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Hypogonadism final

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hypogonadism

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Hypogonadism final

  1. 1. HYPOGONADISM DEPT OF ENDOCRINOLOGY CHIEF:DR.SANGUMANI MD ASST PROF:DR.SRIDHAR MD DM DR.SOMASUNDHARAM MD
  2. 2. NORMAL PUBERTAL DEVELOPEMENT
  3. 3. ANDROGEN METABOLISM AND ACTIONS
  4. 4. LH SECRETORY PATTERN
  5. 5. IN A PT WITH HYPOGONADOTROPIC HYPOGONADISM
  6. 6. FETAL ANDROGEN DEFECIENCY
  7. 7. PRE PUBERTAL ANDROGEN DEFICIENCY- SYMPTOMS
  8. 8. SIGNS OF ANDROGEN INSUFFIENCY
  9. 9. PSYCHOLOGICAL SYMPTOMS PSYCHOLOGICAL Poor concentratio n and memory Fine facial skin wrinkling(l ateral to orbit and mouth) Increased sleepiness Feeling sad or blue /irritability
  10. 10. HYPOGONADISM
  11. 11. PRIMARY AND SECONDARY SUB CLASSIFICATIONS
  12. 12. PRIMARY HYPOGONADISM –COMBINED DEFECIENCY OF ANDROGEN AND SPERM PRODUCTION CONGENITAL • Klinefelter • Myotonic dystrophy • Noonan • B/L Cong. Anorchia • Down Syndrome • LH Receptor Mutations • Poly glandular Autoimmune Syndrome ACQUIRED • B/L Surgical Castration • Drugs • Radiation SYSTEMIC • CKD • CLD • Aging • Malignancy • Sickle Cell • Spinal Cord Injury • Infiltrative Disorders
  13. 13. PRIMARY HYPOGONADISM-ISOLATED IMPAIREMENT OF SPERM PRODUCTION CONGENITAL • Cryptorchidism • Varicocele • Down • Myotonic Dystrophy • Sertoli Cell Only Syndrome • Primary Ciliary Dyskinesia ACQUIRED • Orchitis • Radiation • Drugs SYSTEMIC • Acute Febrile Illness • Malignancy • Idiopathic Azoospermia • Spinal Cord Injury
  14. 14. SECONDARY HYPOGONADISM –COMBINED ANDROGEN DEFICIENCY AND SPERM PRODUCTION CONGENITAL Constitutional Hemochromatosis IHH ACQUIRED Hyperprolactinemia Drugs Hypopituitarism Lymphocytic. SYSTEMIC Glucocorticoid Excess Chronic Organ Failure Chr. Systemic Illness
  15. 15. SECONDARY HYPOGONADISM-ISOLATED IMPAIREMENT OF SPERM PRODUCTIONCONGENITAL CONGENITAL ADRENAL HYPERPLASIA Isolated FSH Deficiency FSH-ß Mutations ACQUIRED Testosterone And Anabolic Steroids Malignancy Hyper prolactinemia Androgen Secreting Tumors
  16. 16. KLINEFELTER’S SYNDROME 47xxy(mater nal non dysjunction) Small firm testis,eunuchoidi sm,azoospermia, inc Gnrs Taurodontism, increased lower segment Cag repeats Systemic disorders
  17. 17. HORMONAL PROFILE IN A PATIENT WITH KLINEFELTER
  18. 18. CONGENITAL DISORDERS CNTD…. CRYPTORCHIDISM B/L CONGENITAL ANORCHIA(Vanishing testes syn./testicular regression sequence) Premature/LBW/ SGA Testicular dysgenesis Azoospermia- 50%,oligo-75% Ectopic/r etractile testis Phenotypically and genotypically male B-hcg stimulati on testing Amh
  19. 19. CNTD…. Apeced-1(primary hypogonadism) Type 2-circulating steroid cell antibodies DOWN SYNDROME Primary Hypogonadism With Selective Elevation Of Fsh CAH CAH Testicular Adrenal Rest Tumours Increased Androgen-sec Hypogonadism Treatment With Steroids Reduces Tumour Size But Semniferous Atrophy And Leydig Loss
  20. 20. EXTERNAL INFLUENCES LH RECEPTOR MUTATIONS • Micropenis • Hypospadias • Undervirilization DRUGS AND RADIATION • Ketoconazole>400 Mg/D • Spironolactone • Active Cell Replication • Radiation 600-800 Cgy INFECTIONS •Mumps-10days after parotitis,orchitis even. clinically u/l degenerative changes occur b/l •HIV per se –sec hypogonadism •primary in HIV oppurtunistic(cmv,mac,toxoplasmosis)
  21. 21. SYSTEMIC DISEASES increased SHBG,dec free testosterone Alcohol increases estrogen synthesis Prolactin-supresses FSH,LH Spironolactone(ascites)- supresses androgen CHRONIC LIVER DISEASE
  22. 22. CNTD… Combined Primary And Secondary Increased FSH,LH due to reduced clearance HD/PD does not restore testosterone levels Transplantation restores testosterone. CHRONIC KIDNEY DISEASE
  23. 23. SECONDARY HYPOGONADISM
  24. 24. GROWTH PATTERNS
  25. 25. HEMOCHROMATOSIS Hemochromatosis presents with combined secondary hypogonadism Occurs when serum ferritin levels exceed 1500 micro/dl. With hepatic cirrhosis ,SHBG levels increases reducing levels of free testosterone. Hypogonadism reverses with therapeutic phlebotomy early in trhe course of iron overload
  26. 26. IHH Fail to undergo puberty with incomplete sexual maturation low FSH,LH and low testosterone(absent pulsatile LH) 60%present with hyposmia isolated Gntr defeciency with otherwise normal pituitary function. IHH(hypogonadotropic eunuchoidism)
  27. 27. KALLMAN AND VARIANTS
  28. 28. ACQUIRED DISORDERS
  29. 29. SYSTEMIC DISEASES CUSHING SYNDROME Hypothalamic Inhibition Of Gnrh,direct Effect On Testis Doses As Low As 7.5 Mg/Dl Can Cause Hypogonadism. CHRONIC LIVER DISEASE Regardless Of Etiology- primary In Mild To Moderate Secondary In Severe COPD Hypoxia Malnutrition Steroids
  30. 30. CNTD… nutritional/anorexia-3-5 days of starvation supresses GnRH,testosterone Adequate food intake and weight gain replaces LH pulse Chronic endurance exercise Acute starvation supresses leptin.HUMAN r LEPTIN increase testosterone. Moderate obesity-secondary hypogonadism
  31. 31. SHBG CONCENTRATIONS
  32. 32. HORMONAL PROFILE
  33. 33. GOALS OF THERAPY RESTORE LIBIDO AND ERCETILE FUNCTION INCRASE MUSCLE MASS AND STRENGTH AND IMPROVING PHYSICAL FUNCTION AND PERFORMANCE INCREASE BMD HEMATOC RIT MALE HAIR GROWTH
  34. 34. PRINCIPLES OF THERAPY TO TREAT ANDROGEN DEFECIENCY • PARENTERAL(Tes. Enanthate/Cypionate/Undecanoate) • TRANSDERMAL(Non Scrotal Patch/1% Gel) • TRANSBUCCAL TO INITIATE AND MAINTAIN SPERM PRODUCTION IN MEN WITH HYPO. HYPOGONADISM • Added Initially To Stimulate Testosterone And Sperm Production(HCG) • ADDED TO HCG TO STIMULATE SPERM Production(FSH,hMG,hFSH/rhFSH) • TO STIMULATE SPERM Production(GnRH)
  35. 35. SERUM TOTAL TESTOSTERONE CONC IN MEN TREATED WITH TES.ENANTHATE FOR 12 WEEKS
  36. 36. TOTAL SPERM COUNT RESPONSE TO GONADOTROPIN THERAPY
  37. 37. MONITORING DURING THERAPY
  38. 38. NEWER FORMULATIONS TESTOSTERONE BUCICLATE SUBLINGUAL/BUCCAL TESTOSTERONE SARM- ENOBOSARM,LIGANDROL(under preclinical testing)

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