Essential Endocrinology and Diabetes. Richard I. G. Holt
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Imaging in endocrinology
Ultrasound
Ultrasound travels as sound waves beyond the range of human hearing and, according to the surface encountered, is reflected back towards the emitting source (the ultrasound probe). Different tissues have different reflective properties. By knowing the speed of the waves and the time between emission and detection, the distance between the reflective surfaces and the source can be calculated. These data allow a two‐dimensional image to be generated (Figure 4.6). The major advantage of ultrasound is its simplicity, safety and non‐invasiveness. Machines are portable. It is helpful as an initial imaging investigation of many endocrine organs. For instance, the thyroid has a characteristic appearance in Graves disease because of its increased vascularity (Chapter 8). The ovaries can be delineated transabdominally, or with specific consent, transvaginally, when the shorter distance between probe and ovary and fewer reflective surfaces create higher resolution images (Figure 4.6).
Computed tomography and magnetic resonance imaging
Computed tomography (CT) and magnetic resonance imaging (MRI) provide excellent depiction of the body’s internal organs and tissues. The principle of CT is the same as for X‐ray. X‐rays pass differently through the various organs and tissues of the body. For instance, bone is not penetrated very well so a plain X‐ray image is obtained as if the skeleton has cast a shadow. In CT scanning, the patient lies on a table that slides through a motorized ring, which rotates and emits X‐rays. Data are acquired on penetration from different angles (i.e. as if multiple plain X‐rays had been taken), which are then constructed by computer into a single transverse ‘slice’ through the body (Figure 4.7). The brain is encased by the skull, hence its imaging by CT is limited.
In comparison to CT, MRI does not rely on X‐rays and is particularly useful at imaging intracranial structures, such as the pituitary (Figure 4.8). It is also very useful for screening purposes when a patient will need life‐long monitoring, e.g. to assess tumour formation in MEN. Repeat CT would provide a large cumulative radiation dose, itself a risk factor for tumour formation, which is avoided by MRI. The key components of MRI are magnets. At their centre is a hollow tube, into which the patient passes on a horizontal table. Once inside the tube, the patient is in a very strong magnetic field (this is the reason why MRI is dangerous to people with metallic implants such as pacemakers or aneurysm clips). Within the magnetic field, some of the body’s hydrogen atoms resonate after absorbing energy from a pulse of radio waves. Once the pulse ends, the resonating atoms give up energy as they return to their original state. These emission data are collected and differ slightly for different tissues, allowing the construction of high‐definition images. By altering time (T) constants, different images can be generated. For instance, in T1‐weighted images, cerebrospinal fluid (CSF) appears dark (Figure 4.8a), whereas in T2‐weighted images, CSF appears white (Figure 4.8b).
Figure 4.5 The basic principles of the polymerase chain reaction (PCR). PCR allows the amplification of a user‐defined stretch of genomic DNA. In diagnostic genetics, this is commonly an exonic sequence where a mutation is suspected to underlie the patient phenotype. (a) Starting DNA. (b) The double helix is separated into two single strands by heating to ∼94 °C. (c) Cooling from this high temperature allows binding of user‐designed short stretches of DNA (primers) that are complementary to the opposite strands at each end of the region to be amplified. (d) DNA polymerase catalyzes the addition of deoxynucleotide residues according to the complementary base pairs of the template strand. (e) Once complete, two double‐stranded sequences arise from the original target DNA. Another cycle then recommences at (a) with double the amount of template, making the increase in DNA exponential. Having amplified large amounts of the desired DNA sequence, a modified PCR reaction and analysis sequences the DNA to discover the presence or absence of a mutation.
Contrast agents are useful for both CT and MRI scanning (Figure 4.7). In MRI, agents such as gadolinium can subtly alter the data acquired, for instance allowing the identification of an adenoma within normal anterior pituitary tissue.
Nuclear medicine and uptake marker scans
Simple X‐rays, CT and MRI depict tissues and organs but provide limited insight into the cells that compose these structures or their function. In later life, many organs develop benign tumours of little or no significance. For instance, incidental adrenal tumours (incidentalomas) can affect ∼5% of the population after ∼40 years. In a person with hypertension, it would be important to distinguish these from a phaeochromocytoma that could be the curable cause of elevated blood pressure (Chapter 6). Uptake markers (or ‘tracers’) specific to a particular cell type can provide valuable clues. For instance, meta‐iodobenzylguanidine (mIBG) acts as an analogue of norepinephrine and is taken up by adrenal medulla cells. When labelled with radioactive iodine‐123 (I123) it can be used to distinguish a phaeochromocytoma from other tumours (Figure 4.9). At higher doses, it can even be used as targeted therapy, when instead of marking cells, it kills them. I123 or technetium‐99m pertechnetate can also be used to delineate different causes of hyperthyroidism (Chapter 8) when taken up by the thyroid gland. In Graves disease, the uptake is homogeneous; with a solitary ‘toxic’ adenoma, the uptake is restricted to the relevant nodule.
Figure 4.6 Ultrasound of a polycystic ovary. The presence of multiple small cysts (one shown by the arrow) is consistent with, but not required for, the diagnosis of polycystic ovarian syndrome (Chapter 7). Ultrasound does help to exclude the single mass of an androgen‐secreting tumour (Chapter 7).
Image kindly provided by Dr Sue Ingamells, University of Southampton.