Hyposecretion of anterior pituitary hormones Flashcards

1
Q

Name the 5 anterior pituitary hormones:

A

LH/FSH- gonadotrophins

Prolactin-lactation post-partum

TSH- stimulates thyrotrophin release from thyroid

GH- somatotrophin

ACTH- stimulates cortisol release from adrenal cortex

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2
Q

Outline the disorder category levels of endocrinological disease:

A

Primary endocrine disorder: disease affecting the endocrine gland itself eg: primary hypothyroidism (lack of T3/T4)

Secondary endocrine disorder: disease affecting the adenohypophysis eg: TSH deficiency

Tertiary endocrine disorder: disease affecting hypothalamus

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3
Q

What is hypopituitarism/panhypopituitarism?

What is panhypopituitarism sometime’s called?

A

Decreased production of ALL anterior pituitary hormones.

Can be all or be a specific one.

Causes: congenital (rare) or acquired

Simmond’s disease

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4
Q

Features and causes of congenital panhypopituitarism:

A
  • RARE
  • Caused by mutations in transcription factor genes needed for normal APG development eg PROP1 mutation.
  • usually lack of growth hormone and one other APG hormone
  • Short stature due to lack of GH
  • Hypoplastic (underdeveloped) APG on MRI
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5
Q

What are the causes of acquired panhypopituitarism?

A
  • COMMON
  • Tumours

Hypothalamic: craniopharyngomas

Pituitary: adenomas, mestastases, cysts

•Radiation (effects from cancer treatment)

hypothalamic/pituitary damage

GH most vulnerable, TSH relatively resistant

  • Infection eg meningitis
  • Traumatic brain injury
  • Infiltrative disease – often involves pituitary stalk

eg neurosarcoidosis

  • Inflammatory (hypophysitis)= AI destruction of PG
  • Pituitary apoplexy (damaged PG)
  • haemorrhage (or less commonly infarction)

Peri-partum infarction (Sheehan’s syndrome)

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6
Q

What does panhypopituitarism present with and why?

A

Symptoms are due to deficiency in hormomnes:

FSH/LH- secondary hypogonadism; secondary amennorhoea, reduced libido, ED

TSH- secondary hypothyroidism; fatigue

ACTH- secondary hypoadrenalism; signal missing from PG to make cortisol, fatigue

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7
Q

Explain the aetiology of Sheehan’s syndrome:

A

Sheehan’s syndrome describes post partum hypopituitarism secondary to post partum haemorhage.

In pregnancy APG enlarges due to lactotrophic hyperplasia, increasing the vascular demand of the APG.

During post-partum haemorrhage, hypotension occurs causing decreased blood flow to the APG, causing a pituitary infarction.

Less common in developed country due to lesser risk of PPH.

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8
Q

What is the presenation of Sheehan’s syndrome:

A

Lethargy/anorexia/weightloss:

TSH deficiency/ ACTH defiency (cortisol increases appetite)/ GH deficiency

Failure of lactation

Failure to resume menses post partum

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9
Q

What is pituitary apoplexy, which pituitary is it common in?

A

Intra-pituitary haemorrhage or (less common) infarction.

Dramatic presentation in Patients with pre-existing pituitary adenomas

  • can be the first sign of a pituitary adenoma
  • may be precipitated by anti-coagulants (blood thinners cause a bleed)
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10
Q

What are presentations and symptoms of pituitary apoplexy?

A
  • Sudden severe onset headaches
  • Visual field defects: bleeding compresses optic chiasm= bilateral hemianopia (loss of outer field vision in both eyes
  • bleeding into Cavernous sinus: diplopia (double vision) and ptosis (drooping of eyelid)
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11
Q

Outline two types of diagnosis of hypopituitarism

A

BIOCHEMICAL DIAGNOSIS:

basal plasma conc of pituitary hormone/target endocrine gland hormone

Hormones fluctuate, single measurement is not a good indicator

undetectable cortisol – what time of day? Usually starts higher in the morning, decreases throughout the day.

  • T4 – circulating t1/2 6 days
  • FSH/LH – cyclical
  • GH/ACTH - pulsatile

Stimulated/dynamic pituitary function test:

ACTH/GH stress hormones so induce stress

>2mMol/L hypoglycaemia

Insulin-induced hypoglycaemia stimulates

GH release

ACTH release (cortisol measured)

  • TRH given at same time stimulates TSH release
  • GnRH given at same time stimulates FSH & LH release

RADIOLOGICAL DIAGNOSIS:

PITUITARY MRI: may reveal adenoma, haemorrhage( apoplexy)

Empty sella (thin rim of tissue indicating hypopituitarism has been for a long time

Lok for posterior bright spot on MRI

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12
Q

Which hormone replacament therapy is used in hormone deficiencies, how is the efficacy checked?

A
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13
Q

What is the effect of GH deficiency in adults vs children?

A
  • in children results in short stature (=2 SDs < mean height for children of that age and sex)
  • in adults, effects less clear

Pathological short stature- if GH deficiency proved then GH injections given

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14
Q

What are the different causes of short stature?

A

Genetic

Emotional deproivation -stress shuts down growth axis

endocrine deficiency: Cushings, hypothyroidism, GH deficiency

Systemic disease eg CF

malnutrition

malabsorption- eg coeliac disease

skeletal dysplasias: OI, achondroplasia

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15
Q

Describe the growth axis:

A

Adenohypophysis is under hypothalamic control.

Hypothalamic signal GHRH is released, stimulating somatotrophs to secrete GH.

This travels to target tissues: muscle and liver

In the liver: stimulated to make somatomedins (IGF1 (metabolic) and IGF2 (fetal development) which also have effects on the target tissues

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16
Q

Outline the causes of short stature in children with refernece to the growth axis:

A

Hypothalamic cause: Prader-Wili Syndrome- GHRH deficiency secondary to hypothalamic dysfuction

Pituitary cause- PITUITARY DWARFISM- GH deficiency= short stature

GH receptor deficiency= LARON DWARFISM= no somatomedins produced

17
Q

Compare and contrast different types of dwarfism, outlining causes and symptoms:

A

PWS: GH deficiency secondary to ypothalamic dysfunction.

Learning difficulties, food seeking tendencies

Achondraplasia: mutation in FGR3 (fibroblast growth factor receptor 3) causing mutation in growth plate chondrocytes.

Average size trunk, short limbs

Pituitary dwarfism:

childhood GH deficiency, patient falls off growth chart.

Laron dwarfism:

mutation in GHR- they make GH but no IGF1, so IGF1 injections given

18
Q

How would you diagnose short stature in children?

A

MID PARENTAL HEIGHT

A predicted adult height –

based on father’s & mother’s height

GROWTH CHART MONITORING (see image)

9th centile at aged 5y, started to fall down the curves – a drop of more than 2 centiles is flagged, by aged 11y, below the 0.4th centile – diagnosis of coeliac disease made, gluten free diet – starts to grow as predicted

At 11, diagnosed with coeliac disease: malabsorption.

Diet improves: back on trajectory

19
Q

What are the causes of acquired GH deficiency in adults?

A

TRauma, pituitary tumour, pituitary surgery, cranial, radiotherapy

20
Q

How to diagnose GH deficiency in adults?

A

Random GH measurement is useless- GH is pulsaltile

use provocation tests:

GHRH + ARGININE (i.v.) (in combination more effective than each alone)- arginine given in the form of marmite. mechanism unknown but may inhibit SS relase, and stimulate GHRH.

INSULIN (i.v.) – via hypoglycaemia- GH spurt. If GH defiency= no spurt (see image) NICE cut off =3mcg/L so if less than 3= deficient.

GLUCAGON (i.m.)

EXERCISE (e.g. 10 min step climbing; when appropriate)

Measure plasma GH at specific time-points (before and after)

21
Q

What is the treatment of GH deficiency and adminstration?

A

•Preparation:

–Human recombinant GH

  • (approved name: SOMATOTROPIN)
  • Administration:

–Daily, subcutaneous injection

–Monitor clinical response &

adjust dose to IGF-1

22
Q

GH DEFICIENCY IN ADULTS:
SIGNS AND SYMPTOMS

A
  • Reduced lean mass, increased adiposity, increased waist:hip ratio
  • Reduced muscle strength & bulk à reduced exercise performance
  • Decreased plasma HDL-cholesterol & raised LDL-cholesterol ( bad lipid profile)
  • Impaired ‘psychological well being’ and reduced quality of life
23
Q

What are the potential benefits and risks of GH therapy in adults:

A

Benefits:

  • Improved body composition – decreased waist circumference, less visceral fat- decrease CVS risk
  • Improved muscle strength and exercise capacity
  • More favourable lipid profile - higher HDL-cholesterol, lower LDL-cholesterol
  • Increased bone mineral density
  • Improved psychological well being and quality of life

Risks:

Increased susceptibility to cancer

– no data to support this currently

Expensive – NICE estimated cost of lifelong GH treatment in adult = £42K