9 The Endocrine System

9

The Endocrine System

237

For the purposes of post mortem dissection, the endocrine system is com- posed of the thyroid gland, the parathyroid glands, the adrenal glands, and the pituitary gland; and the removal of these glands has been discussed earlier. Although there are obviously other endocrine organs, they either form part of a diffuse endocrine system, such as in the bronchial and intes- tinal mucosa, or are embedded within another organ, such as the endocrine pancreas.

This chapter includes:

• Further dissection of the separated glands

• Special techniques that may be necessary

• Examination of the paraganglia

Pathology within the endocrine system is not found particularly often at autopsy, and when identified it is even less commonly related to the cause of death. Nevertheless, the examination of the endocrine system is part of any thorough post mortem examination, and does occasionally produce surprises, particularly on histological examination.

A set of scales that are accurate at small weights are an absolute neces- sity for the adequate assessment of endocrine glands.

The Thyroid Gland

If an infiltrative tumour has been identified during evisceration that is

causing attachment of the thyroid gland to adjacent structures, the gland

should be examined in continuity with the neck organs (see p. 240). Other-

wise, all attached strap muscles and connective tissue should be removed

from the now separate gland, using forceps and scissors. The gland is com-

posed of right and left lobes, joined by an isthmus (Fig. 9.1). The thyroid

can now be weighed and measured, to identify and quantify any atrophy or

hyperplasia:

Average weight of thyroid gland [1] 40 g (range 30–70 g) Average size of each lobe [1] 6 ¥ 3.5 ¥ 2cm

Incomplete vertical slices can then be made from the anterior surface, about 0.5 cm apart, thus retaining continuity at the posterior surface to keep the gland intact (Fig. 9.2). The cut surfaces should then be examined.

Figure 9.1. The normal thyroid gland, stripped of all attached muscle for weighing.

(Courtesy of Mr. Dean Jansen, Whittington Hospital.)

Figure 9.2. Dissection of the thyroid gland. Incomplete slices have been made from the anterior surface to allow examination of the parenchyma but keep the gland intact. (Courtesy of Mr. Dean Jansen, Whittington Hospital.)

Any focal lesions identified should be measured and examined, and then submitted for histology in their entirety. Standard routine histology, how- ever, should include a single block of thyroid tissue even in the absence of obvious abnormality, providing appropriate permission has been obtained.

Clinical Correlation

A weight that is significantly below the normal range indicates atrophy or hypoplasia. Atrophy may be due to previous thyroiditis or may be a consequence of overtreatment of hyperthyroidism. Hypoplasia is a developmental anomaly that is congenital in origin. The presence of either atrophy or hypoplasia should alert the prosector to look for other indications and associations of hypothyroidism.

A weight that is significantly above the normal range indicates hyper- plasia, in the absence of a focal lesion. Such enlargement of the gland is termed a goitre, and may be caused by Grave’s disease or a dietary defi- ciency of iodine, or it may be idiopathic. The presence of hyperplasia should alert the prosector to look for other signs of hyperthyroidism.

Focal lesions may be cystic, “colloid,” or solid. “Colloid” nodules are also often multiple. Cystic lesions may either be simple cysts or may rep- resent “colloid” or solid lesions that have undergone cystic degeneration.

Solid lesions are likely to be neoplastic.

The Parathyroid Glands

If an infiltrative tumour has been identified during evisceration that is causing attachment of the parathyroid gland(s) to adjacent structures, the glands should be examined in continuity with the neck organs (see p. 240).

Otherwise, the now separate glands should be stripped of any attached fat and weighed together, using scales that are specially designed for very low weights.

Average combined weight of 0.12–0.18 g (0.03–0.045 g each) parathyroid glands [1]

Average size of each gland [1] 0.3–0.6 cm in maximum diameter

Glands of normal size should be submitted for histology if indicated by the clinical details or the post mortem findings, providing appropriate per- mission has been obtained. Any glands that are grossly enlarged should be cut into separate slices, examined, and submitted in their entirety for his- tology, providing that appropriate consent has been obtained.

The Parathyroid Glands 239

Clinical Correlation

Enlargement may be due to hyperplasia or neoplasia; the latter obvi- ously includes both adenomas and carcinomas. It is extremely difficult to distinguish hyperplasia from an adenoma histologically, so the diagnosis often rests on the macroscopical findings. Enlargement of all glands indi- cates hyperplasia whereas enlargement of only one or two glands indi- cates an adenoma (or more rarely a carcinoma). Both hyperplasia and neoplasia usually produce hyperparathyroidism, and therefore parathy- roid gland enlargement should prompt the prosector to look for other signs and associations of gland overfunction.

Parathyroid glands may also be absent or unidentifiable because of hypoplasia or as a consequence of previous surgery. Hypoparathyroidism is a largely functional disorder, however, and produces few anatomical changes that are identifiable at post mortem.

Special Techniques

Examination of the Thyroid or Parathyroid Glands When an Infiltrative Tumour Is Present

If an infiltrative carcinoma of the thyroid or parathyroid glands is expected or identified during evisceration the thyroid and parathyroid glands should be left attached to the neck organ block and examined in continuity. This allows assessment of the extent of local invasion. Whichever post mortem technique is used, the neck organs need to be removed from the thoracic organs by cutting through the lower trachea, oesophagus, and surrounding soft tissues. The thyroid gland, parathyroid glands, and attached neck struc- tures should then be sliced from the anterior surface, at intervals of about 1 cm, using a large knife. These slices should be complete, and can then be laid out flat and examined separately. If either senile cartilaginous or tumour calcification is encountered, a hand saw or shears may be necessary to complete the slices. An extremely large thyroid or parathyroid tumour may extend to the hyoid bone, in which case it is easier to arrange the slices so that they fall either side of the bone than it is to attempt to section the bone itself. Alternatively, the entire tissue block can be decalcified prior to

Relevant blocks of tumour, including the infiltrative margin, can then be taken for histology, decalcifying before processing if necessary, and provid- ing that appropriate permission has been obtained.

This method does have the disadvantage of destroying the thyroid and

parathyroid glands before they can be weighed; however, in these circum-

stances the weight is less important than the identification of the extent of

invasion.

The Adrenal Gland

Infiltration of the surrounding structures is extremely unusual in adrenal tumours, but if identified during evisceration this requires special dissection of the retroperitoneum (see p. 211).

When no infiltrative tumour is present, all attached fat should be painstakingly removed from the glands, using forceps and scissors, if weigh- ing is to be accurate (see Fig. 9.3). The adrenals can then be weighed and measured, and any atrophy or hyperplasia assessed.

Average weight single stripped adrenal gland [2] 5.75 g (up to 10 g) Average size single stripped adrenal gland [1] 4.5 ¥ 3 ¥ 0.5cm

Incomplete vertical slices should now be made, about 0.5 cm apart, retain- ing continuity at one border to keep the gland intact (see Fig. 9.4). The cut

Figure 9.3. The normal adrenal gland, stripped of all fat for weighing. (Courtesy of Mr. Dean Jansen, Whittington Hospital.)

Figure 9.4. Dissection of the adrenal gland. Incomplete slices have been made from one border to allow examination of the parenchyma but keep the gland intact.

(Courtesy of Mr. Dean Jansen, Whittington Hospital.)

surfaces can now be examined and any focal lesions identified. All focal lesions should be measured and examined and then appropriate blocks submitted for histology. Standard routine histology should include a block of each adrenal gland, however, even if no lesions are identified, providing the appropriate consent has been obtained.

Clinical Correlation

A significant reduction in gland weight indicates atrophy and is usually a consequence of systemic steroid therapy although may be caused by previous adrenalitis. It should alert the prosector to look for other indi- cations of adrenal underfunction. A significant increase in gland weight, in the absence of a focal lesion, indicates hyperplasia and should prompt the prosector to look for signs and associations of adrenal overfunction.

Focal lesions may be caused by nodular hyperplasia or neoplasia; the latter obviously include both adenomas and carcinomas. Most such lesions are functional and should lead the prosector to look for other indications of gland overfunction. Destructive lesions such as tuberculo- sis and metastatic deposits also usually produce macroscopically identi- fiable lesions. These may be associated with underfunction of the gland and should prompt a search for the signs and associations of gland underfunction.

Special Techniques

Examination of a Suspected Pheochromocytoma

If an adrenal tumour is present, it could be a pheochromocytoma that is secreting adrenaline or noradrenaline. This can be identified at the time of post mortem using a macroscopic dye technique. To do this, a slice of tumour should be placed in a 10% solution of potassium dichromate (pH 5 to 6) for about 5 minutes. If either adrenaline or noradrenaline is present, the tissue will become dark brown. The tissue can then either be discarded or washed thoroughly before being fixed and retained.

The Pituitary Gland

If a mass is macroscopically visible or a large tumour has been identified

pre mortem, the pituitary gland should be removed in continuity with the

sphenoid bone (see p. 243), to assess the extent of any local invasion. In all

other situations, the pituitary will have already been removed from the sella

turcica (see Fig. 9.5). The gland can then be weighed and measured, to iden-

tify and quantify any atrophy or hyperplasia.

Average weight of pituitary gland [1] 0.6 g (up to 1 g in pregnant women) Average size of pituitary gland [1] 2.1 ¥ 1.4 ¥ 0.5cm

The gland should then be bisected through the stalk in a sagittal plane, and the cut surfaces of the anterior and posterior lobes examined to iden- tify any small focal lesions (see Fig. 9.6). Any focal lesion should be sampled in its entirety for histology. Apparently normal pituitary should also be sub- mitted for histology if indicated by the clinical history or macroscopical findings, providing that the appropriate consent has been obtained.

Clinical Correlation

A significant reduction in gland weight indicates atrophy and should prompt the prosector to look for other signs and associations of pituitary underfunction. A significant increase in gland weight usually indicates a pituitary tumour, although more rarely it can be caused by hyperplasia.

Focal lesions are usually adenomas and can be typed histologically using immunohistochemistry for secretory hormones. Carcinomas are very rare.

Special Techniques

Examination of the Pituitary Gland When a Large Tumour Is Present

If a large pituitary gland tumour has been identified clinically or is sus- pected at post mortem, it is preferable to remove the entire sella turcica en

Figure 9.5. Photograph of the normal pituitary gland with the stalk inferiorly.

(Courtesy of Mr. Dean Jansen, Whittington Hospital.)

bloc rather than removing the pituitary gland in the normal way. This en bloc removal allows an accurate assessment of size and extent of invasion that is not possible from the sellar pituitary tissue alone.

The brain should be removed in the normal way, and the dura mater stripped completely from the base of the skull. An electric saw with a fan- shaped blade should then be used to remove the central portion of the base of the skull, including the sella turcica and the surrounding bone. The tech- nique is a difficult one, and therefore should be undertaken with great care and only when necessary. The main risk is of causing fractures within the base of the skull, which may produce instability, and if they involve the orbital plate can lead to sinking of the globes and thus make reconstitution difficult. Nevertheless, providing this technique is undertaken (or at least supervised) by someone with experience in using an electrical saw (usually a technician) there will be no external evidence that this procedure has taken place.

Coronal cuts should be made about 1 cm in front of the anterior clinoid process and about 2 cm behind the posterior clinoid process, anterior to the foramen magnum. These two cuts should extend about 1 cm lateral to the sella turcica on each side. They should then be joined by two parasagittal cuts. Figure 9.7 illustrates the saw cuts that need to be made. All such cuts need to be made through the full thickness of the base of the skull, where-

Figure 9.6. Photograph of the pituitary and stalk bisected in the sagittal plane and showing the cut surfaces. (Courtesy of Mr. Dean Jansen, Whittington Hospital.)

upon an immediate lack of resistance will be felt. The central bony section produced can then be levered to each side and a scalpel used to cut through the soft tissues of the nasopharynx. This should completely free the block of bone and allow its removal. The entire block can then be decalcified, fol- lowing which it can be sectioned, examined, and appropriate tissue blocks taken for histology. The need for decalcification will inevitably lead to a delay in the report. If a histological diagnosis has not previously been made, therefore, and is needed more urgently, a small piece of the tumour can be removed (either with a biopsy needle or scalpel) and submitted for imme- diate histology while the residual tissue block is being decalcified.

Other Special Techniques

Examination of the Paraganglion System

Anatomy

The paraganglion system is composed of clusters of cells of neuroendocrine derivation secreting various bioactive amines and peptides, the most

Other Special Techniques 245

Figure 9.7. Photograph of the base of the skull. The box indicates the position of the saw cuts necessary to remove the sella turcica en bloc. (Courtesy of Mr. Dean Jansem Whittington Hospital.)

important of which are the catecholamines. The largest paraganglion is the adrenal medulla. The extra-adrenal paraganglion system is closely associ- ated with the autonomic nervous system and is composed of paraganglia that are very difficult to identify macroscopically unless they are enlarged by tumour. They are divided into three groups based on their anatomical distribution: branchiomeric, intravagal, and aortosympathetic. The bran- chiomeric and intravagal paraganglia are associated with the parasympa- thetic system and are located close to the arteries and nerves of the head and neck; the intravagal are closely associated, as the name implies, with the vagal nerve. Some of the branchial paraganglia are also chemorecep- tors. The aortosympathetic paraganglia are associated with the chain of sympathetic ganglia and are therefore distributed about the abdominal aorta. Most paraganglia are named according to nearby structures, but there is a group about the aortic bifurcation at the origin of the inferior mesen- teric artery called the organs of Zuckerkandl!

parotid gland

masseter muscle carotid body

external carotid artery

anterior belly digastric muscle

mylohyoid muscle

hyoid bone

hypoglossal nerve

“strap”

muscles

clavide sternocleidomastoid muscle

vagus nerve internal jugular vein accessory nerve

common carotid artery internal carotid artery posterior belly digastric muscle

sternocleidomastoid muscle

ear

Figure 9.8. Diagram illustrating the position of the carotid body in relation to the surrounding structures of the neck. The lymph nodes and submandibular salivary gland have been removed.

The examination of the paraganglion system is likely to be necessary only when a known primary tumour is present, in which case it will be easy to identify macroscopically, and can simply be removed, weighed, sliced, and appropriate tissue samples submitted for histology.

In certain circumstances, however, it may be necessary to examine the carotid body, for example, in cases of pulmonary hypertension. It is a very small, flattened ovoid mass of tissue attached to the outer wall of the common carotid artery, just in the curve of the bifurcation into external and internal branches. Figure 9.8 illustrates the position of the carotid body in relation to the other neck structures and Fig. 9.9 is a photograph of the carotid body. It should be dissected carefully from the soft tissue at this site, before the carotid artery has been opened. It can then be weighed and submitted for histology. A significant increase in weight suggests chronic hypoxia.

Average weight of single carotid body [2] 0.02 g (range 0.004–0.034 g)

IC EC

Figure 9.9. A normal carotid body (arrow) at the carotid bifurcation, after the over- lying soft tissue has been carefully dissected free. C, Common carotid artery; S, carotid sinus; IC, internal carotid; EC, external carotid. (Adapted with permission from Harris P and Heath D. The human pulmonary circulation. Churchill Living- stone, 1986, p. 486.)

References

1. Sunderman WF, Boerner F. Normal values in clinical medicine. Philadelphia: WB Saunders, 1949.

2. Furbank RA. Conversion data, normal values, normograms and other standards.

In: Simpson K, editor. Modern trends in forensic medicine. New York: Appleton- Century-Crofts, 1967; pp. 344–364.