ENDO CHECKLIST

1. Diagnosis of diabetes mellitus

 Diabetes symptoms (polyuria, polydipsia and unexplained weight loss) plus:
1. A random venous plasma glucose concentration > 11.1 mmol/L or
2. A fasting plasma glucose concentration > 7.0 mmol/L or
3. Plasma glucose concentration > 11.1 mmol/L two hours after 75g anhydrous glucose
in an oral glucose tolerance test (OGTT).
4. An HbA1c of >48 mmol/L or 6.5 %
 Two HbA1c results ≥ 48mmol/mol ( ≥ 6.5% ) 2-3 months apart confirms a
diagnosis of diabetes
 HbA1c < 48 mmol/mol ( <6.5% ) does not out-rule the possibility of diabetes
 HbA1C blood test is not recommended in the following situations
➢ Children, young adults, diagnosis of Type 1 Diabetes
➢ Acutely ill
➢ Symptoms of hyperglycaemia less than two months
➢ Glycogenic medications e.g. steroids, anti-psychotics
➢ Pregnancy
➢ Anaemias
➢ Haemoglobinopathies

2. Pharmacological tx for diabetes mellitus

Restore physiological pattern of insulin release / ❖ Insulin secretogugues / incretin agents

increase insulin release (sulphonylureas)
Restore sensitivity of target organ to insulin action ❖ Insulin – sensitisin agent

Replace insulin when it is completely deficient ❖ Insulin – long / short – acting

Decrease glucose by non – insulin dependent ❖ Inhibit GIT absorption / promote kidney excretion
mechanism
 Drugs
Sulfonylureas – eg glyburide,
chlorpropamide, glimepiride,
glipzide
PPAR gamma receptor agonist
(Thiazolidinediones)
Metformin (eg Biguanide)
Disaccharide / alpha – glucosidease
inhibitors (eg acarbose)
SGLT2 inhibitor (eg Dapagliflozin)
GLP 1 analogue ( eg exenatide)
DPP4 inhibitors (eg Gliptin) ;
weight neutral
Effects
 Bind to beta cell, increase insulin production
 Weight gain, cause hypoglycemia
 Most commonly use because cheap
 Weight gain
 Hypoglycaemia (low blood sugar) including dizziness, lack of energy,
drowsiness, headache, and sweating have been observed.
 Diarrhoea, nausea .
 Increase insulin action; improve insulin action
 Fluid retention / weight gain, headache, liver damage, anaemia
 Increase insulin sensitivity
 Drug of choice; DM2
 SE : Nausea, vomiting, stomach upset, diarrhea, weakness, or a metallic
taste, lactic acidosis
 Not allow sucrose etc convert to glucose.Block glucose absorption
 Flatulence, diarrhoea
 Block glucose transport in urine (prevent absorption)
 Cause glycosuria
 Can cause thrush, candiadis, UTI
 Gastrointestinal side effects : nausea, vomiting

 Sitagliptin side effects: angioedema, increased risk of acute pancreatitis
3. Insulin regimen
 Subcutaneous insulin : short-, medium-, or long-acting. Strength: 100U/mL.
 Ultra-fast acting (Humalog®; Novorapid®); inject at start of meal, or just after
(unless sugar-laden)—helps match what is actually eaten (vs what is planned)
 Pre-mixed insulins, with ultra-fast component (eg NovoMix® 30).
 Long-acting recombinant human insulin analogues (insulin glargine, eg 0.4U/
kg/d) are used at bedtime in type 1 or 2 DM.18 There is no awkward peak, so
good if nocturnal hypoglycaemia is an issue.Caution if considering pregnancy.
 Common insulin regimen
 Plan the regimen to suit the lifestyle, not vice versa. Disposable pens (FlexPen®
?more accurate than SoloStar®): dial dose; insert needle 90° to skin. Vary
injection site (outer thigh/abdomen); change needle daily.
 BD biphasic regimen’: twice daily premixed insulins by pen (eg NovoMix
30®)— useful in type 2 DM or type 1 with regular lifestyle.
 ‘QDS regimen’: before meals ultra-fast insulin + bedtime long-acting analogue:
useful in type 1 DM for achieving a flexible life-style (eg for adjusting doses
with size of meals, or exercise)
 Dose adjustment based on normal eating (DAFNE)
 Based on carb intake
 Multidisciplinary teams promoting autonomy can save lives. DAFNE found
that training in flexible, intensive insulin dosing improved glycaemic control
as well as wellbeing. It is resource intensive
 Subcutaneous insulin dosing during intercurrent illnesses (eg influenza)
 Illness often increases insulin requirements despite reduced food intake.
 Maintain calorie intake, eg using milk.
 Check blood glucose ≥ 4 times a day and look for ketonuria. Increase insulin
dose if glucose rising. Advise to get help from a specialist diabetes nurse or GP
if concerned (esp. if glucose levels are rising or ketonuria). One option is 2-
hourly ultra fast-acting insulin (eg 6–8U) preceded by a fingerprick glucose
check.
 Admit if vomiting, dehydrated, ketotic, a child, or pregnant
 4. Diabetes mellitus type 1 vs 2

Type 1 Type 2
Onset Sudden Gradual
Age Any (mostly young) Mostly adults
Body habitus Thin / normal Often obese
Ketoacidosis Common Rare
Autoantibodies Usually have Absent / present; slowly
progressive AI disease
Fasting insulin & c – Higher
peptide
Endogenous insulin Low / absent Normal, increase / decrease
Concordance in identical 50% 90%
twins
Prevalence Less prevalent More prevalent

5. Diabetes mellitus complications

Macrovascular Microvascular
 Retinopathy  Risk of stroke
Blindness is preventable. Annual retinal screening manda- tory for all patients not  Risk of heart
already under ophthalmology care. Refer to an ophthal- mologist if pre-proliferative attack
changes or if any uncertainty at or near the macula (the only place capable of 6/6  Peripheral
vision) vascular
Retinopathy & maculopathy, cataracts disease – poor
circulation to
Rubeosis iris : new vessel formation in iris  glaucoma
the limbs
CN palsies
Diabetic retinopathy and maculopathy = Commonest cause of blindness up to 60
years old
Refer if pre – proliferative retinopathy / maculopathy
Investigation : fluorescein angiography
Rx : lase photocoagulation
 Nephropathy
Symmetric sensory neuropathy
Microalbuminaemia : urine albumin : creatinine ≥ 30 mg/mm
If present ACEi / ARA
Refer if urea creatinine ratio > 70
 Neuropathy
Symmetric sensory neuropathy
 Glove and stocking
 Absent ankle jerks
 Numbness, tingling, pain (worse at night)
 Rx : paracetamol, amitriptyline, gabapentin, SSRI, Capasaicin cream, baclofen
Mononeuropathy / mononeuritis multiplex
 Eg CN3 / 6 palsies
Femoral neuropathy / amyotrophy
 Painful asymmetric weakness and wasting quadriceps with loss of knee jerks
  Dx : nerve conduction and electro myography
Autonomic neuropathy
 Postural hypotension; rx : fludrocortisone
 Gastroparesis (early satiety), Gord, BLOATING
 Diarrhoea; x with codeine
 Urinary retention
 Eretile dysfunction

6. Diabetic ketoacidosis
 Diagnosis
 Acidaemia; ph < 7.3
 Hyperglycaemia ≥ 14 mmol/l
 Ketonuria

Symptoms Signs
 Thirst  Flushed appearance
 Polyuria  Kussmaul breathing
 Abdominal pain  Ketone breath
 Dehydration
 Altered mental state progression to coma

 Investigations
 Blood glucose (capillary)
 Test for ketones in plasma or urine
 U&E & Blood glucose (venous)
 Blood gases
 MSU, ECG, Chest x-ray

 Severe DKA is classed as any of: 


 Venous bicarbonate <10mmol/L and/or pH <7.1

 GCS <12

 MI

 Hypotension unresponsive to initial fluid resuscitation.

7. Diabetic ketoacidosis management

 Blood glucose > 20 mmol/ l in the presence of ketones or metabolic acidosis should
be managed vigorously
 IV fluids; Sodium chloride 0.9% in following regimen –
 1L over 1/2 hr
  1L over 1 hr
 1L over 2 hr
 1L over 4 hr
 Further replacement dictated by the patient‟s condition, usually 4-6 L over next
24 hr
 Intravenous Insulin infusion 1 unit /ml in sodium chloride 0.9% via syringe pump at
6 units/hr; if no fall in glucose after 2 hr (very unusual - check pump and patency
on iv cannula) double dose and continue doubling at hourly intervals until response
occurs
 When plasma glucose falls to near-normal values (<15 mmol/L), saline infusion
should be replaced with 5% dextrose [KCl]. Insulin infusion may be switched to SC
insulin. Do no stop insulin infusion until 60mins after recommencement of SC
insulin.
 Potassium need depends on initial plasma concentration
 Insulin therapy leads to uptake of potassium by the cells with a consequent fall in
plasma levels. Potassium is therefore given as soon as insulin is started.
 K < 3.5 infuse at 20 mmol/hr
 Recheck potassium after an hour in all patients
 All patients on iv potassium must have continuous ECG monitoring. Bicarbonate
should not be used routinely and should only be used if the pH fails to improve after
resuscitation with 2-3 L of sodium chloride 0.9%. Discuss with senior doctor.
 Seek the underlying trigger e.g. infection (antibiotics necessary), surgery, MI,
chemotherapy,
 incorrect insulin dose/non-compliance.
 General management
 A nasogastric tube should normally be inserted in unconscious patients and the
stomach aspirated
 Give a broad-spectrum antibiotic after blood cultures taken (eg co-amoxiclav
625 mg orally 8 hrly) if patient is febrile and no obvious cause can be found
 Insert a urethral catheter to monitor urine output if patient is hypotensive or
comatose or fails to pass urine within 3 hr of starting IV fluids
 Although patients with hyperosmolar coma have an increased risk of venous
thromboembolism, prophylactic heparin increases the risk of GI bleeding, so
treat only proven venous thromboembolism

 Target
 Blood ketones should fall by >0.5mmol/L per hour. 

 Bicarbonate should rise by >3mmol/L per hour until >19. 

 Aim for glucose drop of 3mmol/L per hour until within the normal range. 


 Complications of Treatment
 Pulmonary and cerebral oedema (from excessive fluid replacement)
 Aspiration pneumonia
 Hypoglycemia
 Hypokalemia
 Hypomagnesemia
 Hypophosphatemia
  DVT/Thromboembolism
 Hypothermia 

 Hyperchloraemic acidosis: Patients can lose too many negatively charged
electrolytes in 
 treatment, which are replaced with chloride. The kidneys
usually correct this spontaneously within a few days. 


8. Diabetic ketoacidosis causes

 Infection
 Infarction (MI)
 Ischaemia (CVA)
 Intoxication (alcohol)
 Implantation (pregnancy)
 Ignorance (compliance)

9. Hyperglycaemia hyperosmolar state non – ketotic coma

 Hyperosmolar hyperglycemic state (HHS) is a complication of diabetes mellitus in
which high blood sugar results in high osmolarity without significant ketoacidosis
 Typically type 2 DM are at risk of this.
 Still producing insulin (but insufficient to control hyperglycaemia).Only small
amount of insulin needed to inhibit ketogenesis; hence not ketotic
 Symptoms include signs of dehydration, weakness, legs cramps, trouble seeing, and
an altered level of consciousness
 Onset is typically over days to weeks
 Diagnosis is based on blood tests finding a blood sugar greater than 30 mmol/L (600
mg/dL), osmolarity greater than 320 mOsm/kg, and a pH above 7.3
 Triggers

10. Hyperglycaemia hyperosmolar state vs DKA

11. Hyperglycaemia hyperosmolar state management

  Should be treated in the same way as DKA ; but with more cautious IV fluids;
usually 3L over first 24 hr and all these patients should receive prophylactic low
molecular weight heparin

12. Hyperglycaemia hyperosmolar state complications and management

 Complications may include seizures, disseminated intravascular coagulopathy,
mesenteric artery occlusion, or rhabdomyolysis.
 Hyperglycaemia  2 deleterious complications
 Fluid shift under osmosis (extracellular compartment  intravascular
compartment).Thus, causes cellular dehydration
 Osmotic diuresis with subsequent water loss in urine  hypovolemia
 Severe hypovolaemia  vulnerable to shock, thrombosis and neuro impairment
 Occlusive events are danger (focal CNS events, chorea, DIC, leg ischaemia,
rhabdomyolosis)
 DVT – give LMWH prophylaxis to all unless contraindication
 Rehydrate slowly with 0.9% saline over 48 h; typical deficit are 110 – 220 mL/kg
 Replace K once urine starts to flow
 Only use insulin if blood glucose is not falling by 5mmol/L/h with rehydration or if
ketonaemia – start slowly 0.05u/kg/h
 Keep blood glucose at least 10 -15 mmol/L for first 24 h to avoid cerebral oedema
 Look for the cause; eg MI, drugs or bowel infarct

13. Hypoglycaemia
 Plasma glucose ≤ 3 mmol/l
 Common endocrine emergency

14. Hypoglycaemia symptoms

Autonomic (2.5 – 30) Neuro glycopenic (<2.5)

 Sweating  Confusion
 Anxiety  Drowsiness
 Hunger  Seizure
 Tremor  Personality change
 Palpitation  Focal neurology; eg CN 3
 Coma (<2.2)

15. Hypoglycaemia causes

Poor oral intake Increased utilization Toxins, medications Endocrine, metabolic disorder

 Gastroenteritis  Sepsis  Insulin  Idiopathic ketotic

 Malnutrition  Burns  Beta blocker hypoglycaemia
 Intercurrent illness  Large tumours –  Ethanol  Hyperinsulinism
neuroblastoma ,  Salicylates  Congenital
 Wilms tumour  Oral hypoglycaemic hypothyroidism
 Excessive  Alcohol  Glucose 6 phosphate
exercise deficiency

16. Whipple's triad

  Whipple's triad is a collection of three criteria (called Whipple's criteria) that suggest a
patient's symptoms result from hypoglycemia that may indicate insulinoma. The triad
is stated in various versions, but the essential conditions are:
 Low plasma glucose ≤ 3MM
 Symptom consistent with hypoglycaemia
 Relief of symptoms by glucose administration

17. Hypoglycaemia management

Alert and oriented : oral  Rapid – acting : Lucozode

carbohydrate
Drowsy / confused but intact
swallowing : buccal carb
Unconscious / concerned regading
swallowing : iv dextrose
Deteriorating / refractory / insulin
– induced / no access
 Long – acting : toast, sandwich
 Hypostop / glyocogel
 Consider IV access
 100 ml 20% glucose
 1 mg glucagon IM/SC
 Wont work in drunk + short duration of effects (20 min)
 Insulin release may cause rebound hypoglycaemia

18. Hypoglycaemic coma

 Usually rapid onset, maybe preceded by odd behaviour – aggression, also sweating,
increased pulse, seizure
 Management
 Give 20 – 30 g glucose IV . eg 200 – 300 ml of 10 % dextrose
 Expect prompt recovery
 Glucagon 1 mg IV/IM is nearly as rapid as dextrose but wont work in drunk
patients
 Dextrose IVI maybe needed for severe prolonged hypoglycaemia
 Once conscious, give sugary drinks and meals

19. Diabetes mellitus vs diabetes insipidus

Diabetes mellitus Diabetes insipidus

 Characterized by high level of sugar in  Kidney unable to conserve water
blood
Symptoms  High blood glucose, excess urination,  Excess thirst, excess volume of severely diluted
increased thirst & hunger urine
Incidence  7.7 per 1000  3 in 100,000
Causes  Type 1 : autoimmune  Deficiency in ADH
 Type 2 : genetics, lifestyle, infection  Brain tumor, head injury, med (eg lithium),
genetics
Treatment  Insulin, life style management  Typically, desmopressin (nasal spray/musc)
 Iv hypertonic saline solution ( 3% or 5%)
 Thiazide diuretics
Prognosis  Up tp 10 years shorter life expectancy  No effects on life expectancy
Curable  No  No

20. Adrenal gland

 21. Adrenocortical hyperfunction
 Hyperaldosteronism
 Cushing’s syndrome
 Adrenogenital ( excess sex hormone production ) or virilising syndromes

22. Hyperaldosteronism
 Hyperaldosteronism is a medical condition wherein too much aldosterone
(mineralcorticoid) is produced by the adrenal glands, which can lead to lowered levels
of potassium in the blood (hypokalemia) and increased hydrogen ion excretion
(alkalosis).

23. Types of hyperaldosteronism

Primary / Conn syndrome Secondary

 Primary aldosteronism is a condition caused by  Aldosterone release occurs in response to
an excess of the adrenal hormone activation of renin – angiotensin system
aldosterone independent of the renin-angiotensin-  Increased level of plasma renin
aldosterone axis.  Aetiology : anything that decreases blood flow to
 In the vast majority of cases primary aldosteronism is kidneys, lower blood pressure and lowers sodium
caused by adrenal adenomas or adrenal hyperplasia. level
 Aetiology : Congestive heart failure
Liver failure
Kidney disease
Cirrhosis
Dehydration
Hypoalbuminaemia

24. Features of hyperaldosteronism

Signs Symptoms
 Hypokalaemia  Headache
Hypokalaemia may present with non-specific signs and  Vision problems
symptoms. They include fatigue, muscle weakness and  Fatigue
constipation.  Muscle cramps
Patients may develop hypokalaemia induced diabetes  Muscle weakness
insipidus - manifesting with polyuria and polydipsia.  Numbness
 Hypertension  Temporary paralysis
 Long-standing hypertension may result in end-organ  Increased urine
damage: chronic kidney disease, heart failure,  Increased thirst
hypertensive retinopathy, abdominal aortic aneurysm

25. Hyperaldosteronism investigations and diagnosis

 Blood pressure
 Primary aldosteronism is now thought to be a significant cause of secondary
hypertension.
 Suspicion should be higher in younger patients and those with treatment-resistant
hypertension.
 Serum Potassium
 Low serum levels are present in around 30% of patients. Urinary potassium may
demonstrate inappropriate potassium loss in the setting of hypokalaemia.
 In hypokalaemic patients, ECG's can show ST depression, T wave inversion and
U waves.
 Blood gas
 Increased urinary hydrogen excretion, multifactorial, due to hypokalaemia and
direct effects of aldosterone on intercalated cells may result in a metabolic
alkalosis
 Diagnosis

Screening  The aldosterone:renin ratio (ARR) is used as a screen in those with suspected primary
aldosteronism.
 It compares serum levels of aldosterone and renin. A raised ratio should prompt further
investigation.
Diagnostic  Those with a raised ARR require confirmatory testing.
 A number of tests are available:
Serum aldosterone levels
24-hr urinary aldosterone excretion
Salt loading test
Identifying the  Once the diagnosis of primary aldosteronism is confirmed the exact aetiology must be
cause identified. This can require complex testing often involving:
Adrenal CT
Adrenal vein sampling
 In those with a positive family history genetic testing should be considered.

26. Hyperaldosteronism management

 27. Spironolactone side effects
 Vomiting, diarrhea, and stomach pain or cramps
 Dry mouth and thirst
 Dizziness, unsteadiness, and headache
 Gynecomastia (enlarged breast tissue) in men, and breast pain in women
 Irregular menstrual periods and post-menopausal vaginal bleeding
 Erectile dysfunction
 Deepening of the voice and increased hair growth
 Drowsiness, tiredness, and restlessness

28. Phaechromacytoma
 Cathecholamine – producing tumours
 10 % rule : 10 % malignant, 10 % extra – adrenal , 10 % bilateral, 10 % familial
 90 % sporadic, 10 % part of hereditary cancer syndromes – thyroid, MEN 2a and 2b,
neurofibromatosis, von Hippel Lindau syndrome
 Triad : episodic headache, sweating, tachycardia

29. Phaechromacytoma features

Heart  Increased pulse, palpitation / VY, dyspnea, faint, angina, MI/LVF, cardiomyopathy
CNS  Headache, visual disorder, dizziness, tremor, numbness, fit, encephalopathy, Horner’s
syndrome (paraganglioma), subaracahanoid / CNS haemorrhage
Psychological  Anxiety, panic, hyperactivity, confusion, episodic psychosis
Gut  D&V, abdominal pain over tumor site, mass, mesenteric vasoconstriction
Others  Sweat/flushes, heat intolerance, pallor, increased temperature, backache, haemoptysis

30. Phaechromacytoma treatment

Medical Surgery : adrenalectomy

 If malignant,  Alpha beta blocker (eg phenocybenzamine) used pre – operation before beta blocker to
do chemo / avoid crisis from unopposed alpha – adrenergic stimulation
radiolabeled  Beta blocker used if heart disease or tachycardic
MIGB  Post – operation
24 h urine metadrenaline
Monitor BP for 2 weeks; risk of decreased BP

31. Hypertensive crisis / phaehromacytoma emergencies

 Get help, take to ICU
  Principle is combined alpha and beta blockade, but alpha must be started first, as
unopposed alpha blockade can worsen hypertension.
 Start with short-acting, IV alpha -blocker, eg phentolamine 2–5mg IV.58 Repeat to
maintain safe BP.
 When BP controlled, give long-acting alpha -blocker, eg phenoxybenzamine
10mg/24hPO (increase by 10mg/d as needed, up to 30mg/12h PO);
 SE: postural hypotension; dizziness; tachycardia; nasal congestion; miosis;
idiosyncratic marked BP drop after 1st dose.
 The idea is to increase the dose until BP is controlled and there is no
significant postural hypotension. Alternative alpha1-selective blockers, eg
doxazosin, are preferred in some centres, particularly if surgery is not an
option, eg metastatic tumour.
 A beta 1-blocker may also be given at this stage to control any tachycardia or
myocardial ischaemia/dysrhythmias
 Surgery is usually done electively after 4–6wks to allow full alpha -blockade and
volume expansion. When admitted for surgery the phenoxybenzamine dose is
increased until significant postural hypotension.

32. Cushing’s syndrome

 Collection of signs and symptoms due to prolonged exposure to glucocorticoid –
cortisol
 Features

 Prognosis
 Untreated  vascular mortality
  Treated  good prognosis.But myopathy, obesity, menstrual irregularity,
increased BP, osteoporosis, subtle mood and DM often remain; so follow up &
manage carefully

33. Cushing’s syndrome causes

34. Cushing’s syndrome investigations

 Confirm diagnosis (increased plasma cortisol), then localize the source on lab testing.
 Use imaging studies to confirm the likely cause

1st line  Overnight Dexamethasone suppression test : measures whether ACTH secretion by the pituitary
can be suppressed.
Cushing syndrome : failure to suppress. ACTH independent
 24 h urinary free cortisol
2nd line  48 h Dexametahsone suppression
 48 h high dose Dexamethasone suppression :may distinguish pituitary (suppression) form other
causes (no / part suppression)
 Midnight cortisol
Admit unless salivary cortisol is used
Often inaccurate due to measurement issue
Normal circadian rhythm (cortisol lowest at midnight, highest early morning) is lost in Cushing
syndrome
Midnight blood via cannula during sleep show cortisol increase in Cushing’s
Localization  Plasma ACTH
test If no ACTH, adrenal tumor is likely.Do CT adrenal gland . ACTH indep
 If no mass, do adrenal vein sampling / adrenal scintigraphy
If ACTH detectable : distinguish pituitary cause from ectopic ACTH production by high dose
suppression test or corticoprin releasing hormone test
 If test indicates cortisol respond to manipulation, Cushing disease is likely
 Image the pituitary (MRI) and consider bilareral inferior petrosal sinus sampling
 If test indicates cortisol doesn’t respond to manipulation, hunt for source of ectopic ACTH
 Eg IV contrast CT of chest, abdomen pelvis & MRI of neck, thorax and abdomen – can be
small ACTH secreting carcinoid tumor
Others  Adrenal androgen
 Urinary steroid metabolomics
Cancer vs non vs pituitary
  Anterior pituitary function
Bitemporal hemianopia – at optic chiasm pushed by pituitary tumour

35. Cushing’s syndrome treatment

Iatrogenic  Stop medication if possible (steroid)

Cushing’s disease  Selective removal of pituitary adenoma (trans sphenodically)
 Bilateral adrenectomy (unlocatable source / recurrence post – op/ complication post –
operation (Nelson’s syndrome- hyperpigmentation)
Adrenal adenoma  Aderenelctomy : “cares” adenoma but rarely cancer
/ carcinoma  Radiotherapy, adrenolytic drugs (mitotane) following carcinoma
Ectopic ACTH  Surgery if tumour is located and hasn’t spread
 Metyrapone, ketoconazole, fluconazole decreases post – operation cortisol secretion / if
waiting for radiation effects
Metyrapone
 Principally used agent therapy
 ACTH sensitive enzyme
Ketoconazole
 Less used therapeutically
 Powerful inhibitor of steroidogenesis ; at high dose
 Anti fungal
Fluconazole
 Preserve gomerulosa
 Intubation - mifespristone (compete with cortisol and receptor) + etomidate (blocks cortisol
secretion) may be needed ; eg severe ACTH – associated psychosis)

36. Adrenal insufficiency causes

Primary Secondary
 Problem within adrenal gland  Higher up problem; maybe in pituitary which
Acute (adrenal crisis) then cause downstream effects
Chronic (Addison’s disease) ↓ stimulation of adrenals due to ↓ ACTH -
 Aetiology can be primary or secondary
Autoimmune conditions; adrenalitis,  Aetiology
polyglandular autoimmune syndromes Hypothalamic disease
Infections; tuberculosis, fungal infections, CMV Hypopituirism
infection, HIV associated infection Long – term steroid
Adrenal hemorrhage; Waterhouse-Friderichsen  Features
syndrome (bilateral), coagulopathy, traumatic birth Normal mineralocorticoid production
No pigmentation due to ↓ ACTH
Infiltrations; amyloidosis, sarcoidosis,
haemochromatosis
Neoplasms, primary and secondary carcinomas,
lymphomas
Drugs; ketoconazole, fluconazole, phenytoin and
rifampicin
 Destruction of adrenal cortex  glucocorticoid and
mineralocorticoid deficiency
 37. Waterhouse-Friderichsen syndrome
 Adrenal gland failure due to bleeding into adrenal gland; commonly caused by severe
bacterial infection
 Rapid development of adrenal insufficiency associated with massive bilateral adrenal
haemorrhage
 Neisseria meningitidis septicaemia
 Profound hypotension
 DIC with widespread purpura

38. Adrenal insufficiency presentation

Symptoms Signs
 Fatigue, malaise, weakness, anorexia  Weight loss
 Postural dizziness  Hyperpigmentation
 Gastro Skin pigmentation only in primary adrenal
Nausea insufficiency ( Addison’s ) as ACTH cause the skin
Vomiting darkening
Abdominal pain  Hypotension
 Thinning of axillary and pubic hair
Constipation
 Myalgia, arthralgia, rarely flexion  Vertigo
contractures  Hyponatraemia, hyperkalaemia, hypoglycaemia,
 Decreased libido, amenorrhoea hypercalcaemia

39. Addison’s disease investigations

Blood  Decreased Na, increased K (due to decreased mineralcorticoid)

 Decreased glucose(due to decereased cortisol)
 Decreased Ca
 Eosinophilia, Anaemia
Differential  Short ACTH stimulation test / Synacthen test
Do plasma cortisol before and after
Addison is excluded if cortisol increases
Steroid drugs may interfere with assay, ask lab
NB : in pregnancy and contraceptive pill, cortisol level may be reassuring but falsely increased
to to increased cortisol binding globulin
In Addison, ACTH increases at 9 am (usually low)
ACTH is low in secondary causes
Others  21 Hydroxylase antibody : positive in 80% of autoimmune disease
 Plasma renin, aldosterone : to assess mineralocorticoid status
 CXR : evidence of TB; eh upper xone fibrosis or adrenal calcification
 If no antibody, consider further tests; eg adrenal CT for TB, Histoplasma or metastatic disease

40. Addison’s disease treatment

Replace Hydrocortisone
Fludrocortisone
Advice Don’t stop steroid suddenly
Increase steroid during intecurrent illness / injury
Wear medical alert bracelet
Follow up Yearly (BP, U&E)
Watch for autoimmune disease; pernicious anaemia

41. Addisonian’s crisis

Presentation  Shocked : increased HR, postural drop, oliguria (decreaed urine output), confused
 Hypoglycaemia
 Usually known as Addisonian / chronic steroid user
Precipitant  Infection, trauma, surgery, stop long – term steroid
Management  Blood : cortisol, ACTH, U&E, Culture
 Check CBG : glucose may be needed
 Hydrocortisone 100 mg IV may be needed
 IV crystalloid for volume expansion
 Septic screen
 Treat underlying disease

42. Causes of goitre

Diffuse Nodular
 Physiological  Multinodular – goitre
 Graves disease  Adenoma
 Hashimoyo’s thyroiditis  Carcinoma
 Subacute de – Quervain thyroiditis (painful)

43. Hyperthyroidism
 Hyperthyroidism is the condition that occurs due to excessive production of thyroid
hormone by the thyroid gland.
 Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any
cause and therefore includes hyperthyroidism. Some, however, use the terms
interchangeably.

Primary Secondary
 Dysfunction in thyroid gland itself  Secondary to increased TSH
 TSH  TSH
 T4, T3  T4, T3
 Aetiology  Secondary to increased TRH by hypothalamus
Graves disease  Aetiology
Toxic multinodular goiter TSH – secreting pituitary tumout
Solitary toxic adenoma Administration of T4, T3
Subacute and silent thyroiditis

44. Hyperthyroid presentation

Symptoms Signs
Hand Face Neck Graves’s specific
 Diarrhoea  Fast, irregular  Thin hair  Goitre /  Dermopathy
pulse  Lid lag nodules Pre – tibial myoxedema
 Increased appetite +  Warm, moist  Lid  Ophthalmopathy
decreased weight skin retraction Exophthalmus,
 Sweat + heat  Fine tremor ophthalmoplega especially
intolerance  Palmar up – gaze palsy, eye
 Palpitation erythema discomfort & grithnes,
 Tremor photophobia & decreased
 Irritability acuity, chemosis
 Oligomenorrhoea ±  Thyroid acropachy / clubbing
infertility

45. Hyperthyroid investigations

TSH  Free T4 and T3 are more useful than total T4 and T3 as the latter are affected by Thyroxine-
binding globulin (TBG). Total T4 and T3 are increased when TBG is increased and vice versa.
 TBG is increased in pregnancy, oestrogen therapy (HRT, oral contraceptives) and hepatitis.
TBG is decreased in nephrotic syndrome and malnutrition (both from protein loss), drugs
(androgens, corticosteroids, phenytoin), chronic liver disease and acromegaly.
Thyroid  Antithyroid peroxidade antibodies or antithyrohlobulin antibodies may increased in
autoantibodies autoimmune thyroid disease; Hashimoto’s, Graves
 If positive in Graves disease, theres increasing risk of developing hypothyroidism at later stage
TSH receptor  May be increased in Graves disease (useful in pregnancy)
antibody
Serum  Useful in monitoring the treatment of carcinoma and in detection of factitious (self –
thyroglobulin medicated) hyperthyroidism, where it is low
US  This distinguishes cystic (usually, but not always benign) from solid (possibly malignant)
nodules
 If a solitary nodules (or dominant) large nodules, in a multinodular goitre, do a FNA to look
for thyroid cancer
Isotope scan  23Iodine, 99 technetium pertechnetate
 Useful in determining the cause of hyperthyroidism and to detect retrosternal goitre, ectopic
thyroid tissue or thyroid metastases (+ whole body CT)
 If there are suspicious nodules, does the area hot / cold / same uptake of isotope as the
remaining thyroid
 Few natural and almost no hot nodules are malignant
 20% of cold nodules are malignant
 Surgery is more likely to be needed if
Rapid growth
Compression sign
Dominant nodule or scintigraphy
Nodule ≥ 3 cm
Hypo – echogenicity

46. Graves disease

 The most common cause of hyperthyroidism (85%) and has an autoimmune basis
 It is an autoimmune disease mediated by antibodies that stimulate the TSH receptor,
leading to excess secretion of thyroid hormones and hyperplasia of thyroid follicular
cells, resulting in hyperthyroidism and diffuse goitre.
 Female:Male = 10:1
 HLA-B8 and HLA-DR3
  Associated with other autoimmune disorders; eg RA, pernicious anaemia, myasthenia
gravis
 Modest, symmetric enlargement of thyroid
  Radioactive iodine uptake; lights up gland.Most patient doesn’t need this to dx;
based on clinical or blood
 Pathogenesis
 Thyroid-specific defect in suppressor T-cell function
 TSH receptor IgG autoantibodies
 Proliferation of CD4+ helper T cells targeting TSH-receptor epitopes
 Thyroid-stimulating antibodies
 Thyrotropin-binding inhibitor immunoglobulin

47. Thyroid eye disease

 Seen in 25 – 50% people with Graves
 Main RF : smoking
 May not be associated with thyroid disease; patient can be euthyroid, hypo or
hyperthyroid
 Maybe the 1st presenting sign of Graves and can be worsen with treatment especially
radioiodine (usually transient effects)
 Retro – orbital inflammation and lymphocyte infiltration  orbit swelling
 Symptoms and signs

Symptoms Signs
 Eye discomfort  Exophthalmos
 Grithiness  Conjunctival oedema
 Increased tear production  Corneal ulceration
 Photophobia  Papilloedema
 Diplopia  Loss of colour vision
 Decreased acuity  Ophthalmoplegia; especially upward gaze – due to
 Afferent pupillary defect (optic nerve compression) muscle swelling and fibrosis

48. Multinodular goitre

 Most simple goitres become transformed into multinodular goitres
 Can be inactive or toxic
 Inactive / non-toxic may be asymptomatic
  Toxic is associated with hyperthyroidism
 Thyroid cancer is identified in 13.7% of patients operated for multinodular
goitre
 These nodules grow at varying rates and secrete thyroid hormone
autonomously, thereby suppressing TSH-dependent growth and function in the
rest of gland
 Nontoxic or toxic (induce thyrotoxicosis)
 No ophthalmopathy or dermopathy
 May cause cosmetic disfigurement and tracheal compression
 May induce the superior vena cava syndrome (due to compression)- raised hand above
head-face become very red, eye teary, stridor
 Differentiation of dominant nodule from thyroid tumour difficult
 Retrosternal extension (“plunging goitre”)

49. Hyperthyroid treatment

Medical Radiological : radio Surgical :

Symptomatic Anti – thyroid iodine thyroidectomy

 Beta –  Carbimazole : Inhibitis TPO  Must become  Risk damage to

blocker  2 strategies : hypothyroid recurrent laryngeal
Titration  CI : pregnancy, nerve and
Block and replace lactation hypoparathyroidism
 In Graves, maintain either regimen for 12 – 18  Caution in  Patient becomes
months then withdraw active hypothyroid
 50% will relapse; requiring radioiodine / hyperthyroidism
surgery due to risk of
 SE : agranulocytosis (decerased neutrophils  thyroid strorm
leads to dangerous sepsis; rare – 0.03%)
 Warn to stop and get urgent FBC if signs of
infection (eg increased temperature, sore throat,
mouth ulcer)

50. Thyroid storm

Diagnosis  Don’t wait for test result if urgent treatment is needed

 TSH, free T4, free T3
 Confirm by Technetium (thyroid scan tracer) is possible
 The Burch-Wartofsky Point Scale (BWPS) is a quantitative diagnostic tool based on 3
major observations in patients with thyroid storm: Continuum of end organ dysfunction
Features for  Increased temperature
acute onset of  Agitation, confusion, coma
hyperthyroism  Tachycardia, AF
 Acute abdomen
 HF, CV collapse
 Goitre
 Diarrhoea, vomiting
Precipitans  Recent thyroid durgery / radioiodine
 Infection, MI, trauma
 Many occur in those whose treatment stopped / become ineffective of in those with
untreated mild hyperthyroidism who have developed intercurrent llness (eg infection)
Treatment  Primary treatment : organic iodine and antithyroid drugs (prophyl thiouracil /
metronidazole decreases synthesis and release of thyroid
 Temperature control, IV fluid
 Beta blocker to treat symptoms
 Example
Fluid resuscitation
Blood : TFT + culture (if suspect infection)
Propanolol PO/IV
Digoxin may be needed
Carbimazole, then Lugol’s iodine 4h later to inhibit thyroid
Hydrocortisone
Treat cause
Grand strategy  Counterct peripheral effects of thyroid hormone
 Inhibit thyroid hormone synthesis
 Treat systemic complications
51. Hypothyroidism presentation
Symptoms Signs
 Lethargy  Cold hand
 Cold intolerance  Bradycardic
 Decreased appetite + increased weight  Slow – relxing reflexes
 Constipation  Dry hair and skin
 Menorrhagia  Puffy face
 Decreased mood  Goitre
 Myopathy, neuropathy
 Ascites
 Myxoedema
SC tissue swelling in severe hypothyroidism
Typically around eyes, dorsum of hands

52. Hypothyroid causes

Primary Post – surgical Secondary
 Atrophic thyroiditis  Thyroidectomy  Hypopituitarism
 Hashimoto’s thyroiditis  Radiotherapy (very rare)
 Subacute thyroiditis (eg post – partum)
 Iodine deficiency
 Drugs : carbimazole, amiodarone, lithium
 Congenital : thyroid agenesis

53. Hypothyroid investigations

 TFT
 Increased MCV ± normochromic anaemia
 Increased triglyceride, cholesterol
 U&E : Hyponatraemia; SIADH
 Increased CK if myopathy
 Antibody : TPO, TSH

54. Hypothyroid treatment

 Levothyroxine (T4)
 Titrate to normalise T
 Enzyme inducers increase in thyroid metabolism
 Clinical improvement takes 2 weeks
 Check for other autoimmue disease; eg Addisons;s, RA

55. Thyroid nodules

 Thyroid nodules are solid or fluid-filled lumps that form within your thyroid, a small
gland located at the base of your neck, just above your breastbone. The great majority
of thyroid nodules aren't serious and don't cause symptoms.
 Thyroid cancer accounts for only a small percentage of thyroid nodules.
 Thyroid nodules are classified as cold, warm, or hot, depending on whether they
produce thyroid hormones or not: Cold nodules don’t produce thyroid hormones.
Warm nodules act as normal thyroid cells. Hot nodules overproduce thyroid hormones.

56. Thyroid adenoma

 Most are follicular adenomas
 Negligible risk of malignant transformation
 Encapsulated
 Homogeneous, soft, fleshy cut surface
 Foci of haemorrhage
 Cystic degeneration
  Rarely cause hyperthyroidism
 Most are “cold” on isotope thyroid scan

57. Malignant thyroid disease

 Presentation
 Non functional, cold
 Painless neck mass
 Cervical metastases
 Compression symptoms : dysphagia, stridor, SVC obstruction
 Risk factors
 Solitary, Solid, Younger, Male, Cold, Radiation exposure
 Types
 Papillary carcinoma ( 50 -70%)
 Follicular carcinoma ( 10 -15%)
 Medullary carcinoma ( 1 -2 %)
 Associated with MEN
 Anaplastic carcinoma – rare
 Thyroid surgery

Indications  Pressure symptoms

 Relapsed hyperthyroidism ( > 1 failed drug treatment)
 Cosmesis
 Carcinoma
Practicalities  Render euthyroid pre – operative with antithyroid drugs
Stop 10 days prior to surgery (they increase vascularity)
Alternative : just give propanolol
 Check for phaechromacytoma pre – op in medullary carcinoma
 Laryngoscopy : check vocal cord pre and post – operation
Procedure  Collar incision
Complications  Early
Haematoma
Laryngeal odema
Recurrent laryngeal nerve plasy
Hyperparathyroisism
Thyroid storm
 Late
Hypothyroidism
Recurrent hyperthyroisism
Keloid scar

58. Hyperparathyroidism causes

Primary Secondary Tertiary
  PTH   Calcium,  PTH   Calcium,  PTH
 Parathyroid adenoma, hyperplasia,  Renal failure inappropriately
carcinoma Impaired calcitriol production  Prolonged secondary
 MEN 1 or MEN 2b Hyperphosphataemia hyperparathyroid 
 Familial hypocalciuric  Decreased calcium gland undergoes
hypercalcaemia Low oral intake hyperplastic /
 Hyperparathyroid – jaw tumour adenomatous change 
syndrome Vit d deficiency autonomous parathyroid
 Familial isolated Malabsorption secretion
hyperparathyroidism  Inhibition of bone resorption  Seen in chronic disease
Biphophonate
Hungry bone syndrome

59. Hyperparathyroidism presentation

Stone Renal stone, polyuria & polydipsia, nephrocalcinosis

Bone Bone pain, pathological fractures
Moans Depression
Groans Abdominal pain, nausea – vomit – constipation, pamcreatitis, PUD (increase gastrin secretion)
Other Increased BP

60. Hyperparathyroidism investigations

Investigations
Primary  Increased Ca inappropriately, normal PTH, increased ALP, decreasd PO4
 ECG : decreased QT interval  bradycardia  primary heart block
 XRay : osteitis fibrosa cystica  phalangeal erosion
 DEXA : osteoporosis
Secondary  Increased PTH, low Ca, increased PO4, decreased Vitamin D
Tertiary  Increased Ca ,increased PTH, decreased PO4, increased ALP

61. Hyperparathyroidism treatment

 General
 Increase fluid uptake
 Avoid dietary Ca, thiazide (increase serum Ca)
 Surgical / excision of adenoma
 Hypoparathyroidism
 RLN plasy
 Correct causes
 Phosphate binders
 Vitamin D : Calcitonin (active), calciferol (inactive)
 Cinacalcet : increase parathyroid Ca sensitivity

62. Malignant hyperparathyroidism

 Parathyroid – related protein is produced by squamous cell lung cancer, breast and
renal carcinoma  mimics PTH  increase Ca
 63. Acromegaly
 Acromegaly & gigantism are related conditions caused by an excess of growth
hormone (GH)
 Acromegaly occurs in adulthood, following epiphyseal fusion. It typically occurs in
the fourth decade of life. Gigantism, occurring in childhood due to GH prior to
epiphyseal fusion, is defined as height > 2 SD for the patient’s age and sex.
 Increased GH (growth hormone) secretion from pituitary tumor / pituitary
acidophil adenoma
 Hyperplasia (eg via ectopic GH – releasing hormone from carcinoid tumor)
 GH stimulates bone and soft tissue growth through increased IGF

64. Acromegaly aetiology

 Pituitary adenomas acccount for > 90% of cases of acromegaly.
 Pituitary adenomas may be functional (secrete hormones) or non-
functional. Functional pituitary adenomas may lead to excess prolactin secretion
(hyperprolactinaemia), excess ACTH secretion (Cushing's disease), or excess
growth hormone secretion (acromegaly/gigantism).
 Functional pituitary tumours are the commonest causes of acromegaly and
gigantism. In > 90%, excess GH is secreted by a pituitary adenoma.
 Others (rare)
 Other causes of acromegaly are rare. They are usually related to excess secretion
of GH from an ectopic source or hypothalamic dysfunction (e.g. hypothalamic
tumours).

65. Acromegaly presentation

 Acromegaly typically has an insidious onset and is often diagnosed late.
 Gigantism tends to have a more dramatic presentation. Increased linear growth is
marked, yet soft tissue features tend to be less pronounced.
 Clinical features in both conditions may be related to the excess growth hormone
secretion and mass effects of the adenoma.
 Symptoms
 Acroparasthesia, amenorrhoea, decreased libido, headache, snoring, sweating,
arthralgia, backache, carpal tunnel syndrome (50%)
 Signs

Hand  Spade – like, thenar wasting, sweating palms (if active), increased skin fold thickness, carpal tunnel:
decreased sensation + thenar wasting
Face  Prominent supraorbital ridges, scalp folds : cutis verticis gyrata, coarse face with wide nose & big ears
 Prognathism (jaw; look from aside)
 Macroglossia (large tongue)
 Widely – spaced teeth
 Goitre
Others  Puffy, oily, darkened skin
 Proximal weakness + arthropathy (joint disease; whether inflamed or not)
 Pituitary mass effect : bitemporal hemianopia

 Complications
Endocrine  Impaired glucose tolerance (40%)
 DM (15%)
CVS  Increased BP
 LVH
 Cardiomyopathy
 Increased ischaemic heart disease, stroke
Neoplasia  Colorectal cancer

66. Acromegaly investigation

 Increased IGF1
 Increased glucose,Ca, PO4
 Glucose tolerance test
 Growth hormone fails to suppress glucose in acromegaly
 Visual field and acuity
 Brain MRI

67. Acromegaly mx
 The management of acromegaly may involve a number of modalities,
both medical and surgical.
 1st line : trans – sphenoidal excision
 2nd line : somatostatin analogue; octreotide
 3rd line : growth hormone antagonist; pogvisomant
 4th line : radiotherapy
68. Acromegaly vs gigantism

69. Hyperprolactinaemia
 The commonest hormonal disturbance of pituitary
 Present earlier in women (menstrual disturbance), later in males (eg erectile
dysfunction, mass effects)
 Prolactin stimulates lactation
 Increased level  hypogonadism, infertility, osteoporosis by inhibiting secretion of
gonadotrophin releasing hormone; hence decrease LH/FSH and decreased
testosterone/ oestrogen

70. Hyperprolactinaemia causes

Excess pituitary production  Pregnancy, breast feeding

Disinhibition by compression of pituitary
stalk
Dopamine antagonist (commonest cause)
 Prolactinoma ( PRL >5000)
 Hypothyroidism (increased TSH)
 Pituitary adenoma
 Craniopharyngioma
 Antiemetics : metaclopromide
 Antipsychhotics : risperidone, haldol

71. Hyperprolactinaemia presentation

 72. Hyperprolactinaemia investigation
 Basal prolactin; > 5000 – prolactinoma
 Pregnancy test, TFT
 MRI

73. Hyperprolactinaemia mx
 1st line : Cabergoline / bromocriptine
 Dopamine agonist
 Decrease Prolactin secretion, decrease tumor size
 SE : nausea, postural hypotension, fibrosis (lung, heart)
 2nd line : trans – sphenoidal excision
 If usual / pressure symptoms not respond to medical therapy

74. SIADH
 Osmolality is a measure of osmoles of solute per kilogram of solvent (Osm/kg). In
SIADH the release of ADH is inappropriate to the plasma osmolality. This results in
a low plasma osmolality and a euvolaemic hyponatraemia.
 Characterized by excessive unsuppressible release of antidiuretic hormone (ADH)
either from the posterior pituitary gland, or an abnormal non-pituitary source.
 Unsuppressed ADH causes an unrelenting increase in solute-free water being
returned by the tubules of the kidney to the venous circulation.
 SIADH consists of hyponatremia, inappropriately elevated urine osmolality (>100
mOsm/kg), and decreased serum osmolality in a euvolemic patient. SIADH should
be diagnosed when these findings occur in the setting of otherwise normal cardiac,
renal, adrenal, hepatic, and thyroid function; in the absence of diuretic therapy; and
in absence of other factors known to stimulate ADH secretion, such as hypotension,
severe pain, nausea, and stress
 Appropriate ADH secretion is regulated by osmoreceptors on the hypothalamic cells
that synthesize and store ADH: plasma hypertonicity activates these receptors, ADH
is released into the blood stream, the kidney increases solute-free water return to the
circulation, and the hypertonicity is alleviated.
 Inappropriate ADH secretion causes a unrelenting increase in solute-free water
("free water") absorption by the kidneys, with two consequences.
 First, in the extracellular fluid (ECF) space, there is a dilution of blood
solutes, causing hypoosmolality, including a low sodium concentration -
hyponatremia. Then virtually simultaneously, in the intracellular space, cells
swell, i.e. intracellular volume increases. Swelling of brain cells causes
various neurological abnormalities which in severe or acute cases can result
in convulsions, coma, and death.

75. SIADH causes

Central nervous system diseases
that directly stimulate the
hypothalamus, the site of control
of ADH secretion
Various cancers that synthesize
and secrete ectopic ADH
 Infections : Meningitis, encgephalitis, brain abscess, AIDS
 Perinatal asphyxia
 Mass / bleed : trauma, SA hemmorrhage, subdural haematoma, cavernous
sinus thrombosis
 Hydrocephalus
 Lung cancer (SCLC, mesothelioma)
 GI cancer (stomach, duodenum, pancreas)
  Genitourinary cancer (bladder, urethral, prostate, endometrial)
 Lymphoma
 Sarcoma
Various pulmonary diseases  Infection (pneumonia, lung abscess)
 Asthma
 CF
Numerous (at least seventeen)  Chlorpropamide
drugs that chemically stimulate the  Clofibrate
hypothalamus  Phenothiazine
 Ifosfamide
 Cyclophosphamide
 Carbamazepine
 Oxcarbazepine
 Valproic acid
 Selective serotonin reuptake inhibitors (SSRIs, a class of antidepressants)
 3,4-Methylenedioxymethamphetamine (MDMA, commonly called Ecstasy.
SIADH due to taking ecstasy was cited as a factor in the deaths of Anna
Wood and Leah Betts)
 Oxytocin
 Vincristine
 Morphine
 Amitriptyline
Inherited mutations that cause aquaporins always to be "turned on"
Miscellaneous largely transient  Endurance exercise
conditions  General anaesthesia

76. SIADH presentation

Symptoms Signs
 Headache  Seizures
 Confusion  Reduced GCS
 Lethargy  Coma
 Anorexia  Myoclonus
 Ataxia
 Hyporeflexia
 Asterixis
77. SIADH investigation and dx
 In the absence of a single laboratory test to confirm the diagnosis, SIADH is best
defined by the classic Bartter-Schwartz criteria, which can be summarized as follows
 Hyponatremia with corresponding hypo-osmolality
 Continued renal excretion of sodium
 Urine less than maximally dilute
 Absence of clinical evidence of volume depletion
 Absence of other causes of hyponatremia
 Correction of hyponatremia by fluid restriction

 The following laboratory tests may be helpful in the diagnosis of SIADH:

 Serum sodium, potassium, chloride, and bicarbonate
 Plasma osmolality
 Serum creatinine
 Blood urea nitrogen
 Blood glucose
 Urine osmolality
 Serum uric acid
 Serum cortisol
 Thyroid-stimulating hormone
 Plasma AVP level
- The patient’s volume should be assessed clinically to help rule out the presence of
hypovolemia.
- Imaging studies that may be considered include the following:
 Chest radiography (for detection of an underlying pulmonary cause of SIADH)
 Computed tomography or magnetic resonance imaging of the head (for detection of
cerebral edema occurring as a complication of SIADH, for identification of a CNS
disorder responsible for SIADH, or for helping to rule out other potential causes of a
change in neurologic status)

78. SIADH mx
 Treatment of SIADH and the rapidity of correction of hyponatremia depend on the
following:
 Degree of hyponatremia
 Whether the patient is symptomatic
 Whether the syndrome is acute (<48 hours) or chronic
 Urine osmolality and creatinine clearance
 Management of SIADH includes
 Removing the underlying cause when possible.
 Mild and asymptomatic hyponatremia is treated with adequate solute intake
(including salt and protein) and fluid restriction starting at 500 ml per day of
 water with adjustments based on serum sodium levels. Long-term fluid restriction of
1,200–1,800 mL/day may maintain the person in a symptom free state.
 Moderate and symptomatic hyponatremia is treated by raising the serum sodium
level by 0.5 to 1 mmol per liter per hour for a total of 8 mmol per liter during
the first day with the use of furosemide and replacing sodium and potassium
losses with 0.9% saline.
 For people with severe symptoms (severe confusion, convulsions, or coma)
hypertonic saline (3%) 1–2 ml/kg IV in 3–4 h should be given. The presence of
cerebral edema may necessitate intravenous isotonic or hypertonic saline
administration.
 Drugs
 Demeclocycline can be used in chronic situations when fluid restrictions are
difficult to maintain; demeclocycline is the most potent inhibitor of Vasopressin
(ADH/AVP) action. However, demeclocycline has a 2–3 day delay in onset with
extensive side effect profile, including skin photosensitivity, and
nephrotoxicity.[15]
 Urea: oral daily ingestion has shown favorable long-term results with protective
effects in myelinosis and brain damage.[15] Limitations noted to be undesirable
taste and is contraindicated in people with cirrhosis to avoid initiation or
potentiation of hepatic encephalopathy.
 Conivaptan – an antagonist of both V1A and V2 vasopressin receptors.[15]
 Tolvaptan – an antagonist of the V2 vasopressin receptor
 If the duration of hyponatremia is unknown and the patient is asymptomatic, it is
reasonable to presume chronic SIADH. Diagnosis and treatment of the underlying cause
of SIADH are also important.
 In an emergency setting, aggressive treatment of hyponatremia should always be weighed
against the risk of inducing central pontine myelinolysis (CMP). Such treatment is
warranted as follows:
 Indicated in patients who have severe symptoms (eg, seizures, stupor, coma, and
respiratory arrest), regardless of the degree of hyponatremia
 Strongly considered for those who have moderate-to-severe hyponatremia with a
documented duration of less than 48 hours
 The goal is to correct hyponatremia at a rate that does not cause neurologic
complications, as follows
 Raise serum sodium by 0.5-1 mEq/hr, and not more than 10-12 mEq in the first 24
hours
 Aim at maximum serum sodium of 125-130 mEq/L

79. Osmotic demyelination syndrome

 Osmotic demyelination syndrome, also termed cerebral pontine myelinolysis, it is
caused by rapid correction of hyponatraemia.
 This syndrome occurs due to a rapid increase in extracellular osmolality. It can
cause irreversible neurological damage. As such, in the absence of severe
neurological features, sodium correction should not exceed 8-10 mmol/L per 24
hours.

80. SIADH vs Diabetes insipidus

 81. Diabetes insipidus
 Passage of large volume ( > 3 litre/day) of dilute urine due to impaired water
resorption by kidney, because of decreased ADH secretion from posterior pituitary /
impaired response of kidney to ADH
 Presentation
 Polyuria, polydipsisa, dehydration, hyponatraemia, lethargy, thirst, confusion,
coma

82. Diabetes insipidus causes

Cranial Nephrogenic
 Idiopathic (50%)  Congenital
 Congenital : defect in ADH gene; DIADMOAD /  Metabolic : decreased K, increased Ca
Waldram syndrome  Drugs : Lithium, demoxleocycline
 Tumour  Chronic kidney disease
 Trauma  Post obstructive uropathy
 Vascular : haemorrhage (Sheehan’s syndrome)
 Infection : meningoencephalitis
 Infiltration : sarcoidosis

83. Diabetes insipidus ix and dx

 Investigations
 Blood

U&E  In primary polydipsia there may be dilutional hyponatraemia—and as hyponatraemia may

itself cause mania, be cautious of saying “It’s water intoxication from psychogenic
polydipsia”.
Ca
Glucose  Exclude DM
Plasma  Normal plasma osmolality is 285–295mOsmol/kg, and urine can be concentrated to more
osmolality than twice this concentration.
 Significant DI is excluded if urine to plasma (U : P) osmolality ratio is more than 2 : 1,
provided plasma osmolality is no greater than 295mOsmol/kg. In DI, despite raised plasma
osmolality, urine is dilute with a U : P ratio <2

 Imaging
 MRI pituitary : This should be performed in all cases with confirmed central
DI, or documented abnormality of pituitary function and urgently if there is
visual field loss or optic disc pallor.
 PET CT : This may be considered after oncology and multidisciplinary team
review, if a germ cell tumour is suspected.
 Chest radiograph : All patients presenting with a new DI or pituitary mass
should have a CXR performed as an assessment of general health and as a
simple screen for underlying malignancy, inflammatory or granulomatous
disease.
 Others
 Electrocardiogram : This is essential in patients with electrolyte imbalance,
and is usefully performed at presentation as it is required prior to performing
an insulin stress test, or considering general anaesthesia.
 Visual perimetry and acuity : Formal visual field testing is mandatory if
there is clinical or MRI suspicion of chiasmal impingement.

 Diagnosis
 Water deprivation test
 Aims to test the kidney ability to concentrate urine for diagnosis of DI, and
the localize the cause
 It is often difficult to differentiate primary polydipsia from partial DI

 Vasopressin test
 After the water deprivation test, you may be given a small dose of AVP,
usually as an injection.
 This will show how your body reacts to the hormone, which helps to
identify the type of diabetes insipidus you have.
 If the dose of AVP stops you peeing urine, it's likely your condition is the
result of a shortage of AVP.
 If this is the case, you may be diagnosed with cranial diabetes insipidus.
 If you continue to pee despite the dose of AVP, this suggests there's already
enough AVP in your body, but your kidneys are not responding to it.
  In this case, you may be diagnosed with nephrogenic diabetes insipidus.

84. Diabetes insipidus mx

 Emergency
 Do urgent plasma U&E, serum and urine osmolalities
 Monitor urine output carefully and check U&E twice a day initially
 IVI to keep up with urine output. If severe hypernatraemia, do not lower Na+
rapidly
 As this may cause cerebral oedema and brain injury. If Na+ is ≥170, use 0.9%
saline initially—this contains 150mmol/L of sodium. Aim to reduce Na+ at a
rate of less than 12mmol/L per day. Use of 0.45% saline can be dangerous.
 Desmopressin 2μg IM (lasts 12–24h) may be used as a therapeutic trial.

 Treatment
Cranial Nephrogenic
 Find cause  Treat the cause
 Brain MRI  If it persists, try Bendroflumethiazide
 Test anterior pituitary function  NSAID lower urine volume and plasma Na by
 Give desmopressin (a synthetic analogue of ADH) inhibiting prostaglandin synthase; prostaglandin
locally inhibits action of ADH

85. Pituitary tumour

 Pituitary tumours (almost always benign adenomas) account for 10% of
intracranial tumours

Pathology  Many are non – secretory

 ~ 50% produce prolactin
Others produce GH / ACTH
Size  Microadenoma : < 1cm
 Macroadenoma : > 1 cm
Histology  Chromophobe Many non – secratory
(70%) Some cause hypopituitarism
50% produce Prolactin.Few produce ACTH / GH
Local pressure effects : 30%
 Acidophil Secrete GH / prolactin
(15%) Local effects : 10%
 Basophil (15% Secrete ACTH
Local pressure effects is rare

86. Pituitary tumour presentation

Mass effects Hormonal effects

 Headache  Prolactin : galactorrhoea, decreased libido,
 Visual field defect L bitemporal hemianopia (due to amenorrhoea, erectile dysfunction
compression of optic chiasm)  Increased Prolactin  decreased GnRH 
 CN palsies (3, 4, 5, 6); pressure on carvenous sinus decreased LH / FSH
 Diabetes insipidus  GH : acromegaly
 CSF  ACTH : cushing’s disease
 Rhinorrrhoea

87. Pituitary tumour investigations

 MRI
 Visual field test
 Hormoone : PRL, IGF, ACTH, Cortisol, TFT, LH/FSH

88. Pituitary tumour treatment

Medical  Replace hormone

 Treat excess hormone
Surgery (trans – sphenoidal  Pre – op hydrocortisone
excision)  Post – op dynamic pituitary test
Radiotherapy  Sterptactic; good for residual / recurrent adenoma

89. Pituitary apoplexy

 Pituitary apoplexy or pituitary tumor apoplexy is bleeding into or impaired blood
supply of the pituitary gland at the base of the brain.This usually occurs in the
presence of a tumor of the pituitary, although in 80% of cases this has not been
diagnosed previously.
 Presentation

 Diagnosis
 The diagnosis is achieved with magnetic resonance imaging and blood tests.
 Treatment
 Treatment is by the timely correction of hormone deficiencies, and in many cases
surgical decompression is required.
 Many people who have had a pituitary apoplexy develop pituitary hormone
deficiencies and require long-term hormone supplementation.

90. Hypopituitarism causes

Hypothalamus Pituitary stalk Pituitary

 Kallaman’s syndrome  Trauma, surgery  Tumor, irridation, inflammation
 Tumor  Tumor – mass lesion;  Autoimmune (haemachromatosis,
 Inflammation craniopharyngioma, meningioma amyloid, metastases)
 Infection (meningitis,  Carotid artery aneurysm  Ischaemia,; apoplexy, Sheehan’s
TB) syndrome
 Ischaemia
  Acquired hypopituitarism

91. Hypopituitarism presentation

 Hormone deficiency
 GH lack : central obesity, atherosclerosis, decreased CO, decreased strength,
decreased balance, osteoporosis,decreased glucose
 Gonadotrophin (FSH, LH)
 M : decreased libido, erectile dysfunction, decreased hair
 F : decreased libido, amenorrhea, breast atrophy
 TSH : hypopituitarism
 Corticotrophin (ACTH) : secondary adrenal insufficiency
 Prolactin : absent lactation
 Causes
 Pituitary tumor causing mass effect, or hormone secretion with decreased
secretion of other hormone – eg prolactinoma, acromegaly, rarely Cushing’s

92. Hypopituitarism investigation

 The triple stimulation test is now rarely done.
 Basal tests
 LH and FSH (increased or maintained)
 Testosterone or oestradiol (decreased )
 TSH (decreased or maintain)
 T4 (decreased);
 Prolactin (may be increased, from loss of hypothalamic dopamine that normally
inhibits its release)
 Insulin-like growth factor-1 (IGF-1; decreased —used as a measure of GH axis,),
cortisol (decreased)
  Also do U&E (Na+ decreased from dilution), Hb decreased(normochromic,
normocytic).
- Dynamic tests
 Short Synacthen® test: to assess the adrenal axis
 Insulin tolerance test (ITT):
 Done in specialist centers to assess the adrenal and GH axes.
 CI: epilepsy, heart disease, adrenal failure.
 Consult lab first.
 It involves IV insulin to induce hypoglycaemia, causing stress to increase cortisol
and GH secretion. I
 t is done in the morning (water only taken from 22:00h the night before). Have
50% glucose and hydrocortisone to hand and IV access.
 Glucose must fall below 2.2mmol/L and the patient should become symptomatic
when cortisol and GH are taken. Normal: GH >20mU/L, and peak cortisol
>550nmol/L.
 Arginine + growth hormone releasing hormone test.
 Glucagon stimulation test is alternative when ITT is contraindicated.
- Investigate cause: MRI scan to look for a hypothalamic or pituitary lesion.

93. Multiple endocrine neoplasia

 MEN 1, 2a and 2b,
 There are functioning hormone – producing tumours in multiple organs ( inherited as
autosomal dominant)
 They comprise
 MEN 1,2
 Von Hippel – Lindau
 Peutz – Jeghers syndrome
 Carney complex
 MEN 1,2

1 2
a b
 Locus on chromosome 11.  Phaeochromocytoma
 Pancreatic islet cell tumour (insulinoma)  Medullary Ca of the thyroid (almost always bilateral; non MEN2
 Pituitary adenoma (mostly cases are almost always unilateral).
prolactinomas)  MEN 2a (Sipple Syndrome) has:  MEN 2b has: Marfanoid
 Primary hyperparathyroidism Primary hyperparathyroidism. Has habitus, mucosal
been shown to because by RET neuromas.
mutation
Screening  Biochemical  Genetic
Calcitonin, PTH, prolactin RET mutation
Fasting blood glucose  If confirmed, a
Pancreatic polypeptide thyroidectomy should be
Gastrin performed

Mnemonic
MEN I (3 Ps) - Pituitary, Parathyroid, Pancreatic
MEN IIa (1M,2Ps) - Medullary Thyroid Ca, Phaeochromocytoma, Parathyroid MEN IIb
(2Ms,1P) - Medullary Thyroid Ca, Marfanoid habitus/mucosal neuroma, Pheochromocytoma