Hypogonadism (male and female) Flashcards
Which male hypogonadism presents with anosmia and infertility?
Kallmann syndrome - due to a failure of GnRH secretion; patients characteristically suffer from anosmia.
Which male hypogonadism presents with above average height, infertility and gynaecomastia?
Klinefelter’s syndrome
- chromosomal disorder caused by an additional X chromosome (i.e. a 47, XXY karyotype)
- –> small testes, infertility, gynaecomastia, above average height and a lack of secondary sexual characteristics.
Which male syndrome presents with dextrocardia and a history of recurrent sinusitis/bronchiectasis?
Kartagener’s syndrome
Define hypogonadism.
Hypogonadism refers to a condition in which little or no hormone is produced by the testes or ovaries.
The condition can be:
- hypergonadotropic is primary, resulting when the gonads fail so LH is high
- OR hypogonadotropic - can result from failure of the hypothalamic LHRH pulse generator or from the inability of the pituitary to respond with secretion of LH and FSH
What are the causes of primary and secondary hypogonadism in MALES?
Primary hypogonadism - Due to testicular failure, eg from
- Klinefelter’s syndrome (47XXY)—delayed sexual development, small testes, and gynaecomastia
- mutations in LH/FSH receptors
- local trauma, torsion, chemotherapy/irradiation, alkylators
- cryptorchidism (undescended testes)
- androgen biosynthesis disorders
- post-orchitis, eg mumps, hiv, brucellosis, leprosy
- autoimmune damage
- renal failure, liver cirrhosis, or alcohol excess (toxic to Leydig cells)
- varicocele
Secondary hypogonadism - ↓Gonadotropins (LH and FSH), eg from
- hypopituitarism
- prolactinoma
- Kallman’s syndrome—isolated gonadotropin-releasing hormone deficiency, often with anosmia and colour blindness
- systemic illness (eg COPD; HIV; DM)
- Laurence–Moon–Biedl and Prader–Willi syndromes
- Age
What are the causes of primary hypogonadism in FEMALES?
PRIMARY HYPOGONADISM
Congenital
- Turner syndrome (45,X karyotype),
- CAH -17α-hydroxylase deficiency
- Ovarian dysgenesis and agenesis
- Fragile X syndrome,
- Galactosaemia (inability to process the sugar galactose)
Acquired damage to ovaries:
- Medications, e.g. chlorambucil, cyclophosphamide, and alkylators
- Radiotherapy
- Autoimmune diseases e.g. autoimmune polyglandular syndrome type 1
- Viral e.g. mumps oophoritis, TB, malaria, varicella,
- Bacterial e.g. Shigella
- Iatrogenic e.g. post-oophorectomy
What are the causes of secondary hypogonadism in FEMALES?
Congenital
- Kallmann syndrome - gonadotrophin deficiency due to a genetic mutation
Acquired -damage to the pituitary/hypothalamus
- Intracranial space-occupying lesions (eg, tumours and cysts)
- Infiltrative disease eg, sarcoidosis and haemochromatosis
- Infection eg, meningitis and TB
- Pituitary apoplexy (bleeding into pituitary gland)
- Trauma.
Gonadotropins can be suppressed by:
- Chronic disease eg, diabetes, anorexia, obesity, and renal disease
- Excessive exercise → functional hypothalamic amenorrhoea
- Critical illness
- Chronic opiate, glucocorticoid, or anabolic steroid use
- Hyperprolactinaemia (an excess of the milk-inducing hormone prolactin).
What are the signs and symptoms of hypogonadism in females?
- Turner syndrome signs
- Ask age of menarchy
- Extent of androgenisation - pubic/axillary hair growth
- Extent of oestrogenisation - check breast development
After puberty
- Oligomenorrhoea/amenorrhoea
- Lower libido
- Loss of body hair
- Hot flushes
- Skin examination may show acanthosis nigricans, acne, and hirsutism (polycystic ovary syndrome) or purple striae (Cushing’s syndrome)
- Male-pattern baldness, deepening of the voice, wide distribution of terminal hair (male pattern), increase in muscle bulk, breast atrophy, and clitoromegaly, suggesting hyperandrogenaemia
Central causes:
- diplopia
- headaches
- vision impairment
What are the signs of Turner’s and Kleinfelter’s syndrome? (3)
Turner’s:
- short stature
- neck webbing
- wide carrying angle
- peripheral oedema
Klinefelter:
- tall stature and lack of secondary sexual characteristics
- gynaecomastia
- long legs, short trunk
- small firm testes
- infertile
- elevated gonadotrophin levels
What are the signs and symptoms of hypogonadism in males?
- Look for anomalies - hypospadias, micropenis, cryptorchidism
- Examine testes - position and consistency, check scrotum is fused
- Incomplete puberty
- Eunuchoid body
- Reduced secondary sex characteristics
- Virilisation reduced
Post pubertal:
- Gynaecomastia
- Loss of pubic hair
- Reduced libido
- Increased fat
- Reduced mood
- ED
- Reduced muscle strength
- Fatigue
What investigations would you do for hypogonadism?
Males:
- LH and FSH - help distinguish primary and secondary causes (high in primary gonadal defect w/ low testostrone)
- Serum total testosterone - low (<10.4nanomol/L) when measured on at least 2 occasions in males because of diurnal variation (morning sample recommended)
- SHBG (sex hormone binding globulin) - decreased in obesity and so can decrease total testosterone measured (so measure free or bioavailable testosterone). Also low in T2DM, hypothyroid, nephrotic syndrome.
- Semen analysis - sperm count below 5 million/mL indicates severe oligozoospermia
- Karyotyping - 47,XXY confirms Klinefelter syndrome (may be mosaic)
- Testicular biopsy
Females and other:
- Urine/serm pregnancy test - FIRST if secondary amenorrhoea
- Karyotyping - in those <30yrs
- Antiovarian antibody - measure if LH/FSH are high and karyotype is normal
- Serum estradiol - low in primary ovarian failure or suppressed hypothalamic function (lowFSH)
- Serum prolactin (fasting) - elevated in hyperprolactinaemia which may be due to pituitary adenoma
- Serum TSH - hypothyroidism can result in hyperprolactinaemia. Suppressed TSH suggests hyperthyroidism, which may cause oligomenorrhoea.
- DHEAS and free testosterone (serum androgens) - hyperandrogenism in PCOS/tumours producing androgens
- SynACTHen test - ACTH stimulation testing - if congenital adrenal hyperplasia suspected affecting steroid synthesis; ACTH injection given and cortisol levels measured
- LHRH stimulation testing -LHRH is intravenously injected, and LH and FSH levels are determined at 15-minute intervals following LHRH administration
- Neurological examination - peripheral vision changes, suggests an intracranial mass impinging on the optic chiasm
Imaging
- MRI - no olfactory bulbs in Kallmann syndrome; ?pituitary defects;
- US transabdominal/transvaginal - confirm normal anatomy
- DXA scan - long term suppressed testosterone (with low oestrogen) can lead to compromised bone health in men
What is the management of male hypogonadism?
Testosterone therapy - if having signs and symptoms of low testosterone (e.g. low libido, decreased morning erections, loss of body hair) AND 3 low morning readings (8-10am)
What are the complications of testosterone therapy?
Erythrocytosis - check Hct 3-6m after starting treatment
?Prostate cancer/BPH - unknown
What are the complications of male hypogonadism?
- Gynaecomastia and abnormal genitalia → poor self-image
- Reduced libido
- Increased fat
- Infertility
- Reduced mood
- ED
- Osteoporosis
- Reduced muscle strength
- Fatigue
What is the management of Kleinfelter syndrome?
Start testosterone during puberty monthly IM 50-100mg (13-18yrs or until growth stops)
Then full doses testosterone in adulthood
NB: Infertility is not treatable - opt for adoption, donor sperm etc
What are the complications of Kleinfelter syndrome?
In addition to complications of androgen deficiency there is increased:
- Learning and language difficulty
- Metabolic syndrome
- DM
- CVD
- VTE
- AI disease
- Some cancers
Which condition is shown?
Kleinfelter syndrome
What condition is shown in this female?
CAH
What condition is shown?
Webbed neck in Turner’s syndrome
