Tuesday, February 23, 2016


Today's case involved a middle-aged woman who presented with one week of palpitations, anxiety, and tremors.  The patient had a number of physical examination signs of hyperthyroidism, and confirmatory biochemical evidence.  She was treated with beta blockade and investigated on the internal medicine service.

Learning points:

We spoke about the physical examination findings of hyperthyroidism and hypothyroidism (outside the thyroid gland itself).  The easiest way is to break them down by body system:

Vital Signs
Systolic hypertension, tachycardia, hyperthermia, elevated RR
Diastolic Hypertension, bradycardia, hypothermia, reduced RR
Velvety, moist, warm, pretibial myxedema
Cool, dry, non-pitting myxedema
Palmar erythema, thyroid acropatchy (clubbing), onycholysis
Yellow discoloration (carotinemia)
Thin, soft
Grave (exophthalmos, proptosis, chemosis, visual loss, restricted EOM), lid lag, stare
Queen Anne sign (lateral 1/3 of eyebrow missing), periorbital edema
Slow, low mood
Irritable, disinhibited
Tachydysrhythmias, flow murmurs from increased output, Heart failure
Increased respiratory rate
Proximal muscle weakness, brisk reflexes
Proximal muscle weakness, delayed relaxation of reflexes, proximal muscle weakness

The diagnosis of hyperthyroidism can usually be made be examining the serum TSH and free thyroid hormones.  Central hyperthyroidism from something like a TSH-producing pituitary adenoma is very rare, most causes will give you a low TSH.  Grave disease patients will often have positive Thyroid Receptor Anitbodies while patients with Hashimoto thyroiditis will often have positive thyroid peroxidase antibodies.  Thyroglobulin antibodies can also be useful.

If someone has hyperthyroidism clinically and biochemically, the next step is to consider the differential diagnosis:
·      Central causes – TSH-secreting tumours or hypothalamic causes
·      Primary Thyroid Causes
o   Thyroid destruction
§  Hashimoto thyroiditis
§  Subacute (viral) thyroiditis
§  Post-partum thyroditis
§  Other thyroid infections
§  Medication-induced thyroiditis (amiodarone)
o   Excessive Thyroid Hormone production
§  Toxic adenoma
§  Toxic multinodular goitre
§  Jodd-Basedow effect of iodine ingestion
§  Medication-induced J-B effect (amiodarone)
§  Grave disease
§  Cross-stimulation by beta-HCG in molar pregnancy
§  Resistance to feedback of T4/T3 resulting in inappropriate overproduction
§  Surreptitious thyroxine ingestion

The best way to differentiate among these etiologies is to do a Radioactive Iodine Uptake and Scan of the thyroid.  The result of such as can is the percentage of iodine that is taken up.

If it is very low (cold thyroid, less than 1%) then you can assume that some form of thyroiditis is occurring.  If it is very high diffusely, then depending on whether there is a toxic multinodular goiter or Grave disease, you may see very high uptakes (>6%).  The intermediate range of uptake usually occurs with adenomas or Jodd-Basedow effect.

Treatment of hyperthyroidism can be divided into symptomatic management and long-term management.  The first question to talk is regarding stability as thyrotoxicosis or thyroid storm requires different treatment.

Thyroid storm has a mortality of around 20%, and patients presenting with this should be looked after in a critical care setting.  There are no accepted diagnostic criteria for thyroid storm.  Physicians grade patients with hyperthyroidism based on the degree of thermoregulatory dysfunction, central nervous system effects, hepatic/gastrointestinal dysfunction, cardiovascular dysfunction, and presence or absence of heart failure or a precipitant history such as parturition or thyroid surgery.  Treatment of thyroid storm involves several facets: non-selective beta-blockade (propranolol), thionamides such as methimazole or PTU to block hormone synthesis, steroids to block peripheral hormone conversion, and an iodine load (Lugol solution) to prevent release of thyroid hormone.  Long term management usually involves radioactive iodine ablation of the thyroid gland, thyroid surgery, or long-term use of thionamide antithyroid drugs.
In milder cases of hyperthyroidism like the one presented, beta blockade is usually used for symptom control.  If a subacute thyroiditis is the likely precipitant, then prednisone at 0.5-1mg/kg for 2-8 weeks is usually required.  Depending on the reason for the hyperthyroidism, thionamides, radioactive iodine, or surgical removal may be the long-term treatment modality of choice.

Further Reading:

Burch, H. B., & Wartofsky, L. (1993). Life-threatening thyrotoxicosis. Thyroid storm. Endocrinology and metabolism clinics of North America, 22(2), 263-277.

Chiha, M., Samarasinghe, S., & Kabaker, A. S. (2013). Thyroid Storm An Updated Review. Journal of intensive care medicine, 0885066613498053.

Franklyn, J. A. (1994). The management of hyperthyroidism. New England Journal of Medicine, 330(24), 1731-1738.

Image Credit: Alive.com

Friday, February 19, 2016

Sickle Cell Disease

Today’s morning report centred around a patient thought to have Sickle Cell Disease admitted with a pain crisis.  She turned out to have sickle cell trait instead.  She was also found to be significantly polycythemic.

There were multiple learning points in the case presented:

·      Sickle cell disease is the result of a genetic abnormality in the beta-globin gene.  This leads to formation of Hemoglobin S which, when in the deoxygenated state, can lead to polymerization of the hemoglobin molecules and sickling of the RBCs.  The reason this is important is that it leads to vaso-occlusion and hemolysis, which have a number of the deleterious effects of SCD.  Patients with sickle cell trait have only one defective gene copy and typically do not get symptoms. We measure the percentage of hemoglobin S with a hemoglobin electrophoresis.
·      The majority of GIM admissions for SCD patients will be due to a vaso-occlusive pain crisis.  There are a number of other potential consequences to sickle cell disease:
o   Chronic hemolysis can lead to utilization and deficiency of nutrients such as iron and folate.  Furthermore, SCD patients are heavily dependent on a high state of reticulocytosis given their reduced RBC lifespain – acute splenic sequestration of RBCs or infection with parvovirus B19 can lead to an aplastic crisis in these patients.
o   SCD patients are at risk for lung disease including fibrotic diseases and pulmonary hypertension, partially from NO scavenging by cell-free hemoglobin.  Virtually all patients with SCD are functionally asplenic as well, and asplenia in and of itself can result in pulmonary hypertension.
o   From that standpoint, encapsulated organisms like S. pneumonia, H. influenzae, Neisseria spp, and Capnocytophagia as well as Babesia are significantly riskier for these patients.  SCD patients are also at increased risk of infection with gram negative organisms like Salmonella spp.
o   Other vaso-occlusive events can occur including myocardial infarctions, cerebrovascular infarctions, bone infarctions and avascular necrosis, as well as priapism in male patients.
·      Acute chest crisis, which is generally a medical emergency characterized by chest pain, hypoxemia, and infiltrates on the chest x-ray, involves treatment by red cell exchange or transfusion.
·      Treatment of a sickle pain crisis has a number of modalities:
o   Hydration/volume repletion – this should be considered if the patient is hypovolemic.  This will help dilute the RBC mass and increase flow in distal areas of sluggish flow where sickling is occurring the most.
o   Pain control – this usually requires opioid analgesics, but a significant portion of the pain is inflammatory so NSAIDS are also of benefit.
o   Prevention of atelectasis – these patients should all receive incentive spirometry and should be encouraged to ambulate as much as possible.
o   If febrile, obtain cultures and look for a source.  In children, empiric antibiotics are usually given.
o   Obtain a chest X-ray if there are symptoms compatible with acute chest syndrome.
·      We also spoke about Polycythemia given this person’s relatively high hemoglobin.  This can generally be grouped into primary or secondary polycythemia.  Primary occurs as a result of constitutive production of RBCs despite a lack of need.  Secondary polycythemia does not impose the same thrombotic risks as primary, and is due to other factors such as chronic hypoxemia, profound volume contraction, etc.  Useful tests can be JAK-2 mutation testing, and examining the level of erythropoietin.  Peculiar symptoms that patients with myeloproliferative disorders such as PRV and essential thrombocytosis get are erythromelalgia (painful reddening of the hands) and aquagenic pruritis (histamine release secondary to hot water).  All patients with PRV should be on ASA unless contraindicated, but hydroxyurea is added for patients with a high risk of thrombotic events, or in those who have had events.

Further Reading:
Bunn, H. F. (1997). Pathogenesis and treatment of sickle cell disease. New England Journal of Medicine, 337(11), 762-769.

Heeney, M. M., Hoppe, C. C., Abboud, M. R., Inusa, B., Kanter, J., Ogutu, B., ... & Zamoryakhin, D. (2015). A multinational trial of prasugrel for sickle cell vaso-occlusive events. New England Journal of Medicine.

Platt, O. S. (2008). Hydroxyurea for the treatment of sickle cell anemia. New England Journal of Medicine, 358(13), 1362-1369.

Image Credit: www.sicklecellga.org