Chapter 17 Endocrine system
COMMON CLINICAL PROBLEMS FROM ENDOCRINE DISEASE
Pathological basis of endocrine signs and symptoms
Sign or symptom | Pathological basis |
---|---|
Signs or symptoms of hormone excess (hyperfunction) | |
Signs or symptoms of hormone deficiency (hypofunction) | |
Diffuse enlargement of gland | |
Nodular enlargement of gland | Tumour (benign or malignant) |
Some organ-specific features | |
Pituitary tumour | |
Increased thyroid hormone secretion due to hyperplasia or neoplasia of gland | |
Autoimmune involvement of retrobulbar connective tissue in Graves’ disease | |
Adrenocortical hyperplasia or neoplasia | |
Absolute or relative deficiency of insulin (diabetes mellitus) |
NORMAL STRUCTURE AND FUNCTION
An endocrine gland secretes hormones directly into the blood stream to reach distant ‘target organs’ where the secretory products exert their effects. Endocrine glands are thus distinguished from exocrine glands, whose secretions pass into the gut or respiratory tract, or on to the exterior of the body; examples of exocrine glands include the exocrine pancreas and the bronchial mucous glands. Closely related to the endocrine system is the paracrine (diffuse endocrine) system, consisting of regional distributions of specialised cells producing locally acting hormones, such as those regulating gut motility, and forming part of the neuroendocrine system (Ch. 15); autocrine effects are those acting on the cell producing the hormone (Fig. 17.1).
ENDOCRINE PATHOLOGY
The major disorders of an endocrine gland are:
PITUITARY
The pituitary is a small gland, weighing only 500–1000 mg. It is situated in the sella turcica of the skull beneath the hypothalamus. Despite its small size, it exerts many essential control functions over the rest of the endocrine system, earning it the title ‘conductor of the endocrine orchestra’. It consists of two parts (Fig. 17.3), each with separate functions. The anterior pituitary, the adenohypophysis, is developed from Rathke’s pouch, an outpouching of the roof of the embryonic oral cavity; it comprises about 75% of the bulk of the gland. The posterior pituitary, the neurohypophysis, is derived from a downgrowth of the hypothalamus.
ADENOHYPOPHYSIS
Classification of cell types
Modern histological classification of the types of hormone-secreting cell is based on immunohistochemistry, a technique in which antibodies raised to a hormone bind to the cells containing that hormone in tissue sections, leading to a coloured stain (Fig. 17.4). This has enabled the true hormone content of the cells to be determined, and has rendered obsolete the traditional classification of the cells into eosinophil, basophil and chromophobe types according to their staining by haematoxylin and eosin (H&E). By electron microscopy, the cells of the adenohypophysis are seen to contain electron-dense granules ranging from 50 to 500 nm in diameter (Fig. 17.5); these contain stored secretory products. The six types of hormone-secreting cell are shown in Table 17.1.
Table 17.1 Hormone-secreting cells of the adenohypophysis
Cell type | Staining reactionwith H&E | Hormonal product |
---|---|---|
Corticotroph | Basophilic | Adenocorticotrophic hormone (ACTH) |
Thyrotroph | Basophilic | Thyroid-stimulating hormone (TSH) |
Gonadotroph | Basophilic | |
Somatotroph | Eosinophilic | Growth hormone (GH) |
Lactotroph | Eosinophilic | Prolactin (PL) |
Chromophobe | Pale | Unknown |
Control of hormone secretion
Hormonal control factors
The adenohypophysis lacks any direct arterial supply. Blood from the hypothalamus passes down venous portal channels in the pituitary stalk (Fig. 17.3) into sinusoids which ramify within the gland. In this way hormonal control factors produced by neurosecretory cells in the hypothalamus are carried directly to the hormone-producing cells of the adenohypophysis. The known hormonal control factors and their effects are listed in Table 17.2. In general, these factors stimulate the particular secretory cells under their control into activity; the exception is prolactin-inhibiting factor, whose effect on the lactotrophs is inhibitory.
Table 17.2 Hormonal control factors and their effects on the adenohypophysis
Hormonal control factor | Effect |
---|---|
Corticotrophin-releasing factor (CRF) | Corticotrophs release ACTH |
Thyrotrophin-releasing factor (TRF) | Thyrotrophs release TSH |
Gonadotrophin-releasing factor (FSH/LH-RF) | Gonadotrophs release FSH/LH |
Growth hormone-releasing factor (GHRF) | Somatotrophs release GH |
Prolactin-inhibiting factor (PIF) | Lactotrophs inhibited from releasing PL |
Feedback control
In these examples, the level of hormone from the target gland is monitored for feedback control. However, in the case of growth hormone, which has no single target gland, it is the level of metabolites such as glucose that is monitored. A general scheme of the feedback control mechanisms operating in the regulation of a hypophysial hormone is shown in Figure 17.3.
Adenohypophysial hormones
Growth hormone
Growth hormone (GH) is a protein containing 191 amino acids; it binds to receptors on the surface of various cells and thus causes increased protein synthesis, accelerates breakdown of fatty tissue to produce energy, and tends to raise the blood glucose. It is vital for normal growth; deficiency causes dwarfism. Part of its action at tissue level is mediated by a group of peptide growth factors known as somatomedins. The hypothalamic control of GH release from the hypothalamus is complex, there being both a growth hormone-releasing factor (GH-RF) and an inhibitory factor, somatostatin.
Hypofunction
Like other endocrine organs, the adenohypophysis has considerable reserve capacity, and deficiency of its hormones becomes manifest only after extensive destruction; hypofunction is therefore uncommon. Since the pituitary is tightly encased within the sella turcica, any expansile lesion, such as an adenoma, produces compression damage to the adjacent pituitary tissue, in addition to any effect from its own hormonal production. Damage to the hypothalamus or pituitary stalk may also produce adenohypophysial hypofunction through failure of control. Table 17.3 sets out the main causes of hypofunction. These conditions lead to a deficiency of all adenohypophysial hormones, a state known as panhypopituitarism. This is a life-threatening condition, as deficiency of ACTH leads to atrophy of the adrenal cortex and failure of production of vital adrenocorticoids. Diagnosis of hypopituitarism is by measurement of the individual hormones. The commonest causes of pituitary hypofunction are compression by metastatic carcinoma or by an adenoma, but two specific rarer syndromes will be mentioned because they illustrate how congenital and acquired disease may affect the pituitary.
Table 17.3 Causes of adenohypophysial hypofunction
Site | Lesions |
---|---|
Pituitary | Adenoma |
Metastatic carcinoma | |
Trauma | |
Post-partum ischaemic necrosis (Sheehan’s syndrome) | |
Craniopharyngioma | |
Infections | |
Granulomatous diseases | |
Autoimmunity | |
Iatrogenic | |
Hypothalamus | Craniopharyngioma |
Gliomas |
Tumours: adenomas
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Adenomas are the commonest adenohypophysial tumours; carcinomas are rare. Small adenomas may be asymptomatic and found only at postmortem. Histologically, adenomas consist of nodules containing cells similar to those of the normal adenohypophysis, with many small blood vessels between them. They may produce clinical disease in two ways: excess hormone production and pressure effects.
Excess hormone production
Adenomas may produce any adenohypophysial hormone, depending on their cell of origin (Table 17.4); thus presentation may be via excess production of one of the hormones, for example acromegaly due to excess growth hormone production in an adult (Fig. 17.6), or gigantism if this occurs during childhood.
Table 17.4 Types of adenohypophysial adenoma
Type | Remarks |
---|---|
Prolactinoma (chromophobe) | Commonest type |
Produces galactorrhoea and menstrual disturbances | |
GH-secreting (eosinophil) | Produces gigantism in children and acromegaly in adults |
ACTH-secreting (basophil) | Produces Cushing’s disease |
Other | Exceptionally rare |
NEUROHYPOPHYSIS
Neurosecretory cells in the supra-optic and paraventricular nuclei of the hypothalamus give rise to modified nerve fibres which carry the two neurohypophysial hormones—antidiuretic hormone and oxytocin—into the posterior lobe of the pituitary (Fig. 17.3); both hormones are nonapeptides, and are stored until released in response to hypothalamic stimuli.
ADRENALS
The adrenals consist essentially of two separate endocrine glands within a single anatomical organ. The medulla, of neural crest embryological origin, is part of the sympathetic nervous system; it secretes catecholamines, which are essential in the physiological responses to stress, e.g. infection, shock or injury. The cortex, derived from mesoderm, synthesises a range of steroid hormones with generalised effects on metabolism, the immune system, and water and electrolyte balance.
ADRENAL MEDULLA
Histologically, the adrenal medulla consists of chromaffin cells (so called because they produce brown pigments when fixed in solutions of chrome salts) and sympathetic nerve endings. The adrenal medulla is the main source of adrenaline (epinephrine), as it is produced there from noradrenaline (norepinephrine) by the enzyme phenylethanolamine-N-methyl transferase. Elsewhere in the body, sympathetic nerve endings lack this enzyme and their secretory product is thus noradrenaline. Electron microscopy reveals electron-dense granules in the chromaffin cells (Fig. 17.8), similar to those found in other tissues of the so-called amine precursor uptake and decarboxylation (APUD) system. Islands of similar tissue, known as the organs of Zuckerkandl, are sometimes found in other retroperitoneal sites; these have similar functions and a similar pattern of diseases to that seen in the adrenal medulla. Catecholamines are secreted in states of stress and of hypovolaemic shock, when they are vital in the maintenance of blood pressure by causing vasoconstriction in the skin, gut and skeletal muscles. At tissue level, these hormones bind to cell surface receptors, altering cellular levels of a second messenger, cyclic AMP, which brings about rapid functional changes in the cell.
Tumours
Phaeochromocytoma
Phaeochromocytomas are brown, solid nodules, usually under 50 mm in diameter, often with areas of haemorrhagic necrosis (Fig. 17.9). Histologically, they consist of groups of polyhedral cells which give the chromaffin reaction, and are highly vascular (Fig. 17.10).
Neuroblastoma
Neuroblastoma is a rare and highly malignant tumour found in infants and children. Derived from sympathetic nerve cells it may, like phaeochromocytoma, secrete catecholamines, and there may be elevated levels of their metabolites in the urine. Neuroblastomas may also originate from parts of the sympathetic chain outside the adrenal medulla. Secondary spread to liver, skin and bones (especially those of the skull) is common. Surprisingly, neuroblastoma may occasionally mature spontaneously to ganglioneuroma, a benign tumour.
ADRENAL CORTEX
Histologically, the adrenal cortex has three zones (Fig. 17.11). Beneath the capsule lies the zona glomerulosa, so called because the cells are grouped into spherical clusters superficially resembling glomeruli. This zone produces mineralocorticoid steroids such as aldosterone. Most of the adrenal cortex comprises the middle and inner zones—zona fasciculata and zona reticularis, respectively. The middle zone is rich in lipid. The inner zone cells convert lipid into corticosteroids, principally glucocorticoids and sex steroids, for secretion.