Some time ago, I was referred a 21-year old Caucasian man who had had a red rash on his legs a couple of months ago. Over the same period, he had been to the Emergency Department twice with pain and redness in his right eye, diagnosed as acute uveitis. The GP wondered if he had vasculitis.
In his other history, he had lost a stone in weight (6.3 kg) in 6 months without really trying. Over the last 12 months, he had had recurrent pilonidal sinus related infections in his bottom, diagnosed and treated with antibiotics by his GP. There was no history of Raynaud's, oral or genital ulcers, sicca symptoms or psoriasis. There had been no joint pains. He did not smoke but drank lager at weekends.
His GP checked his blood and documented: Hb 10.8 g/dl, MCV 82, WBC 11, Neutrophils 9, ESR 120, CRP 85, urine 300 RBC (normally <45), no proteinuria, normal U&Es & LFTs. RF negative, ANA weak positive in a nucleolar pattern, ENA, dsDNA, ANCA negative.
Examination showed no rash or synovitis, normal systems and an apparently healthy looking man.
I made the diagnosis, but only after calling him at home to ask him a question I had omitted in clinic.
Thoughts?
Thursday, 18 July 2013
Saturday, 6 July 2013
A Sick Lady With An Abnormal Xray
Forty-five year old female, life-long non-smoker presents with with dyspnoea, fever, non productive cough, wheeze, night sweats and weight loss over several weeks. This is her X-ray. What's the diagnosis?
Picture, courtesy UpToDate.
Picture, courtesy UpToDate.
Sunday, 30 June 2013
The Acromegaly That Wasn't
One of the most challenging cases I have ever been asked about was regarding a 31 year old Caucasian man. When he walked into the Rheumatology clinic, referred by his GP with arthralgias and a raised, fluctuating CK, even the junior doctors felt he was a straightforward case of acromegaly. He had the classical facies, a large tongue that he felt was "growing" and tingling in his hands. CK fluctuated between 270 and 2000, yet muscle power, EMG and muscle biopsy were normal, as were numerous tests for metabolic myopathy.
He also reported more than one episode of near loss of consciousness. He saw the neurologists with this, who felt this was syncope. A tilt table test showed a sharp drop in BP while upright, associated with tachycardia.
Baseline IGF-1 and timed levels of Growth Hormone after stimulation with glucose were normal. MRI of pituitary revealed a microadenoma.
ECG was not done.
Echo was reported as normal. However, when you looked at the detail, the LV size was the upper limit of notmal, the left atrium was dilated and the E:A ratio at the mitral inlet was at the upper limit of normal at 1.48.
Nerve conduction studies showed no evidence of entrapment neuropathy at the wrist. Autoimmune screen, including every conceivable autoantibody in the book, was negative. Inflammatory parameters were normal.
Can you suggest a diagnosis?
He also reported more than one episode of near loss of consciousness. He saw the neurologists with this, who felt this was syncope. A tilt table test showed a sharp drop in BP while upright, associated with tachycardia.
Baseline IGF-1 and timed levels of Growth Hormone after stimulation with glucose were normal. MRI of pituitary revealed a microadenoma.
ECG was not done.
Echo was reported as normal. However, when you looked at the detail, the LV size was the upper limit of notmal, the left atrium was dilated and the E:A ratio at the mitral inlet was at the upper limit of normal at 1.48.
Nerve conduction studies showed no evidence of entrapment neuropathy at the wrist. Autoimmune screen, including every conceivable autoantibody in the book, was negative. Inflammatory parameters were normal.
Can you suggest a diagnosis?
Sunday, 23 June 2013
Tuesday, 18 June 2013
A Young Man With Hypercalcaemia
A 32 year old man is referred by his GP with hypercalcaemia. Corrected serum calcium is 2.75 mmol/l (11 mg/dl). Serum PTH is raised at 105 pg/ml (normally up to~70). Serum phosphate is normal. Serum 25(OH)D levels are at the upper limit of normal. Chest Xray is normal, as is a myeloma screen. Alkaline phosphatase is not raised. Renal function is normal, with an egfr of >90 ml/min.
What's the likely diagnosis?
What's the likely diagnosis?
Saturday, 8 June 2013
Trivial Signs?
I recently saw a middle aged man with a swelling at the base of his left middle finger. Just that. Nothing else. He didn't even have much pain. His GP had sent him to Rheumatology because he couldn't explain the symptoms.
He looked well. The left middle MCP was swollen. All other joints were normal. He had had lots of bloods in primary care, including FBC, U&Es, LFTs, ESR, CRP, Rheumatoid factor- all normal. A plain X-ray had revealed an odd looking cyst in the head of the 3rd metacarpal, but all else was normal.
There was no history of trauma.
Thoughts?
He looked well. The left middle MCP was swollen. All other joints were normal. He had had lots of bloods in primary care, including FBC, U&Es, LFTs, ESR, CRP, Rheumatoid factor- all normal. A plain X-ray had revealed an odd looking cyst in the head of the 3rd metacarpal, but all else was normal.
There was no history of trauma.
Thoughts?
Monday, 1 April 2013
Hypokalaemia & Hypertension
A relatively common problem in clinical practice is the young subject with hypertension in association with hypokalaemia and metabolic alkalosis. Physicians should resist the temptation of labeling this subset as "Essential Hypertension". A definitive diagnosis can be achieved with a bit of perseverance.
As medicine evolves, new paradigms displace old ones. Primary hyperaldosteronism was thought to be exceedingly rare. Not so. It is now recognised that 10-15% of subjects with hypertension have primary hyperaldosteronism. This is particularly true in young subjects, subjects with a strong family history of hypertension and those with hypokalaemia.
Yet, too much reliability has been placed on the presence of hypokalaemia as a marker of this condition. In fact, less than 50% of subjects with primary hyperaldosteronism have hypokalaemia. The rest are normokalaemic. Therefore it is important to have a high index of suspicion in young subjects, those with a strong family history of early onset hypertension, those with family history of stroke before age 40, and those with refractory hypertension, i.e. subjects whose BP remains uncontrolled despite three anti-hypertensives, including a diuretic.
The assessment should begin by measuring the ratio of plasma aldosterone to plasma renin activity (PRA). A ratio of >30 with an absolute concentration of aldosterone of>415 pmol/l and in particular, a completely suppressed PRA is virtually diagnostic of primary hyperaldosteronism.
The most common cause of this condition is idiopathic adrenal hyperplasia (IHA), causing bilateral hyperplasia of the adrenals, accounting for 65% of cases. Around 30% of cases are due to unilateral adrenal adenomas. The other 5% comprises 3 rare disorders- hereditary hyperaldosteronism types 1,2 and 3.
Type 1 hereditary hyperaldosteronism is a fascinating condition. Also called glucocorticoid remediable aldosteronism (GRA), this rare autosomal dominant condition is due to the fusion of two genes- CYB11B1 and CYB11B2, whereby the enzyme aldosterone synthase comes under the control of ACTH. Thus, aldosterone is made in the zona fasciculata rather than zona glomerulosa and is suppressible by steroid therapy. Half of these subjects have a normal serum potassium.
Type 2 is simply an inherited predisposition to adrenal adenoma or hyperplasia.
What if the plasma renin and aldosterone are both raised? Think of renovascular hypertension, renin secreting tumours, coarctation of aorta and subjects on diuretics.
Then there are those whose plasma renin and aldosterone are both suppressed. These subjects have a non-aldosterone related cause for their hypertension such as hypercortisolism due to Cushing's syndrome, Syndrome of Apparent Mineralocorticoid Excess (SAME), or excessive liquorice intake, certain causes of congenital adrenal hyperplasia such as 11-beta hydroxylase deficiency, deoxycorticosterone secreting tumours and Liddle's syndrome.
Two inherited conditions deserve special mention. SAME is a rare autosomal recessive condition due to inherited deficiency of 11-beta hydroxysteroid dehydrogenase deficiency. This is a renal enzyme that converts cortisol to inactive cortisone. When this enzyme is deficient or inhibited by liquorice, or overwhelmed by excessive production of cortisol, as in Cushing's syndrome (particularly due to ectopic ACTH production from small cell or other tumours), cortisol is freed up to act on the mineralocorticoid receptors and mimic the action of aldosterone. These patients tend to have a very low serum potassium.
The other inherited disorder with suppressed aldosterone and renin levels is Liddle's syndrome. This is an autosomal dominant condition where epithelial sodium channels responsible for reabsorption of tubular sodium at the expense of potassium remain constitutively open due to inability to remove the beta or gamma subunits of these channels. The removal of these channels from the tubular epithelium depends on an uniquitin ligase called Nedd, which is defective in Liddle's patients. Intuitively, direct potassium channel blockers such as amiloride and triamterene work well in the treatment of hypertension in Liddle's syndrome, while aldosterone antagonists such such as spironolactone do not. It's worth remembering that as in GRA, over half of subjects with Liddle's syndrome have normal serum potassium.
In subjects with high aldosterone:PRA ratio, the next test is salt loading to see if the serum aldosterone levels are suppressible. This can be done as an inpatient after infusing IV saline, or as an outpatient, after loading for 3 days with oral salt tablets. Subjects with primary aldosteronism will not suppress their aldosterone levels after salt loading.
Such subjects should then have a CT scan to pick up an adrenal adenoma putatively responsible for the excess aldosterone. If the CT does not show an adenoma, and irrespective of the CT results in subjects over the age of 40, most authorities would recommend that patients should have adrenal vein sampling for aldosterone:cortisol ratio to distinguish functional adenoma from IHA. Subjects under 40 with an obvious adenoma on CT should be directly considered for surgical adrenalectomy. Conversely, those with IHA would benefit from medical management with spironolactone.
Acknowledgement: uptodate.com
As medicine evolves, new paradigms displace old ones. Primary hyperaldosteronism was thought to be exceedingly rare. Not so. It is now recognised that 10-15% of subjects with hypertension have primary hyperaldosteronism. This is particularly true in young subjects, subjects with a strong family history of hypertension and those with hypokalaemia.
Yet, too much reliability has been placed on the presence of hypokalaemia as a marker of this condition. In fact, less than 50% of subjects with primary hyperaldosteronism have hypokalaemia. The rest are normokalaemic. Therefore it is important to have a high index of suspicion in young subjects, those with a strong family history of early onset hypertension, those with family history of stroke before age 40, and those with refractory hypertension, i.e. subjects whose BP remains uncontrolled despite three anti-hypertensives, including a diuretic.
The assessment should begin by measuring the ratio of plasma aldosterone to plasma renin activity (PRA). A ratio of >30 with an absolute concentration of aldosterone of>415 pmol/l and in particular, a completely suppressed PRA is virtually diagnostic of primary hyperaldosteronism.
The most common cause of this condition is idiopathic adrenal hyperplasia (IHA), causing bilateral hyperplasia of the adrenals, accounting for 65% of cases. Around 30% of cases are due to unilateral adrenal adenomas. The other 5% comprises 3 rare disorders- hereditary hyperaldosteronism types 1,2 and 3.
Type 1 hereditary hyperaldosteronism is a fascinating condition. Also called glucocorticoid remediable aldosteronism (GRA), this rare autosomal dominant condition is due to the fusion of two genes- CYB11B1 and CYB11B2, whereby the enzyme aldosterone synthase comes under the control of ACTH. Thus, aldosterone is made in the zona fasciculata rather than zona glomerulosa and is suppressible by steroid therapy. Half of these subjects have a normal serum potassium.
Type 2 is simply an inherited predisposition to adrenal adenoma or hyperplasia.
What if the plasma renin and aldosterone are both raised? Think of renovascular hypertension, renin secreting tumours, coarctation of aorta and subjects on diuretics.
Then there are those whose plasma renin and aldosterone are both suppressed. These subjects have a non-aldosterone related cause for their hypertension such as hypercortisolism due to Cushing's syndrome, Syndrome of Apparent Mineralocorticoid Excess (SAME), or excessive liquorice intake, certain causes of congenital adrenal hyperplasia such as 11-beta hydroxylase deficiency, deoxycorticosterone secreting tumours and Liddle's syndrome.
Two inherited conditions deserve special mention. SAME is a rare autosomal recessive condition due to inherited deficiency of 11-beta hydroxysteroid dehydrogenase deficiency. This is a renal enzyme that converts cortisol to inactive cortisone. When this enzyme is deficient or inhibited by liquorice, or overwhelmed by excessive production of cortisol, as in Cushing's syndrome (particularly due to ectopic ACTH production from small cell or other tumours), cortisol is freed up to act on the mineralocorticoid receptors and mimic the action of aldosterone. These patients tend to have a very low serum potassium.
The other inherited disorder with suppressed aldosterone and renin levels is Liddle's syndrome. This is an autosomal dominant condition where epithelial sodium channels responsible for reabsorption of tubular sodium at the expense of potassium remain constitutively open due to inability to remove the beta or gamma subunits of these channels. The removal of these channels from the tubular epithelium depends on an uniquitin ligase called Nedd, which is defective in Liddle's patients. Intuitively, direct potassium channel blockers such as amiloride and triamterene work well in the treatment of hypertension in Liddle's syndrome, while aldosterone antagonists such such as spironolactone do not. It's worth remembering that as in GRA, over half of subjects with Liddle's syndrome have normal serum potassium.
In subjects with high aldosterone:PRA ratio, the next test is salt loading to see if the serum aldosterone levels are suppressible. This can be done as an inpatient after infusing IV saline, or as an outpatient, after loading for 3 days with oral salt tablets. Subjects with primary aldosteronism will not suppress their aldosterone levels after salt loading.
Such subjects should then have a CT scan to pick up an adrenal adenoma putatively responsible for the excess aldosterone. If the CT does not show an adenoma, and irrespective of the CT results in subjects over the age of 40, most authorities would recommend that patients should have adrenal vein sampling for aldosterone:cortisol ratio to distinguish functional adenoma from IHA. Subjects under 40 with an obvious adenoma on CT should be directly considered for surgical adrenalectomy. Conversely, those with IHA would benefit from medical management with spironolactone.
Acknowledgement: uptodate.com
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