Acromegaly

What are acromegaly and gigantism?

Acromegaly and gigantism are syndromes caused by an excess of growth hormone in the body.

  • Acromegaly occurs when this excess occurs after puberty (in adulthood)
  • Gigantism is when this excess has occurred in childhood (particularly prior to the fusion of the epiphyseal growth plates)

Here, this will mainly focus on acromegaly, as gigantism is an extremely rare condition.

Epidemiology

  • Estimated prevalence of around 40-90 cases per million population and incidence of 3-4 per million a year (i.e. rare)
  • Most common cause of mortality in these patients is cardiovascular disease
  • Growth hormone (GH) is synthesised by somatotroph cells in the anterior pituitary gland.

Physiology of Growth Hormone

o    GH release is stimulated by Growth Hormone Releasing Hormone (GHRH) and inhibited by somatostatin- both released from the hypothalamus

o    GH synthesis is regulated via a negative feedback loop pathway

  • GH inhibits somatotroph cells
    • Locally generates IGF-1 which inhibits somatotroph cell functions
    • Inhibits GHRH mRNA synthesis and GHRH release at the hypothalamus
    • Stimulates somatostatin mRNA synthesis and release at the hypothalamus.
  • Other feedback mechanisms can feed into this loop
    • e.g. ghrelin (a GI hormone released by the stomach- increases appetite)- which is thought to act in a similar fashion to GHRH to release GH
    • e.g. parasympathetic stimulation can inhibit somatostatin release (and increase GH release) – vice versa with sympathetic activation
    • e.g. glucocorticosteroids (inhibit GH secretion)

o    GH is released in a pulsatile fashion

  • Lowest in the early morning; highest during the night.  Normal (daily) levels <10ng/ml.
  • Growth Hormone circulates round the blood bound to growth hormone binding protein (50% bound) and acts on growth hormone receptors

o    Receptors mainly found in the liver, adipose tissue, heart, kidneys, intestine, lungs, pancreas, cartilage and skeletal muscle.

o    Acts to increase levels of insulin like growth factor (IGF; mainly type I- IGF1) which acts to inhibit apoptosis and stimulate cell growth and proliferations

  • Main mediator of growth during childhood
  • GH is cleared rapidly via kidneys, liver or target tissues (average half-life 10-20 mins)
  • Majority of cases are secondary to somatotroph adenomas (mostly macroadenomas).  Other, extremely rare, causes include GHRH hypothalamic tumours and ectopic production of GH/GHRH from neuroendocrine tumours.
  • Excess GH/IGF-1 has effects on multiple systems: mainly increasing size

Pathophysiology of Acromegaly

o    Cardiovascular system

  • Acromegaly-associated cardiomyopathy: a biventricular concentric hypertrophy
  • ‘hyperkinetic syndrome’- early feature of increased cardiac contractility, high cardiac output and lowered peripheral resistance. Later, fibrosis occurs and both diastolic filling and systolic function is impaired
    • When this is combined with hypertension and/or associated valvular disease, this can cause features of heart failure
  • Patients also can develop Hypertension (common), coronary artery disease and they are at much higher risk of arrhythmias

o    Respiratory System

  • The main respiratory problem that patients present with is sleep apnoea due to swelling/collapse of the pharyngeal walls secondary to GH excess
  • Other problems include growth/thickening of various components of the upper and lower respiratory tracts
    • Upper: e.g. swelling/lengthening of the soft palate; thickening of the true and false vocal folds (deep voice)
    • Lower: e.g. increased lung volume and compliance; small airway narrowing; elongation of ribs/spine kyphosis

o    Musculoskeletal system

  • Arthropathy of both the peripheral and axial skeleton- joint space narrowing (after initial widening), osteophyte formation and other features of osteoarthritis.  Hip and shoulder are common sites.

o    Endocrine/Metabolic systems

  • Diabetes mellitus or impaired glucose tolerance is common in patients with acromegaly.  Hypertriglyceridaemia is also seen.
  • Thought to be due to the effects of IGF-1 on insulin sensitivity.

Clinical Features of Acromegaly

o    Tumour effects: e.g. visual field defects ((bi)temporal hemianopia); cranial nerve palsy; headache

o    May be other features of other pituitary hormone excess/deficiency e.g. galactorrhoea, decreased libido, menstrual abnormalities

o    Musculoskeletal/Skin: Enlargement of the soft tissues, particularly hands and feet; Prognathism (protrusion/prominence of the jawbone); arthralgia/arthritis; carpal tunnel/other nerve entrapment syndromes; proximal myopathy; frontal bone hypertrophy; oily skin; skin tags; facial appearance is said to become ‘more hoarse’

o    Respiratory: Sleep problems (apnoea)- tiredness, snoring etc; deepening voice

o    Cardiovascular: Could present with angina or features of cardiac failure (although this would generally develop quite late); more likely to be picked up as raised BP

o    Visceromegaly: Tongue; thyroid/salivary gland; liver; spleen; kidney; prostate

o    Endocrine: Diabetes mellitus

Investigations

o    Oral glucose tolerance test– the patient is fasted overnight, comes to clinic in the morning and blood test is taken (for fasting glucose and GH).  The patient drinks a glucose solution (75g) and further blood tests are taken at 30 min intervals for 2 hours.

o    Normally, GH levels will fall below baseline levels with the glucose test.  If there is too much GH (acromegaly), this will not occur.

o    Other tests you may want to carry out (depending on the patient) include:

o    Other pituitary hormone tests

  • Insulin stress test for cortisol and GH
  • TRH test for TSH response
  • LHRH test for LH/FSH response

o    MRI brain (CT chest and abdo if this is negative to look for ectopic production sites)

o    Bloods

  • Glucose (you may also want to test fasting glucose for diabetes)

o    Echocardiogram

Management

o    Surgery

o    Indicated for most cases (pituitary micro/macroadenomas).  Trans-sphenoidal approach is commonly used.

  • Reported up to 10% recur (most likely growth of residual tumour) and up to 30% have subsequent hypopituitarism.

o    Radiotherapy

o    Drug-treatment (indicated after surgery if total debulking was not possible/if symptoms remain)

o    Somatostatin receptor ligands e.g. Octreotide and Lanreotide

  • Selective somatostatin receptor SST2/SST5 ligands (expressed mainly by somatotroph cells).
  • Effectiveness is determined by initial levels of GH
  • Shrinkage of tumour occurs in 50% but reverses with cessation of treatment.  More than 80% have a reduction in symptoms.
  • Main side-effects include nausea, vomiting, loose/oily stools, constipation, stomach upset, gas, bloating, dizziness or headaches.

o    GH-receptor antagonists e.g. Pegvisomant

  • Used in patients intolerant to somatostatin analogues without central compressive symptoms and patients with severe diabetes (shown to improve insulin sensitivity)
    • IGF-1 used as a marker of success of treatment
  • Expensive

o    Dopamine Receptor Agonists e.g. Bromocryptine, Cabergoline

  • High doses can potentially induce a reduction of GH levels to baseline
  • Particularly useful where somatostatin analogues have failed; or where there is co-existent hyperprolactinaemia

Monitoring

o    Annual biochemical testing for GH/IGF-1 and annual pituitary MRI if on medical treatment.  If complete resection and resolution of symptoms, then annual monitoring may only be required in the short term.

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Cough

Cough is the one of the most common symptoms presenting to general practice.  It is also the predominant symptom of the common cold.  However, cough is not always a benign symptom, and requires a focused approach to determine the cause and appropriate management.

History

  • Describe the cough: wet/dry, productive, itchy, painful, harsh/barking
  • Duration/onset: acute (<3 weeks); subacute (3-8 weeks); chronic (>8 weeks)
  • Progression: worsening/improving (when were symptoms worst); is the cough worse at certain times of the day; is it present at night
  • Exacerbating/relieving features: anything makes it better/worse e.g. exercise
  • Any associated symptoms:
    • Sore throat
    • Blocked nose
    • Sputum – describe the character/amount etc
    • Shortness of breath
    • Haemoptysis- again, describe appearance/amount etc
    • Wheeze
    • Fever and other constitutional symptoms e.g. fatigue, weight loss, malaise/lethargy, sweats etc
    • Chest pain
  • Ask about past medical history and drug history
    • Asthma and COPD
    • Other airways disease
    • GORD
    • CVS history
    • ACE inhibitors
    • Neuromuscular problems
    • Previous similar episodes
  • Ask about family history/contact history
    • Cough/respiratory tract infection
    • COPD
    • Cancer
    • TB
    • Asthma
  • Ask about social history
    • Smoking
      • + people living with the patient (do they smoke)
    • Occupation (any exposure to chemicals etc)
    • Any travel to ‘exotic’ places?
    • New pets?

Examination (Full Respiratory)

  • General
    • Inspect from the end of the bed: does the patient look well/unwell (do they require ABCDE approach?)?; are there any inhalers?; is the patient on oxygen?; sputum pots? etc
    • Inspect the patient’s hand for clubbing (Lung Ca; bronchiectasis); any nicotine staining; cyanosis; delayed capillary refill; CO2 flap/asterixis (both hands go down at same time cf liver flap)
    • Check the radial pulse
    • Inspect the face for cushingoid features (moon face); signs of anaemia/central cyanosis;
  • Neck
    • Palpate for any lymphadenopathy
    • Inspect the JVP
      • Ask the patient to relax their head/neck and turn it slightly to the left/right by about 30-45°
      • Observe the pulsation of the JVP.
        • If the JVP is not seen or is very faint, deeply push the upper right quadrant up under the ribcage- this may help to see the JVP (hepatojugular reflex)
      • The JVP is measured, in cm, as the vertical height (NOT direct distance) from the sternal angle
    • Palpate above the sternal notch with your middle three fingers to check the trachea is central
      • Trachea deviates away in pneumothorax/effusion and towards collapse/consolidation
  • Chest
    • Inspect for any abnormalities e.g. scars, pigeon chest, barrel chest (COPD),
    • Check respiratory rate
    • Check for chest expansion by placing your hands around the chest with thumbs in the midline.  Ask the patient to take a deep breath (symmetrical reduction in COPD; asymmetrical in effusion/empyema/consolidation/collapse)
    • Percuss the zones of the lungs (front and back), comparing sides as you go (dullness indicates consolidation/fluid/)
    • Auscultate breath sounds in each of the lung zones
    • Perform tactile vocal fremitus and whispering pectoriloquy (see here)

Differential Diagnosis

  • Acute
    • Common cold/URTI
    • Acute Bronchitis
    • Asthma
    • Exacerbation of COPD or chronic bronchitis
    • Influenza
    • Pneumonia
    • Acute bacterial sinusitis
    • Pertussis
    • Allergic rhinitis
    • PE (rarer)
    • Pneumothorax (rare cause of cough)
    • Cancer
    • ACE inhibitor use
  • Chronic
    • COPD
    • Bronchiectasis
    • Chronic bronchitis
    • Chronic postnasal drip
    • Smokers cough
    • Interstitial lung disease (rarer)
    • GORD
    • Occupational exposure
    • Post-infectious cough
    • ACE inhibitor use
  • Other less common causes include cardiovascular causes e.g. heart failure; infection e.g. TB; neoplasia e.g. bronchial carcinoma; aspiration of foreign body; restrictive lung disease e.g. pulmonary fibrosis

Investigations

  • If the patient has abnormal chest signs on examination, a CXR may be warranted.  Other imaging e.g. CT scans, is not often used for investigation of cough in isolation but may be requested if other investigations, symptoms and signs are abnormal
  • If asthma/COPD is suspected, pulmonary function tests (/peak flow) may be useful in assessing the severity
  • A FBC and CRP may be helpful in diagnosing an infective cause; similarly throat swabs/sputum cultures

Management

  • With chronic cough, a ‘test of treatment’ approach to a diagnosis may be helpful, particularly in general practice (provided there are no red flags e.g. copious sputum, fever, sweats, weight loss, haemoptysis, considerable SOB)
    1. Remember to try lifestyle measures first e.g. stopping smoking
    2. Try stopping ACE inhibitors where appropriate
    3. At this stage further investigations e.g. CXR, spirometry/peak flow etc can be useful to exclude need for specialist referral
    4. Depending on the history, trial of asthma treatment, PPIs or antihistamines/nasal steroid (asthma, reflux/GORD, postnasal drip- respectively)

Chest Pain

NB If the patient is acutely unwell with chest pain, treat with ABCDE and/or as an acute coronary syndrome i.e. MONA(C) (morphine; oxygen; nitrates; aspirin +/- clopidogrel).  In a hospital situation, where the history is not so clear cut, you might be able to hold off empiric treatment until investigation results have come back.

History

  • SOCRATES

    • Site (central, diffuse, localised: can the patient point to it)
      • anterior or back
    • onset (sudden/acute; subacute; gradual; with exertion/at rest)
    • character (crushing, heavy, sharp, dull, stabbing, pleuritic)
      • pressure (angina, MI, oesophageal spasm)
      • tearing (aortic dissection)
      • sharp/stabbing (pericarditis, PE, musculoskeletal, pneumothorax)
      • pleuritic (PE, pneumothorax, pneumonia, musculoskeletal, pericarditis, drug causes)
    • radiation (left shoulder/arm, jaw, back)
    • associated symptoms
      • breathlessness
      • cough, sputum, haemoptysis
      • sweating
      • palpitations
      • dizziness, syncope
      • anxiety
      • nausea/vomiting
      • systemic symptoms: fever, chills, sweats, weight loss, fatigue
    • Timing (Has it got better/worse?  Intermittent/constant?)
      • Any previous episodes?
    • Exacerbating/Alleviating factors (e.g. GTN spray, inhalers, position, painkillers, gaviscon etc)
    • Severity
  • You also want to ask about
    • Past medical history
      • Cardiovascular disease- angina, hypertension, peripheral vascular disease
        • Ask about leg pain and differentiate between claudication and DVT (pain on exertion, which is deep, burning, stabbing vs hot, red, swollen, tender, more superficial)
        • how well controlled; any previous admissions/treatments
      • Any lung disease- COPD, asthma
        • again, how well controlled is this
      • Any diabetes
      • Any hypercholesterolaemia
      • Any heartburn
      • Any rheumatoid arthritis or connective tissue disease
      • Ask what drugs the patient is taking/has taken recently
        • Any drug allergies (particularly aspirin)
      • Any allergies
    • Family History
      • In particular, that of heart disease
    • Social history
      • Smoking- quantify
      • Alcohol- quantify
      • Illicit drugs
      • Occupation
      • Home situation
      • If relevant, ask about travel history.
  • Remember ICE

Examination

  • Does the patient look unwell? (Do they require immediate attention and life support?)

General

  • Any end of the bed signs?
    • Is the patient hunched over clutching their chest?  Are there multiple inhalers around the patient?  Does the patient look well/unwell?  Is there anything that stands out?
  • Examine the patients hands
    • Any nail bed/splinter haemorrhages?  Any nicotine stains? Any peripheral cyanosis?  Any Reynaud’s?
    • Check capillary refill by compressing the distal phalanx for 5 secs, releasing and observing a return to normal colour (normal <2 secs)
    • Any pallor of the palmar creases (anaemia)
    • Any Osler’s nodes (painful swellings on the fingertips- infective endocarditis)
    • Any arthritic changes
  • Feel the radial pulse- comment on rate, rhythm, character, strength/volume
    • You might also, at this point, want to check for a radial-radial delay (coarctation of the aorta) and/or a collapsing pulse (aortic regurgitation)
      • Check if the patient has any joint pain; With your dominant hand, feel the radial pulse; with your non-dominant hand on the patient’s elbow, raise the patient’s arm up above the level of the heart; feel for a change of character in the pulse
        • Normally will remain similar
        • A collapsing pulse is one which ‘collapses’ under your fingers (might not completely disappear)
  • Take blood pressure
    • Ideally both sitting and standing and on both arms (difference can be suggestive of aortic dissection/coarctation)
  • Look at the face
    • Any xanthomata (yellowish deposits of lipid around the eyes- hyperlipidaemia) or corneal arcus (ring of lipid around the cornea)
    • Any conjunctival pallor
    • Any malar rash
    • Ask the patient to stick out their tongue and point it upwards
      • Any tongue changes e.g. beefy tongue
      • Any central cyanosis
  • Look at the neck
    • Look at the JVP
      • Ask the patient to relax their head/neck and turn it slightly to the left/right by about 30-45°
      • Observe the pulsation of the JVP.
        • If the JVP is not seen or is very faint, deeply push the upper right quadrant up under the ribcage- this may help to see the JVP (hepatojugular reflex)
      • The JVP is measured, in cm, as the vertical height (NOT direct distance) from the sternal angle
    • You may want to feel the carotid pulse and note characteristics
    • You could auscultate in the neck for bruits now or after auscultation of the chest
  • For full examination of the chest- see here
    • NB In an OSCE, you may only be asked to examine the cardiovascular features i.e. Inspection, palpation of the apex beat/heaves/thrills, auscultation of the heart.
      • You might say that you would also like to auscultate the lungs (particularly the bases)
  • You may also want to examine the peripheral vascular system:
    • Completely expose and look at both legs, comparing left and right for:
      • swelling
      • colour
      • scars
      • dressings
      • pallor
      • loss of hair/nails/toes (or indeed limb)
      • ulcers
      • varicosities
      • venous eczema
      • oedema
      • haemosiderin deposits
      • lipodermatosclerosis – brown/red thickened skin caused by fibrosis of subcutaneous fat
      • “inverted champagne bottle” of the legs – chronic venous insufficiency leading to fibrosis
    • Make sure to inspect the soles of the feet, in between the toes and the toenails for any signs
    • Feel and compare the temperature of both legs
    • Test capillary refill of the big toe
    • Palpate for arterial pulses
      • Dorsalis pedis- dorsum of the foot lateral to the extensor tendon of the great toe
      • Posterior tibial- posterior to the medial malleolus of the tibia
      • Popliteal- taking the weight of the patient’s knee joint at about 45 degrees, feel deep in the popliteal fossa
      • Femoral- midinguinal point, below the inguinal ligament
    • You may also want to palpate any varicosities.  If they are tender, this may be a sign of phlebitis
    • Berger’s test
      • Lift the leg up 45° for 30-60 secs and see if they go pale.  If they do, then drop the leg over the side of the bed
        • If the leg goes a deep red/purple- this is positive test.
          • Reflex hyperaemia- dilation of the peripheral vessels in response to a drop in BP
    • You may also want to test sensation of the lower limb
      • 2 methods- microfilament testing (usually used for diabetic screening) or neurological examination techniques e.g. pin tip/cotton wool (+/- test of vibration and joint position)
        • microfilament testing is probably more appropriate for the glove/stocking loss of sensation seen in diabetes and vascular disease
    • Mention that you would also want to measure the Ankle-Brachial pressure Index (ABPI)
      • Using the sphygmomanometer and a doppler probe (to check for a pulse), you can measure the BP of the lower limb
      • BPleg/BParm = ABPI
        • If <0.9 (+ symptoms of claudication/PAD) or <0.8 (without) suggest arterial disease/obstruction
        • If >1.3, suggests calcification of the arteries/hardening of the arteries
  • Finally, you may also want to examine the abdomen for any pulsatile masses

Investigations

  • ECG
    • +/- Excercise tolerance testing (if intermittent chest pain on exertion)
  • CXR
  • You may want to send the patient to the cath lab for percutaneous coronary intervention (PCI)
    • This may reveal and treat coronary artery blockages
  • Blood tests
    • Troponin (muscle enzymes that are released after muscle infarction)
      • Troponin T (I think) is what is used in Tayside (Troponin I may also be used elsewhere)- normally <40ng/l
      • Troponin levels tend to peak at around 12 hours.  Therefore a level is usually taken ASAP and at 6 hours.  If there is a rise (usually more than double), then this is usually considered a positive test,
    • FBC/U&E (particularly K+)
  • Echocardiogram (particularly if a murmur is heard)
  • CTPA may be used if PE is suspected, as might D-dimers

Differential Diagnosis

  • Cardiac:
    • Ischaemic: stable angina, acute coronary syndrome (ACS), coronary vasospasm (Prinzmetal’s angina), hypertrophic cardiomyopathy, aortic stenosis.
    • Non-ischaemic: arrhythmias, aortic dissection, mitral valve disease,pericarditis.
  • Respiratory: pneumothorax, pulmonary embolism, pneumonia, pleurisy, lung cancer.
  • Musculoskeletal: costochondritis, Tietze’s syndrome, trauma, rib pain (including fracture,bone metastases, osteoporosis), radicular pain, nonspecific musculoskeletal pain (egfibromyalgia).
  • Breast disease.
  • Gastrointestinal: gastro-oesophageal reflux disease (GORD), oesophageal rupture,oesophageal spasm, peptic ulcer disease, cholecystitis, pancreatitis, gastritis.
  • Skin: herpes zoster infection.
  • Psychological, eg anxiety, depression, panic disorder.
  • Others: sickle cell crisis, diabetic mononeuritis, tabes dorsalis

EMERGENCY MANAGEMENT OF CHEST PAIN

  • Manage the patient initially with ABCDE approach
  • Manage appropriately depending on the suspected cause
    • For a tension pneumothorax- decompress ASAP by sticking a needle/venflon into the 2nd intercostal space midclavicular line on the affected side
      • Consider insertion of a chest drain once in hospital/stable
    • For suspected ACS- administer MONA
      • Morphine 2-4mg IV or 5mg IM
      • Oxygen (15l high flow)
      • Nitrates (0.4mg sublingual (crush or spray); 5 microgram/minute IV (increase up to usually ~200 micrograms/min)
      • Aspirin 300mg
    • For acute PE
      • Oxygen and calculate Well’s score
        • CTPA or V/Q scan
          • Massive PE- alteplase 10mg stat and 90mg infusion over 120mins (unless contraindicated)
          • Non-massive- start rivaroxiban 15mg BD for 3 weeks then 20mg BD (OR, if contraindicated, start warfarin/LMWH)

Abdominal Distension

Abdominal distension can be due to a huge number of conditions.  A detailed history and examination is crucial to formulating even an accurate differential diagnosis.

History

  • Ask the patient to define/describe the symptom:
    • Is it a mass/swelling?  Is it generalised/localised (if so, where?)? Is it a sensation (bloatedness) e.g. gassiness, satiety, pain?  Is it a physical enlargement (do their clothes feel tight?)?
      • How long has it been there? Onset, duration, progression, timings etc?
        • Is it associated with eating (if so, any particular foods)?
    • What associated symptoms are there?
      • Abdominal Pain
        • Is this associated with eating and/or defaecation?
      • Flatus
      • Nausea/vomiting
      • Malaise/Lethargy
      • Weight loss/Weight gain
      • Change in Bowel Habit
        • Including any blood?
      • Jaundice
      • Any trauma/bruising?
      • Amenorrhoea/Menorrhagia
      • Lower Urinary Tract Symptoms
    • Take a detailed medical history and drug history; family history; social history and travel history
      • Remember to ask in particular about alcohol consumption; IV drug use; FHx of breast/ovarian cancer (or any cancer)

Examination

(see abdominal examination)

Investigations

  • Pregnancy test (where appropriate)
  • FBC to check for
    • WCC ?infection
    • Hb ?anaemia of chronic disease/malignancy
  • U&Es
    • Renal function: hypokalaemia/uraemia may cause non-mechanical bowel obstruction
  • LFTs
    • Any liver dysfunction may be a cause of ascites
    • Other abnormalities e.g. suggestive of cholestasis, may be a feature of malignancy
  • Abdominal imaging (X-ray, USS +/- CT)
  • Colonoscopy/sigmoidoscopy +/- endoscopy may be appropriate to rule out a primary GI malignancy

Differential Diagnosis

The five F’s account for the majority of causes:

  • Fat
  • Flatus
  • Fluid
  • Faeces
  • Foetus

I.e.

  • Obesity
  • Pregnancy
  • Gas
    • Can (not uncommonly) be due to Irritable bowel syndrome
  • Ascites
    • Liver cirrhosis
    • Peritoneal carcinomatosis
    • Nephrotic syndrome (i.e. renal cause)
    • Others including peritoneal TB, pancreatitis, ovarian hyperstimulation syndrome
  • Constipation
  • Fibroids
  • Enlarged bladder

Generalised- Non-obstructive causes

  • Obesity
    • Ask about lifestyle
  • Pregnancy
    • Ask about menstrual/sexual history
  • Irritable bowel syndrome
    • Ask about symptoms of bloating, distension and if they change with bowel movements/eating
  • Ascites
    • Ask about alcohol, history of malignancy (inc FHx); heart problems; kidney problems; oedema in the legs/any SOB; any abdominal pain; jaundice
  • Lymphadenopathy
  • Intra-abdominal bleeding e.g. ruptured abdominal aortic aneurysm
    • Ask about pain e.g. sudden onset

Obstructive causes (ask about pain, vomiting, passing wind)

  • neoplasms
    • Ask about change in bowel habit?  Any weight loss, night sweats?
  • Adhesions
    • Ask about previous surgery.
  • Infections (diverticular disease, intra-abdominal abscess
    • Pain, fever, nausea
  • Foreign bodies (including a bezoar)
  • Miscellaneous
    • adhesions, endometriosis, pregnancy, strangulated herniavolvulus,intussusceptiongallstones, faecalith/meconium ileus, haematoma, pneumatosis intestinalis (pneumatosis coli), superior mesenteric artery syndrome, annular pancreas, Hirschsprung’s disease, stenosis (radiation, surgical anastomosis site, Crohn’s disease, tuberculous).

Nonmechanical bowel obstruction

  • Vascular insufficiency: thrombosis, embolism.
  • Retroperitoneal irritation: renal colic, neoplasm, infection.
  • Extra-abdominal infection: sepsis, pneumonia, empyema, spinal osteomyelitis.
  • Metabolic/toxic: hypokalaemia, uraemia, lead poisoning.
  • Chemical irritation: perforated peptic ulcerpancreatitis, biliary peritonitis.
  • Miscellaneous: excessive intraluminal gas, intra-abdominal infection, trauma, mechanical ventilation, other causes of peritoneal inflammation, severe pain and non-steroidal anti-inflammatory drugs (NSAIDs).

Menorrhagia

Menorrhagia, or heavy menstrual bleeding, is excessive menstrual blood loss over several consecutive cycles which interferes with a woman’s physical, emotional, social and material quality of life.

The amount of blood constituting menorrhagia varies between patients, but the upper limit ranges from 60-80mls (certainly <10% of women have menses >80mls).  Severe menorrhagia (>120ml) is more likely to cause anaemia.  Another alternative definition is menses lasting >7 days / 28 day cycle.

History

  • Name, DOB, Age, Introduction etc
    • You may want to ask about parity (number of pregnancies) now or later
  • After identifying the presenting complaint, begin by taking a menstrual history
    • Age of menarche
    • Cycle pattern: duration of bleeding, duration between bleeding
    • What has changed?- Have periods always been heavy?
    • Ask whether she uses tampons/towels? How often does she change them?  Does she need to change at night? Any flooding?
    • Any clots?
    • Does it prevent her from doing any activities?
  • Ask about any other bleeding- intermenstrual, or postcoital bleeding?
    • NB Intermenstrual bleeding is not normal and warrants referral for further investigation
  • Ask about any other symptoms
    • Pain (and describe- e.g. crampy, sharp etc)
    • Dyspareunia
    • Discharge
    • Fatigue, breathlessness
    • Weight loss
    • Heat intolerance or cold, skin/hair changes, constipation
    • Any urinary symptoms
  • Ask about contraception and family planning
  • Ask about smear history
  • Ask about any past medical history
    • Gynae problems; Thyroid disease; blood disorders
      • including easy bruising/bleeding (e.g. gums)
    • Also ask about drug history
  • Ask about Family History
    • In particularly any breast or gynaecological cancer, endometriosis
  • Ask about social history- smoking, alcohol, drugs, sexual history

Examination

  • As part of a general examination, look for
    • obesity
    • any signs of anaemia (e.g. pallor)
    • any signs of thyroid disease (any dry skin, hair loss, limb swelling or weakness)
    • any bruising or rashes
    • any acne or hirsutism
  • Examine the abdomen (particularly lower abdomen/pelvis) for any masses and/or tenderness.
    • Also look for any organomegaly
  • A pelvic examination should also be done:

  • Before starting, explain the process, offer a chaperone and gain consent from the patient.
    • Ask the patient to undress from the waste down (offer an enclosed/private space).  If there are leg supports, ask the patient if they could use these; if not- positions the patient so that their feet are together and knees bent down to the side.
      • Offer a sheet to cover the patient.
  • Inspect the external genitalia
    • Any lesions, excoriations, lichenification, whitening, discharge
  • Before using the speculum, make sure to lubricate it with some lubricant
    • Using you non-dominant hand, part the labia to visualise the introitus, insert the speculum at almost vertical, then rotate it horizontally, such that the handle is anteriorly
    • Gently open the speculum and direct it slightly downwards (30-45°) to visualise the cervix
      • Comment on appearance, any erosions (ectropion), any warty lesions etc.
      • Take any smear and/or swabs that may be required
        • Smears should ideally be done mid-cycle (day 14)
        • Remember to rotate the brush clockwise 5 times and push the brush into the pot 10 times
    • Take care when removing the speculum: don’t actively close the speculum but retract it slowly, letting it close itself.
  • For bimanual examination, again use lubrication and a gloved hand
    • Use you non-dominant hand to palpate the abdomen and your dominant hand for internal examination (NB or vice versa depending on what side of the patient you are on)
    • If it is not uncomfortable, use two fingers
      • Palpate the vaginal wall for any abnormalities; if possible, palpate the cervic for any abnormalities also (note specifically any cervical excitation (tenderness))
      • Assess the position, size, mobility, consistency and any tenderness of the uterus by attempting to capture the uterus between your internal hand (pushing up) and external hand on the abdomen (pushing down)
        • NB In a retroverted uterus this is often not possible
      • Palpate the adnexae (tubes/ovaries) in a similar fashion, with your internal fingers in the lateral fornices (right and left, respectively)
        • You should be able to feel the ovaries ‘slip’ between your fingers; normal fallopian tubes should not be palpable.  This can be very difficult in obese women
  • Consider a rectal examination also
  • Thank the patient and let the patient redress in a ‘private’ space

 


 

Investigations

  • Complete Blood Count- check for anaemia and/or bleeding disorders (primary or secondary to liver/other cause)
  • Cervical smear- screen for cervical (and endometrial) cancer
  • Swab for Chlamydia (if suggestive)
  • TFTs (NB only if patient has other symptoms of thyroid dysfunction), LFT, U&E, Coag screen (other systemic causes)
  • Transvaginal USS of the uterus
    • Endometrial thickness
    • Presence of intrauterine disease e.g. fibroids/cancer
  • Endometrial sampling (NB not necessary for initial investigation but is if failed medical management or suspicious history), particularly in patients >45 or patients <45 with a family/personal history of concerning features e.g. intermenstrual bleeding
    • Pipelle biopsies (NB if woman is of reproductive age- a pregnancy test should be done before biopsy to exclude pregnancy; also contraindicated in severe pelvic inflammatory disease and bleeding disorders)
    • Hysteroscopy- most effective but also most invasive, ideally should be performed after a pipelle biopsy has been done and results received
    • Dilation and Curettage

Causes

  • NB In around half (40-60%) of patients, no underlying cause will be found:
    • Dysfunctional Uterine Bleeding
  • Local disorders include:
    • Fibroids
    • Adenomyosis
    • Endocervical or endometrial polyps
    • Cervical eversion
    • Endometrial hyperplasia
    • IUCD
    • Pelvic inflammatory disease
    • Endometriosis
    • Uterine/cervical malignancy
    • Hormone producing tumours
    • Trauma
    • Other e.g. AV malformations

    Systemic causes include

    • Endocrine causes
      • Hyper-/hypothyroid (ask about weight, malaise)
      • Diabetes mellitus
      • Adrenal Disease
      • Prolactin disorders
    • Bleeding disorders (consider in primary menorrhagia / FHx / Signs e.g. bruising)
      • von Willebrand’s disease
      • ITP (Idiopathic thrombocytopaenic purpura)
      • Factor Deficiency
    • Liver or renal disease
    • Anticoagulant therapy

Management

  • Correct any iron deficient anaemia
  • Treat any systemic disorders
  • Medical management
    • Mirena coil is preferred first line treatment- provided long-term contraception and an intra-uterine device is acceptable for the patient
    • Tranexamic acid (antifibrinolytic), NSAIDs (preferably mefenamic acid, naproxen or ibuprofen), or the COC pill can be used second line
      • NSAIDs particularly useful if menorrhagia is accompanied by abdominal pain
    • Oral norethisterone/long-acting progestogens (e.g. depot injection) can be used third line (providing contraception is acceptable)
      • Can be used first line for patients who require rapid cessation of heavy bleeding
    • Combination therapy can be used at any stage if initial treatment fails e.g. Tranexamic acid + NSAIDs
  • Refer patients if there are ‘red-flag’ symptoms e.g. intermenstrual bleeding, abdominal mass, findings of cervical/vulval cancer (suspected); if bleeding persists despite trials of medical treatment; if there is significant anaemia; or if the woman would prefer surgical treatment (e.g. endometrial ablation/hysterectomy) over medical management

Haemoptysis

Coughing up blood originating from the respiratory tract below the level of the larynx.

History

NB Make sure to differentiate between

  • true haemoptysis,
  • pseudohaemoptysis (coughing up blood not coming from below the larynx e.g. bleeding from gums/nose etc that has been partially aspirated and coughed up)
  • haematemesis (vomiting up blood from the GI tract)

In the history:

  • Ask about the onset, progression and timing
    • Did it come on at rest or exertion, sudden vs gradual, decreasing or increasing with time etc
  • Was it fresh red blood, dark blood, frothy, pink, stained sputum etc?  How much blood?
    • NB it can often be difficult to quantify the amount of blood but it is important to try.  Massive Haemoptysis is defined as haemoptysis significant enough to cause asphyxia (i.e. impairs oxygenation of the blood) i.e. NOT by volume of blood
      • the volume of haemoptysis that is classed as ‘massive’ varies from person to person
        • ranges from 100-600ml/24 hours, but in general, anything greater than 250ml/24 hours should be admitted and closely monitored with an ABCDE approach
  • Were there any associated symptoms?
    • Acute cough, sputum and a temperature/fever is suggestive of infection
    • Chronic cough +/- sputum (with underlying lung disease) could indicate chronic bronchitis or bronchiectasis
    • Pleuritic chest pain and shortness of breath could indicate pulmonary embolism
      • Ask also about leg pain
    • Night sweats, fatigue, weight loss +/- changing cough could be signs of cancer
      • +fever could be tuberculosis
    • Bleeding elsewhere?
      • Haematuria may suggest reno-pulmonary disease syndromes e.g. Goodpastures disease/Wegeners granulomatosis
      • Bruising/petechial rash may suggest other bleeding problems
    • Any breathlessness- in particular when lying down (orthopnoea) or being woken from sleep (paroxysmal nocturnal dyspnoea)- both suggestive of congestive heart failure
      • Frothy pink sputum is a classic picture in CHF also (pulmonary oedema)
  • Ask about past medical history?
    • COPD and asthma
    • TB
    • DVT/PE
    • Heart disease/ MIs
  • Ask about drugs
    • Warfarin
    • Clopidogrel
      • Take a full PMHx and RHx
  • Ask about Family History
    • TB/ pneumonia/ URTI/ LRTI
    • Cancer
    • Other
  • Ask about travel history
    • Long-haul flights
    • Exposure to protozoal infections or other tropical diseases
  • Ask about smoking history and alcohol history.
  • Ask about occupational history/exposure

On Examination

Do a full general and cardio-respiratory examination

  • General
    • Look from the end of the bed- is the patient well/unwell? (And do they require an ABCDE approach)
      •  Does the patient appear cachexic
        • Also look for any inhalers, sputum pots, blood-stained tissues etc
    • Look at the hands for clubbing (cancer/bronchiectasis)
      • Look for other signs, e.g. nicotine,
    • Feel the radial pulse and comment on rate; rhythm; strength/volume; character
    • Take a blood pressure
    • Look for any abnormal pigmentation of the skin
    • Look at the face for any pallor/cyanosis
      • Look in the mouth for any signs of gum/dental disease
      • Look at the eyes for any signs of Horners syndrome
    • Do a full neck examination for lymphadenopathy
      • Also look at the JVP and feel for a central trachea
  • Chest
    • Inspect
      • Check resp rate and nature of breathing
      • Look for chest expansion (symmetrical)
      • Any scars, chest abnormalities (e.g. pigeon chest/barrel chest)
    • Palpate
      • Chest expansion
        • Ask the patient to breathe out and place your hands around the ribcage such that your thumbs are just touching in the midline (this should be done quite firmly to ensure movement with chest expansion).  Ask the patient to breathe in deeply and check that the thumbs move apart.
      • Apex beat
        • Using the palmar aspect of your fingers, palpate roughly over the 4th-8th ribs in the mid-axillary line and move medially until you can palpate the most lateral point of the apex beat (normally 5th IC space, mid-clavicular line).  Use two fingertips to localise the apex beat.
      • Heaves/thrills
        • Feel with the hand over the left sternal edge (vertically) and across the sternum over rib 2-3 for any vibrations of heaves/thrills
    • Percuss
      • Comparing sides, percuss down the chest over lungs zones on the front and back
        • NB it may be easier to wait to percuss/auscultate the back until after examination of the front has been done
    • Tactile vocal fremitus
      • Place the medial aspect of your hand over the 2nd, 4th and 6th intercostal spaces, comparing sides.  Each time, ask the patient to speak (usually the word “ninety-nine”, but others are fine)
        • Vocal fremitus (vocal vibrations felt) is usually very fine or absent.  It can be increased over areas of consolidation and decreased over areas of effusion/collapse
    • Auscultate the heart over the 4 valve anatomical areas and over Erb’s point with both the bell and the diaphragm
        • Aortic- Right 2nd IC space, parasternally (near the ascending aorta)
        • Pulmonary- Left 2nd IC space, parasternally (nearest the infundibulum)
        • Erb’s point- Left 3/4th IC space, parasternally (point where S2 is best heard)
        • Tricuspid- Left 5th IC space, parasternally
        • Mitral- Left 5th IC space, mid-clavicularly (or apex beat)
      • Special positions for auscultation of diastolic murmurs
        • To listen for mitral stenosis
          • Listening with the bell in the mitral area, ask the patient to turn onto their left side (about 45-60°)
        • To listen for pulmonary insufficiency (and aortic regurgitation)
          • Listening with the diaphragm in the pulmonary and aortic areas, ask the patient to sit forward, take a deep breath in and breathe all the way out, hold it there (you listen), and breathe in again.
    • Auscultate over the front and back lung zones, comparing sides.
      • Normal breath sounds (vesicular breathing) are quiet and gentle.
        • Note if breath sounds are normal volume or quiet (reduced air entry)
      • Bronchial breathing is harsher, often higher pitched and poor/tubular in quality, often with gaps between the inspiratory and expiratory phase.
        • Suggests consolidation or fibrosis.
      • Note any crackles or fine crepitations, any wheeze (‘musical expiratory sounds’, any pleural rub (‘creaking sound’); any stridor (harsh inspiratory sound)

To listen to some examples, see here (for lung sounds) and here (for heart sounds)

    • Vocal resonance/Whispering pectoriloquy
      • Ask the patient to whisper (usually “ninety-nine” again) and simultaneously listen to the lung zones
      • Normally the voice is muffled through lung.  In areas of consolidation, the voice will become louder/clearer

Investigations

  • CXR- possibly the most useful to confirm the clinical diagnosis suspected from the history and examination
    • Other imaging investigations e.g. CT (non contrast, contrast +/- CT pulmonary angiogram) may be requested if appropriate
  • FBC should be checked for anaemia, WCC.  Other tests, e.g. CRP, U&Es, LFTs/Coagulation may also be appropriate
  • ECG +/- Echocardiogram may be useful, particularly if there is a suspected cardiac cause of haemoptysis
  • Bronchoscopy is often useful in evaluating the site of bleeding (+ biopsies of suspicious lesions may be taken)

Differential Diagnosis

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  • Trachea or bronchus:
    • Malignancy
      • Bronchogenic carcinoma
      • Endobronchial metastatic tumour
      • Kaposi’s sarcoma
      • Carcinoid tumour
    • Bronchitis
    • Bronchiectasis
    • Broncholithiasis
    • Airway trauma
    • Foreign body
  • Lung parenchyma:
    • Lung abscess
    • Pneumonia – bacterial (egStaphylococcus aureusPseudomonas aeruginosa) or viral (eg influenza)
    • Tuberculosis (TB)
    • Fungal infection and mycetoma
    • Hydatid cysts
    • Goodpasture’s syndrome
    • Pulmonary haemosiderosis
    • Wegener’s granulomatosis
    • Lupus pneumonitis
    • Lung contusion
    • “Crack” lung
  • Vascular:
    • Arteriovenous malformation
    • Aortic aneurysm
    • Pulmonary embolism (PE)
    • Mitral stenosis
    • Other cause of pulmonary venous hypertension, eg left ventricular failure (LVF)
    • Trauma
    • Iatrogenic (eg chest drain malposition, secondary to pulmonary artery catheter manipulation)
  • Other:
    • Pulmonary endometriosis
    • Congenital or acquired systemic coagulopathy, eg leukaemia
    • Anticoagulant or thrombolytic agents
    • Factitious haemoptysis

Amenorrhoea

Absence of menstrual bleeding.

Primary amenorrhoea refers to never having menstrual period i.e. absence of the menarche.  By age 16 in a girl with normal secondary sexual characteristics e.g. breast development, pubic hair etc (age 14 if these are absent), if the menses have not occurred, this can be considered primary amenorrhoea.

Secondary amenorrhoea refers to the absence of menstrual bleeding for 6 months (12 if prior oligomenorrhagia) having previously had a regular menstrual cycle.

NB Oligomenorrhoea is defined by NICE as menses occurring less frequently than every 35 days.  Most causes of amenorrhoea are also causes of oligomenorrhoea.

IMPORTANT: In women of reproductive age, the most common cause of amenorrhoea is PREGNANCY.  All women in this category should be investigated for pregnancy to include/exclude this diagnosis prior to (or at the same time as) further investigation.

History

  • As always, ask name and date of birth, and parity
  • Ask about how long? (in general, investigations/treatments are done if there has been no bleeding for more than 3 months
    • If there has been any bleeding, describe this (e.g. regular/irregular, light (spotting)/heavy (flooding))
    • Try and establish how the menses have changed i.e. what was normal
      • how many days between, how many days bleeding, how light/heavy, how regular etc
    • Also ask specifically about:
      • age of menarche
      • contraceptive use
        • If the patient is using contraception (in particular, hormonal contraception), where appropriate, ask how they are using it
        • Ask about the possibility of pregnancy
  • Ask about associated symptoms/causes
    • Symptoms of the menopause
      • Hot flushes, headaches, vaginal dryness, loss of libido, sleeping problems, change in mood
      • NB menopause would be the most common cause of secondary amenorrhagia in patients >50.  In patients <40 with these symptoms, premature ovarian failure may be the cause
    • Symptoms of pregnancy
      • Nausea, change in appetite, breast tenderness
    • Ask about weight loss/exercise
      • Anorexia and excess exercise can be a cause of amenorrhoea (hypothalamic)
        • patients will either usually have a BMI of <17 or exercise >4 hours/day
        • usually underlying psychiatric condition (e.g. anorexia nervosa or body dysmorphic disorder etc)
    • Symptoms of PCOS
      • Excessive (male-pattern) hair growth, weight gain, hair loss/thinning (male pattern), acne/oily skin
    • Thyroid symptoms
      • Heat intolerance, tremor, weight loss, goitre, irritability, fatigue
      • Weight gain, lethargy,
    • Any other symptoms?
      • Visual disturbance, galactorrhoea
      • Change in libido
      • Any infertility issues?
      • Stress/depression
  • Ask about PMHx
    • Any previous episodes of amenorrhoea?
    • Cervical screening up to date?
      • Any abnormalities +/- treatments?
        • D&C can rarely cause Asherman’s syndrome
    • Any other gynaecological history?
    • Any infertility problems?
    • Drugs
      • Particularly antiemetics and antipsychotics (containing phenothiazines/metcoclopramide) which can raise prolactin
      • Steroids
      • Chemotherapy/radiotherapy (the latter can be to the pelvis or to the brain)
    • Other PMHx/RHx
      • e.g. epilepsy and anti-epileptic drugs; diabetes
  • Ask about Family history
    • Premature menopause
    • PCOS
    • Other
    • In primary amenorrhoea, another diagnosis of Turner’s syndrome
  • Ask about social history
    • Diet, exercise, smoking, alcohol, occupation etc
    • Illicit drug use
    • In primary amenorrhoea, ask about progress at school, childhood development and milestones etc
  • If appropriate, ask about sexual history

Examination

  • Take height/weight (calculate BMI)
  • Look at the hands for any signs of
    • thyroid disease- acropachy, palmar erythema, tremor
  • Look at the skin for any
    • acanthosis nigricans (of PCOS or adrenal insufficiency)
    • hirsutism
    • thin skin and striae, easy bruising (Cushings syndrome)
  • Look for any dysmorphic features of Turners
    • Short stature, web neck, low-set ears, pubertal delay (delayed breast development; NB Turner’s normally has normal pubic hair development), short 4th metacarpal, high-arched palat, cubitus valgus)
  • Examine the neck for any thyroid abnormalities
  • Examine the visual fields

Investigations

  •  Pregnancy test
  • Serum LH and FSH
    • High levels of both on more than one occasion suggests premature ovarian failure/menopause
    • Normal/low levels suggest hypothalamic cause
    • Normal FSH and increased LH may suggest PCOS
  • Prolactin
    • May be abnormally high (>1000mIU/l) in prolactinoma tumours
    • Other causes of raised prolactin include
      • Stress
      • Drugs (e.g. antipsychotics, antidepressants, antihypertensives, antihistamines, metachlopramide)
      • PCOS
  • TFTs (TSH, free T4)
  • Total testosterone and sex-hormone binding globulin
    • And calculate free androgen index
      • Total testosterone / total sex-hormone binding globulin
      • Can be raised in PCOS
  • Other tests can be done
    • Oestrodiol
      • May help to differentiate between ovarian and hypothalamic dysfunction (i.e. if oestrogen low and LH/FSH high)
    • USS
      • Can be useful in PCOS
      • Also should be used to assess girls who have not been sexually active (primary)
    • Karyotyping
    • Occasionally you can do progestegen +/- oestrogen challenges
      • i.e. put the patient on the pill for 2-3 weeks and then see if she has a withdrawal bleed.

Causes of Amenorrhoea

Primary

  • Constitutional delay (family history)
  • Genitourinary malformation
    • e.g. imperforate hymen; absent uterus or vagina (usually cyclical pain)
  • Testicular feminisation
    • XY karyotype but with androgen insensitivity
  • Turners syndrome
  • Anorexia nervosa
  • Congenital adrenal hyperplasia
  • Kallman’s syndrome
  • Hypothyroidism
  • Prolactinoma

Secondary

  • Pregnancy
  • Premature Ovarian Failure
  • Contraception
  • Asherman’s syndrome
  • Anorexia Nervosa
  • Polycystic ovaries
  • Hyperprolactinaemia
  • Sheehan’s syndrome
  • Cushing’s syndrome
  • CAH

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