Medullary Thyroid Cancer

Yesterday in morning report we had a really interesting case of medullary thyroid cancer presenting with chronic diarrhea and complicated by heart failure, likely secondary to amyloidosis.

A little more about medullary thyroid cancer (MTC):

- MTC can be either sporadic or inherited. Inherited forms involve mutations to the RET proto-oncogene and can be either be alone or as part of one of the Multiple Endocrine Neoplasia syndromes- MEN 2A or MEN 2B.

- MEN 2A is characterized by MTC with hyperparathyroidism and/or pheochromocytoma

- MEN 2B is characterized by MTC with typical phenotyic features such as marfanoid body habitus or mucosal neuromas with or without pheochromocytoma.

- Most patients present with a thyroid mass, but some present with symptoms of local spread such as dysphagia, dyspnea, or hoarseness. Roughly 10% will present with systemic symptoms related to the production of neuroendocrine mediators such as calcitonin, resulting in bone pain, flushing, and/or diarrhea.

- Those that present with systemic symptoms usually have metastatic disease.

- More in a review from Cancer here

We also found out through our group searching excercise that MTC is associated with secondary amyloidosis casued by calcitonin.

-A good related article sent out by Dr. Abrams here.

- More on amyloidosis from a prior post here.

Takotsubo cardiomyopathy

The amuse-bouche today was a case of Takotsubo cardiomyopathy. A few points:
•It is also known as :Stress-induced cardiomyopathy, apical ballooning syndrome, or broken heart syndrome
•Characterize d by transient systolic dysfunction of the apical and/or mid segments of the left ventricle
–mimics myocardial infarction with ST segment changes
–absence of obstructive coronary artery disease
•Typically presets w. RSCP, but occassionaly with new onset dyspnea
–Women >> Men
–Often at time of intense physical or emiotional stress
•Pathogenesis not well understood
–? Catecholamine surge
–? Vasospasm

See a nice brief article in CMAJ here.

Acute Cardiac Tamponade

Today's morning report case was of a patient with cancer presenting with sudden onset dyspnea and a new pericardial effusion. We had a great discussion about cardiac tamponade. A few points:
Cardiac tamponade is a clinical syndrome with a few defining characteristics:
-hemodynamic instability (hypotension, tachycardia)
-dyspnea
-pulsus paradoxus >10 mmHg
-jugular venous distention
- reduced heart sounds

The primary physiologic abnormality is compression of all cardiac chambers as a result of increasing intrapericardial pressure, which is mostly determined by the rapidity of fluid accumulation, rather than the absolute size of an effusion.

The diagnostic modality of choice is doppler echocardiography. In the presence of an effusion, some echocardiographic signs of tamponade:
- Early diastolic collapse of the right ventricle
- Late diastolic collapse of the right atrial free wall

• Less specific than RV collapse unless lasting for >30% of cardiac cycle

-Left atrial collapse

• Only in 25% of cases, but is highly specific

-Accentuated respiratory variation in peak mitral and tricuspid inflow velocities

-Reduction/absence of the normal decrease in inferior vena cava diameter during inspiration

See here for a good NEJM review
See here for the JAMA acticle "Does This Patient With a Pericardial Effusion Have Cardiac Tamponade?"

Auricular cartilage calcification

The amuse-bouche today was auricular cartilage calcification in adrenal insufficiency taken from the NEJM images in medicine series.

Auricular cartilage calcification and even true ossification of the auricular cartilages have been described in association with:
–mechanical tissue injury
–exposure to cold
–inflammatory conditions
–endocrinopathies including adrenal isufficiency

See more from NEJM here.

Hemoptysis

Morning report today was a great case of hemoptysis. See here for a prior post with links to a few good review articles.

Digitalis Effect

Today our amuse-bouche was an ECG with typical changes from digoxin.
The classic digitalis effect has 4 typical findings on ECG:
1.T-wave changes

• Virtually any: flattening, inversion, other abnormal waveforms such as peaking of the terminal portion (seen in about 10% of patients)
  

2.QT-interval shortening

3.Sagging or “scooped” ST-segment with concomitant ST-segment depression

• More pronounced in leads with tall R waves (e.g. lateral leads)
  

4.Increase in the U-wave amplitude

It is important to remember that these do not correlate with toxicity as they can be seen at levels well within normal therapeutic range.

For a good review on this and the other important arrythmias assiociated with digoxin toxixicy, see here.

Systolic heart failure

Today in morning report we had a case of new grade 4 systolic heart failure. See here for a prior post on diagnosis. We talked briefly at the end about device therapies, see here for a prior post on the topic, with links to some of the major trials.

von Recklinghausen disease

Today the amuse-bouche was a case of von Recklinghausen disease, better known as neurofibromatosis type 1.

A few points about NF-1:

•It is a neurocutaneous syndrome resulting from a mutation in NF1 gene
–Autosomal dominant inheritance

–1/2 are familial; 1/2 new mutations
–New mutations primarily in paternal chromosomes
–Complete penetrance but variable expression

•At least 2 of the following features needed to make the diagnosis:
–6 or more café-au-lait macules
–2 or more neurofibromas of any type or one plexiform neurofibroma
–Freckling in the axillary or inguinal regions
–Optic glioma
–2 or more Lisch nodules (iris hamartomas)
–A distinctive bony lesion such as sphenoid dysplasia or thinning of the long bone cortex

–A first-degree relative (parent, sibling, or offspring) with NF1 based upon the above criteria

See here for a good review paper in the Lancet

Palliative feeding

Today in morning report we talked about a few palliative issues, but the issue of feeding at the end of life came up. See here for a prior post on that contains a link to a good review article on the topic of nutrition and hydration at the end of life.

Vertigo

Morning Report today was a case of vertigo, likely Benign Paroxysmal Positional Vertigo.

A prior post on differentiating the central and peripheral casues of vertigo here. See the bootom for more info on the Eply manuvers.

Infective endocarditis

Morning report today was a case of presumed endocarditis in a VERY susceptible host. See a prior post here with a link at the bottom to the AHA 2008 update.

ECG limb-lead reversal

Amuse-bouche yesterday was an ECG with limb-lead reversal. These are important to pick-up as some can mimic clinical scenarios.
Findings and clinical mimics of common limb-lead changes:
Right arm-Left arm:

• Q wave I, aVL


• Inverted p-wave I, II, II, aVF


• Mimics: old lateral infarct, non-sinus atrial activity, dextrocardia (limb lead reversal will still have normal R-wave progression, dextrocardia will not)

Right arm- Left leg:

• Q wave II, III, aVF


• Inverted p-wave II, III, aVF


• Mimics: old inferior infarct, non-sinus atrial activity

Right arm- Right leg:

• Diffuse low voltage in limb leads (esp. lead II)


• Mimics: any condition causing low voltage (limb-lead reversal will have normal precordial voltages)

Other limb lead reversals causing only minor changes with no real clinical mimics include Left arm- Left leg, Left arm- Right leg and leg-leg reversals. Precordial lead changes will interfere mostly with R-wave progression.

More from an old but concise review here.

Thrombotic thrombocytopenic purpura

Morning report today was a great case of Thrombotic thrombocytopenic purpura (TTP). Please see here for a prior post on TTP, with links at the bottom to two good NEJM articles.

Mesothelioma

AB today was on mesothelioma.

A few points on mesothelioma, with more in NEJM here:
–Malignancy of pleura (<90%) or peritoneum (>10%)
–~90% of patients will have a history of exposure to asbestos, with mean time from exposure to diagnosis ~35y (wide range)

-Usually presents with local pain, cough or dyspnea, and often assocaited with weight loss/fatigue

- Pleural biopsy (VATS or open) is usually definitive, but special stains are required to differentiate from adenocarcinoma

- Despite some advances, including agressive multi-modal therapy (chemo/radical surgery/radiation) and new active agents (pemetrexed), survival is poor with <10% surviving past 2 years.

- Although Canadian and US incidence is dropping (likely due to asbestos regulation), the overall worldwide incidence is increasing- for which Canada is playing no small part (see here).

Hyponatremia

Morning Report today was on hyponatremia. See an old post here for a good overview. There are two good papers linked at the bottom of the post.

Familial Adenomatous Polyposis

Amuse-bouche today was Familial Adenomatous Polyposis (FAP). This results from a mutation of the tumor suppressor gene APC on chromosome 5. A quick review of the features:

Develop hundreds of adenomatous colon polyps during adolescence

Have a 100% risk of developing colorectal cancer (mean age ~40y)

Associated with:

• Upper-GI tumors: Fundic gland polyps, duodenal adenomas



• Adenocarcinoma of the ampula of Vater



• Extra-intestinal features: osteomas, desmoid/soft-tissue tumors, retinal pigment hypertrophy

Here is a link to a basic BMJ review on hereditary colorectal cancer.

Renal failure in multiple myeloma

Today in morning report, a good case of renal failure in multiple myeloma. A good prior post on all of the causes here with a link at the bottom to a review article.

Dermatomyositis

Amuse-bouche today was Gottron's papules and dermatomyositis. A prior post on dermatomyositis here.

A quick review of the associated dermatologic findings:

Gottron’s papules-80% of patients

Hyperkeratotic, erythematous, flat papules

Dorsum MCP and IP joints, less commonly wrists/elbows/knees

Heliotrope rash- <50% of patients

Periorbital violaceous/erythematous rash

One or both eyelids

May be accompanied by edema

Shawl sign

Macular erythema in V shape at nape of neck

Mechanic's hands

Rough and scaly with fissuring

Lateral and palmar areas of fingers

Nail changes

Periungal erythmea

Telangiectasias on the proximal nail fold

Renal failure and hyperkalemia

In morning report today was a case of acute renal failure. A good prior post with a link at the bottom to a good NEJM article here.

We didn't get in to the management of hyperkalemia, but as Dr. Bunce said- you should know it by tomorrow, so here is a prior post with a good link to a review at the bottom.

Pendred's syndrome

The amuse-bouche today was Pendred's syndrome. A link to a good article here.

Pendred's syndrome is an autosomal-recessive disorder of iodine organification caused by mutations in iodine transport protein pendrin.
It is characterized by the combination of congenital sensorineural hearing and goiter, and accounts for up to 10% of cases of hereditary deafness.
Patients have a positive perchlorate discharge test because they cannot provide substrate for the organification step in thyroid hormone synthesis.