172. Adrenal Cortex Flashcards
Most common type of isolated hypoaldosteronism
AKA type IV renal tubular acidosis
Hyporeninemic hypoaldosteronism
Located in:
- liver
- lung
- omental fat
Converts cortisone to cortisol
11B-hydroxysteroid DH Type I
Clinical manifestations:
- hirsutism, acne, temporal/central balding
- ruddy complexion, purple striae
- increased red cell mass
- irregular periods
Adrenal androgen excess
Leads to:
- hyponatremia
- hyperkalemia
- dehydration
- hypotension
Rare for this to occur in an isolated manner
Aldosterone deficiency
Measure in women:
- DHEA-S
- Androstenedione
- Testosterone
Measure in men:
- Testosterone
Androgen testing
Expressed in:
- vasculature
- heart
- kidney
- adrenal
- pituitary
Action: when acted on by angiotensin II
- vasoconstriction
- aldosterone synthesis
- vasopressin secretion
AT receptor type 1
Can be due to aberrant receptor expression:
- GIP
- Vasopressin
- LH
- IL-1
Type of nodular adrenal hyperplasia leading to glucocorticoid excess
Macronodular
Clinical manifestations:
- weight gain, redistribution of fat
- Na+ retention, fluid retention, HTN
- K+ depletion, hypokalemia
- Hyperglycemia, CHO intolerance, diabetes
- Ruddy complexion, purple striae
- Hyperphagia
- Depression, euphoria, inability to concentrate
- Osteoporosis
- Myopathy, muscle loss, weakness
Cushing’s Syndrome (glucocorticoid excess) Chronic
Used to differentiate b/w Cushing’s Disease and Ectopic ACTH syndrome
Cushing’s: ACTH and cortisol decrease
Ectopic: ACTH will stay elevated
Dexamethasone testing
Genetic enzyme deficiencies lead to defect of cortisol and excess of precursors
Mixed hypo- and hyperfunction
Congenital adrenal hyperplasia
Basal plasma cortisol and ACTH Cosyntropin (synthetic ACTH) stimulation test
Direct pituitary stimulation tests for ACTH
- insulin tolerance
- CRH Plasma aldosterone and renin
Endocrine testing in adrenal insuffiency
Important middle product of cholesterol conversion into adrenal cortex products
Used as a marker for enzyme blockage down the road
17-OH-progesterone
Leads to a decrease in K+ absorption (increase in excretion) and an increase in Na+ absorption (decrease in excretion)
Aldosterone
Decreases protein synthesis and AA uptake in extrahepatic tissues
AA diverted to gluconeogenesis in the liver
Decrease growth hormone secretion and action
Catabolic effects of cortisol
Etiologies:
- aldosterone-producing adenoma
- bilateral nodular hyperplasia HTN, hypokalemia (50%), alkalosis
Primary selective mineralocorticoid excess
Senses decreased osmotic pressure leading to renin release
Located b/w afferent and efferent arteriole in the kidney just in front of the glomerulus
Macula densa
Products of the adrenal cortex all derive from what being made into what
- except DHEA which comes from pregnenolone (middle product of this reaction)
Cholesterol –> progesterone
Most common cause is prolonged steroid use
- longterm prednisone
Could be 2/2 pituitary disease:
- tumor
- granuloma
- autoimmune
- hemorrhage
ACTH deficiency (secondary adrenal disease)
Electrolytes: in kidney, guts, and sweat glands
- Na+ retention
- K+ excretion
Adipose:
- redistribution of fat (fat pads)
Red cell mass decreases
Depresses all aspects of the immune response
Anti-inflammatory
CNS effects:
- stimulates appetite
- mood modulation (euphoria and depression)
Cortisol
Etiologies:
- Autoimmune
- Addison’s
- Infectious/granuloma
- tuberculosis (most common worldwide)
- Hemorrhage
- seen in shock
- Metastases
- Genetic ACTH receptor or MRAP deficiency
Primary adrenal disease
This enzyme is important in men for bone health
Converts testosterone to estradiol
Enzyme blocked in women w/ breast cancer
Aromatase
Effects:
- Na+ retention
- K+ excretion
- H+ excretion
Diseases involving these are call “salt-wasting”
- pts crave salt
Mineralocorticoid
Carcinoma of lung
Carcinoma of pancreas
Thymoma
Benign bronchial adenoma (including carcinoid)
Sources of ectopic ACTH
Enzyme responsible for conversion of 11-deoxycortisol –> cortisol Second most commonly mutated in pathway - can’t make cortisol, but aldosterone is fine - 11-DOC builds up –> hypertension and salt retention —> congenital adrenal hyperplasia
p450c11Beta (11-hydroxylase)
What kind of sweet snack blocks 11B-hydroxysteroid Type II
Black licorice
Mineralocorticoids are made in this zone of the adrenal cortex
- aldosterone
Zona glomerulosa
Structural similarity amongst all the separate types
- can have activity on each others’
Used for:
- Glucocorticoid
- Mineralocorticoid
- Progesterone
- Androgen
- Estrogen
Steroid receptors
Unable to convert to cortisol
Clinical manifestations:
- Girls: ambiguous genitalia
- Na+ retention, hypertension (bc 11-DOC is a mineralocorticoid)
- Short stature
- Hirsutism
- Hypo/amenorrhea
11-hydroxylase deficiency
Enzyme responsible for transporting cholesterol into mitochondria
StAR
Leads to pigmentation in Addison’s
Excess ACTH
Located in kidneys Converted cortisol to cortisone
11B-hydroxysteroid Type II
Leads to:
- anorexia
- nausea
- weakness
- salt craving
- hypoglycemia
- hyponatremia (SIADH)
- hyperkalemia
- dehydration
- death
- adrenal crisis in a pt w/ adrenal insufficiency
Cortisol deficiency
Causes these hyperglycemic actions:
- gluconeogenesis
- glycogen deposition in liver
- insulin antagonism in peripheral tissues
Cortisol
Leads to axillary and pubic hair loss
Also leads to loss of libido (women only)
Adrenal androgen deficiency
Genetic deficiency in steroidogenic enzymes
- most common: 21-hydroxylase deficiency
- second most common: 11-hydroxylase deficiency
Unable to make cortisol or aldosterone in 21-hydroxlyase
Unable to make cortisol in 11-hydroxylase
Cortisol deficiency causes ACTH overproduction, which leads to adrenal hyperplasia, excess production of precursor steroids, and shunting of precursors into the non-blocked androgen pathway
Congenital adrenal hyperplasia
Androgens are made in this zone of the adrenal cortex
Zona reticularis
There is cortisol and adrenal androgen deficiency, but largely normal aldosterone secretion
Secondary adrenal insufficiency (ACTH deficiency)
Effects:
- hair growth (beard, pubic, axillary, body)
- central and temporal balding - sebum production –> acne - penile and clitoral growth - Erythropoietic –> Increase O2 carrying capacity by increasing Hb
- Anabolic (muscle mass)
- Anti-estrogen
- Voice changes
Androgens
DHEA-sulfur Androstenedione Androstenediol
Main androgens from adrenal cortex
Aldosterone receptor antagonists used to treat HTN and hyperaldosteronism
spironolactone and eplerenone
Low SHBG will lower But bioavailability may be normal
Total testosterone
This mineralocorticoid is brought about by way of:
- RAS
- derives from angiotensin II
- Hyperkalemia
- ACTH
Aldosterone
Unable to convert to cortisol or aldosterone
Clinical manifestations:
- Girls: ambigious genitalia
- sodium wasting, shock
- short stature
- hirsutism
- hypo/amenorrhea
21-hydroxylase deficiency
In 11-hydroxylase deficiency, one of the immediate precursors preceding the block is __
- accumulates in large quantities
Strong mineralocorticoid
Its accumulation causes Na+ retention and hypertension
11-DOC (deoxycorticosterone)
Highly protein bound to albumin and sex binding globulin (SHBG) Inactive when bound to SHBG Active when bound to albumin or free
Testosterone
Corticosteroids are made in this zone of the adrenal cortex
- cortisol
Zona fasciculata
Clinical manifestations:
- Weight loss
- Psychosis
- Pigmentation
- HTN
- Acne
- Hypokalemic acidosis
- Hyperglycemia
- Weakness (hypokalemia)
- Polyuria-polydipsia (hypokalemic nephropathy, hyperglycemia)
Ectopic ACTH
Acute
MSH receptor located in hypothalamus
Its action leads to satiety
Mutations in this receptor cause Auto dominant obesity
MCR-4
Widely expressed throughout the system
Action: when acted on by angiotensin II
- cell growth and differentiation
- incompletely understood
AT receptor type 2
Breakdown product of ACTH
Melanocyte stimulating hormone to help melanocytes differentiate and proliferate
Expressed in the skin
- keratinocytes and melanocytes
alpha-MSH
Acts on AT receptor types 1 and 2
Angiotensin II
Replace with hydrocortisone
- lowest does needed
- risk of iatrogenic
Cushing’s Replace with fludrocortisone if necessary
- can monitor renin level
Endocrine therapy of congenital adrenal hyperplasia - 21-hydroxylase deficiency
Most common in Ashkenazi Jews and Hispanic populations 20-50% of 21-hydroxylase activity preserved so no salt wasting or adrenal insufficiency
Main symptoms are d/t androgen excess
Phenotypically similar to polycystic ovarian syndrome
Nonclassical congenital adrenal hyperplasia
Autoimmune primary adrenal disease
Adrenal cortex is destroyed by antibodies
Excess ACTH causes hyperpigmentation (bronze skin)
Addison’s Disease
ACTH receptor expressed in the adrenal cortex
Its action leads to steroid production
Requires accessory protein for membrane display and function
MCR-2
Senses lowering blood pressure leading to renin release
Juxtaglomerular apparatus
Enzyme responsible for 21-hydroxylation of 17-OH-progesterone –> 11-deoxycortisol
Most commonly mutated enzyme in the pathway - can’t make cortisol or aldosterone –> congenital adrenal hyperplasia
P450c21 (21 hydroxylase)
Replacement therapy with hydrocortisone = cortisol
Replacement therapy with 9-alpha-fluorocortisol (fludrocortisone, a synthetic mineralocorticoid)
Replacement of adrenal androgens not generally necessary
Adrenal hypofunction therapy
Diagnostic testing shows:
- renin and aldosterone high
- renin and aldosterone are suppressible (Na+ loading, volume repletion)
Secondary hyperaldosteronism
Performed in IR Sample ACTH and prolactin coming from both sides to see where it is coming from
Looks for Cushing’s Syndrome results
Inferior petrosal vein sampling
Diagnostic testing shows:
- renin suppressed and aldosterone high
- renin not stimulatable (Na+ depletion, posture)
- Aldosterone not suppressible (Na+ loading)
Primary hyperaldosteronism
Glucocorticoid receptor antagonist
- also a progesterone receptor antagonist
Can lower cortisol action
Mifepristone
Androgen receptor antagonists used to treat adrenal androgen excess
Flutamide, finasteride, and spironolactone
Can be part of Carney complex
- mutation of a subunit of protein kinase A
Type of nodular adrenal hyperplasia leading to glucocorticoid excess
Micronodular
