Adrenal Flashcards
1
Q
What are the layers of adrenal cortex and what do they produce?
A
- Zone glomerulosa →aldosterone (mineralocorticoids)
- Zona fasciculata → cortisol (glucocorticoid)
- Zona reticularis → androgens e.g. adrenosterone (converted to testosterone) and dihydrotestosterone
2
Q
What are the principle cells of medulla of adrenal gland
A
chromaffin cells
3
Q
What processes are suppressed by glucocorticoids
A
- Amino acid uptake
- Protein synthesis
- Peripheral uptake of glucose Increase proteolysis in most tissue (not liver
4
Q
What processes are stimulated by glucocorticoids
A
- Hepatic gluconeogenesis and glycogenolysis
* Lipolysis in adipose tissue but really high levels of cortisol increases lipogenesis
5
Q
What are the two types of addison’s disease
A
- Primary: inability of adrenal to produce enough steroids
* Secondary: insufficient stimulation from pituitary or hypothalamus
6
Q
What is the incidence of primary addison’s
A
o 0.1/1000/year
o Age: 30-50
o ↑↑F
7
Q
What is the most common underlying cause of Addison’s in children
A
congenital adrenal hyperplasia
8
Q
What are the causes of Primary AD
A
Surgical removal
Trauma
Infections: TB, histoplasmosis, cryptococcosis, syphilis, HIV
Haemorrhage e.g. anticoagulation
Infarction i.e. antiphospholipid syndrome
Invasion i.e. neoplasia, amyloidosis
9
Q
How can HIV predispose to primary AD
A
medications and opportunistic infections
10
Q
What infections can cause primary AD
A
TB, syphilis, HIV (drugs + other infections), Cryptococcosis
11
Q
What are the principle causes of secondary AD
A
- Iatrogenic →long term steroid use
* Skull fractures, neoplasia, congenital, CRH deficiency, infection (TB), infiltration (sarcoidosis)
12
Q
What are the symptoms of AD i.e CVS, GI, neuri, others
A
- Fatigue and weakness
- GI symptoms: Anorexia, Nausea and vomiting, Weight loss, Abdominal pain, Diarrhoea or constipation
- CVS symptoms: Dizziness and syncope, Confusion
- Neurological: Personality change and irritability
- Amenorrhoea
13
Q
What are the signs of AD
A
hyperpigmentation, hypotension/postural
14
Q
What sort of blood tests are useful in AD and what might they show (autoimmune)
A
21-Hydroxylase adrenal autoantibodies
• Adrenal autoantibodies i.e. 21-Hydroxylase adrenal autoantibodies
15
Q
What tests can be run to exclude secondary caused of AD
A
- ECG → tented T; prolonged PR and QT
- CXR: ?lung neoplasia, TB
- AXR: ?TB
16
Q
What specialist tests can be used in diagnosis of AD
A
Short Synacthen test and
Synacthen test
17
Q
What are the test in Synacthen test
A
- 250 micrograms ACTH per day for 3-5 days IV
2. Daily urine check for 17-hydroxysteroid levels
18
Q
What are the steps in short Synacthen test
A
- Baseline cortisol
- 250 micrograms of Synacthen IM
- 30 min cortisol check
19
Q
What does Synacthen test demonstrates
A
a. Normal in primary
b. 3-5 x increase in secondary
20
Q
What does short Synacthen test demonstrates
A
Exclude if 30 min level >550nmol/L (↑ by >200 nmol/l)
21
Q
what are the problems with short Synacthen test
A
- May be affected by steroids, pregnancy COCP
* Less useful for secondary causes
22
Q
What is multi gland failure
A
Autoimmune condition presenting with multi-gland failure including T1DM, chronic hypoparathyroidism, autoimmune thyroid disease etc.
23
Q
what is the genetics and presentation of multi gland failure
A
- Autosomal recessive (T1) OR polygenic (T2)
- Often seen in children
- Range of symptoms depending on glands affected
24
Q
What do patients with AD should be educated about
A
- Info. About disease + not missing steroids
- Medical alert bracelet
- Steroid card
- Actions with activities/exercise → add 5-10mg hydrocortisone
- Double steroid dose with illness
25
What is the hormone replacement regime in AD?
* Glucocorticoid: Hydrocortisone →10mg/5mg morning/lunch
| * Mineralocorticoid: Fludrocortisone 50 – 200 micrograms
26
What is the follow up in primary AD
* Yearly (BP, U&E)
| * Screening for other autoimmune diseases
27
What are the principles of management of secondary AD
* Try to stop/↓ steroids if iatrogenic
* Hormone replacement
* Manage secondary cause
28
What are the complications of AD
* Addisonian crises: 8% annual admission
* ↓ quality of life → ongoing symptoms i.e. fatigue, loss of libido, recurrent admissions
* Osteoporosis
29
What is the prognosis in AD
management dependent i.e. addisonian crises or infection can cause death
30
What are the causes of addisonian crises (AC)
* Addison’s disease → poor compliance
* Long-term steroid use
* Haemorrhage into adrenals
* Drugs i.e. phenytoin
31
What factors may precipitate AC
Infection, trauma, surgery, missed medications
32
What is the presentation of AC
* Sudden, severe back and abdominal pain
* D&V
* Shock: ↑HR, vasoconstriction, postural hypotension, oligoria, weakness, confusion, coma
33
What is the immediate management of AC
* Suspected →treat before biochemical results
* Urgent bloods→ ACTH, U&Es
* Hydrocortisone 100mg IV/IM stat (children 50-100/50/25 mg in >6/1-6/
34
What is later management of AC
* Glucose IV for hypoglycaemia
* IV fluids →U+Es guided
* Hydrocortisone 200mg/8h IV/IM
* Oral steroids after 72h
* Treat underlying cause
35
What is the difference between cushion's disease and syndrome
* Disease increased circulating ACTH from pituitary
| * Syndrome symptoms related to prolonged exposure to glucocorticoids and loss of normal mechanism of HPA axis
36
what is the prevalence of Cushion's
10-15/million
37
what is the previlence of cushion's in IDDM with HTN and poor glucose control
2-5%
38
what are the RF for cushion's
* Female →adrenal/pituitary tumours 5:1
| * Small lung cancer →smoking etc
39
What are the ACTH dependent causes of cushions and how previlent are they
```
80% of cushion's
Pituitary adenoma or cancer i.e. ectopic secretion o Small cell lung cancer and bronchial carcinoid tumour
o Pancreatic neuroendocrine tumour
o Medullary thyroid cancer
o GI carcinoids
```
40
What sort of symptoms may point towards ectopic ACTH secretion
↓weight, ↑↑pigmentation, hypokalemic metabolic ankylosis and hyperglycaemia
41
What sort of test can be used if pituitary adenoma is suspected and what are the results
(low dose dexamethasone ↓↓ cortisol as in normal)
42
What are the ACTH independent causes of cushion's
* Iatrogenic i.e. medications
| * Unilateral adrenal tumour (adenoma/carcinoma →60/40%)
43
What are the symptoms of cushions related to adipost tissue
truncal, supraclavicular facial (moon face) fat, buffalo hum
44
What are the symptoms of cushions related to skin
atrophy, purple striae, bruising, hirsutism, acne, ↑pigmentation
45
What are the symptoms of cushions related to glucose
DM/Impaired glucose tolerance • Glycosuria - Thirst, polydipsia, polyuria
• diabetes
46
What are the symptoms of cushions related to gonads
• Gonadal dysfunction/ ↓ libido
47
What are the symptoms of cushions related to psychiatry
depression, cognitive dysfunction emotional lability
48
What are the symptoms of cushions related to bones
• Osteoporosis, osteopenia
49
What are the symptoms of cushions related to pituitary tumour
headaches, visual problems, and galactorrhoea
50
What are the symptoms of cushions related to menstruation
irregular menses/amenorrhoea due to hypothyroidism
51
What are the symptoms of cushions
* Adipost tissue redistribution: truncal, supraclavicular facial (moon face) fat, buffalo hum
* Proximal muscle wastage
* DM/Impaired glucose tolerance Glycosuria - Thirst, polydipsia, polyuria
* Gonadal dysfunction/ ↓ libido
* HTN, kidney stones
* Skin: atrophy, purple striae, bruising, hirsutism, acne, ↑pigmentation
* Psychological: depression, cognitive dysfunction emotional lability
* Osteoporosis, osteopenia
* Oedema
* F: irregular menses/amenorrhoea due to hypothyroidism
* Cataracts
* Impaired immune function: increased infections, difficulty with wound healing
* Child: growth restriction
* Pituitary tumour: headaches, visual problems, and galactorrhoea
52
what are the DD for cushion's
* Prolonged+ excessive alcohol use
* Obesity
* Poorly controlled DM
* HIV
* Anxiety and depression
53
When is the cortisol high and low
high morning
| low midnight
54
What are the possible tests for CS
Overnight dexamethasone suppression test
24h urine free cortisol
48 hour dexamethasone suppression tests
48 hour high-dose dexamethasone suppression tests
Midnight cortisol
ACTH level
CRH + cortisol level
55
what are the principles of 48 hour dexamethasone suppression tests
* Give dexamethasone 0.5mg/6h PO for 2 days
* Measure cortisol at 0 hours and 6 hours after final dose
* In CS → failure to suppress cortisol
56
what are the principles of Overnight dexamethasone suppression test
1. PO dexamethasone at midnight
2. Serum cortisol at 8am
• Normal → suppression to
57
what are the principles of 24h urine free cortisol
• Normal →
58
what are the principles of 48 hour high-dose dexamethasone suppression test
* 2mg/6h
* Pituitary suppression vs other causes
* Pituitary adenoma (Cushing’s disease) suppression of more than 50%
* Other causes no suppression
59
what are the principles of Midnight cortisol
CS high cortisol at night
60
what are the principles of CRH administration
100 micrograms of CRH ↑ cortisol at 2h in pituitary not ectopic
61
What are the results of overnight dexomethasone supression test and what are the causes for false positives
Normal → suppression to
62
What are the ACTH levels indicative of
• Undetectable → adrenal tumour (CT or venous sampling)
63
what investigations can be used with ectopic ACTH release
• ? ectopic ACTH → CT chest, abdo, pelvis/MRI
64
What is Nelson's syndrome
Complication of bilateral adrenectomy due to pituitary tumour
Nelson’s syndrome rapid enlargement of pituitary adenoma post bilateral adenectomy→ bitemporal hemianopia
65
What is the treatment for CD
removal of pituitary adenoma (transphenoidal) OR bilateral adrenectomy
66
What is the treatment for Iatrogenic causes of CS
stop medication if possible
67
what is the management of adrenal adenoma and carcinoma
Adrenal adenoma: adrenalectomy
| Adrenal carcinoma: adrenalectomy + radiotherapy + adrenolytic drugs mitotane
68
what is the management of CS in ectopic causes
* Surgery for non-metastatic tumours
* Metyrapone, ketoconazole and fluconazole → ↓ cortisol secretion pre-surgery
* Etomidate →blocks cortisol synthesis (i.e. if cortisol induced psychosis)
69
what is the prognosis for CS
* ↑ vascular mortality if untreated
| * Symptoms i.e. HTN, ↑BMI, mood changes etc.
70
What is Pheochromocytoma
Rare catecholamine-producing tumours → from chromaffin cells OR rare extraadrenal
71
What are the parameters of role of role of 10% in pheoochromocytoma
* 10% are malignant
* 10% are extra-adrenal
* 10% are bilateral
* 10% are familial/hereditary
72
What is the parentage of sporadic cases of pheoochromocytoma
10%
73
What is the triad of symptoms in pheoochromocytoma
Episodic headache, sweating, and tachycardia (± BP↑,↓ or ↔)
74
What investigations can be used for diagnosis of pheochromocytoma
• ↑WCC
• Plasma + 3 x 24h urines for free metadrenaline and normetadrenaline
• Clonidine suppression test → measure catecholamines at 0 and 3h post 0.3mg dose
o +ve if normal levels
• Imaging → CT/MRI OR isotope for extraadrenal (MIBG)
75
What is the suppression test pheochromocytoma
• Clonidine suppression test → measure catecholamines at 0 and 3h post 0.3mg dose
o +ve if normal levels
76
What are the management steps in pheochromocytoma
1. Short acting α IV phentolamine→ control BP
2. When stable BP → long-acting α i.e. phenoxybenzamine 10mg/24h PO
a. ↑by 10 mg/day as needed up to 30mg/12h PO
b. SE: postural hypotension, tachycardia, tiredness, nasal congestion
3. BP controlled + no postural hypotension → start β1-blocker
4. Surgery after 4-6 weeks
77
what is the post-op management of pheochromocytoma
• 24h urine metadrenalines 2wks post-op, monitor BP (risk of ↓↓BP)
78
What is the follow-up fro pheochromocytoma and why
* Lifelong: malignant recurrence may present late
| * Genetic screening
79
what are the triggers for pheochromocytoma crises
stress i.e. surgery, GA, contrast
80
What is the presentation of pheochromocytoma crises
```
• Pallor, Pulsating headache, Hypertension
• Feels ‘about to die’
• Pyrexial
• ECG:
o Signs of LVF,
o ↑ ST segment
o VT and cardiogenic shock
```
81
define Primary Hyperaldosteronism and primary findings
Excess production of aldosterone independent of RAAS
• Sodium and water retention
• ↓ renin relase
• HTN, hypokalaemia +alkalosis (without diuretics)
82
what are the symptoms of Primary Hyperaldosteronism
Asymptomatic or signs of hypokalaemia i.e. weakness, cramps, paraesthesia polydipsia, polyuria, ↑BP
83
what are the causes of Primary Hyperaldosteronism + proportions
2/3 conn's
1/3 bilateral adrenocortical hyperplasia
• Rare genetic i.e. GRA
84
define Conn's syndrome
solitary aldosterone producing adenoma
85
what are the investigations in Primary Hyperaldosteronism
* U+Es: ?hypokalaemia (may be normal)
| * Renin and aldosterone
86
what is Secondary Hyperaldosteronism
Due to a high renin from ↓renal perfusion, e.g. in renal artery stenosis, accelerated hypertension, diuretics, CCF or hepatic failure.
87
What is Bartter's syndrome
Major cause of congenital (autosomal recessive) salt wasting—via a sodium and chloride leak in the loop of Henle via a defective channel
88
How does Bartter's syndrome present
* Presents in childhood with failure to thrive, polyuria and polydipsia. BP is normal
* Sodium loss leads to volume depletion, causing ↑ renin and aldosterone production → hypokalaemia and metabolic alkalosis + ↑ urinary K+ and Cl–
89
what is the management of Bartter's syndrome
* K+ replacement
| * NSAIDS (to inhibit prostaglandins), and ACE-i
90
Define congenital adrenal hyperplasia (CAH)
* Group of autosomal recessive disorders of cortisol synthesis e.g. 21-hydroxyl deficiency (95% of causes)
* Salt lousing or non-salt lousing
91
What is the epidemiology of CAH
1/18000
| boys wors i.e. salt lousing
92
What are the findings in CAH
↓Cortisol ± ↓aldosterone (salt lousing) and ↑androgen
93
what are the change sin females with CAH
ambiguous genitalia and urogenital sinus instead of normal separation
94
What are the changes in males with CAH
hyperpigmentation and penile enlargement
95
What is non classical presentation of CAH
• Non-classic CAH can present with early pubarche, infertility, oligomonorrhoea
96
What are the possible symptoms in adults with CAH
o Hyperandrogenism
o Iatrogenic Cushing's syndrome
o Infertility
o Metabolic syndrome
97
What are the investigations in CAH
* U&Es
* Serum 17-hydroxyprogesterone (high diagnostic of 21-hydroxylase deficiency)
* Bone age
* USS
* Karyotype
98
What is the management of CAH
```
• Glucocorticosteroids
o Children → hydrocortisone
o Adults → dexamethasone or prednisolone i.e. long-acting
• Mineralocorticoids
o Fludrocortisone
o Sodium chloride supplements in infancy with salt-lousing presentation
• ↑ stress → trauma, illness, surgery
o Double the dose of hydrocortisone
```
99
What are the complications of CAH
* ↓ height
* ↑ weight
* Precocious puberty
* Polycystic overies
* Infertility
100
What are the causes of endocrine hypertension
```
• Neurogenic hypertension → pheochromocytoma
o Resistant as due to ↑adrenalin and noradrenalin
• Conn’s syndrome ↑ aldosterone
• Idiopathic hyperaldosteronism
• Cushion’s syndrome→ ↑glucocorticoids
• Hyperparathyroidism
• Acromegaly
• Hyper and hypothyroidism
```
101
What is the adrenal incidentaloma and how can it be tested
Asymptomatic adrenal tumour from imaging i.e. lesion of >1cm
• ?primary/ metastatic/ benign
• Overnight dexamethasone test? Cushin’s or hyperaldosteronism
• 85% benign/non-functional
