Endocrine Flashcards
1
Q
What is the function of the thyroid gland?
A
- Thyroid hormones control the metabolic rate of many tissues.
- Thyroid gland secretes T4 predominantly and only a small amount of biologically active T3
- Most circulating T3 is made by conversion of T4 to T3 in periphery
2
Q
What is unique about the thyroid amongst endocrine glands?
A
- There is sufficient iodinated thyroglobulin stored within follicles of the thyroid to provide thyroid hormone for several weeks even in the absence of dietary iodine
- Iodine is therefore an essential requirement for thyroid protection.
3
Q
What are the thyroid hormones?
A
T4 - Thyroxine
T3 - Triiodothryonine
Tyrosine + 1 Iodine Molecule -= Monoiodothyrosine
- Drugs and illnesses can alter the concentration of binding proteins or the action of binding so levels may not always be concordant
E.g. oestrogen increases level of thyroid binding globulin and hence total T4
4
Q
How is thyroid function measured?
A
Thyroid function (for both hyper and hypo) is measured by
- Serum TSH concentration
- Serum free T4 (or T3) concentration
5
Q
What is Hyperthyroidism? (Thyrotoxicosis)
A
Overactivity of the thyroid gland –> overproduction of thyroid hormone
6
Q
What is Hypothyroidism? (myxoedema)
A
Underactivity of the thyroid gland –> underproduction of thyroid hormone
- May be due to primary (from disease of the thyroid gland) –> reduced T4 and thus T3
or secondary (pituitary/hypothalamic disease) –> reduced TSH from anterior pituitary - HYPOPITUITARISM
7
Q
Describe the epidemiology of hyperthyroidism?
A
- Affects females more than males
- Affects 2-5% of all women at some time
- Presentation mainly between 20-40
8
Q
What are the causes of Hyperthyroidism?
A
1) Graves’ disease – most common
2) Toxic multinodular goitre –
3) Toxic thyroid adenoma
4) Pituitary adenoma –> causes more TSH to be produced –> more T3/4
5) De Quervain’s thyroiditis
6) Drug induced
9
Q
How does drug induced hyperthyroidism occur?
A
AMIODARONE - anti-arrhythmic drug:
- Can cause both hyperthyroidism (due to the high iodine content of amiodarone) and hypothyroidism (since it also inhibits the conversion of T4 to T3)
• Iodine
• Lithium
10
Q
How does do toxic multinodular goitre cause hyperthyroidism?
A
- Nodules that secrete thyroid hormones
- Occurs commonly in older women
- Drug therapy rarely successful in inducing a prolonged remission
11
Q
How does De Quervain’s thyroiditis cause hyperthyroidism?
A
- Transient hyperthyroidism sometimes from acute inflammation or the thyroid gland – probably viral
- Usually accompanied by fever, malaise and neck pain
- Treat with aspirin and only give prednisolone for severe
12
Q
What are the risk factors for hyperthyroidism?
A
- Female
- Family History/Genetic – association with HLA-B8, DR3 and DR4
- Stress
- Smoking
- Amiodarone
- High iodine intake
- Autoimmune disease
- E.coli and other gram-NEGATIVE organisms contain TSH-binding sites so may initiate pathogenesis via ‘molecular mimicry’
13
Q
Explain the pathophysiology of Graves’ Disease
A
- Serum IgG antibodies called TSH receptor stimulating antibodies (TRAb) bind to TSH receptors on the thyroid and stimulate T3/4 production
- This results in excess secretion, hyperplasia of the thyroid follicular cells, hyperthyroidism and goitre
14
Q
What are the Graves’ specific symptoms?
A
1) Graves Ophthalmology
- Extra-ocular muscle swelling –> protruding eyes (exophthalamos)
- Eye discomfort
- Lacrimation
- Diplopia – double vision
2) Pretibial myxoedema
- Raised purple-red symmetrical skin lesions over anterolateral aspects of the shins
3) Thyroid Acropachy
- Clubbing – swelling of fingers and toes
4) Goitre
- A swelling of the thyroid gland that causes a lump in the front of the neck.
- The lump will move up and down when you swallow.
15
Q
What are the common symptoms of hyperthyroidism?
A
• Weight loss
• Irritability
• Heat intolerance
• Insomnia
• Diarrhoea
• Sweats
• Palpitations
• Anxiety
• Menstrual disturbance (oligomenorrhoea and amenorrhoea)
16
Q
What are the common signs of hyperthyroidism?
A
• Tachycardia/AF
• Goitre
• Tremor
• Hyperkinesia – increase in muscle activity
• Lid lag
• Lid retraction
• Thin hair and hair loss
• Onycholysis – painless separation of the nail from the nail bed
• Exophthalmos – bulging of the eye out of the orbit
17
Q
Explain the differential diagnosis of symptoms in patients
A
1) Elderly:
- Atrial fibrillation
- Other tachycardias and/or heart failure
2) Children:
- Excessive height or excessive growth rate
- Behavioural problems like hyperactivity
- Usually is clinically obvious
Differentiation of mild cases from anxiety can be difficult, look for:
- Eye signs e.g lid lag and stare
- Diffuse goitre
- Proximal myopathy and wasting
18
Q
What investigations should take place to diagnose hyperthyroidism?
A
1) Thyroid Function tests
- Primary (negative feedback due to hyperthyroidism) – low TSH, high T3/T4
- Secondary (e.g. pituitary secreting adenoma) – high TSH, high T3/T4
2) Thyroid autoantibodies
- Thyroid peroxidase antibodies – more often seen in hypothyroidism
- Thyroglobulin antibodies
- TSH receptor antibody (TRAb) – Graves only
3) Thyroid ultrasound
- Helps to differentiate Graves’ from toxic adenoma
4) Radioactive iodine isotope uptake scan
– Much greater uptake in Graves’ Disease
Note – if it is drug induced, everything will be normal except for raised thyroid hormones.
19
Q
What is the treatment for hyperthyroidism?
A
1) BETA BLOCKERS for rapid system control in attacks
- Decreases CNS activation (HR + BP)
2) CARBIMAZOLE – anti-thyroid drug
- Blocks thyroid hormone synthesis and also has immunosuppressive effects which affects Graves’ disease
Two strategies:
- Titration – oral Carbimazole for 4 weeks then reduce according to TFTs
- Block and replace – oral Carbimazole and thyroxine (less risk of going hypo)
- Aim is to maintain normal free T4 and TSH levels
- Severe side effect is agranulocytosis –> neutropenia
3) RADIOIODINE THERAPY
- Contraindicated in pregnancy and breast feeding
- Iodine taken up and local irradiation and tissue damage causes return to normal function
- Could potentially lead to hypothyroidism
4) THYROIDECTOMY – removal of the thyroid gland leaving a small remnant in order to maintain thyroid function - indicated for those with large goitre, poor response to drugs and have drug side-effects
- Anti-thyroid drugs are stopped 10-14 days prior and replaced with oral potassium iodide
Complications:
- Bleeding
- Post-op infection
- Hypocalcaemia
- Hypothyroidism
- Hypoparathyroidism
- Recurrent laryngeal palsy – due to laceration
- Recurrent hyperthyroidism
20
Q
What are the complications of hyperthyroidism?
A
- Congestive HF
- Atrial Fibrillation
- Osteoporosis
- Graves ophthalmopathy complications
- Graves dermopathy - elephantitis
21
Q
What is a thyroid crisis (storm)?
A
- Rare life-threatening condition in which there is a rapid deterioration of thyrotoxicosis with
- Hyperpyrexia
- Tachycardia
- Extreme restlessness
- Even delirium, coma and death
22
Q
What is a thyroid storm usually precipitated by?
A
- Infection
- Stress
- Surgery
- Radioactive iodine therapy
23
Q
What is the treatment for a thyroid storm?
A
- Large doses of Carbimazole
- Propranolol
- Potassium iodide – to acutely block release of thyroid hormone from gland
- Hydrocortisone – to inhibit peripheral conversion of T4 to T3
24
Q
Describe the pathophysiology of hypothyroidism
A
Under-activity of the thyroid gland.
May be primary (from disease of the thyroid gland) or less commonly secondary to pituitary or hypothalamic disease (secondary hypothyroidism) resulting in reduced TSH drive.
25
Describe the epidemiology of hypothyroidism
- Affects females more than males
- Affects 0.1-2% of the population
- Autoimmune hypothyroidism is associated with other autoimmune disease e.g. DMT1, Addisons’, pernicious anaemia
- In general hypothyroidism is associated with Turner’s (only affects females, only have one X chromosome as opposed to the normal XX) & Down’s (trisomy 21) syndrome, cystic fibrosis, primary biliary cirrhosis and ovarian hyper-stimulation
26
What are the causes of hypothyroidism?
1) Post-partum thyroiditis – following child birth
- Usually transient phenomenon observed following pregnancy
- If conventional antibodies are present, there is a high chance of proceeding to permanent hypothyroidism
2) Autoimmune thyroiditis – may be associated with a goitre (Hashimoto’s thyroiditis or thyroid atrophy)
3) Iodine deficiency – occurs particularly in mountainous areas
4) Drug-induced
o Carbimazole
o Lithium
o Amiodarone
Amiodarone can cause hyperthyroidism due to high iodine content
Can cause hypothyroidism as it inhibits the conversion of T4 to T3
5) Latrogenic – caused by treatment or examination
- Thyroidectomy – for treatment of hyperthyroidism or goitre
- Radioactive iodine treatment or external neck irradiation for head and neck cancer
6) Congenital hypothyroidism:
--> Related to thyroid aplasia or dysplasia or defective synthesis of thyroid hormones
27
What is autoimmune thyroiditis? (Hashimoto's thyroiditis)
- Autoimmune thyroiditis may be associated with a goitre (Hashimoto’s thyroiditis or thyroid atrophy)
- Associated with anti-thyroid autoantibodies leading to lymphocytic infiltration of the gland and eventual atrophy and fibrosis of normal follicles
- Thyroid peroxidase is an enzyme essential for the production and
storage of thyroid hormone
- Thyroid peroxidase antibodies (TPO-Ab) are present in HIGH TITRES
- Since there is atrophy, there is NO GOITRE
- Almost all patients have serum antibodies to thyroglobulin and thyroid peroxidase (TPO)
- Associated with other autoimmune conditions e.g. pernicious anaemia and Addison’s disease
- CD8 mediated
28
What are the symptoms of hypothyroidism?
• Hoarse voice
• Goitre
• Weight gain
• Constipation
• Cold intolerance
• Menorrhagia – heavy periods
• Tiredness
• Lethargy
• Poor memory
• Puffy eyes
• Arthralgia/myalgia
29
What are the signs of hypothyroidism?
BRADYCARDIC
• Bradycardia
• Reflexes relax slowly
• Ataxia
• Dry thin hair/skin
• Yawning
• Cold hands
• Ascites
• Round puffy face
• Defeated demeanour
• Immobile – ileus (temporary arrest of intestinal peristalsis)
• Congestive HF
Note – young women should always have hypothyroidism excluded in any period problems
30
What investigations should be undertaken to diagnose hypothyroidism?
1) Thyroid function test
- Primary - High TSH, low free T4
- Secondary – inappropriately low TSH, low T3/T4 (since issue is in pituitary)
2) Thyroid antibodies
- Thyroid antibodies (TPO) in Hashimoto’s
3) Other
FBC
- Normocytic and normochromic anaemia
- May be macrocytic in women due to menorrhagia
- May be microcytic due to pernicious anaemia
o Hyperlipidaemia
o Hyponatraemia (due to increased ADH and impaired clearance of free water)
o Increased serum creatine kinase levels with associated myopathy
31
Describe the management of hypothyroidism
Lifelong oral Levothyroxine (T4)
o Start 25mcg and increase incrementally every 3-6 weeks
o Aim is to get TSH to >0.5
o Primary – titrate dose until TSH normalises
o Secondary – TSH will always be low, T4 monitored
32
What are the complications of hypothyroidism?
Myxoedema coma:
- Severe hypothyroidism (REDUCED T4) that may rarely present
with confusion and coma - particularly in elderly
- Typical features include hypothermia, cardiac failure,
hypoventilation, hypoglycaemia and hyponatraemia
- MEDICAL EMERGENCY and given IV/ORAL T3 & glucose infusion
as well as gradual rewarming
33
What are the differential diagnoses in hypothyroidism?
1) Children with hypothyroidism:
• May not show the classic features but often have a slow growth velocity,
poor school performance and sometimes an arrest in puberty
2) Young women with hypothyroidism:
• May not show obvious signs
• Hypothyroidism should be excluded in all people with oligomenorrhea/
amenorrhoea, menorrhagia, infertility or hyperprolactinaemia -
3) Hypothyroidism in the elderly:
• Hard to differentiate clinical features from normal ageing - should exclude hypothyroidism in those with cognitive impairment
34
Explain the pathpphysiology of thyroid cancer
- Thyroid cancer is uncommon and most present as asymptomatic thyroid nodules.
- Minimally active hormonally
- Over 90% secrete thyroglobulin which can be used as a tumour marker after thyroid ablation
- Carcinomas derived from thyroid epithelium may be:
- Differentiated - papillary or follicular
- Undifferentiated - anaplastic
35
What are the different types of thyroid carcinoma?
Papillary (70%)
- Young people
- Local
- Good
Follicular (20%)
- Middle age
Lung/bone
Usually good
Medullary cell (5%)
Often familial
Local and metastases
Poor
Lymphoma (2%)
Variable
Usually poor
Anaplastic (<5%)
Aggressive
Local
Very poor
36
What are the symptoms of thyroid carcinoma?
• Thyroid nodules – increased size, hardness and irregularity
• Dysphagia
• Hoarseness of voice – tumour pressing on recurrent laryngeal nerve
37
What are the signs of thyroid carcinoma?
• Lymph node metastases
• Lung or bone metastases (rare)
• Thyroid nodule with history of progressive increase in size
• Hard and irregular nodule
• Enlarged lymph nodes
38
What is the differential diagnosis of thyroid carcinoma?
Goitre
39
What are the investigations for thyroid carcinoma?
• Fine needle aspiration cytology biopsy best for distinguishing between benign and malignant thyroid nodules
• Thyroid ultrasound
• TFTs – hyper/hypothyroidism needs to be treated before surgery
40
What is the treatment for thyroid carcinoma?
+ Follicular and papillary cancers
-Total thyroidectomy with neck dissection for local nodal spread
- Ablative radioiodine subsequently given – taken up by remaining thyroid tissue or metastatic lesions
+ Anaplastic and lymphoma
- External radiotherapy may produce brief respite
- Otherwise treatment is largely palliative
41
What does the adrenal gland consist of?
• Adrenal glands consist of:
Outer cortex – steroids (aldosterone, cortisol and androgens):
1) Zona glomerulosa (G) – Mineralocorticoids e.g. aldosterone
2) Zona fasciculata (F) – Glucocorticoids e.g. cortisol
3) Zona reticularis (R) – Androgens (sex hormones)
* GFR – Makes Good Sex
• Inner medulla:
Catecholamines --> Under sympathetic control and secretes catecholamines e.g. adrenaline and noradrenaline
42
What is Cushing’s Syndrome?
- Abnormalities resulting from a chronic excess of glucocorticoids (CORTISOL) whatever the cause
- Loss of hypothalamic
pituitary axis feedback
- Loss of circadian rhythm
- Most cases result from administration of synthetic steroids or ACTH for medical treatment
Syndrome = Steroid use
43
What is Cushing's disease?
Cushing’s disease specifically refers to excess glucocorticoids resulting from inappropriate ACTH secretion from the pituitary - (typically a pituitary adenoma)
Disease = aDenoma
44
Describe the epidemiology of Cushing's.
• Most common cause is oral steroids i.e. glucocorticoid therapy
• Spontaneous endogenous causes are rare – of these, 80% are due to raised ACTH (with pituitary adenoma most common cause)
45
What are the causes of Cushing's?
ACTH Independent causes
o Oral steroid use (iatrogenic) – most common
o Adrenal adenomas/carcinomas – tumour of adrenal gland that releases cortisol
ACTH dependent causes
o Cushing’s disease
- Bilateral adrenal hyperplasia due to ACTH hypersecretion by pituitary adenoma
o Ectopic Cushing’s Syndrome – coming from elsewhere
- Due to paraneoplastic syndrome e.g. small cell lung cancer producing ACTH
46
What is the pathology of excess cortisol?
Excess can result from:
1) Excess ACTH which in turn stimulates excess cortisol production
2) Neoplasms in adrenals which stimulate zona reticularis to produce more cortisol
- Ingesting excess glucocorticoids itself e.g. prednisolone
47
What are the symptoms of Cushing's?
• CUSHING
o Cataracts
o Ulcers
o Striae – purple strokes on skin
o Hypertension and hyperglycaemia (due to impaired glucose tolerance)
o Increased risk of infection – dampening of inflammatory response
o Necrosis
o Glucosuria
• Amenorrhoea
48
What are the signs of Cushings?
• Truncal/central obesity
• Moon face
• Buffalo hump – fatty hump on upper back
• Acne
• Hirsutism – unwanted male pattern hair growth in women
• Thin skin/bruising
• Osteoporosis
49
What is the differential diagnosis for Cushing's?
• Pseudo-Cushing’s syndrome
o Caused by alcohol excess
o Resolves after 1-3 weeks of alcohol abstinence
50
What investigations would you do to diagnose Cushings? (1st line)
• Random cortisol – if high then proceed to first line test (may mislead as cortisol varies throughout the day)
• 1st line – overnight dexamethasone suppression test
o Dexamethasone usually suppresses cortisol level
o Failure to suppress over 24-hour period is diagnostic of Cushing’s syndrome
o Low dose dexamethasone
- Most reliable screening tests
- Normal individuals suppress cortisol to <50 nmol 2 hours after last dose of dexamethasone
o High dose dexamethasone
- Most patients with pituitary-dependent Cushing’s disease suppress plasma cortisol by 48 hours
- Failure of suppression suggests an ectopic source of ACTH or an adrenal tumour
• Check 24-hour urinary free cortisol measurement – normal levels mean Cushing’s is unlikely
51
What investigations would you do to diagnose Cushings? (2nd line)
• 2nd line - If no suppression, then 48hr dexamethasone test
• Plasma ACTH
o Low --> adrenal imaging (CT/MRI to detect adenoma or carcinoma)
o High --> distinguish pituitary and ectopic cause
- Suppression by high dose dexamethasone = pituitary adenoma followed by pituitary MRI to find lesion
- No suppression by high dose = look for ectopic
• IV contract CT chest, abdomen and pelvis
• MRI of neck, thorax and abdomen
• CXR to look at lungs for small cell lung cancer
- Or do CRH test
• If cortisol increases = pituitary disease
• If cortisol doesn’t increase = ectopic
• CT or MRI
o To detect adrenal carcinomas and adenomas
o To detect pituitary
52
Describe the treatment of Cushing's.
• If iatrogenic – stop steroids
• Cushing’s Disease – transphenoidal removal of pituitary adenoma
• Adrenal adenoma – adrenalectomy*, radiotherapy
o *May cause Nelson’s syndrome
- If you remove the adrenal glands, then no cortisol will be produced in response to ACTH produced by the pituitary gland.
- If no cortisol is produced, then there is no negative feedback on ACTH levels which can cause ACTH to build up in the body tissues.
- This can cause a bronze pigmentation of the skin, visual disturbances and headache
- Adrenal carcinoma – adrenalectomy + RT and adrenolytic drugs e.g. mitotane
- Ectopic ACTH – surgery to remove tumour if location known and it hasn’t spread
53
What is Acromegaly?
• Acromegaly = excessive production of growth hormone occurring in adults after fusion of the epiphyseal plates
• Gigantism = excessive production of growth hormone occurring in children before fusion of the epiphyses of long bones
54
How is GH secreted?
Pituitary GH is secreted in a pulsatile fashion under the control of GHRH (stimulates GH production) and somatostatin (inhibits GH production).
Hypothalamus --> GHRH --> Anterior Pituitary --> GH --> Liver --> IGF-1 --> Protein synthesis + cell division
GH is Inhibited by somatostatin and high glucose.
Ghrelin, which is synthesised in the stomach, also increases GH secretion.
55
What is the function of GH?
Function of GH:
• Direct – acts on tissues such as liver, muscles, bones and fat to induce metabolic changes
• Indirect – IFG-1
o Stimulate growth by protein synthesis and cell division
o Increases lipolysis and calcium retention
o Decrease blood glucose
o Stimulate hypertrophy and hyperplasia of bone, skeletal muscle etc.
56
Describe the epidemiology of Acromegaly.
• Rare – 3 per million/year
• Incidence – mean age of diagnosis is 40 years old
• Males and females affected equally
• Associated with multiple endocrine neoplasia-1 (MEN-1)
57
What are the causes of acromegaly?
•Benign GH-producing pituitary adenoma – very slow insidious onset over many years
•Ectopic GH-releasing hormone from a carcinoid tumour (rare)
58
Describe the pathology of Acromegaly.
• Increased GH usually due to a pituitary adenoma travels to tissues such as liver where it binds to receptors resulting in an increase in IGF-1
• Stimulates skeletal and soft tissue growth giving rise to “giant-like” appearance and symptoms
• Local tumour expansion in pituitary causes compression of surrounding structures resulting in headaches and visual field loss
59
Describe the symptoms of Acromegaly.
• Result of local tumour expansion
o Headaches
o Bitemporal hemianopia – visual field loss
o Hypopituitarism
• Metabolic effects of excess GH
o Acroparaesthesia
o Sweating
o Arthralgia
o Decreased libido or impotence
o Amenorrhoea or oligomenorrhea in women
o Galactorrhoea
60
Describe the symptoms of Acromegaly
• Acral enlargement (massive growth of hands, feet and jaw) – often say they can’t wear their wedding ring, hats, gloves etc. anymore
• Big tongue with widely spaced teeth
• Prominent supraorbital ridge
• Puffy lips, eyelids and skin
• Darkening skin
• Thick skin
• Obstructive sleep apnoea
• Deep voice
• Hypertension
• HF
61
What investigations would you do to diagnose Acromegaly?
• Oral glucose tolerance test
o Normally a rise in blood glucose will suppress GH levels
o Give glucose and then test GH levels – if they remain high this is diagnostic for acromegaly
• Serum IGF-1 levels – almost always raised in acromegaly and fluctuate less than those of GH
o Normal IGF-1 levels are a strong indicator that the patient does not have acromegaly
• MRI of pituitary fossa – evidence of pituitary adenoma
• Visual field tests for defects – bitemporal hemianopia
• ECG and Echocardiogram
• Serum prolactin – can be raised as a result of the adenoma
- Not a random GH test as GH is a pulsatile protein and levels vary throughout the day
62
What is the management of Acromegaly?
• 1st line
Transphenoidal surgical resection to remove the adenoma and correct compression of surrounding structures e.g. optic chiasm
o Complications
- Hypopituitary
- Infection
- Diabetes Insipidus
• 2nd line medical therapy
o Somatostatin analogues e.g. IM octreotide/lanreotide – inhibit GH secretion
- Given by s/c or IM injection
o Dopamine agonists e.g. ORAL bromocriptine or ORAL cabergoline – inhibit GH secretion
- Don’t work as well but can be given orally instead of s/c or IM injection
- GH antagonist e.g. pegvisomant – reserved for treatment of patients whose IGF-1 levels cannot be reduced to safe levels with somatostatin analogues alone
- External radiotherapy
63
What is Conn's Syndrome?
- Conn’s syndrome refers ONLY to PRIMARY Aldosterone producing adenoma
- 2/3 cases – Conn’s Syndrome: A solitary aldosterone producing adrenal adenoma
- 1/3 cases – Bilateral Adrenocortical hyperplasia (technically NOT Conn’s)
64
What are the risk factors for Conn's syndrome?
Hypertension
65
What is the pathology of Conn's syndrome?
- Excess production of aldosterone, independent of RAAS causes
- Increased K+ loss, Na+ and water retention + raised BP
- Decreased renin release
- Hypokalaemia
66
What are the symptoms of Conn's syndrome?
- Usually asymptomatic
- Symptoms of Hypokalaemia:
o Constipation
o Muscle weakness and cramps
o Polyuria and polydipsia
o Paraesthesia
- Unusual symptoms - sweating attacks
67
What are the signs of Conn's syndrome?
- Hypertension due to increased blood volume
- Increased risk of cardiac arrhythmias, particularly in patients with cardiac disease
68
What is the differential diagnosis for Conn's syndrome?
- Secondary hyperaldosteronism – arises when there is excess renin (and hence angiotensin II) which stimulates aldosterone release
- Causes:
o Renal artery stenosis
o Accelerated hypertension
o Diuretics
o Congestive HF
o Hepatic failure
69
What are the investigations for Conn's syndrome?
• U&Es
o Decreased renin
o Increased aldosterone
• ECG - Rhyme – U have no Pot (K+) and no Tea (shallow t-wave) but a Long PR and a Long QT:
o Flat T waves
o ST depression
o Long QT intervals
o Long PR intervals
o Pathological U waves
• Adrenal CT/MRI – for confirmation of aldosterone producing adenoma
70
What is the treatment for Conn's syndrome?
• Laparoscopic adrenalectomy
• Oral spironolactone – aldosterone antagonist (K+ sparing diuretic)
71
What is Addison's disease?
- Addison’s is an autoimmune condition in which there is destruction of the adrenal cortex.
- Results in mineralocorticoid (aldosterone), glucocorticoid (cortisol) and androgen (sex hormones) deficiency.
- It is a subset of primary adrenal insufficiency
- Simpler terms – opposite of Cushing’s syndrome
• Very rare 0.8 per 100,000
• Can be fatal
• More common in females
72
What is the pathology of Addison's disease?
• Destruction of the entire adrenal cortex resulting in reduced glucocorticoid (cortisol), mineralocorticoid (aldosterone) and androgen production
• All steroids are reduced which differs from hypothalamic-pituitary disease in which mineralocorticoid and androgen secretion remains largely intact due to their relative independence from the pituitary
• In Addison’s, the reduced cortisol levels lead (through feedback), to increased CRH and ACTH production (ACTH responsible for hyperpigmentation)
73
What are the causes of Addison's disease?
• Primary
o Addison’s - autoimmune adrenalitis (90% of cases)
o Adrenal TB
o Surgical removal of adrenal glands
o Adrenal haemorrhage/infarction (in meningococcal septicaemia)
o Malignant infiltration – from lung, breast or renal cancer
• Secondary
o Steroids
o Congenital
o CRH deficiency
o Trauma
o Radiotherapy
74
Common exam question – What is the commonest cause of primary adrenal insufficiency?
1. Worldwide = TB
2. In UK = Addison’s (autoimmune adrenalitis)
75
What other autoimmune conditions is Addison's disease associated with?
• Pernicious anaemia
• T1DM
• Autoimmune thyroid disease
• Ovarian failure
76
What are the symptoms of Addison's disease?
• Presents with non-specific symptoms
o Nausea and vomiting
o Abdominal pain
o Weight loss
o Lethargy
o Depression (and tearfulness)
o Anorexia
• Impotence
• Amenorrhoea
77
What are the signs of Addison's disease?
•Postural hypotension caused by salt and water loss
•Hyperpigmentation caused by stimulation of melanocytes by excess ACTH in primary hypoadrenalism
•Vitiligo and loss of body hair in females due to dependence on adrenal androgens
•Hypoglycaemia
REMEMBER – Thin, Tanned, Tired, Toned and Tearful
78
What are the complications of Addison's disease?
Can present as an emergency (Addisonian crisis) – sudden need for aldosterone and cortisol
• Vomiting + nausea
• Abdominal and back pain
• Muscle cramps
• Confusion
• Hypotension
• Hypoglycaemia
• Hypovolaemic shock
- Treat with fluids and IV Hydrocortisone
79
What is the first line investigation for Addison's disease?
• Short ACTH stimulation test
o Take baselines cortisol
o Give ACTH (synACTHen) then measure cortisol level – shows failure of exogenous ACTH to increase plasma cortisol
- In Addison’s – cortisol remains low after giving ACTH
o Doesn’t distinguish between primary and secondary
80
What do plasma ACTH levels tell you in regards to Addison's disease?
o HIGH ACTH with low or normal cortisol confirms primary hypoadrenalism
o LOW ACTH and cortisol indicates secondary or tertiary hypoadrenalism
81
What do U&E's tell you in regards to Addison's disease?
o Shows high plasma renin (low sodium, high potassium) due to low aldosterone
o Eosinophilia
o Raised Urea
• Adrenal antibodies – 21-hydroxylase
• Adrenal/CXR
82
What is the treatment for Addison's disease?
• Glucocorticoids - oral Hydrocortisone/prednisolone to replace cortisol
• Mineralocorticoids - fludrocortisone to replace aldosterone
Note – double dose of steroids when there is infection, trauma, surgery, nightshift work
Dextrose - hyperglycaemic
83
What is the pathology of Diabetes insipidus?
Not enough ADH is being produced, either due to:
• Cranial DI – too little ADH from posterior pituitary gland
• Nephrogenic DI – kidney not responding to ADH
84
What are the cranial causes of DI?
o Neurosurgery
o Head trauma
o Pituitary tumour
o Infiltrative disease – sarcoidosis, histiocytosis
o Idiopathic
o Congenital defect in ADH gene
NOTE – damage to the Hypothalamo-neurohyophysial tract or posterior pituitary with an intact hypothalamus does NOT cause ADH deficiency as ADH can still “leak” from the damaged end of the intact neurone
85
What are the nephrogenic causes of DI?
o Drugs e.g. lithium chloride, demeclocycline
o Hypokalaemia
o Hypercalcaemia
o Renal tubular acidosis
o Sickle cell disease
o Familial – mutation in ADH receptor
86
What are the signs and symptoms of DI?
• Polyuria/Nocturia
• Polydipsia
• Dehydration
87
What are the investigations for DI?
• Water deprivation test - aims to determine whether kidneys continue to produce dilute urine despite dehydration
o Normal responses is for urine osmolality to remain within normal range and urine will be concentrated as a normal response
o Restrict fluid
o Measure urine osmolarity (positive for DI if urine osmolarity is low)
88
How can you differentiate between cranial and nephrogenic DI?
o Desmopressin (ADH analogues) is given to differentiate cranial or nephrogenic
- If urine osmolarity remains the same – Nephrogenic DI
- If urine osmolarity increased – Cranial DI
89
What other investigations can be done to help diagnose DI?
• MRI of hypothalamus
• Plasma biochemistry
o High or normal-high Na+
o Blood glucose, serum K+ and Ca2+ should be measured to exclude other causes of polyuria
• Urine volume to confirm polyuria
90
What is the treatment for DI?
• Cranial DI – desmopressin
• Nephrogenic DI
o Bendroflumethiazide (diuretic) – causes more Na+ secretion in DCT --> decreases sodium in the blood --> increases plasma osmolality --> decreases thirst--> increased water lost makes body respond by reducing GFR
o NSAIDs – reduce GFR by inhibiting prostaglandin synthase (prostaglandins locally inhibit ADH action)
91
What is Syndrome of inappropriate ADH secretion? (SIADH)
- Continued secretion of ADH despite plasma being very dilute --> water retention, excess blood volume and hyponatraemia (as Na+ becomes less concentrated)
- So basically, too much ADH
92
Describe the pathology of SIADH?
• Excess ADH --> insertion of aquaporin 2 increases --> water retention --> dilution of blood plasma --> hyponatraemia
• BUT ALSO
• Excess ADH --> insertion of aquaporin 2 increases --> water retention --> decreased RAAS – aldosterone --> secretion of Na+ --> excess water being excreted WITH Na+ (body is removing sodium from blood that already has a low concentration of sodium) --> NORMOVOLAEMIC yet HYPONATRAEMIC
93
Describe the aetiology of SIADH?
- Disordered hypothalamic-pituitary secretion or ectopic production of ADH
94
What are the causes of SIADH?
- Malignancy
o Small cell lung carcinoma most common
o Prostate
o Thymus
o Pancreas
- Drugs
o Opiates
o Chlorpropamide
o Carbamazepine
o Vincristine
- Brain issues
o Meningitis
o Cerebral abscess
o Head injury
o Tumour
- Lung
o Pneumonia
o TB
o Abscesses
o Asthma
o CF
- Metabolic
o Porphyria - group of very rare metabolic disorders that occur when the body can’t produce Haem
o Alcohol withdrawal
95
What are the symptoms of SIADH?
• Reduction in GCS and confusion with drowsiness
• Irritability
• Headaches
• Anorexia
• Nausea
96
What are the signs of SIADH?
• Concentrated urine
• Mild dilutional hyponatraemia – could lead to fits and coma
97
How can SIADH be differentiated from hyponatremia? What is the diagnostic criteria?
Diagnostic criteria:
o Low serum sodium
o Low plasma osmolality with “inappropriate” urine osmolarity
o Continued urinary sodium excretion
o Absence of hypokalaemia, hypotension and hypovolaemia
o Normal renal, adrenal and thyroid function
Note – HypoNa common in elderly and may be difficult to distinguish between SIADH and salt/water depletion
• Test with 1-2L of 0.9% saline – sodium depletion WILL respond, SIADH will NOT
98
What is the treatment of SIADH?
• Treat underlying cause
• Restrict fluid – to increase Na+ concentration
• Demeclocycline – inhibits action of vasopressin on kidney i.e. causes nephrogenic DI
• Vasopressin receptor antagonists (vaptans) – V2 blocker
o TOLVAPTAN – used for treatment of hyponatraemia secondary to SIADH as promotes water excretion with no loss of electrolytes
• Oral furosemide – salt and loop diuretics if severe and to prevent circulatory overload.
99
Why is potassium important in the body?
- Potassium is charged and is important in maintaining the resting potential of all muscles in the body.
- Imbalance to hyper/hypo polarisation of the membrane results in different symptoms
100
What is potassium controlled by?
• Uptake of K+ into cells
• Renal excretion – mainly controlled by aldosterone
• Extrarenal losses e.g. GI
101
Describe the pathology of Hyperkalaemia?
• The amount in the blood determines the excitability of nerve and muscle cells including the heart muscle (myocardium)
• When K+ levels in blood rise, this reduces the difference in electrical potential between cardiac myocytes and outside of the cells --> threshold for action potential significantly decreases --> abnormal action potential --> arrhythmias --> cardiac arrest
102
What are the causes of Hyperkalaemia?
- Due to excessive consumption at a fast rate:
o IV fluids
- Low levels of aldosterone in kidneys – adrenal insufficiency:
o Majority of K+ excretion is through the kidneys
o Aldosterone stimulates secretion of K+
- Drugs
o ACE inhibitors – block the binding of aldosterone to receptor
o Spironolactone – potassium-sparing diuretic
o NSAIDs
o Ciclosporin
o Heparin
• Acute kidney injury – decreased filtration rate so more K+ is maintained in blood
103
What are the symptoms of hyperkalaemia?
• Typically, asymptomatic until high enough to cause cardiac arrest
• Muscle weakness
• Impaired neuromuscular transmission
• Flaccid paralysis
• Chest pain
• Light-headedness
104
What are the signs of hyperkalaemia?
• Metabolic acidosis causing Kussmaul's respiration - low, deep, sighing inspiration and expiration
• Tachycardia
105
What are the investigations for hyperkalaemia?
• U&Es
o Over 5.5mmol/L = hyperkalaemic
o Over 6.5mmol/l = MEDICAL EMERGENCY
• ECG
o Tall tented T waves
o Small P waves
o Wide QRS complex
106
What is the treatment for mild to moderate hyperkalaemia?
o Treat underlying cause
o Dietary potassium restriction
o Restriction of drugs causing hyperkalaemia
o Loop diuretics e.g. furosemide – increase urinary K+ excretion
107
What is the treatment for severe hyperkalaemia?
o Calcium gluconate – decreases VF risk in the heart and protects myocardium by reducing excitability of cardiac myocytes
o Insulin and dextrose – drives K+ into the cells
o Polystyrene sulphonate resin – binds K+ in the gut decreasing uptake
108
What is the pathology of hyperkalaemia?
• Low K+ in the serum (ECF) causes a water concentration gradient out of the cell (ICF)
• Increased leakage from ICF causing hyperpolarisation of the myocyte membrane decreasing myocyte excitability
109
What is the pathology of hypokalaemia?
• Low K+ in the serum (ECF) causes a water concentration gradient out of the cell (ICF)
• Increased leakage from ICF causing hyperpolarisation of the myocyte membrane decreasing myocyte excitability
110
What are the causes of hypokalaemia?
- Fasting
- Anorexia
- High levels of aldosterone in kidneys
o Majority of K+ excretion is through the kidneys
o Aldosterone stimulates secretion of K+
o Cushing’s and Conn’s
- Increased renal excretion
o Thiazides diuretics e.g. Bendroflumethiazide
o Loop diuretics e.g. furosemide
- GI losses – vomiting, severe diarrhoea and laxative abuse
111
What are the symptoms of hypokalaemia?
• Usually asymptomatic
• Muscle weakness
• Cramps
• Tetany – intermittent muscle spasms
• Palpitations
• Constipation
112
What are the investigations for hypokalaemia?
• U&E’s
o Serum K+ < 3.5mmol/L = hypokalaemia
o Serum K+ < 2.5mmol/L = MEDICAL EMERGENCY
113
What would an ECG show in hypokalaemia?
ECG:
o U waves
o Small or inverted T waves
o Depressed ST segments
o Long PR
o Long QT
Rhyme - U have no Pot (K+) and no Tea but a Long PR and a Long QT
114
What is the treatment of hypokalaemia?
• Mild – Oral K+ e.g. oral Sando-K and spironolactone (K+ sparing)
• Severe- IV K+
115
What is parathyroid hormone?
- Parathyroid hormone is secreted from the 4 parathyroid glands which lie posterior to the thyroid gland, in response to a decrease in calcium levels.
- PTH is secreted by CHIEF CELLS in response to Hypocalcaemia
116
What is the action of PTH?
• Increased Ca2+ resorption from bone by osteoclasts - rapid
• Increased intestinal calcium absorption - slow
• Activates 1, 25 – dihydroxy-vitamin D (calcitriol) in kidney
• Increased calcium reabsorption and phosphate excretion in the kidney
117
What is calcitriol?
Calcitriol is the active form of Vitamin-D and has many roles:
• Increased Ca2+ and phosphate absorption in the gut
• Inhibits PTH release – negative feedback
• Enhanced bone turnover by increasing osteoclasts
• Increased Ca2+ and phosphate reabsorption in the kidney
118
What is calcitonin?
It acts to reduce blood calcium, opposing the effects of parathyroid hormone.
• Made in C-cells of thyroid
• Causes a decrease in plasma Ca2+ and phosphate
119
What is primary hyperparathyroidism?
• Primary – excessive PTH secretion
o Affects ~0.1% of population
o Usually caused by single parathyroid adenoma
120
What is secondary hyperparathyroidism?
o Physiological compensatory hypertrophy of all the glands in response to hypocalcaemia
- E.g. in Chronic Kidney Disease, Crohn’s or Vitamin D deficiency
121
What is tertiary hyperparathyroidism?
o Development of apparently autonomous parathyroid hyperplasia after long-standing secondary hyperparathyroidism – most commonly in renal disease
o Plasma calcium and PTH are both raised
o Treated by parathyroidectomy
122
What are the symptoms of hypercalcaemia?
Symptoms – shows symptoms of hypercalcaemia
- Painful bones
o Painful bone condition – typically osteitis fibrosa cystica
- Renal stones
o Renal colic from renal stones (can lead to renal failure)
o Biliary stones
- Psychiatric moans – effects on nervous system
o Lethargy
o Fatigue
o Memory loss
o Psychosis
o Depression
o Insomnia
- Abdominal groans – GI symptoms
o Nausea
o Vomiting
o Constipation
o Indigestion
- Thirst
- Polyuria
123
What are the signs of hypercalcaemia?
- Fractures, pain and osteoporosis caused by bone resorption
- Hypertension
124
What are the investigations for hypercalcaemia?
- Bloods
o Primary - ↑PTH, ↑Ca, ↓Phosphate
o Secondary - ↑ PTH, ↓ Ca, ↑ Phosphate (due to renal disease)
o Tertiary - ↑ everything (progression of secondary)
- Increased 24-hour urinary calcium excretion
- DEXA bone scan for osteoporosis
- Abdominal X-ray – renal calculi or nephrocalcinosis
- Radioisotope scanning – 90% sensitive for detecting adenomas
125
What is the treatment for hypercalcaemia?
- Primary
o Parathyroid adenoma – surgical removal
o Parathyroid hyperplasia – all 4 glands are removed surgically (hypocalcaemia is a complication)
o Give calcimietic that increases sensitivity of parathyroid cells to Ca2+ less PTH secretions e.g. oral Cinacalcet
o Avoid thiazide diuretics and high Ca2+ and Vitamin D intake
- Secondary and tertiary
o Treat the cause
- Emergency
o Rehydrate with IV 0.9% - to prevent stones
o Give bisphosphonates (to prevent bone resorption by inhibiting osteoclasts) after rehydration – IV PAMIDRONATE
o Measure serum U&Es daily
126
What are the causes of hypoparathyroidism?
• Autoimmune destruction of parathyroid glands – Di-George syndrome
• Vitamin D deficiency - results in less Ca2+
o Can cause mild and occasionally severe hypocalcaemia and osteomalacia
• Congenital
• Parathyroidectomy (secondary)
• Magnesium deficiency
127
What are the symptoms of hypoparathyroidism?
Symptoms of hypocalcaemia:
• Spasms
o Hands and feet
o Larynx – can obstruct airway
o Premature labour – uterus contractions
• Peripheral paraesthesia
• Anxious
• Seizures
• Muscle tone increase
128
What are the signs of hypoparathyroidism?
• Convulsion
• Arrhythmias
• Tetany
• Spasm and stridor
• Chvostek’s sign – tapping over facial nerve in region of parotid gland causes twitching of ipsilateral facial muscles
• Trousseau’s sign – carpopedal spasm induced by inflation of the sphygmomanometer cuff to ~20 mmHg above systolic BP
SPASMODIC
• Spasms – carpopedal spasms = trousseau’s sign
• Perioral paraesthesia (around mouth)
• Anxious, irritable, irritational
• Seizures
• Muscle tone increases
• Orientation impaired and confusion
• Dermatitis
• Impetigo herpetiformis – psoriatic pustules
• Chvostek’s sign, cataracts, cardiomyopathy
129
What is the treatment of hypoparathyroidism?
• Calcium supplement
• Calcitriol (active vitamin D)
• Synthetic PTH
130
What is Pseudohypoparathyroidism?
• Resistance to PTH hormone due to mutation with Gz subunit on parathyroid
• Bloodwork shows
o Low Calcium
o High PTH
• Treat as normal hypoparathyroidism
• Associated with short stature, short metacarpals (especially 4th and 5th), subcutaneous calcification and sometimes intellectual impairment
131
Where is most calcium stored?
99% of Calcium is stored in bone as calcium phosphate.
132
What 3 things is calcium balance controlled by?
• Parathyroid gland – PTH
o Causes stimulation of kidneys and GI tract to increase absorption of calcium and causes stimulation of osteoclasts to break down bone and release calcium stored there
o CALCITRIOL (active vitamin D) levels are increased by PTH and cause increased GI and kidney absorption of Calcium.
• Thyroid – CALCITONIN
o When levels rise too high receptors on the thyroid are stimulated which cause the realise of calcitonin which inhibits GI reabsorption and increases osteoblast activity.
133
What do calcium disorders show on an ECG?
• If calcium is TOO HIGH the QT, interval gets SHORTER
• If calcium is TOO LOW, the QT interval gets LONGER
134
Define hypocalcaemia
Low serum Calcium
135
What are the causes of hypocalcaemia?
1) Vitamin D deficiency – presents with low phosphate
o Poor calcium uptake in the GI tract and decreased absorption in kidneys
o Leads to osteomalacia
o 50% of people are vitamin D deficient
2) Hypoparathyroidism – presents with high phosphate
o Secondary - post parathyroidectomy or thyroidectomy
3) Acute pancreatitis – presents with low phosphate
4) Osteomalacia – presents with low phosphate
o Soft bones partially due to low calcium and vitamin D deficiency
- Serum calcium low because Ca2+ can’t be absorbed from blood
- Parathyroid gland recognises this and produces PTH to suck calcium from kidneys and resorb bone
5) Chronic Kidney Disease – presents with high phosphate
o Causes poor uptake of calcium in the kidneys
o Caused by inadequate production of active vitamin D and renal phosphate retention --> microprecipitation of calcium phosphate in tissues
6) Pseudohypoparathyroidism – resistance to PTH due to a mutation with Gz subunit on the parathyroid gland
7) Drugs
o Calcitonin – decreases Ca2+ and phosphate
o Bisphosphonates – reduce osteoclast activity resulting in reduced Ca2+
136
What are the symptoms of hypocalcaemia?
• Spasms
o Hands and feet
o Larynx – can obstruct airway
o Premature labour – uterus contractions
• Peripheral paraesthesia
• Anxious
• Seizures
• Muscle tone increase
137
What are the signs of hypocalcaemia?
• Convulsion
• Arrhythmias
• Tetany
• Spasm and stridor
• Chvostek’s sign – tapping over facial nerve in region of parotid gland causes twitching of ipsilateral facial muscles
• Trousseau’s sign – carpopedal spasm induced by inflation of the sphygmomanometer cuff to ~20 mmHg above systolic BP
SPASMODIC
• Spasms – carpopedal spasms = trousseau’s sign
• Perioral paraesthesia
• Anxious, irritable, irritational
• Seizures
• Muscle tone increases
• Orientation impaired and confusion
• Dermatitis
• Impetigo herpetiformis
• Chvostek’s sign, cataracts, cardiomyopathy
138
What are the investigations for hypocalcaemia?
• ECG – long QT interval
• Bloods
139
What is the treatment for hypocalcaemia?
• Mild – Adcal supplement (calcium carbonate) or cholecalciferol
• Severe – Calcium gluconate
140
Define hypercalcaemia
High serum Calcium
Check – is it really high calcium?
• Tourniquet on too long
• Sample old and haemolysed blood
141
Describe the epidemiology of hypercalcaemia.
• ~1 in 1000 have mild asymptomatic hypercalcaemia
• Typically affects older women
142
What are the causes of hypercalcaemia?
Causes – 90% of cases due to hyperparathyroidism and cancer
• Primary hyperparathyroidism – bones, stones, moans and groans
• Malignancy - causes unregulated bone breakdown leading to increased calcium levels in the blood
o Non-Hodgkin’s Lymphoma
o Myeloma
o Bone metastases and production of local factors that mobilise calcium
o PTHrP – Parathyroid Hormone relating peptide, occurs in some kidney and lung cancers, behaves similarly to PTH but isn’t measured on assay
CHIMPANZEES
• Calcium supplementation
• Hyperparathyroidism
• Latrogenic drugs – thiazides
• Milk alkali syndrome
• Paget’s disease of bone
• Acromegaly and Addison’s
• Zolinger-Ellison Syndrome – MEN type I
• Excess vitamin D
• Excess vitamin A
• Sarcoidosis
143
What are the symptoms of hypercalcaemia?
• Painful bones
o Painful bone condition – typically osteitis fibrosa cystica
• Renal stones
o Calcium deposition in renal tubules causes polyuria and nocturia
o Can lead to kidney stones and kidney failure
• Psychiatric moans – effects on nervous system
o Lethargy
o Fatigue
o Memory loss
o Psychosis
o Depression
• Abdominal groans – GI symptoms
o Nausea
o Vomiting
o Constipation
o Indigestion
• Cardiac Arrest
144
What are the investigations for hypercalcaemia?
• ECG – tented T, short QT interval
• CXR – to rule out myeloma and Non-Hodgkin’s
lymphoma
• 24-hour urinary calcium
o Measured in young patients and those with a family history to exclude familial hypocalciuric hypercalcaemia
• Bloods - Calcium and PTH
o Undetectable PTH in context of hypercalcaemia excludes primary hyperparathyroidism and requires further investigation – tumour secreting an alike protein which results in hypercalcaemia but not increased PTH
• X-ray and protein electrophoresis for myeloma
• DEXA bone scan
• High resolution CT
• TSH to exclude hyperthyroidism
• Tetracosactide test to exclude Addison’s
145
What is the treatment of hypercalcaemia?
• Lowering calcium levels and treatment of underlying cause
o Primary hyperparathyroidism – surgical removal of symptomatic parathyroid adenoma
• IV saline – helps to dilute levels of calcium in blood
• Bisphosphonates – encourage osteoclasts to undergo apoptosis so there is less bone breakdown
146
How can you differentiate between hypercalcaemia due to hyperparathyroidism or due to cancer?
Hyperparathyroidism:
- Corrected calcium levels = mild increase
- PTH = high
Cancer:
- Corrected Calcium levels = severe increase
- PTH = Low
147
If you have a pituitary mass – what might they be?
• Non-functioning pituitary adenomas
• Functioning tumour
• Malignant pituitary tumour – may be functioning or non-functioning carcinoma
• Pituitary cysts: e.g. Rathke’s cleft
• Developmental abnormalities: craniopharyngioma, germinoma
• Malignant systemic disease: Hodgkin’s/ non Hodgekins lymphoma
• Granulomatous disease: Wegner’s, TB
148
What are the three vital signs to look at when assessing a tumour?
1. Pressure on local structures: e.g. optic nerves
2. Pressure on the normal pituitary (--> hypopituitary)
3. Functioning tumour (--> Prolactinoma, acromegaly or cushings)
149
What symptoms can pressure on local structures cause?
- Headaches (stretching of the dura)
- Hydrocephalus
- Visual field defects (bitemporal hemianopia)
- Cranial nerve palsies- pressure in the cavernous sinus of III, IV and VI lesions
- Pressure on the hypothalamic centres: obesity, thirst, precocious --> Cerebrospinal fluid rhinorrhoea (downward extension through the pituitary fossa) --> CSF dripping out of the nose
150
What symptoms can pressure on the normal pituitary cause? (underproduction/ hypopituitarism)
• Can cause hypopituitarism
• This has slow onset
• In adult it causes pallor, loss of body hair, central obesity, soft skin – but essentially it relates to what they are deficient in!
• Children won’t grow
• You need to do a different test to test each different axis – this is in the lecture notes
• Sometimes people need bracelets to say they are hypo – they will need cortisol in an emergency!
151
What symptoms can a functioning pituitary tumour cause? (overproduction/ hyperpituitarism)
• If the tumour is derived from the cell type that normally creates the hormone – it can be functioning!
• This comes in three ways normally:
- Prolactinoma
o Most commonly seen is the Prolactinoma microadenoema
- Acromegaly and gigantism (see earlier)
- Cushing’s disease (see earlier)
- VERY RARELY: TSH, LH, FSH secreting
152
What is Hyperprolactinaemia?
• Prolactin release is under tonic inhibition by dopamine from the hypothalamus
• Thus, the factors that increase prolactin e.g. TSH are probably of less relevance
153
What is the Aetiology of Hyperprolactinaemia?
• The most common cause of hyperprolactinaemia is a prolactin secreting pituitary adenoma (prolactinoma)
• PITUITARY STALK DAMAGE - Other tumours may also cause high prolactin by inhibiting dopamine and so reducing its inhibitory effects on prolactin
• Other causes are primary hyperthyroidism (high TSH stimulates prolactin)
• Drugs such as oestrogens, metoclopramide can also cause it
154
What is the epidemiology of hyperprolactinoma?
• Prolactinoma is common in young women
155
What symptoms does Hyperprolactinaemia present with?
• Increased prolactin --> increased milk production in the breast (also galactorrhoea)
• Also causes reduced infertility as prolactin inhibits GnRH
• Decreased libido, erectile dysfunction
• Menstruation stops (amenorrhoea)
156
What are the investigations for Hyperprolactinaemia?
• Serum prolactin level (at least 3 measurements)
• Thyroid function tests
• MRI of the pituitary
157
What is the treatment for Hyperprolactinaemia?
• Dopamine agonist – CABERGOLINE or BROMOCRIPTINE
158
What are the 4 types of non-functioning pituitary tumours?
1) Pituitary adenoma
2) Craniopharyngioma
3) Rathke’s cyst
4) Meningioma
159
What are Pituitary adenomas?
• Pituitary adenomas make up to 10 -15% of all tumours that develop in the skull
• Pituitary adenomas can be functioning or non-functioning
• About 1/3 of pituitary tumours are non-functioning pituitary adenomas
• They normally become large before they are found – but they are slow growing and benign normally
• 50% are incidentalomas
• They’re labelled based on their size: micro and macroadenomas
• Signs of aggressiveness
o Large size
o Cavernous sinus invasion
o Lobular suprasellar margins
160
What are Craniopharyngiomas?
• Arises from squamous epithelial remnants of Rathke’s pouch
• Benign but infiltrates into surroundings
• Peak ages: 5-14 and 50-74
161
What is Rathke’s cyst?
• Derived from Rathke’s pouch – from a single layer of epithelial cells with mucoid, cellular or serous components in the cyst fluid
162
What is a Meningioma?
• This is the commonest tumour of the region after pituitary adenoma
• Complication of radiotherapy
• Associated with visual disturbance and endocrine dysfunction
163
What are the 3 Vital presentation points of a pituitary tumour?
1) Pressure on local structures
2) Optic chiasm - resulting in bitemporal hemianopia
3) Can cause hydrocephalus (CSF leak)
