Androgen Deficiency in Men Flashcards by Hannah Meiklejohn

How are testosterone levels measured?

As total (TT) or free (FT) testosterone

How well did you know this?

Not at all

Perfectly

List 11 symptoms of androgen deficiency in men (9 negative and 4 positive)

DECREASED:

Sexual development (eunuchoidism, aspermia)

Fertility (low or zero sperm count)

Libido

Spontaneous erections

Body hair

Testes (esp less than 5mL)

Height (low trauma fracture, low bone mineral density)

Muscle bulk and strength

Energy, motivation, initiative, aggression, concentration, mood, sleep

POSITIVE Sx:

Breast discomfort and gynaecomastia

Hot flushes and sweats

Increased fat mass

Mild anaemia

How well did you know this?

Not at all

Perfectly

Describe the clinical presentation of male hypogonadism with onset in 1st trimester

If partial virilisation: ambiguous genitalia If complete deficiency: female external genitalia

How well did you know this?

Not at all

Perfectly

Describe the clinical presentation of male hypogonadism with onset in 3rd trimester

Micropenis

Cryptochidism

How well did you know this?

Not at all

Perfectly

Describe the clinical presentation of male hypogonadism with onset pre-puberty

Incomplete pubertal maturation

Testes ≤ 4mL

Eunochoidal body habitus (long-limbed, slim, underweight)

Gynaecomastia

Decreased peak bone mass

How well did you know this?

Not at all

Perfectly

Describe the clinical presentation of male hypogonadism with onset in adulthood

Decreased libido

Decreased mood and stamina

Decreased muscle mass and strength

Decreased bone density Increased fat mass

How well did you know this?

Not at all

Perfectly

List 4 conditions associated with decreased SHBG concentrations

Moderate obesity*

Nephrotic syndrome*

Hypothyroidism

Use of GCS, progestins and androgenic steroids

*Particularly common conditions associated with alterations in SHBG concentrations

How well did you know this?

Not at all

Perfectly

SHBG

Sex hormone-binding globulin

How well did you know this?

Not at all

Perfectly

List 6 conditions associated with increased SHBG concentrations

Ageing*

Hepatic cirrhosis*

Hyperthyroidism

Use of anticonvulsants* and oestrogens

HIV infection

*Particularly common conditions associated with alterations in SHBG concentrations

How well did you know this?

Not at all

Perfectly

Describe the regulation and production of testosterone

How well did you know this?

Not at all

Perfectly

What is the reference range for normal testosterone?

No age-related reference ranges

How well did you know this?

Not at all

Perfectly

What are the major limitations of testosterone assays?

Lack of standardisation

Inaccuracy in low range

How well did you know this?

Not at all

Perfectly

How is the clinical syndrome of androgen deficiency defined?

Characteristic symptoms and signs

Unequivocally low testosterone levels with absence of transient or reversible causes of low testosterone levels

How well did you know this?

Not at all

Perfectly

What actions should be taken if a low TT result is received?

Repeat the test: any normal level received = eugonadal

How well did you know this?

Not at all

Perfectly

What is the significance of calculated FT (cFT)?

If TT is borderline but SHBG is abnormal, look at cFT to rule out falsely low TT

How well did you know this?

Not at all

Perfectly

What might an elevated LH indicate?

Decreased testosterone secretion

How well did you know this?

Not at all

Perfectly

List some acquired causes of primary androgen deficiency

Testicular damage: trauma, orchitis, chemotherapy, radiotherapy, toxins

Drugs: spironolactone, ketoconazole

List 5 congenital causes of primary androgen deficiency

Klinefelter syndrome

Cryptorchidism

Mutations in androgen biosynthesis enzymes

LH/FSH-receptor mutations

Myotonic dystrophy

Identify some causes of secondary androgen deficiency

Structural (pituitary/hypothalamus): tumour, surgery, radiation, trauma, infiltration (haemochromatosis, sarcoid, histiocytosis)

Genetic: Kallmann’s syndrome, “idiopathic” HH, LH/FSH beta subunit mutations

Functional: hyperprolactinaemia, morbid obesity, Cushing’s syndrome

What blood results would be expected in primary vs secondary androgen deficiency?

Primary: LH/FSH elevated

Secondary: LH/FSH low/normal

List 3 partial/transient causes of androgen deficiency

Acute illness

Chronic disease: ESKD, COPD, HIV, T2DM

Drugs: glucocorticoids, opioids, GnRH agonists, anabolic steroids

Describe the natural Hx of Klinefelter’s syndrome

Puberty triggers germ cell extinction

More rapid TT decrease with ageing

What are the main features of Klinefelter’s syndrome?

Testes less than 4cm, firm (“pea-like”)

Azoospermia: usually infertile, occasionally spearm retrievable with testicular microdissection

Require speech therapy and educational support

What blood test results are expected with Klinefelter’s syndrome?

TT commonly low or normal (more rapid decrease with ageing)

LH high

What is Klinefelter's syndrome?

XXY

What does a non-palpable testis suggest?

Anorchism Bilateral cryptorchidism

What does a testis less than 5mL suggest?

Kallmann's syndrome, hypogonadotropic hypogonadism Klinefelter's syndrome Other hypergonadotropic syndromes

What does a testis 8-15mL suggest?

Germinal damage Toxins Idiopathic

What does a testis 15-20mL indicate?

Varicocele Drugs Idiopathic

What does a testis 10-20mL suggest?

Adult-acquired hypogonadotropic hypogonadism Senescence

Describe an approach for diagnostic evaluation of adult men suspected of having androgen deficiency

Mr KF, 24 year old electrician, presents with wife of 2 years for evaluation of infertility; his wife has a child from a previous marriage which she conceived without difficulty She reports that Mr KF is "quite passive sexually" and needs to be prompted to "perform his marital duties"; Mr KF agrees he "rarely feels like doing it" Mr KF reports that his pubertal development has been "a bit slower" than his peers; he shaves every 3 days and is the tallest in the family, and although he works out he does not "bulk up like the other guys" No Hx of testicular trauma or infections Reports no significant health issues and takes no regular medications; recalls a childhood Dx of mild attention deficit disorder O/E: note boyish-looking facial features and scant pubic hair, slight gynaecomastia, pea-sized testes (4 mL in volume) and firm Ix?

Morning fasting TT FSH LH Chromosomal analysis Semen analysis

Mr KF, 24 year old electrician, presents with Sx and signs of androgen deficiency Morning fasting TT: 4.7nmol/L, repeat 5.6 nmol/L (RR 12-27) FSH: 23.8 mIU/mL (RR 1.0-9.0) LH: 14.3 mIU/mL (RR 1.0-10.0) Chromosomal analysis: 47, XXY Semen analysis: azoospermia Dx?

Klinefelter's syndrome

Mr. ED, a 62 year-old accountant presents because he is “unhappy with his sex life”; hs libido is strong, but he has difficulty maintaining an erection His wife is 15 years younger and unhappy about his performance; they often argue He has tried an expensive intranasal spray that he obtained over the Internet but it “did not work”; he has come to ask about “hormone therapy for men” Has not seen a “doctor for years” but denies other health issues; in recent years, he feels “more tired” and “lost some strength”, but denies headaches or visual disturbance Smokes “10 cigarettes” a day and has “a few stubbies with the mates” on weekends, does not exercise O/E: BP 150/90, BMI 30 kg/m2, appears well virilised and testicular volume is 25 ml bilaterally, visual fields normal to confrontation, 105cm waist circumference, R carotid bruit and reduced pedal pulses Ix?

Morning fasting TT SHBG Calculated FT FSH and LH PLN Iron studies FPG Lipids MRI pituitary

Mr ED presents with erectile dysfunction and complains of feeling "tired" in recent years Examination unremarkable except for R carotid bruit and reduced pedal pulses, waist circumference 105cm Morning fasting TT: 8.4 nmol/L, repeat 7.6 nmol/L (RR 10-27) SHBG: 22 nmol/L (RR 10-50) Calculated FT: 190 pmol/L, repeat 210 pmol/L (RR \>230 pmol/L) FSH: 3.2 mIU/mL (N 1.0-9.0) LH: 4.1 mIU/mL (N 1.0-10.0) Normal PLN Normal iron studies FPG: 7.9 LDL cholesterol: 4.5 nmol/L MRI pituitary normal Dx?

Non classical androgen deficiency, common in ageing and chronic disease

Steps in testosterone therapy

Establish treatment goals Achieve adequate TT levels Monitor treatment response Monitor for adverse effects

How can testosterone therapy be delivered in Aus?

Injection (deep IM) of testosterone esters or enanthate every 2 weeks (cheapest and widely available) Transdermal testosterone patch (suitable in bleeding disorders; also cream) Subdermal implant of testosterone pellet (convenience - infrequent administration) Oral testosterone undecanoate daily (safe, suitable in bleeding disorders) Non-proprietary forms: troche, dragee, ointment Recent additions: testosterone undecanoate (long-acting) 3-monthly IM injections (more reliable levels), gel daily application

What are the indications for a PBS authority requirement for testosterone therapy in men with androgen deficiency?

Classic androgen deficiency due to hypothalamo-pituitary or testicular disorders: qualify Men without classic androgen deficiency: men 40 and older with no established pituitary or testicular disorders other than ageing, confirmed by at least 2 morning blood samples taken on different mornings - androgen deficiency is confirmed by testosterone level under 8nM or 8-15nM with high LH (less than 1.5x upper limit of eugonadal RR \> for young men)

CIs to TRT

Evidence of prostate Ca (abnormal DRE, elevated PSA \>3ng/mL, diagnosed prostate cancer) Breast cancer Erythrocytosis (HCT at least 52%) or hyperviscosity Untreated OSA Severe LUTS Class III or IV HF Desire to have child

Potential adverse effects of testosterone replacement

Erythrocytosis Acne, oily skin Detection of subclinical prostate Ca Growth of metastatic prostate Ca Reduced sperm production and fertility, testicular atrophy Fluid retention Weak evidence of gynaecomastia, male pattern balding, worsening of BPH Sx, growth of breast Ca, induction or worsening of OSA

What monitoring is indicated for male patients on testosterone therapy?

Hx and physical every 3-4/12 initially then annually Testosterone 3/12 post-treatment until stable in normal range PSA and DRE: baseline at 3/12, every 6-12/12 after depending on patient's age Annual lipids Haematocrit: baseline, every 3/12, then annually BMD of lumbar spine, femoral neck, hip: after 1-2 years of therapy in men with OP or low trauma #