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Endocrinology > 1. Hyposecretion of anterior pituitary hormones > Flashcards

1. Hyposecretion of anterior pituitary hormones Flashcards

1
Q

What is hypopituitarism?

A

Decreased production of all anterior pituitary hormones (panhypopituitarism) or of specific hormones

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2
Q

Give examples of causes of panhypopituitarism

A
  • Congenital defects (rare)

* Gene mutations (very rare) e.g. PROP1 - transcription factor involved in development of pit. gland

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3
Q

In who does panhypopituitarism usually develop?

A
  • Adults

* Presents with progressive loss of pituitary secretion

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4
Q

In what order does the loss of secretion usually happen in panhypopituitarism?

A 
• Gonadotrophins (LH and FSH)
• GH
• Thyrotrophin
• Corticotrophin
(• Prolactin deficiency is uncommon)
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5
Q

What are the 3 main types of panhypopituitarism?

A
  • Simmond’s Disease
  • Sheehan’s Syndrome
  • Pituitary Apoplexy
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6
Q

What are the causes of Simmond’s Disease?

A 
• Infiltrative processes
• Pituitary adenomas
• Craniopharyngiomas
• Cranial injury
• Surgery
(• Insidious onset - develops very slowly)
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7
Q

What are the symptoms of Simmond’s Disease?

A 
(• Mainly due to decreased thyroidal, adrenal and gonadal function)
• Secondary amenorrhoea or oligomenorrhoea
• Impotence
• Loss of libido
• Tiredness
• Waxy skin
• Loss of body hair
• Hypotension
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8
Q

Outline the development of Sheehan’s Syndrome

A

• Specific in women
• Develops acutely following post-partum heamorrhage which leads to pituitary infarction
- blood loss => vasoconstrictor spasm of hypophysial arteries
- ischaemia of pituitary
- necrosis of pituitary
• Very fast development

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9
Q

Outline the development of Pituitary Apoplexy

A

• Similar to Sheehan’s but not specific to women
• Intra-pituitary infarction or haemorrhage
• Rapid presentation
- especially in patients with pre-existing pituitary tumours which suddenly infarct

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10
Q

Why is more than one measurement needed to diagnose hypopituitarism?

A
  • Hypothalamus mostly releases in pulses

* More than one measurement needed

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11
Q

What types of hormones are measured to diagnose hypopituitarism?

A
  • Hypothalamic hormones can’t be measured

* Measure basal plasma values of pituitary or target endocrine gland hormones instead

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12
Q

What tests can be done to diagnose hypopituitarism?

A

• Stimulation (or provocation) test - find out if hormone is produced at normal level
- done using a combine function test (administration of various releasing hormones)
- hormones administered IV
- one releasing hormone if testing for a specific hypothyroidism
• Insulin-induced hypoglycaemia test for GH

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13
Q

A deficiency in a single adenohypophysial hormone can result in which secondary endocrine gland failures?

A

Deficiency of:
• Gonadotrophins - Hypogonadism
• Thyrotrophin - Hypothyroidism
• Corticotrophin - Hypoadrenocorticalism

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14
Q

What are the effect of a lack of Somatotrophin in children and adults?

A
  • Children - pituitary dwarfism

* Adults - uncertain

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15
Q

What are causes of short stature in children?

A
  • Genetic
  • Malnutrition
  • Emotional deprivation
  • Endocrine disorders (e.g. lack of T3 and T4)
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16
Q

What are the congenital causes of GH deficiency in children?

A
  • Deficiency of hypothalamic GHRH (largest endocrine cause)
  • Mutations of GH gene
  • Development abnormalities (e.g. aplasia or hypoplasia of the pituitary gland)
17
Q

What are the acquired causes of GH deficiency in children?

A
  • Tumours of the hypothalamus of pituitary
  • Other nearby intracranial tumours e.g. optic nerve glioma
  • Irradiation can affect somatotrophs
  • Head injuries
  • Infection or inflammation
  • Severe psychosocial deprivation
18
Q

What is growth hormone controlled by at a hypothalamic level?

A
  • GHRH (mainly)

* Somatostatin

19
Q

Which protein in the liver does growth hormone stimulate the production of?

A
  • Insulin-like Growth Factor I (IGF I)
  • Also produced by many other tissues in the body
  • Mediates growth effects
20
Q

What is Laron Dwarfism?

A
  • GH receptor defect

* Therefore, low IGF I

21
Q

Which people can be considered when identifying the importance of IGF I?

A

• Pygmies in Africa

  • short stature
  • have IGF I but doesn’t work normally
  • lack growth that we normally associate with IGF I
22
Q

What is Tertiary Hypopituitarism?

A
  • Diminished secretion of pituitary hormones caused by…
  • Specific hypothalamic hormone defects
  • e.g. Gonadotrophin-releasing hormone (GnRH) deficiency
23
Q

Describe 2 examples of tertiary hypopituitarism

A

Kallmann’s Syndrome
• Hypogonadism
• Associated with anosmia (loss of sense of smell)
• Genetic defect - neurones in embryo to produce GnRH (and develop sense of smell) don’t migrate to hypothalamus

Prader-Willi Syndrome
• Hypogonadism is one of the aspects of this disorder
• Problem at the level of the hypothalamus

24
Q

What are the different GH Provocation tests

A

• Use IV GHRH to stimulate GH production (alternatives being used as GHRH is hard to get)
• Gold standard - Insulin-induced Hypoglycaemia
- hypoglycaemia is a potent stimulus for GH release
• Arginine (IV) - stimulates GH release
• Glucagon (IM) - usually causes hyperglycaemia, but stimulates GH release in people who lack GH (could be a direct stimulatory effect on somatotrophs)
• Exercise - e.g. 10 mins step climbing

• Measure GH before and after the tests

25
Q

What are the replacement hormones for the following deficient hormones in hypopituitarism, and how do you check them?

1) ACTH
2) TSH
3) Women LH/FSH
4) Men LH/FSH
5) GH

A

1) Hydrocortisone - serum cortisol
2) Thyroxine - serum T3
3) Ethinyloestradiol, Medroxyprogesterone - oestrogen deficiency, libido
4) Testosterone undecanoate - serum testosterone, libido
5) GH - IGF I, growth chart

26
Q

What needs to be considered when deciding to start growth hormone therapy in children?

A
  • Resistance may develop (antibody formation)
  • Younger children respond better
  • Obese children also respond better
  • Other hormones may be affected - therefore other hormone replacement needed as well as GH
27
Q

How is replacement Growth Hormone administered?

A
  • Subcutaneous or IM
  • Daily or 4/5 times per week
  • Tend to give in afternoon - GH varies during the day and high at night anyway
  • Adjust dose to size
28
Q

What is the maximal plasma concentration time for GH replacement?

A

2-6 hours

29
Q

Where is GH replacement metabolised and what is the half-life?

A
  • Hepatic/renal

* Relatively short half life - 20 mins

30
Q

What is the duration of action for GH replacement therapy and why?

A
  • IGF I levels peak after 20 hours

* Works on protein synthesis, so quite long

31
Q

What are the adverse effects of GH replacement therapy (in children)?

A
  • Lipoatrophy at the site of injection
  • Intracranial hypertension => headaches
  • Stimulates tumours e.g. increased incidence of leukaemia
32
Q

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

A
  • Reduced lean mass
  • Increased waist:hip ratio
  • Reduced muscle strength and bulk
  • Decreased HDL and increased LDL
  • Impaired psychological wellbeing and reduced quality of life
33
Q

What are the 3 main ways of diagnosing GH deficiency in adults?

A
  • Lack of response to GH stimulation test
  • Low plasma IGF I
  • Low plasma IGF-BP3
34
Q

What are 5 potential benefits of GH therapy in adults?

A
  • Improved body composition
  • Improved muscle strength and exercise capacity
  • Normalisation of HDL-LDL balance
  • Increased bone mineral content (relevance to middle aged women)
  • Improved psychological wellbeing
35
Q

What are the potential risks of GH therapy in adults?

A
  • Increased risk of CV accidents (growth promoting => cardiomegaly)
  • Increased soft tissue growth (general)
  • Increased susceptibility to cancer

Endocrinology (17 decks)

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