Download - Hypogonadism final
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HYPOGONADISM
DEPT OF ENDOCRINOLOGYCHIEF:DR.SANGUMANI MD ASST PROF:DR.SRIDHAR MD DM DR.SOMASUNDHARAM MD
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NORMAL PUBERTAL DEVELOPEMENT
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ANDROGEN METABOLISM AND ACTIONS
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LH SECRETORY PATTERN
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IN A PT WITH HYPOGONADOTROPIC HYPOGONADISM
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FETAL ANDROGEN DEFECIENCY
AMBIGOUS GENITALIA
Microphallus
Pseudovaginal
Perineoscrotal Hypospadias
Bifid Scrotum
Cryptorchidism
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PRE PUBERTAL ANDROGEN DEFICIENCY-SYMPTOMS
DELAYED PUBERTY
• Loss Of Libido• Reduced Nighttime Or
Morning Spontaneous Erections
• Reduced Motivation And Initiative
• Dimi. Strength And Physical Performance
• Breast Enlargement And Tenderness
• No Spermarche/Infertility
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SIGNS OF ANDROGEN INSUFFIENCY
eunuchoidism,
Infantile genitalia
Small testis
Loss of male hair pattern
DispoportionatelyLong arms and legs relative
to heightAdults-low bone mineral
density
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PSYCHOLOGICAL SYMPTOMS
PSYCHOLOGICAL
Poor concentration and memory
Fine facial skin wrinkling(lateral
to orbit and mouth)
Increased sleepiness
Feeling sad or blue
/irritability
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HYPOGONADISM
PRIMARY
•Androgen Def. With Impaired Sperm Production•Isolated Impairment In Sperm Production
SECONDARY
•Androgen Def. With Impaired Sperm Production•Isolated Impairment In Sperm Production
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PRIMARY AND SECONDARY SUB CLASSIFICATIONS
COMBINED ANDROGEN AND SPERM
Congenital Acquired Systemic
ISOLATED IMPAIREMENT IN SPERM PRODUCTION
Congenital Acquired Systemic
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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
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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
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SECONDARY HYPOGONADISM –COMBINED ANDROGEN DEFICIENCY AND SPERM PRODUCTION
CONGENITAL
Constitutional
Hemochromatosis
IHH
ACQUIRED
Hyperprolactinemia
Drugs
Hypopituitarism
Lymphocytic.
SYSTE
MIC
Glucocorticoid Excess
Chronic Organ Failure
Chr. Systemic Illness
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SECONDARY HYPOGONADISM-ISOLATED IMPAIREMENT OF SPERM PRODUCTION
CONGENITA
L
CONGENITAL ADRENAL HYPERPLASIA
Isolated FSH Deficiency
FSH-ß Mutations
ACQUIREDTestosterone And Anabolic SteroidsMalignancyHyper prolactinemiaAndrogen Secreting Tumors
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KLINEFELTER’S SYNDROME47xxy(ma
ternal non
dysjunction)
Small firm testis,eunuchoidism,azoospermia,inc
Gnrs
Taurodontism,increased lower segment
Cag repeats
Systemic disorders
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HORMONAL PROFILE IN A PATIENT WITH KLINEFELTER
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CONGENITAL DISORDERS CNTD….
CRYPTORCHIDISM B/L CONGENITAL ANORCHIA(Vanishing testes syn./testicular regression sequence)
Premature/LBW/SGA
Testicular dysgenesis
Azoospermia-50%,oligo-75%
Ectopic/retractile testis
Phenotypically and genotypically male
B-hcg stimulation testing
Amh
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CNTD….
Apeced-1(primary hypogonadism)
Type 2-circulating steroid cell antibodies
DOWN SYNDROMEPrimary
Hypogonadism With Selective Elevation
Of Fsh
CAH
CAHTesticular Adrenal Rest
TumoursIncreased Androgen-sec
HypogonadismTreatment With Steroids Reduces Tumour Size But Semniferous Atrophy And
Leydig Loss
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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)
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SYSTEMIC DISEASESincreased SHBG,dec free testosterone
Alcohol increases estrogen synthesis
Prolactin-supresses FSH,LH
Spironolactone(ascites)-supresses androgen
CHRONIC LIVER
DISEASE
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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
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SECONDARY HYPOGONADISMCONSTITUTIONAL DELAY IN
GROWTH AND PUBERTY
CDGP-transient secondary hypogonadism cause of delayed puberty in 65%.
Delayed puberty suspected if sexual maturation and testis size less than 4ml
at 14yrs os age.
Increased prevalence in families with IHH.so considered a variant of IHH
Height age and bone age less than chronological age.
Eventually boys with CDGP undergo normal growth and sexual
development
Normal height is attained but midparental height may not be
acheieved.
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GROWTH PATTERNS
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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
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IHH
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KALLMAN AND VARIANTST
1-KAL1
Failure Of Gnrh Neuronal MigrationSynkinesiaU/L Renal Agenesis
T2-FGFR
Normosmic IHHDental AbnormalitiesCleftlipSyndactylyBrachydactyly
T3/
4-PROK,PROKR
severe kallmans to normosmic IHH
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ACQUIRED DISORDERS
•Prolactin Secreting Adenoma(>250ng/Dl)•Pituitary Stalk Deisease(stalk Compression From Non Prolactin Adenoma,traumatic)-dopamine Mediated(20-250 Ng/Dl)
HYPERPROLACTINEMIA
•Antipsychotics/prokinetics/antihypertensives•<100ng/dl
DRUGS•Mild hyperprolactinemia does not cause clinically significant hypogonadism•Long standing and severe-enlarged pituitary
HYPOTHYROIDISM
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SYSTEMIC DISEASES
CUSHING SYNDROMEHypothalamic Inhibition Of Gnrh,direct Effect On
TestisDoses As Low As 7.5
Mg/Dl Can Cause Hypogonadism.
CHRONIC LIVER DISEASE
Regardless Of Etiology-primary In Mild To
ModerateSecondary In Severe
COPDHypoxia
MalnutritionSteroids
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CNTD…nutritional/anorexia-3-5 days of starvation
supresses GnRH,testosteroneAdequate food intake and weight gain replaces LH
pulse
Chronic endurance exercise
Acute starvation supresses leptin.HUMAN r LEPTIN increase testosterone.
Moderate obesity-secondary hypogonadism
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SHBG CONCENTRATIONS
MODERATE OBESITYT2-DM
NEPHROTIC SYNDROMECORTICOIDS
ADROGENS,PROGESTINSHYPOTHYROIDISM
ACROMEGALY
AGINGHEPATIC CIRRHOSIS
ESTROGENSHYPERTHYROIDISMANTICONVULSANTS
HIV
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HORMONAL PROFILE
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GOALS OF THERAPY
RESTORE LIBIDO AND ERCETILE
FUNCTION
INCRASE MUSCLE MASS AND
STRENGTH AND IMPROVING
PHYSICAL FUNCTION AND PERFORMANCE
INCREASE BMD
HEMATOCRIT
MALE HAIR GROWTH
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PRINCIPLES OF THERAPY
TO TREAT AN
DROGEN DEFECIENCY
•PARENTERAL(Tes. Enanthate/Cypionate/Undecanoate)•TRANSDERMAL(Non Scrotal Patch/1% Gel)•TRANSBUCCAL
TO INITIATE AND MAINTAI
N SPER
M PRODUCTION
IN MEN WIT
H 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)
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SERUM TOTAL TESTOSTERONE CONC IN MEN TREATED WITH TES.ENANTHATE FOR 12 WEEKS
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TOTAL SPERM COUNT RESPONSE TO GONADOTROPIN THERAPY
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MONITORING DURING THERAPY
INCREASED Hcr(IF Hcr>54% REDUCE DOSAGE UNTIL Hcr REUCES TO
NORMAL AND REINITIATE AT LOWER DOSE)
PSA increase>1.4 ng/ml within 12mnth period
PSA velocity >0.4 ng/ml/yr after 6mnths of treatment with
TESTOSTERONENodule/induration on DRE
AUA/IPSS SCORE>19
OSAS
ERYTHROCYTOSIS HYPERTENSION CCF /WEIGHT GAIN
ACNE AND OILY SKIN GYNECOMASTIA
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NEWER FORMULATIONS
TESTOSTERONE BUCICLATE SUBLINGUAL/BUCCAL TESTOSTERONE
SARM-ENOBOSARM,LIGANDROL(under
preclinical testing)
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