A 32-year-old woman presents to her GP concerned over her periods. She used to have regular 28-d cycles but over the past 2 years she has experienced these becoming irregular and then ceasing for the past 4 months. Her GP arranges for her to have some blood tests, which are shown below:

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|--------------|:-------:|---------------|
|Luteinising Hormone|12.2 IU/L|1 - 11 (Luteal)|
|Follicle Stimulating Hormone|42.3 IU/L|2 - 8 (Luteal)|
|Testosterone|1.1 nmol/L|(M) 9.9 - 27.8, (F) 0.2 - 2.9|
|Prolactin|520 IU/L|(M) 90 - 320, (F) 100 - 500|
|Thyroid Stimulating Hormone|4.5 mU/L|0.3 - 4.2|
|Oestradiol|22 pmol/L|45 - 854|
|Anti-Müllerian hormone (AMH)|2.2 pmol/L|6.8 - 47.8|


What is the most likely diagnosis?

Options:
explanation: Pituitary apoplexy is bleeding or infarction of the pituitary, usually in the context of a pre-existing pituitary adenoma or in postpartum haemorrhage. This would lead to a fall in the pituitary hormones LH and FSH and subsequently low levels of oestrogen. In this case, there is no history consistent with pituitary apoplexy, such as a sudden-onset headache, and the levels of FSH and LH are high, indicating primary ovarian failure.
name: Pituitary apoplexy
label: d
answer: no
explanation: Primary ovarian failure results in a reduction of ovarian oestrogen production. The drop in oestrogen reduces negative feedback on the pituitary gland, which produces more LH and FSH in response. Her AMH is also low; this is a measure of the number of eggs that the patient has remaining, further pointing towards ovarian failure.
name: Primary ovarian failure
label: a
answer: yes
explanation: Hypothyroidism can cause amenorrhoea and infertility in females. It causes a hypogonadotrophic hypogonadism as raised thyrotropin-releasing hormone levels stimulate prolactin release, which suppresses gonadotropin-releasing hormone release. In this patient, the LH/FSH are raised, making this less likely. This patient also lacks other features of hypothyroidism, such as weight gain, hair loss and cold intolerance.
name: Hypothyroidism
label: e
answer: no
explanation: During pregnancy, LH and FSH levels are low due to negative feedback from higher levels of oestrogen. This patient has low oestrogen levels alongside low FSH and LH. This indicates ovarian failure rather than pregnancy. They do not report any symptoms in keeping with pregnancy either, such as morning sickness, weight gain or breast tenderness. However, in practice a pregnancy test would be conducted to definitively rule this out in any patient presenting with secondary amenorrhea.
name: Current pregnancy
label: b
answer: no
explanation: Hypothalamic hypogonadism would result in low levels of LH, FSH and subsequently oestrogen, due to lack of gonadotropin-releasing hormone release stimulating the pituitary gland. This usually occurs in the context of anorexia or excess exercise. The patient in this case has a normal body mass index and there is no mention of excessive exercise.
name: Hypothalamic hypogonadism
label: c
answer: no

Correct answer: a


Learning point: Primary ovarian failure is characterised by elevated LH and FSH levels, low oestradiol, and decreased anti-Müllerian hormone, indicating reduced ovarian function.