Endocrine glandsEndocrine glands

Morphology and embryologyMorphology and embryologyCourse: Endocrine systemCourse: Endocrine system

David Kachlik and Petr ZachDavid Kachlik and Petr Zach

Endocrine glandsEndocrine glandsGlandulae endocrinaeGlandulae endocrinae

►One of regulatory systemsOne of regulatory systems►hormone hormone (greek (greek hormanhorman – to awake, – to awake,

stimulate)stimulate) Chemical messenger produced by Chemical messenger produced by

endocrine gland and transported by blood endocrine gland and transported by blood to target organsto target organs

proteins (polypeptides) - proteins (polypeptides) - insulininsulin Biogennic amines - Biogennic amines - adrenalinadrenalin steroids - steroids - estrogensestrogens

Endocrine glandsEndocrine glandsHistoryHistory

►Thomas Thomas WhartonWharton ►1614-16731614-1673► ''AdenographiaAdenographia‚‚►First detailed First detailed

description of description of endocrine glandsendocrine glands

Endocrine glandsEndocrine glandsHistoryHistory

►Ernest Henry Ernest Henry StarlingStarling ►1866-19271866-1927►Created general rules of Created general rules of

„internal secretion “„internal secretion “►He used already existing He used already existing

word „hormones“ word „hormones“ Sir William Bate Hardy, Sir William Bate Hardy,

physiologist from physiologist from CambridgeCambridge

Endocrine glandsEndocrine glandsOrganizationOrganization

1.1. glandsglands

2.2. Disseminated cellsDisseminated cells

3.3. neuroendocrine cellsneuroendocrine cells

Endocrine glandsEndocrine glandsGlandsGlands

►HypothalamusHypothalamus►Hypophysis; Gl. pituitariaHypophysis; Gl. pituitaria►Glandula thyroidea, thyroid glandGlandula thyroidea, thyroid gland►Gll. parathyroidealesGll. parathyroideales

►Gll. Suprarenales, suprarenal glandGll. Suprarenales, suprarenal gland►Langerhans islets (Langerhans islets (Insulae pancreaticaeInsulae pancreaticae))►Gl. pinealis; Corpus pinealeGl. pinealis; Corpus pineale

Hypothalamus + Hypothalamus + hypophysishypophysis

Hypotalamo-hypophyseal Hypotalamo-hypophyseal axisaxis

Systema hypothalamo-hypophysiale

Hypophysis; Glandula pituitariaHypophysis; Glandula pituitariaHistoryHistory

►GalénGalén – mucus produced for nasal mucosa – mucus produced for nasal mucosa►SchneiderSchneider – 1655 rejects Galén theory – 1655 rejects Galén theory►Minkowski, HutchinsonMinkowski, Hutchinson – connection between – connection between

growth problems and hypertrophy of growth problems and hypertrophy of hypophysishypophysis

►CushingCushing – explained function of hypophysis – explained function of hypophysis

„„dirigent of endocrine system, minister head“dirigent of endocrine system, minister head“

HypothalamusHypothalamus

►Bazal part of diencephalon Bazal part of diencephalon ((Diencephalon), Diencephalon), bazally to IIIrd ventriclebazally to IIIrd ventricle

►FunctionFunction Gathers info from body and surroundingsGathers info from body and surroundings Highest autonomic center (vegetative)Highest autonomic center (vegetative) Part of limbic systemPart of limbic system Directs other endocrine glandsDirects other endocrine glands

►Corpora mamillaria, tuber cinereum, Corpora mamillaria, tuber cinereum, infundibulum, hypophysisinfundibulum, hypophysis

HypothalamusHypothalamus

►Anterior hypothalamus – ncl. Anterior hypothalamus – ncl. magnocellularismagnocellularis Ncl. paraventricularis + supraopticus – Ncl. paraventricularis + supraopticus –

oxytocin and vasopressin (ADH)oxytocin and vasopressin (ADH)

►Middle hypothalamus (tuber cinereum) Middle hypothalamus (tuber cinereum) – ncl. parvocelularis– ncl. parvocelularis Ncl. arcuatus – regulation of Ncl. arcuatus – regulation of

adenohypophysisadenohypophysis

►Posterior hypothalamusPosterior hypothalamus

HypothalamusHypothalamus - Hormones - Hormones

►Ncl. arcuatus - productionNcl. arcuatus - production►Eminetia mediana – release into first Eminetia mediana – release into first

capillary bedstreamcapillary bedstream

►Releasing hormones (releasing)Releasing hormones (releasing) SRH, PRH, GnRH, TRH, CRHSRH, PRH, GnRH, TRH, CRH

►Supressing hormones (inhibiting)Supressing hormones (inhibiting) somatostatin, PIH (= dopamin)somatostatin, PIH (= dopamin)

Hypophysis - Hypophysis - anatomyanatomy

►Formed by two lobesFormed by two lobes ventral - adenohypophysisventral - adenohypophysis dorsal – neurohypophysisdorsal – neurohypophysis

►Located in Located in sella turcica ossis sphenoidalissella turcica ossis sphenoidalis►Covered by dura mater – Covered by dura mater – diaphragma diaphragma

sellaesellae foramen diaphragmatis Pacchioni – for foramen diaphragmatis Pacchioni – for

hypophyseal infundibulumhypophyseal infundibulum

►Transsphenoid approachTranssphenoid approach

Hypophysis - Hypophysis - anatomyanatomy

►Ventral lobe (Ventral lobe (Adenohypophysis; Lobus Adenohypophysis; Lobus anterioranterior)) Pars distalisPars distalis (principalis) (principalis) – biggest – biggest Pars intermedia – between both lobesPars intermedia – between both lobes Pars tuberalis – part by infundibulumPars tuberalis – part by infundibulum

►Posterior lobe Posterior lobe (Neurohypohysis; Lobus (Neurohypohysis; Lobus posteriorposterior)) Lobus nervosus (Pars nervosa) – proper Lobus nervosus (Pars nervosa) – proper

posterior lobeposterior lobe Infundibulum – stalk leading to hypotalamusInfundibulum – stalk leading to hypotalamus

Blood supply of hypophysisBlood supply of hypophysis

►Hypophyseal portal systemHypophyseal portal system A. hypophysialis inferior (from pars A. hypophysialis inferior (from pars

cavernosa to neurohypophysis)cavernosa to neurohypophysis) A. hypophysialis superior (from pars A. hypophysialis superior (from pars

cerebralis via hypothalamus into cerebralis via hypothalamus into adenohypophysis)adenohypophysis)

►Vv. hypophysiales into sinus Vv. hypophysiales into sinus cavernosuscavernosus

Hypophysis - Hypophysis - developmentdevelopment

►Ratkhe pouch (from ectoderm)Ratkhe pouch (from ectoderm) 3rd week – in the roof of mouth cavity3rd week – in the roof of mouth cavity Exagination towards diencephalonExagination towards diencephalon Separation of exagination, proliferation of Separation of exagination, proliferation of

ventral wallventral wall

►Exagination of basis of diencephalonExagination of basis of diencephalon Creates posterior lobeCreates posterior lobe Differentiation into pituicytes (glia)Differentiation into pituicytes (glia)

Hypophysis - Hypophysis - developmentdevelopment

Hypophysis - Hypophysis - developmentdevelopment

Ventral lobe = Ventral lobe = AdenohypophysisAdenohypophysis

►Pars distalisPars distalis biggest (75%)biggest (75%)

►Pars tuberalisPars tuberalis craniallycranially

►Pars intermediaPars intermedia between adeno- and neurohypophysisbetween adeno- and neurohypophysis

Pars distalis Pars distalis adenohypophysisadenohypophysis

►Strand of cells (Strand of cells (chordae chordae endocrinocytorumendocrinocytorum), between them ), between them capillariescapillaries

►on HE 3 types of cellson HE 3 types of cells acidophilicacidophilic bazophilicbazophilic

►PAS-pozitivePAS-pozitive

chromophobicchromophobic►w/o granules, non-differentiated elementsw/o granules, non-differentiated elements

Pars distalis – Pars distalis – Acidophilic Acidophilic cellscells

►α – cells (α – cells (Endocrinocytus Endocrinocytus somatotropicussomatotropicus)) Rough granules, GERRough granules, GER Around nucleus zone w/o granules - GAAround nucleus zone w/o granules - GA Growth hormone (somatotropin, GH)Growth hormone (somatotropin, GH)

►ε – cells (ε – cells (Endocrinocytus prolactinicusEndocrinocytus prolactinicus)) Usually small, not numerous (x gravidity, Usually small, not numerous (x gravidity,

lactation)lactation) Small granules (enlargement in gravidity)Small granules (enlargement in gravidity) prolaktin (PRL)prolaktin (PRL)

Pars distalis – Pars distalis – bazophilic cellsbazophilic cells

►ββ1 1 – cells (– cells (Endocrinocytus corticotropicusEndocrinocytus corticotropicus)) Big granules close to cell membraneBig granules close to cell membrane ACTH, β-MSHACTH, β-MSH, Met-enkefalin, endorfin, Met-enkefalin, endorfin

►ββ2 2 – cells (– cells (Endocrinocytus thyrotropicusEndocrinocytus thyrotropicus)) Large cells, small granules by BMLarge cells, small granules by BM TSHTSH

►δ – cells (δ – cells (Endocrinocytus gonadotropicusEndocrinocytus gonadotropicus)) Large cells, middle size granulesLarge cells, middle size granules FSH, LHFSH, LH

► HEHEmodifikovaný Azanimunoperoxidase reaction to LH

AdenohypophysiAdenohypophysiss

elec

tron

mic

rosc

ope

Pars tuberalis Pars tuberalis adenohypophysisadenohypophysis

►surrounds infundibulumsurrounds infundibulum►Numerous capillariesNumerous capillaries►mostly δ – cells mostly δ – cells

Little bit βLittle bit β2 2 – cells– cells

Pars intermedia Pars intermedia adenohyophysisadenohyophysis

►rudimentaryrudimentary►Cells compose celumnsCells compose celumns►Bazophilic cellsBazophilic cells►Could be present sac (Ratkhe´s Could be present sac (Ratkhe´s

folliculus)folliculus)

Posterior lobe = Posterior lobe = NeurohypophysisNeurohypophysis

►Eminentia medianaEminentia mediana Bottom of IIIrd ventricleBottom of IIIrd ventricle Numerous non-myelinated nerve fibersNumerous non-myelinated nerve fibers

►stalk = stalk = InfundibulumInfundibulum Tractus hypothalamohypophysialisTractus hypothalamohypophysialis Neurofibra neurosecretoria (+ vesicula Neurofibra neurosecretoria (+ vesicula

neurosecretoria) – non myelinated nerve neurosecretoria) – non myelinated nerve fibers)fibers)►Some terminate by capillariesSome terminate by capillaries

►Lobus nervosus; Pars nervosaLobus nervosus; Pars nervosa

Lobus nervosus / Pars Lobus nervosus / Pars nervosa neurohypophysisnervosa neurohypophysis

►Nerve fibersNerve fibers Axons of neurons from hypotalamusAxons of neurons from hypotalamus Corpusculum neurosecretorium (Herring Corpusculum neurosecretorium (Herring

corpuscles) – accumulation of granulescorpuscles) – accumulation of granules oxytocinoxytocin + ADH (antidiuretic hormone = + ADH (antidiuretic hormone =

vasopressin)vasopressin)

►pituicytespituicytes Glial cellsGlial cells

►capillaries (capillaries (synapsis neurohaemalissynapsis neurohaemalis))

Examination and diseasesExamination and diseases

►CTCT►Levels of hormonesLevels of hormones

►Tumors of hypophysis – usually Tumors of hypophysis – usually benign, hormally activebenign, hormally active

►Sheehan syndrome – after delivery Sheehan syndrome – after delivery bleeding into hypophysisbleeding into hypophysis

Thyroid glandThyroid gland

Glandula thyroideaGlandula thyroidea

Thyroid gland – Thyroid gland – historyhistory

►Galén – to water inside of pharynxGalén – to water inside of pharynx► Paracelsus – struma + cretenismParacelsus – struma + cretenism

►Wharton Wharton 1614-16731614-1673 – to make neck more beautiful – to make neck more beautiful► 1844 Simon – endocrine gland1844 Simon – endocrine gland► 1891 Murray – administration of extract 1891 Murray – administration of extract

from TGfrom TG► 1895 Baumann – TG contains iodine 1895 Baumann – TG contains iodine

componentscomponents

Thyroid gland - Thyroid gland - anatomyanatomy►Glandula thyroideaGlandula thyroidea►thyroxinthyroxin T T44, , trijodtyronintrijodtyronin T T33

►kalcitoninkalcitonin►Located at the level C6-C7Located at the level C6-C7►2 lobes – lobus dexter + sinister2 lobes – lobus dexter + sinister► isthmus (on 2nd-4th tracheal cartillage)isthmus (on 2nd-4th tracheal cartillage)►capsula fibrosa – 2 sheets – stromacapsula fibrosa – 2 sheets – stroma►parenchyma + lobuliparenchyma + lobuli

Thyroid gland – arteries and Thyroid gland – arteries and veinsveins

► A. thyroidea superior (from a. carotis A. thyroidea superior (from a. carotis externa)externa)

► A. thyroidea inferior (z truncus A. thyroidea inferior (z truncus thyrocervicalis) – thyrocervicalis) – crossing with n. crossing with n. laryngeus recurrenslaryngeus recurrens

► A. thyroidea ima A. thyroidea ima Neubaueri Neubaueri (from arcus (from arcus aortae) - 2 %aortae) - 2 %

► Vv. thyroideae superiores et mediae Vv. thyroideae superiores et mediae LichačevaLichačeva (into V. jugularis interna) (into V. jugularis interna)

► Plexus thyroideus impar (into v. Plexus thyroideus impar (into v. brachiocephalica sinistra)brachiocephalica sinistra)

Thyroid gland - Thyroid gland - developmentdevelopment

►Development since 24th dayDevelopment since 24th day► Exagination of endoderm of primitive pharynxExagination of endoderm of primitive pharynx► Relative and absolute descencus - Relative and absolute descencus - ductus ductus

thyroglossusthyroglossus► foramen caecumforamen caecum► gll. thyroideae accessoriaegll. thyroideae accessoriae► Lobes origin Lobes origin ► lobus pyramidalislobus pyramidalis► ligamentum suspensorium gl. thyroideae / ligamentum suspensorium gl. thyroideae /

musculus levator glandulae thyroideaemusculus levator glandulae thyroideae (smooth)(smooth)

Thyroid gland - Thyroid gland - developmentdevelopment

Thyroid gland - Thyroid gland - histogenesishistogenesis

►solid endoderm formationsolid endoderm formation► Ingrowth of surrounding mezenchyme Ingrowth of surrounding mezenchyme

and blood vesselsand blood vessels► Ingrowth of ultimobranchial corpusclesIngrowth of ultimobranchial corpuscles►10th week – separation of cells into 10th week – separation of cells into

groupsgroups►Single layer epithelium around luminaSingle layer epithelium around lumina►11th week – production of koloid11th week – production of koloid

Thyroid gland - Thyroid gland - compositioncomposition

► capsule (capsula fibrosa)capsule (capsula fibrosa)► stroma - septum (septas between lobes)stroma - septum (septas between lobes)► lobus lobus lobulus lobulus folliculus folliculus► follicles (50 - 900 follicles (50 - 900 μμm)m)

sphericalspherical Single layer epithelium of follicular cellsSingle layer epithelium of follicular cells contains contains colloidumcolloidum (coloid) - thyroglobulin (coloid) - thyroglobulin

► Follicular cells (Follicular cells (thyrocytus T)thyrocytus T)► Parafollicular cells (Parafollicular cells (thyrocytus Cthyrocytus C))

Follicular cells (Follicular cells (Thyrocytus T)Thyrocytus T)

►Spherical nucleusSpherical nucleus►numerous gER (bazally) and MITnumerous gER (bazally) and MIT►Numerous lyzosomesNumerous lyzosomes

►thyroglobulin, cleavage of Tthyroglobulin, cleavage of T44 and T and T33

Synthesis of hormones of thyroid Synthesis of hormones of thyroid glandgland

► 1. iodine pump using ATP recirculates 1. iodine pump using ATP recirculates iodine from blood into colloidiodine from blood into colloid

► 2. and 3. synthesis of thyroglobulin and 2. and 3. synthesis of thyroglobulin and peroxidase, deposition in one secretory peroxidase, deposition in one secretory vesicle and its release into colloid by vesicle and its release into colloid by exocytosisexocytosis

► 4. iodination off thyroglobulin using 4. iodination off thyroglobulin using peroxidase in colloid and formation of peroxidase in colloid and formation of iodinethyroglobuliniodinethyroglobulin

► Endocytosis of iodinethyroglobulinEndocytosis of iodinethyroglobulin► 5. fusion of primary lyzozome with 5. fusion of primary lyzozome with

this vesiclethis vesicle► Proteolysis of iodinethyroglobulin into Proteolysis of iodinethyroglobulin into

T3, T4 and other fragmentsT3, T4 and other fragments► Release of T3 and T4 into circulationRelease of T3 and T4 into circulation► 6. binding of transport plasmatic 6. binding of transport plasmatic

proteinprotein

Parafolicular cells (Parafolicular cells (thyrocytus thyrocytus CC))

►C-cellsC-cells►Located between follicles (individually, Located between follicles (individually,

also goups)also goups)►Bigger, lighterBigger, lighter►numerous gER as well as GA, MITnumerous gER as well as GA, MIT►granules – spherical, darkgranules – spherical, dark►Prooduction and accumulation of Prooduction and accumulation of

kalcitoninkalcitonin

Follicles of thyroid Follicles of thyroid glandgland

Thyroid glandThyroid gland – – examinationexamination

►ultrasoundultrasound►Scintigraphy with radioactive iodine Scintigraphy with radioactive iodine

131131

Thyroid glandThyroid gland – disease – disease

► ultrasoundultrasound► scintigraphy with radioactive iodine 131scintigraphy with radioactive iodine 131

► Less then 10Less then 10μμg iodine per day g iodine per day struma from struma from lack of iodinelack of iodine

► hypotyroidizmus hypotyroidizmus kretenizmus (kretenizmus (childrenchildren) – screening in newborns) – screening in newborns Myxedema (Myxedema (adultsadults)) autoimmune – Hashimoto strumaautoimmune – Hashimoto struma

► hypertytoidizmus (tyreotoxicosis)hypertytoidizmus (tyreotoxicosis) autoimmune – exophtalmic struma = Graves-autoimmune – exophtalmic struma = Graves-

Basedow diseaseBasedow disease

Parathyroid glandParathyroid gland

Glandulae Glandulae parathyroideaeparathyroideae

Parathyroid gland - Parathyroid gland - characteristiccharacteristic

►Gll. parathyroidea superior et inferiorGll. parathyroidea superior et inferior►2 pairs of small spheroid structures on 2 pairs of small spheroid structures on

the posterior side of lobes of thyroid the posterior side of lobes of thyroid glandgland

► Individual branches from a. thyroidea Individual branches from a. thyroidea inferiorinferior

►Role in bone metabolismRole in bone metabolism►parathormonparathormon (PTH) (PTH)

Parathyroid gland - Parathyroid gland - developmentdevelopment

►Dorsal part of IIIrd and IVth branchial Dorsal part of IIIrd and IVth branchial exaginationexagination

►5th week – proliferation of endoderm, loss 5th week – proliferation of endoderm, loss of lumenof lumen

► Ingrowth of vessels from mesenchymeIngrowth of vessels from mesenchyme

►Principal cells – fetal metabolism of Principal cells – fetal metabolism of calciumcalcium

►Oxyphilic cells – origin in 7th year of lifeOxyphilic cells – origin in 7th year of life

Parathyroid gland - Parathyroid gland - developmentdevelopment

Parathyroid gland - Parathyroid gland - compositioncomposition

►capsule + septascapsule + septas►parenchyme parcellated into columnsparenchyme parcellated into columns►Principal cells (Principal cells (parathyrocytus endocrinusparathyrocytus endocrinus))

Relatively large (4-8 um)Relatively large (4-8 um) light cytoplasmlight cytoplasm Granules containing PTHGranules containing PTH

►Oxyphilic cells (Oxyphilic cells (ParathyrocytusParathyrocytus oxyphilicusoxyphilicus)) Rare, biggerRare, bigger cytoplazm darker, w/o granules, numerous MITcytoplazm darker, w/o granules, numerous MIT Function not clearFunction not clear

Parathyroid gland Parathyroid gland diseasedisease

►hyperparatyroidizmushyperparatyroidizmus primary (adenoma)primary (adenoma)

►Patological calcification of tissue (based on Patological calcification of tissue (based on hypercalcemia)hypercalcemia)

►Recklinghausen bony osteodystrofia Recklinghausen bony osteodystrofia (fractures)(fractures)

►nephrolitiasisnephrolitiasis

secondary (reactive hyperplazia PT in secondary (reactive hyperplazia PT in hypocalcemia in kidney diseases)hypocalcemia in kidney diseases)

terciary (in case of successful kidney terciary (in case of successful kidney transplantation)transplantation)

Parathyroid gland - Parathyroid gland - diseasedisease►hypoparatyroidizmushypoparatyroidizmus

tetanytetany iatrogenic in case of tumor excisioniatrogenic in case of tumor excision

►Transplantation of gland on the forearm Transplantation of gland on the forearm subcutaneouslysubcutaneously

►examination – nuclear medicineexamination – nuclear medicine