intro Flashcards
The glands
-hypothalamus- within brain -> releasing hormones -> effect pituitary gland
-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
Directly innervated by hypothalamic neurons via the pituitary stalk:
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
primary organ/problem** vs secondary vs tertiary
PRIMARY:
-the distal organ that actually has the disease
-primary problem is in the target organ/peripheral endocrine gland
-ex. decrease T4 production -> dysfunction in thyroid gland itself -> primary hypothyroidism
2ndary problem
- pituitary problem
-ex. hypo functioning of the pituitary gland -> no stimulation to thyroid gland to produce T4 -> secondary hypothyroidism
Tertiary problem
- hypothalamus problem (rare)
endocrinology
Endocrinology: “to set in motion”
-endocrine = ductless
-works elicit cellular responses and regulate physiologic processes through feedback mechanisms
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
Posterior pituitary hormones
1) oxytocin
2) Vasoactive peptide (AVP)/ antidiuretic hormone (ADH)
-AVP/ADH deficiency = diabetes insipidus (DI) -> lots of dilute urine and extreme thirst
-excessive or inappropriate AVP production = hyponatremia if water intake is not reduced in parallel with urine output
Hypothalamus Hormones
TRH, CRH, GnRH, GHRH, Somatostatin, Dopamine
(The Coolest Girls Get Sick D*ck)
What are the anterior pituitary hormones?
TSH, FSH, LH ,ACTH , MSH , Growth Hormone and Prolactin
What are the thyroid hormones? T3 and T4 repress…..
T3 and T4
T3 and T4 repress TSH
-NEGATIVE feedback
- -increase in hormone from target organ (ex. T4) -> sends signal to pituitary and hypothalamus to decrease stimulating hormones (decrease TSH and TRH)
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
-Insulin synthesis requires ongoing gene transcription but at the translational level is controlled by the glucose & amino acid levels
physiology: what type of binding, receptor types, and what is the Hypothalamic- pituitary relationship
Selective binding
- regulation of gene function and enzyme action
Receptors
- membrane
- nuclear
Hypothalamic- pituitary relationship -> middle man
-varying degrees of control
-negative feedback control mechanism
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
-GH- affects glucose
-TSH can affect 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?
What factors stimulate growth vs what leads to epiphyseal closure
stimulate growth:
-GH
- IGF-I
- thyroid
epiphyseal closure:
- sex steroids
Factors involved in short stature
-GH deficiency,
-hypothyroidism
- Cushing’s syndrome,
-precocious puberty,
-malnutrition or chronic illness
- genetic abnormalities
reproduction
Sex determination, puberty, pregnancy, menopause
What factors involved in maintaining homeostasis?
-TSH
- PTH
- Cortisol**
- Vasopressin
- Insulin
hyperfunction
OVERSECRETION of hormones
-produced by a certain set of cells
Causes:
-tumors (benign (MOST) or malignant)* MC
-hyperplasia of endocrine gland
-ectopic secretion of hormones by other tumors
-ex. lung cancer -> increase ADH (malignant)
hypofunction
Under stimulation from pituitary or abnormal tissue response
tx: replacement of hormone or hormone stimulating drugs
hormone secretion, transport, and degradation
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
-frequency of dosing and the time required to reach steady state are closely linked to RATE of hormone decay
The circulating level of a hormone is determined by:
- rate of secretion and its circulating half life
-half life important for achieving physiologic hormone replacement
hypothalamo- pituitary axis
adenohypophysis = anterior pituitary
-portal vascular system: blood vessels connect hypothalamus and anterior pituitary
Neurohypophysis- neuronal control; posterior pituitary
Cyclical release of hormones:
-pulsatile release of hormones
-circadian rhythms- it matters when you do the blood draw (morning vs night) for ACTH, GH, prolactin
-month long rhythms with superimposed circadian rhythms: LH, FSH
If pituitary stalk is severed what increases and what decreases?
Pituitary stalk is severed:
- prolactin release INCREASES because it is regulated by INHIBITORY STIMULI
- release of all other anterior pituitary hormones DECREASE because it is regulated by POSITIVE FEEDBACK
hypothalamus
-receives input from virtually all other areas of the CNS
-regulation of most anterior pituitary hormones depends on stimulatory signals: + feedback
-prolactin: inhibitory stimuli
Hypothalamic abnormalities (tumors and encephalitis and other inflammatory lesions):
-neurohormones- synthesized in different centers within hypothalamus
- some disorders affect only one neurohormone, whereas others affect several
-under section or over secretion of neurohormones can result
anatomy of pituitary gland
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
-expanding intrasellar pathologic processes -> central mass effects and endocrinologic impact
Where is the pituitary gland located? + what is the sella contiguous to
-located within the sella turcica (bone)
Sella is Contiguous to:
- cavernous sinuses
- cranial nerves
-optic chiasm
Contents of the CS are:
-internal carotid artery
-CN III and IV
- first and second divisions of CN V and VI
anterior lobe/Adenohypophysis
-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
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
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
adrenocorticotropic hormone
-ACTH aka corticotropin
CRH is primary stimulator of ACTH release
-CRH-ACTH-cortisol axis is a central component of the response to stress -> ADH too plays a role in stress
Role of ACTH:
-induces the adrenal cortex to release cortisol, several weak androgens, DHEA
-without ACTH, adrenal cortex ATROPHIES and cortisol release virtually ceases >
-hydrocortisone (a synthetic form of cortisol): when administered as a med -> causes a decrease in the body’s own production of cortisol through negative feedback mechanisms
note aldosterone - NOT STIMULATED by ACTH -> 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
Stimulated by:
- gonadotropin releasing hormone (GnRH)
Suppressed by:
- estrogen and testosterone
Women: LH and FSH stimulate
- ovarian follicular development
- ovulation
Men:
- FSH acts on sertoli cells and is essential for spermatogenesis
-LH acts on Leydig cells of the testis to stimulate testosterone
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
Function:
- stimulating milk production
-release also during sexual activity and stress
why is prolactin sometimes a sensitive indicator of pituitary dysfunction?
- prolactin hormone is 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 defect 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
