Hypopituitarism Flashcards
Define hypopituitarism.
Hypopituitarism refers to the partial or complete deficiency of one or more pituitary hormones.
How common is hypopituitarism?
Rare
Cardiovascular and cerebrovascular death rates are higher in patients with hypopituitarism compared with the normal population. GH deficiency is most probably responsible for this increased mortality from cardiovascular disease
What is the aetiology of hypopituitarism?
-
Neoplastic
- Pituitary adenoma - MOST COMMON
- Craniopharyngioma
- Other SOLs - sellar meningiomas, metastases, plasmacytomas, germ cell tumours, astrocytomas of optic nerve, chorndromas
-
Vascular
- Pituitary apoplexy
- Sheehan syndrome - after substantial blood loss with hypotension during childbirth
- Intersellar aneurysms of carotid arteries
-
Inflammatory and infiltrative lesions
- Lymphocytic hypophysitis - particularly in the setting of pregnancy or postpartum
- Haemachromatosis - iron deposition in pituitary cells
- Sarcoidosis, TB, Langerhans cell histocytosis
-
Infection
- Abscess
- Tuberculomas
- Fungal pituitary disease - HIV complication
- Congenital - mutations, deficiencies etc
- Radiotherapy
- Pituitary surgery
-
Other
- TBI
- Empty sella syndrome
- Chronic opiate use
Which hormones are lost first and last in sequential anterior pituitary hormone loss secondary to mass effect?
- GH and gonadotrophins (LH and FSH) - less importnat
- adrenocorticotrophic hormone (ACTH)
- TSH
The hormones least needed for survival are lost first and the ones critical for survival are preserved till later
How does empty sella syndrome cause hypopituitarism?
- Primary empty sella - defect in diaphragm sella which allows CSF pressure to enlarge the sella - this is NOT ASSOCIATED with hypopituitarism
- Secondary empty sella - mass such as adenoma enlarges the sella and is later removed by surgery, radiation or infarction and subsequently leaves CSF vacuum. Pituitary hormone dysfunction only results from mass effect of the removed tumour.
What are the signs and symptoms of hypopituitarism?
Manifestations depens on duration and degree of hormone deficiencies
- Cranial nerve palsies, temporal lobe epilepsy, and CSF rhinorrhoea
- Pregnancy related:
- Failure to lactate postpartum
- Pituitary apoplexy - headache, nausea, vomiting, fatigue, weakness, dizziness, and circulatory collapse secondary to acute loss of ACTH and thus cortisol deficiency.
-
LH/FSH deficiency -
- M: erectile dysfunction, infertility, reduced bone and muscle mass, loss of hair, gynaecomastia, and testicular atrophy/
- F: oligomenorrhoea, infertility, reduced libido, breast atrophy, hot flushes, osteoporosis, and premature atherosclerosis
- ACTH deficiency - anorexia, weight loss, nausea, myalgias, hypoglycaemia, pallor, and loss of axillary and pubic hair in women, hypotension
- ADH deficiency - DI - nocturia, polyuria, and polydipsia
-
GH deficiency - obesity, reduced lean body and bone mass, reduced exercise capacity, fatigue
- Children - failure to thrive, short stature, delayed dentition, delayed puberty, obesity, and sequelae of hypoglycaemia.
Which investigations would you do for hypopituitarism?
Pituitary hormone tests: combined pituitary function test (“triple test”) is best for measuring these.
- ACTH
- Cortisol
- TSH
- Free thyroxine (T4) and triiodothyronine (T3)
- FSH/LH
- Prolactin
Other:
- Estradiol and testosterone
- U&E
- Serum and urine osmolality - hyponatraemia in ACTH/TSH deficiency (hypernatraemia = DI)
- 8am morning cortisol and ACTH
- Cosyntropin/tetracosactide stimulation test - 250microg IM/IV and serum cortisol measured at 30 and 60min
- Insulin tolerance test (ITT) - adrenal reserve test
- Water deprivation and desmopressin response test - for DI
- TFTs
- MRI pituitary
How do you manage hypopituitarism acutely?
Pituitary apoplexy - IV hydrocortisone
Hypopituitarism e.g. functioning pituitary macroadenoma
- URGENT hydrocortisone replacement (fludrocortisone is not necessary as adrenals should still be able to make aldosterone as it is independent of the HPA)
-
Total therapy (ordered):
- Hydrocortisone replacement
- Thyroxine replacement
- Oestrogen replacement
- GH replacement
- (Cabergoline or Bromocriptine – if prolactinoma is the cause of the failure –> shrinks tumour)
- Dopamine agonists
What is the difference between dosing of carbegoline and bromocriptine?
Bromocriptine TDS
Carbegoline once weekly
What are the complications of hypopituitarism and its treatment?
- Infertility
- Overreplacement can cause hormone excess manifestations e.g. Cushing’s, arrhythmias, osteoporosis, hyponatraemia, oedema, prostatic hypertrophy, hyperlipidaemia, high heamatocrit.
What is the prognosis with hypopituitarism?
x1.8 greater mortality compared with age and sex-matched population
CVA deaths are more common - GH deficiency id potentially responsible for this
Does pituitary failure cause hypotension?
No - still have aldosterone
What are the 6 hormones in the anterior pituitary?
- GHRH –> GH
- TRH –> TSH, prolactin
- Dopamine – > lowers prolactin
- LHRH/GnRH –> LH, FSH
- CRH –> ACTH
Why does primary hypothyroidism cause hyperprolactinaemia?
TRH stimulates its production
What is a macroadenoma in the pituitary?
>1cm
What are some clinical features of pituitary failure due to macroadenoma?
- Galactorrhoea
- Amenorrhoea
- Bitemporal hemianopia
If prolactin in >6000 what is the diagnosis?
Prolactinoma is the only cause of such high prolactin
Normal prolactin is <600
How do you test for bitemporal hemianopia?
Humphreys 30-2 test - blind spot should always be dark
What is administered in the combined pituitary function test?
Triple test:
GnRH/LHRH given → LH/FSH rise
TRH given → TSH and prolactin rise
Insulin given →
- CRH → ACTH → cortisol → glucose
- GHRH rise → GH → glucose
How do you correct hypoglycaemia in CFT?
50ml 20% glucose - must have good IV access for this test
What is the method for the CPFT?
Fast overnight
IV access
Calculate insulin required (0.15U/kg) and give alongside TRH 200mcg, and LHRH/GnRH 100mg
Take bloods at 0, 30, 60min and measure glucose, cortisol, GH, LH/FSH, TSH/T4 and prolactin.
Take bloods additionally at 90 and 120mins to check glucose, cortisol and GH.
Interpret this CPFT.
Pit macroadenoma (functioning) - requires replacement of all hormones but hydrocortisone urgently. If the patient only presented with a bitemporal hemianopia then this would be a non-functioning adenoma. Non-functioning adenomas still require replacement of all hormones but they can still rescue themselves with adrenaline so no need for rescue therapy.
How does a non-functioning pituitary adenoma present?
Bitemporal hemianopia
Hyperprolactinaemia - because it presses on pituitary stalk so no negative inhibition from dopamine on prolactin release.
Which steroid is used as replacement in pituitary failure?
Hydrocortisone (BD or TDS) is used more nowadays but prednisolone would only need to be given OD and actually matched circadian rhythm better so probably will be used more in the future.
