Pathophysiology

_________ can be ectopic or induced by alteration of target tissue

_________ can be ectopic or induced by alteration of target tissue

endocrine dysfunction

endocrine disorders can be classified as

primary (intrinsic), secondary or tertiary (disorders of pituitary/hypothalamus)

endocrine syndromes determined by ectopic secretion is usually associated with

malignant tumour

Endocrine syndromes due to____________ : the target tissue it is unable to respond to hormone action

resistance of the target tissue (end-organ resistance)

____________ can include receptor disorders, atb blocking receptors, post-receptor defects

acquired mechanisms of hormonal resistance

_________ is characterized by AVP deficiency and excretion of large volumes of dilute urine

diabetes insipidus

mechanisms of polyuria in DI

• hypothalamic DI - ADH deficit

• nephrogenic DI - renal resistance to vasopressin

• primary polydipsia - excess fluid

• gestational DI - excess vasopressin enzyme in placenta

primary vs secondary etiology of DI

• primary - genetic, idiopathic, cns defect, autoimmune

• secondary - cranial trauma, pituitary tumour, ischemia

pathophysio of DI

avp deficit (constant renal loss water, hypernatremia), polyuria, increased plasma osmolality (→ polydipsia)

diagnosis of DI is based on

polyuria, low urine osmolality, water deprivation test, AVP measurement

treatment DI

administration vasopressin (except for nephrogenic DI)

SIADH (syndrome of inappropriate antidiuretic hormone secretion) - pathophysio

excess ADH secretion by ectopic secretion or stimulation of hypothalamic ADH secretion (by brain trauma, meningitis) → renal water retention and v expansion of fluids → hyponatremia, decreased plasma osmolality

diseases of hyper/hyposecretion of pituitary

hyper - adenoma

hypo - non-secreting adenoma, dwarfism

neurological syndrome of pituitary adenoma

chiasmal syndrome, cranial n lesions, ICH

endocrine syndromes of pituitary adenoma depending on types

• GH - gigantism

• PRL - galactorrhea, amenorrhea

• ACTH - Cushing

• POMC - melanodermia

• TSH - hyperthyroidism

• non-secreting - pituitary hormone decrease

clinical presentation of prolactinoma

women - menstrual irregularities, galactorrhea

men - hypogonadism

etiology of GH secretory pituitary adenoma

usually macroadenoma but also microadenoma, rarely ectopic

gigantism from GH secreting pituitary adenoma in children pathophysio

excess GH stimulates IGF-1 → increased protein + glucose synthesis, glycogenolysis, lipolysis → growth cartilages + dev soft tissue → increased height (epiphyseal plates grow)

for gh secreting pituitary adenoma, in

acromegaly, GH and IGF-1 excess will determine

increased bone size, massive skeletal aspect, thick extracell matrix, interstitial edema, fibrous CT proliferation, visceromegaly

GH deficit classification based on its pathogeny

decreased secretion due to brain tumours, radiotherapy, head trauma

impaired GH action

impaired IGF-1 generation

GH deficit in the prepubertal stage it is manifested through

pituitary dwarfism (growth retardation, short stature), smooth and translucent skin, excess adipose tissue on torso, hypoglycemia

adult GH deficiency includes

reduced bone density, decreased m strength, increased fat, glucose intolerance, impaired psyche

thyrotoxicosis vs hyperthyroidism

thyrotoxicosis - syndrome from excess circulating thyroid hormones

hyperthyroidism - thyroid hyperfunction

primary vs secondary/tertiary thyrotoxicosis

primary - elevated total or free T4 and/or T3, suppressed TSH

secondary/tertiary - elevated total or free T4 and/or T3, elevated TSH

basedow graves disease

autoimmune disease with genetic susceptibility + associated w/ environmental factors

characteristics basedow graves disease

diffuse goiter, hyperthyroidism (thyrotoxicosis), ophthalmopathy, dermopathy

basedow graves disease occurs due to defect of

Ts Ly induce anti TRAb+ anti-TPO abs → large B Ly infiltration of thyroid, adipocytes

effects of basedow graves disease

thyroid stimulating Ig - increased production thyroid hormones

thyroid growth-stimulating Ig - proliferation thyroid follicular epithelium

TSH-binding inhibitor Ig - inhibit thyroid cell fxn

graves ophthalmopathy

presence TSHR → eye m hypertrophy, increased v retro-bulbar CT and adipose tissue, GAG (high osmotic p)

___________ is caused by dermal deposition of glycosaminoglycans associated fibroblast proliferation

Infiltrative dermopathy or pretibial myxedema from graves

multinodular toxic goiter

nodules become autonomic and secrete hormones independently of tsh control

toxic thyroidian adenoma

benign tumour, autonomic fxning w/o tsh control

hashitoxicosis

increased thyroid hormone levels from thyroid follicular destruction

thyrotoxicosis metabolic effects

hyperglycemia, protein catabolism intensification, lipolysis

cardiovasc effects thyrotoxicosis

AF, palpitations, divergent a htn

neurom thyrotoxicosis features

asthenia, myalgia

digestive feature of thyrotoxicosis

polyphagia

dermographism and pruritis are features of

thyrotoxicosis

hypothyroidism

decreased conc thyroid hormones in blood

thyroiditis, colloid goiter, irradiation and surgical removal of thyroid - effects

hypothyroidism

hashimoto thyroiditis

diffuse thyroid hypofxn, autoimmune mediated due to production TgAb and TPO-Ab

_________ has increased risk for the development of B-cell non-Hodgkin lymphomas

hashimoto

pathophysio hashimoto thyroiditis

cellular (T cytotoxic Ly) and humoral (TgAb and TPOAb) → killing thyroid epithelial cells, cytokine and cytotoxic cell death

evolution hashimoto thyroiditis

goiter → fibrous, hashitoxicosis → hypothyroidism, compensatory increase TSH from fall T4, T3

clinical features hypothyroidism

mucopolysacccharydic infiltration, weight gain, cold intolerance, bradycardia, macroglossia, carotenodermic aspect, asthenia

myxedema

severe hypothyroidism with natural evolution to myxedematous coma after being triggered by treatment interruption, cold exposure or stress

clinical features myxedema

hypoventilation, bradycardia, urine retention, loss consciousness

clinical presentation of Graves

weight loss, exhaustion alternating with restlessness, heat intolerance, palpitations

investigations graves disease

elevated thyroid hormones, undetectable TSH, TSHR stimulating antibody assay

diagnosis myxedema

primary hypothyroidism - TSH elevated

central hypothyroidism - TSH decreased

anti thyroid hormone atbs

clinical presentation Cushing

htn, central obesity, hirsutism, menstrual irregularities, skin fragility, depression, edema

Cushing disease vs syndrome

disease - excess glucocorticoid by ACTH excess

syndrome - excess glucocorticoid from therapy

etiology cushing

iatrogenic, acth excess, adrenal neoplasm, ectopic production

mechanism cushing disease

increased rates gluconeogenesis, glycogenolysis, increased insulin resistance, catabolism proteins, immune disruptions

diagnosis cushing disease

overnight low dose dexamethasone suppression test, 24h urine free cortisol, late night salivary cortisol

diagnosis of cushing based on levels of ACTH

decreased - adrenal cause

increased - ectopic

increased + partial suppression - pituitary excess (disease)