Sunday, 18 April 2010


Hyper secretion of growth hormone due to a pituitary tumour.
Hyperplasia due to GHRH excess is very rare.
Overall incidence is approximately 3-4/million per year and prevalence 50-80/million.

Clinical features :
Symptoms result from mass effect of the adenoma or effect of the growth hormone.
One-third of patients present with changes in appearance,
One-quarter with visual field defects or headaches;
In the remainder the diagnosis is made by an alert observer in another clinic, e.g. GP, diabetic, hypertension, dental, dermatology.


1. Sleep apnea
2. Multiple skin tags
3. Adenomatus polyps
4. Hypercalcurea and renal stones
5. MEN I in 6%

Investigations :
1. GH levels may exclude acromegaly if undetectable but a detectable value is non-diagnostic. Normal adult levels are < 1 mU/L for most of the day except during stress or a 'GH pulse'.
2. The glucose tolerance test is diagnostic. Acromegalics fail to suppress GH below 1 mU/L and some show a paradoxical rise; about 25% of acromegalics have a diabetic glucose tolerance test.
3. IGF-1 levels are almost always raised in acromegaly - a single plasma level of IGF-1 reflects mean 24-hour GH levels and is useful in diagnosis.
4. Visual field defects are common.
5. MRI scan of pituitary - will almost always reveal the pituitary adenoma.
6. Pituitary function - partial or complete anterior hypopituitarism is common.
7. Prolactin - mild to moderate hyperprolactinaemia occurs in 30% of patients. In some, the adenoma secretes both GH and prolactin.

Management and treatment :
Untreated acromegaly results in markedly reduced survival with most deaths from heart failure, coronary artery disease and hypertension-related causes. In addition, there is an increase in deaths due to neoplasia, particularly large-bowel tumours.
Treatment is therefore indicated in all except the elderly or those with minimal abnormalities.

There is now consensus agreement that the aim of therapy should be to achieve a mean growth hormone level below 5 mU/L, which has been shown to reduce mortality to normal levels.

Complete cure is often slow, if possible at all.
The choice lies between :
→ trans-sphenoidal surgery,
→ pituitary radiotherapy,
→ somatostatin analogues,
→ Growth hormone agonists dopamine agonists.
Progress can be assessed by monitoring GH and IGF-1 levels..
When present, hypopituitarism should be corrected and concurrent DM and/or hypertension should be treated conventionally; both usually improve with treatment of the acromegaly

1-Surgery :
Trans-sphenoidal surgery is generally agreed as the appropriate first-line therapy.
It will result in clinical remission in a majority of cases (60-90%) with pituitary microadenoma, but in only 50% of those with macroadenoma.
Surgical success rates are variable and highly dependent upon experience, and a specialist pituitary surgeon is essential.
Transfrontal surgery is rarely required except for massive macroadenomas.

2-Pituitary radiotherapy :
External radiotherapy is normally used after pituitary surgery fails to normalize GH levels rather than as primary therapy.
It is often combined with medium-term treatment with a somatostatin analogue or a dopamine agonist because of the slow biochemical response to radiotherapy, which may take 10 years or more. Stereotactic radiotherapy is used in some centres.

3-Somatostatin analogues :
Octreotide and lanreotide are synthetic analogues of somatostatin which are the treatment of choice in resistant cases, and employed as a short-term treatment while other modalities become effective.
They reduce GH and IGF levels in most patients.
Both drugs are typically administered as monthly depot injections and are generally well tolerated but are associated with an increased incidence of gallstones and are expensive.

4-Dopamine agonists :
Dopamine agonists were the original medical therapy for acromegaly, and remain useful in some cases.
They can be given to shrink tumours prior to definitive therapy or to control symptoms and persisting GH secretion;
They are probably most effective in mixed growth-hormone-producing (somatotroph) and prolactin-producing (mammotroph) tumours.
The doses are bromocriptine 10-60 mg daily or cabergoline 0.5 mg daily (higher than for prolactinomas) but should be started slowly.
Given alone they reduce GH to 'safe' levels in only a minority of cases - but may be useful for mild residual disease or in combination with somatostatin analogues.

5-Growth hormone antagonists :
Pegvisomant (a genetically modified analogue of GH) is a GH receptor antagonist which has its effect by binding to and preventing dimerization of the GH receptor. It has been shown to normalize IGF-1 levels in 90% of patients. Its main role at the present time is treatment of patients in whom GH and IGF levels cannot be reduced to safe levels with somatostatin analogues alone, surgery or radiotheraphy.

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Syndrome of inappropriate antidiuretic hormone (SIADH)

ADH is secreted by supraoptic and paraventricular nuclei in the hypothalamus and transmitted via the neuronal axons to the posterior pituitary where it is secreted.
It is released when a decrease in the effective circulatory volume is sensed by vascular baroreceptors primarily located in the large arterial vessels.

ADH continues to be secreted regardless of the plasma osmolality.
Usually ADH is secreted when plasma osmolality increase.
As a result urine continues to concentrate while plasma osmolality remain low.

Urine concentration and urinary Na inappropriately high in a patient with hyponatraemia and hypo osmolar serum.

Clinical features:
Inappropriate secretion of ADH leads to retention of water and hyponatraemia.
Mild symptoms usually occur with plasma sodium levels below 125 mmol/L and serious manifestations are likely below 115 mmol/L. The elderly may show symptoms with milder abnormalities.

Common causes:
Tumours :
1. Small-cell carcinoma of lung
2. Prostate
3. Thymus
4. Pancreas
5. Lymphomas
Pulmonary lesions:
1. Pneumonia
2. Tuberculosis
3. Lung abscess
CNS causes:
1. Meningitis
2. Tumours
3. Head injury
4. Subdural haematoma
5. Cerebral abscess
6. SLE vasculitis
Metabolic causes :
1. Alcohol withdrawal
2. Porphyria
Drugs :
1. Chlorpropamide
2. Carbamazepine
3. Cyclophosphamide
4. Vincristine
5. Phenothiazines

Urine osmolality above plasma osmolality is diagnostic

Dil plasma : plasma osmo <260 , plasma Na <120
Conc urine : urine osmo > 280 , urine Na > 20

The usual features are:
• dilutional hyponatraemia due to excessive water retention
• low plasma osmolality with 'inappropriate' urine osmolality which is higher than plasma osmolality
• continued urinary sodium excretion > 30 mmol/L
• absence of hypokalaemia (or hypotension)
• Normal renal and adrenal and thyroid function.

The underlying cause should be corrected where possible. Symptomatic relief can be obtained by the following measures:
1. Fluid intake should be restricted to 500-1000 mL daily. If tolerated, and complied with, this will correct the biochemical abnormalities in almost every case.
2. Plasma osmolality and sodium and bodyweight should be measured frequently.
3. If water restriction is poorly tolerated or ineffective, demeclocycline (600-1200 mg daily) may be given; this inhibits the action of vasopressin on the kidney, causing a reversible form of nephrogenic diabetes insipidus. It often, however, causes photosensitive rashes.
4. When the syndrome is very severe, rarely hypertonic saline (300 mmol/L slowly i.v.) is given and furosemide may be used. These treatments are potentially dangerous and should only be used with extreme caution.

furhter reading

endocrinology Q1

A 65-year-old female is admitted with an intracranial bleed under the care of the neurosurgeons. Following Magnetic resonance angiography she undergoes clipping of an cerebral arterial aneurysm and was well the following morning.
The surgical team document the following blood chemistry results on successive postoperative days:
Day 1:Plasma Sodium 130 mmol/L, Potassium 3.5 mmol/L, Urea 4.2 mmol/L, Creatinine 95 µmol/L
Day 2:Plasma Sodium 127 mmol/L, Potassium 3.4 mmol/L, Urea 4.2 mmol/L, Creatinine 90 µmol/L
Day 3:Plasma Sodium 124 mmol/L, Potassium 3.4 mmol/L, Urea 4.4 mmol/L, Creatinine 76 µmol/L
Day 4:Plasma sodium 120 mmol/L, Potassium 3.5 mmol/L, Urea 5 mmol/L, Creatinine 70 µmol/L
Normal Range:Plasma sodium 137-144 mmol/L, Potassium 3.5-4.9 mmol/L, Urea 2.5-7.5 mmol/L, Creatinine 60-110 µmol/L
On day 4 she was commenced on a fluid restriction of 1 litre per day. Investigations at that time show:
Plasma osmolality:262 mOsmol/L (278-305)
Urine osmolality:700 mOsmol/L (350-1000)
Urine sodium:70 mmol/L

Select the most likely diagnosis to explain these findings?
1-Cranial diabetes insipidus
3-Fluid overload
4-Syndrome of inappropriate ADH (SIADH)
5-Sick cell syndrome

endocrinology Q2

a 70 years old man is admitted in a confused state.on examination he is apyrexial and ther is no focal neurological signs.HR 75 bpm, Bp 130/90 without postural drop.the chest is clear and abdomen is unremarkable.these are the blood findings:
Hb 13.5
WBC 5.5
plt 220

Na 108
K 4.5
urea 10
creatinie 80
glucose 4.5

bili 8
AST 20
ALT 21
ALP 65

what is the most likely cause?
1-diabetes insipidus
4-addison's disease
5-water intoxication

what investigation should be organised next?
1-water deprivation
2-short synachtin test
3-paired urine and serum osmolalties
5-CT head

Thursday, 16 July 2009

Atrial fibrillation

Atrial fibrillation;


Guide to rate control


• Digoxin is ineffective in controlling ventricular rate during acute episodes and    paroxysmal episodes and in states with high sympathetic tone such as

Thyrotoxicosis, critical illness, and postoperative states.

Digoxin is also ineffective for cardioversion


• In patients with good left ventricular function, beta blockers (metoprolol, propranolol, and atenolol) or non-dihydropyridine calcium antagonists (verapamil and diltiazem) are the drugs of choice, provided no contraindications exist


• In patients with acute or chronic heart failure, digoxin or Amiodarone should be used.

The chronic use of amiodarone is limited by its side effects.

Beta blockers may be considered in patients with stable heart failure


• Although digoxin does not provide good rate control in acute episodes, it is generally effective for rate control in persistent atrial fibrillation when used

in combination with beta  blockers and rate limiting calcium antagonists


• The adequacy of rate control should be assessed by the clinical symptoms


• Target heart rates vary with age. They should generally be 60-90 beats per minutes at rest and 90-115 beats per minute during exercise. This requires

careful dose titration


• Poor ventricular rate control in the long term leads to a reversible deterioration of left ventricular function (tachycardiomyopathy)



Guide to rhythm control


• Identify and treat all reversible causes of atrial fibrillation before considering drug treatment for maintenance of sinus rhythm.

Pharmacological cardioversion is effective when initiated within 7 days of the onset of arrhythmia.


• The selection of antiarrhythmic drug needs to be tailored individually to the patient, depending on cardiac status, comorbidities, and contraindications.

With the potential side effect of antiarrhythmic drugs, pharmacological cardioversion should be reserved for haemodynamically stable patients with symptoms.



Sotalol or amiodarone can also be used in such patients.


Amiodarone can be used to maintain sinus rhythm in patients with heart failure. Although not currently licensed in the United Kingdom, dofetilide is an



Beta blockers are the drugs of choice for patients with coronary artery disease.


• If sinus rhythm cannot be maintained despite repeated cardioversions and antiarrhythmic treatment, a “rate control” strategy should be adopted. This has

been shown to be as effective as rhythm control.


• Patients who find the symptoms of the arrhythmia unacceptable despite rate control may be considered for non-pharmacological methods to restore sinus rhythm.


Electrical cardioversion is a save procedure with success rate of 70-90%.

  It is used acutely in patients who are haemodynamically compromised or electively as alternative to pharmacological cardioversion.

Tuesday, 14 July 2009

Proliferative glomerulonepheritis

Proliferative glomerulonepheritis


  1. diffuse GN
  2. focal segmental GN
  3. rapidly progressive GN
  4. mesangiocappilary GN
  5. Ig A nephropathy



1-Diffuse glomerulonepheritis


Mostly young patients

Clinical features:

Minor Proteinurea

Nephritic syndrome

Mostly post infective


Good prognosis

Light microscopy: proliferation of the endothelial and mesangial cells with neutrophills.all glomeruli similarly affected

Immune florescence: Ig G,C3

Electrone microscopy: subepithilial deposits


Acute phase: antihypertensive, duretics, salt restriction and dialysis if needed.



Post streptococcal GN (group A β haemolytic streptococci)

  Typically preceded by sorethroat or skin disease (impetigo) 10-14 days






2-Focal segmental glomerulonepheritis


any age

Clinical features:


Nephrotic syndrome


Renal failure


Good prognosis

Light microscopy: focal sclerosis with hyaline deposits

                             Only some glomeruli show the Proliferative changes

Immune florecence: Ig M ,C3

Electrone microscopy:




Shunt nephritis






IV drug user




 3-Rapidly progressive glomerulonepheritis


Mostly older pateints

Clinical features:

Acute renal failure





bad prognosis

 Light microscopy: hypercellularity

                              Crescent formation: aggregation of macrophages and epithelial cell         

                              In bowman capsule in 80% of glomeruli

Immune florescence: Ig G C3

Electrone microscopy:






Anti GBM antibodies



Microscopic polyangitis






4-Mesangiocappilary glomerulonepheritis


under age

Clinical features:

Proteinurea, haematourea

Nephrotic syndrome

Renal failure


Bad prognosis

 Light microscopy: celluar expansion of the mesangium

                            BM appears split;tram track

Immune florecence:C3 nepheritic factor(Ig G to C3)

Electrone microscopy: type I subendothial deposits

                                    Type II basement membrane deposit



Shunt nephritis



Sickle cell disease

Alfa antitrypsin def


C3 nepheritic factor


Kartager’s syndrome

Hep C




5-Ig A nephropathy (Berger’s disease)


Mostly young adults

The most common cause of microscopic haematourea


Clinical features:

Macro or microscopic haematourea

Minor proteinurea

Usually 0-3 days post URT infection

Increase serum Ig A in 50%


10% progress to renal failure

 Light microscopy: mesangial cell proliferation

Immune florecence:Ig A ,C3

Electron microscopy:

 Histology is similar to HLP



Proteinurea and mild disease: steroids

Progressive disease: prednisolone with Cyclophosphamide for 3 month

Consider tonsillectomy



Dermatitis herpictiformis

Celiac disease

Mycosis fungoides

Wiskott - Aldrich syndrome



Primary Hyperlipidaemia:

Frederickson’s classification


  1. Type I

Lipoprotein lipase deficiency

Defect: mutant or absent LDL, elevated chylomicrons.

Result in failure to metabolize chylomicrone and elevated triglycerides

Present in childhood with:

  1. Eruptive xanthomas
  2. Lipaemia retinalis
  3. Retinal vein thrombosis
  4. Pancreatitis
  5. Hepatosplenomegaly

      Chylomicrons floating like cream on top of fasting plasma suggest the diagnosis

      Cholesterol normal or ↑, triglyceride↑↑↑↑

      2-type II

Primary hypercholesterolemia

Defect: LDL receptor dysfunction

Typical features:

  1. Xanthelasmas
  2. Cuneal arcus
  3. Tendon xanthomas (Achilles tendon & extensor tendons of the hand)

       IIa elevated LDL, IIb elevated LDL, VLDL.

       Cholesterol ↑↑, triglyceride normal


3-type III

Remnant hyperlipidaemia/apo E homozygosity

Defect: mutant apo E, elevated IDL

Additional risk factor leads to accumulation of chylomicrone and VLDL

Plasma cholesterol and triglycerides are elevated

Typical features:

  1. CHD
  2. PVD
  3. Tuberoruptive xanthomas
  4. Palmer xanthomas

The xanthomata are triglyceride rich; they are irritant and may redden with scratch marks

Cholesterol↑↑, triglyceride↑↑↑






4-type IV

Familial combined Hyperlipidaemia

Both cholesterol and triglycerides are elevated

CHD common

The occurrence of different types of lipidaemia, with absence of peripheral stigmata, suggests the diagnosis.

Elevated VLDL

Cholesterol normal or ↑, triglyceride↑↑



5-type V

Familial hypertriglyceridaemia

Defect: unkown

Elevated VLDL and chylomicrons.                     

Cholesterol or ↑, triglyceride↑↑