Endocrinology Flashcards
Composition of thyroid follicle
follicular cells
colloidal substance inside
Composition of colloid substance in thyroid follicle
A glycoprotein called thyroglobulin
Function of thyroglobulin
Store thyroids hormones extracellular
Thyroid hormones are the reserves of which amino acid
Tyrosine
Why are thyroid hormones bones to pretend carriers in circulation
Because they are hydrophobic molecules
Function of thyroid hormones
Maintain metabolic homeostasis (Intermediary metabolism, body weights, oxygen requirements, body temperature)
Control of growth , reproduction, differentiation
Names of thyroid hormones
Thyroxine T4
3,5,3’ triiodothyronine T3
Which thyroid hormones is secreted in larger amounts
T4 (80 µg)
T3 is only 5 µg
Which territories has a greater biological activity than the other one
T3 about 10 times more activity 24
Major sources of iodine for thyroid hormone
IodiZed salt
Iodated bread
dairy products
Daily requirement of iodide in diet for thyroid hormone
75 µg a day (10g of iodated salt )
Steps of iodide cycle
Uptake oxidation Organification coupling storage release
Iodide uptake
Transported from interstitial fluid
Concentrated in epithelial cells through Na/I symporter
Iodide uptake regulation
Uptake influenced by TSH and inhibited by perchlorate and thiocyanate
Oxidation of iodide
Thyroid peroxidase oxidize iodide and form I2
Iodide organification
Thyroid peroxidase helps form Mono-iodotyrosine and then di-iodotyrosine
Coupling of iodide
Catalyzed by thyroid peroxidase
2 x diiodotyrosine form T4
1 diiodotyrosine and 1 mono iodiotyrosine (T3)
Requires thyroglobulin for ether o bridges
Iodide storage
8000 ug of iodide stored in thyroid
Iodide release
Colloid droplets containing thyroglobulin with the hormones fuse with lysosomes
Hydrolysis of content with digestion of thyroglobulin and release of iodinated AA
Iodothyronine deiodinases function
Activation and inactivation of thyroid hormones
Types of Iodothyronine deiodinases
Type 1 deiodinase
Type 2 deiodinase
Type 3 deiodinase
Type 1 deiodinase
Converts t4 to T3 in liver kidney thyroid and brain
Type 2 deiodinase
Source of intracellular and circulatory T3
Type 3 deiodinase
Inactivation of T3 and t4
Wolf chaikoffs effect
Adaption to increase in plasma iodine
Inhibitor of NIS to reduce iodine extraction
Inhibits organification process
Which thyroid hormone is more potent
T3 (10x more than t4)
Main source of circulating T3
Monodeiodination of t4 (80%)
Transport of thyroid hormones
Thyroid binding hormones (70%)
Transthyretin (10% of T4)
Albumin (25% of T3 , 15% T4)
Primary carrier of T4 in CSF
Transthyretin
Excretion of thyroid hormones
Glucuronidqtion
Excreted via bile into feces
2 mechanisms of control of thyroid hormones synthesis
Autorégulation with iodine levels
Hypothalamus and anterior pituitary regulation
TSH action
Increases iodide transport into follicular cells
Increases production and iodination of thyroglobulin
Increases endocytosis of colloid form lumen into follicular cells
TSH MOA
Bind GPCR in thyroid follicle
Activated Gs
Increase of cAMP and PKA activation .
TSH release regulation
Inhibited by thyroid hormone with negative feedback at anterior pituitary ( reduce synthesis of TSH, decrease pituitary receptors for TRH, inhibit TRH synthesis)
Thyrotropin releasing hormone (TRH) released from hypothalamus stimulate release of TSH ( GPCR with IP3 and DAG action )
Dopamine, somatostatin, glucocorticoids inhibits TSH release
Impact of diet on thyroid hormone.
High carbohydrates diet increases T3 and metabolic rate ( diet induced thermogenesis)
Low carbohydrates diet decrease T3
Carbohydrate metabolism of T3 and T4
Low amount enhance glycogenesis with insulin
Large amount promotes glycogenolysis
Lipid metabolism of T3 and T4
Increase fat mobilization and oxidation of fatty acids when high amount
Low amount lead to increased serum cholesterol
Effects of TH on cardiovascular
Increase heart rate, contractility, cardiac output
Promote vasodilation , increase blood flow
Th effect on CNS
Alterations. In mental state
When small -> sluggish state
When high -> anxiety , nervousness
Th effect on reproductive system
Low levels can be linked to infertility
Thyroid hormone action
GH, prolactin production and secretion
GH action
Glucose intestinal réabsorption
Increase in mitochondrial oxidative phosphorylation
Enzyme synthesis
Hypothyroidism more common in men or women
Women
Hypothyroidism impact in infancy
Growth and mental retardation ( cretinism )
Hypothyroidism types
Primary
Secondary
Severe generalized hormone resistance
Causes of primary hypothyroidism
Endemic iodine deficiency
Destruction of thyroid tissue by surgery or during treatment of hyperthyroidism
Characteristics of primary hypothyroidism
Low thyroid hormones with high TSH stimulation
Enlarged goiter due to increased activity
Primary hypothyroidism symptoms
Cold intolerance Lethargy constipation slow mental function and motor activity weight gain decreased appetite abnormal menses .m dry thick skin hair loss horse voice stroke volume and heart rate decreased
Hyper thyroidism more common in men or women
Woman
Main causes of hyperthyroidism
Graves’ disease which is auto immune
Toxic uni nodular of multi nodular goiter’s or inflammation of thyroid gland
Characteristics of Hyper thyroidism
Hi thyroid hormones level
low response of TSH to TRH
Hyperthyroidism symptoms
Heat intolerance nervousness irritability emotional instability pounding heart Fatigue weight loss increased food ingestion increased bowel movements abnormal menses . tachycardia atrial arrhythmias
What’s unique feature appear in the Hyperthyroidism
Infiltrative ophtalmopathy
Which is protuberance of eyes
Composition of endocrine system
Endocrine glands
Hormones
Target organ
Endocrine gland
Ductless glands which secrete chemical products in interstitial space to reach circulation
Hormones
Chemical products released in very small amounts from cell and exert biological action on target cell
Classic Endocrine organs
Hypothalamus thyroid gland adrenal glands ovaries Pituitary gland parathyroid glands testes pancreas
Hormones released by the hypothalamus
GHRH (gonadotropin releasing hormone)
CRH( corticotropin releasing hormone)
TRH (thyrotropin releasing hormone)
GnRH (gonadotrophin releasing hormone )
Somatostatin
Dopamin
antidiuretic hormone
oxytocin
Hot hormones released by the thyroid gland
T3
T4
Calcitonin
Hormone released by adrenal glands
Cortisol Aldosterone adrenal androgens Epinephrine norepinephrine
Hormones released by the ovaries
Estrogen
progesterone
Hormones released by the pituitary gland
Growth hormone
Prolactin
ACTH (adrenocorticotropic hormone)
MSH (mélanocyte stimulating hormone)
TSH (thyroid stimulating hormone )
FSH (follicle stimulating hormone)
LH (luteinizing hormone)
Hormone released by the parathyroid glands
Parathyroid hormone
Hormones produced by the pancreas
Insulin
glucagon
somatostatin
Hormones released by the testes
Testosterone
Possible chemical structure of hormones
Proteins
Glycoproteins
steroids
amines
Most Abundant form of hormone
Protein glycoproteins
Pathway of protein hormone synthesis and release
Sensitized as a pre-prohormone
Converted to prohormone
Packaged in the Golgi apparatus to a hormone
Stored in secretory vesicles
Secreted through exocytosis in the interstitium with a calcium intake gradients
What are steroid hormone Derived from
Cholesterol
What are Amine Hormone derived from
Tyrosine
Two means of transport of hormones
As free hormone
bound to carrier proteins
What type of hormone can be transported as free hormone
Peptides Protein and glycoprotein
What type of four months require carrier proteins
Steroid hormone
thyroid hormone
Main type of hormone carrier proteins
Globulins Synthetized by the liver
What factor determines half life of Hormones
Binding to carrier proteins which regulates excretion from circulation and dynamic equilibrium
What organs are responsible for the inactivation of hormones
The liver via bile And kidney
What is l Hormone receptor desensitization
Decreased response to prolong exposure to Hormone
What are or some cases of hormone receptor desensitization
Down regulation with sequestration and hormone receptor endocytosis
Inactivation through phosphorylation
Truncation of intracellular signaling
What are Some factors controlling hormones
Central nervous system through Autonomic centers
Hormonal control with some hormones stimulating or inhibiting release of other hormones
Nutrient or ion regulation like glucose with insulin and glucagon
Negative and positive feedback
Name of rhythm of most hormones
Circadian rhythm
What rythm exist within the circadian rhythm and control cortisol levels
Ultradian rythm
Two types of neurons which mediates endocrine function
Magnocellular (posterior pituitary)
Parvocellular (anterior pituitary)
What’s structure connect the pituitary gland to the hypothalamus
Pituitary stalk
Three parts of pituitary glands
Anterior / adenohypophysis
Posterior / neurohypophysis
intermediates / pars intermedia
Why if there is disconnection of the pituitary stalk to the hypothalamus only prolactin levels increases
PIF ( prolactin releasing inhibiting factor) released normally by hypothalamus is not acting on prolactin anymore
All hormones of hypothalamic pituitary axis are pulsation except … ?
TRH
Sheehan syndrome
Occur in pregnancy
Enlargement of pituitary glands which becomes vulnerable to infarction
Hypothalamic control of GH
GHRH
GHIH/ somatostatin
What can increase secretion of growth hormones
Sleep starvation stress puberty related hormones exercise hypoglycemia
What can decrease secretion of growth hormone
Somatostatin Somatomedins obesity hyperglycemia pregnancy
Direct Actions of growthhormone
Decreases Cellular glucose uptake Increases lipolysis Increases Protein synthesis in muscle mass increases lean body mass Increase production of IGF
Causes of Laron dwarfism due to deficiency in GH
Lack of anterior pituitary GH
hypothalamic dysfunction
D’ailier to generate IGF
GH receptor deficiency
Excess GH before puberty
Gigantism
Excès Gh After oubeeety
Acromegaly
Adrenal glands different parts
Adrenal cortex outer layer
adrenal medulla inner layer
Type of hormones secreted in adrenal cortex
Steroid hormones
Type of steroid hormones found in the adrenal cortex
glucocorticoids
mineralocorticood
androgens
What Hormone from the pituitary gland triggers secretion of the steroid hormones in the adrenal cortex
ACTH
Glucocorticoids function
Increase glucose level by gluconeogenesis in liver
Increase protein and fats catabolism
Inhibits ACTH secretion
Sensitize arterioles to action of noradrenaline (blood pressure action )
Allow water excretion
Anti-inflammation effects on the body
How do you use glucocorticoids in therapy
In auto immune disease like rheumatoid arthritis
in transplantations of organs
Control asthma
Example of glucocorticoids
cortisol
How is cortisol transported into the blood
Cortisol binding globulin transcortin
Rhythm of secretion of cortisol
Diurnal -
Highest in the morning lowest at night
What time should you take a sample of cortisol levels
Between 8 AM to 9 AM
Main mineralocorticoid
Aldosterone
Function of aldosterone
Conserve sodium in the kidney help in secretion of potassium and allow water retention to stabilize blood pressure
Increase sensitivity of the taste buds to sources of sodium
Act on sweat glands to reduce less of sodium in perspiration
Secretion of aldosterone stimulated by
Sodium level drop in blood
Potassium levels rise in blood
Angiotensin II
AC TH in stress condition and in congenital adrenal hyperplasia
Type of androgens
Androstenedione (A)
Dehydroepiandrosterone (DHEA)
DHEA sulphate
At what stage of life do you have a rise in androgens
During puberty
Disorders of hyper function of adrenal cortex
Cushing’s syndrome ( excess cortisol) Conns syndrome ( excess aldosterone)
What type of people at risk of Cushing’s syndrome
Diabetics
Causes of Cushing’s syndrome
ACTH dépendant
ACTH indépendant
Iatrogenic
ACTH dependent Cushing’s syndrome
Pituitary hypersécrétion of ACTH
Mostly due to adenoma (60%)
Ectopic ACTH secretion (bronchial cancer)
ACTH therapy
AC TH independent Cushing syndrome
Excessive production of adrenal hormones themselves
could be due to adenoma, adrenal carcinoma, or in glucocorticoid therapy
Iatrogenic causes
Google cortical therapy for some other disorder like rheumatoid arthritis or in organ transplants
What is the difference between Cushing syndrome and Cushing’s disease
Cashing disease means that the pituitary is involved
Cushing’s syndrome when other cause
Pseudo Cushing syndrome
Patient appear cushingoid
Occur in severe depression and alcoholism
Clinical feature of Cushing syndrome
Truncal obesity (moon face, protuberant abdomen ) Thinning of skin Purple stretch marks on the breasts arms abdomen thighs excessive bruising Hirsutism skin pigmentation (elevated ACTH) hypertension Glucose intolerance muscle weakness menstrual irregularities back pain Psychiatric disturbances Euphoria depression
Cushing syndrome biochemistry
Hypokalemia
Kaliuresis
Glucose intolerance
Metabolic alkalosis
Investigation of Cushing syndrome
Initial screening test for Cushing’s syndrome
24h urinary cortisol excretion
Low dose dexamethasone surpression test.
Diurnal rythm of plasma
Insulin hypoglycemia test
24 h urinary cortisol excretion test
Urine collected over 24h period
Free cortisol measured.
Cushing syndrome excluded if cortisol < 300nmol/24h
Not specific to tell if pseudo Cushing’s syndrome
Disorders of hyper function of adrenal cortex
Cushing’s syndrome ( excess cortisol) Conns syndrome ( excess aldosterone)
What type of people at risk of Cushing’s syndrome
Diabetics
Causes of Cushing’s syndrome
ACTH dépendant
ACTH indépendant
Iatrogenic
ACTH dependent Cushing’s syndrome
Pituitary hypersécrétion of ACTH
Mostly due to adenoma (60%)
Ectopic ACTH secretion (bronchial cancer)
ACTH therapy
AC TH independent Cushing syndrome
Excessive production of adrenal hormones themselves
could be due to adenoma, adrenal carcinoma, or in glucocorticoid therapy
Iatrogenic causes
Google cortical therapy for some other disorder like rheumatoid arthritis or in organ transplants
What is the difference between Cushing syndrome and Cushing’s disease
Cashing disease means that the pituitary is involved
Cushing’s syndrome when other cause
Pseudo Cushing syndrome
Patient appear cushingoid
Occur in severe depression and alcoholism
Clinical feature of Cushing syndrome
Truncal obesity (moon face, protuberant abdomen ) Thinning of skin Purple stretch marks on the breasts arms abdomen thighs excessive bruising Hirsutism skin pigmentation (elevated ACTH) hypertension Glucose intolerance muscle weakness menstrual irregularities back pain Psychiatric disturbances Euphoria depression
Cushing syndrome biochemistry
Hypokalemia
Kaliuresis
Glucose intolerance
Metabolic alkalosis
Investigation of Cushing syndrome
Initial screening test for Cushing’s syndrome
24h urinary cortisol excretion
Low dose dexamethasone surpression test.
Diurnal rythm of plasma
Insulin hypoglycemia test
24 h urinary cortisol excretion test
Urine collected over 24h period
Free cortisol measured.
Cushing syndrome excluded if cortisol < 300nmol/24h
Not specific to tell if pseudo Cushing’s syndrome
Disorders of hyper function of adrenal cortex
Cushing’s syndrome ( excess cortisol) Conns syndrome ( excess aldosterone)
What type of people at risk of Cushing’s syndrome
Diabetics
Causes of Cushing’s syndrome
ACTH dépendant
ACTH indépendant
Iatrogenic
ACTH dependent Cushing’s syndrome
Pituitary hypersécrétion of ACTH
Mostly due to adenoma (60%)
Ectopic ACTH secretion (bronchial cancer)
ACTH therapy
AC TH independent Cushing syndrome
Excessive production of adrenal hormones themselves
could be due to adenoma, adrenal carcinoma, or in glucocorticoid therapy
Iatrogenic causes
Google cortical therapy for some other disorder like rheumatoid arthritis or in organ transplants
What is the difference between Cushing syndrome and Cushing’s disease
Cashing disease means that the pituitary is involved
Cushing’s syndrome when other cause
Pseudo Cushing syndrome
Patient appear cushingoid
Occur in severe depression and alcoholism
Clinical feature of Cushing syndrome
Truncal obesity (moon face, protuberant abdomen ) Thinning of skin Purple stretch marks on the breasts arms abdomen thighs excessive bruising Hirsutism skin pigmentation (elevated ACTH) hypertension Glucose intolerance muscle weakness menstrual irregularities back pain Psychiatric disturbances Euphoria depression
Cushing syndrome biochemistry
Hypokalemia
Kaliuresis
Glucose intolerance
Metabolic alkalosis
Investigation of Cushing syndrome
Initial screening test for Cushing’s syndrome
24h urinary cortisol excretion
Low dose dexamethasone surpression test.
Diurnal rythm of plasma
Insulin hypoglycemia test
24 h urinary cortisol excretion test
Urine collected over 24h period
Free cortisol measured.
Cushing syndrome excluded if cortisol < 300nmol/24h
Not specific to tell if pseudo Cushing’s syndrome
Low dose dexamethasone suppression test
1mg dexamethasone given At night
Blood sample taken next morning
Normal individual have serum cortisol suppressed to less than 50 nmol/l
Failure to suppress suggestive of Cushing syndrome
Not specific
Diurnal rythm of plasma
Normal patients would have high cortisol in the morning and low Cortisol in the knights
Loss of diurnal variation in patient with Cushing syndrome So cortisol level at night could be raised
Not specific
Insulin hypoglycemia test
Insulin given IV to lower blood glucose 2.2 mmol/liter
Blood glucose and cortisol measured at 30 45 60 and 90 minutes
Normal patients ( and pseudo Cushing’s) serum cortisol at max at 60 or 90 minutes
patient with Cushing syndrome show little or no response
Test used to know the cause of Cushing syndrome
Measurement of plasma ACTH
Would be increased or normal in Cushing’s disease
Would be non-detectable in an adrenal tumor
Would be increased or Much increased in Ectopic ACTH secreting tumor
What does is use to confirm diagnosis Of Cushing syndrome and it’s cause
High dose Dexamethasone suppression test
Cortisol levels decreased to less than 50% in Cushing’s disease
Cortisol level not depressed in adrenal tumor and ectopic ACTH secreting tumor
Name of test used to differentiate between Cushing’s disease and ectopic ACTH secretion
CRH stimulation test
Name of adrenocortical hypofunction disease
Addison’s disease
Primary Causes of Addison’s disease
Destruction of adrenal gland by infection or autoimmune adrenalitis
Addison’s disease secondary cause
Infiltrative lesion
CAH / Hypoplasia
Inherited mutation in ACTH receptor on adrenal cells
Biochemistry of Addison’s disease
Hypoglycemia Hypomatremia Hyperkalemia Raised ureA Acid base disturbance
Clinical features of Addison’s disease
Tiredness Weakness Lethargy Anorexia Nausea Vomiting Weight loss Dizziness Pigmentation Loss of body hair Hyperpigmentation when high ACTH (melanocytes stimulating activity)
Adrenal crisis
Chronic form of adrenal disturbance
Precipitated by stress
Clinical symptoms of adrenal crisis
High fever Dehydration Nausea Vomiting Hypotension Hypovolaemia Hypoglycemic shock Hyperkalemia Hyponatremia Hemoconcentration
Diagnosis of primary adrenal hypo function
Cortisol < 50nmol at 9am
ACTH high because lack of negative feedback
Diagnosis of secondary adrenal hypo function
Low cortisol and ACTH
Conns syndrome
Excessive production of aldosterone
Conns syndrome causes
Adrenal Aldosterone producing adenoma
Diffuse hypertrophy of zona glomerulosa of adrenal cortex
Glucocorticoid remediable aldosteronism
Conns syndrome clinical feature
Hypokalemia Hypertension Muscle weakness Polydipsia Polyuria
Biochemistry conns syndrome
Hypokalemia Kaliuresis Impaired glucose tolerance Metabolic alkalosis H
Diagnosis of conns disease
Measure aldosterone , plasma renin activity and do ratio
Very possible if ratio over 2000
Confirmatory diagnosis of conns syndrome
Saline infusion test (if plasma aldosterone superior to 240 pmol/L)
Posture test
