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Y2 LCRS 1 - Pharm, Endo, Reproduction > ENDO; Lecture 1 and 2 & Tutorial 1 - Hyposecretion and Hypersecretion of anterior pituitary hormones; Anterior pituitary disorders > Flashcards

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

1
Q

Which hormones does the anterior pituitary release?

A

FSH/LH, Prolactin, GH, TSH, ACTH

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2
Q

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

A

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

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3
Q

What is hypopituitarism and how does it come about?

A

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

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4
Q

What is congenital panhypopituitarism - cause, symptoms, MRI?

A

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)

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5
Q

What causes acquired panhypopituitarism?

A

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

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6
Q

Which kind of tumours cause acquired panhypopituitarism?

A

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

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7
Q

Radiation to what causes acquired panhypopituitarism?

A

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

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8
Q

How is panhypopituitarism presented?

A

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

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9
Q

What is Sheehan’s syndrome?

A

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

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10
Q

What is the cause of Sheehan’s syndrome?

A

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

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11
Q

What are the presentations of Sheehan’s syndrome?

A

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

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12
Q

What is pituitary apoplexy?

A

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

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13
Q

What are the symptoms of pituitary apoplexy?

A

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

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14
Q

Which compressed cranial nerves lead to diplopia?

A

IV, VI

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15
Q

Which compressed cranial nerves lead to ptosis?

A

III

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16
Q

How are the CN arranged in relation to the pituitary?

A
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17
Q

How do you diagnose biochemically hypopituitarism?

A

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

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18
Q

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

A

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

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19
Q

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

A

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

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20
Q

How would you diagnose hypopituitarism using radiology?

A

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

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21
Q

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

A

Hydrocortisone, checking serum cortisol levels

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22
Q

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

A

Thyroxine and check Serum free T4

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23
Q

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

A

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

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24
Q

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

A

Testosterone checking for symptom improvement and serum testosterone

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25
Q

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

A

GH checking IGF1 and growth chart

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26
Q

What is the effect of somatotrophin deficiency?

A

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

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27
Q

What are the causes of short stature?

A
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28
Q

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

A
29
Q

What is achondroplasia?

A

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

30
Q

What are the different types of dwarfism?

A

Achondroplasia, pit. dwarfism, laron dwarfism

31
Q

What is the cause of pit dwarfism?

A

Childhood GH deficiency

32
Q

What is laron dwarfism?

A

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

33
Q

How do you diagnose short stature?

A

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

34
Q

What are the causes of acquired GH deficiency in adults?

A

Trauma, pit tumour/surgery, cranial radiotherapy

35
Q

How do you diagnose GH deficiency?

A

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

36
Q

What are the kinds of GH provocation tests?

A

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

37
Q

What is the normal and GH deficiency response to hypoglycaemia?

A
38
Q

How is GH therapy prepared and administrated?

A

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

39
Q

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

A

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

40
Q

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

A

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

41
Q

What are the potential benefits of GH therapy in adults?

A

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

42
Q

What are the potential risk of GH therapy in adults?

A

Increased cancer susceptibility and expensive

43
Q

What is hyperpituitarism?

A

Symptoms associated with excess production of adenohypophysial hormones

44
Q

What causes hyperpituitarism?

A

Isolated pit tumours, but also ectopic in origin

45
Q

What is hyperpituitarism associated with?

A

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

46
Q

What is bitemporal hemianopia?

A

Optic chiasm is compressed by growth of suprasellar tumour

47
Q

How would you assess a bitemporal hemianopia?

A
48
Q

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

A
49
Q

What are the causes of hyperprolactinaemia?

A

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

50
Q

What does high prolactin suppress?

A

GnRH pulsatility

51
Q

What is a prolactinoma?

A

Most common functioning pit tumour

52
Q

What are the symptoms in women of hyperprolactinaemia?

A

Galactorrhoea, secondary ammenorrhoea, loss of libido, infertility

53
Q

What are the symptoms in men of hyperprolactinaemia?

A

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

54
Q

How is hyperprolactinaemia treated?

A

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

55
Q

What are some examples of D2 receptor agonists?

A

Bromocriptine, cabergoline

56
Q

What are the eside effects of DA receptor agonists?

A

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

57
Q

What does excess GH result in during childhood and adulthood?

A

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

58
Q

What is acromegaly?

A

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

59
Q

How can patients with acromegaly die?

A

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

60
Q

What grows in acromegaly?

A

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

61
Q

What are the clinical features of acromegaly?

A
62
Q

What are the metabolic effects of acromegaly?

A

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

63
Q

What are the complications of acromegaly?

A
64
Q

What other hormone is secreted with GH in acromegaly?

A

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

65
Q

What can hyperprolactinaemia cause with acromegaly?

A

2ry hypogonadism

66
Q

How do you diagnose acromegaly?

A

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

67
Q

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

A
68
Q

How do you treat acromegaly?

A

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

69
Q

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

A

Y2 LCRS 1 - Pharm, Endo, Reproduction (19 decks)

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