Adrenal - Clinical Flashcards
1
Q
What are the layers of the adrenal gland?
A
Cortex (GFR)
- Zona glomerulosa
- Zona fasciculata
- Zona reticularis
Medulla
2
Q
What is secreted by the zona glomerulosa?
A
Mineralocorticoids - Aldosterone
3
Q
What is secreted by the zona fasciculata in the adrenal cortex?
A
Glucocorticoids
4
Q
What is secreted by the zona reticularis?
A
Sex hormones
5
Q
What is secreted by the medulla of the adrenal glands?
A
Adrenaline/Noradrenaline
6
Q
What is cushing’s syndrome?
A
The term used to describe the clinical state of increased free circulating glucocorticoid. It occurs most often following the therapeutic administration of synthetic steroids or ACTH (see below).
7
Q
What groups are the causes of cushing’s syndrome divided into?
A
- ACTH dependent
- ACTH independent
8
Q
What are causes of ACTH dependent cushing’s syndrome?
A
- Pituitary dependent (Cushing’s Disease)
- Ectopic ACTH production Tumours
- ACTH administration
9
Q
What are non-ACTH dependent causes of Cushing’s Syndrome?
A
- Adrenal Adenoma’s
- Adrenal CArcinoma’s
- Glucocorticoid administration
- Alcohol induced pseudo-Cushing’s syndrome
10
Q
What are ectopic causes of excess ACTH production?
A
- SCLC
- Carcinoid tumours
11
Q
What are features of an ectopic source of ACTH production in someone with Cushing’s Syndrome?
A
- Pigmentation
- Hypokalaemic metabolic alkalosis
- Weight loss
- Hyperglycaemia
Classical features of Cushing’s are often absent
12
Q
What is Cushing’s Disease?
A
Bilateral adrenal hyperplasia caused by an ACTH-secreting pituitary adenoma (ususally microadenoma)
13
Q
What are symptoms of Cushing’s syndrome?
A
- Weight gain
- Depression
- Insomnia
- Irritability
- Psychosis
- Proximal weakness
- Amenorrhoea
- Hirsutism
- Poor Libido
- Polyuria/Polydipsia
- Erectile dysfunction
14
Q
What are signs of Cushing’s Syndrome?
A
- Moon Face
- Plethora
- Acne
- Hirsutism
- Thin Skin
- Bruising
- Poor Wound healing/Skin infections
- Ostoporosis/Pathological Fractures
- Buffalo Hump
- Central Obesity
- Striae/Pigmentation
- Oedema
- Proximal myopathy
- Glycosuria
15
Q
Why do individuals with Cushing’s Syndrome get abdominal striae?
A
There is an increase in hormones thought to have a catabolic effect on fibroblasts (essential to form the collagen and elastin needed to keep skin taut), leading to dermal and epidermal tearing
16
Q
What else can cause a Cushingoid appearence apart from adrenal/pituitary causes?
A
Alcohol - pseudo-Cushing’s syndrome
17
Q
What causes of cushings syndrome cause hyperpigmentation?
A
ACTH-dependent causes.
18
Q
Why do you get bruising in Cushing’s syndrome?
A
Loss of subcutaneous connective tissue, due to the catabolic effects of glucocorticoids, exposes underlying vessels prone to rupture. It is a similar mechanism to that of striae.
19
Q
Why do individuals with Ectopic ACTH secretion get hypokalaemia?
A
Due to the mineralocorticoid activity of cortisol
20
Q
Why can Hirsutism occur in Cushing’s syndrome?
A
The mechanism is not clear. Excess ACTH has been shown to cause hyperstimulation of the zona fasciculata and zona glomerulosa, producing cortisol, androgens and potentially hirsutism.
21
Q
What is the mechanism behind pigmentation seen in Cushing’s Syndrome?
A
In Cushing’s disease, where ACTH is secreted by pituitary tumours, ‘tanning’ may occur by stimulation of melanocytes in a similar process to Addison’s disease.
22
Q
Why can those with Cushing’s be plethoric?
A
In Cushing’s Disease, excess cortisol causes degradation and atrophy of the epidermis and underlying connective tissue. This leads to apparent thinning of the skin and the appearance of facial plethora
23
Q
Why can those with Cushing’s Syndrome experience poluria?
A
Excess glucocorticoids have been shown to inhibit osmosis-stimulated ADH secretion as well as directly enhancing free water clearance, thus producing polyuria.
Hyperglycaemia causing osmotic diuresis is rarely the cause of polyuria in Cushing’s syndrome.
24
Q
Why can proximal myopathy occur in Cushing’s Syndrome?
A
The catabolic effects of glucocorticoids break down proteins in the muscle fibres, causing weakness. Additional factors induced by excess steroids include hypokalaemia, depressed protein synthesis, decreased sarcolemmal activity and increased myosin degeneration.
25
What investigations would you do if you suspected Cushing's Syndrome?
Stepwise Process
1. First line **- overnight dex suppression test + 24hr urinary free cortisol**
2. 2nd line **- 48 hr Low Dose Dex supression Test + Urine Free Cortisol**
3. Localise **- Plasma ACTH levels**
1. ACTH high - **High Dose Dex test**
2. ACTH low **- Pituitary MR/CT; BIPSS; CT chest**
Other investigations
* **U+E's**
26
What is involved in the overnight dexamethasone suppression test?
Patient takes 1mg of dexamethasone at 23:00, plasma cortisol measured next morning at 09:00. Normal test result \<50 nmol/L, whereas no suppression indicates Cushing's
27
What is involved in a 48 hr low-dose dexamethasone suppression test?
0.5mg 6 hourly for 2 days. Plasma cortisol measurements taken on day 0 and day 2. If failed suppression of cortisol after 2 days - Cushing's ***_syndrome_*** present.
28
What is involved in a high-dose dexamethasone suppression test?
2mg dexamethasone 6 hrly over 48 hrs. Cortisol measurements on day 0 and day 2. This test is used to distinguish between pituitary suppression and no pituitary suppression
29
What does failure to suppress cortisol on high-dose dexamethasone suppression test mean?
Failure of significant plasma cortisol suppression suggests an ectopic source of ACTH or an adrenal tumour.
30
What do low/undetectable ACTH levels suggest in someone presenting with suspected Cushing's syndrome?
Two or more occasions are a reliable indicator of non-ACTH-dependent disease.
31
What cause of cushing's syndrome can cause impaired glucose tolerance and hypokalemia?
Ectopic ACTH
32
When measuring plasma ACTH in someone with cushings syndrome, what does a low value indicate?
Adrenal tumour likely
33
How would you treat an iatrogenic cushing syndrome?
Stop therapy
34
How would you teeat someone with Cushing's Disease?
**Surgery**
* Trans-sphenoidal removal of pituitary adenoma
* Bilateral adrenalectomy - if no pituitary source
35
How would you manage someone with an adrenal carcinoma?
Adrenalectomy + adjuvant radiotherapy
36
How would you treat someone with cushing's syndrome that had an Ectopic source?
**Surgery** - if no widespread mets
**Symptom management** - if reasonable
* **Metyrapone or ketoconazole** - beneficial for symptoms
* **Bilateral adrenalectomy**
37
What is Conn's syndrome?
**Primary hyperaldosteronism**
Adrenal adenomas (Conn’s syndrome) originally accounted for 60% of cases of primary hyperaldosteronism but represented a rare cause of hypertension. Bilateral adrenal hyperplasia also falls under the umbrella of conn's syndrome
38
What is the pathophysiology of primary hyperaldosteronism?
Primary hyperaldosteronism is a disorder of the adrenal cortex characterized by excess aldosterone production, leading to:
* **Sodium retention**
* **Potassium loss**
* **Combination of hypokalaemia and hypertension**
39
What distinguishes primary hyperaldosteronism from secondary hyperaldosteronism?
Secondary hyperaldosteronism arises when there is excess renin (and hence angiotensin II) stimulation of the zona glomerulosa. Primary hyperaldosteronism is a disorder of the adrenal cortex overproducing aldosterone, leading to suppressed renin levels
40
What are causes of secondary hyperaldosteronism?
**Hypertensive**
* Malignant hypertension
* Renal artery stenosis
**Normotensive**
* Congestive cardiac failure
* Cirrhosis
* Diuretics
41
What are features of primary hyperaldosteronism?
Often asymptomatic
* **Hypertension**
* **Features of Hypokalaemia -** not frequently present
* Muscle weakness
* Polyuria
* Paraesthesia
* Nocturia
* Tetany
42
What are causes of primary hyperaldosteronism?
* **Adrenal adenoma**
* **Bilateral adrenal hyperplasia**
43
What initial investigations would you do if you suspected primary hyperaldosteronism?
Initial investigations
* **Plasma renin and aldosterone levels**
* **Plasma aldosterone:renin ratio**
* **U+E's**
* **Adrenal vein sampling**
44
What might you see when investigating renin and aldosterone levels in someone with primary hyperaldosteronism?
* **Elevated plasma aldosterone**
* **Suppressed plasma renin levels**
45
What is plasma aldosterone:renin ratio used for?
Screening for hyperaldosteronism
46
What feature of elevated plasma aldosterone levels is indicative of primary hyperaldosteronism?
Not supressed by saline challenge - 2L over 4 hrs; or fludracortisone injections
47
Once a diagnosis of hyperaldosteronism has been made, what investigations would you do to locate the source?
* **CT/MRI**
* **Adrenal Venous sampling**
48
How would you manage someone with Primary hyperaldosteronism?
Conn's
* **Surgical removal of adenoma**
* **Spironolactone**
Hyperplasia
* **Spironolactone/Amiloride**
49
If someone presented with symptoms/signs of hypertension and hypokalaemia, what would you investigate for?
Hyperaldosternism
50
If someone had raised serum aldosterone and lowered serum renin, what would this indicate?
Primary hyperaldosteronism
51
If someone had raised serum aldosterone and renin, what might this indicate?
Secondary hyperaldosteronism
52
What is a phaeochromocytoma?
These are very rare tumours of the sympathetic nervous system (less than 1 in 1000 cases of hypertension) that secrete catecholamines, noradrenaline (norepinephrine) adrenaline (epinephrine) and their metabolites
53
What syndromes is phaeochromocytoma most commonly seen in (when it is seen)?
* **MEN-2 syndromes**
* **Von-Hippel Lindau syndrome**
54
Which catecholamine is most commonly secreted in extra-adrenal phaeochromocytoma?
Almost entirely noradrenaline
55
What are paragangliomas?
Rare extra-adrenal neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen)
56
Why is phaeochromocytoma known at the '10% tumour'?
* **10% extra-adrenal**
* **10% malignant**
* **10% multiple**
* **10% familial**
57
What is the pathophysiology of phaeochromocytoma?
These tumours arise from sympathetic paraganglia cells which are chromaffin cells, which are normally found in the adrenal medulla
58
What are the symptoms of phaeochromocytoma?
Episodes of:
* **Anxiety**
* **Tremors**
* **Sweating**
* **Headache**
* **Flushing**
* **Nausea/vomiting**
* **Weight loss**
* **Constipation/diarrhoea**
* **Raynaud's**
* **Chest pain**
59
What are signs of phaeochromocytoma?
* **Hypertension**
* **Tachycardia/arrhythmias**
* **Bradycardia**
* **Orthostatic hypotension**
* **Pallor/flushing**
* **Glucosuria**
* **Fever**
60
How would you investigate suspected phaeochromocytoma?
* **Urinary catecholamines and metabolites**
* **Plasma metanephrine**
* **CT/MRI abdo**
* **Scanning with meta-iodobenzylguanidine (MIBG)**
* **PET Scan**
61
What does an MIBG scan indicate?
Produces specific uptake in sites of sympathetic activity with about 90% success. It is particularly useful with extra-adrenal tumours. 18F-deoxyglucose PET is also used by some centres in the localization of phaeochromocytomas.
62
How would you manage someone with phaeochromocytoma?
* **Surgical removal if possible**
* **When operation not possible** - alpha/beta-blockade used long term
63
What is important to do pre-operatively before removing phaeochromocytomas?
**Pre and post operative alpha and beta blockade are essential**
* Alpha must precede beta, as worsened hypertension may result
**Lack of blockade can result in severe hyper/hypotension**
64
What is Addison's Disease?
**Primary adrenocortical insifficiency**
There is destruction of the entire adrenal cortex. Glucocorticoid, mineralocorticoid and sex steroid production are therefore all reduced. In Addison’s disease reduced cortisol levels lead, through feedback, to increased CRH and ACTH production, the latter being directly responsible for the hyperpigmentation.
65
What are causes of primary adrenal insufficiency?
* **Autoimmunity**
* **TB**
* **Adrenal mets**
* **Lymphoma**
* **Infections**
* **Adrenal haemorrhage** - Waterhouse-Fredrich syndrome
* **Congenital**
* **Adrenal Removal**
* **21-hydroxylase deficiency**
66
What are causes of secondary adrenal insufficiency?
* **Iatrogenic** - steroid therapy
* **Hypothalamic-pituitary disease** - inadequate ACTH production
67
What are symptoms of addison's disease?
Lean, tanned, tired and treaful
* **Weight loss**
* **Anorexia**
* **Malaise**
* **Fever**
* **Depression**
* **Impotence/amenorrhoea**
* **Nausea/vomiting**
* **Diarrhoea/constipation**
* **Confusion**
* **Syncope from postural hypotension**
* **Abdo pain**
* **Myalgia**
* **Joint/back pain**
68
What are signs of addison's disease?
* **Pigmentation**
* **Buccal pigmentation**
* **Postural hypotension**
* **General wasting**
* **Dehydration**
* **Loss of body hair**
* **Vitiligo**
69
What endocrine disorder would you think of as a cause of unexplained abdominal pain?
Addison's disease
70
What investigations would you consider doing if you suspected addisons disease in someone?
Tests (in order)
1. **Routine bloods:** U&E, glucose, FBC, renin levels
2. **Random cortisol**
3. **Synacthen (ACTH response)**
4. **Basal ACTH**
Other
1. **Adrenal autoantibodies**
71
What serum electrolyte abnormality is indicative of addison's disease?
Low sodium, high potassium
72
Why would you perform a plasma glucose in someone with addison's?
They may be hypoglycaemic
73
Why would you perform renin levels in someone with addison's disease?
High due to low serum aldosterone.
74
What might you find on investigation of random cortisol in someone with addisons?
* **\>700 nmol/l (not Addison’s)**
* **\<700 nmol/l (adrenal status uncertain)**
75
What is a short synacthen test?
**Procedure**
* Intravenous cannula for sampling
* Any time of day, but best at 09:00 hours; non-fasting
* Tetracosactide 250 µg, i.v. or i.m. at time 0
* Measure serum cortisol at time 0 and time +30 min
76
What is regarded as a normal response for a short synacthen test?
**30 min cortisol \>600 nmol/La**
400–600 nmol/L borderline and may indicate deficiency
77
What is regarded as an abnormal short synacthen repsonse?
\<550nmol/L cortisol after 30 minutes
78
What might you find on investigation of FBC in someone with addison's disease?
* **Anaemia**
* **Eosinophilia**
79
How would you manage someone with addison's disease?
* **Glucocorticoid replacement** - hydrocortisone, prednisolone
* **Mineralocorticoid replacement** - Fludrocortisone
* **Education regarding crises**.
80
How would you assess adequacy of glucocorticoid medications used to treat addison's disease?
* **Clinical wellbeing**
* **Restoration of normal, but not excessive, weight**
* **Normal cortisol levels during the day while on replacement hydrocortisone**
81
How would you asses adequacy of fludrocortisone use in someone with addison's disease?
* **Restoration of serum electrolytes to normal**
* **Blood pressure response to posture**
* **Suppression of plasma renin activity to normal.**
82
What is an addisonian crisis?
A medical emergency and potentially life-threatening situation requiring immediate emergency treatment. It is a constellation of symptoms that indicate severe adrenal insufficiency caused by insufficient levels of the hormone cortisol.
83
What are features of an addisonian crisis?
Often with a precipitating event such as illness or trauma:
* **Features of Shock**
* **Hyponatreamia/hyperkalaemia**
* **Dehydration**
* **Hypoglycaemia**
84
What can cause an addisonian crisis?
* **Addison's disease** - uncontrolled/when meds are stopped/acute illness
* **Steroid therapy** - removed too quickly
* **Adrenal haemorrhage** - e.g. in meningococcaemia
85
How would you intially manage somone who was in a addisonian crisis?
* **Bloods** - cortisol, ACTH, FBC, U+E's
* **Blood/urine/sputum culture**
* **Hydrocortisone IV stat** - 100mg
* **500ml Bolus saline** - repeat if necessary
* **Dextrose infusion** - if hypoglycaemic
86
What dose of hydrocortisone would you give someone IV in an addisonian crisis?
100mg
87
How soon after an addisonian crisis (initially treated with IV hydrocortisone 100mg) would you swtich to oral steroids?
72 hrs if patients well
88
If someone with addisons disease was having a minor acute illnes, what would you advise them to do?
Double glucocorticoid dose
89
If someone with addisons disease was suffering froma major illness, how would you adjust their management?
* **100mg hydrocortisone iv stat**
* **50-100mg HC iv 8-hourly**
90
What self-care advise would you give someone with addison's disease?
**Never miss steroid dose**
**Double the hydrocortisone dose in the event of intercurrent illness**
**If severe vomiting or diarrhoea** - call help without delay
* Likely to need IM hydrocortisone - some patients or partners are taught to inject
91
What is congenital adrenal hyperplasia?
Deficiency of an enzyme in the cortisol synthetic pathways. There are six major types, but most common is 21-hydroxylase deficiency (CYP21A2), which occurs in about 1 in 15 000 births and which has been shown to be due to defects on chromosome 6 near the HLA region affecting one of the cytochrome p450 enzymes (p450C21).
92
How is congenital adrenal hyperplasia passed on?
Autosomal recessive inheritence
93
What is the pathophysiology of congenital adrenal hyperplasia?
Deficiency of 21-hydroxylase deficiency (CYP21A2), which results in reduced cortisol secretion, leading to reduced feedback to the pituitary. This causes increased ACTH secretion to maintain adequate cortisol – leading to adrenal hyperplasia.
Diversion of the steroid precursors into the androgenic steroid pathways occurs. Thus, 17-hydroxyprogesterone, androstenedione and testosterone levels are increased, leading to virilization. Aldosterone synthesis may be impaired with resultant salt wasting.
94
What is virilization?
Onset of amenorrhoea, clitoromegaly, deep voice, temporal hair recession + hirsutism
95
What is hirsutism?
Implies a male pattern of hair growth in females - usually benign
96
What are causes of hirsutism?
* **Idiopathic**
* **Familial**
* **Increased androgen production** - PCOS, ovarian cancer
* **Late onset adrenal hyperplasia**
* **Cushing's syndrome**
* **Adrenal carcinoma**
* **Drugs** - steroids
97
What are features of severe congenital adrenal hyperplasia?
Severe
1. **Sexual ambiguity**
2. **Adrenal failure** - collapse, hypotension, hypoglycaemia
3. **Neonatal Salt-losing crisis** - hypotension, hyponatraemia
98
What test might you do if you found random cortisol levels to be abnormally low?
Short synacthen test
99
If you found a short synacthen test to be abnormal in someone with suspected addisons, what test would you perform?
Plasma ACTH - determine whether primary or secondary hypoadrenalism
100
If, when investigating plasma ACTH levels in someone with suspected addisons, they had suppressed ACTH levels, what might this indicated about the source of the problem?
The source is secondary - secondary hypoadrenalism
101
What mnemonic can you use for remembering some of the main features of Cushing's syndrome?
SWEDISH
* **S**pinal tenderness
* **W**eight - central obesity
* **E**asy bruising
* **D**iabetes
* **I**nterscapular fat pad
* **S**triae
* **H**ypertension
102
If, when investigating plasma ACTH levels in someone with suspected addisons, they had elevated ACTH levels, what might this indicate about the source of the problem?
The source is primary - primary hypoadrenalism
103
What are features of late onset congenital adrenal hyperplasia?
Precocious puberty (with hirsutism), usually accompanied by primary amenorrhoea in women
104
If someone presented with symptoms of phaeochromocytoma (episodic sympathetic attacks) plus horner's syndrome, what might be the source of the problem?
Paraganglioma in the neck
105
What investigations would you do if you suspected CAH?
All will be raised
* **17-Hydroxyprogesterone levels**
* **Urinary pregnanetriol excretion**
* **Androstenedione levels**
* **Basal ACTH levels**
106
What is hirsutism developing ***_before_*** puberty suggestive of?
Congenital adrenal hyperplasia
107
What is an incidentaloma?
Incidental adrenal masses found on CT/MRI
The two issues of concern with an incidental adrenal mass are:
* **Whether the lesion is functional or non-functional, and**
* **Whether it is benign or malignant.**
