Hypogonadism (male)

Question 1

Define

Answer 1

Failure of testis to produce testosterone, sperm or both

Question 2

Causes

Answer 2

PRIMARY: Due to testicular failure

• Local trauma, torsion, chemotherapy/irradiation
• Infection: Post-orchitis, e.g. mumps, HIV
• AI
• Iatrogenic (chemotherapy, surgery, radiation)
• Renal failure, liver failure or alcohol excess (toxic to Leydig cells)
• Chromosomal abnormalities, e.g. Klinefelter’s syndrome (most common cause of primary hypogonadism)

*Klinefelter’s syndrome (47XXY) - delayed sexual development, small tests and gynecomastia

SECONDARY: Due to ↓gonadotropins (LH and FSH)

• Hypopituitarism
• Prolactinoma (inhibits GnRH secretion)
• Kallmann’s syndrome
• Systemic/chronic illness (e.g. COPD, HIV, DM)
• Laurence–Moon–Biedl and Prader–Willi syndromes
• Age

*Kallmann’s syndrome - isolated GnRH deficiency, with anosmia and colour blindness
Prader–Willi syndrome: Loss of acritical region on Chr15 causing obesity and short stature, small hands, almond-shaped eyes, learning difficulty/postnatal hypotonia

Laurence–Moon–Biedl syndrome: Obesity, polydactyly, retinitis pigmentosa, learning difficulty

Question 3

Epidemiology

Answer 3

primary hypogonadism accounts for 30–40% of cases of male infertility; secondary hypogonadism accounts for ~2%

Question 4

Symtpoms

Answer 4

Symptoms

• ↓Libido
• Impotence, erectile dysfunction, ↓spermatogenesis
• Infertility

Signs

• Small testis
• Loss of pubic/axillary/facial hair
• ↓Muscle bulk
• ↑Fat
• Gynecomastia
• Osteoporosis
• ↓Mood

If Prepubertal → virilisation, delayed and incomplete puberty

Question 5

Investigations

Answer 5

Low serum oestradiol

Serum FSH/LH

• Primary hypogonadism = HIGH
• Secondary hypogonadism = LOW

Primary Hypogonadism Investigations

• Karyotype (look for chromosomal abnormalities)
• Pelvic imaging (US or MRI) - performed in primary amenorrhoea to check for structural defects (e.g. androgen insensitivity)
• Screen for FMR1 gene in patients with unexplained pre-mature ovarian failure

Secondary Hypogonadism Investigations

• Pituitary function tests (e.g. 9 am cortisol, TFTs, prolactin)
• Visual field testing
• Hypothalamic-pituitary MRI
• Smell tests for anosmia
• Serum transferrin saturation (check for haemochromatosis)

Investigating associated conditions

• Turner’s Syndrome - periodic echocardiography, renal US
• Autoimmune Oophoritis - check autoimmune adrenal insufficiency