Endocrine I Flashcards
Which enzyme being suppressed / mutated causes syndrome of apparent mineralocorticoid excess?
11β-Hydroxysteroid dehydrogenase
17-hydroxylase
21-hydroxylase
Which enzyme being suppressed / mutated causes syndrome of apparent mineralocorticoid excess?
11β-Hydroxysteroid dehydrogenase - 11BSD2
Does
State which pathologies MEN1 [3], MEN2A [3] AND MEN2B [3] relate to
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
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
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.
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]
Thyroglobulin antibodies
Describe the results from high-dose dexomethasone testing for Cushings syndrome, Cushing disease and ectopic ACTH [3]
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
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
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
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
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
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
What is the most common endogenous cause of this Cushings?
Adrenal adenoma
Adrenal carcinoma
Glucocorticoid therapy
Micronodular adrenal dysplasia
Pituitary adenoma
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
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]
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.
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
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
A patient presents with low FSH, LH, Oestrogen, Progesterone, Testosterone.
He also has erectile dysfunction.
What is a key differential? [1]
haemochromatosis
- a cause of hypogonadotrophic hypogonadism
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]
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.
[] is the most appropriate investigation for patients with increased urinary cortisol and low plasma ACTH levels
CT adrenal glands is the most appropriate investigation for patients with increased urinary cortisol and low plasma ACTH levels
Name 4 drug classes that could raise prolactin levels [4]
antipsychotics, selective serotonin reuptake inhibitors (SSRIs), cimetidine, and beta-blockers.
How do you treat slighty raised TSH if:
- asymptomatic
- symptomatic
How do you treat raised TSH if:
- symptomatic
- old (< 70)
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
Congenital adrenal hyperplasia is caused by a congenital deficiency of the which enzyme? (In most cases) [1]
21-hydroxylase
- In a small number of cases it is caused by a deficiency of 11-beta-hydroxylase rather than 21-hydroxylase.
What is the role of 21-hydroxylase? [1]
21-hydroxylase is the enzyme responsible for converting progesterone into aldosterone and cortisol.
Describe the pathophysiology congenital Adrenal Hyperplasia [3]
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.
Describe the pathophysiology of Waterhouse-Friderichsen syndrome [1]
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)
Name an iatrogenic cause of hypoadrenalism [1]
Ketoconazole: antifungal but suppresses the adrenals
Name 4 causes of hypoadrenalism [4]
- 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
Aside from running blood tests, what would you test for with a patient you suspect of having hypoadrenalism? [4]
- 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)
Describe the diagnostic test of choice for hypoadrenalism? [1]
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).
Autoantibodies directed at the adrenal cortex to the autoantigens [] and [] can be seen in 70% of patients with idiopathic or primary Addison’s disease
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
Management of Addisonian crisis;
Acute treatment? [2]
Long term treatment? [2]
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
What blood results would you expect to see a ptx with Cushings syndrome? [3]
Hypokalaemia: due to excess cortisol having a mineralocorticoid effect (acts on aldostorone receptors)
Hyperglycaemia
High white blood cell count: Polycythaemia, Neutrophilia, Lymphopenia
Name and explain the diagnostic test of choice for Cushing’s syndrome
Normal: dexamethasone suppresses cortisol release from adrenal glands
Cushings: cortisol levels are high despite dexamethasone suppressing cortisol release
State 4 reasons that can cause increase in cortisol, which would give false positive results in a dexamethasone suppression test [4]
depression
alcohol excess
obesity
acute illness
Ectopic ACTH dependent Cushings is often caused by which type of cancer? [1]
ectopic ACTH: small cell lung cancer
What are the 3 arteries that supply the adrenal glands? [3]
Which arteries do they come from? [3]
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.
What is release of aldosterone stimulated by? [2]
rising K+ [1]
fall in blood volume/BP [1]
Which enzyme being suppressed / mutated causes syndrome of apparent mineralocorticoid excess? [1]
Why does that create symptoms of hyperaldosternism? [1]
When 11BHSD-2 enzyme is supressed/mutated - cortisol is NOT deactivated and will binds to MR.
symptoms of hyperaldosteronism
Describe the three types of adrenal insufficiency
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.
Name three causes of adrenal insufficiency caused infections [3]
Pseudomonas aeruginosa
Meningococcal infection
TB
Label A-F [6]
Cushing syndrome
* Cortisol: Not suppressed
* ACTH: Suppressed
Cushing Disease
* Cortisol: Suppressed
* ACTH: Suppressed
Ectopic ACTH
* Cortisol: Not suppressed
* ACTH: Not suppressed
What are following causes of prolactinoma:
- Physiological [1]
- Drug induced [4]
- Pathological [2]
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
How would you investigate for prolactinoma?
Basal prolactin raised
Pregnancy test
TFT
U&E
MRI pituitary - choce
Drug class used to manage prolactinoma? [1]
Name two drugs that are used to manage prolactinoma [2]
Dopamine agonists (dopamine causes tonic inhibition of prolactin release):
- bromocriptine
- cabergoline
State and explain the standard investigation for acromegaly? [1]
Name two others [2]
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.
Describe vascular and cardiac complicatons of acromegaly [4]
Increased blood pressure:
- Left ventricular hypertrophy
- cardiomyopathy
- arrhythmias
- ischaemic heart disease
Name three drug therapies for acromegaly? [3]
- Octreotide - somatostatin analogue: lowers GH levels / blocks GH release
- Pegvisomont – GH receptor antagonist; subcutaneous injection
- Bromocriptine (Dopamine agonists): block growth hormone release
Name three causes of ATCH independent Cushings syndrome [3]
- Adrenal Carcinoma
- Adrenal Adenomas
- Exogenous steroids (Cushingoid appearance)
Management of Cushing’s syndrome:
- Surgery? [1]
- Drugs? [2]
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
Name and explain what Sheehan’s syndrome is [2]
Explain when this commonly occurs? [2]
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
State and explain the treatment pathway for hypopituitarism [3]
- 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
What is pituitary apoplexy and when does it occur? [2]
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
Presentation of pituitary apoplexy? [4]
▪ acute headache,
▪ meningism,
▪ visual impairment,
▪ ophthalmoplegia,
▪ Low GCS
Treatment plan for ptx with pituitary apoplexy? [2]
Glucocorticoid replacement (e.g hydrocortisone) is the most important first step due to adrenal insufficiency
Followed by urgent surgical decompression
Sheehan’s syndrome causes a lack of the hormones produced by the anterior pituitary, leading to signs and symptoms of [4]
Reduced lactation: lack of prolactin
Amenorrhea: lack of FSH and LH
Adrenal insufficiency & adrenal crisis: low cortisol and ACTH
Hypothyroidism: lack TSH
There are three types of dexamethason suppression test.
Describe them [3]
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.
State the results for the dexamethasone suppression test
What is the order of treatment for:
- Acromegaly [2]
- Prolactinoma [2]
Acromegaly:
- Surgery 1st line
- Drugs 2nd line (octreotide)
Prolactinoma:
- Drugs 1st line (Dopamine agonists: Cabergoline; bromocriptine)
- Surgery 2nd line
What is the first line treatment for acromegaly if surgery is not successful?
Bromocriptine
Pegvisomont
Ketoconazole
Octreotide
Carbergoline
Metyrapone
What is the first line treatment for acromegaly if surgery is not successful?
Bromocriptine - 3rd line
Pegvisomont - 2nd line
Ketoconazole
Octreotide
Carbergoline
Metyrapone
What is the first line treatment for prolactinoma?
Bromocriptine
Pegvisomont
Ketoconazole
Octreotide
Carbergoline
Metyrapone
What is the first line treatment for prolactinoma?
Bromocriptine
Pegvisomont
Ketoconazole
Octreotide
Carbergoline
Metyrapone
Ketoconazole & Metyrapone are used to treat which condition? [2]
Cushing’s syndrome
What is the specific treatment for Addison’s crisis? [1]
Intravenous hydrocortisone
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
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
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?
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.
