Endocrine & Hematological Disorders Overview

1. Endocrine & Hematological Disorders Christopher B. Powe, PhD, ACNP-BC

2. Content Diabetes Insipidus Adrenal disorders Adrenal insufficiency Immunological/hematological disorders: HIV/AIDS Neoplasms Rhumatoid Arthritis Systemic Lupus Erythema

3. Diabetes Insipidus • Impaired renal water conservation • Neurogenic/Central DI-inhibited release of ADH • Closed head injury, anoxic enceph., meningitis • Polyuria –pure water(w/in 24 hours) • Nephrogenic-defective renal response • Low K, aminoglycosides, amphotericin, contrast dyes, ATN, lithium, tetracycline, genetic • Better urine concentrating by kidneys • Gestational……………………………..

4. Diabetes Insipidus • Clinical Presentation • Polyuria and Dilute Urine • Dry mouth to Extreme thirst • Nocturia to bed wetting • Muscle weakness • Sunken appearance to your eyes  • Fever • Headache • Tachycardia • Water Weight loss

5. Diabetes Insipidus • Diagnosis • Low urine osmolarity • <200mOsm/L = central • 200-500 mOsm/L = renal • Fluid Restriction or Water depravation • short trial!! • Uosmo does not increase by >30mOsm/L after 1 hour • Can check ADH levels • Vasopressin response • If Uosmo increases > 50% = central DI • No increase = renal DI

6. Diabetes Insipidus • Treatment • Free water replacement • TBWdeficit L= normal Na TBW – Current Na TBW • Replace over 2-3 days • Replace slowly d/t risk of cerebral edema • Fix the Cause

7. Diabetes Insipidus • Treatment-Central • Vasopressin (ADH) 5-10u SC (PO or nasal spray) Q6 hours for Neurogenic DI only • Risks during resolution of Neurogenic DI • WATCH for Hyponatremia • Water intoxication • Fix the Cause • Treatment-Nephrogenic • HCTZ • Fix the cause/stop the medicine

8. Diabetes Insipidus • Complications • Electrolyte abnormalities • Muscle cramping • Hypotension • Cerebral Edema with correction

9. Adrenal Insufficiency Decreased mineralcorticoid production Primary Chronic with insidious onset Decreased glucocoticoids and androgens Increased ACTH secretion Infections (TB, fungal, HIV), autoimmune, inflammatory dz, drugs (etomidate, ketoconizole, …), metastatic dz Secondary & Tertiary Normal glucocorticoid activity Genetic, ACTH deficiency, Megace, high dose steroid use Causes Septic Shock Bilat. Adrenal hemmorhage/infarction Withdrawal of steroids (PO or INH)

10. Adrenal Insufficiency Clinical Presentation If hem./infarct hypotension or shock, abdominal, flank, back, or lower chest pain, fever, anorexia, nausea, or vomiting, confusion or disorientation, abdominal rigidity or rebound tenderness Pituitary Apoplexy (infarct) Also associated with acute visual loss and severe HA

11. Adrenal Insufficiency Clinical Pres.--Primary Hyperpigmentation and possbile vitiligo Lassitude Fatigue and generalized Weakness; Chronic malaise; arthralgias/myalgias Anorexia, weight loss, nausea, occasionally vomiting, abdominal pain, or diarrhea that may alternate with constipation Salt craving, and craving iced liquids Women-decreased axillary and pubic hair, sexual dysfunction, ammenorhea Depression to psychosis splenomegaly and lymphoid tissue hyperplasia, particularly of the tonsils

12. Adrenal Insufficiency Clinical Pres—Secondary and Tertiary No hyperpigmentation GI effects more rare Headaches Visual field defects

13. Adrenal Insufficiency Diagnosis-Primary EGD usually normal Hypotension Hyponatremia Mild hyperchloremic acidosis Rare hypercalcemia hypoglycemia Diagnosis 2nd and Tertiary ↓Na and hypervolemia ↓glucose more common Hem. /Infarct H/H ↓; K and Na ↑; hypovolemia CT adrenals

14. Adrenal Insufficiency Diagnosis Stage 1: high plasma renin activity and normal or low serum aldosterone Stage 2: impaired serum cortisol response to ACTH stimulation Stage 3: increased morning plasma ACTH with normal serum cortisol Stage 4: low morning serum cortisol and overt clinical adrenal insufficiency [5-7] . Serum Cortisol levels fluctuate and are no use Elevated daytime TSH ACTH stimulation tests-if you can get the lab run 24 hour urine for cortisol

15. Adrenal Insufficiency Treatment-suspected Crisis CK serum cortisol and electrolytes IV NS Replacement with IV Dexamethasone Treatment-Chronic Careful replacement by Endocrinologists

16. Complications Adrenal Crisis Insufficiency + acute infection/stress Rare in Secondary and Tertiary Not taking enough replacement meds Acute infarction or hemorrhage of adrenals anorexia, nausea, vomiting, abdominal pain, weakness, fatigue, lethargy, fever, confusion or coma to SHOCK Main symptom is Hypotension Rarely hypoglycemia

17. HIV/AIDS Chronic Infection (1 versus 2) New theory of treatment-pts live >25 years 1mil in US (1/4 unaware)/8800 in MS (50% untreated) --- Ryan White Care Act Higher in racial/ethnic minorities Only 13% have AIDS Transmission Risky Behaviors

18. HIV/AIDS Clinical Presentation Non-specific Febrile illness (“flu-like”) Frequent infections (ie fungal) THRUSH Rash Mucocutaneous ulcers LAD Chlamydia

19. HIV/AIDS Diagnosis Testing not yet “routine care” Pre-test counseling—ALWAYS Confidential Testing—ALWAYS OK to test B only in MS ELISA (HIV AB presence) sensitive/not specific 4 weeks to AB development….repeat 1,2, and 6 months Western Blot or IgM antibody by immunofluorescence assay (IFA) to confirm = >98% sensitive and specific Absolute CD4 <200 = AIDS = risk for Opportunistic Infection HIV quantitative PCR

20. HIV/AIDS Treatment-Initial-Crossroads Clinic Only if you are committed to continued care!! 3 drugs combo Ongoing, close, drug-specific follow-up Positive Prevention—EDUCATION Genotype resistance testing Treatment-AIDs—as above + Cover OIs with Bactrim, Zithromax Prevent infections Diflucan ONLY for thrush and cryptococcal meningitis

21. HIV/AIDS Complications Superinfection Medication Resistance—all or none with HAART More trouble with lifelong suppression Psychological Stigma!!! Grief Opportunistic Infections Reducing Viral Load and increasing CD4 decreases OIs Oral Candidiasis, Pneumocystis carinii (jiroveci) pneumonia (PCP), MAC

22. Neoplasms AIDS defining Kaposii’s Sarcoma Non-Hodgkin’s Lymphoma Systemic NHL CNS lymphoma Cervical Cancer

23. Neoplasms Oh so many locations ….. Epidemiology and Risks depend on type Manifestations Depend on Site Treatment depends on type

24. Neoplasms Diagnosis Radiographic CT, MRI, Bone Scan, PET FNA/Open Biopsies Immunohistochemistry Use monoclonal antibodies to detect antigen markers on WBCs (ie PSA) Chromosome analysis

25. Neoplasms Chemotherapy Oncology Manage n/v-Zofran Neutropenia-may need isolation Alopecia Psychological care Radiation Lung injury Fibrosis Can be cardiotoxic Can cause thyroid cancer Nausea and vomiting

26. Neoplasms Surgical Removal Pain Management Always scale pain Narcotics-Lortab/Lorcet/Percocet/Tylox Duragesic Patch Methadone Oxycontin Pain Center Referral

27. Rhumatoid Arthritis Autoimmune/unknown etiology Inflammed synovial membranes ↝ eroded cartiledge and bone ↝ adhesions/cysts between joint surfaces Juvenile vs Adult onset 50% is progressive Worsened with stress, infection, trauma, pregnancy Risk-women, age 40-60, smoking, family history

28. RA • Diagnosis/Presentation-Juvenile • Onset at <16 years • 2+ joints with arthritis/ swelling/effusion AND 2+ of: Limited ROM, pain with motion, increased heat • Duration 6 wks to 3 mths • Onset classification • Oligoarthritis/Pauciarthritis- < 4 joints • Polyarthritis- > 5 joints • Systemic Dz- arthritis, intermittent fever, rheumatoid rash , visceral disease

29. RA • Diagnosis/Presentation-Adult • Morning stiffness > 1 hour X >6 weeks • Arthritis of 3+ joints > 6 weeks • Arthritis of hand joints > 6 weeks • Symmetric Arthritis • Rheumatoid Nodules • + Serum RF (high titer = worse prognosis) • Radiographic Changes • Swollen joints soft and spongy • Maybe a + anti- cyclic citrullinated peptide (anti-CCP) antibodies

30. RA • Other Common Joint Problems • Carpal tunnel, shoulder bursitis, Knee Baker’s Cysts, hallux valgus, TMJ, atlantoaxial subluxation (C1-C2) • Extra-articular • Rheumatoid nodules (extensor surfaces), vasculitis, pleurisy, keratoconjunctivitis, pericarditis, periperal neuropathy, Felty’s syndrome (splenomegally + leukopenia) • Systemic • Fever, anorexia, wt loss, sweats, Raynauds

31. RA • Diagnosis • CBC + diff • RF titer • ESR/CRP • UA • For meds: electrolytes, creatinine, liver panel, hepatitis panel, FOBT • Synovial fluid analysis • X-ray selected joints • ANA, CH50-rule out other immune diseases

32. RA • Treatment • Pain Relief • NSAIDS to Narcotics • Joint Preservation • Physical therapy, splints • Exercise, Cold/Heat • Intra-articular corticosteroid injections • Prevent Disease progression • Medications • Refer to Rheumatology and Opthamology • Surgery for structural problems and severe pain • Assistive Devices

33. RA Medications NSAIDS-Pain only **side effects** Corticosteroids (low dose)-treats and prevents inflammation **side effects** DMARDs-Disease-modifying antirheumatic drugs- Plaquenil 200mg BID, Gold as auranofin (Ridaura), sulfasalazine (Azulfidine), minocycline (Dynacin, Minocin), methotrexate Low Side Effects Immunosupressants- leflunomide (Arava), azathioprine (Imuran), cyclosporine (Neoral, Sandimmune), cyclophosphamide (Cytoxan) Infection

34. Severe RA medications • TNF-alpha inhibitors IV- etanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira) • Infection, CHF, blood disorders • Anakinra (Kineret) IV-interleukin-1 receptor antagonist (IL-1Ra) - stops chemical cause of inflammation low WBC, URI, headache • Abatacept (Orencia) IV- inactivates T-cells • Headache, nausea, infections • Rituximab (Rituxan) IV-reduces B-cells • Fever, Chills, aches, nausea, infection, infusion reactions

35. Systemic Lupus Erythematosus Autoimmune and inflammatory in nature Mainly women; ages 15-40, African-American predominance Lupus Nephritis common in Asians and Hispanics Unknown etiology (hyperactive B cells and dysfunctional T cells) Triggers: sunlight, stress, silica, infections, environmental toxins, Epstein-Barr Virus, some Rx medications

36. The Many symptoms of SLE • Fatigue • Fever • Weight loss or gain • Joint pain, stiffness and swelling • Malar Rash-- Butterfly-shaped ,on the face, covers the cheeks and bridge of the nose • Skin lesions that appear or worsen with sun exposure • Mouth sores • Alopecia • Raynaud's phenomenon) • Shortness of breath • Chest pain • Dry eyes • Easy bruising • Anxiety • Depression • Memory loss

37. SLE American college of rheumatology criteria 4 of these 11 + indicates sle • Malar rash • Discoid rash • Photosensitivity • Oral Ulcers • 2+ joint arthritis • Serositis (pleuritis, pericarditis) • Lupus Nephritis • Neurologic disease • Hematologic disorders • Immune disorder………… • Abnormal ANA titer Note Handout

38. SLE • Immune Disorder • + anti-dsDNA antibody • Anti-Sm (marker autoantibody) • False + syphillis for >6 months • + ANA • + anti-phospholipid AB • Abnormal IgG or IgM anti-cardiolipin • + lupus anticoagulant • Active inflammation noted by decreased complements (C3, C4, CH50)

39. SLE • Treatment • Avoid sunlight • Adequate rest, exercise, no smoking, good diet • NSAIDS to COX-2 inhibitors for joint symptoms IF NO CKD • Corticosteroids (low dose) • Plaquinil 200mg BID for cutaneous, joint, pleural, and pericardial sx • Immunosuppressants- Imuran, Cytoxan, Cellcept, methotrexate • Rheumatology Referral for continued care

40. SLE • Treatment • Prevent End Organ damage • CBC • ESR/CRP • Creatinine, UA, Urine protein:creatinine • Liver function tests • CXR • EKG

41. RA and SLE • Cytoxan • For severe disease only • Rheumatology only • Chemotherapeutic • Monthly IV • Severe side effects-gonadal ablation, alopecia, bladder hemmorhage, malignancy • Rituxan-in FDA trials • Linked to “brain infections” in 2 study participants

42. Complications • Increased risk for infection • Osteoporosis • Renal Failure • Mild and treatable to ESRD • Must have kidney biopsy to guide treatment • Pleural hemorrhages