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