Exam 4 Flashcards
Endocrinology
Study of intra and extracellular communication by hormones
Hormone
Chemical substance produced and secreted into the blood by an endocrinological organ or tissue
Endocrine hormone
Synthesized in 1 location and released into blood circulation, binds to specific receptor in cells at a distant site to elicit response
Paracrine hormone
Synthesized in endocrine cells and released into interstitial space, binds to specific receptor of nearby cell and affects it function
Autocrine hormone
Synthesized in endocrine cells and sometimes released into interstitial space, binds to specific receptor on the cell of origin autoregulating its function
Exocrine hormone
Synthesized in endocrine cells and released into lumen of GI, binds to cells lining the GI at varying distances from the endocrine cells affecting their functions
Function of hormones
Maintain homeostasis for efficient function, influence growth and development, part of overall control of bodily function, linked to CNS through hypothalamus and pituitary to regulate and respond to target organs
Mechanism of action of hormones
Binding of a hormone to its receptor on the surface of the cell membrane through cAMP or Phospholipase C pathway
Bioassay
Based on observations of physiological responses that are specific for the hormone being measured
Immunoassay
ELISA. RIA, EMIT, fluorescence polarization and chemiluminescent immunoassay
Radioreceptor assay
An in vitro assay which allows interaction of hormone with its biological receptor
Hypothalamic-pituitary axis location
The portion of the brain located in the walls and floor of the third ventricle, which is connected to the posterior pituitary by the pituitary stalk
Hypothalamic-pituitary axis purpose
Control over pituitary function by direct neurostimulation and neurosecretion events of the hypothalamus, direct relationship with posterior pituitary, indirect relationship with anterior pituitary through the portal system
Pituitary location
Below the hypothalamus anatomically
Pituitary function
Releases hormone such as ADH, oxytocin, ACTH, GH, prolactin, LH, FSH and TSH
General features of over-secretion of pituitary hormones
Overproduction of only 1 hormone, deficient in more than 1 and eventually all the anterior pituitary hormones, sequentially loss of hormones, GH - FSH - LH - TSH - ACTH and prolactin, delayed diagnosis due to slow development of symptoms
Growth hormone physical actions
Promotes growth in soft tissues, cartilage and bone, causes positive nitrogen and phosphorous balance, stimulates hepatic glycogenolysis and antagonizes the effect of insulin on glucose uptake by peripheral cells, promotes linear growth through other hormone factors
Insulin-like growth factors
Polypeptides structurally related to insulin, exhibit metabolic and growth promoting effects similar to insulin
IGF I
One of the major regulators of cell growth and differentiation, synthesis mainly in liver, dependent on GH
Regulation of GH
Stimulated by GHRH, inhibited by somatostatin
Over-secretion of GH
By adenomas of pituitary, impairment of glucose tolerance
Pituitary giant
If overproduction occurs before long-bone growth is complete
Acromegaly
If overproduction occurs after long-bone growth is complete, prior to closure of epiphyseal plates
GH deficiency as an isolated disorder
Pituitary dwarfism in children, no clinical symptoms in adult
GH deficiency as part of panhypopituitarism
Pituitary dwarfism plus symptoms resulted from other hormone deficiency in children, symptoms related from other hormone deficiency (without symptoms caused by GH deficiency) in adults
Prolactin
Initiation and maintenance of lactation through induction of ductal growth, development of the lobular alveolar system and synthesis of specific milk protein, secretion initiated by dopamine and stimulated by TRH and by sucking
Hyperprolactinemia
Caused by a decrease in PIF or autonomous production of prolactin by a pituitary tumor, certain medicine or renal failure, presented with amenorrhea and/or galactorrhea in women and oligospermia or impotence or both in men, diagnosis is radiology and prolactin levels
ADH and oxytocin
Released from posterior lobe of pituitary gland, synthesized in 2 nuclei of hypothalamus, transported through neuronal axons in pituitary stalk to posterior lobe of pituitary, released when stimulation of hypothalamus by ADH or oxytocin, regulated by baroreceptors that respond to alteration in blood volume
Physiological actions of ADH
Regulate water permeability of the collecting tubules, generalized vasoconstriction to increase BP when released in sufficient amount
Physiological actions of ADH
Regulate water permeability of the collecting tubules, generalized vasoconstriction to increase BP when released in sufficient amount
Physiological actions of oxytocin
Stimulate the contraction of the uterus in the estrogen-primed uterus
Diabetes insipidus
Decreased secretion of ADH upon osmoregulatory stimulation, unresponsive to ADH due to nephrogenic problems, failure of the renal tubule to reabsorb water manifested by polyuria, sense of thirst, Hypernatremia and high plasma osmolality
Water deprivation test
Used to diagnose type of diabetes insipidus, measures plasma and urine osmolality before and after DDVAP
Normal Water deprivation results
Plasma: 280-300 (before)
<5% increase (after
Urine: >600 (before)
>700 (after)
Neurogenic diabetes insipidus water deprivation results
Plasma: >300 (before)
Decreased (after)
Urine: <300 (before)
>600 after
Nephrogenic diabetes insipidus water deprivation results
Plasma: >300 (before)
No change (after)
Urine: <300 (before)
<300 (after)
Hypersecretion of ADH
ADH levels inappropriately increased relative to a low plasma osmolality, ADH overproduction due to CNS disorders, pulmonary diseases or malignancy, manifested by low serum Na+, high urine Na+ and urine osmolality > serum osmolality
Thyroid gland
Made of follicular cells, synthesizes thyroid hormone (T3 and T4), parafollicular cells make calcitonin
Metabolism of T3 and T4
> 99.9% are protein bound, TBG, TBPA, TBA, metabolized through successive deiodination (80%) and nondeiodinative mechanisms, formation of T3 by monodeiodination of T4 (80%) in peripheral tissue synthesis of T3 (20%), conversion of T4 -> T3 (30%) T4 -> rT3 (60%), potency of T3 greater than T4 but less concentrated in blood
Growth and development with thyroid hormones
Regulates optimal growth and development of all body tissue, stimulates protein synthesis
Cretinism
Caused by deficiency in iodine, failure of thyroid to develop, present with dwarfism, mental retardation, pale skin, slow heart rate, low body temperature
Calorigenic effect with thyroid hormones
Increase resting or basal metabolic rate of whole organism, increase body temperature
Cardiovascular effects with thyroid hormones
Increase adrenergic activity and sensitivity, increase heart rate, increase force of contraction, increase cardiac output, decrease peripheral vascular resistance
metabolic effects with thyroid hormones
Increase calorigenesis and O2 consumption, increase heat dissipation, increase protein catabolism, increase glucose production, increase glucose uptake
GI effects with thyroid hormones
increase motility, hyperthyroidism with hyperdefecation, hypothyroidism with constipation
Hypothyroidism
Deficiency of thyroid activity, occurs in mild or severe forms, affects women more than men and increases with age, may have obvious or subtle symptoms, commonly caused by diseases or treatments that destroy thyroid tissues or interefere with thyroid biosynthesis and less often by disorders of the pituitary or hypothalamus
Primary hypothyroidism
An impaired synthesis of T4 and T3 due to intrinsic factor or inherited defect in thyroid hormone biosynthesis, hypersecretion of TSH with decreased T4, may be goitrous or nongoitrous, most frequently caused by Hashimoto’s in developed countries and iodine deficiency most common in goitrous worldwide
Primary hypothyroidism symptoms
Weakness, cold intolerance, constipation, weight change, depression, menorrhagia and hoarseness, dry skin, bradycardia
Hashimoto’s disease
Primary hypothyroidism, aka chronic lymphocytic thyroiditis, goiytous, associated with antithyroid antibodies and may coexist with other autoimmune diseases
Iodine deficiency
Primary hypothyroidism, goitrous
Congenital hypothyroidism
May be due to absence of the thyroid gland or defects of thyroid hormone synthesis, is reversible if treated early, can be detected by screening in neonate
Hyperthyroidism
Excessive quantities of thyroid hormone, increased secretion of thyroid hormones by TSA, autonomous production by solitary or multiple thyroid nodules, excessive TSH secretion by pituitary tumors or by increased or leakage of stored T3 or T4
Grave’s disease
most common cause of hyperthyroidism, diffuse goiter, ophthalmopathy and pretibial edema, caused by immunological disorder where serum antibodies bind to thyroid cell membrane at or near TSH receptor, diagnosed by a decreased TSH and in increased free T4 and presence of TSI
Assays for thyroid function
TSH, total and free T4, total and free T3, rT3, T3 uptake, FT4 index, FT3 index, TRH stimulation, TBG, antithyroglobulin antibodies, antimicrosomal antibodies, TSH receptor antibodies
Tests to use if sensitive serum TSH assay is undetectable
Hyperthyroid suspect, Free T4, T3 if free T4 normal
Tests to use if sensitive serum TSH assay is subnormal
Borderline thyroid status, Free T4 and T3, TRH test
Tests to use if sensitive serum TSH assay is normal
No hyperthyroid dysfunction
Tests to use if sensitive serum TSH assay is elevated
Hypothyroid suspect, Free T4
Increased TBG
Caused by pregnancy or oral contraceptives, increased TBG level, decreased saturation, increased binding of T4 and T3, decreased free T4 and T3
Decreased TBG
Caused by androgens, malnutrition and lover disease, decreases TBG and saturation, decreased binding of T4 and T3. increase free T4 and T3
Adrenal glands
On upper pole of each kidney
3 layers of adrenal gland cortex
zona glomerulosa, zona fasciculata, and zona reticularis
Aldosterone
regulation of potassium metabolism, regulation of extracellular fluid volume, and is controlled by the renin-angiotensin system and ACTH
Renin
Produced by the juxtaglomerular apparatus of the kidney in response to decreased renal perfusion pressure and/or decreased serum sodium levels, acts on angiotensinogen to produce angiotensin I which is converted to angiotensin II by angiotensin-converting enzyme present mainly in the lungs
Angiotensin II
constricts blood vessels, stimulates secretion of aldosterone by the zona glomerulosa
physiological function of cortisol
Anti-insulin effects on carbohydrate, stimulate protein catabolism, cause a central distribution of fat in the face, neck and trunk when present in excess, anti-inflammatory, immunosuppressive effects, effects on water and electrolyte balance
Biosynthesis of corticosteroids
the conversion of cholesterol to pregnenolone which is stimulated by ACTH (the rate-limiting step), hydroxylation of progesterone at the 17, 21, and 11 positions in the zona reticularis and zona fasciculata leads to the formation of cortisol, hydroxylation of progesterone at the 21, 11, and 18 in the zona glomerulosa forms aldosterone
Biosynthesis of adrenal androgens
12 alpha-hydroxypregnenolone is the main precursor for adrenal androgens, DHEA-S and DHEA are the most abundant adrenal androgens which can be converted to testosterone which can then be converted to estrogen peripherally, estrogen is largely derived from the gonads and from peripheral conversion of testosterone and androstenedione
Regulation of cortisol
ACTH, stimulated by CRH, positively regulates cortisol secretion, the free circulating cortisol acts in a negative-feedback manner to control the release of ACTH
Characteristics of serum cortisol levels
Diurnal variation with the highest levels present in the morning around 8 AM and the lowest levels present in the late afternoon, mainly bound to carrier protein, increased urine free cortisol levels = a sensitive indicator of adrenal hyper-function
Hypercortisolism
Caused by excessive production of ACTH by a pituitary adenoma (Cushing’s disease), ectopic ACTH by a tumor of non-endocrine tissue, excessive production of cortisol by an adrenal tumor or carcinoma (Cushing’s syndrome), exogenous administration of cortisol
Signs and symptoms of hypercortisolism
Truncal obesity with gain predominantly in the face, neck, shoulders, and abdomen with relatively thin extremities, abnormal glucose metabolism, protein wasting, with thinning of the skin and development of striae, easy bruising, muscle wasting and hypertension
Screening tests for hypercortisolism
overnight low-dose dexamethasone suppression test, 24-h urine free cortisol level, the morning and afternoon serum cortisol determination
Differentiation tests for hypercortisolism
high-dose dexamethasone suppression test, metyrapone stimulation test, plasma ACTH, and bilateral inferior petrosal sinus sampling after CRH administration to differentiate pituitary tumor from ectopic ACTH
Hypoadrenalism causes
primary adrenal disease, secondary to pituitary abnormalities
Addison’s disease
Results from idiopathic atrophy of the gland, characterized by weight loss, weakness, and a variety of GI complaints plus dehydration with hypotension, hyponatremia and hyperkalemia, may show hyperpigmentation of the skin and mucous membranes due to excess pituitary synthesis of ACTH
Studies for Addison’s disease
low serum sodium, high serum potassium, low glucose level, decreased of normal cortisol level, increased ACTH with blunted cortisol response to ACTH stimulation test
Adrenal androgen
Adrenal glands synthesize DHEA-S, DHEA, androstenedione and small amount to testosterone and DHT, regulated or partially regulated by ACTH not by FSH or LH, major source of testosterone in females
Male hormone production in the testis
Part of the hypothalamus-pituitary-gonadal axis, primary site of androgen production in the male, regulated by FSH and LH
Testosterone
Mainly produced by the testis under the control of LHH, converted to dihydrotestosterone by enzyme found in prostate, skin and seminal vesicle, major circulating androgen and responsible for male differentiation of the fetal genital tract and development and maintenance of male secondary sex characteristics and spermatogenesis, bind to SHBG and albumin with free testosterone being biologically active, serum level is used to evaluate hirsutism and virilization
Sex hormone binding proteins
Testosterone and dihydrotestosterone circulate mainly bound to SHBG in men, estradiol, DHEA-S and DHEA are bound to albumin
Primary hypergonadism
Testicular tumor or adrenal disorder, no clinical abnormality in males, early onset of the pubertal changes in the prepubertal male or children, noted high serum androgen levels, low serum gonadotropins and high urinary 17-ketosteroids
Secondary hypergonadism
Secondary to altered pituitary-hypothalamic axis function, resulting in elevation of gonadotropins, characterized by elevated androgens and elevated gonadotropins
Primary hypogonadism
Caused by genetic defect, infection, trauma, radiation, or tumor, show delayed puberty in children and impotence and loss of secondary sex characteristics in adults, manifested by increased serum and urine gonadotropin and by decreased serum androgen levels and decreased urinary 17-ketosteroid levels
Secondary hypogonadism
Results from failure of the pituitary-hypothalamic axis, resulting in a decreased production of FSH and LH, accompanied by other pituitary hormone deficiencies, show delayed puberty in children and impotence and loss of secondary sex characteristics in adults, characterized by decreased serum and urinary gonadotropins with diminished gonadal function after adolescence
The ovary
Made of the basic reproductive unit, primordial follicle which consists of a small oocyte arrested in the diplotene stage of meiotic prophase, function as both producers of ova and secretors of the sex hormones
Functions of estrogen
Growth of the uterus, fallopian tubes and vagina, promotion of breast development, deposition of body fat into the lobules of the breast for lactation, affect calcium homeostasis and plasma proteins
Regulation of estrogens
Regulated by FSH and LH, undergoes changes characteristics of the female reproductive system
Biosynthesis of estrogens
Conversion of androgens to estrogens by aromatase system in ovary, production of estrogens by peripheral aromatization of androgens in adipose tissue, generation of estriol in the placenta
Clinical synthesis of testing estrogen
Evaluate ovarian function, diagnose postmenopausal bleeding, evaluate the fetoplacental unit for fetal distress, intrauterine growth retardation, affect plasma proteins
Primary ovarian hyperfunction
Caused mainly by estrogen-secreting tumors, can occur before puberty, during the period of reproductive life or after menopause, characterized by precocious puberty and intermittent uterine bleeding in the premenarchal years, irregular uterine bleeding and amenorrhea during the active reproduction life or uterine bleeding during the postmenopausal years, associated with low serum FSH and LH levels and elevated or normal estrogen levels
Ovarian hypofunction
Primary amenorrhea during the prepubertal period, secondary amenorrhea during the post-pubertal period
Primary hypofunction
Result from premature ovarian failure, resistant ovary syndrome, ovarian tumors, gonadal agenesis, Turner’s syndrome and 17 a-hydroxylase deficiency, characterized by increased gonadotropins and decreased estrogen levels
Secondary ovarian hypofunction
Characterized by decreased estrogen and progesterone levels associated with decreased gonadotropin levels
Progesterone
Maintain the endometrium, inhibit uterine contractions, stimulate the lobar unit of the breast, used for the synthesis of cortisol and sex hormone precursors
Estriol
Produced in the placenta, major product of estrogen in pregnant women, can be used to predict fetoplacental function
Chorionic gonadotropin
Maintains progesterone production by the corpus luteum in the early pregnancy, stimulates development of fetal gonads and synthesis of androgen by the fetal testes, measured for diagnosis of pregnancy, prediction of spontaneous abortion, detection of multiple pregnancies, and detection and follow-up of HCG-producing tumors
Placental lactogen
Similar to GH and prolactin structurally, immunologically and functionally, act in concert with HCG to stimulate estrogen and progesterone synthesis by the corpus luteum, stimulates development of the mammary gland, used for monitoring conditions associated with a decrease in functioning placental tissue and in diagnosis of intrauterine growth retardation
Catecholamines
Consists of monoamines attached to a benzene ring bearing 2 hydroxyl groups
Norepinephrine
Major substance released by the postganglionic sympathetic nerves
Epinephrine
Most important substance produced by the adrenal medullar
Dopamine
Present in dopaminadenic neurons
Physiological actions of the catecholamines
Influence the vascular system and affect metabolic processes such as carbohydrate metabolism
A-adrenergic (epinephrine and norepinephrine)
Vasoconstriction, decrease in insulin secretion, sweating, stimulation of glycogenolysis in the liver and skeletal muscle
B-adrenergic
Vasodilation, stimulation of insulin release, increase of cardiac contraction rate, relaxation of smooth muscle in the intestinal tract, bronchodilation by relaxation of smooth muscles in bronchi, stimulation of renin release
Pheochromocytoma
Occur in the adrenal medulla (90%) and extra-adrenal sites (10%, paragangliomas), arise from ANS or adrenal medulla, produce excessive amounts of catecholamines or catecholamine metabolites, found in 0.1 to 0.3% of the population
Pheochromocytoma appearance
Sustained or paroxysmal hypertension, weight loss, spells of sweating, headache, palpitation, anxiety
Lab studies for Pheochromocytoma
Increased urinary metanephrines (24 hour urine) and elevated urinary VMA and free catecholamines
Neuroblastoma
One of most common malignant tumors in pediatric patients, manifests as a lump or mass in the abdomen or around the spinal cord in chest, neck, or pelvis, a cancer of the SNS, characterized by rapid growth and widespread metastasis, associated with excessive production of catecholamines and catecholamine metabolites, characterized by increased urinary norepinephrine, VMA, HVA and dopamine
