There are usually four parathyroid glands arranged as two pairs. The upper pair, which develop as a dorsal diverticulum of the fourth pharyngeal pouch, are present at the posterolateral border of the thyroid just beneath the upper poles. The lower pair, derived from the third pharyngeal pouch, are located at the lower poles of the thyroid. They are situated within the pretracheal fascia either on the surface or just within the thyroid tissue. Anomalies of position in the neck and anterior mediastinum may occur. A fifth supernumerary gland occurs in approximately 5% of individuals and is usually present in thymic tissues inferior to the thyroid. Rarely, more than five glands may occur. The glands are ovoid in shape. The weights of individual glands are variable but in the adult the total glandular weight averages 120 mg in males and 142 mg in females. Any single gland weighing more than 60 mg is likely to be abnormal. The average maximal dimension is 5 mm, although the normal range of size extends up to 1 cm.

Histologically, the parathyroid cells are arranged in cords and sheets set within a richly vascular stroma. Small follicles containing colloid-like material may be seen and the appearances can mimic those of the thyroid gland. During puberty and early adult life the glands accumulate adipose tissue, fat cells insinuating themselves amongst the endocrine cells. The endocrine cells have two main histological subtypes: the chief cell and the oxyphil cell. The former predominate and are rounded cells with pale granular or vacuolated cytoplasm. They are rich in glycogen and lipid. Oxyphil cells increase in number with age and may form discrete nodules. These cells are larger with abundant eosinophilic cytoplasm containing numerous mitochondria. Transitional forms between chief cells and oxyphil cells also occur.

The parathyroid glands produce and secrete parathyroid hormone (PTH). This single chain polypeptide contributes to the maintenance of calcium ion homeostasis together with vitamin D metabolites. A fall in the level of extracellular calcium ion concentration cause the release of PTH which promotes the renal excretion of the phosphate ion, enhances renal tubular reabsorption of calcium, stimulates bone resorption and stimulates the synthesis of the active metabolite of vitamin D, 1,25 dihydroxycholecalciferol. The latter promotes intestinal calcium absorption and increases its release from bone. The resulting increase in extracellular calcium ion has a negative feedback action on the parathyroid, decreasing the release of PTH.

Parathyroid lesions may be aspirated as masses in the neck clinically believed to be of thyroid origin and earlier reports of parathyroid cytology indicated the difficulty in distinguishing the findings from thyroid lesions.¹⁶ These include follicular lesions, papillary carcinoma, medullary carcinoma¹⁷ and lymphocytic thyroiditis.¹⁸ The distinction may be complicated as parathyroid lesions may be intrathyroidal and by the observation that parathyroid tumours and thyroid carcinomas may coexist as they share the common aetiological factor of radiation to the neck.¹⁹ Distinguishing between thyroid and parathyroid cells may require the use of special techniques to identify the neurosecretory granules in the parathyroid cells. These include immunocytochemistry for PTH or chromogranin A together with a lack of immunostaining for thyroglobulin or calcitonin as appropriate. Immunoassay for PTH can be carried out on material obtained by FNA²⁰ and reverse transcriptase polymerase chain reaction detection of PTH gene mRNA in needle aspirates has been described.²¹ The morphological distinguishing features are dense nuclear chromatin and lack of a regular architecture in the cell groups of parathyroid lesions. The absence of characteristic features of thyroid tissue, colloid, macrophages and follicular structures may also be helpful,²² although all of these features may be seen in parathyroid lesions.¹⁵ In one comprehensive survey colloid-like material was seen in 21%, macrophages in 10% and follicular arrangements in 15% of parathyroid smears.⁸

The refinement of ultrasonography and other imaging techniques including CT, MRI and technetium-99m sestamibi (Tc99 MIBI) scanning has enabled planned FNA of the enlarged parathyroid gland.² FNA and PTH estimation has been used as an adjunct to imaging prior to minimally invasive parathyroidectomy.²³ It can be particularly helpful in Tc99 MIBI negative parathyroids and where imaging is complicated by coexisting thyroid nodules.²⁴ As well as distinguishing parathyroid from thyroid masses the nature of any coexisting thyroid nodules is determined and this may be an indication for open thyroidectomy and parathyroidectomy rather than minimally invasive parathyroid surgery alone. Combined FNA and PTH estimation is also helpful where parathyroids are ectopic²⁵ and in postoperative recurrent or persistent hyperparathyroidism.²⁶ Non-surgical destructive techniques for parathyroid adenomas also rely on accurate identification of parathyroid tissue. FNA can also contribute to diagnosis of parathyroid cysts and carcinomas.

Complications of parathyroid FNA are rare. Parathyroid tissue is readily engraftable and can be autotransplanted. Inadvertent capsular rupture when removing parathyroid tissue, benign or malignant, can result in seeding and growth of numerous foci of parathyroid cells in the operative field or parathyromatosis. A potential complication of FNA, particularly applicable to parathyroid tissue, is needle tract implantation. This has not been associated with aspiration of benign parathyroid lesions²⁷ but cutaneous and needle track spread after FNA of parathyroid carcinomas has been recorded.^28,29 Needle aspiration of parathyroid lesions can result rarely in damage to the gland. Autoinfarction, with resolution of hypercalcaemia, is recorded after aspiration of a cystic hyperplastic gland.³⁰ FNA induced fibrosis in and around parathyroid adenomas can mimic the histological appearances of parathyroid carcinoma³¹ and complicate subsequent surgery. One study noted a doubling of operative time removing previously aspirated glands.³² Avoiding excessive numbers of needle passes and the use of 25–27 gauge needles may limit this potential complication.

The adrenal glands are situated superomedially to each of the kidneys. On the right side, the adrenal capsule is usually fused with the overlying liver capsule and occasionally the gland may be embedded within the liver. Each adrenal weighs between 5 g and 6.5 g and measures approximately 4×3×0.5 cm.

The adrenal gland is composed of two distinct parts. The medulla is derived from the neural crest and is a sympathetic paraganglion responsible for the secretion of adrenaline and noradrenaline. The cortex, which constitutes 90% of the gland, is mesodermally derived. It is divided into three concentric regions. The outer zona glomerulosa secretes mineralocorticoids, which are responsible for the conservation of sodium ions and water and the excretion of potassium ions. The inner zona fasciculata and reticularis secrete glucocorticoids, which have a wide range of effects on carbohydrate, protein and lipid metabolism, and sex hormones.

Histologically (Fig. 18.4), the zona glomerulosa consists of clumps of endocrine cells surrounded by a delicate but richly vascular connective tissue stroma. The cytoplasm has a poorly staining, clear cell appearance due to the presence of abundant lipid and smooth endoplasmic reticulum. The zona fasciculata consists of cords of secretory cells with abundant clear and foamy appearing cytoplasm. The cells of the zona reticularis are arranged in a network of branching cords and are smaller with a more compact cytoplasm, which may contain lipofuscin granules. The cells, phaeochromocytes, of the adrenal medulla are arranged in clumps in a vascular stroma of sinusoids and larger venous channels. They have abundant granular basophilic cytoplasm and large nuclei. Some sympathetic ganglion cells are also present.

Fig. 18.4 Adrenal gland. Normal histology (H&E).

Adrenal cells may be encountered by chance in attempted aspirates of surrounding structures such as the liver and kidney. Imaging techniques with CT and ultrasound guided aspiration enables planned investigation of adrenal masses. Both adrenals particularly the left adrenal are amenable to sampling by transgastric endoscopic ultrasound directed FNA.³³ Interpretation of an aspirate must be with full knowledge of the clinical, radiological and where appropriate the biochemical findings, e.g. the cytological findings from an adrenal adenoma may be identical to those from a normal adrenal, diffuse hyperplasia or nodular hyperplasia. The findings may be very similar in adrenocortical carcinoma and even in a renal clear cell adenocarcinoma. FNA allows the diagnosis of metastases in the adrenal, adrenocortical tumours, phaeochromocytomas, ganglioneuromas and neuroblastomas. Collection of cell block or liquid based cytology specimens can be helpful for immunostaining. FNA can also be of use in the diagnosis of some infections affecting the adrenal such as tuberculosis and histoplasmosis, allows confirmation of the presence of a simple adrenal cyst and the diagnosis of myelolipoma of the adrenal.

Approximately 3% of those having abdominal CT or MRI show adrenal cortical nodules, either adenomas or nodular hyperplasia, of greater than 1 cm in diameter. Consequently the principal indication for adrenal FNA is the need to investigate incidental adrenal masses (‘incidentalomas’) in patients who have had abdominal imaging as part of their staging investigations for malignancy particularly bronchogenic carcinomas. Adrenal FNA is a highly specific and safe technique for the diagnosis of carcinoma metastatic to the adrenal gland. In some studies the probability of such masses being metastatic cancer or a primary adrenal lesion are approximately equal.^34–38 Several large studies have shown greater than 90% accuracy in the diagnosis of adrenal masses.

Clinically symptomatic functional adrenal masses for example adrenal adenomas and phaeochromocytomas are usually removed without prior FNA. For incidentally detected adrenal lesions where there is no prior history of malignancy there is a case for removing all larger lesions (over 4 cm diameter) without preceding FNA as both a diagnostic and therapeutic procedure. Radiological findings should exclude the diagnosis of myelolipoma and biochemical findings phaeochromocytoma. These are usually adrenocortical neoplasms and larger size as well as any atypical cytological features is an indication for excision. Smaller such nodules may warrant FNA to aid the decision as to whether surgery is necessary.

These include pneumothorax, haemorrhage, abscess formation and needle track tumour implantation. Where aspiration is carried out without prior biochemical testing for phaeochromocytoma, there is also a small risk of provoking a hypertensive crisis.³⁹