L16: Pituitary disorders Flashcards
What are pituitary disorder?
Over- or under-secretion of pituitary hormones
Most common causes is a benign tumour (adenoma)
What are non functioning tumours?
Tumour cells do not produce any hormone
Inadequate production of one or more hormones
Due to compression of tumour on glandular tissue
Lateral growth/ compression–> pain and double vision
Superior growth/ compression –> Bitemporal hemi-anopia (tunnel vision)–> lateral field of view lost
(light travels in straight lines so lateral field will be picked up on middle part of retina which is lost??)
What are functional tumours?
Usually hypersecreting
Over production of hormone
How are pituitary tumours investigated and diagnosed?
- MRI scan–> delineation of the anatomy, size and topographical location of the pituitary or parapituitary mass
- Assessment of visual field defects
- Assessment of endocrine function–> hormonal excess or deficiency–> measurement of hormone levels in blood, or by staining sections from a biopsy with antibody for relevant hormone
How can biochemical assessment be useful for determining pituitary disease?
Basal blood test sufficient for somethings
- Thyroid axis –> fT4, TSH
- Gonadal axis–> LH, FSH
- Prolactin axis–> serum prolactin
Dynamic blood test needed for some
- HPA axis –> cortisol–> circadian rhythm control
- GH axis–> GH/ IGF-1
–> Not enough hormone–> stimulate it see what happen
–> Too much –> supress it see if the level decrease–> if not sign of a tumour
How does the dynamic assessment of adrenal axis work?
Suspect deficiency
–> inject synACTHase–> monitor cortisol level T=0 and T=30–> increase shows adrenal glands functioning
OR
–> Insulin stress test–> stress the body (hypoglycaemic stress)–> See if ACTH and cortisol levels increase–> if so pituitary glands working
Suspect excess
–> Inject steroids (dexamethasone)–> see if cortisol levels decrease–> if they don’t autominal cortisol secretion
How does the dynamic assessment of growth hormone axis work?
Suspect deficiency
–> Insulin stress test–> Hypoglycamic stress–> GH should increase to couteract insulin
Suspect excess
–> Glucose tolerance test–> give glucose–> GH should fall–> if not autominal secretion
What is hypopituitarism? Which hormones are decreased and which are increased? Why?
Insufficient hormone production
Deficiency in all –> panhypopituitarism
Common result of pituitary adenoma–> prevents hormone release
Reduced–> GH (GHRH), LH/FSH (GnRH), TSH (TRH) and ACTH (CRH)
Increased–> prolactin–> dis-inhibition (not inhibited) by dopamine
PP not really affected unless tumour affect hypothalamic function or inflammatory process involved
In which order are the hormones affected in hypopituitarism?
GH lost first (GHRH)–> short stature in children, reduced QoL in adults
LH/FSH second (GnRH)–> delayed puberty in children. loss of sexual characteristics in adults, loss of period in women (early sign)
TSH/ ACTH third (TRH, CRH)–> late feature of tumour
–> TSH–> low T hormones, weight gain, tiredness, slow pulse, Low T4 and Low TSH
–> ACTH–> low cortisol, tired, dizzy, low BP, low Na+
can be LIFE THREATENING!
What are the symptoms of growth hormone deficiency? Why is it difficult to diagnoses? What causes it? How is severe GH deficiency treated?
Symptoms in adults subtle
Decrease tolerance to exercise, decrease muscle strength, increased body fat, reduced sense of ‘well-being’
Severe prenatal deficiency-> hyperglycaemia and jaundice, poor growth and shorten stature
GH released in pulsative fashion
Cause in children generally idiopathic, specific gene mutations identified and autoimmune inflammation in some cases
Recombinant DNA technology to manufacture GH
What are the results of gonadotropin deficiency?
Hypogonadism
Lack of libido, infertility, oligomenorrhea or amenorrhea , impotence
What is hyperpituitarism?
Excess pituitary hormones production
Hypersecreting pituitary adenoma
Three main conditions: Prolactin excess, Growth hormone excess and ACTH excess
What is prolactinoma?
Prolactin-secreting pituitary tumour
large tumour–> macro-adenoma
small tumour–> micro-adenoma
Larger the tumour= higher the prolactin
What is hyperprolactinaemia? What causes it? What are the symptoms?
Abnormally high prolactin level
Prolactinoma (most common cause)
Symptoms
-Galactorrhoea (unexplained milk produciton)
-Gynecomastia (hard breast tissue)
-Hypogonadism (dimished activites of testes and ovaries)
-Amenorrhea (cessation of menstural cycle)
-Erectile dysfunction (men)
What normally causes high prolactin?
Physiological causes such as pregnancy, suckling, stress and exercise and drugs (antipsychotics and antidepressants)
Disinhibition of prolactin
–> compression of infindibulum prevent dopamine secretion (inhibits prolactin)
prolactin <5000–> disinhibition
prolactin >5000–> active prolactin secretion (prolactinoma)
What are the clinical features of non-functioning pituitary adenoma?
Symptoms due to mass effects or symptoms of low pituitary hormones Bitemporal hemi-anopia -Tunnel vision Blood results -->T4 low and TSH low --> Low hormones --> Except prolactin--> dis-inhibition
Why is it important to determine the cause of high prolactin and hyperprolactaemia?
Determines treatment
What is the treatment for prolactinoma?
Disinhibtion (non functioning tumour) –> treatment surgical
Functioning tumour–> medical treatment (dopamine, dopamine receptor agonists–> cabergoline)
What could be another potential cause for high prolactin not caused by tumour?
Some medications
Antagonist for doparmine receptor
Anti-sickness drug, anti-psychotics
Pregnancy
What is acromegaly?
‘Large extremities’
Patient present with large hands, feet and jaws
Excess GH production
GH secreting pituitary tumour
What are complications of untreated acromegaly?
Premature CVD death
Increased risk of colonic tumours
Probably increased risk of thyroid cancer
Disfiguring body changes that may be irreversible
Hypertension and diabetes
Unpleasant symptoms
What are the biochemical test that confirm acromegaly?
Oral glucose tolerance test
Failure to supress GH<1ug/L
Elevated IGF-1 level
Growth hormone day curve (GHDC)–> elevated mean GH
How is acromegaly treated?
Surgical removal of tumour–> trans-sphenoidal hypophysectomy
Medical treatment
1. Reduce GH secretion –> dopmaine agonist (cabergoline and bromocriptine)
–> somatostatin analogues (octreotide, lanreotide and pasireotide)
2. Block GH receptor (pegvisomant)
Radiotherapy
-External beam- multiple short burst over several weeks
-Gamma knife- high concentration over single time
What causes excess of GH? What are the signs?
Pituitary adenoma >10mm in diameter
Local mass–> headaches, visual field defects, cranial nerve palsies
Changes to physical appearance–> broad nose, coarse facial features, thick lips, prominent suborbital ridge
Enlarged hands and feet
Greasy skin and excessive sweating
Deepening of the voice
What causes the systemic effects of GH excess?
GH action on GHR
IGF-1 production–> IGF-1 Receptors
What happens if the excessive GH secretion occurs in childhood? What is a common clinical presentation in children?
Gigantism
Epiphyseal growth plates not fused–> long bones increase in length
Diabetes mellitus–> GH and IGF-1 antagonise insulin action
What is Cushing’s disease? What causes it?
Excess secretion of ACTH
ACTH-secreting pituitary tumour
What does Cushing’s disease result in?
Change in features Round pink face and round abdomen Skinny and weak arms and legs Thin skin and easy bruising Red stretch marks on abdomen High blood pressure and diabetes Osteoporosis (thin bones)
What is the difference between Cushing’s disease and Cushing’s syndrome?
CD–> Pituitary tumour
CS–> can be caused by other pathologies (adrenal tumour, ectopic ACTH, steroid medication)
What is diabetes insipidus? What might cause it?
Posterior pituitary doesn’t produce ADH
Deficiency in ADH
Hypothalamic tumour or pituitary tumour that extend into hypothalamus (crainal radiotherapy, pituitary surgery, autoimmune infiltration and infection may also cause it)
What is the result of diabetes insipidus?
Increased urine output--> Very dilute so very clear Dehydration Polydipsia (thirst) High sodium levels--> hypernatraemia Reduced consiousness, coma and death
What is pituitary apoplexy?
Old fashioned word for stroke
Pituitary tumour–> sudden vascular event
Bleeding within tumour–> haemorrhage
Blood supply cut off–> infarction
What is the clinical presentation for pituitary apoplexy?
Sudden onset headache Double vision Visual field loss Cranial nerve palsy Hypopitutarism--> cortisol deficiency (ACTH deficiency) most dangerous--> DEATH Prompt diagnosis and treatment
