Endocrine I Flashcards
(41 cards)
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.
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
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
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
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
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
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.
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
