Colin M. Feek

The hypothalamic-pituitary-adrenal axis

Anterior pituitary corticotrophin cells secrete ACTH as part of a larger precursor molecule, pro-opiomelanocortin. Post-translational cleavage of this precursor yields three major peptides: ACTH, beta-LPH and N-POMC. Experiments both in vivo and in vitro suggest that N-POMC may act as a prohormone amplifier for ACTH-induced adrenal steroidogenesis and as regulator of adrenocortical cell growth. The secretion of POMC is under the control of CRF. These findings are discussed in relation to the pathophysiology of corticotrophinoma. The primary defect in this condition appears to reside at the level of the anterior pituitary cell and is readily amenable to treatment by trans-sphenoidal microsurgery. The estimation of plasma ACTH concentrations is proving useful in the monitoring of various clinical conditions including Addisons disease and congenital adrenal hyperplasia.

Effects of hyperthyroidism and radioactive iodine given to ablate the thyroid on the composition of whole stimulated saliva

OBJECTIVE For many years there has been speculation about possible damage to the salivary glands following administration of ablative doses of radioactive iodine for treatment of hyperthyroidism. We have investigated the changes that occur in the composition of saliva in hyperthyroidism and after the administration of an ablative dose of radioactive iodine to hyperthyroid subjects.

The Thyroid Gland

Thyroid disease is the commonest endocrine disorder. The hormones secreted by the thyroid, thyroxine (T4) and triiodothyronine (T3), are regulated by anterior pituitary secretion of thyrotrophin (TSH). TSH stimulates not only function but also growth of the thyroid gland. This is mediated through two different regions of the TSH receptor so that function and growth are usually coupled together. In its turn TSH is regulated by the hypothalamic secretion of thyrotrophin-releasing hormone (TRH).

The Adrenal Gland

The steroids secreted by the adrenal cortex are principally glucocorticoid (cortisol), mineralocorticoid (aldosterone) and sex steroids (dehydroepian- drosterone, androstenedione, oestradiol and testosterone) (Fig. 2.1). The adrenal cortex is divided into three zones, with glucocorticoids and sex steroids being secreted by the zona reticularis and zona fasciculata, and mineralocorticoids by the zona glomerulosa. Cortisol secretion is regulated by the anterior pituitary secretion of ACTH (corticotrophin) but the major stimulus to the secretion of aldosterone is angiotensin II, formed by activation of the renin-angiotensin system. Sodium depletion not only stimulates the renin-angiotensin system but also enhances the responses of the zona glomerulosa to angiotensin II. Hyperkalaemia is another stimulus to aldosterone secretion. A factor other than ACTH has been suggested for the control of adrenal androgen production but evidence is far from convincing. In its turn ACTH is regulated by the hypothalamic secretion of cortico- trophin-releasing factor (CRF).

Parathyroid Glands, Calcium and Bone Metabolism

The major organs involved in calcium homeostasis are the intestine, kidneys and bone. Parathyroid hormone (PTH), vitamin D3 and, possibly, calcitonin act to maintain ionised plasma calcium levels within the normal range (Fig. 6.1).

The Endocrine Pancreas

The endocrine pancreas consists of the islets of Langerhans, the cells of which originate from the neuroectoderm and are part of the diffuse endocrine system (APUD cells). The islet is composed of four main types of cells: α-cells mainly secrete glucagon, β-cells secrete insulin, δ-cells secrete somatostatin and PP-cells pancreatic polypeptide. Whilst the physiological roles for glucagon and insulin are well recognised, the functions of the other two hormones are not clear.

The Pituitary Gland

The anterior pituitary gland synthesises and secretes growth hormone (hGH), prolactin (PRL), gonadotrophins (LH and FSH), thyrotrophin (TSH) and corticotrophin (ACTH).