Endocrine Function II - Class Notes PDF

NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Thyroid Hormone - Physiology Review Overview Produced by follicle cells of the thyroid gland Thyroxine (T4) 90% of thyroid hormone secreted by t...

NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Thyroid Hormone - Physiology Review Overview Produced by follicle cells of the thyroid gland Thyroxine (T4) 90% of thyroid hormone secreted by the follicle cells is T4 T4 has a longer half life than T3 Triiodothyronine (T3) Half of T4 is converted to T3 by the time the hormones reach the target cells T3 is more biologically active than T4 Synthesis 1  NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Physiological Effects Main physiological effects are generated through the regulation of transcription of various cellular proteins Stimulates metabolism Normal maturation of the nervous system and promotes effects of growth hormone Increases target cell responsiveness to catecholamines Feedback and Regulation of T3/T4 Thyrotropin releasing hormone (TRH) – released by the hypothalamus Thyroid stimulating (TSH) – released by the anterior pituitary Effects of TRH and TSH 2  NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Negative feedback mechanisms Hyperthyroidism When the tissues are exposed to excessive amount of thyroid hormone (T3/T4). Etiologies Primary hyperthyroidism Genetic predisposition: mutations in the TSH receptor protein causing a variety of familial hyperthyroid disorders Thyroiditis: subacute (15-20%), postpartum, silent Toxic nodular or multinodular goiter (Plummer disease) (15-20%) Thyroid adenomas (3-5%) Thyroid cancer 3  NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Secondary hyperthyroidism TSH-secreting pituitary adenomas Special Cases Graves disease (70%) Overdose of thyroid medication (sometimes called thyrotoxicosis) Pathophysiology Primary hyperthyroidism Increased T3/T4 secretion from thyroid gland leads to TSH suppression Secondary hyperthyroidism Increased TSH secretion from anterior pituitary gland leads to increased T3/T4 secretion Clinical Consequences Due to increased T3/T4 Increased metabolic rate Increase neuromuscular activity Increased SNS stimulation Due to increased TSH Goiter possible with secondary hyperthyroidism 4  NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Special Case of Hyperthyroidism Graves’ Disease An autoimmune disease causing hyperthyroidism Pathophysiology Overproduction of thyroid autoantibodies called thyroid stimulating immunoglobulin (TSI) TSIs mimic effect of TSH Elevated levels of TSI’s stimulate excess T3/T4 secretion Elevated plasma levels of T3/T4 cause TSH suppression Clinical Consequences Problems due to hyperthyroidism Goiter due to TSH-like effects of TSI and accumulation of TSI in thyroid gland tissue Effects of thyroid stimulating immunoglobulins on ocular tissue (95% incidence) - degeneration of extraocular muscles and edematous fluid accumulation in orbit 5  NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Hypothyroidism Overview Primary hypothyroidism Loss of thyroid tissue leads to decreased T3/T4 Secondary hypothyroidism Failure of pituitary to synthesize adequate TSH Etiologies Primary hypothyroidism Iodine deficiency Congenital lack of thyroid tissue Hashimoto’s thyroiditis: Autoimmune destruction of thyroid Secondary hypothyroidism Stroke to hypothalamus or pituitary Pituitary tumor (benign or cancerous) Postpartum pituitary necrosis 6  NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Pathophysiology Primary hypothyroidism Decreased T3/T4 secretion from thyroid gland leads to increased TSH secretion Secondary hypothyroidism Decreased TSH secretion from anterior pituitary gland leads to decreased T3/T4 secretion General Myxedema: collagen in connective tissues is replace by other proteins and muco- polysaccharides creating a complex that binds to water. Clinical Consequences Due to decreased T3/T4 Decreased metabolic rate Decreased neuromuscular activity Decreased SNS activity Due to increased TSH Goiter possible with primary hypothyroidism from iodine deficiency 7  NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Cortisol - Physiology Review Overview Cortisol is the predominate glucocorticoid hormone secreted by the adrenal cortex Note: Adrenal cortex also secretes aldosterone and androgens (i.e., testosterone) Physiological Effects Main physiological effects are to promote survival during periods of extreme stress Glucose metabolism Raises blood glucose levels, decreases glucose uptake in most tissues, stimulates gluconeogenesis Protein metabolism Promotes breakdown of proteins in muscle and collagen Lipid metabolism Lipolysis in extremities; lipogenesis in face and trunk Inhibition of immune and inflammatory responses Decreased numbers and activity of T-cells and B-cells Decreased macrophage, neutrophil and mast cell activity Decreased release of inflammatory mediators Increases target cell responsiveness to catecholamines (permissive effect) Feedback and Regulation of Cortisol Corticotropin-releasing hormone/factor (CRH/CRF) – released by the hypothalamus 8  NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Adrenocorticotropic hormone (ACTH) – released by the anterior pituitary Effects of CRH and ACTH Negative feedback mechanisms 9  NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Hypercortisolism Overview Primary Hypercortisolism (Cushing Syndrome) Excess levels of cortisol due to hyperfunction of adrenal cortex or ectopic cortisol production Secondary Hypercortisolism (Cushing Disease) Excessive secretion of ACTH leads to increased cortisol secretion Etiologies Primary Hypercortisolism Adrenal adenomas or carcinomas Non-adrenal tumor synthesizes and secretes excessive amounts of cortisol Administration of cortisol-like medications (hydrocortisone, prednisone, etc.) Secondary Hypercortisolism Pituitary adenomas with hypersecretion of ACTH (75% to 80% of cases) Non-pituitary tumor synthesizes and secretes excessive amounts of ACTH Pathophysiology Primary hypercortisolism Increased cortisol secretion from adrenal cortex leads to ACTH suppression Secondary hypercortisolism Increased ACTH secretion from anterior pituitary gland leads to increased cortisol and androgen secretion 10  NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Clinical Consequences Due to Cortisol excess Hyperglycemia Collagen breakdown Increased SNS activity Immunosuppression Physical body changes: weight gain; round face/fat pad development on upper back, central obesity, thin extremities Due to increased ACTH in secondary hypercortisolism Hyperpigmentation of skin Hirsutism/acne/male pattern baldness (due to elevated androgens) 11  NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Hypocortisolism Also know as adrenocortical insufficiency or Addison disease Overview Primary hypocortisolism Atrophy or destruction of adrenal cortex leads to decreased cortisol and aldosterone secretion Secondary hypocortisolism Decreased ACTH secretion leads to decreased cortisol secretion Etiologies Primary hypocortisolism Autoimmune destruction of adrenal cortex Familial adrenal (glucocorticoid) insufficiency (autosomal recessive disease causing mutations in the ACTH receptors or other factors affecting ACTH signaling) Tuberculosis Secondary hypocortisolism Anterior pituitary hypofunction (tumor, stroke...) Special case: Suppression of ACTH by exogenous glucocorticoids can lead to hypocortisolism when medications are discontinued abruptly Pathophysiology Primary hypocortisolism Decreased cortisol secretion from adrenal cortex leads to increased ACTH secretion Secondary hypocortisolism Decreased ACTH secretion from anterior pituitary gland leads to decreased cortisol secretion 12  NURS 7053 – Pathophysiology I for DNP Students Alterations of Endocrine Function II - Class Notes Clinical Consequences Due to Cortisol deficiency Hypoglycemia Decreased SNS activity Due to aldosterone deficiency Inability to conserve sodium and water Impaired renal secretion of potassium ion Impaired renal secretion of hydrogen ion Due to increased ACTH in primary hypocortisolism Hyperpigmentation of skin “We discover a most remarkable and, as far as I know, characteristic discoloration taking place in the skin...sufficiently marked indeed as generally to have attracted the attention of the patient himself, or the patient’s friends...It may be said to present a dingy or smoky appearance, or various shades of deep amber or chestnut brown” (Addison, 1855). 13