DR. RICHARD JORDANDR. RICHARD JORDAN

PROFESSOR OF MEDICINE AND PROGRAM DIRECTOR

CHIEF, DIVISION OF ENDOCRINOLOGY AND METABOLISM

J. H. QUILLEN VA MEDICAL CENTER & EAST TENESSEE STATE UNIVERSITY

JOHNSON CITY, TN

MALE MALE HYPOGONADISMHYPOGONADISM

Secondary HypogonadismSecondary Hypogonadism(Hypogonadotrophic Hypogonadism)(Hypogonadotrophic Hypogonadism)

Kallmann Syndrome

Idiopathic Gonadotrophin Deficiency

Selective Gonadotrophin Deficiency

Prader-Will Syndrome

Acquired Gonadotrophin Deficiency

(Continued)

Secondary HypogonadismSecondary Hypogonadism(Hypogonadotrophic Hypogonadism)(Hypogonadotrophic Hypogonadism)

Kallmann Syndrome

Absent or Deficient GnRH (Mild to Severe)

Eunuchoid with Variable Expression of Hypogonadism, Anosmia, or Hyposmia, R/G Color

Blindness, Cleft Palate, GU Tract Abnormalities, Neurosensory Deafness

Genetics: Sporadic, Dominant, Recessive, X-linked

Etiology: Absent neural cell adhesion molecule (anosmin) in 0-14%, KAL Gene Point Mutation

(Continued)

Secondary HypogonadismSecondary Hypogonadism(Hypogonadotrophic Hypogonadism(Hypogonadotrophic Hypogonadism))

Idiopathic Gonadotrophin Deficiency

No Somatic Abnormalities, No Ansomia, No KAL,

Gene Mutation, Abnormal GnRH Receptor in a Few

Selective Gonadotrophin Deficiency

Isolated LH Deficiency: “Fertile” Eunuch, Absence Virilization with Spermatogenesis

Isolated FSH Deficiency: Somewhat Small Testis, Oligospermia to Azospermia, Normal Virilization

(Continued)

Secondary HypogonadismSecondary Hypogonadism(Hypogonadotrophic Hypogonadism)(Hypogonadotrophic Hypogonadism)

Prader-Willi Syndrome

Obesity, Hypotonia, Hypogonadotrophic Hypogonadism, Retardation, Small Hands and Feet

(Continued)

Secondary HypogonadismSecondary Hypogonadism(Hypogonadotrophic Hypogonadism)(Hypogonadotrophic Hypogonadism)

Acquired Gonadotrophic Deficiency

Prolactinoma

Other Pituitary Tumors

Hypothalamic Tumors

Infiltrative Disorders

Hemochromatosis

Eosinophilic Granuloma

Sarcoidosis

Clinical EvaluationClinical Evaluation

History

Diminished Libido, Weakness, Erectile Dysfunction,

Behavior Abnormalities, Systemic Illness, Headache,

Visual Changes, Multiple Hormone Deficiencies,

Chemotherapy, Radiation Rx, Orchitis, Toxin Exposure,

Anosmia, Family History of Delayed Puberty

(Continued)

Clinical EvaluationClinical Evaluation

Physical Examination

Eunuchoid Proportions, Size of Testis, Gynecomastia,

Characteristic Dysmorphic Features, Secondary Sex

Characteristics Slow to Change

Laboratory EvaluationGonadal Function

Semen AnalysisSperm Count – 20 million/ml, 40 million/ejaculate, >50% normal motility, >30% normal morphology

Testosterone—Total or Free?Decreased Binding—Obesity, Hypothyroidism, AcromegalyIncreased Binding—Old Age, Cirrhosis, ThyrotoxicosisTestosterone Lower in the Afternoon

GonadotropinsLH: Elevated with Leydig Cell DysfunctionFSH: Elevated with Germinal Cell Dysfunction or Leydig Cell DysfunctionGonadotrophins: Normal or Low with Secondary Hypogonadism

TherapyTherapySecondary Hypogonadism1. HCG—1000u 3 times weekly HMG—75u 3 times weekly2. GnRH pulses (pulse q 90 min)

Primary Hypogonadism1. Testosterone Ester Injection2. Testosterone Patch—5 mg/day3. Testosterone Gel—Upper Arms, Shoulders, Abdomen

Side EffectsExacerbation of BPH, Occult Prostate Cancer, Erythrocytosis,Sleep Apnea

Primary Hypogonadism(Hypergonadotrophic Hypogonadism))

Klinefelter SyndromeXX Male (Sex Reversal)Noonan Syndrome (Male Turner Syndrome)Myotonic DystrophyCongenital Anorchia (Vanishing Testis Syndrome)Sertoli-Cell-Only SyndromeAcquired Germinal Cell AplasiaOrchitisChronic Illnesses

(Continued)

Primary Hypogonadism(Hypergonadotrophic Hypogonadism)

Klinefelter Syndrome

46 XXY, 46 XY/XXY, 48 XXXY

Eunuchoid lower segment, Taller than Average, Gynecomastia,

Gynecoid Features, Very Small Testis, Normal to Low

Testosterone, FSH increase >LH, Modest Elevation of Estradiol,

Severe Oligospermia to Azospermia

Associated Conditions: COPD, Cancer of Breast, Germ Cell Tumors, Autoimmune Diseases, Diabetes Mellitus, Osteopenia, Mitral Valve Prolapse, Mental Slowness, Antisocial Behavior

(Continued)

Primary Hypogonadism(Hypergonadotrophic Hypogonadism)

XX Male (Sex Reversal)

Translocation of the SRY gene, Shorter than Average, Normal

Intelligence, Gynecomastia, Small Testis, Azospermia

Noonan Syndrome (Male Turner Syndrome)

46 XY, Short Stature, Webbed Neck, Shield

Chest, Small Testis, Impaired

Spermatogenesis, May Have Low Testosterone

Associated Conditions: Mental Retardation, Pulmonary Stenosis, Hypertrophic Cardiomyopathy, Tyrosine Phosphase Activation?

(Continued)

Primary Hypogonadism(Hypergonadotrophic Hypogonadism)

Myotonic Dystrophy

Autosomal Dominant

Inability to Relax Striated Muscle, Frontal Balding,

Ptosis, Cataracts, Atrophy of Facial Muscles, Distal Muscle

Wasting, Testicular Atrophy after Puberty

Associated Conditions: Cardiomyopathy with Conduction

Abnormalities, Type II Diabetes Mellitus, Mental Retardation,

Decreased Myotonin (transfers phosphate to ATP)

(Continued)

Primary Hypogonadism(Hypergonadotrophic Hypogonadism)

Congenital Anorchcia (Vanishing Testis Syndrome)

46XY, No Discernable Testicular Tissue in Most, Bilateral Testicular Torsion in Utero?

HCG Stimulation—Detect Testicular Remnants

Sertoli-Cell-Only Syndrome

46XY, Germinal Cell Aplasia, FSH>LH

Testosterone Normal

Sertoli Cells Vacuolated—Functional Abnormality?

(Continued)

Primary Hypogonadism(Hypergonadotrophic Hypogonadism)

Acquired Germinal Cell AplasiaChemotherapy, Radiation, Environmental Toxins(Dibromodichloralpropane)

OrchitisPost-Pubertal Mumps: 40% have Orchitis, 40% with Orchitis have Varying Degrees of Testicular Atrophy, Sperm Count Lower in Most with Atrophy but True Impaired Fertility in 15%Autoimmune Orchitis: Type I and II endocrine deficiency

Chronic IllnessesCirrhosis, Chronic Renal Failure, Long-Term Glucocorticoid Therapy