Term
| What are the hormones of the Anterior Pituitary? |
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Definition
1. Growth Hormone (GH)
2. Prolactin
3. Lutenizing Hormone (LH)
4. Follicle-Stimulating Hormone (FSH)
5. Thyroid-Stimulating Hormone (TSH)
6. Adrenocorticotropin (ACTH) |
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Term
| What are the types of Feedback Loops? |
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Definition
-Long, short, ultrashort
-Primary: target organ pathology (problem with Thyroid gland)
-Secondary: pituitary Dz (unable to secrete TSH)
-Tertiary: Hypothalmus problem |
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Term
| What are the 5 types of Endocrine Axis? |
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Definition
1. Hypothalamic-Pituitary-GH Axis
2. Hypothalamic-Pituitary-Prolactin Axis
3. Hypothalamic-Pituitary-Thyroid Axis
4. Hypothalamic-Pituitary-Adrenal Axis
5. Hypothalamic-Pituitary-Reproductive Axis |
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Term
| Discuss the Hypothalamic-Pituitary-GH Axis |
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Definition
-Regulates processes promoting growth
-Regulators of GH secretion
-GHRH enhances secretion
-Somatostatin inhibits secretion
-Ghrelin and GHRH act synergistically on GH release
-GH stimulates IGF-1 secretion, which promotes bone growht
-Ultimate target acts on liver at IGF-1 |
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Term
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Definition
-Growth Hormone Deficiency Tx
MECH Stimulates release of IGF-1 from the liver
DOSE: Usually dosing SC/IM 3X/WK. Depot injxn available monthly
CLIN: Tx of GH deficiency in children (regardless of 1*, 2* or 3*)
SE: Bone pain and edema |
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Term
| What is Growth Hormone Excess? |
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Definition
-Results from somatotroph adenoma (pituitary tumor)
-Gigantism: pediatric onset
-Acromegaly: adult onset
-Standard Tx involves surgical removal of tumor
-Meds available |
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Term
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Definition
-GH Excess Tx: Somatostatin Analogues
-MECH: Inhibits systemic release of insulin, glucagon, and gastrin. Constricts blood vessels. Reduces portal BP in bleeding varices
PHARM-K: Half-Life longer than natural compound
DOSE: SQ/IM 3X/Day. Depot injxn available monthly. Pt on drip fro emergency Tx of esophageal varices
CLIN: Esophageal varices (most common), acromegaly, secretory diarrheas, vasoactive intestinal peptide
SE: Nausea and decrease GI motility |
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Term
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Definition
-GH Excess Tx: GH Receptor Antagonists
-MECH: Decreases IGF-1 levels
-PHARM-K: Long Half-Life (6 days), Once daily SQ; routine monitoring of LFTs
CLIN: Acromegaly (2nd-line therapy)
SE: Nausea and diarrhea |
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Term
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Definition
-GH Excess Tx: Dopamine Agonists
MECH: Acromegaly Pts have a paradoxical decrease in GH secretion
CLIN: Adjunct Tx of acromegaly |
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Term
| Discuss the Hypothalamic-Pituitary-Prolactin Axis |
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Definition
-Anterior pituitary gland produces and secretes prolactin
-TRH enhances prolactin release
-Hypothalamic release of dopamin inhibits lactotrophs - chronically suppressing prolactins
-NOT regulated by negative feedback
-Anything that causes a block of Dopamine release can cause a rise in prolactin levels |
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Term
Bromocriptine
Pergolide
Cabergoline |
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Definition
-Prolactin Excess Tx: Dopamine Receptor Agonists
-MECH: Inhibits lactotroph cell growth
-DOSE: PO
-CLIN: Excess Prolactin
-SE: N/V |
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Term
| Discuss the Hypothalamic-Pituitary-Thyroid Axis |
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Definition
-Hypothalmus secretes TRH secretion/secretion of TSH/secretion of thyroid hormone from the thyroid gland
-Thyroid Hormone negatively controls release of TRH and TSH |
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Term
| Discuss the Hypothalamic-Pituitary-Adrenal Axis |
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Definition
| -Hypothalamus secretes CRH - binds to corticotrophs of the anterior pituitary - release of ACTH - binds to ACTH receptors on the adrenal cortex - stimulates secretion of steroid hormones |
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Term
| Discuss the Hypothalamic-Pituitary-Reproductive Axis |
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Definition
-Gonadotropin-releasing Hormone (GnRH) stimulates gonadotrophs to secrete two hormones:
-Lutenizing Hormone (LH)
-Follicle-stimulating hormone (FSH)
-Gonadotrophins promote synthesis androgens and estrogens
-Gonadotrophs are feedback-inhibited by testosterone and estrogen
-Giving continuous GnRH will cause decreased production of sex hormones |
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Term
Leuprolide
Goserelin
Nafarelin
Histrelin |
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Definition
-Excess Sex Hormone Tx: GnRH Receptor Agonists
-MECH: Synthetic analogues which act as agonists at GnRH receptors. Continuous administration suppresses production of sex hormones
PHARM-K: Gonadotroph suppression is transient
DOSE: Most come as Depot injxn monthly or every 3 months
CLIN: Prostate cancer, endometriosis, precocious puberty
-Leuprolide/Goserelin: prostate cancer
-Nafarelin: nasal spray used for endometriosis
-Histrelin: SQ implant release over 1 year for advanced prostate cancer
SE: hot flashes, bone pain, edema, and diminished libido |
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Term
| What does the posterior pituitary gland secrete? |
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Definition
1. ADH - Plasma volume and osmolarity
2. Oxytocin - uterine contraction and lactation |
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Term
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Definition
-Antidiuretic hormone (produced in hypothalmus)
-Increased osmolarity stimulates ADH secretion
-Two types of receptors:
1. V1 receptors - cause vasoconstriciton
2. V2 receptors - cause increased H2O reabsorption in the collecting duct |
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Term
| What occurs with an Excess secretion of ADH? |
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Definition
-Syndrome of inappropriate ADH (SIADH)
-Stimulation of V1/V2 receptors leads to HTN and fluid retention; Edema and hyponatremia also occurs
-Pt comes in and they are hyponatremic: SIADH, SSRI cna cause SIADH like syndrome; small cell lung cancer can also cause reduced Na
-Tx: Fluid restriction is the main Tx modality; can also use salt tablets; can also use a Demeclocylcine to induce nephrogenic DI |
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Term
| What occurs with a Decreased Respons to ADH? |
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Definition
-Diabetes Insipidus (DI): Two Types:
1. Neurogenic DI: inability of hypothalamus to synthesize or secrete ADH
2. Nephrogenic DI: inability of renal collecting duct cells to respond to ADH |
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Term
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Definition
-ADH Agonist
-MECH: ADH analogue; Selectively stimulates V2 receptors
-DOSE: oral, IV, SC, nasal spray
-CLIN: neurogenic DI, Nocturnal enuresis
-SE: hyponatremia |
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Term
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Definition
-ADH Antagonist
-MECH: Conivaptan selective antagonist of vasopressin V1/V2 receptors; Tolvaptan selective for only V2
-CLIN: euvolemic or hypervolemic hyponatremia |
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Term
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Definition
-Oxytocin Agonist
-MECH: Physiologic roles involve muscular contractions: Lactation, uterine contraction
CLIN: used for labor induction and lactation |
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Term
| What are the types of Thyroid cells? |
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Definition
1. Follicular: thyroxine (T4) converted to T3; T3 active form; reverse (rT3) inactive form
2. Parafollicular C Cells: calcitonin |
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Term
| What are the types of Thyroid Dz? |
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Definition
-Disturbance of the hypothalamic-pituitary-thyroid axis
-Increased or decreased thyroid hormone secretion
-Grave's Dz vs Hashimoto's Thyroiditis |
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Term
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Definition
PATHOLOGY: Thyroid-stimulating immunoglobulin acts on TSH receptor. Stimulates release of thyroid hormone. Thyroid-stimulating immunoglobulin continues to stimulate thyroid fxn.
-Hyperthyroidism occurs |
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Term
| What is Hashimoto's Thyroiditis? |
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Definition
-PATHOLOGY: antibodies selectively destroy the thyroid gland. Gradual inflammatory destruction. Transient elevation (initial elevation) in thyroid hormone occurs early in the Dz then is followed by low thyroid hormone
-Hyperthyroidism occurs |
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Term
Perchlorate
Thiocynate
Pertechnetate |
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Definition
-Hyperthyroidism Tx: Inhibitors of Iodide Uptake
-MECH: Compete with iodide for reuptake (via Na+/I- symporter) into the thyroid follicular cell. Reduce the intrathyroidal supply of iodide available for synthesis of more thyroid hormone
CLIN: Hyperthyroidism Tx
SE: Aplastic anemia |
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Term
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Definition
-Hyperthyroidism Tx: Inhibitors fo Organification and hormone release
-MECH: 131I is a radioactive iodide isotope. Concentrated radioactive iodide destroys the thyroid gland
-CLIN: Alternative to Sx for hyperthyroidism
SE: Tx commonly results in hypothyroidism |
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Term
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Definition
-Hyperthyroidism Tx: Inhibitors fo Organification and hormone release
-MECH: Inhibits thyroid hormone synthesis and release
-PHARM-K: negative feedback effect is reversible and transient meaning it is not useful for long term use
-CLIN: Good for pre-op control of hyperthyroidism in thyroid gland Sx |
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Term
THIOAMINES:
Propylthiouracil
Methimazole |
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Definition
-Hyperthyroidism Tx: Inhibitors fo Organification and hormone release
-MECH: Competes for oxidized iodide; selective decrease in thyroid hormone production.
-Propythiouracil: inhibits thyroid peroxidase AND peripheral T4 to T3 conversion
-Methimazole: Inhibits thyroid peroxidase
-PHARM-K: Effects are not seen for several wks
-CLIN: Propythiouracial: Hyperthyroidism in pregnancy (3X/day); Methimazole: Hyperthyroidism agent preferred overall (2X/Day)
SE: Goiter formation, pruritic rash, arthralgias, agranulocytosis, hepatotoxicity, vasculitis |
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Term
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Definition
-Hyperthyroidism Tx: Inhibitors of Peripheral thyroid hormone metabolism
-MECH: High thyroid hormone levels resemble B-adrenergic stimulation
-CLIN: Provides symptomatic Tx of hyperthyroidism |
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Term
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Definition
-Hypothyroidism Tx
-MECH: Replace missing endogenous thyroid hormone with exogenous thyroid hormone
-DOSE: Large dosing range (25mcg-300mcg); Monitor TSH at 4-6 wks after initiation of dosage change
-CLIN: Hypothyroidism
-SE: Hyperthyroidism |
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Term
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Definition
-Hypothyroidism Tx
-MECH: Replace missing endogenous thyroid hormone with exogenous thyroid hormone. Synthetic T3
-PHARM-K: Short half-life
-CLIN: useful in myxedema coma (rare, life-threatening hypothyroidism)
-SE: Hyperthyroid symptoms |
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Term
| What is the role of the Adrenal Gland (Cortex)? |
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Definition
-Synthesizes and secretes steroid hormones
-Salt balance
-Intermediary metabolism
-Androgenic actions (females)
-3 classes of hormones:
1. Mineralocorticoids
2. Glucocorticoids
3. Androgens |
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Term
| Discuss the Zona Glomerulosa |
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Definition
-HORMONE: Mineralocorticoids (aldosterone)
-REGULATORY SYSTEM: Angiotensin II and plasma K+
-RECEPTORS: receptors confined to excretory organs (kidney, colon, salivary and sweat glands) |
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Term
| Discuss the Zona fasiculata |
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Definition
-HORMONE: Glucocorticoids (cortisol)
-ACTION: involved in normal metabolism and resistance to stress
-REGULATORY SYSTEM: regulated by adrenocorticotropic hormone (ACTH)
-RECEPTORS: receptors widely distributed throughout the body |
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Term
| Discuss the Zona Reicularis |
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Definition
-HORMONE: Androgens (dihydroepiandesrosterone -DHA)
-ACTION: Sex hormones
-REGULATORY SYSTEM: Regulated by adrenocorticotropic hormone (ACTH) |
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Term
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Definition
-Glococorticoid
-SYNTHESIS: From cholesterol
-METABOLISM: Highly protein bound to CBG and albumin; Type I: found in liver, converts inactive cortisone back to cortisol; Type II: found in kidney; converts cortisol to inactive cortisone
-RECEPTORS: Type I: (mineralocorticoid) expressed in organs of excretion; Type II: androgen (glucocorticoid) widely distributed
-->Results in Metabolic and Anti-Inflammatory effects
-REGULATION: Hypothalamic-Pituitary unit coordinates production. Hypothalamus produces and releases CRH and ACTH
-NEGATIVE FEEDBACK REGULATION: High cortisol levels decrease synthesis and release of CRH and ACTH |
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Term
| What occurs with Adrenal insufficiency? |
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Definition
-Addison's Dz (primary): Adrenal cortex destroyed via T cell-mediated AI rxn
-Secondary Adrenal insufficiency: Hypothalamic or pituitary disorders. Hypothalamic-pituitary-adrenal (HPA) axis suppression
-Can be life-threatening |
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Term
| What occurs with Adrenal Excess? |
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Definition
-Cushing's Syndrome
-Symptoms reflect amplification of the normal physiologic actions of glucocorticoids
SE: HTN, fungal infxns, diabetes |
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Term
| What are the effects of Glucocorticoids? |
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Definition
-Promote normal intermediary metabolism
-Increase resistance to stress
-Alters plasma blood cell composition
-Anti-inflammatory action
-Other endocrine effects
-Other system effects |
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Term
| What are the routes of administration for Glucocorticoids? |
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Definition
-Oral
-IM
-IV
-Inhalation
-Topical
-Depot injxn |
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Term
| What are the SE from Glucocorticoids? |
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Definition
| -HTN, edema, osteoporosis, increased risk of infxn, peptic ulcers, glaucoma, increased appetite, emotional disturbances, hypokalemia, hirsutism |
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Term
| What are the clinical uses of Glucocorticoids? |
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Definition
-Inflammation: COPD/asthma, acute gout, RA
-Immunosuppression: Transplantation, AI disorders, Cushing's
-Congenital Adrenal hyperplasia
-Allergies
-Lung maturation |
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Term
| What is Glucocorticoid withdrawal? |
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Definition
-Abrupt removal of glucocorticoids causes an acute adrenal insufficiency syndrome.
-Chronic glucocorticoid Tx must be tapered down. |
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Term
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Definition
-Mineralocorticoid
-SYNTHESIS: from cholesterol; enzymes expressed only in the zona glomerulosa
-METABOLISM: Low binding affinity, short elimination half-life, extensive metabolism through the liver
-REGULATION: -RAAS: stimulates aldosterone synthesis; Plasma K+ levels: increase aldosterone synthesis; ACTH |
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Term
| What are the effects of Aldosterone Hypofxn? |
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Definition
-Decreased aldosterone synthesis
-Addison's Dz (zona glomerulosa destruction)
-Decreased renin production |
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Term
| What are the effects of Aldosterone Hyperfxn? |
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Definition
-Bilateral zona glomerulosa adrenal hyperplasia
-Aldosterone-producing adenoma |
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Term
| What are the effects of Mineralocorticoids? |
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Definition
-Help control the body's water volume
-Help control electrolytes
-Increase reabsorption of Na+, HCO3-, H2O
-Decrease reabsorption of K+ and H+ ion |
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Term
| What are the clinical uses of Mineralocorticoids? |
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Definition
-Adrenal insufficiency: cortisol stem test shows a pt in the trauma unit has adrenal insufficiency - typically treated by hydrocortisone
-Orthostatic hypotension |
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Term
| Dehydroepiandrosterone (seriously?) |
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Definition
-Androgen
-MECH: Prohormone that is converted to more potent androgens (testosterone)
-CLIN: Source of testosterone for females, useful in hypoaldosteronism, chronic fatigue syndrome |
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Term
Aminoglutethimide
Ketoconazole
Metyrapone
Trilostane |
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Definition
-Inhibitors of Hormone Synthesis
-Aminogluthimide: inhibits side-chain cleavage enzyme and aromatase
-Ketoconazole: Antifungal which inhibits fungal P450 enzymes. Enzymes that mediate adrenal and gonadal synthesis. Inhibits side-chain cleavage enzyme. Broadly inhibits adrenocortical hormone synthesis
-Metyrapone: Inhibits 11B-hydroxylation --> Impaired cortisol synthesis. Useful to test for ACTH reserve
-Trilostane: Inhibits 3B-hydroxysteriod dehydrogenase. Reduced aldosterone and cortisol production |
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Term
| What are the Tx goals of Type I DM? |
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Definition
-Must rely on exogneous insulin
-Maintain glucose level as close to normal as possible
-Use long acting insulin throughout the day then use short term for meal time
-Avoid diabetic ketoacidosis (DKA) |
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Term
| What are the Tx goals of Type II DM? |
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Definition
-Maintain blood glucose concentrations within normal limits
-Prevent development of long-term complications
-Wt loss, exercise, and dietary changes decrease insulin resistance |
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Term
| What is the progression of Type II DM? |
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Definition
-3 labs:
1. Fasting (12 hrs): >126 is diagnostic
2. Random (pt comes in off street): >200 is diagnostic
3. A1C: >7 is diagnostic |
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Term
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Definition
-Measures the glycosylation of RBCs (which occurs at a rate proportional to blood glucose levels)
-Estimates average blood glucose over 3-4 mths.
-RBC life span is 120 days |
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Term
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Definition
-DOSE: Pt dependent; avoid insulin stacking by Lispro
-PHARM-K: inactivated by insulin protease - kidney injury can cause hypoglycemia from O/D insulin
-CLIN: only Tx for Type I DM or approved for gestational diabetes
-SE: Site rxns, hypoglycemia, insulin stacking |
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Term
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Definition
-Alpha-glucosidase Inhibitors
-MECH: bind to glucosidase enzymes - which are responsible for cleaving complex carbohydrates to make glucose. Increases the time required for the body to absorb carbohydrates. Only effective with meals.
-PHARM-K: Acarbose is poorly absorbed; miglitol well absorbed (no systemic effects); no risk of hypoglycemia
-CLIN: reduced postprandial blood glucose levels
-SE: Abdominal pain, bloating, diarrhea
-CONTRA: DKA, cirrhosis, IBD, bowel obstruction
-OVERALL: Lowers A1c ~0.7-1.0% |
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Term
Glimepride
Glipizide
Glyburide |
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Definition
-Insulin Secretagogues: Sulfonylureas
-MECH: Increases circulating levels of insulin. No B-cell fxn, won't work
-PHARM-K: longer half-lives; active metabolits (except glipizide)
-CLIN: First line therapy for newly Dx DM II
-SE: Hypoglycemia, dizziness, nausea and diarrhea
-CONTRA: DKA, avoid in renally impaired pts
OVERALL: Lowers A1c ~1.0-2.0% |
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Term
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Definition
-Insulin Secretagogues: Meglitinides
-MECH: If you have no B-cell fxn, won't work
-PHARM-K: very short half-life; metabolized to inactive products
-CLIN: N/A
-SE: Hypoglycemia, dizziness, nausea and diarrhea
-CONTRA: DKA, avoid in renally impaired pts
-OVERALL: Lowers A1c ~1.0-2.0% |
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Term
Pioglitazone
Rosiglitazone |
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Definition
-Insuline Sensitizers: Thiazolidinediones
-MECH: Decreases levels of circulating insulin. You need to have insulin to make this work
-PHARM-K: Metabolized via CYP450 enzymes. Increased LDL (rosi); increased HDL (both)
-CLIN: N/A
-SE: hepatotoxicity (monitor LFTs twice/year), edema, worsening HF
-CONTRA: NYHA class III/I, or any symptomatic HF; Rosi has risk of MI
-OVERALL: Lowers A1c~ 1.0-1.25% |
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Term
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Definition
-Insuline Sensitizers: Bignuanides
-MECH: Inhibits hepatic gluconeogenesis and glycogenolysis; Doesn't promote insulin secretion - it is an insulin synthesizer. Because is doesn't cause insulin release, it doesn't matter if you're eating or not
-PHARM-K: Well absorbed; not metabolized; excreted in urine; associated with wt loss
-CLIN: Commonly used as 1st-line or as part of an escalating therapy
-SE: diarrhea, N/V, lactic acidosis
-CONTRA: HF, EtOH abuse, renal Dz/impairment
-OVERALL: Lowers A1c ~1.5% |
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Term
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Definition
-Dipeptidyl Peptidase: IV inhibitors
-MECH: Increased insuline release in response to meals and reduces inappropriate glucagon secretion
-PHARM-K: excreted in the urine
-CLIN: N/A
-SE: Hypoglycemia, HA, Nausea, diarrhea, pancreatitis; does not alter wt
-CONTRA: Type I DM, DKA
-OVERALL: Lowers A1c ~0.5-0.8% |
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Term
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Definition
-Amylin Analog
-MECH: Delays gastric emptying, decreases postprandial glucagon secretion, and improves satiety
-ADMIN: SubQ injxn (immediately prior to meals)
-CLIN: Adjunct to mealtime insulin in Type I and II DM
-SE: Hypoglycemia, N/V
-CONTRA: gastroperesis, avoid in pts who cannot recognize and manage hypoglycemia
-OVERALL: Lowers Ac1 ~0.5% |
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Term
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Definition
-GLP-1 Agonist
-MECH: Slows gastric emptying, decreases postprandial glucagon secretion, promotes B-cell proliferation, decreases appetite
-CLIN: N/A
-ADMIN: SubQ injxn only, short duration
-SE: wt loss, hypoglycemia, N/V/diarrhea, HA
-CONTRA: Type I DM, DKA
-OVERALL: Lowers Ac1 ~0.5-1.0% |
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Term
| What are Dr. Carr's Tx recommendations? |
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Definition
-Try to max out the meds that the pts are on first
-Type II DM: 1. Start with one of the Sulfonylureas or metformin
2. Pioglitazone next
3. Sitagliptin next
4. Pramlintide or Exenatide next
5. If it is a post-prandial problem, add Acarbose
-If you have a pt with A1c of 10, start with the drug that effects the A1c the most |
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