Endocrinology

1. Endocrinology Need picture on title slide

2. Diabetes Mellulitis Etiologic Classification Type 1 (insulin deficiency) Immune mediated Idiopathic Type 2 (insulin resistance) Gestational Diabetes Mellitus (GDM) Other Types Drug-induced Infection related Diseases of excocrine pancreas

3. Criteria for the Diagnosis of Diabetes Symptoms of diabetes plus a random plasma glucose > 200 mg/dl (11.1 mmol/L) or Fasting glucose > 126 mg/dl (7.0 mmol/L) or 2-hr glucose > 200 mg/dl (11.1 mmol/L) during an oral glucose tolerance test FBS 110-125 is considered impaired fasting glucose Each of the above criteria needs to confirmed on a subsequent day

4. Type 1 DM Autoantibodies present 85-90% [to insulin, islet cells, glutamic acid decarboxylase (GAD)] Concordance in monozygotic twins is less than 50% Nongenetic factors play important role

5. Type 1 DM (Cont�d) Rapid onset in children Other autoimmune disease common Grave�s Disease Hashimoto�s thyroiditis Addison�s Disease Pernicious anemia

6. >80% of patients with diabetes Strong genetic basis � concordance in monozygotic twins is almost 100% Associated features Obesity Hypertension Dyslipidemia (? triglycerides; ? HDL) Type 2 DM

7. Type 2 DM (Cont�d) 30-40% eventually require insulin Increasing incidence in young persons probably related to increasing obesity Minority races higher incidence African Americans Hispanics Native Americans Low birth weight neonates have higher risk of diabetes

8. First detected during pregnancy Screen between 24-28 wks except for low risk � without any risk factors Age <25 Normal weight No history of abnormal glucose tolerance No history of poor obstetric outcome Ethnic group � not high risk High risk populations (previous GDM, LGA birth, obesity, etc) � may warrant screening early in pregnancy Gestational Diabetes (GDM)

9. Insulin Types Rapid Lispro insulin (Humalog) Insulin aspart (Novolog) Injected at meal time or 5-10 minutes before Short Regular Insulin Inject 30-45 minutes before meals Intermediate Lente or NPH Usually given 2x/day

10. Insulin (Cont�d) Long Ultralente or Lantus Usually given 1 x day Lantus in clear, not cloudy; cannot be mixed with other insulins Attempt to stimulate normal pattern of insulin secretion by using: Long acting qd + rapid or short at meals Intermediate + short bid Many other combinations

11. Oral Medications for Diabetes Sulfonylureas (Glyburide, Glipizide) and Meglitinidines (Prandin, Starlix) Insulin secretogogues Biguanide (Metformin) Inhibitors hepatic gluconeogenesis and enhances insulin sensitivity Adverse effect: GI disturbance, Rare lactic acid

12. Oral Medications for Diabetes (Cont�d) Alpha-Glucosidase Inhibitor (Precose) Delays absorption of glucose Adverse effect: GI disturbance May be useful in post prandial glucose control Thiazolidinediones - TZD (Avandia, Actos) Enhances insulin sensitivity Adverse effects: hepatic toxicity, anemia, mild edema LFT monitoring before and q 2mo during 1st yr

13. Starting Oral Agents Metformin and TZD recommended over sulfonylureas in obese patients (promotes WT loss) Titrate upwards every 4-8 weeks If monotherapy doesn�t achieve goals � combination therapy warranted For symptomatic Type 2 DM whose BS >280 mg/dl insulin is general recommended to reduce symptoms and control glucose and often can switch to oral therapy 4-8 weeks later For asymptomatic patients, consider pharmacologic therapy after 6 weeks if FBS >140 mg/dl; initial care weight loss and physical activity

14. Standards of Medical Care for Patients with Diabetes Glycemic control AIG <7.0% Preprandial plasma glucose 90-130 mg/dl Peak postprandial glucose <180 mg/dl BP < 130/80 Lipids Screen yearly LDL <100 mg/dl Tryglycerides <150 mg/dl HDL >40 mg/dl

15. Standards of Medical Care for Patients with Diabetes (Cont�d) Self-monitoring of blood glucose (SMBG) Type 1 � 3 or more daily Type 2 � sufficient for glycemic control AIC 2x/year if at glycemic control 4x/year if not at glycemic control Anti-platelet therapy ASA (75-325 mg/dl) for all adults with macrovascular disease >40 yr for primary prevention, consider 30-40 yr

16. Standards of Medical Care for Patients with Diabetes (Cont�d) CHD Screening Exercise stress test for typical or atypical symptoms; 2 or more risk factors (diplipidemia, HTN, smoking, positive FMH, Micro or Macro-albuminuria); hx of peripheral or carotid disease Nephropathy Screening Perform annual test in Type 1 DM after 5 yr and all Type 2 DM starting at diagnosis Spot albumin/creatinine ratio if UA protein is negative

17. Standards of Medical Care for Patients with Diabetes (Cont�d) Retinopathy Screening Type 1 � after 3-5 yr of diagnosis Type 2 � at diagnosis Repeat annually for all DM Foot Care Comprehensive annual exam with use of Monofilament Visual inspection at each routine visit Immunization Annually influenzae Pneumococcal vaccine and booster if needed (when immunized <65 yr and vaccine given >5 yrs ago)

18. Special DM Situations DAWN Phenomenon Early morning rise in glucose that is a result of hepatic gluconeogenesis Prevented by Metformin and Insulin Intermediate acting given at night Hypoglycemic Unawareness Inability to perceive the adrenergic (tachycardia, anxious) and cholinergic (sweating) warning signs prior to the neuroglycopemic signs (confusion, lethargy and coma) Care involves easing intensiveness of treatment to �reset� awareness on a temporary basis

19. Special DM Situations (Cont�d) Pancreatic Transplantation Usually simultaneously with kidney Glycemic Control 85% at 1 year 50% at 5 years Quality of life improved

20. Diabetic Ketoacidosis Common precipitants Infection Nonadherence to treatment Newly diagnosed disease Diagnostic criteria Arterial PH < 7.3 HCO3 < 15 Moderate ketonemia (euglycemic ketoacidosis � 30% prevalence)

21. DKA Treatment Insulin Bolus 5 to 10 units of regular Infusion 0.1 unit/kg/hr Goal to ? BS by 75-100 mg/dl per hour Double infusion after 1-2 hrs if not decreasing Saline Infuse 1-2 liters to assure normal circulation Potassium 10-30 meq/hr if serum K is not > 5 meq/L and urine output is good

22. DKA Complication � Cerebral Edema Most common in children Symptoms: headache, diminished consciousness Prevention: judicious fluid usually

23. Hyperglycemic Hyperosmolar States (HHS) Occurs after long periods of uncontrolled hyperglycemia Precipitating event: medication, illness, limited access to water (elderly) Adequate insulin to prevent lipolysis and ketogenesis

24. Hyperglycemic Hyperosmolar States (HHS) (Cont�d) Diagnostic criteria Blood glucose > 600 mg/dl Arterial pH > 7.3 HCO3 > 15 meg/Liter Osmolality > 320 Mild to absent ketonemia Treatment: similar to DKA

25. Diabetic Retinopathy Leading cause of new blindness in adult 3 types: nonproliferative, preproliferative, proliferative Control of glycemia reduces risk and slow progression Yearly eye examination by specialist recommended

26. Diabetic Nephropathy Most common cause of end-stage kidney disease in U.S. Presents with microalbuminuria > 30 mg/d Usually accompanied by HTN When overt proteinuria (> 300 mg/d) occurs Usually progressive GFR ? 1 ml/min per month

27. Screen yearly in all adults If UA is negative for protein, perform microalbumin test Treatment / prevention Glycemic control HTN control < 130/80 Antihypertensive agents: ACE, ARB, B-blockers Protein restriction 0.8 gm/Kg per day Diabetic Nephropathy (Cont�d)

28. Diabetic Foot Problems 50% of all nontrauma amputations are the result of DM Screening: with foot exams at regular DM f/u visits Treatment / prevention Glycemic control Stop smoking Regular foot care / shoe wear

29. Neuropathic Complications Most common cause of neuropathy �Pins and needles� � more severe at night Peripheral neuropathies treatment � gabapentin, TCA Automatic Neuropathies Increased heart rate Gastroparesis � metoclopiamide Diabetic diarrhea � loperamide Orthostatic hypotension � fludrocortisone Erectile dysfunction-multiple treatments

30. Coronary Artery Disease in Diabetes More than 50% of all deaths in diabetics Screening recommended for asymptomatic diabetics who have 2 other risk factors HTN, smoking, men over 40, FMH of premature CAD, ? cholesterol) Or other signs of symptoms of vascular disease

31. Hypoglycemia in Nondiabetics Rare disease Diagnostic criteria (all 3) 1 � BS < 50 mg/dl 2 � Symptoms Adrenergic � tachycardia, anxiety Cholinergic � hunger, sweating Neuroglycopenia � confusion, blurred vision 3 � Resolution of symptoms with improvement in BS

32. Hypoglycemia Evaluation (Cont�d) Measurement of plasma insulin, C-peptide and glucose Glucose ? 40 mg/dl + plasma insulin > 60 ?U/ml + C-peptide > 0.2 ?g/ml � suggest insulinoma Screen for sulfonylurea and meglitinidines usage by blood/urine test

33. Hypoglycemia Evaluation (Cont�d) Glucose ? 40 mg/dl + plasma insulin level elevated but C-peptide low � exogenous insulin use

34. Anterior Pituitary Deficiency Hypogonadism (FSH, LH), Hypothyroidism (TSH), Adrenal insufficiency (ACTH), Growth hormone deficiency (GH) Most commonly due to tumor Other causes: brain irradiation, congenital

35. Sheehan�s Syndrome Pituitary infarction associated with uterine hemorrhage at time of delivery Symptoms: absence of lactation, amenorrhea, fatigue, cold intolerance

36. Empty Sella Syndrome Radiologic finding of decreased pituitary gland volume Only 10% of patients have hypopituitarism

37. Diagnostic Testing Blood levels of anterior pituitary hormones usually not worthwhile secondary to wide fluctuations in normal levels and nonbiologically active secretion of �abnormal forms� � exception is Prolactin

38. Measure Morning cortisol ( > 18 ?/dl � normal) ACTH stimulation test (may be normal if done < 6 weeks from pituitary deficiency) Free T4, Free T3 Males� testosterone and if low, check FSH/LH Females� estradiol and if low, check FSH/LH GH stimulation testing Diagnostic Testing (Cont�d)

39. Treatment Cortisol deficiency � oral glucocorticoids Thyroid deficiency � thyroxine replacement; monitor Free T4 Males � testosterone Female � estrogen Growth hormone � controversial; observe / screen for osteoporosis

40. Most common tumor Symptoms Women- amenorrhea, galactorrhea Men � decreased libido, erectile problem Labs: TSH, prolactin Test: MRI � brain Prolactinomas

41. Prolactinomas (Cont�d) Treatment Bromocriptine � start low, titrate � tablet of 2.5 mg Bedtime with snack Cabergoline Fewer side effects (? GI, ? hypotension) Start � tablet of 0.5 mg

42. Acromegaly Rare disease Increased morbidity/mortality Gradual development; 5-15 year delay in diagnosis Symptoms: acral overgrowth, sweating, diabetes, HTN, headache, etc. Diagnosis: elevated IGF-1 on two occasions, MRI � brain Treatment: surgery

43. Cushing Syndrome Cortisol excess Symptoms: central obesity, wide purple striae, spontaneous ecchymosis, hypokalemia, osteopenia. These are relatively specific findings Elevated 24-hr urine free cortisol levels > 250-300 ?g/24 hr virtually diagnostic

44. Cushing Syndrome (Cont�d) Diagnostic Testing Dexamethasone Suppression Test Screening test 1 mg at 11 pm Measure serum cortisol at 8 am Normal result < 5 ?g/dl False positives (obesity, stress, alcoholism, psychiatric illness, test-related artifacts) Treatment: nearly always surgical

45. Pheochromocytoma Suspect if resistant hypertension ( > 3 drugs needed), episodic exacerbations including headache, sweating, palpitations Diagnostic testing: 24-hr urinary catecholamines or metabolites

46. Pheochromocytoma (Cont�d) Localization of lesion MRI � usually unilateral 10% bilateral 10% extra adrenal Sometimes needed 13II MIBG scan Treatment: surgical removal Alpha-blockage to control HTN (phenoxybenzamine)

47. Primary Hyperaldosteronism Suspect in HTN and spontaneous hypokalemia or resistant hypertension Screen paired plasma aldosterone / plasma renin activity ratio > 20 Treatment: surgery, aldosterone antagonist

48. Adrenal Incidentaloma 10% of patients at autopsy Any evidence of adrenal hyperfunction? Check for: Pheochromocytoma � urine catecholamines Cushing�s Syndrome � 24-hr urine cortisol, serum potassium Primary aldolesteronism � aldolesterone / renin ratio Malignancy � serum testosterone in women depending on clinical presentation

49. < 4 cm � unlikely to be malignant f/u 6-12 mo > 4 cm � or enlarging: surgery Adrenal Incidentaloma (Cont�d)

50. Polycystic Ovary Syndrome Most common cause of hirsutism 5% of U.S. population Presentation: acne, obesity (50%), hirsutism, insulin resistance (40%), abnormal lipids, menstrual dysfunction Treatment: weight loss, metformin

51. Androgen Deficiency in Males Diagnosis Appropriate symptoms (? libido, fatigue, erectile dysfunction) Serum testosterone below lower limits of normal Resolution of symptoms with addrogen replacement Treatment Testosterone replacement: injections, patch, gel

52. Male Sexual Dysfunction Erectile dysfunction � inability to achieve an erection capable for sexual intercourse at least 25% of the time

53. Male Sexual Dysfunction (Cont�d) Evaluation History P.E. Drugs (antihypertensive, anti-depressants, alcohol, narcotics) Labs-prolactin, TSH, testotesterone, HgbA1C, chemistry panel, CBC

54. Measure of testosterone in the morning important secondary to diurnal variation which can result in testosterone levels < 100 ng/ml in the afternoon in normal men

55. Male Pattern Balding Occurs in men and women Associated with polycystic ovary syndrome in females Treatment Acceptance Wigs Hair transplants Oral or topical medications

56. Topical Minoxidil Applied twice a day More effective if younger, hair loss on the crown not the front, more recent loss Men: 10% dense, 30% moderate hair regrowth (4 months), 30% minimal, 30% no change Women: less successful than men

57. Evaluation of Thyroid Function TSH � very sensitive and specific marker of thyroid function ? TSH + ? T4 = hyperthyroidism ? TSH + ? T4 = hypothyroidism Reliable if pituitary function normal

58. Evaluation of Thyroid Function (Cont�d) Radionuclide scans 123I (RAI) Nonfunctional area � �cold� nodule Hyperfunctional area � �hot� nodule If hyperthyroidism present then ? uptake ? Grave�s Disease Uptake ? exogenous thyroid usage Thyroiditis

59. Thyroid Ultrasound A nodule which concentrates iodine �hot� is very unlikely to be malignant Nodule can be detected and classified as cystic, solid or mixed

60. Hyperthyroidism Symptoms � weight loss, palpitation, heat intolerance, amenorrhea, tachycardia, lid lag or stare, osteopenia, goiter (Grave�s disease), atrial fibrillation Apathetic � more common elderly

61. Hyperthyroidism Etiology Grave�s Disease Due to stimulating factor antibodies detected > 80% of the time RAI uptake very high Multinodular or uni- toxic goiter Autonomous function RAI � elevated

62. Thyroiditis Rupture of pre-formed hormone RAI � very low Exogenous hormone Surreptitious use or over-treatment RAI � very low Serum thyroglobulin level � very low Hyperthyroidism Etiology (Cont�d)

63. Hyperthyroidism Treatment Graves PTU, methimazole RAI Surgery Thyroiditis Self-limited B-blockers for adrenergic Sx

64. Hypothyroidism SX: weight gain, apathy, constipation, dry skin, cold intolerance, menorrhagia Lab: elevated TSH Treatment: levothyroxine, follow TSH in 6-8 weeks

65. Amiodarone Therapy Some patients develop hypo or hyperthyroidism 35% of drug by weight in iodine, 200 mg tablet release 20x the optimal daily intake of iodine Monitor TSH

66. Amiodarone Therapy (Cont�d) Hypothyroidism � Rx levothyroxine Hyperthyroidism � depends on mechanism Mild � observe Thyroiditis � Prednisone Amiodarone induced � stop if possible Graves, multinodualr goiter � PTU/Methimazole, radiation, surgery

67. Thyroid Nodules Very common and mostly benign Functional nodules �hot� �warm� Evaluate by ultrasound or nuclear scan �Cold� nodule � 90% benign FNA is best step in �cold� nodule evaluation, if cytology shows microfollicular pattern after review by expert cytopathologist, surgery consultation warranted