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• Anterior (adenohypophysis): consists of glandular tissue and secretes ACTH, TSH, growth hormone, prolactin, FSH and LH
• Posterior (neurohypophysis): contains nervous tissue rather than glandular, and neurons in the posterior pituitary store ADH and oxytocin (released in response from nerve stimulation in the hypothalamus)
Anterior Pituitary AgentsGROWTH HORMONE (GH)somatropinMOA: Recombinant form of human GH; acts through GH
receptors to increase production of IGF-I
Effects: Restores normal growth and metabolic GH effects in GH-deficient individuals Increases final adult height in some children with short stature not due to GH deficiency
Clinical Applications:
Replacement in GH deficiency Increased final adult height in children with certain conditions associated with short statureWasting in HIV infectionShort bowel syndrome
Effects: Inhibits production of GH and, to a lesser extent, of TSH, glucagon, insulin and gastrin
Clinical Applications:
Acromegaly and several other hormone-secreting tumors Octreotide: Acute control of bleeding from esophageal varicesLanreotide: similar to octreotide; available as a long-acting formulation for acromegaly
In patients who have been treated surgically for thyroid carcinoma, to test for recurrence by assessing TSH-stimulated whole-body 131I scans and serum thyroglobulin determinations
Adrenocorticotropin(ACTH, Cosyntropin)
In patients suspected of adrenal insufficiency, either central (CRH/ACTH deficiency) or peripheral (cortisol deficiency), in particular in suspected cases of congenital adrenal hyperplasia
Thyroid Physiology• Secretes sufficient amounts of the thyroid hormones (tri-
iodothyronine (T3) and thyroxine (T4)) to maintain the basal metabolic rate which ensures normal growth and development
• Hormones contain iodine as an essential part of the molecule
• Hashimoto’s thyroiditis: autoimmune destruction of thyroid; most common presentation of HYPOthyroidism
• Graves' disease: autoimmune disorder in which helper T lymphocytes stimulate B lymphocytes to synthesize antibodies to thyroidal antigens; most common form of HYPERthyroidism
• Adjunct therapy for hyperthyroidism: beta-adrenoceptor-
MOA: Inhibit organification and hormone release reduce the size and vascularity of the gland
Indication: Preparation for surgical thyroidectomy
Comments: Oral; acute onset within 2–7 days
RADIOACTIVE IODINE131I (RAI)
MOA: Radiation destruction of thyroid parenchyma
Indication: Hyperthyroidism
Comments: Oral; half-life 5 days; onset of 6–12 weeks, maximum effect in 3–6 months; patients should be euthyroid or on beta-blockers before RAI; avoid in pregnancy/nursing mothers
Adrenal Glands: Physiology ReviewSecrete 3 essential classes of steroids:1. Gonadocorticoids:
Androgens > estrogens (less than testes or ovaries)2. Mineralocorticoids:
Aldosterone accounts for 95% Primary function is to regulate plasma volume (promote Na reabsorption and K
excretion by the renal tubules) Decreased plasma volume kidneys secrete renin production of angiotensin II aldosterone secretion promotes Na and water retention
Hyperaldosteronism: excessive aldosterone secretion usually a result of adrenal tumors, characterized by HTN and hypokalemia
3. Glucocorticoids: More than 30 glucocorticoids are secreted Cortisol (hydrocortisone) secreted in highest amount Influence the function of most cells in the body
Effects of GlucocorticoidsPhysiologic Effects Permissive effects: without glucocorticoids many normal
functions become deficient: response of vascular and bronchial smooth muscle to catecholamines is diminished in the absence of cortisol and restored by physiologic amountsEffects are dose-related: become magnified when large amounts are administered
Metabolic Effects Influence carbohydrate, protein and fat metabolism; stimulategluconeogenesis
Catabolic and Anti-anabolic Effects
Involved in lymphoid and connective tissue, muscle, peripheral fat, bone and skin
Anti-Inflammatory & Immunosuppressive Effects
Reduce inflammation through suppression of inflammatory cytokines; inhibit macrophage function; reduce prostaglandin synthesis
Other Effects Influence the nervous system; produce behavioraldisturbances, suppress pituitary release of ACTH, GH, TSH
Select Indications for GlucocorticoidsIndication CommentsAdrenocortical Insufficiency Acute: Initiate treatment immediately
hydrocortisone (usually large doses initially) supplementation with mineralcorticoid (fludrocortisone) is delayed until hydrocortisone is reduced to 50 mg/day
Chronic(Addison's Disease):
Hydrocortisone supplemented with a mineralocorticoid (fludrocortisone)
Use of Glucocorticoids for Diagnostic PurposesDexamethasonesuppression test
Diagnosis of Cushing's syndrome
Cosyntropin stimulation test
Diagnose or exclude primary and secondary adrenal insufficiency; Measurement of cortisol in serum for evaluation of adrenal dysfunctionCosyntropin 250 mcg IV x1 then check cortisol level at 30 minutes and 60 minutes
Select Indications for GlucocorticoidsIndication Comments
Hyperaldosteronism
Primary: usually results from excessive production of aldosterone by an adrenal adenoma
Secondary: spironolactone, an aldosterone receptor-blocking agent can be used
MiscellaneousCorticosteroids and stimulation of lung maturation in the fetus
When delivery is anticipated before 34 weeks of gestation, intramuscular betamethasone 12 mg, followed by an additional dose of 12 mg 18-24 hours later, is commonly used
Insulin SecretagoguesIndications: Monotherapy or combination therapy for Type 2 DMAgents: nateglinide (Starlix), repaglinide (Prandin)MOA: stimulates insulin release from pancreasAdverse
MOA: stimulates insulin release from pancreas, enhances beta cell sensitivity to glucose
AdverseEffects:
hypoglycemia, nausea, bloating, weight gain, photosensitivity, disulfiram reaction (chlorpropamide)
Comments: Use with caution in liver dysfunctionDose adjustment required for renal dysfunction Several drug-drug interactionsOver time response to therapy may diminishSulfonylureas
MOA: increases receptor sensitivity to insulin, decreases both insulin resistance and hepatic gluconeogenesis
AdverseEffects:
hepatotoxicity, weight gain, peripheral edema, rash, macular edema, heart failure exacerbation, increased risk of MI (rosiglitazone)
Comments: Use with caution (if at all) in liver dysfunctionBaseline LFT’s then periodically thereafterSeveral drug-drug interactionsContraindicated in NYHA class III or IVMay increase risk of osteoporosisMay increase risk of bladder cancer (pioglitazone)REMS program (rosiglitazone)
Alpha-glucosidase InhibitorsIndications: Adjunct therapy only for Type 2 DMAgents: acarbose (Precose), miglitol (Glyset)MOA: reduces rate and extent of CHO digestion and
absorptionAdverseEffects:
flatulence, diarrhea, abdominal pain, decrease absorption of iron (anemia)
Comments: Do not use in renal dysfunction (creatinine > 2.0)Baseline LFT’s then periodically thereafter (acarbose)May influence the absorption of other drugsContraindicated in malabsorption, IBD or intestinal obstructionGlucose (dextrose) is recommended for treating hypoglycemia as sucrose metabolism is inhibited
Comments: Several drug-drug interactionsContraindicated in severe renal dysfunction (both), h/o pancreatitis (both) or h/o thyroid cancer (liraglutide)Does NOT replace insulinREMS program
Amylin Receptor AgonistsIndications: Adjunct therapy for Type 1 and Type 2 DM
Agents: pramlintide (Symlin)MOA: Inhibit the degradation of GIP and GLP-1AdverseEffects:
abdominal pain, loss of appetite, nausea, vomiting,hypoglycemia, dizziness, headache, cough, fatigue
Comments: Contraindicated in patients with hypoglycemic unawareness or gastroparesisBlack box warning for individuals while drivingSevere hypoglycemia with concurrent insulin or oral hypoglycemic agentWhen initiating pramlintide: reduce dose of any secretagogues; reduce insulin dose by at least 50%
Comments: Adjust dose in renal impairmentAvoid use in severe liver impairmentCan cause severe hypoglycemiaSafety/effectiveness not established in patients younger than 18 yearsLong-term safety issues (cardiovascular, cancer risk)Role not addressed in recent ADA guidelinesMore clinical trials will better establish their role
Inzucchi SE, Bergenstal RM, Buse JB, et al.; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012;35:1364–1379