Endocrine I

Question 1

Which enzyme being suppressed / mutated causes syndrome of apparent mineralocorticoid excess?

11β-Hydroxysteroid dehydrogenase
17-hydroxylase
21-hydroxylase

Answer 1

Which enzyme being suppressed / mutated causes syndrome of apparent mineralocorticoid excess?

11β-Hydroxysteroid dehydrogenase - 11BSD2

Does

Question 2

State which pathologies MEN1 [3], MEN2A [3] AND MEN2B [3] relate to

Answer 2

MEN1: 3Ps-
* Pituitary
* Pancreas
* Parathyroid

MEN2a- 3Cs
* Calcitonin- medullary thyroid
* Calcium- parathyroid
* Catecholamines- phaeochromocytoma

MEN2b- big and belly (the big ones and in the tummy)
* Medullary thyroid
* Phaeochromocytoma
* Mucosal tumours- eg GI tract

Question 3

How you calculate alcohol intake? [1]

E.g He says the wine he drinks is 13% alcohol by volume (ABV) and the bottles are 750 ml. He drinks 5 bottles per week

Answer 3

Number of units of alcohol in drink = total volume of a drink (ml) x ABV (%)/1000.

Therefore this patient has (750 ml x 5 bottles) x 13%/1000

= 3750 ml x 13% /1000 = 48.75 units per week

This is 34.75 units above the recommended limit of 14 units per week. This answer is rounded to 35 units.

Question 4

Which thyroid antibodies are not useful for clinically distinguishing between different types of thyroid disease, may be used as part of thyroid cancer follow up? [1]

Answer 4

Thyroglobulin antibodies

Question 5

Describe the results from high-dose dexomethasone testing for Cushings syndrome, Cushing disease and ectopic ACTH [3]

Answer 5

Question 6

A 34 year old woman presents with weight loss, irregular menstrual cycles and anxiety. On examination she has a fine tremor, a diffuse goitre, and mild proptosis. On examination, she has a skin condition.

Which is the most likely skin condition be present?

Acanthosis nigricans

Erythema nodosum

Granuloma annulare

Pyoderma gangrenosum

Vitiligo

Answer 6

A 34 year old woman presents with weight loss, irregular menstrual cycles and anxiety. On examination she has a fine tremor, a diffuse goitre, and mild proptosis. On examination, she has a skin condition.

Which is the most likely skin condition be present?

Acanthosis nigricans

Erythema nodosum

Granuloma annulare

Pyoderma gangrenosum

Vitiligo

Question 7

A 25 year old man is admitted with severe headache, and is noted to have a blood pressure of 204/110 mmHg, with a pulse rate of 120 BPM, regular. He mentions about getting episodes of headache, anxiety and sweating 3-4 times per month, which last around 30 minutes. His GP has commenced him on propranolol, but his symptoms have worsened. He is now being commenced on another treatment from the list of bendroflumethiazide, doxazosin, losartan, moxonidine and ramipril.

Which treatment should be the most appropriate one to commence initially?

Bendroflumethiazide

Doxazosin

Losartan

Moxonidine

Ramipril

Answer 7

A 25 year old man is admitted with severe headache, and is noted to have a blood pressure of 204/110 mmHg, with a pulse rate of 120 BPM, regular. He mentions about getting episodes of headache, anxiety and sweating 3-4 times per month, which last around 30 minutes. His GP has commenced him on propranolol, but his symptoms have worsened. He is now being commenced on another treatment from the list of bendroflumethiazide, doxazosin, losartan, moxonidine and ramipril.

Which treatment should be the most appropriate one to commence initially?

Bendroflumethiazide

Doxazosin - alpha blocker

Losartan

Moxonidine

Cross
Ramipril

Question 8

A 67 year old man is admitted with confusion and severe dehydration. Urgent blood tests show an acute kidney injury, but normal liver function and full blood count.

Corrected serum calcium is 3.45 mmol/L (2.3-2.7).

Serum parathyroid hormone is 1.0 pmol/l (5-12).

Chest x-ray is normal.

He has undergone several investigations including CT chest abdomen and pelvis, X ray lumbar spine, serum lactate dehydrogenase, serum parathyroid hormone related peptide and serum vitamin D.

Which investigation is most likely to help determine the cause of his serum calcium result?

CT chest abdomen and pelvis

X ray Lumbar spine

Serum lactate dehydrogenase

Serum parathyroid hormone related peptide

Serum vitamin D

Answer 8

A 67 year old man is admitted with confusion and severe dehydration. Urgent blood tests show an acute kidney injury, but normal liver function and full blood count.

Corrected serum calcium is 3.45 mmol/L (2.3-2.7).

Serum parathyroid hormone is 1.0 pmol/l (5-12).

Chest x-ray is normal.

He has undergone several investigations including CT chest abdomen and pelvis, X ray lumbar spine, serum lactate dehydrogenase, serum parathyroid hormone related peptide and serum vitamin D.

Which investigation is most likely to help determine the cause of his serum calcium result?

CT chest abdomen and pelvis

X ray Lumbar spine

Serum lactate dehydrogenase

Serum parathyroid hormone related peptide

Serum vitamin D

Question 9

What is the most common endogenous cause of this Cushings?

Adrenal adenoma

Adrenal carcinoma

Glucocorticoid therapy

Micronodular adrenal dysplasia

Pituitary adenoma

Answer 9

What is the most common endogenous cause of this Cushings?

Adrenal adenoma
- adrenal adenoma (5-10%)

Adrenal carcinoma

Glucocorticoid therapy

Micronodular adrenal dysplasia

Pituitary adenoma

Question 10

Secondary hypothyroidism is very rare and results in a low TSH and low T4. In these cases, pituitary insufficiency is most likely and therefore what investigation should occur? [1]

Answer 10

Secondary hypothyroidism is very rare and results in a low TSH and low T4. In these cases, pituitary insufficiency is most likely and therefore an MRI of the gland should be performed.
- the cause is suggestive of a central lesion.

Question 11

A patient has recently started a new medication that has caused them to have decreased free T3/4 levels.

What medication could it be?

• Interaction with calcium carbonate
• Interaction with amlodipine
• Iodine deficiency
• Interaction with aspirin
• Poor adherence to levothyroxine

Answer 11

A patient has recently started a new medication that has caused them to have decreased free T3/4 levels.

What medication could it be?

Interaction with calcium carbonate

• Interaction with amlodipine
• Iodine deficiency
• Interaction with aspirin
• Poor adherence to levothyroxine

Question 12

A patient presents with low FSH, LH, Oestrogen, Progesterone, Testosterone.

He also has erectile dysfunction.

What is a key differential? [1]

Answer 12

haemochromatosis
- a cause of hypogonadotrophic hypogonadism

Question 13

A patient presents with amenorrhoea and secondary gallactorrhoea. You suspect prolactinoma might be the cause.

What test should you perfom before requesting a MRI pituitary? [1]

Answer 13

Pregnancy needs to be excluded in patients with secondary amenorrhoea and a raised prolactin level.

Other causes of raised prolactin levels include prolactinoma, drug induced hyperprolactinaema, non- functioning pituitary adenoma.

Question 14

[] is the most appropriate investigation for patients with increased urinary cortisol and low plasma ACTH levels

Answer 14

CT adrenal glands is the most appropriate investigation for patients with increased urinary cortisol and low plasma ACTH levels

Question 15

Name 4 drug classes that could raise prolactin levels [4]

Answer 15

antipsychotics, selective serotonin reuptake inhibitors (SSRIs), cimetidine, and beta-blockers.

Question 16

How do you treat slighty raised TSH if:
- asymptomatic
- symptomatic

How do you treat raised TSH if:
- symptomatic
- old (< 70)

Answer 16

If TSH slightly raised (< 10) + asymptomatic
* repeat test after 6 months

If TSH slightly raised (< 10) + SYMPTOMATIC
* give levothyroxine trial

If TSH high positive (>10)
* levothyroxine treatment

If old patient (>70y/o)
* watch and wait
* Only treat if symptomatic

Question 17

Congenital adrenal hyperplasia is caused by a congenital deficiency of the which enzyme? (In most cases) [1]

Answer 17

21-hydroxylase
- In a small number of cases it is caused by a deficiency of 11-beta-hydroxylase rather than 21-hydroxylase.

Question 18

What is the role of 21-hydroxylase? [1]

Answer 18

21-hydroxylase is the enzyme responsible for converting progesterone into aldosterone and cortisol.

Question 19

Describe the pathophysiology congenital Adrenal Hyperplasia [3]

Answer 19

21-hydroxylase is the enzyme responsible for converting progesterone into aldosterone and cortisol.

Progesterone is also used to create testosterone, but this conversion does not rely on the 21-hydroxylase enzyme

In CAH, there is a defect in the 21-hydroxylase enzyme

Therefore, because there is extra progesterone floating about that cannot be converted to aldosterone or cortisol, it gets converted to testosterone instead.

The result is a patient with low aldosterone, low cortisol and abnormally high testosterone.

Question 20

Describe the pathophysiology of Waterhouse-Friderichsen syndrome [1]

Answer 20

blood vessels in the adrenal gland rupture during a severe bacterial infection, turning the adrenal glands into sacks of blood

(Blood clots occur during an infection, due to the toxins produced by the bacteria having pro-coagulant nature. This forms septic emboli. Adrenal vessels are small, so often get stuck there. Causes ischaemia and necrosis of the adrenal glands. Risk of adrenal crisis)

Question 21

Name an iatrogenic cause of hypoadrenalism [1]

Answer 21

Ketoconazole: antifungal but suppresses the adrenals

Question 22

Name 4 causes of hypoadrenalism [4]

Answer 22

• Addison’s–autoimmuneadrenalitis
• Infections: TB/fungal
• Waterhouse-Friedrichson syndrome –adrenal haemorrhage due to meningococcal infection
• Congenital adrenal hyperplasia
• Drugs: long term steroids suppressing adrenals. Ketoconazole

Question 23

Aside from running blood tests, what would you test for with a patient you suspect of having hypoadrenalism? [4]

Answer 23

• Short synthetic ACTH [synacthen] test
• If synacthen test not available: Random cortisol and ACTH: 9am ATCH raised
• 21 hydroyxlase adrenal antibodies positive in 80% patients
• Abdomen x-ray (if TB has caused calcification of adrenal glands)

Question 24

Describe the diagnostic test of choice for hypoadrenalism? [1]

Answer 24

Short synthetic ACTH [synacthen] test:
-The blood cortisol is measured at baseline, 30 and 60 minutes after administration.
- The synthetic ACTH will stimulate healthy adrenal glands to produce cortisol.
- The cortisol level should at least double in response to synacthen.
- A failure of cortisol to rise (less than double the baseline) indicates primary adrenal insufficiency (Addison’s disease).

Question 25

Autoantibodies directed at the adrenal cortex to the autoantigens [] and [] can be seen in 70% of patients with idiopathic or primary Addison's disease

Answer 25

Autoantibodies directed at the adrenal cortex to the autoantigens **21-hydroxylase and 17 alpha hydroxylase can be seen in 70% of patients** with idiopathic or primary Addison's disease

Question 26

Management of Addisonian crisis; Acute treatment? [2] Long term treatment? [2]

Answer 26

Acute treatment: * **0.9% saline** * **IV hydrocortisone 100mg bolus stat**; then IM doses until can take tablets Long term treatment: * **Oral hydrocortisone** – usually **10mg/5mg/5mg** * **Oral fludrocortisone** (mineralocorticoid) - **100 / 200 mg**

Question 27

What blood results would you expect to see a ptx with Cushings syndrome? [3]

Answer 27

**Hypokalaemia**: due to excess cortisol having a mineralocorticoid effect (acts on aldostorone receptors) **Hyperglycaemia** High white blood cell count: **Polycythaemia, Neutrophilia, Lymphopenia**

Question 28

Name and explain the diagnostic test of choice for Cushing's syndrome

Answer 28

**Normal**: dexamethasone suppresses cortisol release from adrenal glands **Cushings**: cortisol levels are high despite dexamethasone suppressing cortisol release

Question 29

State 4 reasons that can cause increase in cortisol, which would give false positive results in a dexamethasone suppression test [4]

Answer 29

depression alcohol excess obesity acute illness

Question 30

Ectopic ACTH dependent Cushings is often caused by which type of cancer? [1]

Answer 30

ectopic ACTH: **small cell lung cancer**

Question 31

What are the 3 arteries that supply the adrenal glands? [3] Which arteries do they come from? [3]

Answer 31

Superior adrenal artery – arises from the inferior phrenic artery Middle adrenal artery – arises from the abdominal aorta. Inferior adrenal artery – arises from the renal arteries.

Question 32

What is release of aldosterone stimulated by? [2]

Answer 32

rising K+ [1] fall in blood volume/BP [1]

Question 33

Which enzyme being suppressed / mutated causes syndrome of apparent mineralocorticoid excess? [1] Why does that create symptoms of hyperaldosternism? [1]

Answer 33

When **11BHSD-2 enzyme is supressed/mutated** - **cortisol is NOT** **deactivated** and will binds to MR. symptoms of hyperaldosteronism

Question 34

Describe the three types of adrenal insufficiency

Answer 34

**Primary (adrenal):** * destruction or dysfunction of the adrenal gland resulting from **intrinsic diseases of the adrenal cortex** and leading to impairment in steroid hormone synthesis and secretion **Central**: the term central adrenal insufficiency is often used to refer to hypocortisolaemia secondary to a deficiency in adrenocorticotrophic hormone (ACTH) secretion: **Secondary (pituitary)**: * **inadequate pituitary ACTH release** and **subsequent production of cortisol and dehydroepiandrosterone (DHEA)/** Intrinsic pituitary disease includes tumours, irradiation, and inflammation (hypophysitis). **Tertiary (hypothalamus):** * **inadequate hypothalamic CRH and subsequent ACTH release**. Diseases include inflammatory disease (e.g., **tuberculosis, sarcoidosis)**, or tumours such as craniopharyngiomas. Hypothalamic suppression of ACTH secretion is caused by prolonged (more than 2 weeks) treatment with exogenous glucocorticoids.

Question 35

Name three causes of adrenal insufficiency caused infections [3]

Answer 35

Pseudomonas aeruginosa Meningococcal infection TB

Question 36

Label A-F [6]

Answer 36

**Cushing syndrome** * Cortisol: **Not suppressed** * ACTH: **Suppressed** **Cushing Disease** * Cortisol: **Suppressed** * ACTH: **Suppressed** **Ectopic ACTH** * Cortisol: **Not** **suppressed** * ACTH: **Not suppressed**

Question 37

What are following causes of prolactinoma: - Physiological [1] - Drug induced [4] - Pathological [2]

Answer 37

**Physiological**: - **Pregnancy**: breastfeeding - **Stress** **Drug induced:** - **Anti-physotics**: Haloperidol; Methyldopa; Chlorpromazine - **Anti-acid**: ranitidine - **Anti-emetic**: prochlorperazine; metoclopromide - **MDMA** **Pathological:** - **Prolactinoma** (micro or macro) - **Stalk damage:** pituitary adenomas, trauma, surgery - **Hypothalamic disease**

Question 38

How would you investigate for prolactinoma?

Answer 38

**Basal prolactin raised** **Pregnancy test** **TFT** **U&E** **MRI pituitary** - choce

Question 39

Drug class used to manage prolactinoma? [1] Name two drugs that are used to manage prolactinoma [2]

Answer 39

**Dopamine agonists** (dopamine causes tonic inhibition of prolactin release): - **bromocriptine** - **cabergoline**

Question 40

State and explain the standard investigation for acromegaly? [1] Name two others [2]

Answer 40

**OGTT**: - Make patient fast - At time 0, check glucose and GH - Give 75g dose of glucose and wait 2hrs - Normal response: suppression of GH when glucose given - **Acromegaly response: GH increases despite glucose given** **Insulin-like growth factor-1 (IGF-1):** can be tested on a blood sample. It indicates the growth hormone level and is raised in acromegaly. **MRI pituitary** | Testing growth hormone directly is unreliable: fluctuates in the day.

Question 41

Describe vascular and cardiac complicatons of acromegaly [4]

Answer 41

Increased blood pressure: - **Left ventricular hypertrophy** - **cardiomyopathy** - **arrhythmias** - **ischaemic heart disease**

Question 42

Name three drug therapies for acromegaly? [3]

Answer 42

1. **Octreotide** - somatostatin analogue: lowers GH levels / blocks GH release 2. **Pegvisomont** – GH receptor antagonist; subcutaneous injection 3. **Bromocriptine** (Dopamine agonists): block growth hormone release

Question 43

Name three causes of ATCH independent Cushings syndrome [3]

Answer 43

* Adrenal Carcinoma * Adrenal Adenomas * Exogenous steroids (Cushingoid appearance)

Question 44

Management of Cushing's syndrome: - Surgery? [1] - Drugs? [2]

Answer 44

** Trans-sphenoidal surgery** Adrenolytics:  **Ketoconazole**: causes steroidogenesis inhibition.  **Metyrapone**: reduces the production of cortisol in the adrenals and is occasionally used in treating of Cushing’s

Question 45

Name and explain what Sheehan's syndrome is [2] Explain when this commonly occurs? [2]

Answer 45

**Pituitary infarction** - Commonly after childbirth: develop an **increased vasculature around pituitary gland** - If suffer from **PPH** then **blood pressure drops** and causes **infarction** - Results in **hypopituitarism**

Question 46

State and explain the treatment pathway for hypopituitarism [3]

Answer 46

- **Hydrocortisone**: if give thyroxine first and have a lack of glucocorticoids then can cause adrenal crisis by increasing metabolic rate from thyroxine - **Thyroxine** - **Testosterone / HRT / Ovulation induction**

Question 47

What is pituitary apoplexy and when does it occur? [2]

Answer 47

If someone has a **long standing pituitary tumour**, can **develop abrupt acute hemorrhagic infarction of a pituitary adenoma** The term pituitary apoplexy or apoplexia refers to the "sudden death" of the pituitary gland, usually caused by an acute ischemic infarction or hemorrhage

Question 48

Presentation of pituitary apoplexy? [4]

Answer 48

▪ acute headache, ▪ meningism, ▪ visual impairment, ▪ ophthalmoplegia, ▪ Low GCS

Question 49

Treatment plan for ptx with pituitary apoplexy? [2]

Answer 49

**Glucocorticoid** **replacement** (e.g **hydrocortisone**) is the most important first step due to adrenal insufficiency Followed by **urgent surgical decompression**

Question 50

Sheehan’s syndrome causes a lack of the hormones produced by the anterior pituitary, leading to signs and symptoms of [4]

Answer 50

**Reduced lactation**: lack of prolactin **Amenorrhea**: lack of FSH and LH **Adrenal insufficiency** & **adrenal crisis**: low cortisol and ACTH **Hypothyroidism**: lack TSH

Question 51

There are three types of dexamethason suppression test. Describe them [3]

Answer 51

**Low-dose overnight test (used as a screening test to exclude Cushing’s syndrome**) - A **normal** result is that the **cortisol** level is **suppressed**. - **Failure** of the dexamethasone **to suppress the morning cortisol** could indicate **Cushing**’s **syndrome**, and further assessment is required. THINK CAPE **Low-dose 48-hour test (used in suspected Cushing’s syndrome)** - **0.5mg** is taken every **6 hours for 8 doses,** starting at **9 am on the first day**. - Cortisol is **checked at 9 am on day 1** (before the first dose) and **9 am on day 3** (after the last dose) - A **normal** result is that the **cortisol level on day 3 is suppressed** - Failure of the dexamethasone to suppress the **day 3 cortisol could indicate Cushing’s syndrome, and further assessment is required**. **High-dose 48-hour test (used to determine the cause in patients with confirmed Cushing’s syndrome)** - carried out the same way as the low-dose test, other than using **2mg per dose** (rather than 0.5mg). - This **higher dose is enough to suppress the cortisol in Cushing’s disease**, but **not when it is caused by an adrenal adenoma or ectopic ACTH.**

Question 52

Answer 52

Question 53

State the results for the dexamethasone suppression test

Answer 53

Question 54

Answer 54

Question 55

Answer 55

Question 56

What is the order of treatment for: - Acromegaly [2] - Prolactinoma [2]

Answer 56

Acromegaly: - **Surgery 1st line** - **Drugs 2nd line** (octreotide) Prolactinoma: - **Drugs 1st line** (Dopamine agonists: Cabergoline; bromocriptine) - **Surgery 2nd line**

Question 57

What is the first line treatment for acromegaly if surgery is not successful? Bromocriptine Pegvisomont Ketoconazole Octreotide Carbergoline Metyrapone

Answer 57

What is the first line treatment for acromegaly if surgery is not successful? Bromocriptine - 3rd line Pegvisomont - 2nd line Ketoconazole **Octreotide** Carbergoline Metyrapone

Question 58

What is the first line treatment for prolactinoma? Bromocriptine Pegvisomont Ketoconazole Octreotide Carbergoline Metyrapone

Answer 58

What is the first line treatment for prolactinoma? Bromocriptine Pegvisomont Ketoconazole Octreotide **Carbergoline** Metyrapone

Question 59

Ketoconazole & Metyrapone are used to treat which condition? [2]

Answer 59

**Cushing's syndrome**

Question 60

What is the specific treatment for Addison's crisis? [1]

Answer 60

**Intravenous hydrocortisone**

Question 61

You wish to start Carbimazole. Which of the following best describes it's mechanism of action? Blocks the sodium dependent iodide transporters on follicular cells 1 Inhibits peripherally expressed deiodinases 2 Blocks TSH stimulating antibodies 3 Removes the TSH receptor from the thyroid gland 4 Inhibits Thyroid Peroxidase enzyme

Answer 61

You wish to start Carbimazole. Which of the following best describes it's mechanism of action? Blocks the sodium dependent iodide transporters on follicular cells 1 Inhibits peripherally expressed deiodinases 2 Blocks TSH stimulating antibodies 3 Removes the TSH receptor from the thyroid gland 4 **Inhibits Thyroid Peroxidase enzyme**

Question 62

A 25-year-old female is seen on the surgical ward round. Three days ago, she underwent a thyroidectomy for Graves disease. For the past day, she has been feeling nauseous and complaining of numbness and a tingling sensation around her mouth. What is the cause of her symptoms?

Answer 62

This patient is experience **perioral** **paraesthesia**, a symptom of low calcium. **Hypocalcaemia** is a potential complication of thyroid surgery due to accidental removal or injury to the parathyroid glands.