ENDO; Lecture 1 and 2 & Tutorial 1 - Hyposecretion and Hypersecretion of anterior pituitary hormones; Anterior pituitary disorders Flashcards
Which hormones does the anterior pituitary release?
FSH/LH, Prolactin, GH, TSH, ACTH
Where would a disorder in the endocrine gland, the anterior pituitary, hypothalamus result in?
3ry isn’t clinically referenced but due to hypothalamic neurones not working
What is hypopituitarism and how does it come about?
Decreased production of all anterior pituitary hormones (a.k.a panhypopituitarism) or of specific hormones -> acquired or congenital (rare)
What is congenital panhypopituitarism - cause, symptoms, MRI?
Rare, due to mutations of TF genes needed for normal pituitary development (PROP1); deficient in GH and >1 pit hormone -> short stature (w/other features); hypoplastic anterior pit gland on MRI (underdeveloped)
What causes acquired panhypopituitarism?
Tumours, radiation, infection, traumatic brain injury, infiltrative disease (often involving pit stalk), inflammatory (hypophysitis), pituitary apoplexy (haemorrhage), peri-partum infarction (Sheehan’s syndrome)
Which kind of tumours cause acquired panhypopituitarism?
Hypothalamic (craniopharyngiomas), pituitary (adenomas, metastases, cysts)
Radiation to what causes acquired panhypopituitarism?
Hypothalamic/pituitary damage - GH most vulnerable, TSH relatively resistant
How is panhypopituitarism presented?
2ry means there is nothing wrong with the endocrine gland but with the pituitary so there is nothing to tell the gland to work/function
What is Sheehan’s syndrome?
Post-partum hypopituitarism secondary to hypotension (PP-haemorrhage) -> less common in developed countries
What is the cause of Sheehan’s syndrome?
Anterior pituitary enlarges in pregnancy (lactotroph hyperplasia) as prolactin increases to prepare to feed the child -> PPH leads to (mainly anterior) pituitary infarction as post-Partum haemorrhage leading to poor perfusion of pit, hence infarction
What are the presentations of Sheehan’s syndrome?
Lethargy, anorexia, weight loss -> TSH/ACTH/(GH) deficiency; failure of lactation (Prolactin deficiency); failure to resume menses post delivery; post. pit. usually not affected
What is pituitary apoplexy?
Intra-pituitary haemorrhage or (rarer) infarction -> dramatic presentation in patients with pre-existing pit. adenomas (may be first presentation) -> can be precipitated by anticoagulants
What are the symptoms of pituitary apoplexy?
SEVERE sudden onset headache, visual field defect (compressed optic chiasm; “bitemporal hemianopia”), cavernous sinus involvement may lead to diplopia, ptosis
Which compressed cranial nerves lead to diplopia?
IV, VI
Which compressed cranial nerves lead to ptosis?
III
How are the CN arranged in relation to the pituitary?
How do you diagnose biochemically hypopituitarism?
Basal plasma conc of pit/target endocrine gland hormones or stimulated “dynamic” pit function tests
What are the problems associated with diagnosing hypopituitarism using basal plasma conc?
Interpretation may be limited, undetectable cortisol, T4 with circulating 1/2 life 6 days, LH/FSH cyclical, GH/ACTH pulsatile
What are the problems associated with diagnosing hypopituitarism using stimulated pit. function tests?
ACTH/GH = stress hormones, in the lab hypoglycaemia (2.2mM) can represent a stressor -> which if insulin-induced stimulates GH and ACTH release - measuring cortisol and GH (rises if normal);TRH (injected) stimulates TSH and GnRH (injected) stimulates FSH/LH released -> if patient has increased levels of all hormones then normal, but if levels stay low or below a threshold then there could be problems
How would you diagnose hypopituitarism using radiology?
Pit. MRI, which may reveal specific pathology (haemorrhage, apoplexy, adenoma) or empty sella turcica meaning there’s a thin rim of tissue
What would you use in hormone replacement therapy for ACTH and what would you check?
Hydrocortisone, checking serum cortisol levels
What would you use in hormone replacement therapy for TSH and what would you check?
Thyroxine and check Serum free T4
What would you use in hormone replacement therapy for Women LH/FSH and what would you check?
HRT (E2 plus progestagen) checking symptom improvement and withdrawal bleeds
What would you use in hormone replacement therapy for men LH/FSH and what would you check?
Testosterone checking for symptom improvement and serum testosterone
What would you use in hormone replacement therapy for GH and what would you check?
GH checking IGF1 and growth chart
What is the effect of somatotrophin deficiency?
Children: short stature (<2SDs mean height for child same age and sex). Adults: effects less clear
What are the causes of short stature?
What is the effect of short stature in children on the growth axis?
What is achondroplasia?
Mutation in fibroblast GF receptor 3 (FGF3), with abnormality in growth plate chondrocytes -> impaired linear growth so average size trunk but short arms and legs
What are the different types of dwarfism?
Achondroplasia, pit. dwarfism, laron dwarfism
What is the cause of pit dwarfism?
Childhood GH deficiency
What is laron dwarfism?
Mutation in GH receptor (primary) with IGF-1 treatment in childhood increasing height -> high incidence in village in Ecuador with apparently low cancer incidence
How do you diagnose short stature?
Mid parental height -> Predicted adult height based on father & mother’s height -> monitored on growth chart
What are the causes of acquired GH deficiency in adults?
Trauma, pit tumour/surgery, cranial radiotherapy
How do you diagnose GH deficiency?
Random GH - pulsatile; use a provocative challenge (stimulation test)
What are the kinds of GH provocation tests?
GHRH + arginine (i.v. - combined= more effective); insulin (iv - via hypoglycaemia), glucagon (im), exercise (when appropriate) -> measure plasma GH at specific timepoints
What is the normal and GH deficiency response to hypoglycaemia?
How is GH therapy prepared and administrated?
Human recombinant GH (somatotropin) prepared and administered daily subcutaeneously, monitoring clinical response with dose-adjustment to IGF-1
How is GH therapy absorbed, distributed, metabolised and how long does it last?
A&D: max plasma conc in 2-6h; metabolism: hepatic/renal with t1/2 approx 20 min; lasts beyond clearance with peak IGF1 levels at approx 20h
What are the signs and symptoms of GH deficiency in adults?
Reduced lean mass, increased adiposity, increased hip:waist; reduced muscle strength&bulk, reduced exercise performance, decreased plasma HDL-cholesterol & raised LDL cholesterol, impaired psych well being and reduced QOL
What are the potential benefits of GH therapy in adults?
Improves body comp, decreases waist circumference, less visceral fat; improves muscle strength and exercise capacity; more favourable lipid profile; increased bone mineral density; improved physiological well being and QOL
What are the potential risk of GH therapy in adults?
Increased cancer susceptibility and expensive
What is hyperpituitarism?
Symptoms associated with excess production of adenohypophysial hormones
What causes hyperpituitarism?
Isolated pit tumours, but also ectopic in origin
What is hyperpituitarism associated with?
Visual field and other (CN associated) defects as well as endocrine related signs and symptoms
What is bitemporal hemianopia?
Optic chiasm is compressed by growth of suprasellar tumour
How would you assess a bitemporal hemianopia?
What are the results of excess ACTH, TSH, LH/FSH, prolactin and GH in hyperptuitarism?
What are the causes of hyperprolactinaemia?
Physiological: pregnancy, breastfeeding. Pathological: prolactinoma (microadenomas)
What does high prolactin suppress?
GnRH pulsatility
What is a prolactinoma?
Most common functioning pit tumour
What are the symptoms in women of hyperprolactinaemia?
Galactorrhoea, secondary ammenorrhoea, loss of libido, infertility
What are the symptoms in men of hyperprolactinaemia?
Galactorrhoea is uncommon, loss of libido, erectile dysfunction, infertility
How is hyperprolactinaemia treated?
D2 receptor agonists: decrease prolactin secretion and reduce tumour size (given orally)
What are some examples of D2 receptor agonists?
Bromocriptine, cabergoline
What are the eside effects of DA receptor agonists?
N&V, postural hypotension, dyskinesias, depression, pathological gambling
What does excess GH result in during childhood and adulthood?
Child: Gigantism; adult: acromegaly -> usually due to benign GH-secreting pit adenoma
What is acromegaly?
Insidious onset with S&S progressing gradually -> untreated= excess GH associated with ^ morbidity and mortality
How can patients with acromegaly die?
CVD =60%, Resp complications =25%, Cancer =15%
What grows in acromegaly?
Periosteal bone, cartilage, fibrous tissue, connective tissue, internal organs (cardio/spleno/hepatomegaly)
What are the clinical features of acromegaly?
What are the metabolic effects of acromegaly?
Excess GH -> inhibits insulin signalling -> increases insulin resistance -> impaired glucose tolerance -> diabetes mellitus
What are the complications of acromegaly?
What other hormone is secreted with GH in acromegaly?
Prolactin -> which is often high and could be indicating tumour secreting both GH& prolactin
What can hyperprolactinaemia cause with acromegaly?
2ry hypogonadism
How do you diagnose acromegaly?
GH pulsatile, elevated serum IGF-1, failed suppression (paradoxical rise) of GH following oral glucose load (oral glucose tolerance test)
What does the glucose tolerance test look like in a normal and an acromegalic patient?
How do you treat acromegaly?
Surgery (trans-sphenoidal), medical: somatostatin analogues (octreotide), DA agonists (cabergoline), radiotherapy
What are somatostatin analogues - administration, side effects, action?
