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Metabolic and Thyroidal Dysfunction in HIV

Metabolic and Thyroidal Dysfunction in HIV. Louis Haenel, IV, DO Endocrinology. Terminology. Lipodystrophy Lipoatrophy Lipohypertrophy HIV HAART (Highly Active Anti-Retroviral Therapy). Facial lipoatrophy. Buffalo Hump. Peripheral Lipoatrophy. Body-Fat Abnormalities.

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Metabolic and Thyroidal Dysfunction in HIV

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  1. Metabolic and Thyroidal Dysfunction in HIV Louis Haenel, IV, DO Endocrinology

  2. Terminology • Lipodystrophy • Lipoatrophy • Lipohypertrophy • HIV • HAART (Highly Active Anti-Retroviral Therapy)

  3. Facial lipoatrophy

  4. Buffalo Hump

  5. Peripheral Lipoatrophy

  6. Body-Fat Abnormalities • Reported in 40-50% of ambulatory HIV-infected patients • Preliminary case definition by DEXA and CT imaging not ready for widespread clinical practice • Central fat accumulation tends to be visceral in location

  7. Etiology • HIV – Direct virus mediated effect • Protease Inhibitor • Nucleoside analogue reverse-transcriptase inhibitors • Nonnucleoside reverse transcriptase inhibitors • Cytokine mediated effect (Adipocytokine)

  8. Pathogenesis • Inhibiting sterol regulatory enhancer- binding protein 1 (SREBP1) mediated activation of retinoid X and PPARλ • Disruption of adipogenesis • Inhibit mitochondrial DNA polymerase alpha (DNA replication) • TNFα receptor alteration

  9. Clinical Implications • Physical changes • Hypertriglyceridemia • Low HDL cholesterol • Modest increases in LDL cholesterol • Increased diastolic BP • Increased Metabolic syndrome profile • Increased cardiovascular risk

  10. Update on Lipodystrophy Dr. Louis C. Haenel, IV Endocrinology UMDNJ-SOM Volunteer Faculty

  11. Dyslipidemia • Cholesterol elevation seen in 27% pts on combination tx (>240 mg/dl) • Triglyceride elevation seen in 40% pts (>200 mg/dl) • HDL <35 mg/dl seen in 27%

  12. .

  13. Carbohydrate Metabolism • Impaired glucose tolerance seen in more than 35% of HIV infected pts compared to 5% in age and BMI matched controls • DM was 3.1X as likely to develop in HIV pts treated with combination therapy vs control population

  14. Pathogenesis • ↑ circulating free fatty acids • Accumulation of intramyocellular lipids • Low level of adiponectin • Reduced pparα activity which leads to reducing glucose transport mediated via Glut4 transporter • Reduce Beta cell insulin secretion

  15. Assessment • Before initiating HIV therapy, patients should be tested for fasting blood glucose and cholesterol levels • Rechecked several weeks after change in therapy and yearly • Oral glucose tolerance test

  16. Cardiovascular Disease • Diabetes Mellitus is considered a coronary risk equivalent • Established risk factors • Hypertension is seen at higher rates in patients in HAART therapy than for age-matched controls • PI therapy may promote atherosclerosis by ↑ CD-36 dependent cholesterol ester accumulation in macrophages

  17. Risk Factor Modification • Dyslipidemia • Hypertension • Insulin resistance • Sedentary lifestyle • Weight • Family history • Tobacco

  18. Treatment of Lipodystrophy • Change in HAART therapy • Exercise • Metformin • Thiazolidinediones • Leptin • Recombinant Growth Hormone therapy • Recombinant testosterone therapy • Oral testosterone therapy

  19. Treatment of Metabolic Syndrome • Diet • Exercise • Metformin • Thiazolidinediones • Additional diabetes mellitus treatment strategies

  20. Treatment of Hypertension • Ace inhibitor therapy • Angiotensin receptor blocker therapy • Hydrochlorothiazide • Beta blocker therapy

  21. Treatment of Dyslipidemia • Fibric Acid derivatives (Tricor, Lopid) • Cholesterol absorption inhibitors (Zetia) • Thiazolidinediones • Statin therapy • Pravachol • Crestor • Beware of Lescol, Zocor, Mevacor

  22. Improvement of Appearance • Surgery • Liposuction • Injectable agents • Polylactic acid (promotes collagen formation)

  23. Thyroid • Infectious and Infiltrative Diseases • Laboratory • Medication

  24. Infectious/Infiltrative Diseases • CMV *MAI • Cryptococcus *PCP • Kaposi’s Sarcoma • True Infection vs Postmortem Findings • Inflammatory Thyroiditis

  25. Laboratory Findings • Lowered T3 Levels • 46 patients evaluated and found to have  T3 levels and normal TSH in stable HIV • T3 levels on admission correlated to mortality in 3 separate studies • T3 seems to follow typical trend seen in euthyroid sick individuals but rT3 levels remain low in asymptomatic and ill pts.

  26. Thyroid Labs • TBG levels are  with normal CBG & SHBG • TSH values in stable HIV are higher on average than controls with the absolute levels in the upper limit of normal • Normal pulse frequency and  amplitude • Role of cytokines -- IL-6 and TNF

  27. HIV Related Medications • Rifampin (used in the treatment of MAI prophylaxis) induces hepatic microsomal enzymes and increases thyroid hormone clearance • Results >  T4 (T4 replace requires  dose) normal T3  rT3 no change in TSH

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