Hypogonadism

Hypothalamic-pituitary-gonadotropin axis

• HypothIalamus → anterior Pituitary →Pulsatile LH ,FSH

secretion

• Leydig cells →Testosterone

• Sertoli cells →Spermatogenesis

• Inhibin B →Negative feedback for FSH

 Types

• Primary ( Hypergonodotropic hypogonodism)

• Secondary ( Hypogonodotropic hypogonodism)

 Hypogonodotropic hypogonadism

• Due to impaired secretion of FSH and LH

• Testosterone - low

• FSH, LH - Low or Normal

 Congenital Gonadotropin Deficiency

• Mutations in genes involved in development and migration of GnRH neurons or in

regulation of GnRH secretion
 Syndromes associated with Congenital gonodotropin
deficiency

• CHARGE syndrome

• Adrenal hypoplasia Congenita

• Prader - Willi syndrome

• Lawrence Moon syndrome

 CHARGE SYNDROME

• Mutations in the CHD7 gene that encodes for the chromodomain helicase DNA
binding protein 7

• CHARGE syndrome characterized by eye coloboma, heart anomalies, choanal

atresia, growth and developmental retardation, genitourinary anomalies,
hypogonadism, and ear abnormalities.
 Adrenal hypoplasia congenita
• Mutations in the DAX1 gene, which encodes a nuclear receptor in the adrenal
gland and reproductive axis.

• Adrenal hypoplasia congenita is characterized by absent development of the adult

zone of the adrenal cortex, leading to neonatal adrenal insuffi- ciency.

• Puberty usually does not occur or is arrested, reflecting variable degrees of

gonadotropin deficiency. Although sexual differentiation is normal, some patients
have testicular dysgenesis and impaired spermatogenesis despite gonadotropin
replacement.
 Prader-Willi syndrome

• Prader-Willi syndrome (PWS) is characterized by obesity, hypo- tonic

musculature, intellectual disability, hypogonadism, short stat- ure, and small hands
and feet.

• Prader-Willi syndrome is a genomic imprinting disorder caused by deletions of the

proximal portion of the paternally derived chromosome 15q11-15q13 region,
which contains a bipartite imprinting center; uniparental disomy of the maternal
alleles; or mutations of the genes/loci involved in imprinting.
 Acquired Gonodotropin deficiency
• Severe illness

• Stress

• Malnutrition

• Exercise

• Obesity

• Hyperprolactinemia

• Opioid/ cannabis use

• Sellar mass lesions

 Laurence Moon syndrome

• Laurence-Moon syndrome is an autosomal recessive disorder char- acterized by

obesity, hypogonadism, mental retardation, polydactyly, and retinitis pigmentosa.

• Recessive mutations of leptin, or its receptor, cause severe obesity and pubertal
arrest, apparently because of hypo-thalamic GnRH deficiency.
 Primary Hypogonadism
• Congenital causes :

• Klinefelter syndrome (47,XXY, male phenotype)

• Turner syndrome (45,X, female phenotype)

• Cryptorchidism/Anarchidism in males

• Disorders of sexual development

• Steroid biosynthetic defects

Clinical Features of Chromosomal Disorders of Sex Development
• Acquired causes :

• Viral orchitis

• Leprosy

• Cancer chemotherapy

• Therapeutic radiation for ALL

• Drugs like Ketoconazole, Spironolactone, Chemotherapy

• Excessive alcohol

• Pesticides

• Industrial pollutants like heavy metals

• Microwaves

• Polyglandular autoimmune insufficiency

• Systemic illness like cirrhosis, CKD - hyperprolactinemia, Sickle cell anaemia - testicular atrophy
 Clinical features
• Decreased sex drive

• Inability to maintain erections

• Reduced beard growth

• Loss of muscle mass

• Decreased testicular size

• Gynecomastia
Laboratory Evaluation
 Management

• Testosterone replacement is clearly indicated in younger men with significant

hypogonadism to prevent osteoporosis and to restore muscle power and libido.

• Testosterone therapy can aggravate prostatic carcinoma; prostate-specic

antigen (PSA) should be measured before commencing testosterone therapy in
men older than 50 years and monitored annually thereafter.

• Haemoglobin concentration should also be monitored, as androgen replacement

can cause polycythaemia.
Thank You