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Endocrine and Reproductive System (Green Boxes for Endocrine System…

- - - - Pulsatile GnRH administration increases FSH and LH levels
        
        Kallmann Syndrome where disordered migration of GnRH cells in hypothalamus BUT the pituitary and gonads function properly
        
        Hypogonadotropic Hypogonadism (low testosterone and low LH)
        
        Anosmia (loss of sense of smell)
        
        Amenorrhea in women
      - Continuous GnRH administration decreases FSH and LH levels
        
        Endometriosis is a condition were endometrial tissue appears outside the uterine cavity. The tissue releases endrogens and causes pain so the treatment goal is to decrease estrogens allowing for involution and diminution of endometriotic tissue
        
        Leiomyomas are estrogen dependent smooth muscle tumors. Our treatment goal is to decrease estrogen levels by continuous GnRH administration
    - - Levels of Leptin are an indicator of energy stores. Leptin promotes GnRH release by hypothalamic neurons.
      - Low leptin due to starvation, anorexia, strenuous exercise is associated with amenorrhea
    - - Types of Oral Contraceptives
        
        Multi-phasic or Varying-Dose OCPs
        
        Pills of different estrogen and progestin amounts are taken at different phases. Low risk of endometrial bleeding due to low dose.
        
        Progestin-Only OCPs
        
        Taken for 21 days. Ideal for nursing mothers and women with estrogen contraindications. Progestin only have higher failure rate as they do not effect ovulation.
        
        Monophasic or Fixed-Combination OCPs
        
        Pills taken for first 21 days of the 28 day cycle
      - Biological Action of Oral Contraceptives
        
        Without eliminating gonadotropin secretion or ovarian function low LH levels prevent ovulation. Progestin thickens uterine wall to prevent sperm penetration of sperm or implantation of ovum
  - - - Oocyte Retrieval (Extracts follicular fluid to yield 8-15 oocytes)
      - Insemination by ICSI (used with low male fertility)
      - Cycle Monitoring (Physician tracks follicles by estradiol levels then injects hCG to promote LH surge)
      - Embryo Transfer/TET (While receiving supplemental progesterone physician directs fertilized eggs into uterine cavity)
      - Ovarian Stimulation (GnRH to prevent premature LH surge then FSH and/or LH administration to create multiple follicles necessary for the procedure)
      - Success Rates is about 33%
      - Indications for IVF-ET (anything that would impair fertilization at distal portion of Fallopian Tube as endometriosis, peritoneal adhesions, occlusions)
      - GIFT (through laparoscopic techniques games are transferred directly to fallopian tube)
  - - - NO by raising cGMP levels increase smooth-muscle tone. Medications for ED degrade the enzymes cGMP phosphodiesterase type 5 that would break down cGMP and decrease smooth-muscle tone. Side Effect is blue vision by inhibiting the breakdown of cGMP in the retina.
    - - Only Sertoli Cells and not Germ Cells line semineferous tubules. FSH is elevated.
    - - Failure of the Internal Urethral Sphincter to constrict thus sperm passes down toward urinary bladder.thus diagnose with presence of sperm in urine. Other causes include interference of innervation of vas deferens and bladder neck as well as surgery. Treatment includes restoration of sympathetic tone such as alpha adrenergic agonist or enhancing NE release.
    - - As estrogen levels are altered in women during menopause so do testosterone levels decline with age. LH levels are not elevated.
  - - - Main Risk Factor
        
        Prematurity
      - Cause
        
        Low pulmonary surfactant
      - Diagnosis
        
        Chest Radiograph shows Atelectasis with air-filled bronchi
      - Symptoms: Cyanosis, tachypnea, nasal flaring, intercostal and subostal retractions, use of accessory musculature, grunting (signs that show straining for a breath). These symptoms develop over longer period of time for more mature preterm infants.
    - - Effects
        
        Switch to anaerobic respiration causes lactic acid buildup, decrease in ATP/ADP ratio
        
        luekotrienes, prostaglandins vasoactive compounds accumulate
        
        low O2, high CO2, acidosis, decrease myocardial function
        
        delayed breathing after birth but corrected in neonate after 24 hours
      - Causes
        
        Maternal Hypotension
        
        Prolapsed Umbilical Cord
        
        Umbilical Cord Falls in Birth Canal in Front of Head or Fetus
        
        Abruptio Placentae
        
        Portion of Placenta Broken From Uterine Wall
    - - Intermediate IUGR
        
        Combination of I and II most likely occurring between hyperplastic and hypertrophic gestational phases
      - Type II (asymmetric IUGR)
        
        Restricted infant grwoth caused by uteroplacental insufficiency. Most common of IUGR. Insult to fetus later in gestational period. Normal cell number by hypertrophic cells that are larger than normal. Normal fetal length and head circumference, but abdominal growth slows in 2nd or 3rd trimesters.Associated with maternal diseases such ask kidney disease, hypertension, diabetes. Hypertrophic Phase
      - Type I (symmetrical IUGR)
        
        Infant has decreased growth potential. Entire fetus small for gestational age. Due to growth inhibition during hyperplastic stage of fetal development (4-20 weeks). Results in few cells in the fetus.
  - - - Male Pseydohermaphroditism (Normal Karotype but Ambiguous Genetalia)
        
        Example
        
        Guevedoces (Children appear as girls at birth due to low levels of 5-alpha reductase then undergo masculinization at puberty)
        
        Causes
        
        androgen-receptor defects
        
        5-alpha reductase deficiency
    - - Mixed Gonadal Dysgenesis
        
        Aberrant expression of SRY
      - Pure Gonadal Dysgenesis
    - - Recall that ACTH has trophic effects on the adrenal gland so we expect that deficiency of enzymes such as 21 alpha hydroxylase to shunt pathways toward creating androgens and away from creating cortisol. Low cortisol means little negative feedback on the anterior pituitary and thus we expect high levels of ACTH.
    - - Turner Syndrome XO (cells lack one X chromosome in females. normal internal and external genitalia except that they are small)
        
        Causes
        
        X-Chromosome Ring whereby the free ends of the chromosome join together
        
        Partial Deletion of the X Chromosome
    - - Testicular Descent as Outlined in Figure 53-10 A-C is an androgen dependent process. The absence of 5-alpha reductase would prevent testes descent resulting in testicular feminization syndrome.
- - - - If and only if pituitary function is normal, TSH is a good measure to assess thyroid hormone status. After the administration of bolus of TRH we expect TSH levels to rise more dramatically in patients with hypothyroidism
      - Most of T4 is bound
      - Administer bolus of radioactive iodine. Differentiation of hyperthyroidism between thyroiditis (expect low uptake) vs. Graves disease (expect high uptake). High does or radioactive iodine used to treat patients with hyperthyroidism.
    - - Hypothyroidism
        
        Symptomology
        
        Constipation
        
        Weight Gain, Loss Appetite
        
        Decrease Reflexes
        
        Cold Intolerance (Decrease Heat Production)
        
        Myxedema (facial/periorbital)
        
        Dry, Cool skin; coarse, brittle hair
        
        Bradycardia, dyspnea on exertion
        
        Hypoactivity, Lethargy
        
        LAB FINDINGS
        
        Hypercholesterolemia (due to decrease LDL recepter expression)
        
        Low Free T3 and T4
        
        Increase TSH
        
        SPECIFIC TYPES
        
        Hashimoto Thyroiditis
        
        Antithyroid antibodies attack thyroid follicular cells, microsomes, and TSH receptors
        
        Cretinism
        
        Iodine deficiency that occurs at critical developmental times in infancy
        
        Goiter
        
        TSH has trophic effect on thyroid
        
        Myxedema coma (rae but deadly)
      - Hyperthyroidism
        
        Symptomology
        
        Increase Reflexes
        
        Weight Loss, Gain Appetite
        
        Pretibial myxedema (Graves Disease), Periorbital Edema
        
        Heat Intolerance (Increase Heat Production)
        
        Chest pain, palpitations, arrhythmias, increase number and sensitivity of beta-adrenergic receptors
        
        Exophthalmos (forward protrusion of the eyes)
        
        Diarrhea
        
        LAB FINDINGS
        
        Hypocholesterolemia (due to increase LDL receptor expression)
        
        High Free Total T3 and T4
        
        Low TSH
        
        SPECIFIC TYPES
        
        Graves Disease
        
        Most common cause of hyperthyroidism autoantibodies (IgG) stimulate TSH receptors on thyroid
        
        Inflitration of extraocular muscles (Infiltrative Ophthalmopathy)
        
        Diplopia (double vision)
        
        Exophthalmos (protrusion of the eyes)
        
        Impairs muscle funtion
        
        Pretibial Myxedema (localized thickening of the skin)
        
        Goiter
    - - High TSH
        
        Leads to Goiter due to the hypertrophic effects of TSH
      - Cretinism (iodine deficiency that occurs during development leads to severe mental retardation
      - Low Thyroid Hormone due to Low Iodine Leading to High TSH
  - - - Spironolactone (K sparing diuretic) in conjunction with thiazide diuretic and ACE Inhibitors
    - - Patient treated with glucocorticoids we expect centripetal location of fat (moon facies). Fat in the center. Muscle wasting in the periphery.
      - Effects on bone and inhibition of intestinal calcium absortpion produce osteopenia which can be manifested as osteoporosis
      - Remember: Glucocorticoid antagonizes the action of insulin
      - Endogenouse glucocorticoid (cortisol) has weak mineralcorticoid effect but exogenous lacks mineralocorticoid effect.
    - - Medullary Hyperplasia. Think Fight or Flight Response and your home free. Increased catecholamines in urine. Treatment to take our affected adrenal gland (adrenalectomy) then glucocorticoid and mineralcorcticoid replacement is necessary.
      - Other Medullary Issues (Conn and Bartter Syndrome)
        
        Conn Syndrome (Primary Hyperadlosteronism)
        
        Hypertension, hypokalemia, metabolic alkalosis, low renin. Treat with removal of tumor or spironolactone.
        
        Bartter Syndrome
        
        Autosomal recessive renal tubular disorder characterized by hypokalemia, hypochloremia, metabolic alkalosis. This is due to ion channel defects.
    - - decrease mineralcorticoids, decrease cortisol, increase in sex hormones pathway shunts to androgen side leading to ambiguous genitalia in females, decrease blood pressure since low mineralcorticoids, salt wasting, hypoglycemia, high ACTH due to no negative feedback from cortisol leads to hypertrophic adrenal gland, high potassium levels since low mineralcorticoid. In the lab we expect to find high renin activity and high 17-hydroxyprogesterone
    - - Cushing Syndrome (Tumor or Neoplastic Issue on Adrenal Gland)
      - Cushing Disease (Issue with Pituitary Gland)
      - Adrenal Insufficiency or Addision's Disease (Most common cause autoimmune issue)
      - Symptomology (Cortisol excess in Cushing Syndrome and Disease results in hypertention, potassium wasting, centripetal fat stores, hyperglycemia, muscle wasting) whereas (Addison Disease we see hypotension, hyperkalemia, hypoglycemia)
  - - - Gigantism (excess GH in children)
      - Acromegaly (GH excess in adults)
      - Laron Dwarfism (mutated GH receptors) thus no IGF-1
    - - Positives (increase muscle mass and strength); Negatives (Oily skin, acne, hair growth, liver function abnormalities,
    - - Though ob/ob mice lack the gene that creates the protein leptin when administered leptin lose weight. The administration of leptin is not the solution for treating obesity in humans because a percentage of obese people are leptin resistant
      - Some drugs decrease body weight by blocking the action of endocannadinoids
  - - - Leperchaunism is when there are autoantibodies against insulin receptor
      - autoantibodies can act as agonists or antagonists to the insulin receptor. Phoshorylation on the serine residue that insulin typically attaches to is common in models of insulin resistance and type 2 diabetes
    - - Type I Diabetes/IDDM
        
        Ketoacidosis/Kussmal Breathing (deep, rapid)
      - Type II Diabetes/NIDDM
        
        Insulin Resistance, rare ketoacidosis because sufficient insulin to balance the effect of glucagon thus modulating the production of glucose and ketones in the liver. Insulin resistance prior full onset Type II is metabolic syndrome characterized by high TAGs, low HDLs, hypertension, insulin resistance
    - - By binding to SUR subunits of Katp channels sulfonyureas case depolarization in functioning beta cells and stimulate insulin release. Note since Type I Diabetes has few functioning beta cells it is an effective Type II Diabetes Treatment.
    - - Glucose intolerance or frank diabetes may result in patients with mutant form of insulin
    - - Hypoglycemia (palpitations, tachycardia, diaphoresis, anxiety, hyperventilation, shakiness, weakness, hunger, and nausea seizures or neurological deficits)
      - Hyperglycemia (weakness, poly
  - - - apparent low parathyroid hormone levels because the G-protein is not functioning properly
      - LAB RESULTS
        
        Low Calcium Levels
        
        High Phosphate Levels
        
        High PTH Levels
      - Increased Risk of Hypothyroidism as well as gonadal dysfunction
    - - lung cancers from squamous cells secrete PTH-related peptide
        
        Result: Paraneoplastic Syndromes
      - lung cancers from small cells secrete AVP, ACTH, other hormones
        
        Result: Paraneoplastic Syndromes
      - ectopic tumors produce hormones from places other than where expected
    - - Principle: The Number of Steroid Receptors is correlated with being a good candidate for antiestrogen treatment
        Question: How do we measure steroid receptors. By tracking the relationship between free hormone to bound hormone a saturation curve can be created and then linearized. The slope gives of binding affinity. This is useful in breast cancer treatment. The principle is decreasing estrogen levels to control cancer cell growth.
        
        Administer continuous exogenous GnRH which decreases LH and FSH paradoxically
        
        Administer Anti-Estrogen IF sufficient estrogen receptors
  - - - Paget Disease of Bone (Localized Regions of Bone Resorption and Reactive Sclerosis)
      - Risk Factors
        
        Declining Estrogen
        
        Low Calcium intake, alcoholism, cigarette smoking, sedentary life
        
        Hyperthyroidism, Hyperparathyroidism, Hypercortisolism
      - Treatment
        
        Meds
        
        Agents that stimulate bone growth
        
        Absorptive Drugs
        
        Estrogen
        
        High Calcium Intake
    - - Hypoparathyroidism
        
        Symptoms
        
        Hypocalcemia
        
        Tetany
      - Hyperparathyroidism
      - Pseudohypoparathroidism
        
        PTH is not low but it appears low because of the unresponsiveness of the kidney to PTH
    - - Rickets (Vitamin D deficiency in children)
        
        Bowing of legs due to incomplete longitudinal growth
      - Osteomalacia (Vitamin D deficiency in adults)
        
        No Bowing of the legs due to complete longitudinal growth
      - Potential Effects
        
        Secondary Hyperparathyroidism to further bone resorption and worsening osteoporosis
      - Potential Causes
        
        Impairment of 1 hydroxylase activity
    - - High Calcium Levels
      - Hypocalciuric (less calcium in urine than the average person)
      - Asymptomatic
      - normal PTH
      - Set-Point for Calcium is right-shifted
      - Homozygous infants for defective CaSR have high calcium and high PTH levels
      - Calcimimetics decrease PTH secretion and decrease plasma Calcium so effective treatment for hyperparathyroidism