Endocrine / Reproductive

Question 1

Where do the testes develop?

Answer 1

Abdomen and then gradually migrate down - through the inguinal canal into the scrotum

They have normally reached the scrotum prior to birth.

In about 5% of boys the testes have not made it out of the abdomen by birth. At this point they are called undescended testes. This can also be referred to as cryptorchidism.

Question 2

If you can’t palpate the testes in the scrotum of a newborn boy, where else could they be?

Answer 2

They might be palpable in the inguinal canal (in the inguinal region), which is not technically classed as undescended testes, although they have not fully descended at that point.

Question 3

What are the 3 major complications of undescended testes?

Answer 3

• Testicular torsion
• Infertility
• Testicular torsion

Question 4

Risk factors for undescended testes

Answer 4

• Family history of undescended testes
• Low birth weight
• Small for gestational age
• Prematurity
• Maternal smoking during pregnancy

Question 5

Management of undescended testes

Answer 5

• 3-6 months: Watch and wait (most descend)
• 6-12 months: Orchidopexy (surgical correction of undescended testes)

Question 6

What is the cresmasteric reflex?

Answer 6

It is normal in boys that have not reached puberty for the testes to move out of the scrotum and into the inguinal canal when it is cold or the cremasteric reflex is activated

Question 7

What are retractile testicles?

Answer 7

Considered a normal variant
* They have the cremasteric reflex - but usually resolves as they go through puberty and the testes settle in the scrotum. Occasionally they may fully retract or fail to descend and require surgical correction with orchidopexy

Question 8

A 2-day-old male neonate is not feeding well, appears lethargic and dehydrated. Bedside glucose monitoring reveals hypoglycaemia. They are found to have profound hyponatraemia on blood tests. Possible diagnosis?

Answer 8

Congenital adrenal hyperplasia?

Question 9

What is congenital adrenal hyperplasia caused by?

Answer 9

Congenital deficiency of the 21-hydroxylase enzyme

This causes, from birth:
* Underproduction of cortisol + aldosterone
* Overproduction of androgens

Question 10

What is the inheritence pattern of congenital adrenal hyperplasia?

Answer 10

Autosomal recessive

In a small number of cases it is caused by a deficiency of 11-beta-hydroxylase rather than 21-hydroxylase

Question 11

Congenital adrenal hyperplasia pathophysiology

Answer 11

• 21-hydroxylase = enzyme responsible for converting: progesterone → aldosterone + cortisol

In CAH:
* Defect in 21-hydroxylase enzyme → therefore there is extra progesterone floating around - that cannot be converted to aldosterone + cortisol → gets converted into testosterone instead

As a result:
* Low aldosterone
* Low cortisol
* High testosterone

• 21-hydroxylase = converts progesterone into aldosterone + cortisol.
• Progesterone is also used to create testosterone, but this conversion does not rely on the 21-hydroxylase enzyme

Question 12

What are the abnormal hormone levels does congenital hyperplasia cause?

Answer 12

• Low aldosterone
• Low cortisol
• High testosterone

Question 13

How do severe cases of CAH present?

Answer 13

Features of mineralcorticoid + glucocortoid deficiency:
* Hypoglycaemia
* Hyponatraemia
* Hyperkalaemia

Leads to:
* Poor feeding
* Vomiting
* Dehydration
* Arrhythmias

• Females: virilised genitalia AKA “ambiguous genitalia” (due to high testosterone)
• Males: virilised genitalia (large penis)

Question 14

How do mild cases of CAH generally present?

Answer 14

Patients who are less severely affected present during childhood or after puberty. Their symptoms tend to be related to high androgen levels.

Question 15

How do mild case of CAH present in females?

Answer 15

• Tall for their age
• Facial hair
• Absent periods
• Deep voice
• Early puberty

Question 16

How do mild case of CAH present in males?

Answer 16

• Tall for their age
• Deep voice
• Large penis
• Small testicles
• Early puberty

Question 17

Tom Tip: Congenital adrenal hyperplasia

Answer 17

TOM TIP: A textbook and exam clue that a patient has CAH is skin hyperpigmentation. Hyperpigmentation occurs because the anterior pituitary gland responds to the low levels of cortisol by producing increasing amounts of ACTH. A byproduct of the production of ACTH is melanocyte simulating hormone. This hormone stimulates the production of melanin (pigment) within skin cells.

Question 18

Investigations for congenital adrenal hyperplasia

Answer 18

• Serum 17-hydroxyprogesterone levels: this is precursor of the enzyme, 21-hydroxylase and is diagnostic of classical 21-hydroxylase deficiency (21-OHD)
• Serum electrolytes: To assess for hyponatremia, hyperkalemia, and acidosis
• Serum hormone levels: elevated ACTH + renin will be expected in salt-wasting CAH, with associated low cortisol + aldosterone

Ix to consider:
* Genetic testing: To confirm the specific enzyme deficiency, as well as to karyotype for genotypic sex
* Imaging: Pelvic ultrasound for internal genital anatomy in cases of ambiguous genitalia

Question 19

Management for congenital adrenal hyperplasia

Answer 19

• Cortisol replacement: Hydrocortisone (similar to adrenal insufficiency)
• Alsosterone replacement: fludrocortisone
• Corrective surgery for female patients with ‘virilised’ genitals

Question 19

Complications for congenital adrenal hyperplasia

Answer 19

• Adrenal crisis
• Infertility
• Psychological issues: gender identity + body image

Question 20

What is androgen insensitivity syndrome?

Answer 20

Androgen insensitivity syndrome = cells are unable to respond to androgen hormones - due to a lack of androgen receptors

Previoulsy known as testicular feminisation syndrome

Question 21

What is the inheritence pattern for androgen insensitivity syndrome?

Answer 21

X-linked recessive genetic condition → caused by a mutation in the androgen receptor gene on the X chromosome

Question 22

Pathophysiology of androgen insensitivity syndrome

Answer 22

• Mutation in the androgen receptor gene on the X chromosome
• Extra androgens = converted into oestrogen → resulting in female secondary sexual characteristics
• Patients = genetically male with XY sex chromosome → However, no response to testerone + additional androgens to oestrogen → result in female phenotype externally → male sexual characteristics don’t develop + develop normal female external genitalia + breast tissue

Question 23

Apart from reproductive organs, how else may patients with androgen insensitivity syndrome present?

Answer 23

Due to the insensitivity to androgens:
* Lack of pubic hair
* Facial hair
* Male muscle development
* Slightly taller than female average
* Infertile
* Increased risk of testicular cancer (unless removed)

Question 23

What reproductive organs do patients with androgen insensitivity syndrome have?

Answer 23

• Testes in the abdomen or inguinal canal
• No uterus, upper vagina, cervix, fallopian tubes, ovaries → The female internal organs do not develop because the testes produce anti-Müllerian hormone, which prevents males from developing an upper vagina, uterus, cervix and fallopian tubes.
• Normal female external genitalia + breast tissue

Question 24

What is partial androgen insensitivity syndrome?

Answer 24

Where there the cells have a partial response to androgens. This presents with more ambiguous signs and symptoms:
* Micropenis or clitoromegaly,
* Bifid scrotum
* Hypospadias
* Diminished male characteristics.

Question 25

How may androgen insensitivity syndrome initially present?

Answer 25

• Infancy → inguinal hernias (containing testes)
• Puberty → primary amenorrhoea

Question 26

You suspect androgen insensitivity syndrome, what do blood tests look like?

Answer 26

• Raised LH
• Normal or raised FSH
• Normal or raised testosterone levels (for a male)
• Raised oestrogen level (for a male)

Question 27

Summary: Presentation of androgen insensitivity syndrome

Answer 27

Infancy → inguinal hernias (containing testes)
Puberty → primary amenorrhoea

Puberty onwards:
* Normal female external genitalia
* Normal breast tissue
* No uterus, upper vagina, cervix, fallopian tubes and ovaries
* Testes in abdomen or inguinal canal

• Lack of pubic hair
• Facial hair
• Male type muscle development
• Slightly taler than female average

Question 28

Management of androgen insensitivity syndrome

Answer 28

• Bilateral orchidectomy (removal of testes) to avoid testicular tumours
• Oestrogen therapy
• Vaginal dilators or vaginal surgery → create an adequate vaginal length
• Psyhcological therapy (patients are often raised female)