Hyperprolactinaemia and hypopituitarism Flashcards
What is the most common hormonal disturbance of the pituitary
- Hyperprolactinaemia
What does prolactin stimulate
- Prolactin stimulates lactation
What can raised level of prolactin lead to and why
- hypogonadism
- infertility
- osteoporosis
does this by inhibiting secretion of GnRH and this reduces LH/FSH and reduction in testosterone or oestrogen
what can inhibit prolactin
PRL is secreted from the anterior pituitary and release is inhibited by dopamine from the hypothalamus
Define hyperprolactinaemia
> 390mU/L
What are the causes of hyperprolactinaemia
- excess production from the pituitary - prolactinoma
- loss of inhibition by dopamine
- stalk compression - pituitary adenoma
- stalk damage - surgery, trauma
- hypothalamic disease - craniopharyngioma and other tumours - use of dopamine antagonists (most common cause) - metoclopramide, haloperidol, methyldopa, oestrogen’s, ecstasy/MDMA, antipsychotics
- physiological - pregnancy, breastfeeding, stress, post-orgasm
- other - hypothyrdoism
What are the female symptoms of hyperprolactinaemia
- Amenorrhoea
- infertility
- galactorrhea
- loss of libido
- weight gain
- dry vagina
What are the male symptoms of hyperprolactinaemia
- ED
- reduced facial hair
- galactorrhea
- may present late: osteoporosis, local pressure effects from the tumour
What are the pressure effects of hyperprolactinaemia
- decreased acuity
- hemianopia
- diplopia
- ophthalmoplegia
- optic atrophy
what investigations do you use for a hyperprolactinaemia
- Basal PRL - non stressful venepuncture between 09:00-16:00 hours
- pregnancy test, TFT, U&Es
- MRI pituitary - if all other causes are ruled out
How do you manage hyperprolactinaemia
- dopamine agonists
- trans-sphenoidal surgery
Name some dopamine agonists
- Bromocriptine
- cabergoline
describe the management of microprolactinomas
- Dopamine agonist – bromocriptine, cabergoline
- Reduce PRL, restore menstrual cycles and decrease tumour size
- Dose is titrated up: 1.25mg/d PO increase weekly by 1.25-2.5mg/d until ~2.5mg/12h
- Cabergoline more effective and less SEs but less data on safety in pregnancy - Trans-sphenoidal surgery – if intolerant to dopamine agonists
- High success rate but carries risks of permanent hormone deficiency and prolactinoma recurrence, and so it is usually reserved as 2nd line treatment
What are the side effects of microprolactinomas
SEs – nausea, depression, postural hypotension
What is the difference between microprolactinomas and macroprolactinomas
- Microprolactinomas = <10mm
- Macroprolactinomas = >10mm
how do you manage macroprolactinoma
- Dopamine agonist – bromocriptine, cabergoline
- Trans-sphenoidal surgery
- Rarely needed but consider if visual symptoms or pressure effects which fail to respond to treatment
- Bromocriptine ± radiotherapy may be required post-op as complete surgical resection is uncommon
what is hypopituitarism
- decreased secretion ofanterior pituitary hormones
- affected in the following order: GH, FSH&LH, TSH, ACTH, PRL
What is panhypopituitarism
- this is deficiency of all anterior hormones usually caused by irradiation, surgery or pituitary tumour
What are the causes of hypopituitarism
- Hypothalamus – Kallman’s syndrome, tumour, inflammation, infection (meningitis, TB), ischaemia
- Pituitary stalk – trauma, surgery, mass lesion (craniopharyngioma), meningioma, carotid artery aneurysm
- Pituitary – tumour, irradiation, inflammation, autoimmunity, infiltration (haemochromatosis, amyloid, metastases), ischaemia (pituitary apoplexy, DIC, Sheehan’s syndrome)
what are the symptoms of hypopituitarism
- GH – central obesity, atherosclerosis, dry wrinkly skin, ↓strength, ↓balance, ↓well-being, ↓exercise ability, ↓CO, osteoporosis, ↓glucose
- FSH&LH
- Women: oligomenorrhoea or amenorrhoea, ↓fertility, loss of libido, osteoporosis, breast atrophy, dyspareunia
- Men: ED, loss of libido, ↓muscle bulk, hypogonadism (↓body hair, small testes, ↓ejaculate volume, ↓spermatogenesis) - TSH – as for hypothyroidism
- ACTH – as for adrenal insufficiency (note no skin pigmentation as ↓ACTH
- PRL – rare; absent lactation
What do blood tests show in hypopituitarism
- LH and FSH ↓ or ↔
- Testosterone or oestradiol ↓
- TSH (↓ or ↔) and T4 ↓
- PRL ↑
- IGF-1 ↓
- Cortisol ↓
- U&Es – ↓Na+ from dilution
- FBC – ↓Hb (normochromic, normocytic)
what do dynamic tests show in hypopituitarism
- Short Synacthen test – to assess adrenal axis
- Insulin tolerance test (ITT) – to assess adrenal and GH axes
- CI: epilepsy, heart disease, adrenal failure 🡪 glucagon stimulation test
- Induces hypoglycaemia, causing stress to ↑cortisol and GH - Arginine + GHRH test
What is the management of hypopituitarism
Hormone replacement therapy and treatment of underlying cause
- hydrocortisone - fro secondary adrenal failure before any other hormones are given
- Thyroxine - if hypothyroid
Hypogonadism
- men - testosterone enanthate 250mg IM every 3 weeks, daily topical gels, buccal mucoadhesive tablets or patches
- Women - oestrogen: transdermal estradiol patches or COCP, +/- testosterone or dehydroepiandrosterone
- gonadotrophin therapy to induce fertility
- GH - somatotrophin mimics human GH, addresses problems of increased fat mass, decreased bone mass, decreased muscle bulk, decreased exercise capacity and problems with heat intolerance
