Hypothalamic-Pituitary Relationships pt2 Flashcards
Describe the HPA axis
Hypothalamus releases CRH
Anterior pituitary releases ACTH
Adrenal cortex releases cortisol
Cortisol = negative feedback to anterior pituitary and hypothalamus
What are the main functions of cortisol?
Immune suppression, gluconeogenesis in liver to increase BGL, protein catabolism in muscle, lipolysis in adipose tissue
When is cortisol secreted at its highest level?
High in the morning, low at night. Pulsatile secretion
What stimulates aldosterone release by the adrenal gland?
Low BP/Na+ and angiotensin II
Low BP leads to Renin increase, which forms Angiotensin 1…which continues to II… then eventually increases water/Na+ reabsorption and raises BP by making Aldosterone
What glucocorticoid is elevated in Cushing’s syndrome?
Cortisol
What is the dexamethasone suppression test?
Dexamethasone suppresses ACTH
Low-dose- differentiates CS vs not CS (no suppression=CS+)
High-dose- differentiates Cushing’s disease (Decreased ACTH=pituitary ACTH-secreting tumor) vs CS of other cause (no ACTH change=ectopic ACTH-secreting tumor)
What are consequences of excess glucocorticoids?
Short-term cortisol = lipolysis, but long term = adipocyte formation, increased BGL, breakdown of protein impairs CT/collagen formation, antagonist of ADH = HTN
What different types of Cushing’s syndrome are there?
- Adrenal tumor that secretes cortisol (neg feedback causes low ACTH)
- Pituitary tumor secreting ACTH (causes high cortisol) “Cushing’s Disease”
- Ectopic ACTH-secreting tumor (causes increased cortisol which causes decrease of pituitary secretion of ACTH)—high dose test has no ACTH effect
- Iatrogenic- excess exogenous glucocorticoids causes decreased CRH and ACTH due to negative feedback
Describe the HPA axis in Addison’s disease
Decreased cortisol output from adrenal gland, so high CRH from hypothalamus and high ACTH from pituitary—basically the excess ACTH must find other means of dispersement (one of which is the pigment increase)
What is the primary action of aldosterone?
Renal sodium reabsorption
Explain hyperpigmentation seen in
Addison’s disease
High levels of ACTH activate receptors in melanocytes which causes skin darkening—ACTH and alpha-MSH lead to increased Melanin synthesis
Explain primary vs secondary/tertiary adrenal insufficiency
and review the cosyntropin stimulation test for determining which
Primary - adrenal cortex not secreting cortisol or aldosterone
Secondary/tertiary - decreased ACTH means adrenal cortex not secreting cortisol, but renin/angiotensin system still allows for aldosterone secretion
CST: only used if 8am cortisol level is between 3-15 micro g/dL
- greater than 15= AI is ruled out
- less than 3= definite insufficiency (can skip the test and measure ACTH straight for type-determining)
give dose of cosyntropin (synthetic acth)… wait 30 min… if there is less than 18 micro g/dL after time, you then measure ACTH levels to determine type (elevated levels=Primary AI///Low/normal levels=secondary or tertiary
What is Conn’s syndrome?
Primary hyperaldosteronism - excessive release of aldosterone from adrenal cortex (can be due to adenoma)
What is secondary hyperaldosteronism?
Excessive renin secretion by kidney = high aldosterone levels
What is hypoaldosteronism?
Inadequate stimulation of aldosterone secretion, can be due to destruction of adrenal cortex or defects in aldosterone synthesis
In the pathways for synthesizing adrenal steroid hormones, what are the common key enzymes?
Aldosterone- 21B, 11B
Cortisol- 17a, 21B, 11B
Androgens- 17a
A deficiency is one of these will increase the production of the other paths, which explains the symptoms that will present in the case
Congenital adrenal enzyme deficiencies are characterized by what?
Enlargement of both adrenal glands (adrenal hyperplasia) due to increased ACTH stimulation (bc of decreased cortisol)
What is a pheochromocytoma?
Benign, unilateral adrenal tumor that causes an increase in BP by stimulating alpha/beta adrenergic receptors with elevated levels of catecholamines
- it is a rare and dangerous cause of hypertension
- presents commonly with headaches, palpitations (heart), and sweating
What are the layers of the Adrenal Glands?
Cali Girls F Real Men Capsule Glomerulosa (Salt) Fasciculata (Sugar) Reticularis (Sex) Medulla (chromaffin cells)
Application of exogenous glucocorticoid does what?
Same negative feedback as cortisol, but over time can atrophy the adrenal cells that actually produce cortisol
Some major causes of Primary adrenal insufficiency (Addison’s disease)
- Autoimmune disease that destroys the Adrenal Gland
- Adrenal Hemorrhage (secondary effects to Meningitidis or caused by anticoagulant treatment)
- infection from Tuberculosis or Meningitidis
- Tumor metastases to the AG
Cortisol upregulates what enzyme, that does what?
PNMT- turns Norepinephrine–>Epinephrine
Karius would be proud
Also Ach is the signal for secretion of Catecholamines in case that also was punted after the last neuro exam
Catecholamine action lasts about how long?
What degrades them?
about 10 seconds
COMT and MAO
