6. Pituitary Flashcards

1
Q

Why is hypopituitarism not a cause of hypotension?

A

If the pituitary gland fails you can still produce Aldosterone from the adrenals which will maintain normal BP

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2
Q

What are the 6 hormones produced by the anterior pituitary and which hypothalamic hormone are they stimulated by?

A
  1. Growth hormone - stimulated by GHRH
  2. ACTH - stimulated by CRH
  3. Prolactin - stimulated by TRH, inhibited by dopamine
  4. TSH - stimulated by TRH
  5. LH and FSH - stimulated by LHRH
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3
Q

What happens in hypothyroid patients with TRH stimulated prolactin release?

A

high TRH leads to hyperprolactinaemia

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4
Q

Are the compartments of the cells for each hormone separated or mixed in the pituitary?

A

Mixed

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5
Q

How may a person with pituitary failure present?

A

Galactorrhoea, amenorrhoea. If pt has macroadenoma >1cm, may have bitermporal hemianopia.

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6
Q

How is bitemporal hemianopia assessed?

A

Visual field test (Humphreys 30-2 test). In this test you must be able to see the blind spot or it has not been conducted properly.

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7
Q

In what case would a tumour resulting in bitemporal hemianopia be inoperable?

A

If the tumour is in very close contact with the carotid arteries, it is considered inoperable and can be reduced with medical management

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8
Q

If prolactin levels are >6000, what is the likely cause?

A

Prolactinoma, pregnancy and other causes of hyperprolactinaemia will never cause such high levels of prolactin

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9
Q

A large tumour overproducing prolactin is not usually a huge problem but what could be the issue?

A

it could stop the production of other pituitary hormones e.g. ACTH, GH, TSH 🡪 therefore we need to assess the pituitary has adequate responsiveness to metabolic stress such as ACTH and GH and to ensure gonadotrophs and thyrotrophs are functional.

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10
Q

What does pituitary function testing try to do?

A

Pituitary function testing will try and increase the levels of anterior pituitary hormones, this can be done by administering LHRH, TRH and applying a metabolic stress e.g. hypoglycaemia.

The body is good at resisting hypoglycaemia by glycogenolysis, gluconeogenesis and ketone body production.

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11
Q

What are three stimuli for pituitary secretion?

A
  1. Insulin (hypoglycaemic stress) - Increases CRH and then ACTH, increases GHRH and then GH
  2. TRH - Stimulates TSH and prolactin
  3. LHRH - Stimulates LH and FSH

This forms the Combined Pituitary Function Test (COMBINED RAPID ANTERIOR PITUITARY EVALUATION PANEL) - Triple Test

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12
Q

CPFT Triple Test (combines rapid anterior pituitary evaluation panel) involves which three stimuli?

A

hypoglycaemia, TRH, LHRH

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13
Q

Inducing hypoglycaemia in CPFT triple test can be dangerous. What should we ensure?

A
  • Ensure the patient has no cardiac risk factors, angina and ECG is normal.
  • There is no history of epilepsy.
  • Ensure there is good IV access.
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14
Q

What happens in hypoglycaemia?

A

Initially in hypoglycaemia as the plasma levels start to decrease it will activate the SNS 🡪 sweating, tachycardia etc

  • When glucose is very low <1.5mM neuroglycopenia may occur and the patient may lose consciousness or become confused or become aggressive
  • Blood glucose must be checked regularly
  • Hypoglycaemia of <2.2mM is sufficient for adequate stimulation of the pituitary gland
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15
Q

What to do if severe hypoglycaemia occurs or patient is unconscious during CPFT triple test?

A

The patient should be rescued with 50ml 20% dextrose. It can be difficult to administer in an aggressive patient so a line must already be in place

NOTE: some books say 50% dextrose but this is very thick and viscous and can cause necrosis

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16
Q

Provide a summary of CPFT method

A
  1. Fast patient overnight
  2. Ensure good IV access
  3. Weigh patient and calculate dose of insulin required (0.15 U/kg) e.g. 70kg woman will need 10.5U
  4. Mix the following in a 5ml syringe: Insulin 0.15U/kg, TRH 200mcg, LHRH 100mcg.
  5. This is administered IV 🡪 patients will have a warm flush when the infusion reaches the brain and so may vomit
  6. Bloods must be taken to measure glucose, cortisol, GH, LH, FSH, TSH and prolactin every 30mins up to 60mins + basal thyroxine
  7. Glucose, cortisol and GH should be measured up to 120mins
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17
Q

What is a normal response in a CPFT?

A

Glucose <2.2 mM (if not give more insulin)
Cortisol >550nM
GH >10 IU/L

If the patient has a normal pituitary the blood sugar will go down and then rise again without any need for external help. This is because the patients pituitary will respond to the metabolic stress by producing GH and cortisol. (As TRH has increased the prolactin will also rise) LHRH?

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18
Q

If the tumour is pressing the pituitary all cells may fail leading to reduced production of all hormones. What should be done first?

A

URGENTLY replace with hydrocortisone. Other hormones e.g. thyroxine are important but hydrocortisone needs to be given most urgently. (Fludrocortisone is an aldosterone analogue and is not necessary as the adrenals should still be able to produce aldosterone 🡪 remember its not part of the HPA axis )

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19
Q

What is the order of hormone replacement when the pituitary fails to make hormones in the CPFT test?

A

hydrocortisone -> thyroxine -> oestrogen(/testosterone) -> GH replacement

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20
Q

If a patient has a prolactinoma what should be given?

A

Give dopamine agonist e.g. bromocriptine or cabergoline to shrink tumour size and surgery can be avoided 🡪 patient will therefore not need lifelong hormone replacement

21
Q

What is disconnection hyperprolactinaemia?

A

A large non-functioning pituitary tumour can cause hyperprolactinaemia. Hyperprolactinaemia in this case occurs when a tumour compresses the pituitary stalk and prevents dopamine from reaching the pituitary

22
Q

How much will prolactin levels be raised in hyperprolactinaemia?

A

The prolactin levels will be raised but much lower than the values seen in a prolactinoma

23
Q

What is the treatment for disconnection hyperprolactinaemia?

A

As they are non-functioning i.e. not a tumour of prolactin producing lactotrophs they do not respond to dopamine therapy and require surgery

24
Q

What is typically used as steroid replacement for hypopituitarism?

A

Hydrocortisone

25
Q

What else can be used as steroid replacement for hypopituitarism which is not hydrocortisone?

A

Typically hydrocortisone is used. BUT prednisolone is a more potent steroid with a longer half-life (resistant to degradation)

  • Therefore giving prednisolone once daily resembles normal circadian rhythm of cortisol
  • In the future prednisolone may be used instead of hydrocortisone
26
Q

How does acromegaly typically present?

A

Typically older patients with a pituitary adenoma an visual field defect present with marked GH increase

27
Q

How do you test for acromegaly?

A
  1. Tested dynamically with oral glucose tolerance test. A bolus of glucose will suppress the pulsatile release of GH, if GH is not suppressed = acromegaly.
  2. Serum IGF-1 levels and exercise test will also confirm the diagnosis
    Reference ranges for IGF-1 have not been fully resolved as it changes considerably with age
28
Q

What is the treatment for acromegaly?

A

Best Tx is pituitary surgery

29
Q

Should you do a GH provocation test in a child who isn’t growing?

A

No, this is dangerous, take a random plasma GH measurement

30
Q

How to test for lack of GH in child

A
  1. Plasma GH measurement - GH is normally low but if you catch pt at time of a pulse, detectable GH tells you they are producing GH
  2. Exercise tolerance test causes stress induced GH release which can be measured in plasma
  3. The insulin tolerance test is very effective but should not be used straight away as it is dangerous
31
Q

What are the adrenal layers?

A

(Innermost) medulla, z. reticularis, z.glomerulosa, z.fasciculata, periadrenal fat (outermost)

32
Q

What can cause adrenal atrophy?

A

Addisons or long term steroid therapy

33
Q

What can cause bilateral cortical hyperplasia in the adrenal glands?

A

Cushing’s disease (pituitary adenoma secreting ACTH), Cushings syndrome from ectopic CTH, idiopathic

34
Q

What do the adrenals look like (histology) in Waterhouse-Friderichsen syndrome?

A

Black-red adrenals from extensive haemorrhage in patient with meningococcemia Waterhouse-Friderichsen syndrome

35
Q

What does Waterhouse-Friderichsen syndrome look like in a child

A

W-F syndrome with sepsis, DIC and marked purpura

36
Q

Histology of metastatic carcinoma

A

Cross section of enlarged adrenal gland shows tan white metastatic carcinoma infiltrating into and around the golden-yellow cortex. (Common site for primary adrenal metastases is lung)

37
Q

Histology of tuberculosisin adrenals?

A

Caseating granuloma of adrenal TB. TB used to be a common cause of chronic adrenal insufficiency. Now idiopathic Addisons is a more common caused of chronic adrenal insufficiency.

38
Q

How can amyloid deposits be seen in adrenal histology?

A

Congo red stained deposits of amyloid in adrenal cortex

39
Q

How does histology and microscopic appearance look like in a neonate with congenital neuroblastoma?

A

The neoplasm caused by the neuroblastoma displaces the liver to the left of the body.

Microscopic appearance of neuroblastoma is ‘small round blue cell’ tumours are seen in paediatric age range. Often arise in adrenal gland and increase in size in retroperitoneum before being detected. They contain areas of necrosis and calcification. Rosette formation 🡪 cell arranges around centre of cellular fibrillar extensions. The round cells have prominent blue nuclei, granular chromatin and minimal cytoplasm

40
Q

Histology of adrenal cortical adenoma

A

Atrophy, adenoma is made of yellow firm tissue like the adrenal cortex, neoplasm well circumscribed and made of well differentiated cells resembling normal cortical zona fasciculata. This is benign.

41
Q

Adrenal adenoma in a patient with hypertension. The patient had hypokalaemia, high serum aldosterone and low serum renin 🡪 aldosterone secreting adenoma = Conn’s syndrome. This accounts for 2/3rds of primary hyperaldosteronism, bilateral adrenal hyperplasia accounts for 30%. What do these adenomas look like?

A

These adenomas are <2cm and yellow on the cut surface.

42
Q

Large adrenal cortical adenomas have a good prognosis true or false? as they are diagnosed at a high stage since there is room for them to enlarge in the retroperitoneum before being detected.

A

False, poor diagnosis because they are diagnosed at a high stage since there is room for them to enlarge in the retroperitoneum before being detected.

43
Q

Most endocrine neoplasms are benign adenomas, true or false?

A

true

44
Q

both benign and malignant endocrine neoplasms show some degree of cellular pleomorphism so it is not a simple to differentiate between benign and malignant from just histology. What is a pleomorphism?

A

Pleomorphism is a term used in histology and cytopathology to describe variability in the size, shape and staining of cells and/or their nuclei. Several key determinants of cell and nuclear size, like ploidy and the regulation of cellular metabolism, are commonly disrupted in tumors.

45
Q

What does histology of phaeochromocytoma show?

A

Large adrenal neoplasm. Has a grey tan colour of tumour vs yellow cortex stretched around it. A part of the adrenal becomes very enlarged. May show chromaffin reaction. When a section of the tumour has been placed into dichromate fixative turning the tissue brown as catecholamines are oxidised.

46
Q

What does phaeochromocytoma look like microscopically?

A

Microscopically the phaeochromocytoma is made of large cells strained pink and mauve and arranged in nests with capillaries in between.
10% are bilateral, 10% are in children, 10% are malignant

47
Q

What is the most likely site for extra-adrenal phaeochromocytoma?

A

The paraganglia.

(The paraganglion system includes carotid bodies, aortic bodies, organ of Zuckerkandl and chromaffin tissue scattered in other places e.g. bladder wall. These tissues are derived from the neural crest and have neuroendocrine function. )

48
Q

What does electron microscopy imaging of neoplastic phaeochromocytoma cells show?

A

Neoplastic phaeochromocytoma cells containing neuroscretory granules which contain catecholamines. They are small round black objects in the cytoplasm.