Week 6 - Pituitary Tumour Flashcards
What are the characteristics of endocrine glands?
- Hormone secreted into circulation
- Homrone out of circulation to target organ
- TSH and thyroid hormones T3 amd T4
What are the characteristics of autocrine and paracrine glands?
Autocrine:
- Hormone travels short distance in intersitital fluid to act on same cell than made substance
- Prostaglandins i.e.
Paracrine:
- Hormone travels short distance in interstitial fluid to neighbouring cell
- Somatostatin on insulin secretion i.e.
What are the characteristics of neuroendocrine glands?
- Hormones travel from nerve cell, in circulation, to target cell
- Neurohormones
- Oxytocin and arginine vasopressin i.e.
How and where are peptide hormones synthesised, released and metabolised?
- Chains of AAs
- From hypothalamus and pituitary, pancreas, and gastrointestinal tract
- Synthesis:
- Gene transcribed to mRNA, into cytoplasm, translation
- Preprohormone forms and RER folding and cleavage
- Prohormone = additional processing and cleavage
- Hormone in secretory granule = mature
- Stored until release via exocytosis
- Controlled by regulating exocytosis
How are steroid hormones synthesised, released and metabolised?
- Derived from cholesterol
- Cortisol, aldosterone and sex hormones
- Synthesis:
- Precursor molecule and biosynthetic enzymes
- Hormone not stored
- Released via simple diffusion
- Lipid soluble so readily crossed plasma membrane via plasma proteins
- Enter blood
- steroid hormone release = dependet on hormone synthesis
What hormones are derived from tyrosine?
Thyroid hormones
Catecholamines
What are the key differences between peptide and steroid hormone properties?
Peptides:
- Hydrophilic
- No plasma protein binding
- Half life = minutes
Steroids:
- Lipophilic
- Bind to plasma proteins
- Half life = days
How is hormone release regulated?
- Feedback regulation
- Neuroendocrine reflexes
- Diurnal or circadian rhythm
What is involved in feedback regulation?
- Consequences of a process acts to regulate rate next process occurs
- Negative feedback = consequence negatively controls next process
- Positive feedback = consequence enhances next process further
- Simple or involvement of hypothalamic and pituitary tropic hormones
What are the mechanism by which endocrine disorders may develop?
- Hormone excess
- Hypersecretion, tumour. Grave’s disease
- Cushing’s syndrome (excess cortisol)
- Lack of hormone
- Hyposecretion, genetic, immunological attack, destruction by disease, surgical removal
- Decreased target-cell responsiveness
- At level of receptor or downstream enzyme
How do you investigate endocrine disorders?
- Signs and symptoms
- Endocrine and hormone levels
- Baseline, dynamic test, stimulation test, suppression test
- Imaging
- Tumour
How can you treat endocrine disorders?
- Hormone replacement
- Drugs to block hormone production
- Drugs to enhance cellular hormone response
- Radiotherapy and surgery if a tumour
What is the role of the posterior lobe in secretion of pituitary hormones?
- Neurohypophysis
- Neural tissue attached to hypothalamus via pituitary stalk
- Secretes ADH and oxytocin
- Hormones synthesised in cell bodies of neuron and stored in terminal ends of axons
- Secreted by neurosecretion
- Act on non-endocrine tissues
- Blood supply = middle and inferior hyophyseal arteries
What is the role of the anterior lobe in pituitary hormone secretion?
- Adenohypophysis
- Glandular tissue growing from Rathke’s pouch
- Main bulk = pars distalis = curls around pars tuberalis
- Piece next to posterior pituitary = pars intermedia = secretes melanocyte stimulating hormone
What are the properties of anterior secreiton of pituitary hormones?
- Mediated by hypothalamic releasing hormones
- Blood supply is superioe hypophyseal arteries
- External plexus collects from hypothalamus via pituitary protal system
- Pituitary hormones secreted into lower capillary bed and drain into hypophyseal veins
- Blood supply enters via pituitary stalk
What are the 2 main posterior pituitary hormones?
- Arginine vasopression (AVP) / ADH
- Oxytocin
What is the role of AVP / ADH in the posterior pituitary?
- Stimulated by increase in bodily fluid osmolality
- Cases vasoconstriction via V1 receptors
- Act on DCT and CD in kindeys to increade permeability and reabsorption of water via V2 receptors
- Stimulate ACTH release
What is the role of oxytocin in the posterior pituitary?
- Release stimulated by suckling and cervical stimulation
- Stimulates milk let-down
- Uterine smooth muscle contraction
- Sexual behaviour
- Used in labour to reduce pain
What are the role of somatotrophs, lactotrophs, corticotrophs, thyrotrophs, and gonadotrophs?
Somatotrophs = somatotropin = growth hormone
Lactotrophs = prolactin = stimulates mammary glands
Corticotrophs = corticotrophin = stimulates cortisol release
Thyrotrophs = thyrotropin = TSH
Gonadotrophs = gonadotropins = LH, FSH, steroid homrone synthesis, follicular development / spermatogenesis
What is the difference between tropic and trophic?
Tropic = have effect on endocrine gland
Trophic = promote growth and tissue integrity
What are the causes, symtpoms, and treatment for hyperprolactinaemia?
Cause = prolactinoma
Symptoms = fertility loss, libido loss, galactorrhea, gynaecomastia
High rpolactin = inhibition of GnRH release
Treatment = dopamine receptor agonist, surgery, radiotherapy
What are the causes, symptoms, and treatment for acromegaly?
Cause = GH-secreting tumour
Symptoms = coarsening facial features, englarged hands + feet, headaches, sleep apnoea, hypertension, glucose intolerance, loss of periods
Treatment = surgery, radiotherapym somatostatin analogues to inhibit GH release
What are the causes and treatment of Cushing’s syndrome?
Cause = excess glucocorticoid activity, ACTH-secreting anterior pituitary tumour
Treatment = tumour removal and radiotherapy
What are the causes and treatment of hypopituitarism?
Cause = deficiency of 1+ hormones, pituitary adenoma
Treatment = hormone replacememt
What is the difference between synergistic and permissive hormone actions?
Synergistic = hormone produces + enhanced response than sum of either hormones alone
Permissive = effects of hormones oppose eachother
How does GH act?
- Synthesised in somatotrophs
- Major growth role
- Important in metabolism
- Acts via GH receptors on target cell
What is the role of IGF-1?
What is the role of insulin in growth?
Required for action of growth hormone
What is the role of sex hormones in growth?
- during puberty
- Liner growth and + muscle
- Stop bone elongation
- Promote epiphyseal plate closure
What is the role of cortisol / glucocorticoids in growth?
- gluconeogenesis
- lipolysis
- protein breakdown
- Can inhibit GH release
- Can cause growth retardation in children
How does GH act to cause growth?
- gluconeogenesis
- lipolysis
- AA uptake and protein synthesis
What is the action of thyroid hormones on growth?
- Permissive action
- Role on GH activity in promoting growth
- role in CNS development
What are causes and treatment of stunted growth?
- Pituitary dwarfism (GH deficiency)
- Hypothyroidism (insufficient THs for GH activity)
- Cushing’s syndrome (excess cortisol)
- Congenital adrenal hyperplasia (+ androgens = early bone maturation)
- Sexual precocity (F = before 8, M = before 9)
Treatment = human growth hormone therapy
What are S&S of GH deficiency in adults?
- Psychological changes
- Malaise, anxiety, depression
- Osteoporosis
- Poor muscle tone
- Impaired hair growth
- Increase in adipose tissue
What are causes of accelerated growth?
- Gigantism
- Acromegaly (GH secreting tumour)
- Hyperthyroidism (excess THs = GH promotion)
- Sexual precocity (inital + bone gorwth, short adult height, early bone maturation)
- Eunuchoidism (hypogonadism)
What is the role of TSHR-stimulating antibodies in Grave’s disease?
What causes Grave’s ophthalmopathy?
Autoantibodies stimulate TSH receptors
- Swelling behind eyeballs
- TSH receptors recognised
- Inflammation
- Cytokine release
- Oedema and fibrosis
What causes pre-tibial myxoedema?
Additional hylauronic acid deposition and liquid retention
What happens in atrophic thyroiditis and Hashimoto’s thyroiditis?
- Hypothyroidism
- TSHR blocking antibodies involved
- Hypothyroidism
- Low BMR, weight gain
- Pain, numbness
- Goitre
- Cold sensitive
- Tissue destruction due to CD8 + T cell activation
- Macrophage activation and tissue damage
What happens during pernicious anaemia and diabetes mellitus?
- Gastric autoimmunity
- Parietal cells produce intrinsic factor, essential for ileal B12 absorption
- Parietal cells = targetes to less B12 absorption
- Autoantibodies to intrinsic factor
- Autoimmune attack on beta cells of islets of Langerhans in pancreas
What happens in myasthenia gravis and autoimmune haemolytic anaemia?
- Autoantibodies inhibit ACh receptors
- Prevention of neuromuscular signalling
- Type 2 sensitivity
- Causes opsonization of RBC
- Enhances phagocytosis through Fc receptor recognition
- Active compliment causes RBC lysis
What happens during Goodpasture’s disease and Pemphigus vulgaris?
- Type 2
- Autoantibodies bind directly to glomerular basement membrane
- Autoantibodies to epidermal cadherin
- Fragile blisters on skin
What happens to kidney, skin, and blood vessels in systemic lupus erythematosus?
- Autoantibodies to DNA, histones, ribonuclear proteins, and cytoskeletal proteins
- Deposits in kidney glomeruli
- Red rash on skin (photosensitivity)
- Inflammation
- Vasculitis
