Ant. Pituitary Hormones
Hypothalamus - CRH -
ACTH (Adrenal Cortex; Diurnal variation) - Cholesterol to Pregnenolone - Cortisol (Feedback on Hypothalamus, Reduce CRH), Aldosterone, Androgens, Estrogens
Adrenal Gland Hormones
Cortisol (Glucocorticoid - Zona fasciculata)
Aldosterone (Mineralocorticoid - Zona glomerulosa)
Adrenal Androgens (Androstenedione and Dehydroepiandrosterone - DHEA - Zona reticularis)
Epinephrine (Adrenaline)
Enkephalin (Both in Medulla)
Inner Medulla and Outer Cortex - Cortex from Mesoderm and Medulla from NC Cells
Inhibited by Ketoconazole
17a-hydroxylase
17,20 lyase
Adrenal Steroids Pharmacokinetics
Cortisol and Progesterone - Bind Corticosteroid-Binding Globulin (CBG) also called Transcortin and Albumin
CBG w/ high affinity for cortisol but low capacity
Albumin w/ low affinity for cortisol but high capacity
Unbound cortisol exterts biologic activity - Affinity and capacity of plasma proteins regulate availability and activity
Amt of transcortin in plasma elevates by female sex hormones (estrogens) and lowered by liver disease, amyloid disease or multiple myeloma
Aldosterone, dehydroepiandrosterone and androstenedione transported diff from cortisol - Bound to albumin
Liver and kidney responsible for cortisol metabolism
Cortisol reduced in liver and conjugated to glucuronic acid and excreted in kidney
Cortisol activity regulated by 11beta-hydroxysteroid dehydrogenase (Liver and adipose tissue w/Type I, Kidney collecting duct cells w/Type 2)
11 Beta-Hydroxysteroid Dehydrogenase
Type I - Liver - Ketone to Hydroxygroup
Type II - Kidney - Hydroxygroup to Ketone
Inactive Metabolites
Peripheral tissues and by liver
Conversion to inactive tetrahydro-derivatives
Conjugated to glucuronic or sulfuric acid and excreted in urine
Genomic Glucocorticoids Action
Increase blood glucose, Gluconeogenesis, Brain activity, Stress resistance, Decrease Inflammation, Immune response
(Also increase resistance to stress, Increase WBC, Decrease water excretion;
Permissive effects - allow Epi/NE to work better)
Nongenomic Glucocorticoids Action
Occur fast (<5min)
Not stopped blocking MR and GR
Effect don’t rely on protein synthesis
Effect on receptors other than MR or GR
Described in brain, lungs, liver, muscle, fat, kidney and immune system;
Behavior aggression, Memory, Risk taking, Mood (Euphoria-depression)
Alter membrane fluidity
Effect on ion channels (Ca++)
Neurotransmitter release
Intracellular but non-nuclear proteins, kinases
Glucocorticoid importers and CBG
Cortisol
Glucocorticoid
Counter-regulatory to insulin
Elevates blood glucose and promotes Gluconeogenesis (Inhibits peripheral protein synthesis and stimulates breakdown of muscle protein; Amino acids then available for liver Gluconeogenesis)
Induces synthesis of gluconeogenic enzymes in liver
Increases glycogen deposition and glucose release by liver
Physiologic Effect of Glucocorticoids - Inflammation
Antiinflammatory
Decrease NFkB - Decrease cytokine from immune cells
Suppress genes for IL 1-6,8, IFN-y leading to decrease Tcell proliferation
Stimulate Lipocortin (Annexin A1) production which inhibit PLA2 - Inhibit 2 products of inflammation, prostaglandins and leukotrienes - Inhibit various leukocyte inflammatory events and suppress COX expression
Physiologic Effect of Glucocorticoids - Development
Promote maturation of lung and production of surfactant necessary for extra-uterine lung function
Physiologic Effect of Glucocorticoids - Brain Function
Form memories w/emotion
Arousal and alertness
Adrenal insufficiency w/ depression
Increase initial cause euphoria and insomnia then depression
ACTH treat infantile spasms w/hypsarrythmia
Physiologic Effect of Glucocorticoids - Bone
Inhibit bone formation (Reduce osteoblasts)
Increase RANK - Increase osteoclasts
Decrease osteoblast function directly and indirect through modulation of growth factor expression, receptor binding or binding protein levels
GIOP treat w/bisphosphonates, anabolic hormones and PTH
Adverse Effects of Glucocorticoids
Endocrine - Decrease GH, Decrease TSH, LH, FSH
GI - Peptic ulcers
Brain - CNS depression, Psychosis
Bone - Decrease bone formation, Decrease bone mass, Osteoporosis
Skeletal m./CT - Protein catabolism, Muscle atrophy, Collagen breakdown, Skin thicken
Eye - Cataract, Glaucoma
Carb - Increase Gluconeogenesis, Free FA production, Increase insulin resistance, Increase hepatic glycogen deposition, Visceral fat
Cardio/Renal - Increase BP, Salt and water retention
Growth - Decrease linear growth
Immune system - Immunosuppressive, Antiinflammatory
Adrenal Androgens
Anabolic
Increase protein synthesis in peripheral tissues
Opposite of cortisol
Pubertal growth spurt in F
Masculinization if excessive (Adrenal tumor)
Androstenedione - Substrate for estrogen synthesis in adipose tissue and estrogen-secreting endocrine glands
Steroids
(Memorize chart)
Slight Soluble in Water
Cortisol (Hydrocortisone) (Cortef)
Prednisolone (Hydeltra)
Triamcinolone (Kenacort)
Oral, Topical
Insoluble in Water
Hydrocortisone Acetate (Cortef Acetate) Prednisolone Bytylacetate (Hydeltra-T,B,A) Triamcinolone Acetonide (Kenalog) Intra-articular, Topical,
Very Soluble in Water
Hydrocortisone Sodium Succinate (Solu-Cortef)
Prednisolone Sodium Phosphate (Hydeltrasol)
IM, IV, Topical
Medrol Dosepak
Reduce interference with HPA control axis - Provided in descending dosage regimen for six day anti-inflammatory treatment
Prolong inhibition of HPA leads to prolonged loss of natural corticosteroid release
TMJ Arthritis Treatment
Steroid Injection Prednisolone Acetate (Meticortelone Acetate), 10-15mg (25mg/mL in 5mL vials), 3-4days
Oral Lesion Treatment
Steroid Topical Triamcinolone Acetonide (Kenalog) - 0.1% paste in Orabase, Apply thing film 2-3Xd for 5d
Fludrocortisone
Florinef
Glucocorticoid and Mineralocorticoid activity (Widely used Mineralocorticoid)
Adrenocortical insufficiency
Aldosterone insufficiency
Deoxycorticosterone (DOC)
Precursor of Aldosterone
Secretion under control of ACTH
Cushing Syndrome Cause
Endogenous Cause: Bilateral adrenal hyperplasia, Secondary to ACTH-secreting pituitary adenoma; Due to adrenal tumors or production of ACTH from ectopic lung tumors
Exogenous Cause: Large doses of steroids given for management - asthma, rheumatoid arthritis, lupus or chronic skin conditions can increase cortisol levels in blood
Cushing Syndrome Signs and Symptoms
Emotional disturbance, Enlarged sella turcica, Truncal adiposity (abdomen, neck, face), Round face (moon like), Osteoporosis, Hypertension, Obesity, Adrenal tumor/Hyperplasia, Loss of subcutaneous adipose tissue, Thin and wrinkled skin, Abdominal striae, Amenorrhea, Bruising, Striae, Hyperglycemia, Muscle wasting, Poor wound healing, Mental disorders, Purpura, Skin ulcers
Cushing Syndrome Treatment
Surgery, Radiation, Medication
Mifepristone (GR receptor antagonist) approved to control hyperglycemia in adult patients who are not good surgical candidates
Cushing Syndrome Dental Alerts
Increase risk for systemic diseases - Modify management
Monitor BP routinely, Aspirin and NSAIDs should be avoided bc of high incidence of peptic ulcer
Increased risk of periodontitis, oral candidiasis and bleeding gums
Excess steroids in system lower immune system activity - Increase risk of infections and poor wound healing
Adequate antibiotic coverage for 7days following major surgery
Assess and treat oral cavity for oral and esophageal candidiasis when present
General osteoporosis also affect mandible and patients w/dentures need readjustment
Addison Disease
Adrenal insufficiency mostly autoimmune
Bronze pigmentation of skin, Weight loss, GI disturbance, Change in body hair distribution, Hypoglycemia, Hypotension, Hyperkalemia, Fatigue, Muscle weakness, Pigmented mucous memrane patches and pigmentation around mouth (due to ACTH binding to MSH receptors or MSH from POMC)
Congenital Adrenal Hyperplasia
Defects in cortisol synthesis
Lack of 21beta-hydroxylase activity - Decrease cortisol, Increase ACTH, gland is hyper plastic and increase precursors like 17-hydroxyprogesterone that make androgens to cause virilzation (adrenal androgens)
Metabolite pregnanetriol in urine is diagnostic
Addisons Disease Dental Alerts
Steroids to fight stress w/infection, inflammation, bleeding, post procedure starvation, preop and postop pain and trauma
Consult w/physician and provide steroid coverage to compensate stress
Fail to provide coverage precipitates acute adrenal insufficiency and cardiovascular collapse
Steroids for more than 2wks w/adrenal insufficiency and could need coverage for 2yrs for HPA to recover
Treat oral infections aggressively to prevent hypoadrenal crisis or acute adrenal insufficiency
Best to treat in first appointment of day
Night shift workers may have circadian rhythm reversal - Max release in evening
Patient on steroids - Best to take steroid 2hrs before appt
Minor procedure - No steroid supplement
Avoid barbiturates (Decrease cortisol)
Mild Stress Steroid Dose
(1-4 extractions/1 quad flap)
Double steroid dose
Patient not currently on steroids - Use 1/3 1h before surgery: 1. 6mg Prednisone PO 2. 25mg Hydrocortisone PO/IV 3. 5mg Prednisone PO
Moderate Stress Steroid Dose
(5-16 extractions/2quad flap)
Use 1/2 1h before surgery:
1. 15-20mg Prednisone PO
2. 50-75mg Hydrocortisone PO/IV
Severe Stress Steroid Dose
(17> extractions/3quad flap)
Use 1/2 1h before surgery:
1. 25-40mg Prednisone PO
2. 100-150mg Hydrocortisone PO/IV
Commonly Used Steroids
Cortisol and Cortisone - Replacement in adrenal insufficiency, Small doses
Addisons disease patients
Abrupt withdrawal after long-term therapy glucocorticoid induces deficiency
Most freq use is treatment of allergic condition, inflammation (ex. rheumatoid arthritis, dermatitis, seasonal rhinitis, bronchial asthma, stomatitis, gingivitis, TMJ dysfunction)
Pharm (large, anti-inflammatory) doses used
Exudation inhibited
Cell proliferation inhibited
Phagocytosis suppression
