Module 3: Endocrine System Disorders & Nervous System Disorders Flashcards
Discuss the etiology of endocrine disorders in general.
Disorders occur because of hyposecretion, hypersecretion, or nonresponsiveness by target cells.
Etiology may be congenital, infectious, autoimmune, neoplastic, idiopathic, or iatrogenic.
Causes of hypersecretion
secreting tumors, autoimmune disease, or excessive stimulation of the gland by trophic signals.
Causes of hyopsecretion
failure or congenital absence of glandular tissue, autoimmune destruction, surgical removal of the gland, or lack of normal trophic signals.
Hyporesponsiveness
Clinically similar to hyposecretion; due to target tissue dysfunction - also called tissue resistance.
Functional disorders
Caused by non-endocrine disease such as chronic renal failure, liver disease, or heart failure
Tissue resistance
Occurs when target tissue fails to respond to a hormone (hormone resistance or target tissue resistance)
Iatrogenic
Induced by medical treatments such as chemotherapy, radiation therapy, or surgical removal of glands
Treatment for endocrine hyperfunction involves removal or destruction of glandular tissue with resultant chronic hypofunction
Chronic hormone replacement therapy may be required
Classification of Endocrine Disorders
Primary: intrinsic malfunction of the hormone-producing gland
Secondary: abnormal pituitary secretion of trophic signals
Since clinical manifestations are similar, lab results can help distinguish between primary and secondary
Explain the feedback-loop systems in thyroid disorders and how laboratory testing is based on feedback loop communications.
There is a feedback loop communication between the hypothalmic-pituitary system and the target gland.
Ex. In primary hypothyroidism, the thyroid fails to secrete thyroid hormones and serum T4 (thyroxine) drops. TSH levels rise as the pituitary gland attempts to stimulate the malfunctioning thyroid.
In secondary hypothyroidism, the pituitary gland fails to release TSH, secondarily reducing thyroid gland production, so both T4 and TSH are low.
Hypothyroidism Etiology and Pathogenesis
primary & secondary
Deficient Thyroid hormone
Primary (majority are primary due to intrinsic dysfunction)
Congenital, defective hormone synthesis, iodine deficiency, anti-thyroid drugs, iatrogenic loss of thyroid tissue
Secondary – related to pituitary or hypothalamic failure – cause pituitary tumor or treatment of tumor
Clinical manifestations of primary hypothyroidism (which includes acute and subacute thyroiditis, painless thyroiditis, pp thyroiditis, autoimmune thyroiditis, iodine deficiency, iatrogenic)
.
(lab results and general symptoms)
Low T4 and high TSH Lethargy Weakness Dry, pale, cool, coarse skin Cold Intolerance Weight gain Constipation Bradycardia, wide pulse pressure Dyspnea, chest pain Possible goiter Coarse hair Sluggish reflexes, mental impairment, forgetful, depressed affect, deafness Facial edema (esp. periorbital) Heavy, prolonged menses, infertility, decreased libido
Clinical manifestation in an infant.
Few sx present at birth. Usually become sx in the first few months of life: dull appearance, thick protuberant tongue, thick lips (poor feeding), prolonged neonatal jaundice, poor muscle tone, bradycardia, mottled extremities, umbilical hernia, and hoarse cry.
Hashimoto’s disease
1) Most common cause of acquired thyroiditis
2) AKA autoimmune thyroiditis – will cause destruction of thyroid tissue by circulating auto-antibodies and infiltration by lymphocytes
3) Postpartum thyroiditis – like Hashimoto’s – occurs 6-8 months pp – spontaneous recovery in 95% of cases
Clinical manifestations in older children
Growth retardation, delayed bone development and delayed or precocious puberty may occur in addition to the symptoms displayed by adults.
Define Myxedema
Generalized non-pitting edema which occurs in severe or prolonged thyroid deficiency.
Etiology and pathogenesis of Hyperthyroidism
1) Excessive thyroid hormone synthesis & secretion
2) Grave’s disease – most common cause – result of stimulation of thyroid with antibodies against TSH receptor (Type II). Target is not destroyed but malfunctions.
3) Auto-antibodies bind with receptors for TSH and stimulate production of T4
- Feedback loop out of commission
Clinical manifestations of hyperthyroidism (Graves)
1) Adrenergic stimulation – tachycardia, nervousness, lid lag, tremor, increased B/P
2) Excess T4 – increased O2 consumption, changes in protein metabolism
3) Immunologic stimulation – goiter
4) Triad = hyperthroidism, exophthalmus, goiter
5) Thyroid Storm
General symptoms: sleeplessness, nervousness muscle weakness susceptible to infection skin: warm, silky, damp heat intolerance Increased appetite with wt. loss increased gastric motility tachycardia dyspnea diffuse or nodular enlarged thyroid silky hair, loose nails hyperreflexia eyes: burning, tearing, diplopia, lid lag, prominent (exophthalmia with Graves) absence of forehead wrinkling decreased or absent menses
Explain stress hyperglycemia.
Hormones released during stress increase blood glucose levels and oppose the effects of insulin. Stress hyperglycemia can be precipitated by catecholamines, glucocorticoids, and glucagon.
Modifiable risk factors for diabetes
Type 2 - Obesity, sedentary lifestyle
Non-modifiable risk factors for diabetes
Type 1 - genetic, viral infection or environmental exposure triggers autoimmune response, idiopathic
Type 2- family history, member ethnic minority, female, most are over age 40
Type 1 Diabetes definition.
Characterized by destruction of the B cells of the pancreas. Peak ages: 2, 4-6, 10-14, but can occur at any age. More prevalent in caucasians and males.
Type 1 Diabetes etiology.
1A is immune mediated (most common of type 1). 80-90% are polygenic. Monogenic is rare.
- Result of autoimmune attack on B cells of pancreas. Can be triggered by virus or environmental exposure.
- Strongly associated with presence of a gene in the major histocompatibility complex on chromosome 6 & HLA associated.
1B etiology is not known - idiopathic B-cell destruction without autoimmune markers or HLA association.
Diabetes Type 1 Pathogenesis
1) Autoantigens form on insulin producing beta cells and begin circulating.
2) Processing and presentation of autoantigen occurs by APC’s (antigen presenting cells).
3) T helper 1 & 2 lymphocytes are activated.
4a) T helper 1 activates macrophages with release of Interleuken 1 and tumor necrosis factor alpha. Also activates autoantigen specific T cytotoxic (CD8) cells.
4b) T helper 2 cells activate B lymphocytes to produce islet cell autoantibodies and antiGAD65 antibodies.
5) These cause destruction of beta cells with decreased insulin secretion.
Type 1 Diabetes clinical manifestations.
Hyperglycemia
Polydipsia – fluid loss increases thirst
Polyuria- increased serum glucose causes osmotic diuresis
Polyphagia – starved cells trigger neural response to eat more
Weight loss – fat is being burned for energy
Fatigue
Type 2 Diabetes etiology.
1) Resistant to the action of insulin on peripheral tissues.
2) More common and continues to rise in incidence
3) Native Americans (Pima Indians, esp.), Hispanics, Blacks
4) Mostly >40 years old but may be seen in adolescents
Type 2 Diabetes pathogenesis
1) Genes influence insulin resistance (60-80% of cases) or beta cell dysfunction OR both
2) May also see abnormal glucagon secretion
3) Beta cell function is affected due to amyloid deposits, fatty deposits in pancreas and liver, or pancreatic fibrosis or cytokine toxicity but insulin is still produced for a time
* Insulin resistance and b-cell dysfunction produce a relative lack of insulin. Pancreas produces sufficient insulin, but it is resistant to effective use resulting in increased blood glucose levels.
Define GDM
Glucose intolerance of variable severity with onset or first recognition during pregnancy.
GDM etiology
1) Normal pregnancy is a diabetogenic state
2) Resembles type 2 - tissue insulin resistance (most likely precipitated by placental hormones)
3) Wt. gain in pregnancy also increases insulin resistance
Risk factors for GDM
Risk factors: family history, ethnic group, >25 years old, prior history of GDM or PCOS, overweight, OB complication, large baby
