hypogonadism

1. HYPOGONADISM
DEPT OF ENDOCRINOLOGY
CHIEF:DR.SANGUMANI MD
ASST PROF:DR.SRIDHAR MD DM
DR.SOMASUNDHARAM MD

2. NORMAL PUBERTAL DEVELOPEMENT

3. ANDROGEN METABOLISM AND ACTIONS

4. LH SECRETORY PATTERN

5. IN A PT WITH HYPOGONADOTROPIC HYPOGONADISM

6. FETAL ANDROGEN DEFECIENCY

7. PRE PUBERTAL ANDROGEN DEFICIENCY-
SYMPTOMS

8. SIGNS OF ANDROGEN INSUFFIENCY

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. HYPOGONADISM

11. PRIMARY AND SECONDARY SUB
CLASSIFICATIONS

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. 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. 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. 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. 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. HORMONAL PROFILE IN A PATIENT WITH KLINEFELTER

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. 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. 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. SYSTEMIC DISEASES
increased SHBG,dec free
testosterone
Alcohol increases
estrogen synthesis
Prolactin-supresses
FSH,LH
Spironolactone(ascites)-
supresses androgen
CHRONIC LIVER
DISEASE

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. SECONDARY HYPOGONADISM

24. GROWTH PATTERNS

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. 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. KALLMAN AND VARIANTS

28. ACQUIRED DISORDERS

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. 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. SHBG CONCENTRATIONS

32. HORMONAL PROFILE

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. 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. SERUM TOTAL TESTOSTERONE CONC IN MEN TREATED WITH
TES.ENANTHATE FOR 12 WEEKS

36. TOTAL SPERM COUNT RESPONSE TO
GONADOTROPIN THERAPY

37. MONITORING DURING THERAPY

38. NEWER FORMULATIONS
TESTOSTERONE BUCICLATE
SUBLINGUAL/BUCCAL
TESTOSTERONE
SARM-
ENOBOSARM,LIGANDROL(under
preclinical testing)