Endocrinology and Metabolism

Once target control is achieved and the results of self-monitoring become quite predictable, there is little gained in most individuals from repeatedly confirming this state. There are many exceptions, such as acute illness, when new medications are added, when weight fluctuates significantly, when A1c targets drift off course and in individuals who need monitoring to maintain targets. Self-monitoring is beneficial as long as one is learning and adjusting therapy based on the result of the monitoring.

Thyroid ultrasound is used to identify and characterize thyroid nodules, and is not part of the routine evaluation of abnormal thyroid function tests (over- or underactive thyroid function) unless the patient also has a large goiter or a lumpy thyroid. Incidentally discovered thyroid nodules are common. Overzealous use of ultrasound will frequently identify nodules, which are unrelated to the abnormal thyroid function, and may divert the clinical evaluation to assess the nodules, rather than the thyroid dysfunction. Imaging may be needed in thyrotoxic patients; when needed, a thyroid scan, not an ultrasound, is used to assess the etiology of the thyrotoxicosis and the possibility of focal autonomy in a thyroid nodule.

T4 is converted into T3 at the cellular level in virtually all organs. Intracellular T3 levels regulate pituitary secretion and blood levels of TSH, as well as the effects of thyroid hormone in multiple organs. Therefore, in most people a normal TSH indicates either normal endogenous thyroid function or an adequate T4 replacement dose. TSH only becomes unreliable in patients with suspected or known pituitary or hypothalamic disease when TSH cannot respond physiologically to altered levels of T4 or T3. Patients should have access to additional testing, as required.

Many of the symptoms attributed to male hypogonadism are commonly seen in normal male aging or in the presence of comorbid conditions. Testosterone therapy has the potential for serious side effects and represents a significant expense. It is therefore important to confirm the clinical suspicion of hypogonadism with biochemical testing. Current guidelines recommend the use of a total testosterone level obtained in the morning. A low level should be confirmed on a different day, again measuring the total testosterone. In some situations, a free or bioavailable testosterone may be of additional value.

Positive anti-TPO titres are not unusual in the ‘normal’ population. Their presence in the context of thyroid disease only assists in indicating that the pathogenesis is probably autoimmune. As thyroid autoimmunity is a chronic condition, once diagnosed there is rarely a need to re-measure anti-TPO titres. In euthyroid pregnant patients deemed at high risk of developing thyroid disease, anti-TPO antibodies may influence the frequency of surveillance for hypothyroidism during the pregnancy. It is uncommon that measurement of anti-TPO antibodies influences patient management.

Metanephrines are consistently secreted in pheochromocytomas and paragangliomas (PPGL), whereas catecholamine production is intermittent. The risk of false-negative results is therefore high when plasma catecholamines are used as a first-line screening test (sensitivity 85% and specificity 81%). Current guidelines recommend metanephrines (plasma or urinary) as the preferred initial screening test for PPGL.

Plasma metanephrine testing however has limitations including posture related variability, as patients should ideally be supine for at least 20 mins before sampling via a pre-installed intravenous catheter. Additionally, the samples must be transported on ice because metanephrines are unstable in whole blood if they cannot be processed promptly by the laboratory. This instability is not an issue in urine as collection occurs in acidified containers. These preanalytical challenges make urinary metanephrines a more practical alternative for outpatients as failure to meet these conditions increases the risk of false positives for plasma metanephrines. Both plasma and urinary metanephrines have high sensitivity for screening (99% and 97% respectively) and combining these tests do not improve diagnostic performance.

Joint recommendation with the Canadian Association of Medical Biochemist

Short stature is defined as height more than 2 SD below the mean (or <2.3rd percentile) for age and sex, assessed using WHO growth charts for Canada. Common nonpathological causes include familial short stature and constitutional delay of growth and puberty. Pathologic causes (e.g. systemic illness, malnutrition, endocrine and genetic causes) should be investigated when growth velocity is reduced on serial measurements over at least 6 to 12 months. Growth hormone (GH) deficiency is rare and should only be suspected when the child’s height is greater than 2 SD below the expected mid-parental range with normal weight, and reduced growth velocity.

Random GH levels should not be ordered: secretion is pulsatile with significant diurnal fluctuations, sleep dependent and influenced by exercise, fasting, intercurrent illness and stress making single measurements unreliable. Diagnosis of GH deficiency requires formal stimulation testing, only indicated in selected circumstances and under endocrinology guidance. IGF-1 level is more stable and may be used as a surrogate marker. However, low IGF-1 is non-specific and can result from malnutrition, systemic illness, liver dysfunction, inflammation, pubertal delay, diabetes or hypothyroidism. GH deficiency is unlikely when IGF-1 is above the mean for age and sex, in a child with normal growth velocity and bone age.

Joint recommendation with the Canadian Association of Medical Biochemist