Week 8: Adrenal hypofunction Flashcards
Adrenal problems for the clinician
7 listed
Clinical Case Vignette
Identify
Identify
Steroid hormone synthesis
Hydrocortisone AKA
Cortisol
How do steroid hormones work?
Describe the regulatory relationships of the HPA axis
Describe the circadian and ultradian variation in HPA activity
When should you measure cortisol for Cushing’s syndrome?
Midnight
When should you measure cortisol for adrenal insufficiency?
Morning so adrenals are usually high at this time
CRH is made in?
hypothalamus
How is CRH measured?
really diluted in systemic circulation so would have to get from the hypothalamus pituitary protal system
So instead we measure ACTH
Describe the free-hormone hypothesis
many steroids have a binding protein however the free portion of the steroid is the biologically active fraction
Usually, the protein-bound form can be high and total steroid count can seem high but it could be in the inactive protein-bound form
*Measure total not free*
one big issue with exoogenous corticosteroids
Negative feedback inhibition on ACTH of the Ant. Pit. causing adrenal insufficiency
Describe the regulation of aldosterone secretion
Angiotensin II is the main positive regulator for aldosterone secretion
Aldosterone secretion positive regulators
6 listed
- Angiotensin II (main stimulatory regulator)
- Hyperkalemia
- Adrenocorticotropin
- Hyponatremia
- Angiotensin III
- Aldosterone-stimulating factor
Negative regulators of Aldosterone secretion
2 listed
- Atrial natriuretic factor
- Dopamine
Things that promote renal secretion of renin
5 listed
↓ effective blood volume
↓ blood pressure
↓ [NaCl] and [K+] at the diistal tubule
↑ prostaglandins
β-adrenergic stimulation
Primary Adrenal insufficiency hormones deficient
No aldosterone and no cortisone
Combined cortisol and aldosterone deficiency
Secondary vs primary adrenal insufficiency
Primary
- aldosterone and cortisol deficiency
- High levels of ACTH (due to loss of cortisol feedback on the pituitary)
Secondary
- Aldosterone is preserved
- cortisol deficiency is deficient
- low levels of ACTH
Adrenal medulla
SNS and the adrenal medulla
Describe the pathophysiology of adrenal disorders
Types of adrenal insufficiency
- Primary means the target organ is deficient (Adrenals are non-functioning)
- Secondary means other organ is failing to activate the target organ (pituitary not secreting ACTH to activate cortisol secretion by the adrenals)
- Acute (ie adrenal hemorrhage or pituitary hemorrhage)
- chronic
- acute-on-chronic (has had adrenal insufficiency and some other problem occurs that causes an adrenal crisis) (hypotensions is the cardinal feature)
Primary AI epidemiolgy
Rare
Primary AI associations
- Autoimmune
- AIDS
- Adrenoleukodystrophy (disorder of long-chain FAs that accumulate in the adrenals)
- CAH (Congenital adrenal hyperplasia)
- Fungal (histoplasmosis, Coxsie)
- TB (probably most common cause worldwide)
Primary AI clinical presentation
GI symptoms prominent
- Hyponatremia
- Hyperkalemia
- acidosis
- eosinophilia
- lymphocytosis
- mild hypercalcemia
- azotemia
Mineralocorticoid as well as glucocorticoid deficiency
- hypotension
- hyperpigmentation (almost pathognomonic)
- weight loss
- fatigue
Adrenoleukodystrophy description
(a disorder of long-chain FAs that accumulate in the adrenals)
Adrenoleukodystrophy etiologies
X-linked syndrome
CAH AKA
Congenital adrenal hyperplasia
CAH etiologies
the common form is 21-hydroxylase deficiency so decreased ability to make cortisol
Why hyperpigmentation for Primary AI
because the precursor of ACTH is proopiomelanocortin so high levels of ACTH cause hyperpigmentation of the skin
Causes of Primary AI
7 listed
Infectious causes of Primary AI
3 listed
- TB
- Coccidiomyocosis
- histoplasmosis
Autoimmune causes of Primary AI
Addison’s Disease
Polyglandular autoimmune disease
CAH etiologies
Deficiencies of these enzymes
- 17-hydroxylase
- 11-hydroxylase
- 21-hydroxylase
Medications that can cause Primary AI
- Abiraterone
- Metyrapone
- Ketoconazole
Abiraterone MOA
used in prostate cancer because blocks first stemp is cortisol biosynthesis so it also blocks adrenal androgen production
HPA axis and negative feedback mechanisms
What is this?
hyperpigmentation from primary AI
Evaluation of Primary AI
- imaging of adrenals for hemorrhage or infiltrative disease, infections or malignant tumors
- VLCFAs for adrenoleukodystrphy
- Serological for autoimmune or congenital
cortisol synthesis
Some babies from primary/secondary adrenal AI can have ambiguous genitalia from androgen dysfunction
look back at primary vs secondary to determine this because lecturer got a little lost
Secondary adrenal insufficiency
ACTH deficiency
Insufficiency of ACTH or could be even higher up the axis tertiary etc.
Chronic adrenotrophic hormone deficiency
leads to reversible atrophy of adrenal cortex
Secondary/Tertiary AI epidemiology
Common & difficult to recognize clinically
Secondary/Tertiary AI etiologies
- hypopituitarism or isolated ACTH deficiency
- exogenous corticosteroids
Gold standard tests for Secondary/Tertiary AI
- Insulin tolerance test
- Metyrapone
What to do from hypotension in the setting of Secondary/Tertiary AI
Empirical glucocorticoid replacement
Describe the cortisol secretion rate as a function of ACTH concentration
Chronic exogenous corticosteroids blunted cortisol response to ACTH
It is reversible and if needed, is managed with an intermediate-term ACTH replacement
If there is long-term ACTH deficiency and a regular dose of ACTH is given why don’t you get a normal response
Because if there is long-term ACTH deficiency the response has been blunted and the adrenals don’t respond appropriately
Scondary/Tertiary AI associations
- Hypopituitarism (pituitary tumor removal, pituitary surgery, pituitary irradiation, pituitary apoplexy)
- Cure after Cushing’s (pituitary tumor secreting ACTH if you cure the tumor th patient would immediately go into AI because of the long-term from endogenous cortisol negative feedback on ACTH) (will recover normal if wait long enough)
Adrenal hormone synthesis pathways
How does Secondary/Tertiary AI differ from Primary AI
- No dehydration because mineralocorticoid activity remains intact (maintained by the renin-angiotensin axis in absence of ACTH)
- No hyperpigmentation (because this is caused by ACTH overload)
- Difficult to diagnose because (ACTH stimulation test is often positive but a significant % of false positives)
- hypotension is less prominent
- hyperkalemia not present (making aldosterone)
- hyponatremia might be present
- hypoglycemia is more common (glucocorticoids raise blood sugar)
Treatment OF AI
6 listed
For #3 we don’t give aldosterone because hard to supplement so give Fludrocortisone in primary AI
give people Injectable dexamethasone for emergencies such as an adrenal crisis
Clinical assessment of AI
- Exogenous corticosteroids (Cushing’s-Like features)
- Hyperpigmentation, hypotension, weight loss, orthostatic hypotension
- Evidence of anterior pituitary deficiencies (especially secondary sexual characteristics)
- Other clinical conditions that increase probability
- Routine labs and imaging studies
Diagnostics tests for AI
How to monitor adrenocorticosteroid replacement therapy?
Just have to try your best because there’s no way to measure it reliably so try to mimic diurnal variations
Adrenal Crisis AKA
Acute Adrenal Insufficiency
Acute Adrenal Insufficiency AKA
Adrenal crisis
Clinical features of adrenal crisis
How to identify a patient with AI are critically ill
CIRCI AKA
Critical Illness Related Corticosteroid Insufficiency
Critical Illness Related Corticosteroid Insufficiency AKA
CIRCI
Adrenal Crisis resistant to vasopressors
Adrenal insufficiency hypotension is resistant to vasopressors because glucocorticoids potentiate vasopressors so glucocorticoid deficiency can result in hypotensions that is resistant to vasopressor therapy
Critical Illness Related Corticosteroid Insufficiency
HArd to interpret the cortisol because CBG levels frop so the % of free cortisol will have gone way up
Decreased cortisol clearance rates and increased cortisol production rates
CIRCI & Septic shock
CIRCI literature
CIRCI Dx and Tx
