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Mechanisms of Hormonal Alterations
- Abnormalities in endocrine function may be caused by elevated or depressed hormone levels that result from (a) faulty feedback systems, (b) dysfunction of the gland, (c) altered metabolism of hormones, or (d) production of hormones from nonendocrine tissues.
- Target cells may fail to respond to hormones because of (a) cell surface receptor-associated disorders, (b) intracellular disorders, or (c) circulating inhibitors.
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Alterations of the Hypothalamic-Pituitary System
- Dysfunction in the release of hypothalamic hormones is probably related to interruption of the connection between the hypothalamus and pituitary, the pituitary stalk.
- Disorders of the posterior pituitary include syndrome of inappropriate ADH secretion (SIADH) and diabetes insipidus. SIADH secretion is characterized by abnormally high ADH secretion; diabetes insipidus is characterized by abnormally low ADH secretion.
- In SIADH, high ADH levels interfere with renal free water clearance, leading to hyponatremia and hypoosmolality, and is associated with brain injury and with certain forms of cancer, apparently because of ectopic secretion of ADH by tumor cells.
- Diabetes insipidus may be neurogenic (caused by insufficient amounts of ADH) or nephrogenic (caused by an inadequate response to ADH). Its principal clinical features are polyuria and polydipsia.
- Hypopituitarism can be primary (dysfunction of the pituitary) or secondary (dysfunction of the hypothalamus). Primary Hypopituitarism can result from pituitary tumor, trauma, infections, stroke, or surgical removal.
- Hypopituitarism can affect any or all of the pituitary hormones and symptoms may range from mild to life threatening.
- Hypopituitarism is caused by pituitary adenomas. These are usually benign, slow-growing tumors that arise from cells of the anterior pituitary.
- Expansion of a pituitary adenoma causes both neurologic and secretory effects. Pressure from the expanding tumor causes hyposecretion of cells, dysfunction of the optic chiasma (leading to visual disturbances), and dysfunction of the hypothalamus and some crania nerves.
- Hypersecretion of growth hormone (GH) causes acromegaly, in which GH secretion becomes high and unpredictable. Pituitary adenoma is the most common cause of acromegaly.
- Prolonged, abnormally high levels of GH lead to proliferation of body and connective tissue and slowly developing renal, thyroid, and reproductive dysfunction.
- Prolactinomas result in galactorrhea, hirsutism, amenorrhea, hypogonadism, and osteopenia.
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Alterations of Thyroid Function
- Thyrotoxicosis is a general condition in which elevated thyroid hormone (TH) levels cause greater than normal physiologic responses. The condition can be caused by a variety of specific diseases, each of which has its own pathophysiology and course of treatment.
- In general, hyperthyroidism has a range of endocrine, reproductive, gastrointestinal, integumenatry and ocular manifestations. These are caused by increases circulating levels of TH and by stimulation of sympathetic division of the autonomic nervous system.
- Graves disease, the most common form of
- hyperthyroidism, is caused by an autoimmune mechanism that overrides normal
- mechanisms for control of TH secretion and is characterized by thyrotoxicosis,
- ophthalmopathy, and circulating thyroid-stimulating immunoglobulins.
- Toxic modular goiter and toxic multinodular goiter occur when TH-regulating mechanisms and abnormally hypertrophy of the thyroid gland cause hyperthyroidism. Toxic multinodular goiter is caused by independently functioning follicular cell adenomas.
- Thyrotoxic crisis is a severe form of hyperthyroidism that is often associated with physiologic or psychologic stress. Without treatment, death occurs quickly.
- Primary hypothyroidism is caused by deficient production of TH by the thyroid gland. Secondary hypothyroidism is caused by hypothalamic or pituitary dysfunction. Symptoms depend on the degree of TH deficiency. Common manifestations include decreased energy metabolism, decreased heat production, and myxedema.
- Acute thyroiditis is inflammation of the thyroid gland, often caused by a bacterium that can result in hypothyroidism.
- Subacute thyroiditis is a self-limiting nonbacterial inflammation of the thyroid gland. The inflammatory process damages follicular cells, causing leakage of T3 and T4. Hyperthyroidism then is followed by transient hypothyroidism, which is corrected by cellular repair and a return to normal levels in the thyroid.
- Autoimmune thyroiditis is associated with infiltration of fibrosis of the thyroid, circulating thyroid antibodies, and gradual loss of thyroid function. Autoimmune thyroiditis occurs in those individuals with genetic susceptibility to an autoimmune mechanism that causes thyroid damage and eventual hypothyroidism.
- Myxedema is a sign of hypothyroidism caused by alterations in connective tissue with water-binding proteins that leads to edema and thickened mucous membranes.
- Myxedema coma is a severe form of hypothyroidism that may be life threatening without emergency medical treatment
- Congenital hypothyroidism is absence of thyroid tissue during fetal development or defects in hormone synthesis.
- Thyroid carcinoma is a relatively rare cancer. The most consistent causal risk factor associated with thyroid carcinoma is exposure to ionizing radiation, especially in childhood.
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Alterations of Parathyroid Function
- Hyperparathyroidism, which may be primary or secondary, is characterized by greater than normal secretion of parathyroid hormone (PT)
- Primary hyperparathyroidism is caused by an interruption of the normal mechanisms that regulate calcium and PTH levels. Manifestations include chronic hypercalcemia, increased bone resorption, and hypercalciuria.
- Secondary hyperparathyroidism is a compensatory response to hypocalcemia and often occurs with chronic renal failure.
- Hypoparathyroidism, define by abnormally low PTH levels, is caused by thyroid surgery, autoimmunity, or genetic mechanisms.
- The lack of circulating PTH in hypoparathyroidism causes depressed serum calcium levels, increased serum phosphate levels, decreased bone resorption, and eventual hypocalciuria.
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Dysfunction of the Endocrine Pancreas: Diabetes Mellitus
- Diabetes mellitus is a group of disorders characterized by glucose intolerance, chronic hyperglycemia, and disturbances of carbohydrate, protein, and fat metabolism.
- A diagnosis of diabetes mellitus is based on elevated plasma glucose concentrations and measurement of glycosolated hemoglobin. Classic signs and symptoms are often present as well.
- The two most common types of diabetes mellitus are type 1 and type 2.
- Type 1 diabetes mellitus is characterized by loss of beta cells, islet cell antibody, a lack of insulin, and excess of glucagon, which causes improper metabolism of fat, protein, and carbohydrates.
- Type 1 diabetes mellitus seems to be caused by a gradual process of autoimmune destruction of beta cells in genetically susceptible individuals.
- In type 1 diabetes mellitus, hyperglycemia causes polyuria and polydipsia resulting from osmotic dieresis.
- Ketoacidosis is caused by increased levels of circulating ketones without the inhibiting effects of insulin. Increased levels of circulating fatty acids and weight loss are all manifestations of type 1 uncontrolled diabetes mellitus.
- Type 2 diabetes mellitus is caused by genetic susceptibility that is triggered by environmental factors. The most compelling environmental risk factor is obesity.
- In the obese, insulin has a diminished ability to influence glucose uptake and metabolism.
- Some insulin production continues in type 2 diabetes mellitus, but the weight and number of beta cells decrease. There are dysfunctional levels of both insulin and glucagon.
- Gestational diabetes is glucose intolerance during pregnancy.
- Acute complications of diabetes mellitus include hypoglycemia, diabetic ketoacidosis, hyperosmolar hyperglycemic nonketotic coma, the Somogyi effect, and the dawn phenomenon.
- Hypoglycemia is a complication related to insulin treatment.
- Diabetic Ketoacidosis develops when there is an absolute or relative deficiency of insulin and an increase in the insulin counterregulatory hormones of catecholamines, cortisol, glucagon, and growth hormone.
- Hyperosmolar hyperglycemic nonketotic syndrome is pathophysiologically similar to diabetic Ketoacidosis, although levels of free fatty acids are lower in hyperosmolar nonacidotic diabetes and lack of ketosis indicates that some level of insulin is present.
- The Somogyi effect is a combination of hypoglycemia and rebound hyperglycemia.
- The dawn phenomenon is an early morning rise in glucose levels caused by nocturnal elevations in growth hormone.
- Chronic seqeulae of diabetes mellitus include diabetic neuropathies, microvascular disease (e.g., retinopathy, nephropathy), macrovascular disease (e.g., coronary artery disease, stroke peripheral vascular disease), and infection.
- Microangiopathy is caused by thickening of the capillary basement membrane and eventual decreased tissue perfusion affecting the microcirculation.
- Macrovascular diseases associated with diabetes mellitus is most often related to the proliferation of fibrous plaques in the arterial wall and to elevated lipid levels.
- Incidence of coronary heart disease, peripheral vascular disease, and stroke is greater in those with diabetes than in nondiabetic individuals.
- Individuals with diabetes are at risk for a variety of infections.
- Infection may be related to sensory impairment and resulting injury, hypoxia, increased proliferation of pathogens in elevated concentrations of glucose, decreased blood supply associated with vascular damage, and impaired white cell function.
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Alterations of Adrenal Functions
- Disorders of the adrenal cortex are related to hyperfunction or hypofunction. No known disorders are associated with hypofunction of the adrenal medulla, but medullary hyperfunction causes clinically defined syndromes.
- Cortical hyperfunction, or hypercortisolism, causes Cushing syndrome, which may or may not involve the pituitary gland, and Cushing disease, which is hypercortisolism with pituitary involvement.
- Hypercortisolism is usually caused by Cushing disease but can also be caused by ectopic production of cortisol or by adrenocortical tumors. Complications include obesity, diabetes, protein wasting, immune suppression, and mental status changes.
- Excessive aldosterone secretion causes hyperaldosteronism, which may be primary or secondary. Primary hyperaldosteronism is caused by an abnormality of the adrenal cortex. Secondary hyperaldosteronism involves an extra-adrenal stimulus, often angiotensin.
- Hyperaldosteronism promotes increased sodium reabsorption, corresponding hypervolemia, increased extracellular volume (which is variable), and hypokalemia related to renal reabsorption of sodium.
- Hypersecretion of adrenal androgens and estrogens can be a result of adrenal tumors, either adenomas or carcinomas. Hypersecretion of estrogens causes feminization, the development of female sex characteristics. Hypersecretion of estrogens causes feminization, the development of female sex characteristics. Hypersecretion of androgens causes virilization, the development of male sex characteristics.
- Hypofunction of the adrenal cortex can affect glucocorticoids or mineralocorticoid secretion or both. Hypofunction can be caused by a deficiency of ACTH or by a primary deficiency in the gland itself.
- Hypercortisolism, or low levels of cortisol, is caused by inadequate adrenal stimulation by ACTH or by primary cortisol hyposecretion. Primary adrenal insufficiency is termed Addison disease.
- Addison disease is characterized by elevated ACTH levels with inadequate corticosteroid synthesis and output.
- Manifestations of Addison disease are related to hypercortisolism and hypoaldosteronism. Symptoms include weakness, fatigability, hypoglycemia, and related metabolic problems, lowered response to stressors, vitiligo, and manifestations of hypovolemia and hyperkalemia.
- Hyperfunction of the adrenal medulla is usually caused by a pheochromocytoma, a catecholamine producing tumor. Symptoms of catecholamine excess are related to their sympathetic nervous system effects and include hypertension, palpitations, tachycardia, glucose intolerance, excessive sweating, and constipation.
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