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MRCP Combined > Endocrine > Flashcards

Endocrine Flashcards

1
Q

what is the most common cause of hyperthyroidism in the uk?

A

Anti-TSH receptor stimulating autoantibodies (often referred to as Thyroid Stimulating
Immunoglobulins) are almost diagnostic of Graves’ disease, the most common cause of
thyrotoxicosis in the UK

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2
Q

what features are seen in grave’s disease but not other causes of thyrotoxicosis?

A

• Eye signs: exophthalmos, ophthalmoplegia
• Pretibial myxedema
• Thyroid acropachy

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3
Q

what autoantibodies are found in raves disease?

A

Autoantibodies
• Anti-TSH receptor stimulating antibodies (90%)
• Anti-thyroid peroxidase antibodies (50%)

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4
Q

what is the TSH level and the total T4 level found in graves disease?

A

Labs:
• Low TSH (0.5 – 5.5)
• Elevated Total T4 (9-22)

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5
Q

what is the management of graves disease?

A

ATD titration
Block-and-Replace
Radioiodine treatment and surgery
Propranolol is often given initially to block adrenergic effec

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6
Q

describe the anti-thyroid drug titration management of graves disease?

A

ATD titration
• Carbimazole is started at 40mg and ↓ gradually to maintain euthyroidism
• Typically continued for 12-18 months
• Patients following an ATD titration regime have been shown to suffer fewer side-effects than those
on a block-and-replace regime

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7
Q

describe the block and replace management of graves disease?

A

Block-and-Replace
• Carbimazole is started at 40mg
• Thyroxine is added when the patient is euthyroid
• Treatment typically lasts for 6-9 months

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8
Q

what is the major complication of carbimazole therapy?

A

The major complication of carbimazole therapy is agranulocytosis (pancytopenia)

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9
Q

describe radioiodine therapy in the management of graves disease?
-what are contraindications?
-what is the most common side effect?

A

Radioiodine Treatment
• Contraindications include 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
• The 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, so hypothyroidism is the most common side effect of radioiodine Rx.

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10
Q

what are the seven causes of hyperthyroidism?

A

• Graves’ disease
• Toxic nodule goitres
• Subacute (de Quervain’s) thyroiditis
• Post-partum thyroiditis
• Acute phase of Hashimoto’s thyroiditis (later results in hypothyroidism)
• Toxic adenoma (Plummer’s disease)
• Amiodarone therapy

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11
Q

what is done to investigate hyperthyroid?

A

Investigation
• TSH down, T4 and T3 up
• Thyroid autoantibodies
• Other investigations are not routinely done but includes isotope scanning

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12
Q

what is toxic multinodular goitre?
-what is used in diagnosis?
-what is the treatment of choice?

A

Toxic Multinodular Goitre describes a thyroid gland that contains a number of autonomously functioning thyroid nodules that secrete excess thyroid hormones. Nuclear scintigraphy
reveals patchy uptake. The treatment of choice is radioiodine therapy

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13
Q

what is plummers disease?

A

Toxic adenoma (Plummer’s disease) Management:
• Radioiodine
• Subtotal thyroidectomy
• In pregnancy; medical management but if failed, subtotal thyroidectomy

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14
Q

what is a thyroid storm?

A

Thyroid Storm is a rare but life-threatening complication of thyrotoxicosis. It is typically seen in patients with established thyrotoxicosis and is rarely seen as the presenting feature. Iatrogenic thyroxine excess does not usually result in thyroid storm

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15
Q

what are the clinical features of a thyroid storm?

A

• Fever > 38.5oc
• Tachycardia
• Confusion and agitation
• Nausea and vomiting
• Hypertension
• Heart failure
• Abnormal liver function test

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16
Q

what is the treatment for a thyroid storm?

A

• Symptomatic treatment e.g. Paracetamol
• Treatment of underlying precipitating event
• Anti-thyroid drugs: e.g. Methimazole or propylthiouracil
• Lugol’ s iodine
• Dexamethasone - e.g. 4mg IV QDS - blocks the conversion of T4 to T3
• Propranolol

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17
Q

what is subacute thyroiditis?

A

Subacute Thyroiditis (De Quervain’s Thyroiditis) is thought to occur following viral infection and typically presents with hyperthyroidism

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18
Q

Tender goitre, hyperthyroidism and raised ESR + globally reduced uptake on technetium thyroid scan is typical of…

A

Subacute Thyroiditis (De Quervain’s Thyroiditis)

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19
Q

what are the features of thyroiditis?

A

Features
• Hyperthyroidism
• Painful goiter
• Raised ESR
• Globally ↓ uptake on iodine-131 scan

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20
Q

what is the management of subacute thyroiditis?

A

Management
• Usually self-limiting - most patients do not require treatment
• Thyroid pain may respond to aspirin or other NSAIDs
• In more severe cases steroids are used, particularly if hypothyroidism develops

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21
Q

what is hashimotos thyroiditis and who is this most commonly seen in?

A

Hashimoto’s Thyroiditis is an autoimmune disorder of the thyroid gland. It is typically associated with hypothyroidism although there may be a transient thyrotoxicosis in the acute phase. It is 10 times more common in women

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22
Q

what are the features of hashimoto thyroiditis?
-what antibodies exist?

A

Features
• Features of hypothyroidism
• Goitre: firm, non-tender
• Positive microsomal antibodies, anti-thyroid peroxidase (Anti-TPO) and anti-Tg antibodies.

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23
Q

what is subclinical hypothyroidism?

A

• Normal T3 – T4
• ↓ TSH (usually < 0.1 mu/l)

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24
Q

what are the causes of subclinical hyperthyroidism?

A

Causes
• Multinodular goitre, particularly in elderly ♀s
• Excessive thyroxine may give a similar biochemical picture

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25
Q

why is it important to recognise subclinical hyperthyroidism?

A

The importance in recognising subclinical hyperthyroidism lies in the potential effect on the cardiovascular system (atrial fibrillation) and bone metabolism (osteoporosis). It may also impact on quality of life and ↑ the likelihood of dementia

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26
Q

what is the management of subclinical hyperthyroidism?

A

Management
• TSH levels often revert back to normal - therefore levels must be persistently low to warrant
intervention
• A reasonable treatment option is a therapeutic trial of low-dose antithyroid agents for
approximately 6 months in an effort to induce a remission

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27
Q

what is subclinical hypothyroidism?

A

Basics
• Normal T3 – T4
• ↑TSH
• No obvious symptoms

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28
Q

what is the significance of subclinical hypothyroidism?

A

Significance
• Risk of progressing to overt hypothyroidism is 2-5% per year (higher in men)
• Risk ↑ by presence of thyroid autoantibodies

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29
Q

when should subclinical hypothyroidism be treated?

A

Treat if
• TSH>10
• Thyroid autoantibodies positive
• Other autoimmune disorder
• Previous treatment of graves’ disease

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30
Q

what is the most common cause of hypothyroidism?

A

In European countries primary atrophic hypothyroidism is the most cause causes of
hypothyroidism, whereas in North America Hashimoto’s thyroiditis appears to account for the
majority of cases. The reason for this discrepancy is unclear

Hypothyroidism affects around 1-2% of women in the UK and is around 5-10 times more common in ♀s than ♂s.

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31
Q

what are 5 causes of primary hypothyroidism?

A
  1. primary atrophic hypothyroidism
  2. Hashimoto’s thyroiditis
  3. After thyroidectomy or radioiodine treatment
  4. Drug therapy (e.g. lithium, amiodarone or anti-thyroid drugs such as carbimazole)
  5. Dietary iodine deficiency
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32
Q

primary atrophic hypothyroidism:
-what is this caused by?
-what is this assoc. with?

A

• Most common cause in Europe
• Autoimmune disease, associated with IDDM, Addison’s or pernicious anemia
• 5 times more common in women

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33
Q

what is secondary hypothyroidism caused by?

A
  1. From pituitary failure
  2. Other associated conditions
    • Down’s syndrome
    • Turner’s syndrome
    • Coeliac disease
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34
Q

what is a preferable TSH value?

A

A TSH value between 0.5 to 2.5 mU/l is now considered preferable

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35
Q

hypothyroid management:
-when should the starting dose of levothyroxine be lower?
-when should TFTs be checked after changing thyroxine dose?
-what is the overall goal of therapy?

A

• Initial starting dose of levothyroxine should be lower in elderly patients and those with ischemic heart disease (e.g. 25–50 mcg/day).
• Following a change in thyroxine dose thyroid function tests should be checked after 6-8 weeks
• The therapeutic goal is ‘normalisation’ of the thyroid stimulating hormone (TSH) level. As the majority unaffected people have a TSH value 0.5–2.5 mu/l it is now thought preferable to aim
for a TSH in this range. Dosage changes should of course also take account of symptoms
• There is no evidence to support combination therapy with levothyroxine and liothyronine

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36
Q

what are side effects of levothyroxine?

A

• Hyperthyroidism: due to over treatment
• ↓ bone mineral density
• Worsening of angina
• Atrial fibrillation

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37
Q

in secondary hypothyroidism what treatment is given prior to thyroxine?

A

Steroid therapy is required prior to thyroxine

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38
Q

what are the test results for sick euthyroid syndrome? who is this commonly seen in and what is the treatment?

A

low/normal TSH
low T4

common in inpatients, changes are
reversible upon recovery from the systemic illness. Usually in hospitalized patients.

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39
Q

what are the test results for poor compliance with thyroxine?

A

high TSH
normal or high T4

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40
Q

what are the TFTs found in steroid therapy?

A

low TSH, high T4

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41
Q

what is pendred’s syndrome?

A

Pendred’s Syndrome Autosomal recessive disorder of defective iodine uptake

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42
Q

what are the features of pendreds syndrome?

A

Features:
• Sensorineural deafness
• Goitre
• Euthyroid or mild hypothyroidism

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43
Q

describe the skin features seen in hyperthyroidism

A

• Pretibial myxedema: erythematous, edematous lesions above the lateral malleoli
• Thyroid acropachy: clubbing
• Scalp hair thinning
• ↑ sweating

Pruritus can occur in both hyper- and hypothyroidism

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44
Q

describe the skin features in hypothyroidism

A

• Dry (anhydrosis), cold, yellowish skin
• Non-pitting edema (e.g. Hands, face)
• Dry, coarse scalp hair, loss of lateral
aspect of eyebrows
• Eczema
• Xanthomata

Pruritus can occur in both hyper- and hypothyroidism

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45
Q

what drug is used as the antithyroid drug in preg.?

A

Propylthiouracil is traditionally taught as the antithyroid drug of choice in pregnancy. This
approach was supported by the 2007 Endocrine Society consensus guidelines. It also has the
advantage of being excreted to a lesser extent than carbimazole in breast milk.

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46
Q

describe what happen to thyroid hormones in pregnancy and why?

A

Pregnancy: Thyroid Problems in pregnancy there is ↑ in the levels of thyroxine-binding globulin (TBG). This causes ↑ in the levels of total thyroxine but does not affect the free thyroxine level

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47
Q

what can happen in untreated thyrotoxicosis in pregnancy

A

Thyrotoxicosis
• Untreated thyrotoxicosis ↑ the risk of fetal loss, maternal heart failure and premature labour

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48
Q

what are the common causes of hyperthyroidism in pregnancy?

A

• Graves’ disease is the most common cause of thyrotoxicosis in pregnancy. It is also recognised that activation of the TSH receptor by HCG may also occur - often termed transient
gestational hyperthyroidism. HCG levels will fall in second and third trimester

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49
Q

describe the management of thyrotoxicosis in pregnancy
-what should maternal free thyroxine levels kept at
-what should be checked at 30-36 weeks
-which therapies should not be used?

A

• Propylthiouracil has traditionally been the antithyroid drug of choice. This approach was supported by the 2007 endocrine society consensus guidelines
• Maternal free thyroxine levels should be kept in the upper third of the normal reference range to avoid fetal hypothyroidism
• Thyrotrophin receptor stimulating antibodies should be checked at 30-36 weeks gestation - helps to determine risk of neonatal thyroid problems
• Block-and-replace regimes should not be used in pregnancy
• Radioiodine therapy is contraindicated

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50
Q

hypothyroidism in pregnancy:
-is thyroxine safe?
-how often is TSH levels checked?
-breastfeeding?

A

Key points
• Thyroxine is safe during pregnancy
• Serum thyroid stimulating hormone measured in each trimester and 6-8 weeks post-partum
• Some women require an ↑ dose of thyroxine during pregnancy
• Breast feeding is safe whilst on thyroxine

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51
Q

what are the 5 different types of thyroid cancer?
-are features of hyper- / hypo- thyroidism commonly seen?`

A

Papillary: 70%
- Often young ♀s - excellent prognosis (associated with FAP)

Follicular: 20%
Spreads through blood vessels

Medullary: 5%
Cancer of parafollicular cells, secrete calcitonin, part of MEN-2

Anaplastic: 1%
Not responsive to treatment, can cause pressure symptoms

L ymphoma: Rare
Associated with Hashimoto’s and other autoimmune disorders

Features of hyperthyroidism or hypothyroidism are not commonly seen in patients with thyroid malignancies as they rarely secrete thyroid hormones

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52
Q

describe the management of papillary and follicular cancer

A

Management of papillary and follicular cancer
• Total thyroidectomy
• Followed by radioiodine (I-131) to kill residual cells
• Yearly thyroglobulin levels to detect early recurrent disease (only after total thyroid ablation)

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53
Q

primary hyperparathyroidism:
-what is the typical presentation?
-what is this most commonly caused by?

A

Primary Hyperparathyroidism: In postgraduate exams primary hyperparathyroidism is stereotypically seen in elderly ♀s with an unquenchable thirst and an inappropriately normal or raised parathyroid hormone level. It is most commonly due to a solitary adenoma

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54
Q

what are the features of hyperparathyroidism?

A

Features:
‘Bones, stones, abdominal groans and psychic moans’
• Polydipsia, polyuria
• Peptic ulceration/constipation/pancreatitis
• Bone pain/fracture
• Renal stones
• Depression
• Hypertension

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55
Q

what is hyperparathyroidism assoc with?

A

Associations
• Hypertension
• Multiple endocrine neoplasia: MEN I and II

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56
Q

what do investigations show in hyperparathyroidism?

A

Investigations
• Raised calcium, low phosphate
• PTH may be raised or normal
• Technetium-MIBI subtraction scan

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57
Q

what is the treatment for hyperparathyroidism?

A

Treatment
• IV Fluids
• Total parathyroidectomy
• Bisphosphonates

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58
Q

what is primary hypoparathyroidism?
-what do tests show?
-what is the treatment?

A

Primary hypoparathyroidism
• ↓ PTH secretion
• E.g. Secondary to thyroid surgery
• Low calcium, high phosphate
• Treat with alfacalcidol

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59
Q

what is psuedohypoparathyroidism?
-what is it due to?
-how is this inherited?
-what is the clinical syndrome?
-what is seen on blood test?
-how is diagnosis made?

A

• Target cells being insensitive to PTH
• In type I pseudohypoparathyroidism there is a complete receptor defect whereas in type II the
cell receptor is intact.
• Due to abnormality in a G protein
• Autosomal dominant fashion
• Associated with low IQ, short stature, shortened 4th and 5th metacarpals
• Low calcium, high phosphate, high PTH
• Diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of
PTH. In hypoparathyroidism this will cause ↑ in both cAMP and phosphate levels. In pseudohypoparathyroidism type I neither cAMP nor phosphate levels are ↑ whilst in pseudohypoparathyroidism type II only cAMP rises.

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60
Q

what is pseudopseudohypothyroidism/

A

Pseudopseudohypoparathyroidism
• Similar phenotype to pseudohypoparathyroidism but normal biochemistry

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61
Q

what are causes of cranial diabetes insipidus?

A

Causes of Cranial DI
• Idiopathic
• Post head injury
• Pituitary surgery
• Craniopharyngiomas
• Histiocytosis X

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62
Q

what is DIDMOAD?
-what is this AKA

A

DIDMOAD is the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram’s syndrome)

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63
Q

what are the causes of nephrogenic diabetes insipidus?

A

Causes of nephrogenic DI
• Genetic (primary)
• Electrolytes: hypercalcemia, Hypokalemia
• Drugs: demeclocycline, lithium
• Tubulo-interstitial disease: obstruction, sickle-cell, pyelonephritis

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64
Q

what’s the investigation for diabetes insipidus?

A

Investigation
• High plasma osmolarity, low urine osmolarity
• Water deprivation test

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65
Q

how to diagnose DM:
-symptomatic
-asymptomatic

what is impaired fasting glucose?
what is impaired glucose tolerance?

A

If the patient is symptomatic:
• Fasting glucose ≥7.0 mmol/l
• Random glucose ≥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.

Impaired fasting glucose (IFG): fasting glucose 6.1 - 7.0 mmol/l implies impaired fasting glucose

Impaired glucose tolerance (IGT): fasting plasma glucose < 7.0 and OGTT 2-hour 7.8 - 11.1

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66
Q

how to diagnose DM:
-symptomatic
-asymptomatic

what is impaired fasting glucose?
what is impaired glucose tolerance?

A

If the patient is symptomatic:
• Fasting glucose ≥7.0 mmol/l
• Random glucose ≥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.

Impaired fasting glucose (IFG): fasting glucose 6.1 - 7.0 mmol/l implies impaired fasting glucose

Impaired glucose tolerance (IGT): fasting plasma glucose < 7.0 and OGTT 2-hour 7.8 - 11.1

a HbA1c of greater than or equal to 6.5% (48 mmol/mol) is diagnostic of diabetes mellitus
a HbAlc value of less than 6.5% does not exclude diabetes (i.e. it is not as sensitive as fasting samples for detecting diabetes)
in patients without symptoms, the test must be repeated to confirm the diagnosis
it should be remembered that misleading HbA1c results can be caused by increased red cell turnover
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67
Q

what are common adverse effects of sulfonylurea?
what are rarer side effects?

A

Common adverse effects
• Hypoglycaemic episodes (more common with long acting preparations such as chlorpropamide)
• ↑ appetite and weight gain

Rarer adverse effects
• Syndrome of inappropriate ADH secretion
• Bone marrow suppression
• Liver damage (cholestatic)
• Photosensitivity
• Peripheral neuropathy
• Sulfonylureas should be avoided in breast feeding and pregnancy

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68
Q

what is metformin and how does it work?

A

Metformin is a biguanide used mainly in the treatment of type 2 diabetes mellitus.
Mechanism of action
• ↑ Insulin sensitivity
• ↓ hepatic gluconeogenesis
• May also ↓ gastrointestinal absorption of carbohydrates

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69
Q

When should metformin be used?
-what other conditions is metformin used in?

A

Unlike sulphonylureas it does not cause hypoglycemia and weight gain and is therefore first-line if the patient is overweight. Metformin is also used in polycystic ovarian syndrome and non-alcoholic fatty liver disease

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70
Q

what are th adverse effects of metformin - how should this drug be initiated to reduce the risk of these?

A

Adverse effects
• Gastrointestinal upsets are common (nausea, anorexia, diarrhea), intolerable in 20%
• ↓ vitamin B12 absorption - rarely a clinical problem
• Lactic acidosis* with severe liver disease or renal failure
• High dose (>2gm) interferes with enterohepatic circulation of bile salt → diarrhea.

Gastrointestinal side-effects are more likely to occur if metformin is not slowly titrated up. The BNF advises leaving at least 1 week before increasing the dose. If a patient is intolerant to standard metformin then modified release preparations should be tried

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71
Q

what are the contraindications to metformin?

A

• Chronic kidney disease: NICE recommend reviewing metformin if the creatinine is > 130
μmol/l and stopping metformin if > 150 μmol/l
• Do not use during suspected episodes of tissue hypoxia (e.g. Recent MI, sepsis)
• Alcohol abuse is a relative contraindication
• Stop 2 days before general anaesthetic, restart when renal function normal
• Stop prior to IV contrast e.g. Angiography, restart when renal function normal

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72
Q

what are thiazolidinediones and how do they work?

A

Thiazolidinediones are a new class of agents used in the treatment of type 2 diabetes mellitus. They are agonists to the PPAR-gamma receptor and ↓ peripheral insulin resistance
Peroxisome Proliferator-Activated Receptor Gamma (PPAR-gamma receptor) is an intracellular nuclear receptor. Its natural ligands are free fatty acids and it is thought to control adipocyte differentiation and function

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73
Q

what are the adverse effects of thiazolidinediones and when are they contraindicated?

A

Adverse effects
• Weight gain
• Liver impairment: monitor LFTs
• Fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is ↑
if the patient also takes insulin
• Recent studies have indicated an ↑ risk of fractures
• Rosiglitazone is not recommended for use in patients with ischemic heart disease or peripheral
arterial disease. The risk of complications may be ↑ if rosiglitazone is combined with insuli

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74
Q

when are thiazolidinediones considered?

A

NICE guidance on thiazolidinediones
• Only continue if there is a reduction of > 0.5 percentage points in HbA1c in 6 months

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75
Q

how does GLP-1 work?

A

a hormone released by the small intestine in response to an oral glucose load

In normal physiology an oral glucose load results in a greater release of insulin than if the same load is given intravenously - this known as the incretin effect. This effect is largely mediated by GLP-1 and is known to be ↓ in T2DM.

Increasing GLP-1 levels, either by the administration of an analogue or inhibiting its breakdown, is therefore the target of two recent classes of drug

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76
Q

Exenatide (GLP-1)

A

• ↑ insulin secretion and inhibit glucagon secretion
• Licensed for use in T2DM
• Must be given by subcutaneous injection within 60 minutes before the morning and evening
meals. It should not be given after a meal
• May be combined with metformin, a sulfonylurea or a thiazolidinedione
• Typically results in weight loss
• Major adverse effect is nausea and vomiting
• The Medicines and Healthcare products Regulatory Agency has issued specific warnings on the
use of exenatide:
o increased risk of severe pancreatitis o increased risk of renal impairment

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77
Q

Exenatide (GLP-1 mimetic)
-what is the overall effect on insulin secretion and glucagon
-how is this given
-what are the side effects
-what do these drugs increase the risk of?

A

• ↑ insulin secretion and inhibit glucagon secretion
• Licensed for use in T2DM
• Must be given by subcutaneous injection within 60 minutes before the morning and evening
meals. It should not be given after a meal
• May be combined with metformin, a sulfonylurea or a thiazolidinedione
• Typically results in weight loss
• Major adverse effect is nausea and vomiting
• The Medicines and Healthcare products Regulatory Agency has issued specific warnings on the
use of exenatide:
o increased risk of severe pancreatitis
o increased risk of renal impairment

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78
Q

NICE guidelines:
-when should exenatide be used?
-when should exenatide be continued after starting?

A

NICE guidelines on the use of Exenatide
if triple therapy is not effective, not tolerated or contraindicated then NICE advise that we consider combination therapy with metformin, a sulfonylurea and a glucagonlike peptide1 (GLP1) mimetic if:
BMI >= 35 kg/m² and specific psychological or other medical problems associated with obesity or
BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or

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79
Q

what are the advantages of DPP-4 inhibitors to exenatide? (gliptin)

A

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors (e.g. Vildagliptin, sitagliptin)
• Oral preparation
• Trials show that the drugs are relatively well tolerated with no ↑ incidence of hypoglycemia
• Do not cause weight gain

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80
Q

DPP4 inhibitors - what does NICE advise RE when should therapy be continued and when would a DPP4 inhibitor be preferable to a thiazolidinedione

A

NICE Guidelines on DPP-4 Inhibitors
• Continue DPP-4 inhibitor only if there is ↓ of > 0.5 percentage points in HbA1c in 6 months
• NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight
gain would cause significant problems, a thiazolidinedione is contraindicated or the person has had a poor response to a thiazolidinedione

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81
Q

describe the dietary advice that should be given to patients with T2DM

A

• Encourage high fibre, low glycaemic index sources of carbohydrates
• Include low-fat dairy products and oily fish
• Control the intake of foods containing saturated fats and trans fatty acids
• Limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care
should be taken to avoid excess energy intake
• Discourage use of foods marketed specifically at people with diabetes
• Initial target weight loss in an overweight person is 5-10%

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82
Q

what are the HbA1c targets for T2DM:
controlled with lifestyle
controlled with metformin
controlled with any drug that could cause hypo

A

Lifestyle 48 mmol/mol (6.5%)

Lifestyle + metformin 48 mmol/mol (6.5%)

Includes any drug which may cause hypoglycaemia (e.g. lifestyle + sulfonylurea) 53 mmol/mol (7.0%)

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83
Q

HbA1c targets:
-is this the same for everyone?
-how often should HbA1c be checked?
-what are targets dependant on?

A

This is area which has changed in 2015

individual targets should be agreed with patients to encourage motivation
HbA1c should be checked every 3-6 months until stable, then 6 monthly
NICE encourage us to consider relaxing targets on 'a case-by-case basis, with particular consideration for people who are older or frail, for adults with type 2 diabetes'
in 2015 the guidelines changed so HbA1c targets are now dependent on treatment
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84
Q

what are the targets BPs in T2DM?

A

Same as non-diabetics
clinic BP HBPM/ABPM
Age < 80 years 140/90 mmHg 135/85 mmHg
Age > 80 years 150/90 mmHg 145/85 mmHg)
• ACE inhibitors are first-line

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85
Q

describe the treatment in T2DM if patients can tolerate metformin?

A

metformin is still first-line and should be offered if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions
if the HbA1c has risen to 58 mmol/mol (7.5%) then a second drug should be added from the following list:
sulfonylurea
gliptin
pioglitazone
SGLT-2 inhibitor
if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then triple therapy with one of the following combinations should be offered:
metformin + gliptin + sulfonylurea
metformin + pioglitazone + sulfonylurea
metformin + sulfonylurea + SGLT-2 inhibitor
metformin + pioglitazone + SGLT-2 inhibitor
OR insulin therapy should be considered

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86
Q

describe the treatment in T2DM if patients can’t tolerate metformin?

A

if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions, consider one of the following:
sulfonylurea
gliptin
pioglitazone
if the HbA1c has risen to 58 mmol/mol (7.5%) then a one of the following combinations should be used:
gliptin + pioglitazone
gliptin + sulfonylurea
pioglitazone + sulfonylurea
if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy

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87
Q

when should diabetes patients be offered a statin?

A

following the 2014 NICE lipid modification guidelines only patients with a 10-year cardiovascular risk > 10% (using QRISK2) should be offered a statin. The first-line statin of choice is atorvastatin 20mg on

• If serum cholesterol target is not reached consider increasing simvastatin to 80mg HS.
• If target still not reached consider using a more effective statin (e.g. Atorvastatin) or adding
ezetimibe
• Target total cholesterol is < 4.0 mmol/l

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88
Q

when should T2DM patients be offered insulin?

A

Starting insulin
• Usually commenced if HbA1c > 7.5%
• NICE recommend starting with human NPH insulin (isophane, intermediate acting) taken at
bed-time or twice daily according to need

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89
Q

when is aspirin given to patients with T2DM?

A

• Aspirin to all patients > 50 years and to younger patients with other significant risk factors

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90
Q

what should be prescribed for T2DM patients if serum triglycerides are > 4.5

A

• If serum triglyceride levels are > 4.5 mmol/l prescribe fenofibrate

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91
Q

what is the first and second line therapy of diabetic neuropathy?
-what other options are available?

A

• First-line: oral duloxetine. Oral amitriptyline if duloxetine is contraindicated.
• Second-line treatment: if first-line treatment was with duloxetine, switch to amitriptyline or
pregabalin, or combine with pregabalin. If first-line treatment was with amitriptyline, switch to
or combine with pregabalin
• Other options: pain management clinic, tramadol (not other strong opioids), topical lidocaine
for localised pain if patients unable to take oral medication
• Consider capsaicin ointment (red pepper extract) local application

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92
Q

what are the symptoms of gastroparesis?
-what are the management options?

A

Gastroparesis
• Symptoms include erratic blood glucose control, bloating and vomiting
• Management options include metoclopramide, domperidone or erythromycin

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93
Q

Hypoglycaemia: drug abuse
↑ Insulin with ↓ C-Peptide level points to a diagnosis of?
C-Peptide level ↑ with?

A

↑ Insulin with ↓ C-Peptide level points to a diagnosis of insulin abuse
C-Peptide level ↑ with Sulfonylurea abuse

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94
Q

what are the causes of hypoglycaemia?

A

Causes
• Insulinoma - ↑ ratio of proinsulin to insulin
• Self-administration of insulin/sulphonylureas
• Liver failure
• Addison’s disease
• Alcohol

Other possible causes in children
• Nesidioblastosis - β cell hyperplasia

95
Q

what is HbA1c dependant on?

A

Glycosylated hemoglobin (HbA1c) is the most widely used measure of long-term glycaemic control in DM. HbA1c is produced by the glycosylation of hemoglobin at a rate proportional to the glucose concentration. The level of HbA1c therefore is dependent on
• Red blood cell lifespan
• Average blood glucose concentration
HbA1c is generally thought to reflect the blood glucose over the previous ‘2-3 months’ although there is some evidence it is weighed more strongly to glucose levels of the past 2-4 week

96
Q

what is the diagnosis of hyperosmolar, hyperglycaemic state?

A
  1. Glucose > 33.3 mmol/l
  2. pH > 7.30
  3. Serum bicarbonate > 15 mmol/l
  4. Serum osmolality > 320 mosmol/kg
  5. Traces of ketones may be present in urines
97
Q

what is the pathophysiology of HHS?

A

Pathophysiology
-Hyperglycaemia results in osmotic diuresis with associated loss of sodium and potassium
-Severe volume depletion results in a significant raised serum osmolarity (typically > than 320 mosmol/kg), resulting in hyperviscosity of blood.
-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.

98
Q

what are the clinical features of HHS:
-general
-Neurological
-haematological
-cardiovascular

A

General: fatigue, lethargy, nausea and vomiting
Neurological: altered level of consciousness, headaches, papilloedema, weakness
Haematological: hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis)
Cardiovascular: dehydration, hypotension, tachycardia

99
Q

what is the treatment of HHS?

A
  1. Normalise the osmolality (gradually)
    1. Replace fluid and electrolyte losses
    2. Normalise blood glucose (gradually)
100
Q

describe the fluid therapy for HHS

A

Intravenous (IV) 0.9% sodium chloride solution is the first line fluid for restoring total body fluid
-If the serum osmolarity is not declining despite positive balance with 0.9% sodium chloride, then the fluid should be switched to 0.45% sodium chloride solution which is more hypotonic relative to the HHS patients serum osmolarity
-IV fluid replacement should aim to achieve a positive balance of 3-6 litres by 12 hours and the remaining replacement of estimated fluid losses within the next 12 hours.

101
Q

should insulin therapy be used in HHS?

A

If significant ketonaemia is present (3β-hydroxy butyrate is more than 1 mmol/L) this indicates relative hypoinsulinaemia and insulin should be started at time zero (e.g. mixed DKA / HHS picture). The recommended insulin dose is a fixed rate intravenous insulin infusion given at 0.05 units per kg per hour.
If significant ketonaemia is not present (3β-hydroxy butyrate is less than 1 mmol/L) then do NOT start insulin.

102
Q

Describe how DKA develops

A

The low-insulin condition in DKA stimulate → lipolysis → production of ketone bodies, β- hydroxybutyrate and acetoacetate, which can be used as metabolic fuel

103
Q

what is the diagnosis of DKA?

A

British joint diabetes society
Key points
glucose > 11 mmol/l or known diabetes mellitus
pH < 7.3
bicarbonate < 15 mmol/l
ketones > 3 mmol/l or urine ketones ++ on dipstick

American diabetes assoc
Key points
glucose > 13.8 mmol/l
pH < 7.30
serum bicarbonate <18 mmol/l
anion gap > 10
ketonaemia

104
Q

describe the management of DKA

A

fluid replacement: most patients with DKA are deplete around 5-8 litres. Isotonic saline is used initially.

-insulin: an intravenous infusion should be started at 0.1 unit/kg/hour. Once blood glucose is < 15 mmol/l an infusion of 5% dextrose should be started
-correction of hypokalaemia
-long-acting insulin should be continued, short-acting insulin should be stopped

105
Q

what are the complications of DKA and its treatment?

A

• Gastric stasis
• Cerebral edema
• Thromboembolism
• Acute respiratory distress syndrome
• Acute renal failure

106
Q

is diabetes common in pregnancy?

A

Pregnancy: Diabetes Mellitus
Diabetes mellitus may be a pre-existing problem or develop during pregnancy, gestational diabetes. It
complicates around 1 in 40 pregnancies

107
Q

what are risk factors for gestational diabetes?

A

Risk factors for gestational diabetes
• BMI of > 30 kg/m2
• Previous macrosomic baby weighing 4.5 kg or above.
• Previous gestational diabetes
• First-degree relative with diabetes
• Family origin with a high prevalence of diabetes (South Asian, black Caribbean and Middle
Eastern)

108
Q

what is the screening for gestational diabetes?

A

Screening for gestational diabetes
• If a women has had gestational diabetes previously an oral glucose tolerance test (OGTT)
should be performed at 16-18 weeks and at 28 weeks if the first test is normal
• Women with any of the other risk factors should be offered an OGTT at 24–28 weeks

109
Q

what is the management for gestational diabetes?

A

Management
• Weight loss for women with BMI of > 27 kg/m2
• Stop oral hypoglycaemic agents, apart from metformin*, and commence insulin
• Folic acid 5 mg/day from pre-conception to 12 weeks gestation
• Detailed anomaly scan at 18-20 weeks including 4-chamber view of the heart and outflow tracts
• Tight glycaemic control ↓ complication rates
• Treat retinopathy as can worsen during pregnancy

110
Q

How are patients with gestational diabetes treated after they have delivered?

A

Women who develop gestational diabetes should stop taking hypoglycaemic medication following delivery. A fasting glucose should be checked at the 6 week postnatal check

111
Q

what is type 1 diabetes assoc HLA? how much genetic concordance is shown in identical twins?

A

Type 1 Diabetes Mellitus is caused by autoimmune destruction of the β-cells of the pancreas. Identical twins show a genetic concordance of 40%. It is associated with HLA-DR3 and DR4. It is inherited in a polygenic fashion

112
Q

describe the pathophysiology of T1DM?

A

Type 1 DM Pathophysiology:
• Autoimmune disease
• Antibodies against β cells of pancreas
• HLA DR4 > HLA DR3
• Various antibodies such as islet-associated antigen (IAA) antibody and glutamic acid
decarboxylase (GAD) antibody are detected in patients who later go on to develop type 1 DM - their prognostic significance is not yet clear

113
Q

what will 40% of T1DM develop?

A

Adhesive capsulitis (frozen shoulder) is strongly associated with diabetes type-I with as many as
40% of patients developing this problem at some stage

114
Q

what is type 2 diabetes caused by? what is the concordance in identical twins?

A

Type 2 diabetes mellitus is thought to be caused by a relative deficiency of insulin and the phenomenon of insulin resistance. Age, obesity and ethnicity are important aetiological factors. There is almost 100% concordance in identical twins and no HLA associations

115
Q

what is MODY:
-how is it inherited
-how many different genetic mutations have been found

A

Maturity-Onset Diabetes Of The Young (MODY) is characterized by the development of type 2 diabetes mellitus in patients < 25 years old.
It is typically inherited as an autosomal dominant condition.
Over six different genetic mutations have so far been identified as leading to MODY.
Ketosis is not a feature at presentation. Usually there is a strong family history

116
Q

MODY 3, MODY 2, MODY1:
-percentage of cases
-due to a defect in what gene?

A

MODY 3
• 60% of cases
• Due to a defect in the HNF-1 α gene (Hepatocyte Nuclear Factor).
MODY 2
• 20% of cases
• Due to a defect in the glucokinase gene
MODY 1
• <10%
• Due to defect in HNF-4 α gene.

117
Q

Describe DVLA rules for:
if on insulin - ?HGV ?Car
if on tablets
if on diet controlled alone

A

Specific rules
• If on insulin then can hold HGV license if:
there has not been any severe hypoglycaemic event in the previous 12 months
the driver has full hypoglycaemic awareness
the driver must show adequate control of the condition by regular blood glucose monitoring*, at least twice daily and at times relevant to driving
the driver must demonstrate an understanding of the risks of hypoglycaemia
here are no other debarring complications of diabetes

• If on insulin then patient can drive a car as long as they have hypoglycaemic awareness and no relevant visual impairment
• If on tablets, exenatide or gliptin no need to notify DVLA
• If diet controlled alone and no relevant complications (e.g. Maculopathy) then no requirement
to inform DVLA

118
Q

what is an insulinoma?
-is this common?
-malignant?
-which MEN is assoc?

A

Insulinoma is a neuroendocrine tumour deriving mainly from pancreatic Islets of Langerhans cells Basics
• Most common pancreatic endocrine tumour
• 10% malignant, 10% multiple
• Of patients with multiple tumours, 50% have MEN-1

119
Q

what are the features of insulinoma:
-hypoglycaemia
-weight
-blood tests: insulin/proinsulin:insulin ratio/c peptide

A

Features
• Of hypoglycemia: typically early in morning or just before meal, e.g. Diplopia, weakness etc
• Rapid weight gain may be seen
• High insulin, raised proinsulin:insulin ratio
• High C-peptide

120
Q

what is the diagnosis of insulinoma?

A

Diagnosis
• Supervised, prolonged fasting (up to 72 hours)
• CT pancreas

121
Q

Insulin stress test:
-how does this work?
-what can this differentiate between?

A

Basics
• Used in investigation of hypopituitarism
• IV insulin given, GH and cortisol levels measured
• With normal pituitary function GH and cortisol should rise

nsulin stress tests are also occasionally used to differentiate Cushing’s from pseudo-Cushing

122
Q

what are the contraindications to insulin stress test?

A

Contraindications
• Epilepsy
• Ischemic heart disease
• Adrenal insufficiency

123
Q

what is the most common cause of cushings syndrome?

A

Cushing’s disease (pituitary tumor) is the most common, non-iatrogenic, cause of Cushing’s syndrome

124
Q

what are the ACTH dependant causes of cushings syndrome?

A

ACTH dependent causes
• Cushing’s disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia
• Ectopic ACTH production (5-10%): e.g. Small cell lung cancer

Small cell lung cancer accounts 50-75% of case of ectopic ACTH

125
Q

what are the ACTH independant causes of cushings syndrome?

A

ACTH independent causes
• Iatrogenic: steroids
• Adrenal adenoma (5-10%)
• Adrenal carcinoma (rare)
• Carney complex: syndrome including cardiac myxoma
• Micronodular adrenal dysplasia (very rare)

126
Q

what is pseudo-cushings often due to? what can be used to differentiate?

A

Pseudo-Cushing’s
• Mimics Cushing’s
• Often due to alcohol excess or severe depression
• Causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
• Insulin stress test may be used to differentiate

127
Q

which two tests confirm cushings syndrome?

A

The two most commonly used tests are:
overnight dexamethasone suppression test (most sensitive)
24 hr urinary free cortisol

128
Q

describe the level of:
Cortisol following low-dose dexamethasone
Cortisol following high-dose dexamethasone
ACTH
in normal patient

A

Cortisol following low-dose dexamethasone: low
Cortisol following high-dose dexamethasone: low
ACTH: normal

129
Q

describe the level of:
Cortisol following low-dose dexamethasone
Cortisol following high-dose dexamethasone
ACTH
in Cushing’s syndrome due to other causes (e.g. adrenal adenomas)

A

Cortisol following low-dose dexamethasone: unequiv.
Cortisol following high-dose dexamethasone: unequiv.
ACTH: low

130
Q

describe the level of:
Cortisol following low-dose dexamethasone
Cortisol following high-dose dexamethasone
ACTH
in Cushing’s disease (i.e. pituitary adenoma → ACTH secretion)

A

Cortisol following low-dose dexamethasone: unequiv.
Cortisol following high-dose dexamethasone: low
ACTH: high

131
Q

Cortisol following low-dose dexamethasone
Cortisol following high-dose dexamethasone
ACTH
in Ectopic ACTH syndrome l

A

Cortisol following low-dose dexamethasone: uneiquiv
Cortisol following high-dose dexamethasone: unequiv
ACTH: high

132
Q

what happens to cortisol in high-dose dex sup test if pituitary source vs ectopic/adrenal

A

High-dose dexamethasone suppression test
• If pituitary source then cortisol suppressed
• If ectopic/adrenal then no change in cortisol

133
Q

what happens to cortisol in CRH stimulation if pituitary source vs ectopic/adrenal

A

CRH (corticotrophin-releasing hormone) stimulation
• If pituitary source then cortisol rises
• If ectopic/adrenal then no change in cortisol

134
Q

what is liddle’s syndrome
-how is this inherited
-what does it result in?

A

Liddle’s Syndrome is an autosomal dominant disorder that mimics hyperaldosteronism, resulting in Hypokalemia associated with hypertension. It is thought to be caused by disordered sodium channels in the distal tubules leading to increased reabsorption of sodium, leading to hypokalemia and alkalosis.

↓ rennin - ↓ aldesterone

135
Q

what is the treatment of liddle’s syndrome?

A

Treatment is with either amiloride or triamterene

136
Q

what is gitelmans syndrome?

A

Gitelman’s Syndrome: defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule

Little minded people (Liddle) would’ve HTN but gentlemen would not develop HTN

Features
• Hypokalemia
• Hypomagnesemia
• Hypocalciuria
• Metabolic alkalosis
• Normotension

↑ rennin - ↑ aldesterone

137
Q

what is Bartter’s Syndrome?
-how is this inherited?
-what is the pathophysiology?
-is this assoc with hypotension?

A

Bartter’s Syndrome is an inherited cause (usually autosomal recessive) of severe Hypokalemia due to defective chloride absorption at the Na+ K+ 2Cl- cotransporter in the ascending loop of Henle. It should be noted that is associated with normotension (unlike other endocrine causes of Hypokalemia such as Conn’s, Cushing’s and Liddle’s syndrome which are associated with hypertension)

138
Q

what are the features of bartter’s syndrome?

A

Features:
• Usually presents in childhood, e.g. Failure to thrive
• Polyuria, polydipsia
• Renal stones, nephrocalcinosis is commom
• W eakness

↑ rennin - ↑ aldesterone

139
Q

• Hypokalemia
• NO Hypomagnesemia
• Normotension
-what should you think of?

A

bartter’s syndrome

140
Q

what is the most common cause of primary hyperaldosteronism?

A

Primary Hyperaldosteronism: primary hyperaldosteronism was previously thought to be
most commonly caused by an adrenal adenoma, termed Conn’s Syndrome. However, recent studies have shown that bilateral idiopathic adrenal hyperplasia is the cause in 70% of cases.

141
Q

what are the features of primary hyperaldosteronism?

A

Features
• Hypertension
• Hypokalemia (e.g. Muscle weakness)
• Alkalosis
• Hypernatremia
• Not related to posture

142
Q

what are the investigations for primary hyperaldosteronism?

A

the 2016 Endocrine Society recommend that a plasma aldosterone/renin ratio is the first-line investigation in suspected primary hyperaldosteronism
should show high aldosterone levels alongside low renin levels (negative feedback due to sodium retention from aldosterone)
following this a high-resolution CT abdomen and adrenal vein sampling is used to differentiate between unilateral and bilateral sources of aldosterone excess
Adrenal Venous Sampling (AVS) can be done to identify the gland secreting excess hormone in primary hyperaldosteronism

143
Q

what is the management of primary hyperaldesteronism?

A

Sodium restrict
adrenal adenoma: surgery
bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone

144
Q

what is addison’s disease?

A

Addison’s Disease: autoimmune destruction of the adrenal glands is the commonest cause of hypoadrenalism in the UK, accounting for 80% of cases

145
Q

what are the clinical features of addison’s disease?

A

Features
• Lethargy, weakness, anorexia, nausea & vomiting, weight loss
• Hyperpigmentation, vitiligo, loss of pubic hair in women
• Crisis: collapse, shock, pyrexia

Typical history of Addison’s: abdominal pain and vomiting. Patients may have a history of other
autoimmune conditions such as thyroid disorders. Steroids should be given as soon as possible

146
Q

what are primary causes of hypoadrenalism? other than addisons?

A

•Tuberculosis
•Metastases (e.g. Bronchial Carcinoma)
•Meningococcal septicemia (Waterhouse-Friderichsen Syndrome)
•HIV
•Antiphospholipid Syndrome
•Severe illness

147
Q

what are secondary causes of hypoadrenalism?

A

•Pituitary disorders (e.g. Tumours, Irradiation, Infiltration)
•Drugs: ACE-I – Heparin – Lead poisoning

148
Q

what drug therapy can cause hypoadrenalism?

A
  1. Exogenous glucocorticoid therapy
149
Q

what is pseudohypoaldosteronism?

A

Pseudohypoaldosteronism: due to primary aldosterone resistance (rare, but may occur due to Spirnolactone)

150
Q

what is Dehydroepiandrosterone and how is this affected in addisons disease?

A

Dehydroepiandrosterone is the most abundant circulating adrenal steroid. Adrenal glands are the
main source of DHEA in ♀s - loss of functioning adrenal tissue as in Addison’s disease may result
in symptoms secondary to androgen deficiency, such as loss of libido. Research is ongoing as to
whether routine replacement of DHEA is beneficial

151
Q

Hyponatremia and high potassium in a patient with lethargy is highly suggestive of?

A

Hyponatremia and high potassium in a patient with lethargy is highly suggestive of Addison’s

152
Q

what is the best test to diagnose addisons disease?
what antibodies can be looked for?
what if a short synacthen test isnt available?

A

The short synacthen test is the best test to diagnose Addison’s disease

Investigations: in a patient with suspected Addison’s disease the definite investigation is a short ACTH test. Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated

If an ACTH stimulation test is not readily available (e.g. in primary care) then sending a 9 am serum cortisol can be useful:

> 500 nmol/l makes Addison's very unlikely
< 100 nmol/l is definitely abnormal
100-500 nmol/l should prompt a ACTH stimulation test to be performed
153
Q

what happens to:
K+
Renin
Aldosterone
sodium
glucose
pH

in addisons

A

Associated electrolyte abnormalities
• Hyperkalemia
• Hyper-Renin
• Hypo-Aldosterone
• Hyponatremia
• Hypoglycemia
• Metabolic acidosis (Hypo pH)

154
Q

what is the criteria for SIADH?
-what are other points to consider?

A

Criteria:
• Normal Renal, Normal Adrenal and Normal Thyorid
• Hyponatremia <135 mEq/L
• Hypotonic plasma - POsm <270 mOsm/kg.
• Inappropriately ↑ urine osmolality
• Urine sodium >20 mEq/L (inappropriate natriuresis)

• Maintained hypervolemia
• Suppression of renin-angiotensin system (RAS)
• No equal concentration of atrial natriuretic peptide • ↓BUN
• Normal S.Creatinine
• ↓ uric acid
• ↓ albumin
• Normal Acid-Base, K+ balance

155
Q

what are the different causes of SIADH

A
  1. Malignancy
    • Especially small cell lung cancer
    • Also: pancreas, prostate
  2. Neurological
    • Stroke
    • Subarachnoid hemorrhage
    • Subdural hemorrhage
    • Meningitis/encephalitis/abscess
  3. Infections
    • TB
    • Pneumonia
  4. Drugs
    • Sulfonylureas
    • SSRIs, tricyclics
    • Carbamazepine
    • Vincristine
    • Cyclophosphamide
  5. Other causes
    • Positive end-expiratory pressure (PEEP)
    • Porphyrias
156
Q

what is the treatment for SIADH?

A

Treatment:
• Demeclocycline

157
Q

what is a pheochromocytoma?
-what does this secrete?

A

Pheochromocytoma: is a rare catecholamine secreting neuroendocrine tumor of the medulla of the adrenal glands (originating in the chromaffin cells), or extra-adrenal chromaffin tissue. It secretes excessive amounts of catecholamines, usually adrenaline if in the adrenal gland (not extra-adrenal) and noradrenaline.

158
Q

what are the signs/symptoms phaeochromocytoma:

A

Features are typically episodic

hypertension (around 90% of cases, may be sustained)
headaches
palpitations
sweating
anxiety
159
Q

phaeochromocytoma:
-familial in what %
-bilateral in what %
-malignant in what %
-extra-adrenal in what %`

A

• Familial 10%
• Bilateral in 10% • Malignant in 10%
• Extra-adrenal in 10% (most common site = organ of zuckerkandl, adjacent to the bifurcation of the aorta)

160
Q

what is the diagnosis of phaeochromocytoma?

A

24hr urinary collection of catecholamines is preferred to one of vanillylmandelic acid as it has a higher sensitivity. Three 24 hour collections are needed as some patients have intermittently raised levels

161
Q

what is the management of pheochromacytoma?

A

Surgery is the definitive management. The patient must be pre-stabilized with medical management: PHEochromocytoma - give PHEnoxybenzamine before beta-blockers
• α-blocker (e.g. Phenoxybenzamine), given before a
• β-blocker (e.g. Propranolol)

162
Q

what are the causes of hypokalemia with hypertension

A

• Cushing’s syndrome
• Conn’s syndrome (primary hyperaldosteronismm)
• Liddle’s syndrome
• 11-β-hydroxylase deficiency*
• Carbenoxolone (anti-ulcer drug)
• High liquorice intake

163
Q

what are the causes of hypokalaemia without hypertension?

A

• Diuretics
• GI loss (e.g. diarrhea, vomiting)
• Renal tubular acidosis (type 1 and 2**)
• Bartter’s syndrome
• Gitelman syndrome

164
Q

what does each area of the adrenal secrete:
• Zona Glomerulosa (on outside)
• Zona Fasciculata (middle)
• Zona Reticularis (on inside)

A

• Zona Glomerulosa (on outside): mineralocorticoids, mainly Aldosterone
• Zona Fasciculata (middle): glucocorticoids, mainly Cortisol
• Zona Reticularis (on inside): androgens, mainly Dehydroepiandrosterone

165
Q

describe dynamic pituitary function test
-what should be seen?

A

Insulin, TRH and LHRH are given to the patient following that the serum glucose, cortisol, growth hormone, TSH, LH and FSH levels are recorded at regular intervals. Prolactin levels are also sometimes measured*

A normal dynamic pituitary function test has the following characteristics:
• GH level rises > 20mu/l
• Cortisol level rises > 550 mmol/l
• TSH level rises by > 2 mu/l from baseline level
• LH and FSH should double

*dopamine antagonist tests using metoclopramide may also be used in the investigation of hyperprolactinemia. A normal response is at least a two-fold rise in prolactin. A blunted prolactin response suggests a prolactinoma

166
Q

what is growth hormone?

A

Growth hormone (GH) is an anabolic hormone secreted by the somatotroph cells of the anterior lobe of the pituitary gland.

167
Q

what is the mechanism of action of growth hormone?

A

Mechanism of action
• Acts on a transmembrane receptor for growth
• Binding of GH to the receptor leads to receptor dimerization
• Acts directly on tissues and also indirectly via insulin-like growth factor 1 (IGF-1), primarily
secreted by the liver

168
Q

Conditions associated with GH disorders
• Excess GH
• GH deficiency

A

Conditions associated with GH disorders
• Excess GH: acromegaly
• GH deficiency: resulting in short stature

169
Q

what are the causes of acromegaly?

A

Acromegaly there is excess growth hormone secondary to a pituitary adenoma in over 95% of cases. A minority of cases are caused by ectopic GHRH or GH production by tumours e.g. pancreatic.

170
Q

what are the features of acromegaly?

A

Features
• Coarse, oily skin , large tongue, prognathism, interdental spaces
• Spade-like hands, ↑ in shoe size
• Sweating due to sweat gland hypertrophy
• Features of pituitary tumour: hypopituitarism, headaches,
bitemporal hemianopia
• Raised prolactin in 1/3 of cases → galactorrhoea
• 6% of patients have MEN-1

171
Q

what are the complications of acromegaly
-4 complications

A

Complications
• Hypertension
• Diabetes (>10%)
• Cardiomyopathy
• Colorectal cancer

172
Q

Is acromegaly assoc with systemic or pulmonary hypertension?

A

Acromegaly is associated with systemic rather than pulmonary hypertension.

173
Q

what investigations are used for GH?

A

Investigations: Growth hormone (GH) levels vary during the day and are therefore not diagnostic. Serum IGF-1 levels have now overtaken the oral glucose tolerance test (OGTT) with serial GH measurements as the first-line test. The OGTT test is recommended to confirm the diagnosis if IGF-1 levels are raised.

174
Q

what investigation findings do you see in an oral GTT in acromegaly

A

Oral glucose tolerance test
• In normal patients GH is suppressed to < 2 mu/L with hyperglycemia
• In acromegaly there is no suppression of GH
• May also demonstrate impaired glucose tolerance which is associated with acromegaly
A pituitary MRI may demonstrate a pituitary tumour

175
Q

Cushing

Cushing- vs. Pseudo-cushing

Addison

Pheochromocytoma

Acromegaly

tests

A

Cushing: Overnight Dexamethasone Test

Cushing- vs. Pseudo-cushing: Insulin Stress Test

Addison: Short Synacthen Test

Pheochromocytoma: 24H Urinary Catecholamines

Acromegaly: Oral Glucose Tolerance Test

176
Q

describe the management options for acromegaly?
-what is the first line treatment
-what are the three medical options

A

Management:
Trans-sphenoidal surgery is first-line treatment for acromegaly in the majority of patients

Dopamine agonists
• For example bromocriptine.
• The first effective medical treatment for acromegaly, however now superseded by somatostatin
analogues
• Effective only in a minority of patients

Somatostatin analogue
• For example octreotide
• Effective in 50-70% of patients
• May be used as an adjunct as it helps to control cardiometabolic risk factors prior to surgery.

Pegvisomant
• GH receptor antagonist - prevents dimerization of the GH receptor
• Once daily S/C administration
• Very effective - ↓ IGF-1 levels in 90% of patients to normal
• Doesn’t ↓ tumour volume therefore surgery still needed if mass effect

External irradiation is sometimes used for older patients or following failed surgical/medical treatment

177
Q

describe the features of excess prolactin in men and women

A

Features of excess prolactin
• Men: impotence, loss of libido, galactorrhoea
• Women: amenorrhoea, galactorrhoea

178
Q

where is prolactin secreted from?
-how does dopamine affect prolactin?

A

Prolactin is secreted by the anterior pituitary gland with release being controlled by a wide variety of physiological factors. Dopamine acts as the primary prolactin releasing inhibitor and hence dopamine agonists such as bromocriptine may be used to control galactorrhoea

179
Q

How does the hypothalamus affect prolactin?

A

Prolactin is unique amongst the pituitary hormones in being tonically (continuous) inhibited by
the hypothalamus

180
Q

what are non-drug causes of raised prolactin?

A

Causes of raised prolactin
• Prolactinoma
• Pregnancy
• Estrogens
• Physiological: stress, exercise, sleep
• Acromegaly: 1/3 of patients
• Polycystic ovarian syndrome
• PRIMARY HYPOTHYROIDISM (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)

181
Q

what are drug causes of raised prolactin?

A

• Metoclopramide, domperidone
• Phenothiazines
• Haloperidol
• Very rare: SSRIs, opioids

182
Q

what is the management of raised prolactin?

A

Prolactinomas are unusual as medical therapy is first line, even if visual field defects are present. The main indications for surgery are tumours resistant to dopamine agonists

183
Q

what is gynaecomastia?

A

Gynaecomastia describes an abnormal amount of breast tissue in ♂s and is usually caused by ↑ estrogen:androgen ratio.

184
Q

what are non-drug causes of gynaecomastia?

A

Causes of gynaecomastia
• Physiological: normal in puberty
• Syndromes with androgen deficiency: kallman’s, klinefelter’s
• Testicular failure: e.g. Mumps
• Testicular cancer e.g. Seminoma secreting HCG
• Liver disease
• Ectopic tumour secretion
• HYPERTHYROIDISM NOT HYPOTHYROIDISM
• Hemodialysis

185
Q

list some drug causes of gynaecomastia?

A

Drug causes of gynaecomastia
• Spironolactone (most common drug cause)
• Cimetidine
• Digoxin
• Cannabis
• Finasteride
• GnRH agonists e.g. goserelin, buserelin
• Estrogens, anabolic steroids
Very rare drug causes of gynaecomastia
• Tricyclics
• Isoniazid
• Calcium channel blockers
• Heroin
• Busulfan
• Methyldopa

186
Q

what is the SIGN criteria for metabolic syndrome?

A

SIGN recommend using criteria similar to those from the American Heart Association. For a diagnosis of metabolic syndrome at least 3 of the following should be identified:
• Elevated waist circumference: men > 102 cm, women > 88 cm
• Elevated triglycerides: > 1.7 mmol/l
• ↓ HDL: < 1.03 mmol/l in ♂s and < 1.29 mmol/l in ♀s
• Raised blood pressure: > 130/85 mmHg, or active treatment of hypertension
• Raised fasting plasma glucose > 5.6 mmol/l, or previously diagnosed type 2 diabetes

Other associated features include:
• Raised uric acid levels (Hyperuricemia)
• Non-alcoholic fatty liver disease
• Polycystic ovarian syndrome

187
Q

when should orlistat be considered for use?

A

NICE have defined criteria for the use of orlistat. It should only be prescribed as part of an overall plan for managing obesity in adults who have:
• BMI of 28 kg/m2 or more with associated risk factors, or
• BMI of 30 kg/ m2 or more
• Continued weight loss e.g. 5% at 3 months
• Orlistat is normally used for < 1 year

188
Q

how does orlistat work?

A

Orlistat is a pancreatic lipase inhibitor used in the management of obesity. Adverse effects include faecal urgency/incontinence and flatulence. A lower dose version is now available without prescription (‘Alli’).

189
Q

what is the NICE bariatric cut offs in obesity?

A

Obesity - NICE bariatric referral cut-offs
• With risk factors (T2DM, BP etc): > 35 kg/m2
• no risk factors: > 40 kg/m2

190
Q

what are the three obesity hormones?

A

Obesity hormones
• Leptin ↓ appetite
• Ghrelin ↑ appetite
• Thyroxine ↑ appetite but not in obese pt.

191
Q

where is leptin produced? what affect does it have on the body? how are leptin levels increased in the body?

A

Leptin is thought to play a key role in the regulation of body weight. It is produced by adipose tissue and acts on satiety centres in the hypothalamus to ↓ appetite. More adipose tissue (e.g. in obesity) results in high leptin levels. Leptin stimulates the release of melanocyte-stimulating hormone (MSH) and corticotrophin-releasing hormone (CRH). Low levels of leptin stimulates the release of neuropeptide Y (NPY)

192
Q

where is ghrelin produced and what does it do?

A

Ghrelin Where as leptin induces satiety, ghrelin stimulates hunger. It is produced mainly by the fundus of the stomach and the pancreas. Ghrelin levels ↑ before meals and ↓ after meals

193
Q

what is gylcaemic index?

A

Glycaemic index (GI) describes the capacity of a food to raise blood glucose in normal glucose-tolerant individuals. Foods with a high GI may be associated with ↑ risk of obesity and the post-prandial hyperglycemia associated with such foods may also ↑ the risk of T2DM

194
Q

what foods have a high glycaemic index?

A

White rice (87), baked potato (85), white bread (70), corn flakes, rice krispies, watermelon, croissants, extruded breakfast cereals, straight glucose (100)

195
Q

what foods have a medium glycaemic index?

A

Couscous (65), boiled new potato (62), digestive biscuit (59), basmati rice (58), whole wheat products, sweet potato, table sugar, most white rices (e.g. jasmine)

196
Q

what food have a low glycaemic index?

A

Fruit and vegetables (except potatoes, watermelon), peanuts, grainy breads, pasta, legumes/pulses, milk, products extremely low in carbohydrates (fish, eggs, meat, some cheeses, nuts, cooking oil), brown rice

197
Q

what clinical conditions are assoc. with hypercholesterolemia rather than hypertriglyceridaemia?

A

Hypercholesterolemia rather than hypertriglyceridemia:
nephrotic syndrome, cholestasis, hypothyroidism

198
Q

list some causes of predominantly hypertriglyceridemia (secondary causes)

A

• Diabetes Mellitus (types 1 and 2)
• Obesity
• Alcohol
• Chronic renal failure
• Drugs: thiazides, non-selective β-blockers, unopposed estrogen
• Liver disease

199
Q

what is Remnant hyperlipidemia?
-what is this also known as?
-what is this assoc. with?
-what is the pathophysiology?

A

Overview
• Rare cause of mixed hyperlipidemia (raised cholesterol and triglyceride levels)
• Also known as Fredrickson type III hyperlipidemia, broad-β disease and
dysbetalipoproteinemia
• Associated with APO-E2 homozygosity
• High incidence of ischemic heart disease and peripheral vascular disease
• Thought to be caused by impaired removal of intermediate density lipoprotein from the
circulation by the liver

200
Q

what are the features of remnant hyperlipidaemia?

A

Features
• Y ellow palmar creases
• Palmer xanthomas
• Tuberous xanthomas

201
Q

what is the management of remnant hyperlipidaemia?

A

Management
• Fibrates are first line treatment

202
Q

what is familial hypercholesterolaemia?
-how is this inherited?
-what is this caused by?

A

Familial hypercholesterolemia (FH) is an autosomal dominant condition that is thought to affect around 1 in 500 people. It results in high levels of LDL-cholesterol which, if untreated, may cause early cardiovascular disease (CVD). FH is caused by mutations in the hepatic proteins involved in clearance of LDL-cholesterol from the circulation

203
Q

what is the clinical diagnosis of familial hypercholesterolaemia based on?

A

Clinical diagnosis is now based on the Simon Broome criteria:
• In adults total cholesterol (TC) > 7.5 mmol/l and LDL-C > 4.9 mmol/l or children TC > 6.7
mmol/l and LDL-C > 4.0 mmol/l, plus:
• For definite FH: tendon xanthoma in patient or 1st or 2nd degree relatives or DNA-based
evidence of FH
• For possible FH: family history of myocardial infarction below age 50 years in 2nd degree
relative, below age 60 in 1st degree relative, or a family history of raised cholesterol levels

204
Q

what is the management of familial hypercholesterolaemia?

A

Management
• The use of CVD risk estimation using standard tables is not appropriate in FH as they do not
accurately reflect the risk of CVD
• Referral to a specialist lipid clinic is usually required
• The maximum dose of potent statins are usually required
• First-degree relatives have a 50% chance of having the disorder and should therefore be offered
screening
• Statins should be discontinued in women 3 months before conception due to the risk of
congenital defects

205
Q

describe how people are identified as having a high risk of cardiovascular disease?
-what equation is used?
-when should adjustments to this be made?

A

Primary prevention: a systematic strategy should be used to identify people aged 40-74 who are likely to be at high risk of cardiovascular disease (CVD), defined as a 10-year risk of 20% or greater.
The 1991 Framingham equations are still recommended to assess 10-year CVD risk.

It is however recommended that adjustments are made in the following situations:
• First-degree relative with a history of premature coronary heart disease (defined as < 55 years in ♂s and < 65 years in ♀s) - ↑ risk by 1.5 times if one relative affected or up to 2.0 times if more than one relative affected
• South asian ethnicity - ↑ risk by 1.4 times

206
Q

when should statins be used?

A

Along with lifestyle changes drug treatment should be considered for patients with a 10-year CVD risk of 20% or greater
• Simvastatin 40mg on is the first line treatment
• There is no target level for total or LDL cholesterol for primary prevention
• Liver function tests should be check at baseline, within 3 months and at 12 months but not again
unless clinically indicated

Secondary prevention
• All patients with CVD should be taking a statin in the absence of any contraindication
• NICE recommend increasing to simvastatin 80 mg if a total cholesterol of less than 4 mmol/litre
or an LDL cholesterol of less than 2 mmol/litre is not attained

207
Q

in prolonged cholestasis:
-what cholesterol levels are found
-what xanthomas are seen and when would these normally occur?

A

In prolonged cholestasis features include: ↑ serum cholesterol, moderate ↑ in triglyceride, serum
is not lipaemic, ↓ HDL levels.

Clinical features include: palmar xanthomas; tuberous xanthomas
(particularly on extensor surfaces); tendinous xanthomas are rare.

Xanthomas usually only occur
if cholestasis has persisted for more than 3 months sometimes fat deposits may involve bone and
peripheral nerves.

208
Q

The presence of tendon xanthomata and ↑LDL, ↑T.chol ≡ HDL meet the diagnostic criteria for ?

A

The presence of tendon xanthomata and ↑LDL, ↑T.chol ≡ HDL meet the diagnostic criteria for
familial hypercholesterolemia.

209
Q

Palmar xanthoma - which condition is this more likely seen in?

A

• Remnant hyperlipidemia
• May less commonly be seen in familial hypercholesterolemia

210
Q

what are eruptive xanthomas?

A

Eruptive xanthoma are due to high triglyceride levels and present as multiple red/yellow vesicles on the extensor surfaces (e.g. elbows, knees)

211
Q

what are causes of eruptive xanthoma?

A

Causes of eruptive xanthoma
• Familial hypertriglyceridemia
• Lipoprotein lipase deficiency

212
Q

what are causes of Tendon xanthoma, tuberous xanthoma, xanthelasma

A

Tendon xanthoma, tuberous xanthoma, xanthelasma
• Familial hypercholesterolemia
• Remnant hyperlipidemia

213
Q

what is included in the management of xanthelasma?

A

Management of xanthelasma, options include:
• Surgical excision
• Topical trichloroacetic acid
• Laser therapy
• Electrodesiccation

214
Q

Flushing, diarrhea, bronchospasm, tricuspid stenosis, pellagra - what does this make you think of? what is the diagnosis?

A

Flushing, diarrhea, bronchospasm, tricuspid stenosis, pellagra → carcinoid with liver mets
diagnosis: urinary 5-HIAA

215
Q

what is carcinoid syndrome?

A

• Usually occurs when metastases are present in the liver and release serotonin into the systemic circulation
• May also occur with lung carcinoid as mediators are not ‘cleared’ by the liver

216
Q

what are the features of carcinoid syndrome:
-what is the earliest symptom?
-what are three other symptoms?
-what happens to the heart?
-what hormones can be secreted?

A

Features
• Flushing (often earliest symptom)
• Diarrhea
• Bronchospasm
• Hypotension
• Right heart valvular stenosis (left heart can be affected in bronchial carcinoid)
• ACTH and GHRH may also be secreted resulting in, for example, cushing’s syndrome
• Pellagra can rarely develop as dietary tryptophan is diverted to serotonin by the tumour

217
Q

what are the investigations for carcinoid syndrome?

A

Investigation
• Urinary 5-HIAA
• Plasma chromogranin A y

218
Q

what is the management of carcinoid syndrome?

A

Management
• Somatostatin analogues e.g. Octreotide
• Diarrhea: cyproheptadine may help

219
Q

How many distinct types of autoimmune polyendocrinopathy syndrome exist?

A

There are two distinct types of autoimmune polyendocrinopathy syndrome (APS), with type 2 (sometimes referred to as Schmidt’s syndrome) being much more common.

220
Q

what is autoimmune polyendocrinopathy syndrome 1?
-what is it caused by?
-what are 3 features?

A

APS1 is Multiple Endocrine Deficiency Autoimmune Candidiasis (MEDAC). It is a very rare autosomal recessive disorder caused by mutation of AIRE1 gene on chromosome 21
Features of APS type 1 (2 out of 3 needed)
• Chronic mucocutaneous candidiasis (typically first feature as young child)
• Addison’s disease
• Primary hypoparathyroidism

Vitiligo can occur in both types

221
Q

what is autoimmune polyendocrinopathy syndrome 2?
-what HLA ls it assoc with?
-what 3 conditions is it assoc with?

A

APS2 has a polygenic inheritance and is linked to HLA DR3/DR4. Patients have Addison’s disease plus either:
• Type 1 diabetes mellitus
• Autoimmune thyroid disease (Hypothyroid)

Vitiligo can occur in both types

222
Q

Primary hypo/hyper?parathyroidism is usually the first endocrine manifestation of type 1 autoimmune POLYendocrinopathy syndrome.
While (MEN) → hypo/hyper?parathyroidism is a common finding

A

Primary HYPOparathyroidism is usually the first endocrine manifestation of type 1 autoimmune
POLYendocrinopathy syndrome.
While (MEN) → hyperparathyroidism is a common finding

223
Q

what is MEN 1 AKA?
What tumours are the three ‘p’s?
What is the presentation?

A

Werner’s Syndrom

Mnemonic ‘three P’s’:
• Parathyroid (95%):
hyperparathyroidism due to
parathyroid hyperplasia
• Pituitary (70%)
• Pancreas (50%, e.g
gastrinoma)
• Also: adrenal and thyroid

Presentation → hypercalcemia

224
Q

what is MEN type IIa AKA?
-what 3 tumours assoc?
-what oncogene is assoc?

A

Sipple syndrome

• Pheochromocytoma 95%
• Medullary thyroid CA 70%
• Parathyroid (60%)

RET oncogene

225
Q

What tumours are assoc. with MEN type IIb?
-what oncogene is assoc?

A

• Medullary thyroid cancer
• PHEOCHROMOCYTOMA
• Marfanoid body habitus
• Neuromas
• Intestinal polyps
(identified histologically as ganglioneromas are usually asymptomatic)

RET oncogene

226
Q

what can be used as a useful indicator of MEN type 1?

A

The high incidence of parathyroid tumours and hypercalcemia make serum calcium a useful
indicator of MEN type 1 in suspected individuals

227
Q

what is androgen insensitivity syndrome?
-how is it inherited?

A

Androgen Insensitivity Syndrome: is an X-linked recessive condition due to end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype. Complete androgen insensitivity syndrome is the new term for testicular feminisation syndrome

228
Q

what are the features of androgen insensitivity syndrome?

A

Features
• ‘Primary amennorhoea’
• Undescended testes causing groin swellings
• Breast development may occur as a result of conversion of testosterone to oestradiol

229
Q

what is the diagnosis of androgen insensitivity syndrome?

A

Diagnosis
• Buccal smear or chromosomal analysis to reveal 46XY genotype

230
Q

what is the management of androgen insensitivity syndrome?

A

Management
• Counselling - raise child as female
• Bilateral orchidectomy (increased risk of testicular cancer due to undescended testes)
• Estrogen therapy

231
Q

what is congenital adrenal hyperplasia?

A

group of autosomal recessive disorders
affect adrenal steroid biosynthesis
in response to resultant low cortisol levels the anterior pituitary secretes high levels of ACTH
ACTH stimulates the production of adrenal androgens that may virilize a female infant

232
Q

what are the causes of congenital adrenal hyperplasia?

A

Cause

21-hydroxylase deficiency (90%)
11-beta hydroxylase deficiency (5%)
17-hydroxylase deficiency (very rare)
233
Q

for patients with thyroid eye disease - what constitutes urgent ophth. referral?

A

unexplained deterioration in vision
awareness of change in intensity or quality of colour vision in one or both eyes
history of eye suddenly ‘popping out’ (globe subluxation)
obvious corneal opacity
cornea still visible when the eyelids are closed
disc swelling

234
Q

what are 5 causes of macroglossia?

A

Causes
• Hypothyroidism
• Acromegaly
• Amyloidosis
• Duchenne muscular dystrophy
• Mucopolysaccharidosis (e.g. Hurler syndrome)

MRCP Combined (58 decks)

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