DISORDERS OF DISORDERS OF ENDOCRINE SYSTEMENDOCRINE SYSTEM

Prof. J. HanáčekProf. J. Hanáček, MD, PhD, MD, PhD

Technical co-operation: L. Šurinová, T.Zaťko, Ing.M.VrabecTechnical co-operation: L. Šurinová, T.Zaťko, Ing.M.Vrabec

Endocrine systemEndocrine system -- together with the nervous system, together with the nervous system, acts as acts as

the the body´s communicationbody´s communication networknetwork

- it is composed of it is composed of various various endocrineendocrine glandsglands and endocrine cells and endocrine cells

- the glands are capable of synthethe glands are capable of synthettizing and izing and releasing special chemicalreleasing special chemical mesengers - mesengers - hormoneshormones

HormonesHormones - substances which are secreted by - substances which are secreted by specialised cells specialised cells in in

very very low concentrationslow concentrations and they are able to influence and they are able to influence

secreted cell itselfsecreted cell itself (autocrine influence), (autocrine influence), adjacent cellsadjacent cells

(paracrine influence) or (paracrine influence) or remote cellsremote cells (hormonal influence) (hormonal influence)

The main groups of hormonesThe main groups of hormones

Classic hormonesClassic hormones (produced by specialised glands) (produced by specialised glands) are divided inare divided intoto

three groups:three groups:

1.1. low molecular low molecular ((amineamine)) hormones hormones (catecholamines, thyroid hormones, (catecholamines, thyroid hormones,

prostaglandins, leucotrienes, dopamine, serotonine, GABAprostaglandins, leucotrienes, dopamine, serotonine, GABA, ,

melatoninmelatonin ...) ...)

2.2. steroid hormonessteroid hormones (e.g.gluco- and mineralocorticoids) (e.g.gluco- and mineralocorticoids)

3.3. polypeptidic and protein hormonespolypeptidic and protein hormones (e.g. insulin, leptin...) (e.g. insulin, leptin...)

Another groups of Another groups of hormoneshormones

A. hypothalamic hormonesA. hypothalamic hormones (discovered in 1969) (discovered in 1969)

B. gastrointestinal hormonesB. gastrointestinal hormones ( (more than more than 26 GI polypeptides)26 GI polypeptides)

C. opioid peptidesC. opioid peptides (endogenic opioids) (endogenic opioids)

D. tissue growth factorsD. tissue growth factors (epidermal growth factor, nerve growth factor, (epidermal growth factor, nerve growth factor, PDGF, insuline-like growth factor ...)PDGF, insuline-like growth factor ...)

E. atrial natriuretic hormoneE. atrial natriuretic hormone (ANF) (ANF)

F. transforming growth factors and hematopoietic F. transforming growth factors and hematopoietic and other and other growth factorsgrowth factors (FGF....) (FGF....)

G. endothelial factorsG. endothelial factors (endothelins, EDRF...) (endothelins, EDRF...)

H. H. ccytokinesytokines (interleukiny, interferón, TNF....) (interleukiny, interferón, TNF....)

General characteristic of hormonesGeneral characteristic of hormones

1. 1. they have they have specific ratesspecific rates andand patternspatterns of secretionof secretion (diurnal, pulsatile, (diurnal, pulsatile,

cyclic patterns, pattern that depends on cyclic patterns, pattern that depends on the the level of circulating substrateslevel of circulating substrates))

2. they operate within 2. they operate within feedback systemsfeedback systems,, either positive either positive(rare)(rare) or negative, or negative,

to maintain an optimal internal environmentto maintain an optimal internal environment

3. they 3. they affect only cells withaffect only cells with appropriate receptorsappropriate receptors specific specific cell cell

functionfunction(s)(s) is initiated is initiated

4. they are 4. they are excretedexcreted by the by the kidney,kidney, deactivateddeactivated by the by the liverliver or by or by other other

mechanismsmechanisms

Some general effects of hormonesSome general effects of hormones

HormonesHormones regulate theregulate the transport of ions, substrates and metabolittransport of ions, substrates and metabolitees s

across the cell membrane:across the cell membrane:

- they stimulate - they stimulate transport of glucose and amino acidstransport of glucose and amino acids

- they influence of - they influence of ionic transportionic transport across the cell membrane across the cell membrane

- they influence of - they influence of epithelial transporting mechanismsepithelial transporting mechanisms

- they stimulate or inhibit of - they stimulate or inhibit of cellular enzymescellular enzymes

- they influence the - they influence the cells genetic informationcells genetic information

Mechanisms of hormonal alterationsMechanisms of hormonal alterationsA. elevated hormones levelA. elevated hormones level

B. depressed hormones levelB. depressed hormones level

may be caused bymay be caused by::

1. failure of feedback systems1. failure of feedback systems

2. dysfunction of endocrine gland or endocrine function of cells:2. dysfunction of endocrine gland or endocrine function of cells:

a) secretory cells area) secretory cells are unable to produce unable to produce oror do notdo not obtain obtain

an adequate quantity of required an adequate quantity of required hormone precursorshormone precursors

b) secretory cells are b) secretory cells are unable to convert the precursorsunable to convert the precursors to the to the

appropriate appropriate active active formform of hormon of hormon

cc) secretory cells may ) secretory cells may synthetize synthetize and and release excessive amountsrelease excessive amounts

of hormoneof hormone

3. degradation of hormones at an altered rate or they may be 3. degradation of hormones at an altered rate or they may be

inactivinactivatated by antibodies before reachinged by antibodies before reaching the target cellthe target cell

4. ectopic sorces of hormones4. ectopic sorces of hormones

C. failure of the target cells to respond to hormoneC. failure of the target cells to respond to hormone

MMay be caused by:ay be caused by:

1. receptor-associated disorders1. receptor-associated disorders

2. intracellular disorders2. intracellular disorders

AdAd C C 1. 1. Receptor associated disorders Receptor associated disorders

a) a) decrease in the numberdecrease in the number of receptorof receptorss hormone - receptor binding hormone - receptor binding

b) b) impaired receptor functionimpaired receptor function sensitivity to the hormonesensitivity to the hormone

c) c) antibodiesantibodies against specific receptors against specific receptors

d) d) unusual expressionunusual expression of receptor functionof receptor function

AdAd C C 2. 2. Intracellular disordersIntracellular disorders

a) a) inadequateinadequate synthesis of the synthesis of the second messengersecond messengerss

b) b) number of intracellular receptorsnumber of intracellular receptors may be may be decreased decreased or they may or they may

havehave altered afaltered afffinityinity for hormones for hormones

c) c) alterationsalterations inin generation of new mesenger RNAgeneration of new mesenger RNA or absence of or absence of

substrates for new protein synthesissubstrates for new protein synthesis

I. Alterations of the hypothalamic - pituitary systemI. Alterations of the hypothalamic - pituitary system

Deficiency Deficiency of hypothalamic hormones of hypothalamic hormones

Variety of manifestations Variety of manifestations can be seen:can be seen:

- In adult women:- In adult women: menses cease- absence of menses cease- absence of GnRH GnRH

- In adult men:- In adult men: spermatogenesis is impaired spermatogenesis is impaired-absence of -absence of GnRHGnRH

- ACTH responseACTH response to low serum cortisol levels to low serum cortisol levels is decreasedis decreased due to due to absence of CRHabsence of CRH

- Hypothalamic hypothyreoidism- Hypothalamic hypothyreoidism - - absence of TRHabsence of TRH

-- Low levels growth hormoneLow levels growth hormone - - absence ofabsence of GH GH regulatoryregulatory hormoneshormones

- HyperprolactinemiaHyperprolactinemia is caused by an absence of usual is caused by an absence of usual inhibitory controls of prolactin secretioninhibitory controls of prolactin secretion

Diseases of the posterior pituitary glandDiseases of the posterior pituitary gland

Syndrome of inappropriate ADH secretion (SIADH):Syndrome of inappropriate ADH secretion (SIADH):

It is characterised by It is characterised by high levels of ADHhigh levels of ADH in the in the absenceabsence of normal of normal physiologic stimuli for its releasephysiologic stimuli for its release

1. 1. Elevated levels of ADHElevated levels of ADH is caused by is caused by ectopically produced ADHectopically produced ADH (cancer (cancer of the lung, leukemia, response to surgery, inflammation of lung tissue, of the lung, leukemia, response to surgery, inflammation of lung tissue, psychiatric disease, drugs-barbiturates, general anaesthesia, diuretics...)psychiatric disease, drugs-barbiturates, general anaesthesia, diuretics...)

water retention water retention total body H total body H22O O aldosteron production aldosteron production

solute loss (Nasolute loss (Na++) ) hyponatremia hyponatremia hypoosmolality hypoosmolality

ADH is released continuallyADH is released continually

dilutional hyponatremia dilutional hyponatremia suppression of renin suppression of renin production production

aldosterone productionaldosterone production NaNa++ reabsorbtion in kidney reabsorbtion in kidney

eeven if ven if hyponatremiahyponatremia develops slowly, serum sodium levels below 110 develops slowly, serum sodium levels below 110

to 115 mmol/l are likely to cause to 115 mmol/l are likely to cause severesevere and sometimes and sometimes irreversible irreversible neurologic damageneurologic damage

rrapid decrease of serum Naapid decrease of serum Na++ from 140 to 130 mmol/l from 140 to 130 mmol/l thirst, anorexia, thirst, anorexia, dyspnea on exertion, fatigue occurdyspnea on exertion, fatigue occur

2. 2. Diabetes insipidus (DI)Diabetes insipidus (DI) - is related to an - is related to an insufficiency of ADHinsufficiency of ADH leading leading to to polyuria and polydipsiapolyuria and polydipsia

Three forms of DIThree forms of DI do do exist: exist:

a)a) neurogenic or central formneurogenic or central form - - amount of ADH amount of ADH production production

b) nephrogenic formb) nephrogenic form - inadequate response to ADH - inadequate response to ADH

c) psychogenic formc) psychogenic form - extremely large volumes of fluid - extremely large volumes of fluid intake intake inhibition of inhibition of ADHADH production production

Pathophysiology:Pathophysiology:

DIDI - partial to total inability to concentrate urine due to chronic- partial to total inability to concentrate urine due to chronic polyuria polyuria

washout of renal medullary concentration gradientwashout of renal medullary concentration gradient

- increase in plasma osmolality - increase in plasma osmolality thirst thirst polydipsiapolydipsia ((looking forlooking for cold drinks)cold drinks)

-- urine output, urine output, urine specific gravity urine specific gravity (1.00-1.005 (1.00-1.005))

- dehydratation- dehydratation (if not (if not adequate adequate fluidfluid intake intake))

Diseases of the anterior pituitaryDiseases of the anterior pituitary gland gland

HHypopituitarismypopituitarism is caused e.g. by infarction of the gland, removal, or is caused e.g. by infarction of the gland, removal, or

destruction of the glanddestruction of the gland

HHyperpituitarismyperpituitarism - adenoma - adenoma

HypopituitarismHypopituitarism - - insufficient secretion of one (selectiveinsufficient secretion of one (selective formform),), more more

than one or all (panhypopituitarism) hormones of than one or all (panhypopituitarism) hormones of adenohypophadenohypophyysissis

Causes:Causes: idiopathic, organic damage of adenohypoph idiopathic, organic damage of adenohypophyysissis or hypothalamusor hypothalamus, ,

e.g. e.g. pituitary infarction= Sheehan syndrome, pituitary apoplexy, pituitary infarction= Sheehan syndrome, pituitary apoplexy,

shock, shock, DM, DM, head trauma, infections, vascularhead trauma, infections, vascular malformations, malformations, tumorstumors

ConsequencesConsequences - they depend on the affected hormones - they depend on the affected hormones - i- if all hormones aref all hormones are defficient defficient panhypopituitarism:panhypopituitarism: the patients suffer from:the patients suffer from:

- cortisol deficiency- cortisol deficiency - because of lack of ACTH - because of lack of ACTH

- thyroid hormones deficiency- thyroid hormones deficiency - because of lack of TSH - because of lack of TSH

- - ADH defficincyADH defficincy - - diabetes insipidusdiabetes insipidus

- defficiency of defficiency of FSH and LHFSH and LH - - gonadal failure and loss of secondary sex gonadal failure and loss of secondary sex

characteristics characteristics - growth hormonegrowth hormone somatomedin (they affect children somatomedin (they affect children growth growth))

- absence of prolactinabsence of prolactin postpartum women are postpartum women are uunable tonable to lactatelactate

ACTH deficiencyACTH deficiency (within 2 weeks) symptoms of cortisol (within 2 weeks) symptoms of cortisol insufficiency insufficiency are are developdevelopeded

- nausea, vomiting, anorexia, fatigue, weakness- nausea, vomiting, anorexia, fatigue, weakness

- hypoglycemiahypoglycemia (it is caused by increased sensitivity (it is caused by increased sensitivity of tissues to of tissues to insulin,insulin, decreased glycogene reserves, decreased gluconeogenesisdecreased glycogene reserves, decreased gluconeogenesis))

- in women, loss of body hair and decreased libidoin women, loss of body hair and decreased libido

due to decreased adrenal androgen productiondue to decreased adrenal androgen production

- - llimitimited ed maximum aldosteron secretionmaximum aldosteron secretion

TSH deficiencyTSH deficiency (within 4-8 weeks) symptoms of TSH (within 4-8 weeks) symptoms of TSH deficiency deficiency are are developdevelopeded::

- cold intolerance- cold intolerance

- dryness of skin- dryness of skin

- - decreased metabolicdecreased metabolic raterate

- mild myxedema- mild myxedema

- lethargy- lethargy

FSH and LH deficiencesFSH and LH deficiences in in female offemale of reproductive age: reproductive age:

- amenorrhea- amenorrhea

- atrophic changes of vagina, uterus and breastsatrophic changes of vagina, uterus and breasts

in postpubertal in postpubertal menmen::

- atrophy of the testicles- atrophy of the testicles

- decreased beard growth- decreased beard growth

HyperpituitarismHyperpituitarism - - excessive production of adenohypophexcessive production of adenohypophyyssealeal hormoneshormones

Causes:Causes: - adenoma of - adenoma of adenoadenohypophhypophyysissis - hypothalamic form of hyperpituitarism- hypothalamic form of hyperpituitarism

Consequences:Consequences:

a)a) excessive secretion ofexcessive secretion of prolactinprolactin secretion of GnRH secretion of GnRH gonadotrophinsgonadotrophins

In menIn men: impotency, decreased libido: impotency, decreased libido

In womenIn women: amenorrhea, galactorrhea: amenorrhea, galactorrhea

b) excessive secretion ofb) excessive secretion of somatotrophinesomatotrophine (growth hormone(growth hormone))

acromegaly (in adults)acromegaly (in adults)

gigantism (in adolescents whose epiphysealgigantism (in adolescents whose epiphyseal

plates have not yet closed)plates have not yet closed)

a)a)

a)a)

b)-continuingb)-continuing PathomechanismsPathomechanisms involved involved::-The usual GH baseline secretion pattern is lost (as are sleep –The usual GH baseline secretion pattern is lost (as are sleep – related GHrelated GH peaks)peaks)

- A totally unpredictable secretory pattern- A totally unpredictable secretory pattern of GH of GH occurs occurs

- GH secretion is slightly elevated GH secretion is slightly elevated somatomedin somatomedin stimulation of growth stimulation of growth (in adolescent)(in adolescent)

- - CConnective tissue proliferationonnective tissue proliferation

- - BBony proliferation ony proliferation characteristic appearance of acromegaly characteristic appearance of acromegaly

- - PPhosphate reabsorbtion in renal tubules hosphate reabsorbtion in renal tubules hyperphosphatemia hyperphosphatemia

- - IImpairement of carbohydrate tolerancempairement of carbohydrate tolerance

- - M Metabolic rateetabolic rate

- HHyperglycemia - it is a result of GH inhibition of peripheral glucose uptake yperglycemia - it is a result of GH inhibition of peripheral glucose uptake

and increase hepatic glucose production and increase hepatic glucose production compensatory hyperinsulinism compensatory hyperinsulinism insulin resistance insulin resistance diabetes mellitus diabetes mellitus

In adultIn adultss::

b)b)

c) c) excessive secretion of corticotrophinexcessive secretion of corticotrophin (ACTH) (ACTH) central form of central form of

Cushing syndrome (Cushing disease)Cushing syndrome (Cushing disease)

Causes:Causes: micro- or macroadenomas of adenohypoph micro- or macroadenomas of adenohypophyysis, hypothalamic sis, hypothalamic

disordersdisorders

Pathophysiology:Pathophysiology:

CChronic hypercortisolismhronic hypercortisolism is the main disturbance is the main disturbance of of ACTH ACTH

Symptoms and signs:Symptoms and signs: weight gain:weight gain: - - accumulation of adipose tissueaccumulation of adipose tissue in the trunk, facial, and in the trunk, facial, and cervical areas (truncal obesity, moon face, buffalo hump) cervical areas (truncal obesity, moon face, buffalo hump)

- - weight gain from Na and water retentionweight gain from Na and water retention

glucose intoleranceglucose intolerance DM type 2 DM type 2

polyuria:polyuria: osmotic polyuria due to glycosuria osmotic polyuria due to glycosuria

protein wastingprotein wasting: due to catabolic effects of cortisol on peripheral tissue : due to catabolic effects of cortisol on peripheral tissue

(muscle wasting (muscle wasting muscle atrophy and weakness muscle atrophy and weakness thin lower thin lower

extremitiesextremities))

in bone:in bone: - loss of protein matrix - loss of protein matrix osteoporosis osteoporosis - - blood calcium concentration blood calcium concentration renal stones renal stones

in skin:in skin: - loss of collagen loss of collagen thin, weakened integumentary thin, weakened integumentary tissues tissues purple striae; rupture of small vesels purple striae; rupture of small vesels

- thin, atrophic skin is easily damaged, leading to skin breaks thin, atrophic skin is easily damaged, leading to skin breaks and ulcerationand ulceration

hyperpigmentation:hyperpigmentation: due to very high levels of ACTH due to very high levels of ACTH - - manifestation in: manifestation in: mucous membranes,mucous membranes, hair, andhair, and skinskin

hypertension:hypertension: results from permissive effect of cortisol on the actions of results from permissive effect of cortisol on the actions of

the catecholamines (KA) the catecholamines (KA) vascular sensitivity to KA vascular sensitivity to KA vasoconstriction vasoconstriction hypertension hypertension

suppression of the immune systemsuppression of the immune system susceptibility to infections susceptibility to infections

alteration of mental statusalteration of mental status - - from irritability and depression from irritability and depression up to schizophreniaup to schizophrenia

symptoms and signs of symptoms and signs of adrenal androgenadrenal androgenss level level in women:in women:

- - hair growth (especially facial hair) hair growth (especially facial hair)- acne- acne- oligoamenorrhea- oligoamenorrhea

- changes of the vois- changes of the vois

hyperglycemia, glycosuria, hypokalemia, metabolic alkalosishyperglycemia, glycosuria, hypokalemia, metabolic alkalosis

excessive secretion of thyreotrophin and gonadotrophinsexcessive secretion of thyreotrophin and gonadotrophins is rareis rare

Acute adrenal insufficiency

Waterhouse-Friderichsensyndrome

Prostration= very strong fatique

Causes: - infection - trauma - hemorhage - thrombosis

Alterations of thyroid functionAlterations of thyroid function

HyperthyroidismHyperthyroidism is a condition in which thyroid hormones is a condition in which thyroid hormones

(TH) exert greater-than-normal response(TH) exert greater-than-normal response

Causes:Causes:

- Graves disease- Graves disease- exogenous hyperthyroidism (iatrogenic, iodine induced)- exogenous hyperthyroidism (iatrogenic, iodine induced)- thyroiditis- thyroiditis- toxic nodular goiter- toxic nodular goiter- thyroid cancer- thyroid cancer

All forms of hyperthyroidism share some All forms of hyperthyroidism share some commoncommon characteristic:characteristic:

metabolic effect of increased circulating levels of thyroid metabolic effect of increased circulating levels of thyroid

hormones hormones metabolic rate with heat intolerance and increased tissue metabolic rate with heat intolerance and increased tissue

sensitivity to stimulation by sympathetic division of the autonomic sensitivity to stimulation by sympathetic division of the autonomic

nervous system;nervous system;

The major manifestations ofThe major manifestations of hyperthyroidism hyperthyroidism and mechanismsand mechanisms of of their onset their onset

a)a) endokrine:endokrine:

- enlarged thyroid gland (TG) with systolic or continous bruit over - enlarged thyroid gland (TG) with systolic or continous bruit over thyroidthyroid due todue to blood flowblood flow

- - cortisol degradation – cortisol degradation – due to due to metabolic ratemetabolic rate

- hypercalcemia and decreased PTH secretion- hypercalcemia and decreased PTH secretion - due to - due to excess bone excess bone

resorptionresorption

- diminished sensitivity to exogenous insulin- diminished sensitivity to exogenous insulin- due to - due to hyperglycemia hyperglycemia

((glycogenolysis and gluco-neogenesis) glycogenolysis and gluco-neogenesis)

b)b) reproductive:reproductive: - oligomenorrhea or amenorrhe due to- oligomenorrhea or amenorrhe due to hypothalamic or pituitary hypothalamic or pituitary disturbancesdisturbances

- impotence and decreased libido in men- impotence and decreased libido in men

c) gastrointestinalc) gastrointestinal::

- weight loss and associated increase in appetite- weight loss and associated increase in appetite due to due to increased catabolismincreased catabolism

- increased peristalsis increased peristalsis less formed and more frequent less formed and more frequent stools - due to stools - due to malabsorption of fatmalabsorption of fat

- nausea, vomiting, anorexia, abdominal pain- nausea, vomiting, anorexia, abdominal pain

- increased use of hepatic glycogen stores and adipose and protein stores- increased use of hepatic glycogen stores and adipose and protein stores

- decrease of tissue stores of vitaminsdecrease of tissue stores of vitamins

- hyperlipid – acidemia (due to hyperlipid – acidemia (due to lipolysis)lipolysis)

- excessive sweating, flushing, and warm skin- excessive sweating, flushing, and warm skin

- heat loss- heat loss

- hair faint, soft, and straight, temporary hair loss- hair faint, soft, and straight, temporary hair loss

- nails that grow away nail beds- nails that grow away nail beds

d) integumentary:d) integumentary:

All these signs and symptoms are due to metabolicAll these signs and symptoms are due to metabolic effect of THeffect of TH

HypothyroidismHypothyroidism - - deficient production of TH by the thyroiddeficient production of TH by the thyroid

gland and/or gland and/or their action to the tissueaction to the tissue

A. Primary hypothyroidism is caused byA. Primary hypothyroidism is caused by::

1. congenital defects or loss of thyroid tissue1. congenital defects or loss of thyroid tissue

2. defective hormone synthesis - due to: autoimmune2. defective hormone synthesis - due to: autoimmune thyroiditis, endemic iodine deficiency, antithyroid drugsthyroiditis, endemic iodine deficiency, antithyroid drugs

B. Secondary hypothyroidism is caused by:B. Secondary hypothyroidism is caused by:

1. insufficient stimulation of the normal gland1. insufficient stimulation of the normal gland

2. peripheral resistance to TH2. peripheral resistance to TH

The major manifestationsThe major manifestations of hypothyroidism of hypothyroidism and mechanism of their onsetand mechanism of their onset

- Hypothyroidism generally affects - Hypothyroidism generally affects all body systemsall body systems with thewith the extent of the symptoms closely related to the degree of extent of the symptoms closely related to the degree of TH deficiency.TH deficiency.

-- The individual develops a The individual develops a low basal metabolic rate, cold low basal metabolic rate, cold intolerance, slightly lowered basal body temperatureintolerance, slightly lowered basal body temperature

- A decrease in TH - A decrease in TH production of TSH production of TSH goitergoiter

iincreased amount of protein and mucopolysacchancreased amount of protein and mucopolysaccharidesrides

in dermis in dermis water binding water binding nonpitting edema, thickening nonpitting edema, thickening

of the tongue, and the laryngeal and pharyngealof the tongue, and the laryngeal and pharyngeal mucous mucous

membranes membranes thick slurred speech and hoarseness thick slurred speech and hoarseness

- Characteristic sign of hypothyroidism is - Characteristic sign of hypothyroidism is mixedemamixedema

Other manifestations:Other manifestations:

a) neurologic:a) neurologic:- confusion, syncope, slowed thinking, memoryconfusion, syncope, slowed thinking, memory loss, loss, lethargy,lethargy, hearing loss, slow movementshearing loss, slow movements

- cerebellar ataxia- cerebellar ataxia

Mechanisms involved:

- decreased cerebral blood flow - decreased cerebral blood flow cerebral hypoxia cerebral hypoxia

- decreased number of beta-adrenergic receptors- decreased number of beta-adrenergic receptors

b) endocrineb) endocrine:: - - TSH production (in primary hypothyroidism) TSH production (in primary hypothyroidism)

- - serum prolactin levels with galactorrhea serum prolactin levels with galactorrhea

- - rate of cortisol turnover, but normal cortisol levels rate of cortisol turnover, but normal cortisol levels

- - TH TH TSH TSH

Mechanisms involved:

- stimulation of lactotropes by TRH - stimulation of lactotropes by TRH prolactin prolactin

- decreased deactivation of cortisol- decreased deactivation of cortisol

c) reproductivec) reproductive::-- androgen secretion in men androgen secretion in men

-- estriol formation in women due to altered estriol formation in women due to altered metabolismmetabolism of estrogens and androgensof estrogens and androgens

-- anovulation, decreased libido anovulation, decreased libido

-- spontaneous abortion spontaneous abortion

d) hematologicd) hematologic::- - RBC mass RBC mass normocytic, normochromic anemia normocytic, normochromic anemia

- macrocytic anemia due to vitamin Bmacrocytic anemia due to vitamin B1212 deficiency deficiency

and inadequate folate absorptionand inadequate folate absorption

- - basal metabolic rate basal metabolic rate oxygen requirement oxygen requirement

erythropoietin productionerythropoietin production

Mechanisms involved:

f) pulmonaryf) pulmonary::- dyspn- dyspnooea - due to pleural effusionsea - due to pleural effusions - myxedematous changes of respiratory muscles- myxedematous changes of respiratory muscles hypoventilation hypoventilation

g) renalg) renal:: renal blood flow renal blood flow GFR GFR renal excretion renal excretion of waterof water total body fluidtotal body fluid dilutional hyponatremia dilutional hyponatremia

- - production of EPO production of EPO

Mechanisms involvedMechanisms involved::- hemodynamic alteration- hemodynamic alteration

- mucinous deposits in tissue- mucinous deposits in tissue

h) gastrointestinalh) gastrointestinal:: appetite, constipation, weight gainappetite, constipation, weight gain

absorption of most nutrientsabsorption of most nutrients

protein metabolism, protein metabolism, glucose uptake glucose uptake

sensitivity to exogenous insulinsensitivity to exogenous insulin

concentration of serum lipidsconcentration of serum lipids

i) i) musculosceletalmusculosceletal:: - muscle aching and stiffness- muscle aching and stiffness

- slow movement and slow tendon- slow movement and slow tendon jerk reflexesjerk reflexes

- decreased bone formation - decreased bone formation and resorption and resorption bone density bone density

- aching and stiffness in joints- aching and stiffness in joints

- - decreased rate of muscle contraction and relaxationdecreased rate of muscle contraction and relaxation

Mechanisms involved:Mechanisms involved:

j) j) integumentaryintegumentary:: - dry flaky skin- dry flaky skin

- dry, brittle head and body hair- dry, brittle head and body hair

- reduced growth of nails and hair- reduced growth of nails and hair

Mechanisms involved:Mechanisms involved:

- reduced sweat and sebaceous gland secretion- reduced sweat and sebaceous gland secretion

Alterations of parathyroid functionAlterations of parathyroid function

HyperparathyroidismHyperparathyroidism is characterized by greater is characterized by greater than normal secretion of parathormone (PTH)than normal secretion of parathormone (PTH)

Three types do exist:Three types do exist:

primaryprimary - PTH secretion is autonomous and not under - PTH secretion is autonomous and not under the usual feedback control mechanismthe usual feedback control mechanism

secondarysecondary - compensatory response of parathyroid glands - compensatory response of parathyroid glands to chronic hypocalcemiato chronic hypocalcemia

tertiarytertiary - loss of sensitivity of hyperplastic parathyroid gland - loss of sensitivity of hyperplastic parathyroid gland level of autonomous secretion of PTHlevel of autonomous secretion of PTH

TheThe main manifestationsmain manifestations of hyperparathyroidism of hyperparathyroidism and mechanismsand mechanisms of their onsetof their onset

a) a) renal colic, nephrolithiasis, recurrent urinary tract infections,renal colic, nephrolithiasis, recurrent urinary tract infections, renal failure:renal failure:

- they result from hypercalcemia,they result from hypercalcemia, calciuria, calciuria, hyperphosphaturia,hyperphosphaturia, proximal tubular bicarbonate leak,proximal tubular bicarbonate leak, urine pH urine pH 6 6

Mechanisms:Mechanisms: - calcium phosphate salts precipitate- calcium phosphate salts precipitate in alkaline in alkaline urine in renal pelvis,urine in renal pelvis, and in collecting ductsand in collecting ducts

b)b) abdominal pain, peptic ulcer diseaseabdominal pain, peptic ulcer disease

- result from hypercalcemia result from hypercalcemia stimulated hypergastrinemia stimulated hypergastrinemia elevated HCl secretionelevated HCl secretion

d)d) bone diseasebone disease - - osteitis fibrosa and cystica; osteoporosisosteitis fibrosa and cystica; osteoporosis resultresultss from from

PTH PTH hypersecretion hypersecretion stimulated bone resorption stimulated bone resorption

and metabolic acidosisand metabolic acidosis

e)e) muscle weakness, myalgiamuscle weakness, myalgia

- probably due to PTH excess and its direct effect- probably due to PTH excess and its direct effect on striated muscle on striated muscle and on nerves and on nerves myopathic changes, suppressed nerve conduction myopathic changes, suppressed nerve conduction

f)f) neurologic and psychiatric alterationsneurologic and psychiatric alterations - result from hypercalcemia - result from hypercalcemia neuropathy develops neuropathy develops

c)c) pancreatitispancreatitis - due to hypercalcemia - due to hypercalcemia

h) constipationh) constipation - is due to decreased peristalsis induced - is due to decreased peristalsis induced by by

hypercalcemia (smooth muscle weaknesshypercalcemia (smooth muscle weakness))

i)i) anorexia, nausea, vomitinganorexia, nausea, vomiting - due to stimulation - due to stimulation of vomiting center of vomiting center

by hypercalcemiaby hypercalcemia

j) hypertensionj) hypertension - due to - due to secondary secondary renal disease renal disease

g) polyuria, polydipsiag) polyuria, polydipsia

- they result from direct effect of hypercalcemia- they result from direct effect of hypercalcemia on renal tubule on renal tubule responsiveness to ADH responsiveness to ADH

HypoparathyroidismHypoparathyroidism is characteristic by abnormally low PTH levelsis characteristic by abnormally low PTH levels

Causes:Causes: - damage to the parathyroid gland du - damage to the parathyroid gland due to e to thyroid surgerythyroid surgery

a) depressed serum calcium level and increased serum a) depressed serum calcium level and increased serum

phosphate levelphosphate level

Mechanisms involvedMechanisms involved::

- - resorption of Ca from GIT, from bone and from resorption of Ca from GIT, from bone and from renal tubulesrenal tubules

-- reabsorption of phosphates by the renal tubules reabsorption of phosphates by the renal tubules

Consequences:Consequences:

b) lowering of the threshold for nerve and muscle excitationb) lowering of the threshold for nerve and muscle excitation

- - muscle spasms, hyperreflexia, clonic - tonic convulsions, laryngeal muscle spasms, hyperreflexia, clonic - tonic convulsions, laryngeal spasms - spasms - tetantetanyy

c) dry skin, loss of body and scalp hair, hypoplasia of developing c) dry skin, loss of body and scalp hair, hypoplasia of developing

teeth, horizontal ridges on the nails, cataracts,teeth, horizontal ridges on the nails, cataracts, basal ganglia basal ganglia

calcificationscalcifications (Parkinsonian sy.) (Parkinsonian sy.)

Mechanisms involved:Mechanisms involved: unknown up to now unknown up to now

d) hyperphosphatemiad) hyperphosphatemia inhibition of renal enzyme necessary inhibition of renal enzyme necessary for for

the conversion of vitamin D to its most active form the conversion of vitamin D to its most active form further depressifurther depressioon n

of serum calcium level by reducing GITof serum calcium level by reducing GIT absorption of calcium.absorption of calcium.