Endocrinology Flashcards
1
Q
T1DM Ix?
A
- Urine = glucose and ketones
- Bloods = fasting glucose, random glucose, HbA1c, C-peptide, Diabetes-specific antibodies
2
Q
T1DM Antibodies?
A
- anti-GAD (80%)
- anti-ICA (70%)
- IAA (insulin autoantibodies)
- Insulinoma-associated-2 autoantibodies (IA-2A)
3
Q
Insulin autoantibodies (IAA) mushkies?
A
Presence in T1DM correlates strongly with age, found in over 90% of young children with T1DM but only 60% of older patients
4
Q
T1DM diagnostic criteria?
A
- 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)
5
Q
When is polydipsia seen?
A
Fasting plasma glucose >16.6mmol/L
6
Q
How often should HbA1c be checked in T2DM?
A
Every 3-6 months until stable, then 6 monthly
7
Q
HbA1c targets in T2DM for lifestyle/single drug treatment?
A
- Lifestyle = 48mmol/L (6.5%)
- Lifestyle + metformin = 48mmol/mol (6.5%)
- Includes any drug which may cause hypoglycaemia e.g. sulfonylurea = 53mmol/mol (7.0%)
8
Q
HbA1c targets in T2DM for patient already on one drug, but HbA1c has risen to 58mmol/L (7.5%)?
A
53 mmol/mol
9
Q
First-line management of T2DM?
A
- Assess cardiovascular risk –> high risk of CVD or established CVD or chronic HF?
- No –> Metformin
- Yes –> Metformin –> Once established at SGLT2 inhibitor
10
Q
If metformin not tolerated due to GI s/e?
A
Switch to modified release metformin
11
Q
If metformin is C/I and pt has high risk of CVD or established CVD or chronic HF?
A
SGLT2 monotherapy
12
Q
If metformin is C/I and pt is at low risk of CVD or established CVD or chronic HF
A
- DPP4 inhibitor OR Pioglitazone OR Sulfonylurea
- SGLT2 may be used if certain NICE criteria are met
13
Q
2nd line Rx of T2DM?
A
Add one of: DPP4i/Pioglitazone/Sulfonylurea/SGLT2i
14
Q
3rd line Rx of T2DM?
A
- Add another one of: DPP4i/Pioglitazone/Sulfonylurea/SGLT2i OR
- Start insulin-based treatment
15
Q
Further therapy of T2DM?
A
If triple therapy is not effective or tolerated consider switching one of the drugs for a GLP-1 mimetic if BMI >35 or insulin would have occupational implications (GLP-1 mimetics should only be added to insulin under specialist care)
16
Q
At what HbA1c level is further treatment indicated for T2DM?
A
58mmol/mol (7.5%)
17
Q
Starting insulin recommendation?
A
- Start with human NPH insulin (isophane, intermediate-acting) taken at bed-time or twice daily according to need
18
Q
Thiazolidinediones MOA?
A
PPAR-gamma receptor agonists, reduce peripheral insulin resistance (glitazones, e.g. pioglitazone)
19
Q
Thiazolidinedione s/e?
A
- Weight gain
- Liver impairment (monitor LFTs)
- Fluid retention (therefore C/I in HF)
- Fractures
- Bladder cancer
20
Q
When is thyroxine starting dose 25mcg?
A
- Cardiac disease
- Severe hypothyroidism
- > 50 y/o
21
Q
Change in thyroxine dose TFT check time?
A
8-12 weeks later
22
Q
Hypothyroid women become pregnant dose increase?
A
By at least 25-50mcg
23
Q
Levothyroxine s/e?
A
- Hyperthyroidism
- Reduced bone mineral density
- Worsening of angina
- AF
24
Q
Levothyroxine interactions?
A
Iron and calcium carbonate (absorption of levothyroxine reduced, give at least 4 hours apart)
25
Subclinical hypothyroidism bloods?
TSH raised but normal T3/T4
26
Significance of subclinical hypothyroidism?
1. Risk of progressing to overt hypothyroidism 2-5% per year (higher in men)
2. Risk increased by the presence of thyroid autoantibodies
27
Subclinical hypothyroidism Rx classification?
1. TSH 4-10 and normal thyroxine
2. TSH >10 and normal thyroxine
28
TSH 4-10 and normal thyroxine Rx?
1. < 65 y/o with symptoms suggestive of hypothyroidism --> give a trial of levothyroxine, if no improvement then stop
2. > 80 y/o = watch and wait
3. If asymptomatic observe and repeat TFTs in 6m
29
TSH >10 and normal thyroxine Rx?
1. < 70 y/o = start treatment even if asymptomatic
2. > 80 y/o = watch and wait
30
HHS or DKA has higher mortality?
HHS
31
HHS pathophysiology?
1. Hyperglycaemia results in osmotic diuresis with associated loss of sodium and potassium
2. Severe volume depletion results in a significant raised serum osmolarity (typically > than 320 mosmol/kg), resulting in hyperviscosity of blood.
3. Despite these severe electrolyte losses and total body volume depletion, the typical patient with HHS, may not look as dehydrated as they are, because hypertonicity leads to preservation of intravascular volume.
32
HHS Dx?
1. Hypovolaemia
2. Marked hyperglycaemia (>30mmol/L) without significant ketonaemia or acidosis
3. Serum osmolality > 320 mosmol/kg
33
HHS management goals?
1. Normalise the osmolality gradually (the key parameter)
2. Replace fluid and electrolyte losses
3. Normalise blood glucose gradually
34
Serum osmolality estimation?
2Na + Glucose + Urea
35
Fluid losses in HHS estimation?
100-220ml/kg (10-22 litres in an individual weighing 100kg)
36
HHS If the serum osmolarity is not declining despite positive balance with 0.9% sodium chloride?
Switch to 0.45% NaCl which is more hypotonic relative to HHS patient serum osmolality
37
HHS fluid replacement goals?
Aim for a positive balance of 3-6 litres by 12 hours and the remaining replacement of estimated fluid losses within the next 12 hours (aim of treatment should be to replace approximately 50% of estimated fluid loss within the first 12 hours and the remainder in the following 12 hours)
38
When is rising serum Na+ a concern during HHS fluid replacement?
Only a concern if the osmalility is not declining concurrently
39
Plasma glucose fall rate during HHS fluid replacement?
4-6mmol/hr, rate of fall should not exceed 10mmol/L in 24 hours
40
Target blood glucose during HHS treatment?
10-15mmol/L
41
Mixed HHS/DKA picture insulin treatment?
(I.e. if significant ketonaemia is present) --> 0.05 units/kg/hr fixed rate
42
Two conditions accounting for 90% of cases of hypercalcaemia?
1. Primary hyperparathyroidism = commonest cause in non-hospitalised patients
2. Malignancy = most common cause in hospitalised patients
43
Mechanisms by which malignancy can cause hypercalcaemia?
1. PTHrP from tumour e.g. SCLC
2. Bone metastases
3. Myeloma = due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
44
Diuretic causing hypercalcaemia?
Thiazides
45
How to assess for diabetic neuropathy in the feet?
10g monofilament
46
Diabetic foot screening?
Annually
1. Ischaemia = palpating dorsalis pedis and posterior tibial artery
2. Neuropathy = 10g monofilament on various parts of the sole of the foot
47
Risk stratification of diabetic feet?
1. Low = no risk factors except callus alone
2. Moderate = deformity/neuropathy/non-critical limb ischaemia
3. High = previous ulceration/amputation, on renal replacement therapy, neuropathy + non-critical limb ischaemia, neuropathy + callus/deformity, non-critical limb ischaemia + callus/deformity
48
Who should be followed up by local diabetic foot centre?
All moderate and high risk patients
49
Most common cause of thyrotoxicosis in UK?
Graces
50
Thyrotoxicosis causes?
1. Graves' disease
2. Toxic nodule goitre
3. Acute phase = subacute, post-partum, Hashimoto's thyroiditis
4. Amiodarone
5. Contrast
51
DKA pathophysiology?
Uncontrolled lipolysis (not proteolysis) which results in an excess of free fatty acids that are ultimately converted to ketone bodies
52
Most common causes of DKA?
1. Infection
2. Missed insulin doses
3. MI
53
DKA diagnosis?
1. BM > 11
2. pH < 7.3
3. Bicarb < 15
4. Ketones >3 or ++
54
DKA Rx?
1. Fluid replacement (1h, 2h, 2h, 4h, 4h, 5h)
2. 0.1 units/kg/hr fixed rate
3. Once BM <15mmol/l, start 5% dextrose infusion
4. Continue long acting insulin, stop short acting insulin
55
DKA potassium replacement?
1. Over 5.5 = Nil
2. 3.5-5.5 = 40mmol/L
3. <3.5 = senior review as additional potassium needs to be given
56
DKA resolution?
1. pH > 7.3
2. Ketones < 0.6
3. Bicarb > 15
57
If ketonaemia and acidosis hasnt resolved within 24 hours DKA?
Senior review from endocrinologist
58
Suspicion of cerebral oedema during fluid resuscitation in DKA?
CT head and senior review
59
Most common cause of hypothyroidism?
Hashimoto's (autoimmune) thyroiditis
60
Hashimoto's thyroiditis features?
1. 10F:1M
2. Goitre: firm, non-tender
3. Anti-TPO (thyroid peroxidase) and anti-thyroglobulin (anti-Tg) antibodies
61
What lymphoma is associated with Hashimoto's?
MALT lymphoma
62
Addison's disease management?
1. Hydrocortisone = 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
2. Fludrocortisone
63
Addison's disease intercurrent illness management?
1. Double glucocorticoid dose, fludrocortisone dose remains the same
64
A person with Addison's who vomits?
Should take IM hydrocortisone until vomiting stops
65
Addisons disease Dx?
Short Synacthen test
66
Short synacthen test meethod?
Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated.
67
9am serum cortisol interpretation for Addisons if ACTH stimulation test is not readily available?
1. > 500 = unlikely
2. < 100 = abnormal
3. 100-500 = Synacthen test to be performed
68
Very high mineralocorticoid activity steroid?
Fludrocortisone
69
High gluco and mineralocorticoid activity steroid?
Hydrocortisone
70
Predominant glucocorticoid activity?
Prednisolone
71
Very high glucocorticoid activity?
Dexamethasone
72
Mineralocorticoid s/e?
1. Fluid retention
2. Hypertension
73
When should systemic steroids be gradually withdrawn?
1. Received more than 40mg prednisolone daily for one week
2. Received more than 3 weeks of treatment
3. Recently received repeated courses
74
Pituitary adenoma classification?
1. Size (micro <1cm and macro >1cm)
2. Hormonal statues (secretory/non-secretory)
75
Most common type of pituitary adenoma?
Prolactinoma
76
Prolactinoma Dx?
MRI
77
Prolactinoma Rx?
1. Medically = Dopamine agonists e.g. cabergoline, bromocriptine --> inhibit release of prolactin from the pituitary gland
2. Surgery = if cannot tolerate/fails medical therapy. Usually trans-sphenoidal approach.
78
Octreotide use?
Somatostatin analogue used in the treatment of acromegaly
79
Pre-diabetes definition?
1. HbA1c 42-47 mmol/mol (6.0-6.4%)
2. Fasting glucose 6.1-6.9
80
Impaired fasting glucose cause?
Hepatic insulin resistance
81
Impaired glucose tolerance cause?
Muscle insulin resistance
82
IFG definition?
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l
83
IGT definition?
A fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
84
IFG management?
Offer OGTT to rule out a diagnosis of diabetes
85
Diabetic neuropathy management?
1. 1st line = amitryptiline, duloxetine, gabapentin or pregabalin
2. 2nd line = try one of the other 3 drugs
3. Tramadol rescue therapy for exacerbations
4. Topical capsaicin for localised neuropathic pain
5. Pain management clinics for resistant problems
86
GI autonomic neuropathy management?
Prokinetics = metoclopramide, domperidone, erythromycin
87
Falsely low HbA1c readings (reduced RBC lifespan)?
Sickle cell anaemia, G6PD, Hereditary Spherocytosis
88
What is HbA1c dependent upon?
1. Red blood cell lifespan
2. Average blood glucose concentration
89
Falsely high HbA1c (increased RBC lifespan)?
1. B12/folic acid deficiency
2. IDA
3. Splenectomy
90
Average plasma glucose from HbA1c calculation?
(HbA1c x 2) - 4.5
91
Thyrotoxicosis with tender goitre?
Subacute (De Quervain's) Thyroiditis
92
Subacute thyroiditis phases?
1. 3-6 weeks = hyperthyroid, painful goitre, raised ESR
2. 1-3 weeks = euthyroid
3. Weeks-months = hypothyroid
4. Thyroid structure and function returns to normal
93
Subacute thyroiditis Ix?
Thyroid scintigraphy: globally reduced uptake of Iodine-131
94
Subacute thyroiditis Rx?
1. Usually self limiting
2. Thyroid pain may respond to aspirin/NSAIDs
3. In more severe cases steroids are used, particularly if hypothyroidism develops
95
TSH aim?
0.5-2.5
96
T1DM HbA1c aim?
48mmol/mol (6.5%)
97
HbA1c monitoring in T1DM?
1. Every 3-6 months
2. Target <48mmol/mol (6.5%)
98
T1DM self monitoring of glucose?
1. Testing at least 4x a day, including before each meal and before bed
2. More frequent monitoring is recommended if frequency of hypoglycaemic episodes increases; during periods of illness; before, during and after sport; when planning pregnancy, during pregnancy and while breastfeeding
99
T1DM blood glucose targets?
1. 5-7 mmol/l on waking
2. 4-7 mmol/l before meals at other times of the day
100
When should metformin be added in T1DM?
If BMI >=25
101
Sulfonylurea MOA?
They work by increasing pancreatic insulin secretion and hence are only effective if functional B-cells are present. On a molecular level they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells.
102
Sulfonylurea s/e?
1. Hypoglycaemic episodes
2. Weight gain
3. Hyponatraemia due to SIADH
4. Bone marrow suppression
5. Hepatotoxicity (typically cholestatic)
6. Peripheral neuropathy
103
When should sulfonylureas be avoided?
Breastfeeding and pregnancy
104
Steroid therapy effect on TSH and T4?
Low TSH, Normal T4
105
Poor compliance with thyroxine TSH and T4?
High TSH, Normal T4
106
Initial target weight loss in T2DM overweight person?
5-10%
107
HbA1c monitoring in T2DM?
Every 3-6 months until stable, and then 6 monthly
108
Secondary hypothyroidism associated conditions?
1. Down's
2. Turner's
3. Coeliac
109
Secondary hypothyroidism Ix?
MRI brain and pituitary
110
DM medication contraindicated in HF?
Pioglitazone, can cause fluid retention
111
Recurrent UTIs which DM drug to avoid?
SGLT2 inhibitors
112
Cushing's syndrome cause classification?
1. ACTH dependent
2. ACTH independent
113
ACTH dependent causes of Cushing's syndrome?
1. Cushing's disease (80%) = Pituitary tumour secreting ACTH producing adrenal hyperplasia
2. Ectopic ACTH production (5-10%) e.g. SCLC is the most common cause
114
ACTH independent causes of Cushing's syndrome?
1. Iatrogenic = steroids
2. Adrenal adenoma (5-10%)
3. Adrenal carcinoma (rare)
4. Carney complex = incl. cardiac myxoma
5. Micronodula adrenal dysplasia
115
Pseudo-Cushing's mushkies?
1. Mimics Cushings
2. Often due to alcohol excess or severe depression
3. Causes false positive dexamethasone suppression test or 24 hour urinary free cortisol
4. Insulin stress test may be used to differentiate
116
Myxoedema coma presentation?
Confusion and hypothermia
117
Myxoedema coma Rx?
1. IV thyroid replacement
2. IV fluid
3. IV corticosteroids (until the possibility of coexisting adrenal insufficiency has been excluded)
4. Electrolyte imbalance correction
5. Sometimes rewarming
118
Hypoglycaemia community Rx?
1. Oral glucose 10-20g
2. Hypokit = syringe and vial of glucagon for IM or SC injection at home
119
Hypoglycaemia hospital Rx?
1. Given quick acting carbohydrate if pt alert
2. If unconscious/can't swallow --> S/C or IM Glucagon
3. Alternatively 20% glucose through large vein
120
DM medication C/I in bladder cancer?
Pioglitazone
121
Primary hyperaldosteronism causes?
1. Bilateral idiopathic adrenal hyperplasia (70%)
2. Conn's syndrome (adrenal adenoma)
3. Adrenal carcinoma (rare)
122
Primary hyperaldosteronism causes?
1. HTN
2. Hypokalaemia e.g. muscle weakness
3. Alkalosis
123
Primary hyperaldosteronism Ix?
1. Aldosterone:renin ratio
2. High resolution CT abdomen and adrenal vein sampling used to differentiate between unilateral and bilateral sources of aldosterone excess (if the CT is normal adrenal venous sampling (AVS) can be used to distinguish between unilateral adenoma and bilateral hyperplasia)
124
Primary hyperaldosteronism Rx?
1. Adrenal adenoma = surgery
2. Bilateral adrenocortical hyperplasia = aldosterone antagonist e.g. spironolactone
125
Thyroid storm precipitating events?
1. Thyroidal or non-thyroidal surgery
2. Trauma
3. Infection
4. Acute iodine load e.g. CT contrast media
126
Thyroid storm Rx?
1. BB = IV Propranolol
2. Antithyroid = Carbimazole/Propylthiouracil
3. Lugol's iodine
4. Dexamethasone e.g. 4mg IV QDS = blocks conversion of T4 to T3
5. Therapeutic plasma exchange if failed medical therapy
6. Treat underlying precipitating event
127
Hypertension and hypokalaemia?
Primary hyperaldosteronism
128
Graves' features?
1. Eye signs (30%) = exophthalmos, ophthalmoplegia
2. Pretibial myxoedema
3. Thyroid acropachy = triad of digital clubbing, soft tissue swelling of hands and feet, periosteal new bone formation
129
Graves' autoantibodies?
1. TSH receptor stimulating antibodies (90%)
2. anti-thyroid peroxidase antibodies (75%)
130
Graves' thyroid scintigraphy?
Diffuse, homogeneous, increased uptake of radioactive iodine
131
Medication causing hypercalcaemia?
Thiazides
132
High calcium and inappropriately normal/raised PTH level?
Primary hyperparathyroidism
133
Causes of primary hyperparathyroidism?
1. Solitary adenoma (80%)
2. Hyperplasia (15%)
3. Multiple adenoma (4%)
4. Carcinoma (1%)
134
Primary hyperparathyroidism associations?
1. HTN
2. MEN I and II
135
Primary hyperparathyroidism characteristic X-ray finding?
Pepperpot skull
136
Primary hyperparathyroidism Rx?
1. Definitive = Total parathyroidectomy
2. Conservative = If Ca < 0.25mmol/L upper limit of normal AND patient > 50 y/o AND no evidence of end-organ damage
3. Not suitable for surgery = Cinacalcet (calcimimetic)
137
SGLT2 inhibitor MOA?
Reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion
138
SGLT2 inhibitor examples?
1. Canagliflozin
2. Empagliflozin
3. Dapagliflozin
139
SGLT2 inhibitor adverse effect?
1. Urinary and genital infection, Fournier's gangrene
2. Normoglycaemic ketoacidosis
3. Increased risk of lower-limb amputation, feet should be closely monitored
140
What inhibits prolactin release?
Dopamine, so dopamine agonists e.g. bromocriptine can be used
141
Features of raised prolactin?
1. Men = impotence, loss of libido, galactorrhoea
2. Women = amenorrhoea, galactorrhoea
142
Causes of raise prolactin?
1. Prolactinoma
2. Pregnancy and oestrogens
3. Physiological = stress, exercise, sleep
4. Acromegaly = 1/3rd of pts
5. PCOS
6. Primary hypothyroidism (due to TRH stimulating prolactin release)
143
Drug causes of raised prolactin?
1. Metoclopramide, domperidone
2. Phenothiazines
3. Haloperidol
4. Very rare = SSRIs, opioids
144
Cushing's syndrome blood gas?
Hypokalaemic metabolic acidosis
145
Cushing's syndrome Ix?
1. Overnight dexamethasone suppression test = 1st line, most sensitive, pts with Cushing's syndrome do not have their morning cortisol spike suppressed
2. 24 hour urinary free cortisol
146
Cushing's syndrome localisation tests?
1. 9am and midnight plasma ACTH (and cortisol) tests (If ACTH is suppressed then a non-ACTH dependent cause is likely e.g. adrenal adenoma)
2. High dose dexamethasone suppression test
147
Carbimazole dosing?
Given in high doses for 6 weeks until the patient becomes euthyroid before being reduced
148
Carbimazole MOA?
1. Blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
2. In contrast propylthiouracil as well as this central mechanism of action also has a peripheral action by inhibiting 5'-deiodinase which reduces peripheral conversion of T4 to T3
149
Carbimazole s/e?
1. Agranulocytosis
2. Crosses the placenta, but may be used in low doses during pregnancy
150
Lithium effect on thyroid?
Hypothyroidism
151
Primary hypoadrenalism causes?
1. Addisons = autoimmune, commonest cause in UK
2. TB, HIV
3. Metastases
4. Antiphosphoplipid syndrome
152
GLP1 receptor agonist example?
Liraglutide
153
Acromegaly mushkies?
1. Excess GH secondary to pituitary adenoma in >95% cases
2. Minority of cases caused by ectopic GRG or GH production by tumours e.g. pancreatic
154
Acromegaly complications?
1. HTN
2. DM
3. Cardiomyopathy
4. Colorectal cancer
155
Graves' disease ATD therapy?
1. Carbimazole is started at 40mg and reduced gradually to maintain euthyroidism
2. Typically continued for 12-18 months
3. Alternative regimen is termed block and replace
156
Block and replace Graves' therapy?
1. Carbimazole started at 40mg
2. Thyroxine added when patient is euthyroid
3. Treatment typically lasts for 6-9 months
157
Graves' radioiodine treatment?
1. Used in patients who relapse following ATD therapy or are resistant to primary ATD treatment
2. C/I = Pregnancy (should be avoided for 4-6 months following treatment) and age < 16 years. Thyroid eye disease is a relative contraindication, as it may worsen the condition
3. Proportion of patients who become hypothyroid depends on the dose given, but as a rule the majority of patient will require thyroxine supplementation after 5 years
