MET3 Revision: Endocrine I Flashcards
Name three infective organisms that can cause hypoadrenalism [3]
TB
Fungal infections (E.g. candidiasis)
Neisseria meningitidis; Pseudomonas aeruginosa and Haemophilus influenzae causing WATERHOUSE-FRIDERICHSEN Syndrome .
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
What are signs of Addison’s disease? [5]
- anorexia & weight loss
- fatigue, generalised weakness,
- increased pigmentation - particularly in mouth, scars and skin creases
- dizziness on standing
-
nausea & vomiting
(Remember Addison’s is due to decreased cortisol and aldosterone)
State 5 signs of Addison’s disease [5]
(Addison’s disease refers specifically to when the adrenal glands have been damaged, resulting in reduced cortisol and aldosterone secretion)
Postural hypotension (>10 mmHg)
Vitiligo (came up in CBL)
Depression & pyschosis
Abodominal pain (w/ n & v)
Flu like myalgias
Pigmentation – buccal, scars, skin crease
How may an Addisonian crisis present? [5]
Acute presentation of severe adrenal insufficiency, where the absence of steroid hormones (cortisol and aldosterone) leads to a life-threatening emergency. They may present with:
- Reduced consciousness
- Hypotension
- Abdominal pain
- Nausea and vomiting
- Hypoglycaemia
- Hyponatraemia and hyperkalaemia
- Pigmentation – buccal, scars, skin crease
When taking blood tests, what would hypoadrenalism have? [6]
- Na & K levels
- Urea levels
- Glucose levels
- Type of anaemia
- Ca levels
- Effect on leukocytes
Low Na; High K
High urea (increased salt and water loss / dehydration)
Low glucose
Normocytic anaemia
Eoisinophilia
Mild hypercalcemia
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).
Describe the method of conducting a short synthetic ACTH [synacthen] test
- A dose of Synacthen, (synthetic ACTH).
- The blood cortisol is checked before and 30 and 60 minutes after the dose.
- The synthetic ACTH will stimulate healthy adrenal glands to produce cortisol.
- The cortisol level should at least double.
- A failure of cortisol to double indicates either:
- Primary adrenal insufficiency (Addison’s disease)
- Very significant adrenal atrophy after a prolonged absence of ACTH in secondary adrenal insufficiency
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
Long term management of Addisonian crisis is:
Oral hydrocortisone
Oral fludrocortisone
What are the doses and dosing regimen like? [2]
Oral hydrocortisone – usually 10mg/5mg/5mg(reduce dose during the day so can sleep at night (cortisol is lowest at midnight))
Oral fludrocortisone - once daily; first thing at morning. Dose is titrated around BP; normally 100 - 200 mg dose
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
What would differing ACTH levels indicate about the whether Cushings is ACTH dependent or independent?
ACTH elevated: more likely to be pituitary ectopic disease causing an increase in ACTH and therefore more cortisol - ACTH dependent
ACTH suppressed: more likely to be adrenal disease causing more cortisol - ACTH independent
How would you differ imaging to determine whether Cushings was ACTH dependent or ACTH independent? [2]
If ACTH-dependent: Pituitary vs ectopic
- MRI image of the pituitary
If ACTH-independent:
- imaging of adrenals/chest
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]
Explain effect of aldosterone on RAAS system
Renin converts angiotensin -> ANG1
ANG1 converted to ANGII by ACE (from lungs) ANG II:
Causes direct vasoconstricton + binding to ANG II receptors in ZG
ZG cells produce aldosterone: causes vasoconstriction + remodelling - (ininflammation in heart + vasculature).
Second effect of aldosterone: ‘sodium savour’: Na reabsorption + water reabsorption : Have to exchange K+ at the ENAC channels on the distal tubule.
mineralocorticoid receptor is activated by which two substrates? [2]
Why is that important? [1]
mineralocorticoid receptor: activated by cortisol AND aldosterone
So in cells where aldosterone is active, cortisol is deactivated otherwise receptor would be overwhelmed
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
Patients with primary adrenal insufficiency are at risk of developing which autoimmune diseases? [3]
R.A.
Crohn’s Disease
Coealic Disease
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
What is the first line test used for suspected primary hyperaldosteronism? [1]
What result would suggest primary hyperaldosteronism? [1]
A plasma aldosterone/renin ratio is the first-line investigation in suspected primary hyperaldosteronism
Confirmation of the diagnosis is given by an elevated ratio, suggestive of aldosterone raised inappropriately in comparison to normal/low circulating renin.
Describe how a patient with Addison’s disease should alternate their medication during periods of illness? [2]
Double the hydrocortisone dose
Keep the same fludrocortisone dose
In patients with Addison’s disease, it is important to adjust their glucocorticoid replacement therapy during times of stress or illness. This is because the body requires higher levels of cortisol to cope with such situations. Doubling the hydrocortisone dose helps ensure that the patient has enough cortisol to manage her current infection. Fludrocortisone, on the other hand, is a mineralocorticoid that regulates electrolyte balance and blood pressure; it does not need to be adjusted during acute illness.
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
Label A-C
Polydipsia and polyuria are caused by DM.
They are also caused by an increase of which mineral? [1]
Elevated Ca2+
Which hypersecretion syndrome is the most common type of pituituary adenoma? [1]
Name three male symptoms [3]
Name three female symptoms [1]
Prolactinoma:
men:
* impotence
* loss of libido
* galactorrhoea
Female:
* amenorrhoea
* infertility
* galactorrhoea
* osteoporosis
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
What are the classic triad signs of acromegaly? [3]
Name some other symptoms [4]
Headaches, arthralgia, sweating
Increased ring/shoe size, weakness, diabetes, carpal tunnel, atherosclerosis
TOM TIP: When preparing for the PACES exam, the link between bilateral carpal tunnel syndrome and acromegaly came up several times. Cases would present a patient with symptoms of bilateral carpal tunnel syndrome. The challenge was not only to diagnose carpal tunnel syndrome but also to identify the features of the underlying cause. Whenever you see a patient in an OSCE station, and you make a diagnosis, ask yourself whether that diagnosis might have an underlying cause and look for features of that cause.
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)
Pneumonic for causes of Cushing’s syndrome? [4]
CAPE
C – Cushing’s disease (a pituitary adenoma releasing excessive ACTH)
A – Adrenal adenoma (an adrenal tumour secreting excess cortisol)
P – Paraneoplastic syndrome
E – Exogenous steroids (patients taking long-term corticosteroids)
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
Untreated Cushing’s disease increases chance of mortality due to what type of pathology? [1]
Untreated Cushings: increased vascular disease
Name 4 causes of hypopituitarism [4]
Adenoma, Irradiation, Infarction (Sheehans), Infiltration
(Sarcoid, TB)
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 [] pituitary
Sheehan’s syndrome causes a lack of the hormones produced by the anterior pituitary
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
Which one of the following drugs is not a cause of galactorrhoea?
Metoclopramide
Bromocriptine
Chlorpromazine
Haloperidol
Domperidone
Which one of the following drugs is not a cause of galactorrhoea?
Metoclopramide
Bromocriptine
Bromocriptine is a treatment for galactorrhoea, rather than a cause
Chlorpromazine
Haloperidol
Domperidone
