Secondary adrenocortical insufficiency

This condition is the result of ACTH deficiency. ACTH deficiency may appear in 2 settings:

1. Selective АСTН deficiency due to prolonged administration of high doses of glucocorticoids. This leads to suppression of ACTH release from the pituitary gland.

2. Panhypopituitarism.

Clinical features of secondary adrenocortical insufficiency are like those of Addison's disease except the following:

1. These cases lack hyperpigmentation because of suppressed production of melanocyte-stimulating hormone (MSH) from the pituitary.

2. Plasma ACTH levels are low-to-absent in secondary insufficiency but are elevated in Addison's disease.

3. Aldosterone levels are normal due to stimulation by renin.

Hypoaldosteronism

Aldosterone is steroid hormone secreted by the adrenal cortex that regulates the salt and water balance in the body. Isolated deficiency of aldosterone with normal cortisol level may occur in association with reduced renin secretion.

Etiopathogenesis. The causes of hyporeninism are:

1. Congenital defect due to deficiency of an enzyme required for its synthesis.

2. Prolonged administration of heparin.

3. Certain diseases of the brain.

4. Excision of an aldosterone-secreting tumour.

Clinical features. The patients with isolated hypoaldosteronism are adults with mild renal failure and diabetes mellitus. The predominant features are hyperkalaemia and metabolic acidosis.

Pheochromocytoma

Pheochromocytoma is generally a benign tumour arising from the adrenal medulla. Pheochromocytoma may occur at any age but most patients are 20-60 years old. These tumours are commonly sporadic but about 10-20% are associated with familial syndromes of multiple endocrine neoplasia (MEN); and are associated with medullary carcinoma of the thyroid, hyperparathyroidism, pituitary adenoma, mucosal neuromas and von Recklinghausen's neurofibromatosis in varying combinations.

The clinical features of pheochromocytoma are predominantly due to secretion of catecholamines, both epinephrine and norepinephrine. The most common feature is hypertension. Other manifestations due to sudden release of catecholamines are congestive heart failure, myocardial infarction, pulmonary oedema, cerebral haemorrhage, and even death.

 

PATHOPHYSIOLOGY OF THYROID GLAND

Diseases of thyroid gland are manifested by qualitative or quantitative alterations in hormone secretion, enlargement of the thyroid, or both. Insufficient hormone secretion results in hypothyroidism or myxedema, in which hypometabolism is a principal feature. Excessive secretion of hormone results in hypermetabolism and other features, together termed hyperthyroidism or thyrotoxicosis.

Enlargement of the thyroid gland may be generalized or focal. Goiters may be associated with increased, normal or decreased hormone secretion.

Only free hormones are available to tissues. Therefore, the metabolic state correlates, more closely, with the concentration of free hormones, than total hormones in plasma.

However isolated disturbances of thyroid hormone-plasma protein interaction, as well as decreased or increased concentration of hormone binding proteins are not accompanied by the development of hypo- and hyperthyroidism. For example, an increase in thyroxine-binding globulin concentration, initially lowers the concentration of free hormone and thus diminishes the quantity of hormone available to tissues. It causes the release of thyroid stimulating hormone and, therefore, increased production of thyroid hormones by the gland.

 As a result, the concentration of free hormone is restored to normal. Opposite changes occur when the concentration of thyroxine-binding globulin declines..

Thyroid hormone resistance: Generalized thyroid hormone resistance is a syndrome characterized by reduced responsiveness to elevated levels of thyroid hormone. The resistance to thyroid hormone action is associated with elevated circulating levels of free thyroxine and free triiodothyronine, elevated serum thyroid stimulating hormone, and intact thyroid stimulating hormone responsiveness to thyroid releasing hormone.

Clinical features include short height, hyporeactivity, attention deficits with mental deficiency or learning disability, and the goiter. Patients are euthyroid or hypothyroid.

HYPOTHYROIDISM

Hypothyroidism results from abnormalities that lead to insufficient synthesis of thyroid hormone. Hypothyroidism dating from birth and resulting in developmental abnormalities is termed cretinism.

The term myxedema designates severe hypothyroidism in which there is accumulation of hydrophylic mucopolysaccharides in the dermis and other tissues, leading to thikening of the facial features and doughy induration of the skin.

Etiology and pathogenesis

In thyroprivic hypothyroidism, loss of thyroid tissue leads to inadequate synthesis of thyroid hormone, despite maximum stimulation of any thyroid remnant by thyroid stimulating hormone.

The most common causes are surgical or radioiodine ablation of the thyroid gland for the treatment of Graves’ disease, a primary idiopathic disorder, autoimmunity (autoimmune thyroiditis)which associated with circulating cytotoxic antithyroid antibodies or, in some cases, antibodies that block the thyroid stimulating hormone receptor, toxic blockade of iodine uptake and tyrosine compounds

Inability to synthesize enough thyroid hormone leads to hypersecretion of thyroid stimulating hormone and hence goiter and hypothyroidism.

Hashimoto's thyroiditis

Hashimoto thyroiditis is the most common cause of hypothyroidism and it is characterized by gradual thyroid failure. This disorder is more common in women than in men.

Hashimoto's thyroiditis is caused primarily by a defect of T cells and this disorder has several pathophysiologic autoimmune mechanisms. T cells activated by thyroid antigens interact with B cells and stimulate the secretion of antithyroid antibodies.

The latter may activate antibody-dependent cytotoxicty mechanisms. Almost all patients with Hashimoto's thyroiditis have antibodies to both thyroglobulin or thyroid peroxidase. Some patients have antibodies against receptors of the thyroid-stimulating hormone that block the action of thyroid-stimulating hormone.

Goiter

The term goiter is defined as thyroid enlargement caused by compensatory hyperplasia and hypertrophy of the follicular epithelium in response to thyroid hormone deficiency. Epidemiologically, goiter occurs in 2 forms: endemic, and non-endemic or sporadic. Prevalence of goiter in a geographic area in more than 10% of the population is termed endemic goiter. Though most endemic goiter are caused by dietary lack of iodine, some cases occur due to goiterogens and genetic factors. Goiterogens are substances, which interfere with the synthesis of thyroid hormones. These substances are drugs used in the treatment of hyperthyroidism and certain items of food such as cabbage, cauliflower, turnips and cassava roots. The etiology of sporadic goitre is unknown. Deficient thyroid hormone production causes excessive TSH stimulation, which leads to hyperplasia of follicular epithelium as well as formation of new thyroid follicles.