Endocrine (Gonadal disorders and Endocrine disorders) Flashcards
Klinefelter’s syndrome
- 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
presentation of Klinefelters
- 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)
investigations for Klinefelters
FSH and LH:
- Elevated, usually FSH > LH
Testosterone:
- Low
Karyotyping:
- Diagnostic test
management of klinefelters
Management is coordinated by a multidisciplinary team to monitor for long-term complications. Testosterone replacement is often used
Kallmann’s syndrome
- 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).
presentation of kallmans
- Anosmia- TOTAL LACK OF SENSE OF SMELL
- Tall build
- Small testes
- Primary amenorrhoea
- Lack of or poorly defined secondary sexual characteristics
Kallman investigations
FSH and LH:
- Both low
Testosterone:
- Low
Karyotyping:
- May detect chromosomal abnormalities
management of Kallmans
Testosterone / oestrogen replacement
Androgen insensitivity syndrome (AIS)
- 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
Presentation of androgen insensitivity syndrome
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
diagnosis of AIS
- 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
management of AIS
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.
Multiple endocrine neoplasia (MEN)
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
features of MEN1
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
MEN2A
Due to a mutation in the RET oncogene. Features may be:
- Medullary thyroid cancer
- Parathyroid hyperplasia and adenomas
- Phaeochromocytoma
MEN2B
Due to a mutation in the RET oncogene. Features may be:
- Medullary thyroid cancer
- Phaeochromocytoma
- Marfan’s-like body habitus
- Neuromas
- Delayed puberty
management of MEN syndromes
Management involves genetic counselling and surgical removal of affected areas. Replacement hormones are also given.
Familial hypercholesterolaemia (FH)
- 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).
criteria for familia hypercholsterolaemia
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
management of FH
1st-line: high-dose statins + referral to specialist clinic
Obesity
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
BMI is calculated using
weight (kg) divided by height in metres squared (m2)
kg/m^2
first line management of obesity
lifestyle changes and weight management programmes
obesity drug treatment
- Oral Orlistat (pancreatic lipase inhibitor)
- Subcut Liraglutide (GLP-1 mimetic)
Oral orlistat (pancreatic lipase inhibitor):
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
Liraglutide subcutaneous injection – GLP-1 mimetic:
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)
Bariatric surgery:
- 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)
Gynaecomastia
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.
Physiological causes of gynaecomastia
- Newborns – due to maternal oestrogen. Resolves in a few weeks.
- Adolescence – generally resolves within 1-2 years
- Increasing age – due to testosterone decline
pathological causes of gynaecomastia
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
