Biochemistry Pituitary and Adrenal Flashcards
1
Q
Conditions with Increased ACTH (low cortisol/ increase primary production) also present with:
A
- Beta endorphins
- Melanocyte hormone (increased pigmentation)
Cleaved from: pro-opiocortin
2
Q
From Cholesterol produces:
A
- Aldosterone
- Cortisol
- Testosterone (25%)
- Oestradiol
3
Q
cortisol Epi production rate
A
Most important glucocorticoid
Production rate c. 25mg/day
4
Q
Cortisol forms
A
90% protein bound (CBG and Albumin)
Free Fraction physiologically active
5
Q
Cortisol Effects
A
Carbohydrate metabolism • Insulin antagonist • Gluconeogenesis Protein Catabolism Immunosuppression (can be done therapeutic) “Permissive action” • Catecholamines • Free water clearance – w/o cortisol inappropriate ADH production there H2O retention - hyponatraemia
6
Q
Test for Cortisol
A
Total Cortisol level e.g. bound and free
7
Q
Pathology of Cortisol
A
Significant abnormalities in proteins such as loss of proteins or an increase in proteins (pregnancy)
8
Q
Increase production of Cortisol
A
Increase in total and increase in free fraction as binding proteins saturated.
9
Q
Cortisol control
A
- Negative feedback
- Diurnal (lowest at midnight, rise am, decreases in day)
- Stress (exercise, emotion)
10
Q
Primary Causes of Cortisol suppression:
A
- Congenital adrenal hyperplasia
- Enzyme defect
- Selective or total destruction via a variety of causes
11
Q
Selective destruction of cortex causes
A
Autoantibodies
12
Q
Total adrenal destruction cause
A
Bacterial and fungal infections
TB
Metastatic carcinoma
Amyloidosis
13
Q
Secondary Adrenal Insufficiency causes
A
Steroids – ACTH deficiency due to hypothalamic or pituitary disease
14
Q
Adrenal Insufficiency Consequences:
A
- Hypoglycaemia
- Hypo-natraemia
- Hyperkalaemia
- Hypotension
- Pigmentation
- Non-Specific
15
Q
- Hypoglycaemia
A
Uncommon seen in neonates/cause adrenal crisis
16
Q
- Hypo-natraemia
A
Destruction leads to aldosterone loss and so Sodium loss and…
17
Q
- Hyperkalaemia
A
Potassium retention from aldosterone
18
Q
- Hypotension
A
Primary Cause (lack of negative feedback = ADH inappropriate control
19
Q
- Pigmentation
A
Primary Causes – due to cleavage to form ACTH and so melanocyte hormone produced
20
Q
Addison’s Disease symptoms:
A
- Lethargy
- Anorexia
- Pigmentation of hands and mouth – look at non sun-exposed areas.
- Abdominal pain
- Weight loss
21
Q
Acute Adrenal Crisis:
A
- Vomiting
- Nausea
- Dehydration
22
Q
Laboratory Investigations available →
A
Serum Cortisol
Dynamic synacthen (synthetic ACTH) stimulation test
ACTH
23
Q
Serum Cortisol
A
Problems as
- A strong diurnal rhythm
- If the patient is stressed false raised
24
Q
Dynamic synacthen (synthetic ACTH) stimulation test
A
Short: 250 ug given IM Looking for: Rise on cortisol Normal’s: • Incremental rise >200 nmol/L • Absolute rise >600 nmol/L
25
ACTH
Differentiates 1o/20
26
Synacthen stimulation test:
1. Normal rise (+200) and exceeds 600
2. Flat basal, no increase aove +600 – abnormal
3. Baseline normal, response abnormal – poor increase
4. V. high – severe stress
5. V. high – Iatrogenic (hydrocortisone)
27
Causes of poor increase
a. Early stages w/ reserved adrenal function
| b. Patient on steroids recently
28
• Primary adrenal failure
lack aldosterone (cortisol) >Na loss and K secretion
29
Electrolytes failure
• >Hyponatraemia >low plasma osmolality >reduced ADH (not completey reduced) – as cortisol permissive
* Loss of water to correct hyponatraemia
* Salt loss continuous and therefore water loss will be as well
* IV V becomes depleted ADH will eventually be secreted and some reabsorption
30
Electrolytes in adrenal failure
• Hyponatraemia, hyperkalaemia, volume depletion
31
21-hydroxylase enzyme action
1. Aldosterone (progesterone to Deoxycorticosterone)
2. Cortisol (17-OH progesterone to Deoxycortisol)
Gland still stimulated therefore overproduction of androgens.
32
21-hydroxylase Deficiency
Reduced aldosterone an reduced Cortisol
33
CAH Presentation
Ambiguous external genitalia
34
CAH Epi
>90% of cases of CAH
35
CAH Marker
Increased 17 alpha OH progesterone
36
CAH Classical Form
Incidence 1:5,000-1:20,000
Simple virilising
Salt wasting
Late onset
37
CAH Clinical Manifestations New Born
Ambiguous external genitalia
Pigmented scrotum
Salt wasting
Sudden unexplained death (males)
38
CAH Clinical Manifestations Adult
Hirsutism (females) – most common in PCOS
Menstrual cycle disorder
Subfertility
39
CAH Investigations
Blood
Urine
Karyotype
40
CAH Blood investigations
* 17 alpha hydroxyl progesterone (also following synactin as baseline not good but response is diagnostic)
* Electrolytes (hypo Na+, hyper K+)
* Glucose - neonates
* Increased Androstenedione
* Increased Testosterone
* Renin – mineral-corticoid treatment monitor
* 17-OHP profiles (shows under/over treatment monitoring)
41
CAH Renin results
Over: Renin reduced volume expands
Under: Renin increased volume depleted
42
CAH Urine
Electrolytes
| Steroid profile
43
CAH Karyotype
For determining the sex
44
Hypercortisolism (Cushing’s) → 2 types
ACTH High
| ACTH low
45
Hypercortisolism (Cushing’s) → ACTH high causes
Pituitary Cushing’s Disease
| Ectopic (lung)
46
Hypercortisolism (Cushing’s) → ACTH low
Adenoma’s – adrenal feedback
Carcinoma – adrenal feedback
Iatrogenic - overtreatment
47
Clinical features of Cushing’s
1. Mental disturbances
2. Fat redistribution, truncal obesity striae
3. Protein Catabolism
4. Osteoporosis
5. Poor wound healing
6. Bruising
7. Hyperandrogenism
8. Hirsutism
9. Acne
10. Amenerrhoea
11. Insulin resistance
12. Glucose intolerance
13. Salt retention
14. Hypertension
15. Immunosuppression
48
Initial Investigation – define excess cortisol production 7 ways
1. Serum Cortisol
2. Salivary Cortisol
3. Urine Free cortisol
4. Dexa suppression
5. Yanovski
6. CRH testing
7. High dose dexa
49
➢ Serum cortisol
Midnight/ 08:00 am
• Limited value
• Increased in stress
• False negative values in Cushing’s patients
50
➢ Salivary cortisolNB increased in stress illness and obesity
Problems in urine collection
Many assays not specific for cortisol
Midnight/09:00
• Demonstrate loss of diurnal rhythm
• Easy to collect at home, stress free environment
➢ D
51
➢ Urine free cortisol
NB increased in stress illness and obesity
Problems in urine collection
Many assays not specific for cortisol
52
➢ Dexamethasone Suppression
1 mg over night test (to exclude Cushing’s) – 09:00 am cortisol should be <50 nmol/L
53
Dexamethasone problem
High false positive rate
• Absorption dexamethasone
• Failure to take tablet
• Increased metabolism
54
Dexamethasone false negative
Cyclical Cushing’s (wax/waning)
55
Low dose dexamethasone
0.5 mg 6 hourly for 48 hours
→ Normal suppress
→ Cushing’s – no suppression
56
➢ Yanovski
Define excess cortisol production: looking at CRH following dexamethasome
57
Yanovski test
Cushing’s syndrome = massive cortisol increase after 15 mins
| Normal = Cortisol low
58
Serum Cortisol (09:00) =
523 nmol/L 9150-700)
59
UFC =
445/L/ 24 hrs (<120)
60
Post dexamethasone cortisol:
Serum Cortisol (09:00) = 531 nmol/L
61
➢ Ectopic V Pituitary ACTH production
* Bilateral Inferior Petrosal Sinus Sampling (BIPSS) – to differentiate
* Cushing’s disease – Increase ACTH in blood post pituitary
* Central – peripheral gradient +3
62
➢ High Dose Dexamethasone
2 mg 6 hourly for 48-72 hours
• Pituitary dependant (Cushing’s disease) suppress – w/ enough dexa
• Adrenal and Ectopic ACTH no suppression
63
Ectopic sources of ACTH response to CRH
Don’t respond
64
Cushing’s disease response to CRH
Exaggerated ACTH production
