ENDO; Lecture 1 and 2 & Tutorial 1 - Hyposecretion and Hypersecretion of anterior pituitary hormones; Anterior pituitary disorders

Question 1

Which hormones does the anterior pituitary release?

Answer 1

FSH/LH, Prolactin, GH, TSH, ACTH

Question 2

Where would a disorder in the endocrine gland, the anterior pituitary, hypothalamus result in?

Answer 2

3ry isn’t clinically referenced but due to hypothalamic neurones not working

Question 3

What is hypopituitarism and how does it come about?

Answer 3

Decreased production of all anterior pituitary hormones (a.k.a panhypopituitarism) or of specific hormones -> acquired or congenital (rare)

Question 4

What is congenital panhypopituitarism - cause, symptoms, MRI?

Answer 4

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)

Question 5

What causes acquired panhypopituitarism?

Answer 5

Tumours, radiation, infection, traumatic brain injury, infiltrative disease (often involving pit stalk), inflammatory (hypophysitis), pituitary apoplexy (haemorrhage), peri-partum infarction (Sheehan’s syndrome)

Question 6

Which kind of tumours cause acquired panhypopituitarism?

Answer 6

Hypothalamic (craniopharyngiomas), pituitary (adenomas, metastases, cysts)

Question 7

Radiation to what causes acquired panhypopituitarism?

Answer 7

Hypothalamic/pituitary damage - GH most vulnerable, TSH relatively resistant

Question 8

How is panhypopituitarism presented?

Answer 8

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

Question 9

What is Sheehan’s syndrome?

Answer 9

Post-partum hypopituitarism secondary to hypotension (PP-haemorrhage) -> less common in developed countries

Question 10

What is the cause of Sheehan’s syndrome?

Answer 10

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

Question 11

What are the presentations of Sheehan’s syndrome?

Answer 11

Lethargy, anorexia, weight loss -> TSH/ACTH/(GH) deficiency; failure of lactation (Prolactin deficiency); failure to resume menses post delivery; post. pit. usually not affected

Question 12

What is pituitary apoplexy?

Answer 12

Intra-pituitary haemorrhage or (rarer) infarction -> dramatic presentation in patients with pre-existing pit. adenomas (may be first presentation) -> can be precipitated by anticoagulants

Question 13

What are the symptoms of pituitary apoplexy?

Answer 13

SEVERE sudden onset headache, visual field defect (compressed optic chiasm; “bitemporal hemianopia”), cavernous sinus involvement may lead to diplopia, ptosis

Question 14

Which compressed cranial nerves lead to diplopia?

Answer 14

IV, VI

Question 15

Which compressed cranial nerves lead to ptosis?

Answer 15

III

Question 16

How are the CN arranged in relation to the pituitary?

Answer 16

Question 17

How do you diagnose biochemically hypopituitarism?

Answer 17

Basal plasma conc of pit/target endocrine gland hormones or stimulated “dynamic” pit function tests

Question 18

What are the problems associated with diagnosing hypopituitarism using basal plasma conc?

Answer 18

Interpretation may be limited, undetectable cortisol, T4 with circulating 1/2 life 6 days, LH/FSH cyclical, GH/ACTH pulsatile

Question 19

What are the problems associated with diagnosing hypopituitarism using stimulated pit. function tests?

Answer 19

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

Question 20

How would you diagnose hypopituitarism using radiology?

Answer 20

Pit. MRI, which may reveal specific pathology (haemorrhage, apoplexy, adenoma) or empty sella turcica meaning there’s a thin rim of tissue

Question 21

What would you use in hormone replacement therapy for ACTH and what would you check?

Answer 21

Hydrocortisone, checking serum cortisol levels

Question 22

What would you use in hormone replacement therapy for TSH and what would you check?

Answer 22

Thyroxine and check Serum free T4

Question 23

What would you use in hormone replacement therapy for Women LH/FSH and what would you check?

Answer 23

HRT (E2 plus progestagen) checking symptom improvement and withdrawal bleeds

Question 24

What would you use in hormone replacement therapy for men LH/FSH and what would you check?

Answer 24

Testosterone checking for symptom improvement and serum testosterone

Question 25

What would you use in hormone replacement therapy for GH and what would you check?

Answer 25

GH checking IGF1 and growth chart

Question 26

What is the effect of somatotrophin deficiency?

Answer 26

Children: short stature (\<2SDs mean height for child same age and sex). Adults: effects less clear

Question 27

What are the causes of short stature?

Answer 27

Question 28

What is the effect of short stature in children on the growth axis?

Answer 28

Question 29

What is achondroplasia?

Answer 29

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

Question 30

What are the different types of dwarfism?

Answer 30

Achondroplasia, pit. dwarfism, laron dwarfism

Question 31

What is the cause of pit dwarfism?

Answer 31

Childhood GH deficiency

Question 32

What is laron dwarfism?

Answer 32

Mutation in GH receptor (primary) with IGF-1 treatment in childhood increasing height -\> high incidence in village in Ecuador with apparently low cancer incidence

Question 33

How do you diagnose short stature?

Answer 33

Mid parental height -\> Predicted adult height based on father & mother's height -\> monitored on growth chart

Question 34

What are the causes of acquired GH deficiency in adults?

Answer 34

Trauma, pit tumour/surgery, cranial radiotherapy

Question 35

How do you diagnose GH deficiency?

Answer 35

Random GH - pulsatile; use a provocative challenge (stimulation test)

Question 36

What are the kinds of GH provocation tests?

Answer 36

GHRH + arginine (i.v. - combined= more effective); insulin (iv - via hypoglycaemia), glucagon (im), exercise (when appropriate) -\> measure plasma GH at specific timepoints

Question 37

What is the normal and GH deficiency response to hypoglycaemia?

Answer 37

Question 38

How is GH therapy prepared and administrated?

Answer 38

Human recombinant GH (somatotropin) prepared and administered daily subcutaeneously, monitoring clinical response with dose-adjustment to IGF-1

Question 39

How is GH therapy absorbed, distributed, metabolised and how long does it last?

Answer 39

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

Question 40

What are the signs and symptoms of GH deficiency in adults?

Answer 40

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

Question 41

What are the potential benefits of GH therapy in adults?

Answer 41

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

Question 42

What are the potential risk of GH therapy in adults?

Answer 42

Increased cancer susceptibility and expensive

Question 43

What is hyperpituitarism?

Answer 43

Symptoms associated with excess production of adenohypophysial hormones

Question 44

What causes hyperpituitarism?

Answer 44

Isolated pit tumours, but also ectopic in origin

Question 45

What is hyperpituitarism associated with?

Answer 45

Visual field and other (CN associated) defects as well as endocrine related signs and symptoms

Question 46

What is bitemporal hemianopia?

Answer 46

Optic chiasm is compressed by growth of suprasellar tumour

Question 47

How would you assess a bitemporal hemianopia?

Answer 47

Question 48

What are the results of excess ACTH, TSH, LH/FSH, prolactin and GH in hyperptuitarism?

Answer 48

Question 49

What are the causes of hyperprolactinaemia?

Answer 49

Physiological: pregnancy, breastfeeding. Pathological: prolactinoma (microadenomas)

Question 50

What does high prolactin suppress?

Answer 50

GnRH pulsatility

Question 51

What is a prolactinoma?

Answer 51

Most common functioning pit tumour

Question 52

What are the symptoms in women of hyperprolactinaemia?

Answer 52

Galactorrhoea, secondary ammenorrhoea, loss of libido, infertility

Question 53

What are the symptoms in men of hyperprolactinaemia?

Answer 53

Galactorrhoea is uncommon, loss of libido, erectile dysfunction, infertility

Question 54

How is hyperprolactinaemia treated?

Answer 54

D2 receptor agonists: decrease prolactin secretion and reduce tumour size (given orally)

Question 55

What are some examples of D2 receptor agonists?

Answer 55

Bromocriptine, cabergoline

Question 56

What are the eside effects of DA receptor agonists?

Answer 56

N&V, postural hypotension, dyskinesias, depression, pathological gambling

Question 57

What does excess GH result in during childhood and adulthood?

Answer 57

Child: Gigantism; adult: acromegaly -\> usually due to benign GH-secreting pit adenoma

Question 58

What is acromegaly?

Answer 58

Insidious onset with S&S progressing gradually -\> untreated= excess GH associated with ^ morbidity and mortality

Question 59

How can patients with acromegaly die?

Answer 59

CVD =60%, Resp complications =25%, Cancer =15%

Question 60

What grows in acromegaly?

Answer 60

Periosteal bone, cartilage, fibrous tissue, connective tissue, internal organs (cardio/spleno/hepatomegaly)

Question 61

What are the clinical features of acromegaly?

Answer 61

Question 62

What are the metabolic effects of acromegaly?

Answer 62

Excess GH -\> inhibits insulin signalling -\> increases insulin resistance -\> impaired glucose tolerance -\> diabetes mellitus

Question 63

What are the complications of acromegaly?

Answer 63

Question 64

What other hormone is secreted with GH in acromegaly?

Answer 64

Prolactin -\> which is often high and could be indicating tumour secreting both GH& prolactin

Question 65

What can hyperprolactinaemia cause with acromegaly?

Answer 65

2ry hypogonadism

Question 66

How do you diagnose acromegaly?

Answer 66

GH pulsatile, elevated serum IGF-1, failed suppression (paradoxical rise) of GH following oral glucose load (oral glucose tolerance test)

Question 67

What does the glucose tolerance test look like in a normal and an acromegalic patient?

Answer 67

Question 68

How do you treat acromegaly?

Answer 68

Surgery (trans-sphenoidal), medical: somatostatin analogues (octreotide), DA agonists (cabergoline), radiotherapy

Question 69

What are somatostatin analogues - administration, side effects, action?

Answer 69