Intro Flashcards
The glands
-hypothalamus- within brain -> releasing hormones -> effect pituitary gland
-hypothalamus is part of diencephalon
-pituitary- you can see it -> trophic hormones act on distal target organs
-thyroid- TRH (hypothalamus) -> TSH (pituitary)
-parathyroid- 4 small glands
-pancreas- islets of langerhans
-adrenals
-gonads
posterior pituitary gland
-has stored* hormones
-anterior- originates from the gut
-Directly innervated by hypothalamic neurons via the pituitary stalk -> its a continuation of it
Posterior pituitary secretion of
-Vasopressin (antidiuretic hormone; ADH)
-Oxytocin
-Both are very sensitive to neuronal damage by lesions that affect the pituitary stalk or hypothalamus
-neuroendocrine stimulation releases stored hormones
primary organ/problem**
-the distal organ that actually has the disease
-primary problem is in the target organ
-2ndary problem- pituitary problem
-tertiary problem- hypothalamus problem
-ex. decrease T4 production -> dysfunction in thyroid gland itself -> primary hypothyroidism
-ex. hypo functioning of the pituitary gland -> no stimulation to thyroid gland to produce T4 -> secondary hypothyroidism
-ex. primary thyrotoxicosis
-ex. adisons disease- primary
severed pituitary stalk
-increased prolactin
-decreased all other anterior hormones
endocrinology
-to set in motion
-glands and their hormones
-endocrine- ductless
-exocrine- from a cell into the blood system
-elicit cellular responses and regulate physiologic processes through feedback mechanisms
-paracrine effect- exert an effect on cells on the organ from which they were released
-autocrine effect- on the same cell type
different mechanisms of cell signaling (she brushed over this)
-intracrine- within cell
-autocrine- from within cell to outside -> back in
-paracrine- local
-endocrine- general circulation
-neuroendocrine
the hormones
-hypothalamus- GnRH, thyrotropin releasing hormone, cortisol RH, somatostatin, GHRH
-pituitary:
-anterior- GH, ACTH, TSH, FSH, LH, prolactin
-posterior- vasoactive peptide (AVP) or antidiuretic hormone (ADH); oxytocin
-AVP deficiency causes diabetes insipidus (DI);
-excessive or inappropriate AVP production- hyponatremia if water intake is not reduced in parallel with urine output
-thyroid- T3 & T4 (active)
-adrenals-
-mineralocorticoids
-norepinephrine
basic genetics of hormones (she brushed on this…dont really study)
The synthesis of peptide hormones and their receptors occurs through a classic pathway of gene expression ->
Transcription → mRNA → protein → posttranslational protein processing → intracellular sorting, membrane integration, or secretion ->
Have regulatory DNA elements ->
-Control by other hormones also necessitates the presence of specific hormone response elements
-TSH repressed by the thyroid hormones
-Insulin synthesis requires ongoing gene transcription but at the translational level is controlled by the glucose & amino acid levels
physiology
-selective binding- regulation of gene function and enzyme action
-hypothalamic- pituitary relationship -> middle man
-varying degrees of control
-negative feedback control mechanism
-increase in hormone from target organ (ex. T4) -> sends signal to pituitary and hypothalamus to decrease stimulating hormones (decrease TSH and TRH)
-receptors- membrane and nuclear
hormones to target organs image
-cortisol- most important hormone*- you can not live without it -> controls BP and glucose
-every cell needs T4 for metabolism
-FSH & LH - affect testes and ovaries
-prolactin- produces breast milk itself
-ADH -> kidneys
-oxytocin -> breasts and uterus
hormone flow chart
-somatostatin - inhibits GH and TSH
-IGF*- part of GH that affects the tissues and long bones - made in liver
-GH- affects glucose
-TSH can increase prolactin
hyperthyroidism
-increase T4
-tachycardia, sweating, diarrhea, anxiety, tremors
-increased metabolism
-constipation, depressed, gained weight, myxedema, slower movements
-problem is in the thyroid?, pituitary?, hypothalamus?
growth functions
-Stature
-GH deficiency, hypothyroidism, Cushing’s syndrome, precocious puberty, malnutrition or chronic illness, or genetic abnormalities
-Many factors (GH, IGF-I, thyroid hormone) stimulate growth, whereas others (sex steroids) lead to epiphyseal closure
reproduction
Sex determination, puberty, pregnancy, menopause
maintaining homeostasis
-TSH, PTH, Cortisol, Vasopressin, Insulin
hyperfunction
-over secretion of hormones
-often due to tumors (benign (MOST) or malignant)
-hyperplasia of endocrine gland
-ectopic secretion of hormones by other tumors
-produced by a certain set of cells
-ex. lung cancer -> increase ADH (malignant)
hypofunction
-under stimulation from pituitary or abnormal tissue response
hormone secretion, transport, and degradation
-circulating level of a hormone is determined by its rate of secretion and its circulating half life
-stored in secretory granules
-releasing factors or neural signal -> ion channels -> secretion of hormone
-transport and degradation- affect the rapidity with which its signal decays
-half life important for achieving physiologic hormone replacement
-frequency of dosing and the time required to reach steady state are intimately linked to rate of hormone decay
hypothalamo- pituitary axis
-adenohypophysis
-portal vascular system
-neurohypophysis- neuronal control
-pulsatile release of hormones
-circadian rhythms- it matters when you do the blood draw (morning vs night)
-month long rhythms with superimposed circadian rhythms- LH, FSH
hypothalamus
-receives input from virtually all other areas of the CNS
-regulation of most anterior pituitary horomones depends on stimulatory signals- + feedback
-prolactin is regulated by inhibitory stimuli
-if pituitary stalk is severed - prolactin release increases -> whereas release of all other anterior pituitary hormones decrease
-hypothalamic abnormalities (tumors and encephalitis and other inflammatory lesions)
-neurohormones- synthesized in diff centers within hypothalamus -> some disorders affect only one neuropeptide, whereas others affect several
-under section or over secretion of neurohormones can result
anatomy
Lateral view of the brain showing the relationship of the hypothalamus to the median eminence and the pituitary gland
-pituitary gland enlargement >10 -> optic chiasm pressure -> visual field defects
-located within the sella turcica
-comprises antomically and functionally distinct anterior and posterior lobes
-sella is Contiguous to vascular and neurologic structures -> Including the cavernous sinuses, cranial nerves, and optic chiasm [contents of the CS are: internal carotid artery, CN III and IV, first and second divisions of CN V and VI]
-expanding intrasellar pathologic processes -> central mass effects and endocrinologic impact
anterior lobe
-Hypothalamic neural cells synthesize specific releasing and inhibiting hormones
-These are secreted into the portal vessels of the pituitary stalk
-Superior and inferior hypophyseal arteries
melanocyte stimulating hrmones
-Addison disease
-melanocytes are in vicinity -> darker skin
-ACTH but also melanocytes
pituitary gland
-peripheral endocrine organ functions are controlled to varying degrees by pituitary hormones
-functions vary from minimal to extensive control
-master gland/middle man
-hypothalamic-pituitary axis (HPA)- negative feedback system
-pituitary tumors cause characteristic hormone excess syndromes
-hormone deficiency may be inherited or acquired
adenohypophysis
-Specialized portal vascular system regulates synthesis and release of the 6 major peptide hormones of the anterior pituitary
-Hypothalamic-pituitary axis:
-Thyrotropin releasing hormone [TRH → TSH]
-Corticotropin releasing hormone [CRH→ACTH]
-Gonadotropin releasing hormone [GnRH → FSH; LH]
-Growth hormone releasing hormone [GRH → GH]
-Dopamine/TRH → Prolactin
adrenocorticotropic hormone
-ACTH
-aka corticotropin
-CRH is primary stimulator of ACTH release
-induces the adrenal cortex to release cortisol, several weak androgens, DHEA
-CRH-ACTH-cortisol axis is a central component of the response to stress -> ADH too plays a role in stress
-you must slowly taper exogenous cortisol -> can cause crisis -> die
-without ACTH, adrenal cortex atrophies and cortisol release virtually ceases >
-hydrocortisone- gradual decrease due to negative feedback of the hormone while supplementing it
-aldosterone - NOT STIMULATED by ATCH -> renin and volume control
TSH
-regulates the structure and function of the thyroid gland
-stimulated synthesis and release of thyroid hormones
-synthesis and release stimualted by the hypothalamic hormone -> thyrotropin (TRH)
-suppressed by negative feedback
LH and FSH
-control the production of the sex hormones
-these are not life threatening if hyper or hypo
-synthesis and release of LH and FSH are stimulated by- gonadotropin releasing hormone (GnRH)
-and suppressed by- estrogen and testosterone
-in women -> LH and FSH stimulate- ovarian follicular development and ovulation
-in men, FSH acts on -> sertoli cells and is essential for spermatogenesis
-LH acts on leydig cells of the testis to stimulate testosterone
-LH surge after ovulation
-FSH increase gradually
growth hormone
-stimulates somatic growth and regulates metabolism
-synthesis and release of GH- major stimulator -> GHRH
-major inhibitor- somatostatin
-GH controls synthesis of insulin like growth factor 1 (IGF1 AKA somatomedin C) which largely controls growth
-produced by many tissues, the liver is the major source
prolactin
-produced in the cells called lactotrophs
-pituitary doubles in size during pregnancy -hyperplasia- increasing in cell and hypertrophy of lactotrophs
-major function stimulating milk production
-release also during sexual activity and stress
-may be a sensitive indicator of pituitary dysfunction
-hormone most frequently produced in excess by pituitary tumors
-often first hormone to become deficiency from infiltrative disease or tumor compression of the pituitary
other anterior pituitary hormones
-can cause hyperpigmentation of the skin:
-Pro-opiomelanocortin (POMC, - gives rise to ACTH)
α- and β- melanocyte-stimulating hormone (MSH)
-Significant clinically in disorders in which ACTH levels are markedly elevated (i.e. Addison’s disease, Nelson syndrome)
-endogenous opiods:
-encephalins
-endorphins- bind to and activate opioid receptors the CNS
-exercise!!
neurohypophysis
-POSTERIOR PITUITARY
-comprises of axons originating from neuronal cell bodes located in the hypothalamus -> antidiuretic hormone- AKA arginine-vasopressin (AVP) or ADH
-oxytocin- uterine contraction and breast milk ejection
-pulsatile fashion
approach to the patient
-hx and PE
-look for manifestation of hyper or hypo functioning- 1st step
-measurements and endocrine testing
-quantitative hormone measurements and clinical context
-biochemical testing- immunoassay (plasma/serum; urine), mass spectroscopy (various forms of chromatography and enzymatic methods), broad range (circadian rhythm, dynamic test necessary)
-imaging- CT, MRI, US, thyroid scan
-screening
hypofunction disorders- tx
-replacement of the peripheral endocrine hormone
-regardless of whether the dect is primary or secondary (an exception is GH replacement for pituitary dwarfism)
-if resistance exists- drugs that reduce resistance can be used (metformin or thiazolidinedione for type 2 diabetes mellitus)
-hormone stimulating drugs
hyperfunction disorders
-radiation therapy, surgery, drugs that suppress hormone production
-receptor antagonist
