What are the 4 main etiologies of Cushing Syndrome?
1˚ adrenal adenoma, hyperplasia, or CA
ACTH-secreting pituitary adenoma
Paraneoplastic ACTH secretion
Adrenal adenoma, hyperplasia, CA
Where does paraneoplastic ACTH come from? (2)
Small cell lung CA
What are the findings of Cushing syndrome?
Hypertension, hyperglycemia (IR)
Weight gain, moon facies, truncal obesity, buffalo hump
Osteoporosis & Amenorrhea
Skin changes: thinning, striae
What are the 3 tests used to measure cortisol?
Free cortisol 24 urine analysis
Midnight salivary cortisol
Overnight low-dose dexamethasone suppression test
What two things directly regulate prolactin?
How does prolactin ↓ fertility?
Inhibits GnRH synthesis and release
What negative feedback is involved in prolactin secretion?
Prolactin ↑ dopamine synthesis
What things ↑ GH secretion?
GHRH: ↑during exercise and sleep
What things ↓ GH secretion? (2)
Glucose and SST
Where is vasopressin/ADH synthsized?
Hypothalamus - supraoptic nuclei
What is the main function of ADH?
Serum osmolarity regulation
In what part of the kidney does ADH have its effect?
Principal cells of renal collecting duct
ADH is __________ in central diabetes insipidus and ___________ in nephrogenic DI and 1˚ polydipsia.
Decreased = Central DI
Increased = Nephrogenic DI & 1˚ polydipsia
Central DI, bedwetting
What regulates ADH release?
Osmoreceptors in hypothalamus (1˚)
What effects does Cortisol have?
↑ Insulin resistance
↑Gluconeogenesis, lipolysis, and proteolysis
↓ Fibroblast activity (striae)
↓ Inflammatory and Immune responses
How does cortisol increase BP?
Upregulates α1-receptors on arterioles
↑Sensitivity to NE/Epi
How does cortisol ↓ inflammatory and immune responses?
Inhibits production of LT and PG
Inhibits leukocyte adhesion → neutrophilia
Blocks histamine release from mast cells
Blocks IL-2 production
How does cortisol ↓ bone formation?
↓ Osteoblast activity
Exogenous corticosteroids can cause reactivation of TB and candidiasis - what is the mechanism?
Blocked IL-2 production
What secretes PTH?
Chief cells of parathyroid
What are the effects of PTH?
↑ Bone resorption
↑ Kidney reabsorption of Ca in DCT
↓ Kidney reabsorption of PO4 in PT
↑ 1, 25-(OH)2 D3 (calcitriol) via 1α-hydroxylase
What triggers an increase in Ca absorption from the intestine?
1, 25 OH D3
What things will ↑ PTH secretion?
↓ serum Ca
↓ serum Mg - diarrhea, aminoglycosides, diuretics, EtOH abuse
Plasma Ca exists in what 3 forms?
Ionized | 45%
Bound to albumin | 40%
Bound to anions | 15%
What does an ↑ in pH do to Ca levels?
↓ ionized Ca
↑ Ca bound to albumin
Hypocalcemia - cramps, pain, parasthesias, carpopedal spasm
D3 comes from ____________.
D2 comes from ____________.
Both are convereted to 25-OH in the ________.
Sun exposure in skin
What effects does active vitamin D have?
↑ bone resporption
↑ dietary absoption of both Ca and PO4
Calcitonin is released from the _____________ of the thyroid in response to ____________.
Parafollicular cells (C cells)
↑ serum Ca
↓ bone resportion