Hypopituitarism Flashcards
Anterior pituitary hormones
Growth hormone (Somatotrophin) - growth
Prolactin - milk production
Thyroid stimulating hormone (TSH) - T3 and T4
Luteinising hormone (LH) & Follicle stimulating hormone (FSH) - oestrogen, progesterone and testosterone
Adrenocorticotrophic hormone (ACTH, corticotrophin) - cortisol
Hypothalamo-pituitary portal system
Hypothalamic releasing or inhibitory factors travel in the portal circulation (walls of capillaries are leaky and fenestrated) down pituitary stalk to the anterior pituitary to regulate anterior pituitary hormone production
Anterior pituitary failure
Thyroid
Adrenal cortex (cortisol)
Gonads
Can all ‘fail’ due primary disease (gland itself fails) or secondary disease (no signals from hypothalamus or anterior pituitary)
Primary vs Secondary Hypothyroidism
Primary hypothyroidism
eg autoimmune destruction of thyroid gland
T3 & T4 fall, TSH increases (we don’t measure TRH but that would also be high)
Secondary hypothyroidism eg pituitary tumour damaging thyrotrophs Can’t make TSH TSH falls T3 & T4 fall (as no TSH)
Primary vs Secondary Hypoadrenalism
NB cortisol is regulated by ACTH, aldosterone is NOT (renin-angiotensin)
Primary hypoadrenalism
eg destruction of adrenal cortex (eg autoimmune)
Cortisol falls, ACTH increases (we don’t measure CRH but that would also be high)
Secondary hypoadrenalism
eg pituitary tumour damaging corticotrophs
Can’t make ACTH
ACTH falls, cortisol falls
Primary vs Secondary Hypogonadism
Primary hypogonadism
eg destruction of testes (eg mumps) or ovaries (eg chemotherapy)
Testosterone (men) or oestrogen (women) fall, LH & FSH increase (we don’t measure GnRH but that would also be high)
Secondary hypothyroidism
eg pituitary tumour damaging gonadotrophs
Can’t make LH/FSH
LH/FSH fall, Testosterone/oestrogen fall
Causes of hypopituitarism
Congenital
Rare
Usually due to mutations of transcription factor genes needed for normal anterior pituitary development
eg PROP1 mutation
Deficient in GH and at least 1 more anterior pituitary hormone
Short stature
Hypoplastic (underdeveloped) anterior pituitary gland on MRI
Acquired (much more common)
Tumours eg adenomas, metastases, cysts
Radiation (hypothalamic/pituitary damage)
Infection eg meningitis
Traumatic brain injury
Pituitary surgery
Inflammatory (hypophysitis)
Pituitary apoplexy - haemorrhage (or less commonly infarction)
Peri-partum infarction (Sheehan’s syndrome)
Hypopituitarism - nomenclature
May affect one axis, several or all
Often describes anterior pituitary dysfunction, but certain processes - especially inflammation (hypophysitis) or surgery - may cause posterior pituitary dysfunction too
Total loss of anterior & posterior pituitary function is panhypopituitarism
Radiotherapy induced hypopituitarism
Pituitary and hypothalamus both sensitive to radiation
Radiotherapy direct to pituitary eg acromegaly or indirect eg nasopharyngeal carcinoma
Extent depends on total dose of radiotherapy delivered to the hypothalamo-pituitary axis (Gy)
GH and gonadotrophins most sensitive
PRL can increase after radiotherapy (loss of hypothalamic dopamine)
Risk persists up to 10y after radiotherapy, so annual assessment
Presentations of hypopituitarism
FSH/LH Reduced libido Secondary amenorrhoea Erectile dysfunction Reduced pubic hair
ACTH
Fatigue
NB Not a salt losing crisis (renin- angiotensin)
TSH
Fatigue
GH
Reduced quality of life
NB short stature only in children
PRL
Inability to breastfeed
Sheehan’s syndrome
Post-partum hypopituitarism secondary to hypotension (post partum haemorrhage - PPH)
More common in developing countries
Anterior pituitary enlarges in pregnancy (lactotroph hyperplasia)
PPH leads to pituitary infarction
Lethargy, anorexia, weight loss – TSH/ACTH/(GH) deficiency
Failure of lactation – PRL deficiency
Failure to resume menses post-delivery
Posterior pituitary usually not affected
Pituitary apoplexy
Intra-pituitary haemorrhage or (less commonly) infarction
Often dramatic presentation in patients with pre-existing pituitary tumours (adenomas)
May be first presentation of a pituitary adenoma
Can be precipitated by anti-coagulants
Severe sudden onset headache
Visual field defect – compressed optic chiasm, bitemporal hemianopia
Cavernous sinus involvement may lead to diplopia (IV, VI), ptosis (III)
Biochemical diagnosis of hypopituitarism
Caution in interpreting basal plasma hormone concentrations
Cortisol – what time of day?
T4 – circulating t1/2 6 days
FSH/LH – cyclical in women
GH/ACTH - pulsatile
Dynamic pituitary function in the diagnosis of hypopituitarism
ACTH & GH = ‘stress’ hormones Hypoglycaemia (<2.2mM) = ‘stress’ Insulin-induced hypoglycaemia stimulates GH release ACTH release (cortisol measured)
TRH stimulates TSH release
GnRH stimulates FSH & LH release
Radiological diagnosis of hypopituitarism
Pituitary MRI (CT not so good at delineating pituitary gland)
May reveal specific pituitary pathology eg haemorrhage (apoplexy), adenoma
Empty sella – thin rim of pituitary tissue
