Endocrine Aspects of Male Hypogonadism Flashcards

1
Q

Testosterone is a … hormone

A

steroid

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2
Q

Testosterone is secreted in both men and women, where?

A

testes, ovaries, adrenals

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3
Q
  • Normal young men produce how much testosterone a day?
  • how much is derived from adrenal secretions?
A
  • 7mg
  • less than 5% is derived from adrenal secretions
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4
Q
  • Testosterone in blood is largely bound to … protein, with only about …% present as free hormone
    • about … is bound to albumin
    • …% is bound to sex hormone-binding globulin
A
  • Testosterone in blood is largely bound to plasma protein, with only about 2% present as free hormone
    • about half is bound to albumin
    • 44% is bound to sex hormone-binding globulin
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5
Q

The Testes contain two anatomical units:

  1. … tubules in which inhibin B and anti-Mullerian hormone are synthesized by Sertoli cells and sperm are produced
  2. An … containing Leydig cells that produce androgens and peritubular myoid cells
A
  1. Seminiferous tubules in which inhibin B and anti-Mullerian hormone are synthesized by Sertoli cells and sperm are produced
  2. An interstitium containing Leydig cells that produce androgens and peritubular myoid cells
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6
Q

Seminiferous tubules - part of testes

  • inhibin B and anti-Mullerian hormone are synthesized by … cells and … are produced
A

inhibin B and anti-Mullerian hormone are synthesized by Sertoli cells and sperm are produced

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7
Q

What is a Sertoli cell?

A

A Sertoli cell is a “nurse” cell of the testicles that is part of a seminiferous tubule and helps in the process of spermatogenesis, the production of sperm.

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8
Q

What are Leydig cells?

A
  • Leydig cells are interstitial cells located adjacent to the seminiferous tubules in the testes.
  • The best-established function of Leydig cells is to produce the androgen, testosterone, under the pulsatile control of pituitary luteinizing hormone (LH)
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9
Q

What are peritubular myoid cells?

A

A peritubular myoid (PTM) cell is one of the smooth muscle cells which surround the seminiferous tubules in the testis

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10
Q

Androgens are synthesized from … and are produced primarily in the … (testicles and ovaries) and also in the … glands

A

Androgens are synthesized from cholesterol and are produced primarily in the gonads (testicles and ovaries) and also in the adrenal glands.

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11
Q

Androgens: Synthesis

  • … is needed to convert cholesterol to pregnenolone
  • pregnenolone is converted either to … or D…
  • these converted to testosterone
  • once these are in circulation - 5alpha reductase converts testosterone into …
  • Or, aromatase converts it into … (… required)
A
  • LH is needed to convert cholesterol to pregnenolone
  • pregnenolone is converted either to progesterone or DHEA
  • these converted to testosterone
  • once these are in circulation - 5alpha reductase converts testosterone into DHT
  • Or, aromatase converts it into estradiol (FSH required)
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12
Q

Testosterone: The hypothalamic-pituitary-testicular axis

  • In the hypothalamus there is … secretion of … - acts on pituitary leading to …
  • Secretion of LH and FSH
  • LH and FSH are composed of … glycoprotein chains
  • LH is involved in release of …
  • FSH is involved in … and Inhibin B …
A
  • In the hypothalamus there is pulsatile secretion of GnRH - acts on pituitary leading to …
  • Secretion of LH and FSH
  • LH and FSH are composed of two glycoprotein chains
  • LH is involved in release of Testosterone
  • FSH is involved in spermatogenesis and Inhibin B secretion
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13
Q

Testosterone: Mechanism of Action

  • Like other … hormones, testosterone penetrates the target cells whose growth and function it stimulates
  • Androgen target cells generally convert testosterone to … before it binds to the androgen receptor
  • Alternatively, testosterone can be … to …, which exerts effects that are independent of, opposite to, or synergistic to those of androgen
A
  • Like other steroid hormones, testosterone penetrates the target cells whose growth and function it stimulates
  • Androgen target cells generally convert testosterone to 5-alpha dihydrosterone befire it binds to the androgen receptor
  • Alternatively, testosterone can be aromatized to estrogens, which exerts effects that are independent of, opposite to, or synergistic to those of androgen
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14
Q

Testosterone action

  • regulation of … secretion by the hypothalamic-pituitary system
  • initiation and maintenance of …
  • formation of the … phenotype during embryogenesis
  • promotion of sexual … at puberty and it’s maintenance thereafter
  • increase in … body mass and decrease in … mass
A
  • regulation of gonadotropin secretion by the hypothalamic-pituitary system
  • initiation and maintenance of spermatogenesis
  • formation of the male phenotype during embryogenesis
  • promotion of sexual maturation at puberty and it’s maintenance thereafter
  • increase in lean body mass and decrease in fat mass
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15
Q

Why is testosterone important?

  • sharper …
  • increased … mass
  • strong …
  • pleny of ….
  • confidence
A
  • sharper mind
  • increased muscle mass
  • strong bones
  • pleny of energy
  • confidence
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16
Q

Male hypogonadism is defined as decrease in one or both of the two major functions of the testes - what are these?

A

sperm production or testosterone production

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17
Q

Disease of testes is what type of hypogonadism?

A

primary hypogonadism

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18
Q

Disease of the hypothalamus or pituitary is what type of hypogonadism?

A

secondary hypogonadism

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19
Q

Primary hypogonadism:

  • Testerone levels are below normal and the serum … and/or … are above normal

Secondary hypogonadism:

  • Testerone levels are below normal and the serum … and/or … are normal or low
A
  • Testerone levels are below normal and the serum LH and/or FSH are above normal
  • Testerone levels are below normal and the serum LH and/or FSH are normal or low
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20
Q

Causes of Primary Hypogonadism:

  • … syndrome is most common
  • a condition in which one or both of the testes fail to descend from the abdomen into the scrotum - what is this called?
  • Idiopathic causes
  • Torsion
  • Trauma
  • Radiation
  • Infection - such as …
A
  • Klinefelter syndrome is most common
  • Cryptochidism
  • Idiopathic
  • Torsion
  • Trauma
  • Radiation
  • Infection - mumps
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21
Q
  • What is Klinefelter syndrome?
  • It can result in what?
A
  • Klinefelter syndrome is a genetic condition that results when a boy is born with an extra copy of the X chromosome.
  • Can result in primary hypogonadism
22
Q

Causes of Secondary Hypogonadism:

  • Congenital … deficiency
  • Hyper…
  • … analog
  • Androgen
  • Excessive use of …
  • Illness
  • Eating disorder - which one?
  • … disorder
A
  • Congenital GnRH deficiency
  • Hyperprolactinemia
  • GnRH analog
  • Androgen
  • Opioids - excessive use
  • Illness
  • Anorexia Nervosa
  • Pituitary disorder
23
Q

Clinical features of Hypogonadism

  • First trimester - … genitalia to ambiguous genitalia to partial …
  • Third trimester - child will have a …
  • Prepubertal - failure to undergo or complete …
A
  • First trimester - Female genitalia to ambiguous genitalia to partial virilization
  • Third trimester - child will have a micropenis
  • Prepubertal - failure to undergo or complete puberty
    *
24
Q

Symptoms/Signs of hypogonadism

  • Incomplete … development, eunochoidism
  • decreased sexual desire and activity
  • decreased sponatenous …
  • breast discomfort, …
  • decreased body … (Axillary and pubic), decreased …
  • very small or shrinking … (Esp <5ml)
  • inability to …, low/zero sperm counts
  • lose height, low-trauma fracture, low BMD
  • lose … bulk and strength
  • hot …, …
A
  • Incomplete sexual development, eunochoidism
  • decreased sexual desire and activity
  • decreased sponatenous erections
  • breast discomfort, gynecomastia
  • decreased body hair (Axillary and pubic), decreased shaving
  • very small or shrinking testes (Esp <5ml)
  • inability to father children, low/zero sperm counts
  • short height, low-trauma fracture, low BMD
  • lose muscle bulk and strength
  • hot flushes, sweats
25
Q

Less specific symptoms/signs of hypogonadism

  • Lack of …
  • emotions?
  • poor … and …
  • disturbance of …
  • mild …
    • normochromic, normocytic, in the female range
  • increased … …
  • diminished … or … performance
A
  • Lack of energy, motivation, initiative, aggressiveness, self-confidence
  • feeling sad or blue, depressed mood, dysthymia
  • poor concentration and memory
  • sleep disturbance, increased sleepiness
  • mild anaemia
    • normochromic, normocytic, in the female range
  • increased body fat, BMI
  • diminished physical or work performance
26
Q

Conditions with a High Prevalence of hypogonadism (screening suggested)

  • diseases/mass of what part of pituitary?
  • medications such as … (3)
  • … or low trauma … - esp in young
  • infertility
  • type … diabetes mellitus
  • Moderate to severe …
  • ESRD and maintenance hemodialysis
  • …-associated weight loss
A
  • diseases/mass of what part of pituitary - sella turcica
  • meds - glucocorticoids, ketoconazole, opioids
  • Osteoporosis or low trauma fracture - esp in young
  • infertility
  • Type 2 diabetes mellitus
  • Moderate to severe COPD
  • ESRD and maintenance hemodialysis
  • HIV-associated weight loss
27
Q

Relevant medical history - hypogonadism

  • … and sexual development
  • Past/present major …
  • Past/present … deficiency
  • What drugs are we interested in?
  • … and … problems
  • major … events
  • related … Hx
  • Recent changes in body - esp in the …
  • … problems
A
  • Puberty and sexual development
  • Past/present major illnesses
  • Past/present nutritional deficiency
  • All prescription/non prescription drugs
  • relationship and sexual problems
  • major life events
  • related family Hx
  • Recent changes in body - breasts
  • testicle problems
28
Q

Examination - hypogonadism

  • amount of … … - comparison to family members
  • … exam for enlargement/tenderness
  • size and consistency of …
  • size of the …
  • signs of severe and prolonges hypogonadism, including … (4)
    • loss of .. …
    • reduced … … and strength
    • smaller …
  • … span
A
  • amount of body hair
  • breast exam for enlargement/tenderness
  • size and consistency of testicles
  • size of the penis
  • signs of severe and prolonged hypogonadism
    • loss of body hair
    • reduced muscle bulk and strength
    • osteoporosis
    • smaller testicles
  • arm span
29
Q

Investigations - Hypogonadism

  • Serum … - do this before .. am in a … state
  • …/… (2 hormones?)
  • SHBG - known as …
  • … function test
  • … analysis
  • Karoyotyping
  • … function testing
  • CT or MRI?
  • … scan
A
  • Serum testosterone - before 9 am in a fasting state
  • LH/FSH
  • SHBG - known as Sex hormone binding globulin
  • Liver Function Test
  • Semen analysis
  • Karoyotyping
  • Pituitary function testing
  • MRI scan
  • DEXA scan
30
Q

Guidelines on screening - Hypogonadism

Initial screen = … total testosterone

  • Levels are highest in the …
  • Normal testosterone is generally … dependent
  • Confirmation = … … total testosteron
  • Free or bioavailable
  • Do not screen during acute or subacute …
  • Illness, malnutrition, and certain medications may temporarily … testosterone
A

Initial screen = morning total testosterone

  • Levels are highest in the morning
  • Normal testosterone is generally age dependent
  • Confirmation = repeat morning total testosteron
  • Free or bioavailable
  • Do not screen during acute or subacute illness
  • Illness, malnutrition, and certain medications may temporarily lower testosterone
31
Q

What is this flowchart for?

A

Hypogonadism screening

32
Q

Testosterone circulates mostly bound to … (SHBG)

A

Sex hormone binding globulin

33
Q

What lowers SHBG:

  • Moderate …
  • … syndrome
  • …thyroidism
  • Use of
  • … steroids
A
  • Moderate obesity
  • Nephrotic syndrome
  • Hypothyroidism
  • Use of

•Glucocorticoids

•Progestins

•Androgenic steroids

34
Q

What raises SHBG:

  • younger or older?
  • Hepatic …
  • …thyroidism
  • Anti…
  • what sex hormone?
  • … infection
A
  • younger or older - aging
  • Hepatic cirrhosis
  • hyperthyroidism
  • Anticonvulsants
  • what type of hormone? - estrogens
  • HIV infection
35
Q

What is this flowchart for?

A

diagnosing hypogonadism - primary or secondary

36
Q

Treatment for hypogonadism

  • What hormone?
  • How is it given?
  • Inform of side effects!!!!
A
  • Testosterone - given by gel, injection or buccal/patch/pellet
37
Q

Monitoring treatment of hypogonadism

  • testosterone levels … hours after applying gel, if injection - do it when?
  • PSA - what does this stand for?
  • Digitial … exam
  • blood count?
  • DEXA scan - why?
A
  • Testosterone - 4 hours after - injection - check it just before injection
  • PSA - Prostate-Specific Antigen (test)
  • Digital rectal exam
  • Yes - full blood count
  • DEXA - scan is a high-precision type of X-ray that measures your bone mineral density and bone loss - low testosterone affects bone density
38
Q

Contraindications to Testosterone therapy

  • What cancers?
  • Lump/hardness on … exam by DRE
  • PSA >… ng/ml that has not been evaluated for prostate cancer
  • Severe untreated BPH (AUA/IPSS >19) - What does this stand for?
  • Erythrocytosis (hematocrit >…%)
  • Hyperviscosity - what is this?
  • Untreated obstructive … apnea
  • Severe … … (class III or IV)
A
  • Breast or prostate cancer
  • Lump/hardness on prostate exam by DRE
  • PSA >3 ng/ml that has not been evaluated for prostate cancer
  • Severe untreated BPH (AUA/IPSS >19) - Benign prostatic hyperplasia
  • Erythrocytosis (hematocrit >50%)
  • Hyperviscosity - condition in which blood isn’t able to flow freely through your arteries
  • Untreated obstructive sleep apnea
  • Severe heart failure (class III or IV)
39
Q

What is gynecomastia?

A

Gynecomastia, a benign proliferation of the glandular tissue of the male breast

40
Q

Gynecomastia

  • may be … or …
  • diagnosed on … as a palpable mass of tissue of at least … cm in diameter (usually underlying the nipple)
  • imbalance between … and .. hormones
  • …% of boys during puberty - transient
  • …-…% in adult men
A
  • may be unilateral or bilateral
  • diagnosed on exam as a palpable mass of tissue of at least 0.5 cm in diameter (usually underlying the nipple)
  • imbalance between androgen and estrogen
  • 60% of boys during puberty - transient
  • 30-70% in adult men
41
Q

Causes of Gynecomastia

  • Persistent … gynecomastia
  • Can drugs cause it?
  • Idiopathic causes
  • Cirrhosis or malnutrition
  • …gonadism
  • Testicular …
  • …thyroidism
  • Chronic renal … - … cell dysfunction
A
  • Persistent pubertal gynecomastia
  • yes - drugs can
  • Idiopathic causes
  • Cirrhosis or malnutrition
  • Hypogonadism
  • Testicular tumour
  • Hyperthyroidism
  • Chronic renal insufficiency - Leydig cell dysfunction
42
Q

Evaluation - Gynecomastia

  • Is the breast enlargement of recent onset or associated with … or …?
  • Is the breast enlargement due to increased glandular tissue or is it only … tissue (pseudogynecomastia)?
  • Are there findings suggestive of breast …?
  • Is there evidence of a testicular …, which might lead to gynecomastia by producing … or stimulating its production?
  • Can a cause for the breast enlargement be identified?
  • Is the patient … by the breast enlargement?
A
  • Is the breast enlargement of recent onset or associated with pain or tenderness?
  • Is the breast enlargement due to increased glandular tissue or is it only adipose tissue (pseudogynecomastia)?
  • Are there findings suggestive of breast cancer?
  • Is there evidence of a testicular tumor, which might lead to gynecomastia by producing estrogen or stimulating its production?
  • Can a cause for the breast enlargement be identified?
  • Is the patient troubled by the breast enlargement?
43
Q

History - Gynecomastia

  • Duration
  • Breast …/tenderness
  • … disease
  • … gain or loss
  • Use of …
  • Exposure to …
  • Fertility
  • Sexual …
  • … history
A
  • Duration
  • Breast pain/tenderness
  • systemic disease
  • weight gain or loss
  • Use of medical/recreational drugs
  • Exposure to chemicals
  • Fertility
  • Sexual function
  • family history
44
Q

Examination - gynecomastia

  • … is a condition in which women develop male-pattern hair growth and other masculine physical traits
  • Testicular …
  • penis
  • sign of CLD or CRF - what is this?
  • thyroid
  • breast
A
  • Virilisation
  • Testicular size
  • penis
  • sign of CLD or CRF - what is this? - chronic liver disease / chronic renal failure
  • thyroid
  • breast
45
Q

Investigation - gynecomastia

  • Testosterone
  • 2 hormones?
  • Pro…
  • LFT/U&E’s
  • B-hCG
  • … function tests
  • Estrogen
  • U/S chest and …
A
  • Testosterone
  • 2 hormones? - LH and FSH
  • Prolactin
  • LFT/U&E’s
  • B-hCG
  • Thryoid function tests
  • Estrogen
  • U/S chest and a mammogram
46
Q

Treatment - gynecomastia

  • Conservative - reassurance
  • Treatment of …
  • … prescribed - if patient’s are having progressive gynecomastia
  • Affecting psychological wellbeing - … is an option
A
  • Conservative - reassurance
  • Treatment of cause
  • Tamoxifen - if patient’s are having progressive gynecomastia
  • Affecting psychological wellbeing - surgery is an option
47
Q

Are both LH and FSH involved in testosterone production?

A

No - only LH

48
Q

Is GnRH secretion normally continuous?

A

no - pulsatile manner

49
Q

Most testerone is bound to protein (albumin/SHBG)

  • T or F?
A

True

50
Q
  • High LH/FSH and low testosterone - what is the diagnosis?
A

Primary hypogonadism

51
Q
  • Low LH/FSH and low testosterone - what is the diagnosis?
A

secondary hypogonadism

52
Q

Treatment for hypogonadism:

A

testosterone - gel or injection (2 option - 2 weekly or 3 monthly)