Pituitary disease Flashcards
1
Q
Describe the structure of the pituitary gland.
A
- protrusion off the bottom of the hypothalamus (connected via infundibulum)
- sits in the sella turcica
- has an anterior, intermediate and posterior lobe
2
Q
Describe the structural and functional relationship between the pituitary gland + hypothalamus.
A
- Anterior pituitary is connected to the hypothalamus via the hypothalamo-hypophyseal portal system
- ICA branches into the superior hypophyseal artery which passes into the infundibulum and then breaks up into the primary plexus → bood from the hypothalamus can secrete into here
- blood travels from the primary plexus down the hypophyseal portal vein down into the anterior pituitary
- blood vessels then break up into the secondary plexus
- efferent hypophyseal arteries branch off the plexus and go to the cavernous sinus - Posterior pituitary has a neural connection to the hypothalamus
- there are 2 groups of cell bodies in the hypothalamus: supraoptic nuclei and paraventricular nuclei
- hormone synthesised by the nuclei are secreted and travel from the hypothalamus to the posterior pituitary via axons
3
Q
List the hormones secreted by the anterior, intermediate and posterior lobes.
A
- Anterior:
- Growth hormone
- Adrenocorticotropin hormone
- Thyroid stimulating hormone
- Luteinising and follicle stimulating hormone
- Prolactin - Intermediate:
- Melanocyte stimulating hormone - Posterior:
- ADH
- Oxytocin
4
Q
What stimulates and inhibits the release of GH?
A
- Stimulates:
- GHRH (from hypothalamus)
- Hypoglycaemia - inhibits:
- Somatostatin
- IGF and GH (-ve feedback)
5
Q
What stimulates the release of ACTH?
A
- Corticotropin releasing hormone from the hypothalamus
6
Q
What stimulates and inhibits the release of TSH?
A
- Stimulates:
- TRH (form hypothalamus) - Inhibits:
- Somatostatin
7
Q
What stimulates the release of LH and FSH?
A
- GnRH (from hypothalamus)
GnRH is stimulated by Kisspeptin - also found in the hypothalamus
8
Q
What stimulates and inhibits the release of Prolactin?
A
- Stimulates:
- TRH (from hypothalamus) - Inhibits:
- Dopamine (from hypothalamus)
9
Q
Where in the posterior lobe are ADH and oxytocin synthesised?
A
- ADH → supraoptic nuclei
- Oxytocin → paraventricular nuclei
10
Q
Describe the actions of the anterior pituitary hormones.
A
- GH:
- target: liver, cartilage, muscle, fat + skin
- effects: linear + somatic growth; metabolism (lipids, proteins, carbohydrates) - TSH:
- target: thyroid
- effects: thyroid hormone (T3 + T4) production - ACTH:
- target: adrenal glands
- effects: glucocorticoid and DHEA production - LH + FSH:
- target: gonads
- effects: sex steroid production; folliculogenesis + ovulatoin; spermatogenesis - Prolactin:
- target: breast tissue
- effects: lactation
11
Q
Describe the actions of the posterior pituitary hormones.
A
- ADH:
- target: collecting ducts and thick ascending Loop of Henle
- effects: increases water permeability so that solute-free water may pass along an osmotic gradient to the intersitital medulla - Oxytocin:
- target: uterus, cervix, breast duct smooth msucle
- effects: contracts uterus, dilates cervix, breast milk ejection
12
Q
What are the symptoms of acromegaly?
A
- Increased sweating (~80% of patients)
- Headaches
- Tiredness of lethargy
- Joint pain
- Change in ring/shoe size
13
Q
What are the signs of acromegaly?
A
- Facial appearance:
- coarse features
- oily skin
- frontal bossing
- enlarged nose
- deep nasolabial furrow
- projection of lower jaw/chin (prognathism)
- increased intradental separation - Deep voice (laryngeal thickening)
- Macroglossia
- MSK changes:
- enlargement of hands + feet
- degenerative changes in joints lead to osteoarthritis
- generalised myopathy - Soft tissue swelling (leading to entrapment neuropathies such as carpal tunnel)
- Goitre and other organomegaly (liver, heart, kidneys)
14
Q
What are the complications of acromegaly?
A
- Hypertension
- Insulin resistance and impaired glucose tolerance/diabetes mellitus
- Obstructive sleep apnoea
- Increased risk of colonic polyps and colonic carcinoma
- Ischaemic heart disease and cerebrovascular disease
- Congestive caridac failure
15
Q
What are the direct tumour effects in acromegaly caused by pituitary adenoma?
A
- Visual field defects (often bitemporal hemianopia)
- Hypopituitarism
16
Q
Describe the investigations used to diagnose acromegaly.
A
- OGTT:
- failure to suppressGH to <0.33 micrograms/L in response to a 75g oral glucose load - IGF-1:
- useful in addition to OGTT (almost always elevated in acromegaly) - MRI:
- usually demonstrates the tumour (98%)and whether there is extrasellar extension - Pituitary function testing:
- serum PRL should be measured, as some tumours co-secrete btoh GH and PRL - Serum calcium:
- GH stimulates renal 1apha-hydroxylase which increased 1,25-DHCC (calcitriol) → patient smay be hypercalciuric - GHRH:
- may have a GHRH-secreting carcinoid of lung or pancreas rather than pituitary adenoma
17
Q
What are the different management options for acromegaly?
A
- Transsphenoidal surgery
- Radiotherapy
- Drug treatment
18
Q
What is the 1st line management for acromegaly?
A
Transsphenoidal surgery
- cure rates ~2-4x higher in microadenomas compared to macroadenomas
- medical therapy/radiotherapy are only indicated if safe GH levels are not achieved
19
Q
Describe the different drug treatments used in acromegaly.
A
- Somatostatin analogues:
- GH suppression in 20-60% of patients
- may be used as a primary therapy where the tumour does not cause mass effects
- used in patients who have received surgery and/or radiotherapy and still have elvated GH
- example: pasireotide - Dopamine agonists:
- may lower GH levels but rarely leads to normalisation of GH or IGF-1
- useful if there is co-existent secretion or PRL
- example: cabergoline (more effective than bromocriptine) - GH receptor antagonists:
- for somatostatins non-responders
- LFTs should be monitored 6 weekly for 6 months
- MRI of pituitary is indicated 6 monthly in case of pituitary enlargement
20
Q
What are the symptoms of Cushing’s syndrome?
A
- Facial appearance:
- round face (moon face)
- acne
- hirsutism
- thinning of scalp - Weight gain
- Mood disturbance
- Menstrual disturbance
- Low libido and impotence
21
Q
What are the signs of acromegaly?
A
- truncal obseity, buffalo hump, supraclavicular fat pads
- thin + fragile skin, purple striae on abdomen/breasts/thighs/axillae, easy bruising
- proximal muscle weakness
- hypertension
- impaired glucose tolerance/diabetes mellitus
- osteopenia and osteoporosis
- vascular disease
22
Q
Describe the investigations used to diagnose Cushing’s syndrome.
A
- 2-3x 24h urinary free cortisol:
- should not be used alone for diagnosis (falve -ve rate ~5-10%) - Overnight dexamethasone suppression test:
- administration of 1mg dexamethasone at midnight is followed by a serum cortisol measurement at 9am
- cortisol <50 nmol/L makes Cushing’s unliely
- if this test and urinary free cortisol are normal then Cushing’s unliekly - Midnight cortisol (inpatient):
- loss of circadian rhythm of cortisol secretion seen in Cushing’s syndrome
- cortisol level in patients with Cushing’s will be >50 nmol/L at midnight - Low dose dexamethasone suppression test (inpatient):
- administration of 0.5mg/500 micrograms of dexamethasone 6hrly for 48h at 9am, 3pm, 9pm and 3am
- should lead to complete suppression of cortisol to <50 nmol/L in normal subjects
23
Q
What are the main causes of pseudo-Cushing’s?
A
- Alcohol addiction
2. Depression
24
Q
How can you differentiate between pseudo-Cushing’s and true Cushing’s syndrome?
A
- Insulin tolerance test:
- pseudo-Cushing’s will show a normal cortisol rise in response to hypoglycaemia
- true Cushing’s will show a blunted rise - Dexamethasone suppresion:
- pseudo-Cushing’s will show a blunted response to CRH
25
Q
What are the management options for Cushing’s syndrome?
A
- Transsphenoidal surgery
- Pituitary radiotherapy
- Adrenalectomy
- Medical treatment
26
Q
What is the first-line therapy in Cushing’s syndrome?
A
Transsphenoidal surgery
27
Q
What is the medical treatment involved in the management of Cushing’s syndrome?
A
- inhibitors of steroidogenesis
- metyrapone (1st line in adults)
- ketoconazole (1st line in children) - glucocorticoid replacement therapy
- successful treatment of Cushing’s disease leads to cortisol deficiency
28
Q
What are the clinical features of hyperprolactinaemia?
A
- Galactorrhoea
- Disturbed gonadal function in females presents with menstrual disturbance, amenorrhoea, oligomenorrhoea, or with infertility and reduced libido
- Disturbed gonadal function in males presents with loss of libido and/or erectile dysfunction; presentation of reduced fertility, oligospermia, gynaecomastia is unusual
- hyperprolactinaemia is associated with a long-term risk of reduced BMD
- hyperprolactinaemia inhibits GnRH release, leading to reduced LH secretion
29
Q
Describe the investigations used to diagnose hyperprolactinaemia.
A
- Serum PRL:
- serum PRL <2000 U/L is suggestive of a tumour (either a microprolactinoma or a non-functioning macroadenoma compressing the pituitary stalk)
- serum PRL >4000 U/L is diagnostic of macroprolactinoma - TFTs, renal function:
- hypothyroidism and chronic renal failure can cause hyperprolactinaemia - Imaging:
- MRI: microadenomas usually appear as hypo-intense lesions within the pituitary stalk (T1-weighted)
- Stalk deviation or gland asymmetry may also suggest microadenoma
- Macroadenomas are space-occupying tumours, associated with bony erosion and/or cavernous sinus invasion
30
Q
What drugs can cause hyperprolactinaemia?
A
- Antipsychotic agents (haloperidol, chlorpromazine, risperidone etc)
- Opiates
- Cocaine
- Dopamine receptor antagonists (metoclopramide, domperidone)
- Cardiovascular drugs (verapamil, methyldopa, reserpine)
31
Q
Describe the management options for hyperprolactinaemia.
A
- Dopamine agonists
- Cabergoline is the most effective for normalisation or PRL
- suppresses PRL in most patients, normaisation of gonadal function and termination of galactorrhoea - Oestrogen
- may be appropriate in females with idiopathic hyperprolactinaemia or microprolactinomas where fertility and galactorrhoea are not issues - Surgery
- transsphenoidal surgery is only indicated for patients who are resistant to, or intolerant of, dopamine agonist treatment - Radiotherapy
- not indicated in the management of patients with microprolactinomas
- useful in the treatment of macroprolactinomas once the tumour has shrunken away from the chiasm
32
Q
What are the potential causes of hypopituitarism?
A
- pituitary tumours
- parapituitary tumours
- radiotherapy
- pituitary infarction
- infiltration of the pituitary gland (sarcoidosis, haemochromatosis)
- infection (TB, pituitary abscess)
- trauma
- subarachoid haemorrhage
- isolated hypothalamic-releasing hormone deficiency
33
Q
What are the clinical features of hypopituitarism?
A
- GH def:
- reduced exercise capacity
- reduced lean body mass
- impaired psychological well being
- increased CV risk - LH/FSH def:
- anovulatory cycles,
- oligo/amenorrhoea
- dyspareunia
- erectile dysfunction
- testicular atrophy
- loss of secondary sexual hair in males
- reduced libido
- infertility
- osteoporosis - ACTH def:
- same as Addison’s, except lact of hyperpigmentation + absence of hyperK+ - TSH def:
- same as primary hypothyroidism - PRL def:
- failure of lactation - ADH def:
- polyuria and polydipsia
34
Q
What are the investigations used to diagnose hypopituitarism?
A
- Basal hormone levels:
- LH + FSH, and testosterone (9am) or estradiol
- TSH and thyroxine
- 9am cortisol
- PRL
- IGF-1
- dynamic tests → use to assess cortisol and GH reserve - Posterior pituitary function
- Investigating the cuase:
- pituitary imaging → MRI ± contrast
- investigation of hormonal hypersecretion if a pituitaru tumour is demonstrated
- investigation of infiltrative disorders
35
Q
How should hypopituitarism be managed?
A
- adequate and appropriate hormone replacement and management of underlying cause
