Endocrinology Flashcards
(10 cards)
Graves’ disease
Syndrome that may consist of hyperthyroidism, goiter, eye diseases (orbitopathy) and occasionally a dermopathy called periorbial myxedema
Hyperthyroidism is the most common feature of graves
Causes: autoantibodies to TSH receptor called TRAb that activate the receptor - stimulating thyroid hormone synthesis and secretion, thyroid growth causing a diffuse goiter
Pathogenesis of Graves
Thyroid cell expression of HLA molecules
Express MHC II molecules
Could be a direct result of viral or other infections of thyroid epithelial cells or can be induced by cytokines
Clinical significance: Class II molecules activates auto-reactive T cells with the potential for persistence of thyroid disease
Predisposing factors of graves
Association with certain alleles of HLA
Possible infections of the thyroid gland itself (congenital rubella) could initiate MHC II expression
Stress-induced immune expression
Moderate amounts of estrogen enhances immunologic reactivity
Development of postpartum: new onset or recurrence
Clinical manifestations of Graves
Graves opthalmopathy
- Stimulators autoantibodies recognize TSH receptor on orbital fibroblasts
- Increased production of HA by these cells to form new fatty cells
- That causes the accumulation of HA and edema within orbit -> an increase in orbital fat volume and orbital muscles
Skin
Warm and smooth
Increase in sweating due to calorigenesis
Onycholysis (Plummer’s nails): softening of nails as a result of secondary infection, coexistence yeast infection
CV effects
T3 on the heart similar to beta-adrenergic stimulation which increases HR and cardiac contractibility
LVEF and CO
Posterior pituitary syndromes
Central diabetes insipidus Excessive urination (polyuria) due to inability of kidney to rear absorb water properly from urine
Cause: ADH deficiency - collectingduct not permeability to water -> large volume of dilute urine
Etiology: idiopathic, head trainer,tumors, inflammatory, disorders of hypothalamus and pituitary
SIADH
ADH excess causes resorption of excessive amounts of free water -> hypoatremia
Causes: secretion of ectopic ADH malignant neoplasms or drugs that increase ADH secretion
Hashimoto thyroiditis
Chronic autoimmune thyroiditis - the most common cause of hypothyroidism in iodine-sufficient areas
Cause: combo of genetic and environmental factors
Clinical characterization:
Gradual thyroid failure, with or without goiter
High serum concentration of antibodies against thyroid antigens
Follicular destruction
Pathogenesis of Hashimoto
Thyroid antigens:
Thyroglobulin
Thyroid peroxidase
TSH receptor
ROle of B cells: nearly all pts have high serum concentration of antibodies to TG and TPO
TSH receptors antibodies BLOCK action of TSH
Role of T cells:
Apoptotic destruction of thyroid cells by activation cytotoxic T cells
Regulation of local immune response
Hypoadrenalism: adrenal insufficiency
Destruction of adrenal cortex and reduction of adrenal hormones (glucocorticoids - cortisol and/or mineralcorticoids - aldosterone)
Types:
Primary - Addisons = inability of adrenal gland to produce enough steroid hormones, the most common cause is autoimmune adrenalitis
Secondary insufficiency - decreased pituitary or hypothalamic stimulation of adrenal glands
Molecular immunoopathogenesis of primary adrenal insufficiency
DC present adrenocorticol antigens to CD4+ T helper cells within lymph nodes that causes the activation and expression of cytotoxic lymphocytes and autoreactive B cells producing 21-hydroxylase antibodies
The continuing progressive destruction of adrenal cortex is mediated by several mechanisms
Cytotoxicity by CD8+ and CD4+ -> activation of complement system -> cytotoxic effects of inflammatory cytokines and free radicals released by inflammatory cells
Addison’s disease - clinical symptoms
Hyperpigmentation-
due to excess ACTH secretion (loss of negative feedback by cortisol)
ACTH stimulates melanocytes in skin by processing the POMC protein
Hypotension
Due to fluid depletion by aldosterone deficiency
