Endocrine (Gonadal disorders and Endocrine disorders)

Question 1

Klinefelter’s syndrome

Answer 1

• 47, XXY karyotype, where male patients have an additional X-chromosome.
• Symptoms can be subtle and many men may not even be aware they have the condition.
• most common sex chromosome disorder
• often undiagnosed until adulthood

Question 2

presentation of Klinefelters

Answer 2

• Infertility
• Small testes
• Decreased facial and pubic hair
• Reduced libido
• Tall build
• Gynaecomastia

Clinical presentation

• Newborn males with the XXY genetic makeup will appear phenotypically male (normal external male genitalia)
• Children with Klinefelter generally present after puberty with tall stature (long legs compared to trunk), small, firm testes, small penis, decreased pubertal hair, and gynecomastia
• These children are also at higher risk for developing learning disorders (particularly involving speech delay, but also ADHD and dyslexia), bone abnormalities (i.e. osteoporosis), psychiatric conditions (i.e. depression), autism spectrum disorders, and autoimmune disorders (i.e. lupus)

Question 3

investigations for Klinefelters

Answer 3

FSH and LH:

• Elevated, usually FSH > LH

Testosterone:

• Low

Karyotyping:

• Diagnostic test

Question 4

management of klinefelters

Answer 4

Management is coordinated by a multidisciplinary team to monitor for long-term complications. Testosterone replacement is often used

Question 5

Kallmann’s syndrome

Answer 5

• X-linked recessive - more common in men
• is characterised by an inability to initiate or complete puberty secondary to hypogonadotropic (FSH and LH are not released) hypogonadism (the gonads do not work as a result).
• There is an underproduction of gonadotropin-releasing hormone (GnRH).

Question 6

presentation of kallmans

Answer 6

• Anosmia- TOTAL LACK OF SENSE OF SMELL
• Tall build
• Small testes
• Primary amenorrhoea
• Lack of or poorly defined secondary sexual characteristics

Question 7

Kallman investigations

Answer 7

FSH and LH:

• Both low

Testosterone:

• Low

Karyotyping:

• May detect chromosomal abnormalities

Question 8

management of Kallmans

Answer 8

Testosterone / oestrogen replacement

Question 9

Androgen insensitivity syndrome (AIS)

Answer 9

• Is a rare X-linked recessive condition
• Cells are unable to respond to androgen hormones due to a lack of androgen receptors leading to end-organ resistance of testosterone leading to a variable ability to respond to testosterone.
• Extra androgens are converted into oestrogen, resulting in female secondary sexual characteristics
• Genetic males (XY) will have female phenotype

Question 10

Presentation of androgen insensitivity syndrome

Answer 10

Complete androgen insensitivity syndrome (CAIS)

• Primary amenorrhoea
• Bilateral groin swellings – due to undescended testes
• The vagina is blind-ending and there is no uterus

Partial androgen insensitivity syndrome (PAIS)

• The features of PAIS can vary from very few male characteristics with female genitalia or male genitalia.

Mild androgen insensitivity syndrome (MAIS)

• Patients are male and may have:
• Micropenis
• Gynaecomastia
• Infertility

Question 11

diagnosis of AIS

Answer 11

• Sex hormone testing

–> Raised LH
–> Normal or raised FSH
–> Normal or raised testosterone levels (for a male)
–> Raised oestrogen levels (for a male)

• Sex chromosome testing
• Genetic testing
• Ultrasound scans

Question 12

management of AIS

Answer 12

The patient should be raised as female or whichever gender identity they would like.

• A bilateral orchidectomy should also be performed as undescended testes carry an increased risk of testicular cancer.
• Oestrogen therapy
• Vaginal surgery e.g. vaginal dilators -> adequate vaginal length
• Male breast reduction.

Question 13

Multiple endocrine neoplasia (MEN)

Answer 13

describes several syndromes featuring tumours of endocrine organs with different characteristic patterns. MEN is inherited in an autosomal dominant manner.

The main types of MEN are:

• MEN1
• MEN2A
• MEN2B

Question 14

features of MEN1

Answer 14

1) Parathyroid hyperplasia and adenomas:

• Often the presenting feature

2) Pituitary adenomas:

• Most commonly prolactinomas
• May lead to acromegaly and Cushing’s syndrome

3) Pancreatic endocrine tumours:

• Gastrinomas – recurrent peptic ulcers and Zollinger-Ellison syndrome
• Insulinomas – see Hypoglycaemia

4) Angiofibromas

Question 15

MEN2A

Answer 15

Due to a mutation in the RET oncogene. Features may be:

• Medullary thyroid cancer
• Parathyroid hyperplasia and adenomas
• Phaeochromocytoma

Question 16

MEN2B

Answer 16

Due to a mutation in the RET oncogene. Features may be:

• Medullary thyroid cancer
• Phaeochromocytoma
• Marfan’s-like body habitus
• Neuromas
• Delayed puberty

Question 17

management of MEN syndromes

Answer 17

Management involves genetic counselling and surgical removal of affected areas. Replacement hormones are also given.

Question 18

Familial hypercholesterolaemia (FH)

Answer 18

• is an autosomal dominant condition characterised by increased levels of low-density lipoprotein (LDL) cholesterol.
• FH is caused by a mutation in the gene that codes for the LDL-receptor protein, which normally removes LDL from the circulation.
• FH should be suspected if total cholesterol is >7.5 mmol/L and there is a family history of premature coronary heart disease (CHD).

Question 19

criteria for familia hypercholsterolaemia

Answer 19

Simon Broome criteria

Adults with a total cholesterol >7.5 mmol/L + LDL cholesterol >4.9 mmol/L, or children with a total cholesterol >6.7 mmol/L + LDL cholesterol >4.0 mmol/L can be diagnosed with:

• Definite FH if there are xanthomata in a 1st- or 2nd-degree relative or genetic evidence of FH
• Possible FH if there is a family history of myocardial infarction <60 years in a 1st-degree relative, or <50 years in a 2nd-degree relative, or a family history of hypercholesterolaemia

Question 20

management of FH

Answer 20

1st-line: high-dose statins + referral to specialist clinic

Question 21

Obesity

Answer 21

describes excess body fat and is classified according to body mass index (BMI):

• Healthy weight – BMI of 18.5–24.9 kg/m2
• Overweight – BMI of 25–29.9 kg/m2
• Obesity 1 – BMI of 30–34.9 kg/m2
• Obesity 2 – BMI of 35–39.9 kg/m2
• Obesity 3 – BMI of 40 kg/m2 or more

Question 22

BMI is calculated using

Answer 22

weight (kg) divided by height in metres squared (m2)

kg/m^2

Question 23

first line management of obesity

Answer 23

lifestyle changes and weight management programmes

Question 24

obesity drug treatment

Answer 24

• Oral Orlistat (pancreatic lipase inhibitor)
• Subcut Liraglutide (GLP-1 mimetic)

Question 25

Oral orlistat (pancreatic lipase inhibitor):

Answer 25

Prescribed if:
- BMI ≥28 kg/m2 with associated risk factors (e.g. type 2 diabetes mellitus, hypertension, or dyslipidaemia) or
BMI ≥30 kg/m2 or more

Adverse effects:
Bloating, faecal urgency, steatorrhoea

Question 26

Liraglutide subcutaneous injection – GLP-1 mimetic:

Answer 26

Prescribed if:

• BMI ≥35 kg/m2 (or ≥32.5 kg/m2 in members of minority ethnic groups with an increased risk of complications at a lower BMI compared to the white population) and they have one of the following:
• Non-diabetic hyperglycaemia
• High risk of cardiovascular disease (e.g. dyslipidaemia and hypertension)

Question 27

Bariatric surgery:

Answer 27

• If BMI >50 kg/m2 and other interventions have not been effective
• May be considered in people with a BMI >35 kg/m2 with other significant diseases that could be improved with weight loss (e.g. type 2 diabetes, hypertension, or mobility issues)

Question 28

Gynaecomastia

Answer 28

describes an increase in male breast volume which most commonly occurs during times of significant hormonal changes, such as adolescence and old age.
- it occurs due to an** increased oestrogen:androgen ratio**
- The majority of cases of gynaecomastia are idiopathic.

Question 29

Physiological causes of gynaecomastia

Answer 29

• Newborns – due to maternal oestrogen. Resolves in a few weeks.
• Adolescence – generally resolves within 1-2 years
• Increasing age – due to testosterone decline

Question 30

pathological causes of gynaecomastia

Answer 30

Increased oestrogen levels/activity:

• Obesity – due to increased aromatase activity (converts testosterone into oestrogen)
• Anabolic steroid use/excess androgen replacement – extra testosterone is converted into oestrogen
• Testicular cancers (e.g. seminoma) – secrete hCG which stimulates oestrogen production

Decreased testosterone levels/activity:

• Gonadal disorders (e.g. Kallmann’s syndrome)
• Hyperprolactinaemia (e.g. pituitary tumours)
• Testicular failure (e.g. infection such as mumps, haemochromatosis, Klinefelter’s syndrome)

Drug causes:

Drugs stimulating oestrogen receptors:

• Digoxin
• Phenytoin

Drugs reducing testosterone levels/activity:

• Spironolactone – most common
• Gonadotropin-releasing hormone agonists (GnRH)
• Androgen receptor blockers (e.g. bicalutamide)
• 5-alpha reductase inhibitors (e.g. finasteride)
• Cimetidine
• Ketoconazole
• Metronidazole