Lecture 28: Endocrine Pathology and Diabetes Flashcards
what is diabetes mellitus
abnormal metabolic state characterised by glucose intolerance due to inadequate insulin action
difference between T1D and T2D
T1D:
- juvenile onset
- destruction of B cells
- result of viral infection/ autoimmune
- insulin dependent
T2D:
- maturity onset
- due to defective insulin action
- insulin resistant
describe the pathogenesis of T1D
- viral infection (coxsackie B?) in genetically susceptible children
- infection perturbs immune regulation resulting in loss of tolerance
- auto reactive T cells infiltrate islets –> insulinitis and destroy B cells
- autoantibodies detectable against variety of B cell antigens
- abrupt clinical onset when B cell loss becomes critical –> hyperglycaemia / ketoacidosis
describe pathogenesis of T2D
- complex multifactorial and polygenic
- insulin resistance –> reduced ability of peripheral tissues to respond to insulin
- B cell dysfunction –> inadequate insulin secretion in face of hyperglycaemia and insulin resistance
give examples of complications of diabetes
- retinopathy
- nephropathy
- peripheral vascular disease
- infections
- peripheral neuropathy
- autonomic neuropathy
- atherosclerosis
- MI
- Hypertension
etc
outline renal complications of diabetes
- diabetic nephropathy
- glomerular lesions –> diffuse mesangial sclerosis and nodular glomerulosclerosis (damage to basement membrane accompanied by proteinuria
- vascular lesions –> atherosclerosis of large vessels and arteriosclerosis of small vessels; hyaline arteriosclerosis of efferent arteriole
- pyelonephritis w/ papillary necrosis
what is the most common cause of hyperpituitarism
- adenoma of ant. pit.
describe the adenomas the types of adenomas that can cause hyperpituitarism
- can be macro or micro and functional or non functional
- functional assc. w/ distinctive endocrine syndromes
- -> prolactinomas most common and assc. w/ loss of libido and infertility
- macro adenomas assc. w/ mass effects e.g. visual disturbance
what is acromegaly
clinical syndrome assc. w/ excess growth hormone prod. by pituitary adenoma in adulthood
- gigantism similar pathogenesis but exposure occurring prior to epiphyseal fusion
list some causes of pituitary hypofunction
- adenoma
- metastatic carcinoma
- post-partum ischaemic necrosis (Sheehan’s syndrome)
- infection
give examples of how ant. pit. hypofunction can be characterised
- hypothyroidism
- hypoadrenalism
list some types of thyroid disease
- hypothyroidism
- hyperthyroidism
- colloid goitre
give some causes of hypothyroidism
- iodine deficiency
- congenital biosynthetic defect/ dyshormonogenetic goitre
- post-ablative e.g. surgery, radiotherapy
- Hashimoto’s (auto immune thyroiditis) –> most common
- drugs e.g. lithium
describe Hashimoto’s thyroiditis
- lymphocytic infiltrate w/ formation of reactive lymphoid follicles w/ germinal centres
- degenerative changes in thyroid follicular epi cells –> Hurthle cell change
describe the pathogenesis of Hashimoto’s
- thyroid epi –> breakdown in self tolerance and induction of thyroid autoimmunity
- T-cell mediated cytotoxicity
- Thyrocyte injury from activated macrophages (assc. w/ chronic inflammation and fibrosis)
- plasma cells w/ anti-thyroid Ab –> Ab-dependent cell mediated cytotoxicity
give some causes of hyperthyroidism
- diffuse toxic hyperplasia
- -> Grave’s disease
- hyper functioning toxic multi nodular goitre
- hyper functioning toxic adenoma
- thyroiditis
- -> lymphocytic
- -> granulomatous
- struma ovarii
- exogenous thyroid hormone
- thyroid gland tumours –> follicular adenoma
describe Grave’s disease
- breakdown in tolerance to thyroid autoantigens producing autoantibodies incl. thyroid stimulation immunoglobulin
- thyroid stimulating immunoglobulin binds to TSH receptor mimicking impact of TSH
outline types of multinodular goitre
- endemic –> areas of iodine deficiency e.g. mountainous areas
- sporadic –> seen in females, young adulthood, ingestion of foods, substances that interfere w/ synthesis of thyroxine biosynthesis
- rarely dyshomonogenetic goitre due to congenital enzyme defects affecting thyroxine biosynthesis
- usually eythyroid, rarely hyperthyroid –> toxic multinodular goitre
name some clinical effects of multinodular goitre
- difficulty swallowing
- difficulty breathing
- hoarse voice
give examples of differentiated thyroid tumours
- papillary carcinoma –> affects young
- follicular carcinoma –> affects young to middle age
- medullary carcinoma –> affects elderly
describe Cushing’s syndrome
- hypercortisolism due to ACTH producing pituitary microadenoma (Cushing’s disease)
- may also result from adrenal cortical neoplasms, adrenal cortical hyperplasia, or ectopic ACTCH
describe Conn’s syndrome
- primary hyperaldosteronism
- assc. w/ bilateral nodular hyperplasia of adrenal glands
- hypertension and hypokalaemia
list types of Cushing’s syndrome
- pituitary (Cushing’s disease)
- Adrenal
- paraneoplastic
- iatrogenic (from steroids)
describe phaeochromocytoma
- tumour of adrenal medulla
- 10% tumour
- -> 10% extra adrenal
- -> 10% bilateral
- -> 10% malignant
- -> 10% familial
- can cause hypertensive crises during anaesthesia for surgery
- screened w/ urinary catecholamines
describe acute hypoadrenalism
- Waterhouse Friedrickson Syndrome
- assc. w/ neisseria menigitidis, disseminated intravascular coagulation
- haemorrhage into adrenal gland, assc. acute adrenal dysfunction
describe Addison’s disease
- chronic adrenocortical insufficiency
- caused by chronic autoimmune adrenalitis, TB, AIDS and metastatic carcinoma
Symptoms
- fatigue
- weakness
- GI disturbance
- hyperpigmentation (primary –> assc. w/ ^ ACTH levels)
describe hyperparathyroidism
- cause of hypercalcaemia
- 90% assc. w/ adenoma (seen in assc. w/ multiple endocrine neoplasia syndrome)
- 10% assc. w/ parathyroid hyperplasia (seen secondary to chronic renal failure)
