ADRENAL HORMONES All derived from cholesterol Minerocorticoids (aldosterone) from cortex zona glomerulosa Na/water reabsorption, H/K

secretion into tubule BP (b/c volume) Control: RAAS (aldosterone negative feedback to renin)

RAASATIIGq receptorIP3/PLC/DAG/Ca pathway

Glucocorticoids (cortisol) from cortex zona fasciculate Induce stress response: gluconeogenesis, lipolysis (cholesterol), protein catabolism (muscle wasting) Anti-inflamm, immune suppression vascular tone (1 agonist NA effect) Control: ACTH (suppressed by dexamethasone) ACTH levels follow circadian rhythm; highest in morning (cortisol levels follow) Androgens from cortex zona reticularis Kids: enlarged clitoris/precocious puberty (weak effect in adults) Control: ACTH Catecholamines from medulla Fight-or-flight: HR/vascular tone, gluconeogenesis (insulin)/lipolysis, Na reabsorption, renin Control: ACTH

CUSHING (cortisol) PC: HTN (1 effect vascular tone), muscle weakness/wasting, moon face (fat), abdominal striae, osteoporosis, immune suppression Exogenous corticosteroids adrenal atrophy Adrenal adenoma/hyperplasia/carcinoma Pituitary adenoma ACTH Paraneoplastic ACTH secretion (small cell lung carcinoma) Ix: Dexamethasone ACTH suppression (if pituitary adenoma, not if SCLC)

HYPERALDOSTERONISM (aldosterone) Na, hypervolemia, HTN, K, metabolic alkalosis Primary: Adrenal adenoma/hyperplasia/carcinoma (renin) Secondary: RAAS (renal artery stenosis) (renin)

Congenital adrenal hyperplasia: 21-hydroxylase deficiency: X cortisol/all minerocorticoids androgens (hypotension, Na/hypovolemia, clitoral enlargement/precocious puberty

11-hydroxylase deficiency: X cortisol/aldosterone only androgens 17-hydroxylase deficiency: X cortisol/androgens aldosterone WATERHOUSE-FRIDERICHSEN SYNDROME (acute adrenal insufficiency) Children, Hx N. meningiditis, DIC Hemorrhage in adrenal Chronic insufficiency: autoimmune, TB, metastasis (from lung) PHEOCHROMOCYTOMA (medullary tumour) NA episodic HTN/headache/tachycardia Brown tumour on biopsy Tx excision (phenoxybenzamine before Sx: 1-block to avoid NA release during Sx) MEN2A: thyroid medullary carcinoma (calcitonin, amyloid), pheochromocytoma, parathyroid adenoma MEN2B: thyroid medullary carcinoma, pheochromocytoma, mucosal ganglioneuroma (oral mucosa)

ADDISON (adrenal insufficiencyX aldosterone, cortisol, androgen, catecholamine): fatigue, weight, Na/glucose/water, K/H/Ca orthostatic hypotension Hemochromatosis (multiple transfusions): iron deposition in adrenalAddison (slow)

ANTERIOR PITUITARY (ACTH TSH GH FSH&LH/Prolactin) PITUITARY ADENOMA Non-functional: Mass effect: Press optic chiasm bitemporal hemianopsia Press pituitary hypopituitarism Headache Functional: Prolactinoma (GnRH): galactorrhea/amenorrhea (FSH/LH) libido Tx DA agonist (prolactin secretion) GH ( IGF-1 in liver): gigantism, acromegaly Ix Glucose suppression test Tx Octreotide (GHRH receptor block) ACTH: hyperadrenal

SHEEHAN SYNDROME: Pituitary necrosis due to hypovolemia in childbirth EMPTY SELLA SYNDROME POSTERIOR PITUITARY (ADH Oxytocin) SIADH (SCLC, cyclophosphamide): ADH Na/osmolality, cerebral edema (water retention) DIABETES INSIPIDUS: ADH (either hypothalamus or posterior pituitary) polyuria/polydipsia Tx ADH analog (not if nephrogenic (ADH-unresponsive))

HYPERTHYROIDISM basal metabolic rate (by Na/K ATPase) sympathetic nervous system (by 1 receptors) PC weight loss, heat intolerance, tachycardia/arrhythmia, muscle wasting, anxiety, diarrhea, hypercalcemia/bone resorption, hypocholesterolemia, hyperglycemia Graves: T4/T3, TSH, goiter, exophthalmos, pretibial myxedema Scalloping on histo Tx Thioamide, ablation with radioactive iodine, -blockers

Multinodular goiter: b/c iodine deficiency. Most nodules are euthyroid Hashimoto: ass. B-cell lymphoma, Herthel cells Subacute granulomatous thyroiditis: follows viral infection. Tender thyroid, transient hyperthyroidism. Does NOT become hypothyroid (b/c self-limiting) Reidel fibrosing thyroiditis: chronic inflamm & fibrosis, hard/non-tender thyroid. Young female with airway fibrosis (anaplastic carcinoma in old) Iodine uptake: in Graves, nodular goiter; in adenoma, carcinoma (FNA required) Papillary (80%, orphan Annie eye), follicular (invasion beyond capsule = carcinoma), medullary (C-cell, calcitonin overproduction hypocalcemia & localized calcitonin amyloid), anaplastic RET oncogene (familial MEN2A/2B): prophylactic thyroidectomy

PARATHYROID: chief cells regulate free Ca via PTH (osteoclast (via osteoblast activation), Ca/PO4 absorption in small bowel (via vitD activation), Ca / PO4 reabsorption in kidney Primary hyperparathyroidism: adenoma (80%, one gland), hyperplasia, carcinoma PTH Ca kidney stones, CNS (moans), constipation/PUD/pancreatitis (groans), osteitis fibrosa cystica (bones) High PTH/Ca/cAMP/ALP (activates osteoblast activates osteoclast), Low PO4

Secondary hyperparathyroidism: CKD (PO4 excretion binds Ca free serum Ca PTH (all 4 glands) HIGH PO4 Hypoparathyroidism: autoimmune, surgical excision, DiGeorge (malformation) PC numbness, tetany Pseudohypoparathyroidism (faulty Gs GPCR): end-organs are resistant to PTH High PTH but low Ca

HORMONE CLASSES Amine: catecholamine, thyroxine, serotonin

Polypeptide: TRH ADH ANP oxytocin GnRH GH insulin glucagon PTH ACTH calcitonin LH FSH TSH hCG

Steroid: aldosterone cortisol testosterone estrogen progesterone

Cell surface receptors: ion-channel: Acetylcholine, GABA, NMDA influx of ions benzodiazepine, barbituates

enzymatic (tyrosine kinase): insulin, growth factors (nerve NGF)

dimerization, auto-phosphorylation, docking protein (SH), ras-GDP ras-GTP, signaling cascade (MAP kinase, JAK-2, STAT)

GPCR (G-protein coupled receptor): beta-adrenergic, glucagon, TSH, LH, noradrenaline, dopamine ---GDP binds intracellular GPCR subunit, GDP GTP, alpha subunit breaks, ATP cAMP via adenylate cyclase (if Gs. Via phospholipase C, IP3, Ca in Gq)

Thyroid: TSH T3, T4 Leydig cells: LH testosterone

Secondary messengers: cAMP (via PKA), Ca (regulates calmodulin, kinase C)

Gq activate IP3 binds calcium channels in ER Ca influx

ADRENAL GLANDS Blood supply: inferior phrenic artery, aortic branch, renal artery branch, L adrenal vein into L renal vein, R adrenal vein straight into IVC

Cortex (epithelial):

Zona glomerulosa: aldosterone (mineralocorticoids)Na+ K+ distal tubule, collecting duct (sodium/water reabsorption-- BP, preload H+/K+ secretion into tubule) Zona fasciculata: cortisol (glucocorticoids) (glucose in liver, protein breakdown, anti-inflam) by 11--hydroxylase Zona reticularis: androgens (weak action)

All above derived from cholesterol.

Medulla (neurosecretory): NA (sympathetic autonomic)

Minerocorticoids (Aldosterone) control by RAAS (ATIIGq), potassium, ACTH (short -term), ANP (produced in fluid overload in R heart; down-regulatory) Causes fluid retention, alkalosis (H+ loss), cardiac fibrosis RAASATIIGq receptorIP3/PLC/DAG/Ca pathway

Glucocorticoids (cortisol, bound to CBGlobulin in blood, by estrogen/pregnancy) gluconeogenesis, lipolysis, protein catabolism, blood glucose Anti-inflam, immune suppression, vascular response to NA Controlled by ACTH (circadian rhythm, highest in the morning, GC follows)

Androgens Weak effect in adults Controlled by ACTH

Catecholamines (NA) Secretion activated by acetylcholine (in sympathetic activation) Fight or flight (ionotrophic/chronotrophic cardiac effects, vascular tone/PVR, gluconeogenesis, lipolysis, insulin, sodium reabsorption, renin

Catecholamine half-life 30s-1min Parathyroid hormone half-life 2-4min

Dexamethasone is a glucocorticoid, that will block ACTH by negative feedback. (Tx for glucocorticoid-suppressible hyperaldosteronism, an aldosterone-synthase gene regulated by ACTH and not ATII