies TSH receptor stimulating antibodies and anti-thyroid peroxidase antibodies are produced which stimulates TSH production
64
Management of hyperthyroid in primary care?
consider commencing beta blocker such as propranolol for symptom control
consider commencing carbimazole under specialist guidance
65
what is the pathophysiology of DKA?
Due to lack of insulin, and high glucose levels in the blood:
- adipose tissue is broken down by the liver into ketones -> metabolic acidosis
- this leads to kussmaul breathing - to shift CO2 and reduce acidity
- high levels of glucose in the blood causes osmotic diuresis, leading to loss of Na/K/Cl-
- parodixcal increase of K intracellularly, whilst having massive losses of K in the urine
66
what is the pathophysiology of potassium in DKA?
insulin usually drives K into the cells, without insulin, there is significant loss of K from the cells - leading to huge urinary losses. Metabolic acidosis secondary to fat breakdown converting to ketones, also causes a large shift of K out of the cells. This then leads to hypokalaemia.
67
what happens to K when insulin is given in DKA?
as insulin drives K into the cells, the lack of insulin initially causes HYPER kalaemia, but when insulin is replaced, this can cause the potassium to shift from the blood back into the cells, cuasing massive hypokalaemia. Therefore K needs ot be replaced with the DKA protocol.
68
what is the pathophysiology of Na in DKA?
Na is low due to osmotic diuresis, leading to loss of Na within the urine, causing low Na.
69
what are the electrolyte abnormalities in DKA?
hyperglycaemia
hyperkalaemia
hyponatraemia
70
how does DKA present?
abdominal pain
polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
Acetone-smelling breath ('pear drops' smell)
71
how is DKA managed?
cont long acting insulin, stop short acting
replace fluid - usually deplete 5-8L
replace initially with isotonic solution - i.e. first back is 1L NaCL over 1st hour, then second add in K and CL
72
why are patients in DKA so fluid deplete?
In the absence of insulin, blood glucose levels rise (often >250 mg/dL).
Once blood glucose exceeds the renal threshold (~180 mg/dL), glucose spills into the urine, drawing water with it (osmotic diuresis).
Along with water, electrolytes (Na⁺, K⁺, Cl⁻, PO₄³⁻) are lost in urine.
73
what are the 4 types of diabetes?
Type 1
Type 2
Latent autoimmune diabetes in adulthood
Maturity onset diabetes of the young
74
what is latent autoimmune diabetes?
autoimmune diabtes that presents in 6-10% of those with type 2 diabetes.
there is autoimmune destruction of the beta islets of langerhans but it is much slowed to progress than type 1 diabetes
75
at what age does latent autoimmune diabetes present?
usually over the age of 30 years
76
how can you differeniate between latent autoimmune diabetes and T2DM?
latent autoimmune diabetes - slow to progress, often mistaken for T2DM but pt end up needing insulin much quicker, despite having good adherence to oral hypoglycaemic agents
also presence of auto-antibodies
and associated with other autoimmune disorders
77
what antibodies do you test for in latent autoimmune diabetes?
anti-glutamic acid decarboxylase
78
what is maturity onset diabetes of the young?
genetic syndrome that is autosomal dominant , usually there is a family history
gene mutations of HFN1-a
treatment differs on type of genetic mutation
79
what is the blood pressure target for patients with T2DM?
<140/90 - same as rest of population
80
what are the complications of diabetes?
peripheral neuropathy
gastroperesis
diabetic nephropathy
diabetic retinopathy
81
what is the typical sensory loss that occurs in diabetic neuropathy?
usually sensory
in glove and stocking distribution
82
what is the management of diabetic neuropathy?
first-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin
if the first-line drug treatment does not work try one of the other 3 drugs
tramadol may be used as 'rescue therapy' for exacerbations of neuropathic pain
topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia)
pain management clinics may be useful in patients with resistant problems
83
what are the symptoms of gastric peripheral neuropahty in diabetes?
erratic blood sugar readings
bloating
nausea
vomiting
84
management of gastric peripheral neuropathy in diabetes?
metoclopramide, domperidone or erythromycin (prokinetic agents)
85
what is the diagnostic criteria for type 1 diabetes?
If the patient is 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)
If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions
86
what screening is done for diabetic foot changes?
All patients with diabetes should be screened for diabetic foot disease on at least an annual basis
screening for ischaemia: done by palpating for both the dorsalis pedis pulse and posterial tibial artery pulse
screening for neuropathy: a 10 g monofilament is used on various parts of the sole of the foot
87
what is the pathophysiology of diabetic retinopathy?
Increased retinal blood flow and abnormal metabolism in the retinal vessel walls. This precipitates damage to endothelial cells and pericytes
88
what are the three classifications of diabetic retinopathy?
non-proliferative diabetic retinopathy (NPDR), proliferative retinopathy (PDR) and maculopathy.
89
management of diabetic retinopathy maculopathy?
if there is a change in visual acuity then intravitreal vascular endothelial growth factor (VEGF) inhibitors
90
management of diabetic retinopathy non proliferative retinopathy?
regular observation
if severe/very severe consider panretinal laser photocoagulation
91
management of diabetic retinopathy proliferative?
panretinal laser photocoagulation
following treatment around 50% of patients develop a noticeable reduction in their visual fields due to the scarring of peripheral retinal tissue +
VGEF inhibitors
92
which type of retinopathy is more common in type 1 diabetes?
proliferative diabetic retinopathy
93
which type of retinopathy is more common in type 2 diabetes?
maculopathy
94
what are the rules surrounding diabetes and DVLA?
if on insulin then patient can drive a car as long as they have hypoglycaemic awareness, not more than one episode of hypoglycaemia requiring the assistance of another person within the preceding 12 months and no relevant visual impairment. Drivers are normally contacted by DVLA
if on tablets or exenatide no need to notify DVLA. If tablets may induce hypoglycaemia (e.g. sulfonylureas) then there must not have been more than one episode of hypoglycaemia requiring the assistance of another person within the preceding 12 months
if diet controlled alone then no requirement to inform DVLA
insulin diabetics must check blood sugars every 2 hours when driving
95
what is non-ketotic hyperglycaemia?
Non-ketotic hyperglycemia (NKH) refers to a state of severe hyperglycemia without significant ketoacidosis. It is most commonly seen in type 2 diabetes and can lead to a life-threatening condition called hyperosmolar hyperglycemic state (HHS).
96
why are there no ketons in non-ketotic hyperglycaemia in comparison to DKA?
there is still some insulin production which leads to just enough supression of ketone production, but there is still impaired glucose metabolism and so this can lead to very high glucose levels
97
what is HHS?
triggered by illness, infection, dehydration or poor diabetes control
insulin is present enough to prevent ketoacidosis but not severe hyperglycaemia
leads to osmotic dysfunction - profound dehydration, electrolyte loss and rising serum osmolality
98
what is the pathophysiology of HHS?
lack on insulin -> leads to extremely high glucose leves in blood -> filtered into urine -> Glucose in urine pulls water with it (osmotic diuresis), leading to polyuria and dehydration -> Severe fluid and electrolyte losses follow, including Na⁺, K⁺, and phosphate depletion -> As plasma osmolality rises, water shifts out of brain cells, leading to altered mental status, coma, and seizures.
Higher osmolality correlates with worse neurological symptoms.
99
what are some complications of HHS?
cerebral oedema
seizures
altered mental state
arrhythmias
AKI
DVT
100
what are some causes of HHS?
HHS is often triggered by an underlying illness or stressor, which increases counterregulatory hormones (glucagon, cortisol, epinephrine) that worsen insulin resistance.
Common Triggers:
Infections (most common) → Pneumonia, UTI, sepsis
Poor diabetes control → Missed insulin, newly diagnosed diabetes
Medications → Steroids, diuretics, antipsychotics
Acute Illness → Stroke, myocardial infarction, pancreatitis
Dehydration → Inadequate water intake (common in elderly)
101
which are the main thyroid hormones?
thyroxine (T4 - accounts for 80-90% of the thyroid hormones) and triiodothyronine (T3)
102
what is the role thyroid hormones?
T3 is the active hormone which acts to regulate metabolism in the body. T4 is the pre-hormone, and is converted to T3 in peripheral tissues.
103
what are the causes of hypothyroidism?
hashimotos - primary autoimmune hypothyroidism
De quervains thyroiditis (subacute)
Riedel thyroiditis
Iodine deficiency
post partum thyroidits
medications: lithium, amiodarone
104
what is hashimotos thyroiditis?
autoimmune disorder - formation of anti-thyroid peroxidase (TPO) and also anti-thyroglobulin (Tg) antibodies, leading to primary hypothyroidism
105
what are the symptoms of hypothyroidism?
low energy , TATT
dry skin
menorrhagia
weight gain
poor concentration
constipation
loss of deep tendon reflexes
dry coarse hair on scalp
non-pitting oedema
106
who is hashimotos thyroiditis common in?
10 x more common in women
107
what other conditions is hashimotos thyroiditis associated with?
other autoimmune conditions such as coeliac disease, diabetes, vitiligo and MALT syndrome
108
how do you diagnose hashimotos thyroiditis?
Diagnosis is confirmed through elevated TSH levels and low free T4 levels. The presence of anti-TPO antibodies is a key diagnostic marker.
109
what is the management of hashimotos thyroiditis?
replacement with levothyroxine
110
what does of levothyroxine do you usually start?
100mcg initially and recheck levels in 4-6 weeks, then uptitrate by 25mcg until TSH in range
if elderly - start with reduced dose such as 25mcg.
111
what is riedel thyroiditis?
Riedel thyroiditis is a rare form of chronic thyroiditis characterised by the replacement of normal thyroid tissue with fibrous tissue, leading to hypothyroidism. It is considered a form of autoimmune thyroid disease but differs from Hashimoto's thyroiditis in the pathophysiology
112
what is the presentation of riedel thyroiditis?
Patients often present with a firm, painless goitre that may be asymmetrical. Symptoms of hypothyroidism can develop due to glandular destruction. Compression symptoms (e.g., dysphagia, dyspnoea) may occur due to the mass effect of the enlarged gland.
113
how is riedel thyroiditis diagnosed?
Diagnosis is primarily clinical, supported by imaging (ultrasound may show a heterogeneous gland) and fine-needle aspiration biopsy, which typically reveals fibrous tissue rather than typical thyroid cells.
114
how is riedel thyroiditis managed?
combination of steroids to suppress the immune response, and levothyroxine
115
what is subacute (de quervains) thyroiditis?
Subacute thyroiditis, also known as de Quervain's thyroiditis, is an inflammatory condition of the thyroid gland often triggered by a viral infection. It typically presents with a painful, tender thyroid and may lead to transient hypothyroidism.
116
how does de quervains thyroiditis present?
painful tender thyroid
symptoms of hypothyroidism
transient
117
how is de quervains thyroiditis diagnosed?
Diagnosis is primarily clinical, supported by elevated inflammatory markers (e.g., ESR, CRP) and imaging (ultrasound may show a heterogeneous gland). Thyroid autoantibodies are typically negative.
118
what is the management of de quervains thyroiditis
Management includes NSAIDs for pain relief; corticosteroids may be indicated in severe cases. Most patients recover fully within weeks to months
119
what is the prognosis for de quervains thyroidits?
good - but some may go on to have recurrent or long term episodes of hypothyroidism
120
what is post partum thyroiditis?
Postpartum thyroiditis (PPT) is an autoimmune thyroid disorder that occurs within the first year after childbirth. It involves temporary inflammation of the thyroid gland, leading to phases of hyperthyroidism, hypothyroidism, or both.
It is believed to be a variant of Hashimoto's thyroiditis, triggered by immune system changes during pregnancy and postpartum recovery.
121
what are the different phases of post partum thyroiditis?
Hyperthyroid Phase (2-6 months postpartum) – "Thyrotoxic Phase"
Inflammation causes release of preformed thyroid hormones (T₃ & T₄).
Lasts for weeks to months and then transitions to normal or hypothyroid.
Hypothyroid Phase (3-12 months postpartum)
Depletion of stored thyroid hormones leads to transient or permanent hypothyroidism.
Symptoms may persist for months to a year.
Recovery (Euthyroid Phase)
Many women eventually return to normal thyroid function, but some develop permanent hypothyroidism (especially if they have thyroid antibodies).
122
what is the management of post partum thyroiditis?
Hyperthyroid phase: Often no treatment needed; beta-blockers (e.g., propranolol) for symptom relief.
Hypothyroid phase: Levothyroxine (T₄) replacement if symptoms are severe or prolonged.
Monitoring: Regular thyroid tests every 4-6 weeks to assess recovery or progression to permanent hypothyroidism.
123
what is the prognosis of post partum thyroiditis?
50% of women return to normal thyroid function within 1 year.
30-50% develop permanent hypothyroidism (higher risk with anti-TPO antibodies).
Increased risk of thyroid dysfunction in future pregnancies.
124
what is graves disease?
Graves' disease is characterised by the production of autoantibodies, primarily IgG, that stimulate the thyroid-stimulating hormone (TSH). This leads to hyperthyroidism due to increased synthesis and release of thyroid hormones (T3 and T).
125
what are the symptoms of hyperthyroidism?
excessive heat intolerance
diffuse goitre
sweating
weight loss
oliomenorrhoea
palpitations
anxiety
tremor
exophthlamos
126
what signs are seen in graves disease but not in other causes of hyperthyroidism?
eye signs (30% of patients)
- exophthalmos
- ophthalmoplegia
pretibial myxoedema
thyroid acropachy, a triad of:
- digital clubbing
- soft tissue swelling of the hands and feet
- periosteal new bone formation
127
what antibodies are present in graves disease?
TSH receptor stimulating antibodies (90%)
anti-thyroid peroxidase antibodies (75%)
128
what is the management of graves disease?
refer to endocrinology at diagnosis
propranolol to manage symptoms
carbimazole - may give short term relief, but is ineffective in thyroiditis
most are started on radioactive iodine - must stop carbimazole 4 d before and restart after 3 d
surgical intervention - total or partial thyroidectomy
129
how is carbimazole titrated?
initially started at 40mg then slowly downtitrated to achieve euthyorid
130
what is the major complication of carbimazole treatment?
agranulocytosis
131
what is toxic multinodular goitre?
Presence of multiple hyperfunctioning thyroid nodules. TMNG arises from long-standing iodine deficiency or autonomous nodular growth. The nodules produce thyroid hormones independently of TSH regulation, causing negative feedback suppression of TSH.
132
what is thyroid eye disease?
Autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, lid lag, swelling, redness, conjunctivitis, and bulging eyes.
133
what is a significant risk factor for the development of thyroid eye disease?
smoking
134
what is the presentation of thyroid eye disease?
the patient may be eu-, hypo- or hyperthyroid at the time of presentation
exophthalmos
conjunctival oedema
optic disc swelling
ophthalmoplegia
inability to close the eyelids may lead to sore, dry eyes. If severe and untreated patients can be at risk of exposure keratopathy
135
what is the management of thyroid eye disease?
smoking cessation
topical lubricants may be needed to help prevent corneal inflammation caused by exposure
steroids
radiotherapy
surgery
136
what are some complications of thyroid eye disease?
Exposure keratopathy
this is the most common complication of thyroid eye disease
due to eyelid retraction and proptosis (exophthalmos) → cornea becomes excessively exposed, disrupting the normal tear film → dryness, irritation, and corneal ulceration
optic neuropathy
diplopia
strabisumus
137
how common is thyroid cancer?
< 1 % of all cancers, rare
138
what is the most common type of thyroid cancer?
papillary carcinoma
139
what is the prognosis of papillary thyroid cancer?
good prognosis , 10 year survival rate is > 90%
140
what are the symptoms of thyroid Ca?
painless thyroid lump - most common
cervical lymphadenopathy
hoarse voice
dysphagia
diarrhoea, flushing
141
what is the TWR referral criteria for thyroid cancer suspected?
Consider a suspected cancer pathway referral (for an appointment within 2 weeks) for thyroid cancer in people with an unexplained thyroid lump.
142
what is the referral criteria for bariatric surgery?
Bariatric surgery could be considered if a patient has a BMI (body max index) of 40 kg/m^2 or more, or between 35 kg/m^2 and 40 kg/m^2 and other significant disease (for example, type 2 diabetes mellitus, hypertension) that could be improved if they lost weight.
143
what BMI is considered to be underweight?
< 18. 49
144
how does orlistat work?
By inhibiting pancreatic lipase, Orlistat reduces the absorption of approximately 30% of dietary fats, leading to decreased caloric intake.
145
what are some of the side effects of orlistat?
faecal urgency
faecal incontinence
flatulence
146
what is the crtieria for starting orlistat?
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
147
most common SE of prolonged glucocorticoid steroid use?
insomnia
148
what are the three types of steroids released by the adrenal gland?
glucocorticoids - cortisol
mineralocorticoids - aldosterone
sex hormones- testosterone
149
what is cushings syndrome?
excessive cortisol release by the adrenal glands
150
what most commonly causing cushings disease?
It is most commonly caused by a benign pituitary tumour that secretes adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce cortisol - 80%. 20% caused by ectopic ACTH production - for example due to small cell lung ca.
also commonly iatrogenic - due to exogenous administration of prednisolone or corticosteroids
151
what age is cushings disease most common?
30-40yrs
152
what are the symptoms of cushings syndrome?
moon face
truncal obesity
HTN
menstrual disturbance
striae and bruising
osteoporosis
lethargy
depression
acne
polyruia/polydypsia
153
what are the three investigations used to diagnose cushings?
The three most commonly used tests are:
overnight (low-dose) dexamethasone suppression test
this is the most sensitive test and is now used first-line to test for Cushing's syndrome
patients with Cushing's syndrome do not have their morning cortisol spike suppressed
24 hr urinary free cortisol
two measurements are required
bedtime salivary cortisol
two measurements are required
154
describe the physiology behind the overnight dexamethasone suppression test?
Dexamethasone is a synthetic glucocorticoid that mimics cortisol.
In a healthy individual, dexamethasone suppresses ACTH release from the pituitary, leading to low cortisol levels.
In Cushing’s syndrome, the feedback mechanism is disrupted, and cortisol remains high despite dexamethasone administration.
155
how is the overnight dexamethasone test carried out?
11pm - dexamethasone 1g administered
8am - bloods taken, if cortisol remains high - indicative of cushings
156
what is the management of cushings disease?
First-line = trans-sphenoidal removal of pituitary tumour (hypophysectomy)
Second-line = repeat trans-sphenoidal surgery, pituitary radiotherapy
Third-line = bilateral adrenalectomy
157
what is addisons disease?
primary adrenal insufficiency - autoimmune destruction of the adrenal glands
158
symptoms of addisons disease?
lethargy, weakness, anorexia, nausea & vomiting, weight loss, 'salt-craving'
hyperpigmentation (especially palmar creases)
vitiligo
loss of pubic hair in women
hypotension
hypoglycaemia
hyponatraemia and hyperkalaemia may be seen
crisis: collapse, shock, pyrexia
159
what is used to test for addisons disease?
short acting synacthen test
160
describe the short acting synacthen test?
Synacthen (tetracosactide) is a synthetic form of ACTH (adrenocorticotropic hormone).
In a healthy adrenal gland, ACTH stimulates the adrenal cortex to produce cortisol.
In adrenal insufficiency, the adrenal glands fail to respond adequately to ACTH, resulting in low cortisol production. This results in a low cortisol reading
161
what electrolyte imbalances are seen with addisons?
hyperkalaemia
hyponatraemia
hypoglycaemia
metabolic acidosis
162
what is the management of addisons disease
replace with mineralocorticoid and glucocorticoid steroids
This usually means that patients take a combination of:
hydrocortisone: usually given in 2 or 3 divided doses. Patients typically require 20-30 mg per day, with the majority given in the first half of the day
fludrocortisone
163
what are the sick day rules for addisons disease steroids?
in simple terms the glucocorticoid dose should be doubled, with the fludrocortisone dose staying the same
164
what are the blood glucose targets for T1 diabetes
5-7 mmol/l on waking and
4-7 mmol/l before meals at other times of the day
HbA1c < 48
165
what is phaeochromocytoma?
Phaeochromocytoma is a rare neuroendocrine tumour arising from chromaffin cells of the adrenal medulla, leading to excessive catecholamine secretion (epinephrine and norepinephrine).
166
symptoms of phaeochromocytoma?
episodic headaches, palpitations, diaphoresis, pallor, and anxiety. Hypertensive crises may occur, often triggered by stress or certain medications.
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what is the diagnostic test for phaeochromocytoma?
24 hr urinary collection of metanephrines (sensitivity 97%*)
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what is the management of phaeochromocytoma?
surgery is definitive management
Pt stabilised before surgery-
alpha-blocker (e.g. phenoxybenzamine), given before a
beta-blocker (e.g. propranolol)
169
what are the causes of parathypothyroidism?
Parathyroid destruction - iatrogenic (secondary to thyroidectomy, or parathyroidectomy), autoimmune
Absent parathyroidm - Digeorge syndrome - parathyroid glands do not form
170
what blood results are seen with hypoparathyroidsm?
low Ca
low Vit D
+/- variable levels of phosphate , usually low
171
what blood results are seen with hyperparathyroidism?
high Ca
high or low phosphate
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what are the three causes of hyperparathyroidism?
primary hyperparathyroidism
secondary hyperparathyroidism
tertiary
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what are the causes of primary hyperparathyroidism?
Adenoma - tumour of parathyroid gland, accounts for 85%
MEN 1/ MEN 2
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what is MEN 1/2
multiple endocrine neoplasia - group of disorders that leads to the development of multiple endocrine neoplasia's around the body
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what is MEN 1?
MEN 1 - mutation of MEN 1 gene on chr 11
leads to... 3 P's
P- Pituitary
P - pancreatic
P - parathyroid
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what is MEN 2A?
Men 2A - 1M 2P's
M - medullary thyroid cancer
P- Phaeochromocytopenia
P - parathyroid hyperplasia
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what are the causes of secondary hyperparathyroidism?
CKD
low vit D
sarcoidosis
thyrotoxicosis
178
what blood result sod you see in vit D deficiency?
low/normal Ca
high PTH
low vit D
normal phosphate
179
what blood results do you see in CKD?
high Ca
high PTH
low vit D usually
high phosphate
180
what are the complications of hyperparathyroidism?
trousseus sign
arrhythmias
"stones, bones, groans, psychiatric undertones"
kidney stones
osteopenia - osteoporosis / pathological fractures
pancreatitis
nephrogenic diabetes insipidus
bradycardia
181
what is the treatment of hypoparathyroidism?
usually replace calcium - calcium + vit D replacement
also check for Mg, and replace if needed
182
what is the treatment of hyperparathyroidism?
treat underlying cause -
- if adenoma, consider parathyroidectomy
- bisphosphonates - inhibits osteoclast activity
- sevelamer - if high phosphate
183
what is multiple myeloma?
proliferative disorder of PLASMA cells - uncontrolled replication of the plasma cells and immunoglobulins
184
what is the pathophysiology of normal plasma cell production?
haematopoeietic stem cells produced in the bone marrow -> migrate to the lymph tissue in the spleen -> are activated in the spleen by CD 4 + cells -> form mature plasma cells which go back to the bone marrow and live there -> produce antibodies against infection
185
what are the symptoms of multiple myeloma?
C- hypercalcaemia
R- renal insufficiency
A - anaemia
B- bone lesions - due to RANK-L production
Fatigue
weight loss
persistent back pain
186
what tests are done for multiple myeloma?
Protein electrophoresis
raised concentrations of monoclonal IgA/IgG proteins will be present in the serum
in the urine, they are known as Bence Jones proteins
bloods - anaemia, hypercalcaemia
bone marrow aspiration
imaging - xr may see bone lesions
187
what hormones are released from the anterior pituitary gland?
Growth Hormone
ACTH
LH/FSH
Prolactin
TSH
188
what hormones are produced by the posterior pituitary gland?
ADH
Oxytocin
189
what are the symptoms of hypopituitarism?
sx of hypothyroidism
reduced growth
hair loss
hypogonadism
depression
hypotension
visual field defect
headache
loss of appetite
190
what are the causes of hypopituitarism?
surgery
irraditation
tumour - pituitary adenoma - almot all are benign
infectio - TB
sheehans syndrome
191
what is sheehans syndrome?
pituitary necrosis post partum due to massive haemorrhage
192
what is acromegaly?
excessive growth hormone produced by pituitary adenoma
193
what are the features of acromegaly?
coarse facial appearance
spade like hands
large tongue
excessive seating and oiling skin
raised prolactin
194
what are the complications of acromegaly?
hypertension
diabetes
cardiomyopathy
colorectal cancer
195
what is the role of ADH?
causes water retention from the kidney - is released from the anterior pituitary
196
what are the two types of diabetes insipidus?
central and nephrogenic
197
wha is central diabetes insipidus?
there is damage to the anterior pituitary in some way causing reduction of ADH production from the pituitary
198
what are some causes of central diabetes insipidus?
head injury
trauma
sheehans syndrome
apoplexy
surgical intervention
pituitary adenoma
199
what are some causes of nephrogenic diabetes insipidus?
lithium
hypercalcaemia
hydronephrosis / pyelonephritis
hypokalaemia
200
what blood results do you get in diabetes insipidus?
hypernatraemia
increased plasma osmolality
decreased urine osmolality
201
what are the symptoms of diabetes insipidus?
polyuria
polydypsia
hypovolaemia/dehydration
202
what is the test to differentiate between diabetes insipidus?
desmopressin test - give desmopressin and measure urine osmolality - if the osmolality increases, means the receptors have responded, so is central
203
management of DI?
treat underlying cause
204
what is SIADH?
increased production of ADH from posterior pituitary which causes V2 receptors in the kidney ot be stimulated to reabsorb +++ water , which leads to reduced water in urine, and increased water in blood
205
causes of SIADH?
low O2/hypoxia
pneumonia/copd/ARDS/intubation
intracranial disease - stroke/ICH/traumatic brain injury
medications - SSRI/carbamazepine/TCA/sulfonylureas
ectopic ADH production - small cell lung cancer
206
what are the investigations for SIADH?
Urine osmolality: Urine osmolality is inappropriately high (>100 mOsm/kg) in relation to serum osmolality, as the kidneys should normally dilute urine in the setting of low serum osmolality.
Urine sodium concentration: Urine sodium concentration is typically high (>40 mmol/L) due to the action of ADH on the renal tubules.
207
what is the management of SIADH?
correction must be done slowly to avoid precipitating central pontine myelinolysis
fluid restriction
demeclocycline: reduces the responsiveness of the collecting tubule cells to ADH
ADH (vasopressin) receptor antagonists have been developed
208
what is the target hba1c when taking hypoglycaemic diabetic medications?
53
209
what is the starting dose of levothyroxine in < 65 years with no CVD?
1/6mcg/kg + round to nearest 25mcg
210
which antibodies are SPECIFIC to graves disease?
TRAbs - thyroid stimulating hormone antibodies
211
what is the impact of smoking on insulin/diabetes?
increases insulin resistance + prevents glucose metabolism
212
what is the first line management of MODY?
sulfonylureas - stimualte insulin production
213
what is the target HbA1c for patients with type 2 diabetes undergoing elective surgery?
< 69 mmol
214
what monitoring should be done for transgender patients who are taking testosterone?
3 monthly HCT
testosterone stimulate RBC production - can lead to polycythemia
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