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
What are the management options for Cushing's syndrome?
1. Transsphenoidal surgery
2. Pituitary radiotherapy
3. Adrenalectomy
4. Medical treatment
26
What is the first-line therapy in Cushing's syndrome?
Transsphenoidal surgery
27
What is the medical treatment involved in the management of Cushing's syndrome?
1. inhibitors of steroidogenesis
- metyrapone (1st line in adults)
- ketoconazole (1st line in children)
2. glucocorticoid replacement therapy
- successful treatment of Cushing's disease leads to cortisol deficiency
28
What are the clinical features of hyperprolactinaemia?
- 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
Describe the investigations used to diagnose hyperprolactinaemia.
1. 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
2. TFTs, renal function:
- hypothyroidism and chronic renal failure can cause hyperprolactinaemia
3. 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
What drugs can cause hyperprolactinaemia?
- Antipsychotic agents (haloperidol, chlorpromazine, risperidone etc)
- Opiates
- Cocaine
- Dopamine receptor antagonists (metoclopramide, domperidone)
- Cardiovascular drugs (verapamil, methyldopa, reserpine)
31
Describe the management options for hyperprolactinaemia.
1. Dopamine agonists
- Cabergoline is the most effective for normalisation or PRL
- suppresses PRL in most patients, normaisation of gonadal function and termination of galactorrhoea
2. Oestrogen
- may be appropriate in females with idiopathic hyperprolactinaemia or microprolactinomas where fertility and galactorrhoea are not issues
3. Surgery
- transsphenoidal surgery is only indicated for patients who are resistant to, or intolerant of, dopamine agonist treatment
4. 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
What are the potential causes of hypopituitarism?
1. pituitary tumours
2. parapituitary tumours
3. radiotherapy
4. pituitary infarction
5. infiltration of the pituitary gland (sarcoidosis, haemochromatosis)
6. infection (TB, pituitary abscess)
7. trauma
8. subarachoid haemorrhage
9. isolated hypothalamic-releasing hormone deficiency
33
What are the clinical features of hypopituitarism?
1. GH def:
- reduced exercise capacity
- reduced lean body mass
- impaired psychological well being
- increased CV risk
2. LH/FSH def:
- anovulatory cycles,
- oligo/amenorrhoea
- dyspareunia
- erectile dysfunction
- testicular atrophy
- loss of secondary sexual hair in males
- reduced libido
- infertility
- osteoporosis
3. ACTH def:
- same as Addison's, except lact of hyperpigmentation + absence of hyperK+
4. TSH def:
- same as primary hypothyroidism
5. PRL def:
- failure of lactation
6. ADH def:
- polyuria and polydipsia
34
What are the investigations used to diagnose hypopituitarism?
1. 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
2. Posterior pituitary function
3. Investigating the cuase:
- pituitary imaging → MRI ± contrast
- investigation of hormonal hypersecretion if a pituitaru tumour is demonstrated
- investigation of infiltrative disorders
35
How should hypopituitarism be managed?
- adequate and appropriate hormone replacement and management of underlying cause
