Endocrine Flashcards
What are the different types of intercellular messengers?
Endocrine: hormone - blood - target cell Autocrine: cell A - cell A Paracrine: cell A - cell B Neurodendocrine: neurotransmitter - blood - target cell Neurotransmitter: nerve - nerve
Describe peptide hormones
Synthesised as a protein by the cell
Secreted by exocytosis
Travel free in the blood in active form
Short half life
Describe steroid hormones
Precursor molecule (e.g. cholesterol) and enzymes make the hormone
Released by simple diffusion
Hydrophobic so travel bound to protein (inactive)
Long half life
How do peptide hormones elicit a cell response?
Bind to membrane receptor (e.g. G-protein receptor) and lead to secondary messenger response inside cell
How do steroid hormones elicit a response?
Diffuse through target cell membrane and bind with either cytosolic receptor or to nuclear receptor (synthesis of required protein by cell)
How would you test for hyposecretion?
Stimulation test
How would you test for hypersecretion?
Suppression test
What is the embryological origin of the pituitary gland?
Ectodermal upgrowth from roof of primitive mouth (anterior lobe)
Neuroectodermal downgrowth of the brain (posterior lobe)
What is the blood supply to the pituitary?
Inferior and superior hypophyseal artery
What hormones does the hypothalamus secrete?
Releasing hormones - stimulate pituitary to release hormones e.g. corticotrophin releasing hormone (CRH), thyrotropin releasing hormone (TRH), gonadotrophin releasing hormone (GnRH), growth hormone releasing hormone (GHRH)
Somatostatin - stops pituitary releasing GH and TSH
Dopamine - prolactin inhibiting factor
Oxytocin and ADH - synthesised in hypothalamus but released in posterior pituitary
What hormones are secreted by the anterior pituitary?
Thyrotropin (TH) Luteinizing hormone (LH) Follicle-stimulating hormone (FSH) Growth hormone (GH) Prolactin (PRL) Adrenocorticotrophin (ACTH)
What hormones are secreted from the posterior pituitary?
ADH
Oxytocin
What hormones are secreted from the thyroid gland?
Thyroxine (T4)
Triiodothyronine (T3)
Calcitronin
What hormone is released from the parathyroid gland?
Parathyroid hormone (PTH)
What hormones are released from the adrenal medulla?
Adrenaline (epinephrine)
Noradrenaline (norepinephrine)
What hormones are released from the adrenal cortex?
Aldosterone
Cortisol
Androstenedione
Dehydroepiandosterone (DHEA)
What hormones are released from the pancreas?
Insulin
Glucagon
Somatostatin (SS)
How does the anterior pituitary (adenohypophysis) secrete hormones?
Releasing hormones from hypothalamic nerves secreted into capillary plexus
Hypophyseal portal vessels transport releasing hormones to secretory cells where pituitary hormones are secreted
How does the posterior pituitary (neurohypophysis) secrete hormones?
Supraoptic-hypothalamic nerve tract transports oxytocin and ADH from paraventricular and supraoptic nuclei in hypothalamus to inferior hypophyseal artery for secretion
What can an upward growth of a pituitary tumour cause?
Bitemporal hemianopia (loss of peripheral vision). Upwards compression of the optic chiasm by the pituitary
What can a lateral growth of a pituitary tumour into the cavernous sinus cause?
Opthalmoplegia (paralysis of eye movement) due to compression of CNIII, IV and VI, all involved in eye movement
What stimulates the hypothalamus to secrete growth hormone releasing hormone?
Stress, sleep, exercise
What are the direct metabolic effects of growth hormone (GH)?
Lipolysis (increased [FFA]) Hepatic gluconeogenesis Inhibits glycogen synthesis Increased BMR Promotes long bone growth at epiphyseal plates
What hormone is growth hormone antagonistic to?
Insulin
What hormone is growth hormone synergistic with?
Cortisol
Describe stimulation and suppression of growth hormone release?
Stimulated by GHRH but suppressed by somatostatin and food intake (negative feedback from rise in FFA)
What is insulin-like growth factor 1 (IGF1)?
Released from the liver upon stimulation by GH. Negative feedback to hypothalamus and pituitary to regulate release of GH
What are the two types of growth hormone excess?
Gigantism - before bone epiphyseal plate fusion: increased linear bone growth leading to extremely tall final stature
Acromegaly - after epiphyseal plate fusion: no more linear growth so disproportionate growth
What are the clinical concerns with acromegaly?
Cardiac failure due to increased blood pressure
How would you test for GH excess?
Oral glucose administration. Would observe no reduction in GH levels
How would you treat growth hormone excess?
Somatostatin analogue drugs to suppress GH secretion
Dopamine agonists (if tumour secretes prolactin)
Radiotherapy to reduce tumour
What is caused by growth hormone deficiency?
In children - stunted growth
In adults - insidious presentation
How would you test for growth hormone deficiency?
Stimulation testing and identifying low serum IGF1
How would you treat GH deficiency?
Daily injection of hormone
What is the action of prolactin?
Support secretion of breast milk
How is prolactin secretion regulated?
Inhibited by dopamine
What stimulates prolactin secretion?
Thyrotropin releasing hormone (TRH)
Suckling, sleep, stress
What is the differential diagnosis for hyperprolactinaemia?
Pregnancy
Primary hypothyroidism (increased TRH due to fault in negative feedback from thyroid)
Stress
Drug treatment
How would you treat hyperprolactinaemia?
Dopamine agonists
Thyroxine (if due to hypothyroidism)
What are the effects of adrenocorticotrophic hormone (ACTH)?
Acts on adrenal cortex to stimulate conversion of cholesterol to cortisol or adrenal sex steroid precursors
How does ACTH elicit a response on its target cells?
Through G-protein coupled receptors to increase cellular cAMP
What stimulates the release of ACTH?
Corticotrophin releasing hormone (CRH) from hypothalamus.
Stress
What inhibits the release of ACTH?
Cortisol in a negative feedback loop from adrenal cortex
What is an excess of ACTH called?
Cushing syndrome
What happens in a patient with Cushing syndrome?
Overstimulation and enlargement of adrenal glands
What is Nelson syndrome?
After removal of the adrenal glands as a last resort to treat Cushing syndrome, there is no longer negative feedback to the pituitary by cortisol which leads to an enlargement of the pituitary adenoma
What are the effects of thyroid stimulating hormone (TSH)
Regulator of the thyroid gland. Act on thyroid follicular cell surface via G-protein receptor to increase intracellular cAMP
How is TSH production regulated?
By hypothalamic TRH levels
Secretion is inhibited by somatostatin
How does negative feedback of TSH work?
Decreased effectiveness of TRH by reducing receptor numbers
What causes excess TSH levels?
Hypothyroidism (also causes increase TRH which increases FAH and PRL leading to increased testicular volume and galactorrhoea)
What regulates LH and FSH secretion?
Hypothalamic gonadotrophin releasing hormone (GnRH) Stress and prolactin inhibit secretion Negative feedback (and on GnRH) by hormones secreted by testis and ovaries
What is the main cause of excess gonadotrophins?
Loss of negative feedback system
What causes diabetes insipidus?
Decreased ADH secretion
How would you distinguish between cranial diabetes insipidus and nephrogenic diabetes insipidus?
By giving the patient desmopressin (synthetic ADH analogue). If urine now concentrates, then it’s cranial but if not it’s nephrogenic.
What are the effects of oxytocin?
Increases uterine contraction to expel fetus and placenta
Contracts mammary glands to expel milk
How is oxytocin regulated?
Positive feedback by vaginal stretch. Further vaginal distension results in increased oxytocin secretion until birth
What is the embryological origin of the adrenal cortex?
Epithelial cells lining the abdominal cavity of the developing embryo
Which zones are different hormones synthesised in the adrenal cortex?
Zona glomerulosa - aldosterone
Zona fascialata - cortisol
Zona reticularis - sex steroid precursors
How is cortisol transported in the blood?
Steroid hormone so bound to a protein: cortisol binding globulin (CBG)
Not stored, synthesised upon demand
How does ACTH cause an increase in cortisol synthesis?
By increasing the flux of the cholesterol to cortisol pathway
How is cortisol affect by circadian rhythm?
Sharp increase upon waking which slowly decreases throughout day until very low at night
What is the function of cortisol?
To raise circulating FFA and glucose
Permissive action on adrenaline and glucagon which creates insulin resistance
What is the effect of cortisol on muscle?
Catabolic effect reduce protein synthesis and result in atrophy
What is the effect of cortisol on bone?
Shift cell type from osteoblasts (bone forming) to osteoclasts (bone reabsorbing). Predisposes osteoporosis
What is the effect of cortisol on salt and water homeostasis and BP?
Increase Na+ reabsorption and K+ loss at DCT through mineralocorticoid receptors.
Increases GFR
Inhibits ADH
Increases BP by increasing sensitivity of vessels to catecholamines
What is the effect of cortisol on growth and development?
Stimulates cell differentiation to mature phenotype
Stimulates lung surfactant production
Too much inhibits growth (Cushing syndrome)
What are the effects of cortisol on the immune system?
Anti-inflammatory effect by suppressing T-lymphocytes and eosinophils (neutrophils rise)
What type of hormones are produced in the innermost part of the adrenal cortex?
Sex precursor hormones - DHEA and androstenedione which are converted peripherally into androgens and oestrogens.
What is the difference between primary and secondary hypoadrenalism?
Primary = direct destruction of the adrenal gland Secondary = loss of anterior pituitary corticotroph
What is Addison disease?
Primary hypoadrenalism - autoimmune destruction of the adrenal cortex
What are the common clinical signs of Addison disease?
Hyponatraemia and hyperkalaemia
What is the treatment for Addison disease?
Pharmacological cortisol replacement (with caution not to give too much and cause hyperadrenalsim). Body loses ability to alter cortisol short term in response to stress
How do you diagnose Cushing syndrome?
Dexamethasone suppression test - inhibits ACTH production (leading to reduced cortisol production). Cushing syndrome positive if 9am serum cortisol remains elevated
How does the high dose dexamethasone suppression test localise glucocorticoid excess?
What would you do following this test?
If serum cortisol is suppressed >50% at 9am then anterior pituitary source
If serum cortisol is suppressed <50% at 9am then ectopic source or adrenal tumour
Scan either the pituitary or adrenal gland to visualise the tumour
What is the treatment for Cushing syndrome?
Removal of tumour
What can you expect following removal of tumours causing Cushing syndrome?
Signs of Addison disease as the body is not used to lower levels of cortisol and struggles to detect it. Cortisol therapy is needed post op
What is Conn syndrome?
Tumours of zona glomerulosa of adrenal cortex resulting in excess aldosterone
What are the signs of Conn syndrome?
Hypokalaemic hypertension
How would you test for Conn syndrome?
Measure aldosterone levels but be aware of anti-hypertensives drugs such as ACE inhibitors as they will interfere with RAA system and will need to be stopped before testing
How would you treat Conn syndrome?
Potassium soaring diuretic such as spironolactone which is an aldosterone receptor antagonist
What is congenital adrenal hyperplasia and what does it cause?
Inherited condition causing mutation of genes that encode enzymes in pathway to cortisol. Causes reduced cortisol and high ACTH which leads to increased sex hormones
How are glucocorticoids used therapeutically?
Premature labour to stimulate fetal lung surfactant production
Autoimmune and inflammatory disorders due to anti-inflammatory nature
What is the embryological origin of the adrenal medulla?
Derived from neuroectoderm from vertebral column
How doe adrenal medulla chromaffin cells respond to synaptic activation?
By releasing catecholamine hormones (noradrenaline and adrenaline)
What is the process of catecholamine synthesis in the adrenal medulla?
Tyrosine is converted to dopamine which is then converted to noradrenaline. Noradrenaline is then either secreted or converted to adrenaline before excretion
What is convention of noradrenaline to adrenaline dependent on?
Glucocorticoid, present in medulla due to centripetal drainage of venous blood from outer cortex
How are catecholamine actions terminated?
Noradrenaline taken up by postganglionic sympathetic nerve terminals for metabolism by monoamine oxidase (MAO). Adrenaline taken up into platelets
What are the actions of adrenaline?
Increase systolic BP and heart rate Circulation directed to limb muscle beds and away from gut Decrease gut motility Bronchodilation Mydriasis (pupil dilation) Piloerection
What are the actions of noradrenaline?
Increase systolic and diastolic BP
Decrease heart rate
What are the synergistic actions of adrenaline and noradrenaline?
Fight or flight response. Raise BP, divert nutrients away from non essential organs, promote nutrient delivery to muscles active in fight or flight response, increase FFA, glycogenolysis and gluconeogenesis to increase blood glucose
What is phaechromocytoma? How would you treat it?
Overactivity of the adrenal medulla due to tumour of the chromaffin cells. Treatment by blocking catecholamine receptors and surgical removal of the adrenal gland
What is the blood supply to the thyroid?
Superior and inferior thyroid arteries (from external carotid and subclavian)
Describe the histology of thyroid cells
Follicular cells with a colloid lumen
What are the two thyroid hormones?
Thyroxine (T4)
Triiodothyronine (T3)
What are the inactive forms of the thyroid hormones
Reverse T3
Diiodothyronine (T2)
How does iodide enter the follicular cell if the thyroid?
By active transport via a I-/Na+ pump (both pumped in)
Na+ pumped out via Na+/K+ ATP pump
What is thyroglobulin?
Glycoprotein substrate synthesised in the follicle cells of the thyroid. After synthesis, packaged into vesicles and released into colloid for synthesis of T3 and T4.
How is thyroglobulin converted into thyroid hormones (T3 and T4)
Iodination catalysed by thyroid peroxidase (TPO)
Which is the most active thyroid hormone?
T3
How is TRH regulated?
Negative feedback from circulating T3
How is T4 converted to the more active T3?
Via the deiodination selenodeiodinase enzymes (remove an iodine)
What are the different types of selenodeiodinase?
Type 1 (D1) - liver, kidney, muscle. Circulating T3 Type 2 (D2) - brain and pituitary. T3 negative feedback Type 3 (D3) - T4 -> reverse T3
What is the purpose of reverse T3?
When a cell has sufficient T3, switches to produce rT3 which is rapidly cleared
How do thyroid hormones elicit a target cell response?
Bind to nuclear thyroid hormone receptor (TR), altering gene expression
What effect does thyroid hormone have on the anterior pituitary?
Activate GH production and repress TSH production via negative feedback
What other hormone is T3 synergistic with?
Catecholamines to increase heart rate
What is a goitre?
Swelling of the thyroid gland
What is primary hypothyroidism?
Underactivity of the thyroid gland - autoimmune destruction (Hashimoto’s thyroiditis)
What is the function of thyroid hormones?
Increase metabolic rate
What is the sign of primary hypothyroidism in a thyroid function test?
Elevated TSH and low T3 and T4
How do you treat hypothyroidism?
Oral thyroxine with the goal to normalise TSH
What should you consider before prescribing thyroxine to a patient with hypothyroidism?
Presence of Addison disease. If patient has Addison disease then increase of metabolic rate with thyroxine will increase demand for already inadequate cortisol supply
What is secondary hypothyroidism?
Underactivity of anterior pituitary thyrotrophs with low TSH
What is thyrotoxicosis?
Increased circulating thyroid hormones from hyperthyroidism
What is Graves disease?
Autoimmune hyperthyroidism due to thyroid stimulating IgG antibodies activating TSH receptor
What are the signs of hyperthyroidism in a thyroid function test?
Suppressed TSH and elevated T3 and T4. Elevated antithyroglobulin and antithyroid peroxidase
How would you treat Graves’ disease?
Antithyroid drugs (carbimazole)
Surgery - thyroidectomy
Radioactive iodine (when no pregnancy or eye disease)
Beta-blockers (to reduce adrenergic excess)
What is the concern for Graves disease in pregnancy?
Antithyroid drugs cross placenta and block fetal thyroid
Thyroid stimulating antibodies can cross placenta and cause fetal thyrotoxicosis
What is thyroid eye disease (Graves orbitopathy)?
Swelling of the extraocular muscles of the orbit which leads to difficulty fully closing the eyes (staring appearance)
What would you suspect in a patient with high T3 but no goitre?
Toxic adenoma of the thyroid gland (secretes T3)
What is calitonin?
Hormone secreted from C-cells of thyroid gland with the action of reducing calcium
What is parathyroid hormone (PTH)?
Hormone released from chief cells of parathyroid glands that increases calcium levels: increased calcium renal reabsorption, inhibits bone forming osteoblasts to release calcium into blood
