Endocrine Pathology Flashcards
Increased activity of the target tissue often down-regulates the activity of the gland that secretes the stimulating hormone
What is the name of this process
Feedback inhibition
Give the two groups of hormones that trigger biochemical signals upon interacting with cell-surface receptors
Peptide hormones, such as growth hormone and insulin
Small molecules, such as adrenaline
What are the three things which could take place when an lipid insoluble hormone binds to a receptor
an increase in intracellular signaling molecules, termed second messengers, such (cAMP);
•production of mediators from membrane phospholipids, such as inositol 1,4,5-trisphosphate or IP3;
•shifts in the intracellular levels of ionized calcium.
•The elevated levels of one or more of these can control proliferation, differentiation, survival, and functional activity of cells, mainly by regulating the expression of specific genes.
Give some examples of lipid-soluble hormones
Estrogen
Progesterone
Glucocorticoids
Thyroxine
What are some disorders that can affect the normal activity of the endocrine system
Impaired synthesis or release of hormones
•Abnormal interactions between hormones and their target tissues
•Abnormal responses of target organs.
Endocrine diseases can be classified into
Diseases of underproduction or overproduction of hormones and their resulting biochemical and clinical consequences
2.Diseases associated with the development of mass lesions. Such lesions might be
•nonfunctional,
• associated with overproduction or underproduction of hormones.
What is the pineal gland
Pine cone shaped organ weighing 100-180mg lying between the superior colliculi at the base of the brain
•Cells are Pineocytes which are epithelial like cells with photosensory and neuroendocrine functions
•Secretes Melatonin which functions in the circadian rhythm of wake and sleep hence commonly deployed in the management of jet-lag.
•Primary tumours are rare and of embryonic germ cell origin; pinealomas (pineacytomas and pineablastomas)
What are the three major cell types of the adenohypophysis based on appearance with H and E staining
Acidophils: these cells stain bright pink. They produce either
•growth hormone (GH)
•prolactin (Prl).
•Basophils: these cells stain purple they produce
•Thyroid stimulating hormone (TSH)
•Adrenocorticotrophic hormone (ACTH)
•The gonadotrophic hormones –
1. Follicle stimulating hormone (FSH)
2. Luteinizing hormone (LH) known in the male as interstitial cell stimulating hormone (ICSH).
•Chromophobes: these are pale-staining cells that are not associated with specific hormone secretion.
What are the five cell types specific antibodies against the pituitary identify
Somatotrophs, producing growth hormone (GH): They constitute half of all the hormone-producing cells in the anterior pituitary.
•Lactotrophs (mammotrophs), producing prolactin: essential for lactation.
•Corticotrophs: they produce ACTH, MSH
•Thyrotrophs: they produce TSH
•Gonadotrophs: they produce FSH, LH
What is the neurohypophysis
The neurohypophysis is essentially just the termination point of axons derived from the hypothalamus.
•It consists of modified glial cells (termed pituicytes) and axonal processes extending from nerve cell bodies in the supraoptic and paraventricular nuclei of the hypothalamus
These neurons produce two peptide hormones, anti-diuretic hormone (ADH, also called vasopressin ) and oxytocin .
•The hormones vasopressin and oxytocin are synthesized in the hypothalamus and transported down the infundibular stalk to the neurohypophysis from where they are released.
Oxytocin stimulates contraction of the smooth muscle cells in the gravid uterus and cells surrounding the lactiferous ducts of the mammary glands.
•ADH synthesized in the supraoptic nucleus.
•In response to;
•Increased plasma osmotic pressure,
•Reduced left atrial distention,
•Exercise and certain emotional states
What are the pathologies of the pituitary gland
Hyperpituitarism: excess secretion of trophic hormones
•Hypopituitarism: deficiency of trophic hormones
•Local mass effect: compression of the adjoining structures
What are some causes of hyperpituitarism
Pituitary adenoma – most common cause
•Pituitary hyperplasia
•Carcinoma of the anterior pituitary
•Paraneoplastic syndromes
What is pituitary adenoma
They are benign neoplasm of the adenohypophysis usually associated with excess secretion of the corresponding hormones.
•There are however non functioning types that do not produce excess hormones.
What is the etiology of pituitary adenoma
•The aetiology is obscure.
•The most common cause of hyperpituitarism
•They occur in the context of MEN type 1
•G-protein mutations(GNAS1 gene)
•RAS oncogene mutation
•C-myc oncogene mutation
What is the molecular pathology of G protein mutation
G protein plays role in signal transduction from GHRH surface receptors to intracellular effectors (Adenyl cyclase) which then generates second messenger (Camp)
•G protein is heterotrimeric with alpha, beta and gamma cells.
•Gsalpha is bound to GDP in inactive state. On interaction with ligand bound cell surface receptor, bound GTP and is activated to generation of cAMP.
•cAMP acts as mitogenic stimulus for many endocrine cell types
•cAMP is regulated by GTPase activity which reduces GTP to GDP
Alpha subunit of Gs is encoded by GNAS gene located on chromosome 20q13.
•A mutation in the alpha subunits that interferes with its intrinsic GTPase activity will therefore result in constitutive activation of Gsalpha, persistent generation of cAMP and unchecked cellular proliferation.
•Approximately 40% of somatotroph cell adenomas bear GNAS mutation that abbrogate the GTPase activity of Gs alpha.
•GNAS mutation has been described in minority of corticotrophs.
•There is no GNAS mutation in Latotrophs, thytotrophs and gonadotrophs
