INTRODUCTION TO ENDOCRINOLOGY Classes of hormones 00:02:31 1, Aminoacid derivatives * * Thyroid hormones - T3, TA * Catecholamines - Adrenaline, Noradrenaline, Dopamine - These are the derivatives of aminoacid n Cderivatives of tryptophan are not hormones, they are neurotransmitters ie, Serotonin § melatonin ) . Vitamin derivatives + * vita * vito 3. smalll peptides + ( These are glycoproteins They contain 7800 Aminoacids Have common a Subunit 4. large peptides + © Insulin * PTH * Renin 'S. Steroid hormones + * hormones from the Adrenal cortex '* Mineralocorticoid - Aldosterone * Glucocorticoid - Cortisol CC Adrenal androgens/Sex 7 Dinydroepiandrosterone sulfate Androstenedione + Gonadal hormones - Testosterone estrogen Progesterone i i900 engocnine 95 System Hormones Intracellular receptors cell membrane receptors @RouP-1 @Rour - Intracellular cell membrane ey cytoplasmic nuclear &-Protein Tyrosine jakstat serine coupled Kinase threonine kinase Group - I hormones 00:10:24 * Steroid hormones * Gonadal hormones * vita ivitD * Thyroid hormones. ore Type- | Receptors (Geceptors in > 1 [@eceptor in nucleus) | Steroid Gonadal Vit AVEO Thyroid Hormones ‘Hormones ‘Hormones. Steroids receptor is bound. +0 Heat shock protein (HSP) in the resting state 4 Dissociation of HSP confirmational change in receptor when Ligand binds to receptor 4 Receptor with Ligand moves into the nucleus § binds to GRE (Glucocorticoid Responsive elements) — Protein, translation * Thyroid receptors are located inside the nucleus, Binds to TRE (Thyroid Responsive Elements) 4 Protein translation * Steroid receptors - Homodimer receptors - co activator binding, * Thyroid receptors - heterodimer receptors - co repressor Inhibition Followed By coactivator bindingC — receptor —] Thyroid receptors Vit AY Vit PPAR (Peroxisome Proliferator ._ Activated Receptor) 7 PPRR- PPAR Y \ promotes insulin sensitivity ‘ Retivators : Fibrates thiazolidinediones £gj pioglitazones Orphan receptors ‘* Orphan receptors are “ Constitutively activated” SF-1> Required for Gonadotrope cell growth, they are actually © DAX- IPtranseription Factors. *° HNF- 4G - also transcription Factors - mutation produces MODY- Type | (maturity onset Om sagurg) Group- Il hormones 00:20:46 * They have got receptors in the cell membrane L@Pce : [@- Protein Coupled Receptors] * They have Seven membrane Spanning domains - a, B, Y, complex bound to GOP. 4 Cin resting state) then hormone comes and, binds, there will be change in the 4 «op ——— arp 3 G- ETP dissociates and bind to 3 effectors . effector = and messenger (camp,\P3/ oAG, Camp) cAMP- Gs oF i 1P3/ DAG - GQ, came - Gt (transducin)System Hormones acting via. camp + * Vasodilators act vio. camp. Eq} NO, ANF (Atrial Natriuretic Factor) Homones acting via cAMP + came —— inactive Protein Kinase A Retive Protein Kinase A 4 Protein Phosphorylation . So, the System is called came / PHA System. hormone acting via 1P3/ DAG system + Phosphoinositel pyrophosphate (Pipa) Phoscholpase ¢, Diacy! Glycerol (oRG)+ onositol triphosphate(iP > Diacy! Glycerol (oAG) 4 Activate Protein Kinase ‘Cc! 1P3, 4 Petivates “Ca- Calmodulin pathway” most vasoconstrictors act via. 1P3 ORG pathway Hormones acting via cAMP & IP3/ DAG pathway oo27:24 came i) 1e3/oAg, © Hypothalamus cau TRH, GnRH Pituitary (Anterior) ACTH, FSHLH Vv 1 Oxytocin THrvy, * Vosoconstrictors AT-I, substance P * Ponereas Glucagon, Somatostatin( hyperpigmentation - All the anterior pituitary hormones are regulated by hypothalamus ~ Hypothalamus produces trophic hormone Factors — TRH, CH, GNRH, GHRH > trophic Factors are secreted into hypothalamohypophyseal portal system via the pituitary stalk > reach anterior pituitary = Prolactin inhibitory factor produced by hypothalamus regulates prolactin = Prolactin is the only hormone that is under inhibitory control of the hypothalamus ‘ctv space‘594 Endocrine of ‘System = The pathway through which dopamine inhibits prolactin > tububbinfundibular pathway ~ Relationship between hypothalamus and anterior pituitary > hypophysiotrophie relationship J Supraoptic nucleus (major) ——> vasopressin (ADH or AVP) + J Para. ventricular nucleus Arginine vasopressin + Neurohypophysin™ + Co-peptin™ ~ ADH produced in the hypothalamus goes to the posterior pituitary > stored there via nerve Rbers in the stalk ~ The relationship between the posterior pituitary and hypothalamus > neurohypophysial relationship Development of anterior pituitary 00:11:51 = Development of anterior pituitary is from Rathixe’s pouch > neuroectodermal derivative, actually a diverticulum or upgrouth ~ Posterior pituitary develops as 0 down growth from the Sloor of the 3° ventricle most common cause of congenital hypopituitarism —> pituitary dysplasia In pituitary dysplasia, the hormones of posterior pituitary ore intact 1 Celis from the Rathke’s pouch need to migrate across the i midline 40 reach the anterior pituitary > in pituitary dysplasia midline craniofacial defects are presnt emay 1 Anatomy: - The anterior pituitary is situated in a bony cage called Sella turciea,94 Anterior 595 Pituitary ~ Posterior relationship of anterior pituitary is sphenoid sinus - Surgery > preferred approach is trans sphenoidal approach Lateral relationship: - Pituitary tumour can expand to cavernous sinus/ lateral wall of cavernous sinus/ temporal lobe = Inside cavernous sinus ~ "nerve { internal corotid artery - On lateral wall oF cavernous sinus — 3,45 (ophthalmic 5 maxillary branch) ‘Active spacea 596 Endocrine 94 ‘System Anterior/ventral relationship + ~ ventrally covered by a layer of dura > called as Diaphrama. sellae = The line of least resistance for the tumor is ventral = nT, sagittal image, the white spot (or) bright spot helps in the identification of posterior pituitary ~- when a tumor enlarges, it first compresses the pituitary stolk before it Compress the optic chiasma to cause heteronymous - effects of tumor Hormonal effect + Producing acromegaly, prolactinoma ete a. Stolk effect ——_ + Compression on the stalk, affects control o¥ Tiypothalamus on the anterior pituitary hormones. So, hormones reduce. j Prolactin increases, this phenomenon of hypopituitarism + hyperprolactinemia, is called stalk effect 3.mass effect + Compression + ICT symptoms— 94 Anterior 597 Pituitary Superior hypophyseal artery Inferior hypophyseot artery J J portal system the posterior pituitary - metastasis 40 pituitary are carried by inferior hypophyseal ortery i = Me malignancy to metastasise to pituitary * carcinoma, breast 2 - me manifestation of pituitary metastasis absence of ADH Ceentrol diabetes insipidus] - The first cells to develop at & weeks are corticotrophs.= 598 Endocrine ‘System - Transcription factors are required for the release of anterior pituitary hormones — TSH, ACTH, GH, PROLACTIN — Pit -1 | PROP-1 are the tronseription Factors ~ For FSH, LH - SF -14 08x41 ~ % oF total secretory cells in the anterior pituitary — So% are growth hormone secreting cells * Gli cells > FSH, LH > ACTH 7K " -@H cells a” — Prolactin producing cells ~ Inhypopituitarism, the first hormone to decrease is growth hormone Table - Hormone secreting cells of the human anterior pituitary gland cell type | Hormones | % of total [Stain affinity] diameter of secreted | secretory secretory cells granules (om) growth | so Acidophlic | 300-400 hormone Lactotrope _| prolactin | 10-30 Reidophiie | ao0 Corticotrope | ACTH 10 @asophilic | 400-ss0 Thyrotrope | TSH s Gasophilic | 1ao-a00 gonadotrope | FSH, LH | ao Basophitic | aso-400 = Next hormones to decrease are FSH {LH {ACTH Even in the absence of TSH, Thyroid can produce T, § T,) hypothyroidism not a component of hypopituitaris GH § Prolactin producing cells — Reidophiie — twin hormones, ACTH, TSH, FSH {LH producing cells — Basophitic Largest diameter of secretory granules - corticotrophs 1 1 Prolactin 00:37:22 - Produced by lactotrophs and acts via Jak STAT receptor (peptide hormone)L_LL—<—— ee Function: ~ It induces and maintains lactation in a breast already primed by estrogen = Prolactin is also produced from placenta, uterus and other parts oF CNS. Physiological inhibitor: = Physiological inhibitor of prolactin is dopamine > pathway called tubuloinfundibular pathway Physiological stimulators = estrogen - TRH - wie ~ Oxytocin Hyper prolactinemia: - Fasting prolactin levels — normal - aS0 H19/i — Tumor ‘Tumor size corresponds to prolactin levels Causes of prolactin levels between 40- 100 Hig/it Drugs 0) ©, blockers |. Typical antipsychotics — blocks mesocortical, tubuloinfundibular { nigrostriatal pathways Mesocortical block — worsening of negative symptoms Tubuloinfundibular block - f prolactin Nigrostriatal block — extrapyramidal S/e 4. Atypical antipsychotics - Only Risperidone produces hyper prolactinemia, Active spsce600 Endocrine 94 ‘System 'b) Antiemetics — metoclopramide — cross 868 — hyperprolactinemia, Domperidone — doesn't eross 868 — No hyperprolactinemia - Hyperprolactinemia, due to drugs — volue normalises within 72 hours, «. TCA/ SSaI'S — Can cause hyperprolactinemia, mid effect on D, 4 Opiates €. Verapmil $.H, blockers 3 @ = methyldopa. ~ systemic disorders with 40 — 100 [g/l oF prolactin: Lom 4. Chronie liver disease 3. PCOS 4, Hypothyroidism * - TRH levels T TRH can physiologically inerease the prolactin levelsPROLACTINOMA Prolactinoma 00:00:06 — me tumor of pituitary is prolactinoma = G.- Subunit of FSH secreting tumors are more common than Prolactinomas, but they're clinically insignificant - There are 3 types of Prolactinomas: a. 00% of the Prolactinomas have < 1 em size - microadenomas — a0# 1 (F#m) bb. 9% of the Prolactinomas have 1-4 em size — microadenomas — 1: 1 (Fm) ©. 1% of the Prolactinomas have > 4 em size — giant prolactinomas — 1:1 (F +m) = Prolactinomas generally occur at the age of aS- 4syrs, mostly in Females = Prolactinoma which is occurring at an age repeat prolactin levels, sually gets normalized ) = Tumor shrinkage takes months — months — Symptomatically patient gets better by Imonth — IF symptoms are not reduced or prolactin levels are still high, the Patient is considered as dopamine agonist resistant tumor after Imonth of treatment with drugs. = Dopamine agonist resistance is seen in < a0% patients — Generally Dopamine agonist resistant patients are also Dopamine agonist intolerant. = In dopamine agonist resiste 4 surgery dopamine agonist intolerant — 1f patient is improving on drugs, to be given for “ayears” = Risks oF malignancy in prolactinoma, - <0.01% = Marker of malignaney — Kie7 = Gromoeriptine in pregnancy —> stopped 7 days prior to lactation ‘Acthe spsco604 Endocrine 95 ‘System Indications of surgery . Dopamine agonist resistance 'b. Dopamine agonist intolerant & mass effects not improved after tmonth 4. Pregnancy, no response int month €. Bleeding into pituitary — pituitary apoplexy - white on T, image Surgery - Transsphenoidal resection Radiotherapy: —Only if patient is medically unt for surgery, ae P -T,W image showing invasive giant prolactinoma. in abyr old lady Get) TW image of same patient after 9m of medical treatment showing complete disappearance of tumor (right) once nyMANAGEMENT OF PROLACTINOMA ‘Srchide vecordary causes oF mai evdince for prurtary mass == 95 Prolactinoma 60596 607 ACROMEGALY Pituitary adenoma Prolactinoma, > G@Hsecreting = > ACTH most common adenomas seereting adenoma Gmicroadenoma) (macroadenoma) (macroadenoma) FSH LH eco adenoma rare TSH Growth Hormone (GH) 00:02:15, * Produced by soatotrophs * Constitutes 750% cells in anterior pituitary (eidophilic) * GH § Prolactin acts by JAK — STAT pathway Twin hormones + 4%: 5-0 min * Pulsatile release @H vs Prolactin * Increase during stage a —_* Increase during Rem sleep 4 4 Neem sleep * Physiological stimuli * Physiological stimuli D @HRH From hypothalamus — i) estrogen ) Ghrelin from stomach a@TRH * Physiological inhibitor 3) vip Somatostatin ative space608 Endocrine System 96 Stimulating Factor @H For Inhibiting Factor for release GH release * Hypoglycemia, * Aging * exercise be Obesity * Fasting * Hypocaloric state / malnutrition 4 Causes GH resistance Paradoxical 6H release + TRH given to 0 normal person —> GH production will not increase TRH given to a GH secreting —> GH production doubles adenoma pt Parad 4 loxical GH release Peripheral actions of GH + executed by IGF - 1 receptors in liver \GF-1 also knows as somatomedins Structurally similar to insulin 00:09:24 Produced from the liver in response to GH binding to its c GH IGF-1 has no effect on intrauterine height Intrauterine height depends on I@F—a which is produced by diverse tissues eH Na’ Decreased Lipolysis Protein epiphyseal retention insulin synthesis growth sensitivity ter a | Insulin-ike Antiipolytic octivity activity Protein synthesis eppryseal growthAcromegaly / GH secreting adenoma 00:18:37 * Growth hormone secreting tumor / adenoma, * occurs after 40 yrs - after epiphyseal closure * Only peripheral (acrad parts enlarge * Results in acromegaly All the organs, soft tissue, cartilage enlarged Wf GH secreting adenoma occurs < a0 years age Before epiphyseal closure Gigantism = Common in m > F * macroadenomas 7 40 years W occurs in young pt < 20 years (genetic syndromes) Dmen-1 @ Carney's complex 3) meCune-flbright syndrome 98% oF acromegaly are due to GH secreting adenoma Densely or sparsely granulated * OF this, a0 % are somatomammotrophie adenoma. (Prolactin + GH secreting) * Remaining ah couses D Paraneoplastic GH secretion ‘tue to pancreatic islet cell tumor @ GHRH secreting tumor of hypothalamus, ue to Hypothalamic Hamartoma, 3) Paraneoplastic GHRH Release. Due to Bronchial carcinoid > small cell carcinoma. lung, * Patient presents with D Hormonal effect > GH excess @) Stalk eMect 3) moss effect yo” Acromegaly” sus Active spaceFeatures of acromegaly 002808, Coarse Facial features D Prominent supra orbital ridges. @ Thick lips 3) macrogjossia 4) Frontal bossing, 'S) Prognathism © Jaw malocctusion = D deep husky voice ® Large hands and feet ( systemic changes D Nerve, muscle Entrapment neuropathies. myopathy — Due to atrophy of type Ii muscle bres WD Joints —Arthritis involving large joints especially —Due to synovial hypertrophy wD eyes Angle closure glaucoma Cardiovascular system * Hypertension Leads to * Asymmetrical Lvd ——————> Diastolic heart failure Respiratory system + 'SoHt tissue proliferation 4 Obstructive sleep apnea. leads to Pulmonary hypertension Thyromegaly . IGF — Tacts on thyroid — Goitre Colonie polyposis + * Increased risk of malignancy compared to general population96 Acromegaly 611 Increased metabolic rate: * Results in hyperhidrosis * Seborrhoea Increased salt { H,0 retention * ue to f Aldosterone levels * One of the reasons for hypertension Reproductive system * Large tumor — Injury to stalk, Stak effect + | FSH, LH release 4 Hypogonadism * Females with @H excess can have hirsutism metabolic issues D Hyperglycemia — Insulin resistance: @ Hypertrigiyceridemia / Hyperlipidemia 2) f production of 1, a5 (OH), cholecalciferol 4 excess Ca" { phosphorous absorption ‘ Leads to hypercalcemia, hyperphosphatemia, 4 Leads to hyperealeuria 4 Ca" oxalate stones * Ectopic GH - Panereas * Pseudoacromegaly - conditions with acromegalie Facies . Obesity * Hypothyroidism * Phenytoin therapy © \GFa tumors * insulinoma, * GH excess - Insulin resistance - Reanthosis nigricans ActvospaceIncreased metabolic rote: + Results in hyperhidrosis * Seborrhoea Increased salt § H,0 retention * ue to f Aldosterone levels * one of the reasons for hypertension Reproductive system * Large tumor — Injury to stalk Stols effect 4 | Fst, LH rele * 4 Hypogonadism + Females with @H excess can have hirsutism Metabolic issues D Hyperglycemia — Insulin resistance @ Hypertriglyceridemia / Hyperlipidemia. 2) f production of 1, aS (oH), cholecalciferol 4 excess Ca"? § phosphorous absorption 4 Leads to hypercaleemia, hyperphosphatemia, 4 Leads to hypercaleuria, 4 Ca" oxalate stones * Ectopic GH - Pancreas * Pseudoacromegaly - conditions with acromegalic Facies * Obesity * Hypothyroidism * Phenytoin therapy, ¢1GFa tumors # Insulinoma, * GH excess - Insulin resistance - Acanthosis nigricans Active spaceMRI 00:42:48 T, saggital image post contrast * Patchy uptake T, coronal post contrast mei * Patchy uptake F * Henee it is macroadenoma, patchy uptake of contrast GH secreting tumor Young Female facial asymmetry MeCune albright syndrome due to presence of polyostotic Nbrous dysplasia, Diagnosis 0:48:07 D Screening test: * lar -1 levels ore measured \aF -1 > Long +¥%, non pulsatile release & Confirmatory test * Oral glucose suppression test “Sqm oral glucose Hyperglycemia 4 4 After 1 he Suppress GH release 4 GH levels < 1 n9/ mi In normal personWF GH levels are 7 11ng/m! — Acromegaly Git levels normally decreased due to Df gueose @) Somatostatin IF GH level > 40 ng/ mI (very bad prognosis) \nvestigation oF choice: Gadolinium enchanced mei ‘Treatment 00:51:08 D Always surgery - 1 line 4 ‘Transphenoidal surgical resection 4 Only SO% macroadenoma. are cured * microadenoma — 80% cure * Relapse is common * Immediate post - op 6H estimation >—t+— GH detectable GH not detectable * Risk of relapse is high # Risk of relapse is low Drugs — a™ line D Somatostatin analogues * Lanreotide (drug of choice) @ GH receptor antagonist “Pegvisomant? 2) ©, agonists i * Caberogolin i * @romocriptine Relapse cases! * 0 for a™ surgery———————_—————eeeee———— ni nh eee 614 Endocrine 96 System * Patient medically unfit for surgery go for gama. knife stereotactic radiotherapy Pituitary function tests: * Done in all patients with acromegaly * Because these are macroadenoma 1 Stalk effect 4 All the hormones are decreased except prolactinNON-FUNCTIONAL PITUITARY MASSES + Non endocrine tumors of pituitary * These tumors causes stalk effect and mass eect Stalk effect * Hypopituitarism > Because they are under positive control of hypothalamus * Hyperprolactinoma, —> Secouse W's negatively regulated by Dopamine mass effect * Due to compression * due to increased intracranial tension Bleeding in to tumor —> Known as pituitary apoplexy clinical presentation + * Headache * Rpoplexy * visual symptoms * cavernous sinus thrombosis * Hypopituitarism / Hyperprolactinemia. Non functional pituitary masses: D Craniopharyngioma, @) Rathixe’s cyst Craniopharyngioma * most common non-functional Pituitary tumor * @imodal age distribution + S-I5 yrs and SO-74 yrs * 90% ocours in childhood 00:04:00 we ‘Active spaceCroniopharyngioma Oren is 90%——suprasellar + sellar | 1o%——suprasellar mr m=-F Adamantinomatous Papillary cystic with machinery ol | Solid appearance 7227 solid Wet keratin nodules CaleiReation H+ MRI Aindings: ( * T, sagittal precontrast Macroadenoma can be - Sunctional, non functional * Functional Tumors —* Hypointense on T, * Non — Functional Tumors —> Hypo § hyperintense on T, * T, sagittal Post-contrast mei * vivid uptake of contrast —> craniopharyngioma, Clinical features: * Child of S-Is yrs. * Presents with stalk effect Followed by mass effect * GH deficiencyFSH/LH deficiency ACTH deficiency ROH deficiency * Increased prolactin Investigation of choice: * Gadolinium enhanced met Treatment: * No medical treatment * Transphenoidal surgery °T, Sagittal precontrast image of Normal Pituitary D Anterior pituitary Slightly hypointense @ right spot A-T, me! image @-T, Mei image * Slightly hypo to hyperintense lesion * Completely hypotense Suggestive of Craniocharunoion Active spacere 618 Endocrine 97 ‘System Rathkes cyst * Headache and visual disturbance * presents as Stalk effect, Rathke’s cyst v/s craniopharyngioma D4 to s™ decade mostly in children @ site: Rathke’s cleft infundibulum 2) unilocular multilocular 4) well circumscribed May { may not circumscribed S) Sellar mass Suprasellar + sellar mass ©) No calcification Calcification present D Lined by simple Adamantinomatous and columnar epithelium Papillary maI oF rathkes cyst: D T, sagittal Pre contrast image + Hypointense lesion97 Non-Functional 19 Pituitary Masses aT, sagittal Post contrast image * Only margins are takes up the contrast Characteristic of Rathke's cyst This sign is called ‘Claw sign? * Nodule inside the eyst 4 ot sign * Posterior ledge sign case presentation: |. Large lobulated suprasellar mass within 3rd ventricle causing ob- structive hydrocephalus- Germinoma. &. CaleiReation / bony hyperstosis / Pneumosinus dilatans- meningioma, 3. Notochordal remnant with clivus destruction- Chordoma. 4. Ring enhancing lesion- Pitutary abscess (mec) 'S. Claw sign / posterior ledge sign / dot sign-Rathkes cyst ‘Activ spaceCONGENITAL HYPOPITUITARISM Hypopitutarism Congenital Required, Congenital hypopituitarism 00:01:24 Causes: D Pituitary dysplasia which is always associated with midline cranio-Faciol Anomaly midline defects in patients with hypopituitarism, (@) bifid uvula, (©) single central incisor a) Transeription factor defect Prop 1> Pit —1 + most often posterior pituitary will be intact * Because Anterior pituitary development is different From posterior pitultary Aetivospace622 Endocrine System 2) Syndromes associated with congenital hypopituitarism * Hallman syndrome, * Laurence moon Bied! Bardet syndrome * Septo-optic dysplasia * Proder — willi syndrome * Angelman syndrome 4) Other Genetic couse * Leptin Receptor mutation Deficiency of anterior pituitary hormones 00:04:28 Growth FSH AUTH TSH Prolactin Hormone LH | | | Lj— poesnt Thyroid still Not required, Trontestos -marifest- «can produce for chi echortstature MOCHA THT * Hypogonadism So, child presents with * Growth Hormone deficiency * Hypogonadism (Hypogonadotropie hypogonadism) 4 FSH, LH - Low 4 Sex Hormones — Low Growth hormone deficiency 00:06:19 * Normal L@ at every point in time * Normal height at Birth (in utero — It depends on \@F-a) * Child present with hypoglycemia + seizures * Prolonged physiological jaundice + microphallusHypopituitarism As the child grows —> Centripetal obesity Short stature Delayed sexual development Delayed dentition High pitched voice even after puberty, Short neck, Proportionate short stature Growth velocity low since birth micro phaleria delayed puberty short stature Round face with Frontal Bossing, Depressed nasal bridge midline defects — cle* lip / palate / single central incisor / bifd epiglottis, Active space624 Endocrine System Short stature 00:11:07 Height for Age is low by 7a standard deviation Or Height for Age He is a short stature Short stature Proportionate Disproportionate. short stature short stature. US #LS ratio maintained US #LS ratio not maintained. Causes Couses D Constitutional delay D Achondroplasia @ Familial short stature @ Hypothyroidism 2) GH deficiency 2) mMorquios Disease Proportionate short stature 00:14:39 Constitutional short stature: * Normal height at birth, height at | yr age also normal * Normal height in Parents * AbI-3 yr Age — Stops growing * After 3 yr —> Grows normally * Delayed puberty by a yrs * eventually height becomes normal Height Age (HA) = Gone Age (BA) < Chronological Age (CA)pp Familial short stature: * Low height at birth * Parents also have short stature HA << 6A = CA @H deficiency: HA < BA height) * small prostate + Serotum smooth without ragosity * Testicular volume < 6 em* * Penile length <5 em * Testicular length < 2.5 em ‘tive spacePost pubertal onset hypogonadism does not affect: Dprostate size ® penile length 2) scrotum 4)skeletal proportions Syndromes associated with congenital hypopituitarism 00:26:09 septo-opte dysplasia * HeSx1 mutation * Degeneration of septum pellucidum * Hypopituitarism + optionntzanty hallman syndrome * xXlinked recessive + WAL gene on x-chromosome * Agenesis of olfactory bulb —> Anosmia, * Degeneration of GnRH producing neurons in Hypothalamus 4 Hypogenadotrophie hypogonadism * Ws associated with 3¢’s - optic atrophy (very rare) - Cleft palate - Cerebellar ataxia = Color blindness. Laurence moon biedl bardet syndrome Autosomal Recessive condition a Hexadactuly or Polydactyly Obesity, Hypogonadotrapie Hypogonadison Severe mental Retardation Horse-shoe kidney Retinitis Pigmentosa.‘98 Congenital 627 Hypopituitarism Prader willie syndrome vs Angelman syndrome * genomic imprinting * Genomic imprinting + maternal genes are * Paternal genes are imprinted (inactivated / imprinted (inactivated / silenced) silenced) * Paternal gene deletion * maternal gene deletion * Or uniparental maternal * OF uniparental paternal disomy, disomy, Features common in both Prader willie and Angelman * Severe mental retardation * Severe short stature * Severe obesity * Early onset diabetes . Hypogonadism * eromicria (small hands) Specie to angelman syndrome. * Severe muscle hypotonia * Emotional issues — Inappropriate Laughter 4 Happy puppet syndrome Active spaceADULT HYPOPITUITARISM Acquired hypopituitarism Causes : | Stalk effect C me cause of Required hypopituitarism J |. Pituitary macroadenomas C Functional or NonPunctional J &. Infiitrative: |. Sarcoidosis a. Hemochromatosis 3. Langerhan cell histiocytosis 4, Butoimmune — Lymphocytic hypophysitis, Infections LTe a. Pheumocystis carinii pneumoniae 3. Histoplasmosis, 4, Toxoplasmosis, 4. Traumatic resection oF stalk a 1 Pituitary infarction or necrosis, |. Postpartum pituitary necrosis -> Sheehan syndrome 4. Russel viper venom bite . M Secondary Empty Sella Syndrome C Tumor or bleed J Hormones involved 00:05:20 ative space, due to “ stalk effect” Ht shows involvement of Anterior and posterior pituitaryag 630 Endocrine system ~ Que to “ pituitary dysplasia” ~ development of Anterior and posterior pituitary is difSerent . Congenital - So, posterior pituitary is hypopituitarism rot affected Order of Hormones : GH > FSH /LH > ACTH Isolated hormone deficiencies may be seen in any order In emergencies C bleeding or Apoplexy ] > “ ACTH” Adult GH deficiency oo.08:52 impaired quality oF Ife energy or self esteem concentration 4, Body composition C Decrease in lean body mass - centripetal obesity 1 3, Reduced excercise capacity 4. Cardiac Issues |. Amneroscierosis. a. Hyperlipidemia Adult FSH/LM deficiency 00:09:10 = Hypogonadism, male ——* Decreased libido Defective ejaculation / erection Sexual drive | | Penile length C Normal J Skeletal porportions C Normal 7 Prostate C Normal 1 menorrhoea / Oligomennorrhoea, Infertility, Hot flushes—_——— 631 99 Adult Hypopituitarism In Clinical presentation wise : Female > male hupergondicm; —_hypergonem ACTH Deficieny oo:11:24 4 cortisol Fatigue / asthenia / tiredness Loss of appetie Loss of weight Unexplained Hypoglycemia —_ Unexplained Hypotension —— Central diabetes Insipidus Polyuria b- boc mnmary cause. Pituitary Function Test 00:12:53 TSH j FSH} LH j Prolactin ——+Can be estimated directly Tuo hormones cannot be estimated directly oon ACTH ens GH provocative Tests C < ang /dl J In this Test , we administer , |. GHRH a Arginine After giving these, GH level is expected to increase above 2ng /dL. + not, itis considered as GH deficiency CL ~ dopa j clonidine j Glucagan are used but not approved J ACTH: |. Insulin tolerance Test a. metyrapone Test 3. ACTH stimulation Test C cortisol defeiency J Wt iS not a pituitary Sunction test, used to access adrenal reserve ‘Aesivespeco Insulin Tolerance Test C Not done j risky Test J ©. 1unit / Kg oF Reguiar Insulin |v eg + SoKg > S units . After 0 5 20 5 60 390 min etc . look For cortisol levelsystem Done after recording Fasting cortisol { should be Normal J when insulin is administered to a. Normal person > Hypoglycemia > Increase in cortisol level C > AO No/al J IP its 7 20. Ug /aL > low ACTH reserve Interpretation of the Test : LL ACTH low or Cortisol low ——+ Test +ve a. metyrapone Test C Steroid Synthesis Inhibitor J on giving Metyrapone——* Deoxycorttisol is not converted to Corticol ——*So, In normal person ACTH level will be increased . IP ACTH levels fail to increase then it is considered as positive Test . This implies ACTH is poor . metyrapone test is better than insulin tolerance test | because Insulin tolerance test is positive in both adrenal and pituitary Sheehans Syndrome 00: * postpartum pituitary necrosis. #2 73% necrosis required for its manifestation . * Anterior pituitary doubles in size during pregnancy * In post partum Hemorrhage \n W710,000 deliveries, Low pressure portal System is unable to t tse blood supply > Abrupt onset of hypotension > hypoperfusion ~ Infarction or Necrosis . Progression oF hormone loss + GH? FSH 5LH > ACTH > TSH : LH? FSH ; C posterior lobe is spared J 4} Clinical Features : Fatigue Failure to resume periods Failure of lactation Hypothryroidism——————— 9 Adult 633 Hypopituitarism oH 3 > vecreased FSH) LH) ACTH) PRL} TSH AOH -> mostly Normal Sheehan syndrome complications * \.Adrenol crisis > Hypotension a. Severe hyponatremia, 3, Severe osteoporosis 4 Weight loss Important differential diagnosis Lymphocytic Hypophysitis Lymphocytic hypophysitis 00:25:26 Autoimmune inflammation of Pituitary only seen in “post partum period? present as Inflammatory mass in the pituitary mass is made up IgG containing lymphocytes and plasma cells . mostly seen in females having Autoimmune iliness . Naturally have stalk effect + mass effect Any post partum female presenting with o pituitary mass has 40 be given atrial of steroids Aetivespece634 Endocrine system 99 Sheehan Lymphocytic hypophysities Pituitary necrosis mass + No mass, Stalk effect Hormonal profile: Hormonal profile + GH, FSH LH j TSH | ACTH) GH 5 FSH 5 LH 5 ACTH 5 prolactin all are low TSH all are low ADH > Normal Prolactin > ft t ADH > low mass takes up contrast in maging study Macroadenoma. in Reromegaly will take patchy uptakes of contrast . Features of lymphocytic hypophysitis. |. pitutary enlargement. a. headache , visual disturbances 2. hypopitutarism 4. hyperprolactinemia S. associated autoimmune disease. Empty sella syndrome 00:31:26 empty Sella Syndrome -> Sella is empty Primary empty Sella Does not produce Hypopituitarism Secondary empty Sella : Produce Hypopituitarism couse - Tumors ~ Post bleeding99 Adult 635 Hypopituitarism Primary empty sella syndrome 00:32:28, 1 lcT > CSF sweeping doun into pituitary Because Rim oF pituitary is intact patient generally does not develop hypopituitarism 1 ICT > Benign intracranial hypertension or pseudo tumor cerebri. 00:35:14 Pituitary apoplexy Peute Intra. pituitary Hemorrhage . ‘mn patients with post partum necrosis or tumor or Spontaneously C Hypertension or Om or sickle cell Anaemia. } present with History of a days Headache / vomiting = meningeal irritation Clinical presentation -Aeute, Hypoglycemia. / Hypotension / worsening headache In bleeding > Hormone most affected is ACTH In pituitary apoplexy > Bleeding + So, All hormone are “ lou Treatment: I Steroids + urgent surgical decompression ‘Treatment of hypopitutarism 00:08:54 Steroids Que to sort durattioon of action - Oral Hydrocortisone F vorniting or hypotension ~ 1 v hydrocortisone If there is stress / infection - Double the dose @ased on circardian 2hythm omg rg ons_| Le-Gam] Crapm] C4-spm]. ‘Active spaceBB IOC system Conversion dose + Img Dexa. = 4mg methyl Prednisolone = S mg prednisolone = 20 mg Hydrocortisone = aS mg cortisone L- Troxine Somg /day > 200mg /day L- troxine can worsen Hypocortisolemia, $0 L- Troxine given after steroids . FSH/LH replacement 00:42:15 in males + Testosterone gel or patch or |.m Testosterone enanthate aoomg once in every a weeks Desiring Fertility > @nRH 1n Females :C who completed their family 7 Estrogen img Day! > as Progestrone Smg Day leas For Fertility > Gonadotrophins or Ovulation induction agents . Gh therapy in adults GH > Img s/c once daily (or ) oral GH -0.3 mg /day POH ADH > Intranasal desmopressin S-10 mg @D or ‘Oral desmopressin 03-Ole mg once day Genetic syndrome involving pituitary oo:esis1 Patient with prolactinoma or Reromegaly Cin young patient] Consider three syndromes in young patients with prolactnoma. or acromegaly ImeN -1 syndrome Prolactinoma > GH secreting tumor a. me cune Allright Syndrome @S% mutation Features 0) cafe au lait spots '&) precocious puberty © Poly ostotic Fibrous dysplasia. with Facial asymmetry99 Adult 637 Hypopituitarism @) pituitary adenoma. C GH 7 Prolactin ] 3. Carneys Complex / Syndrome PRKAR - Ia gene 0) Lentigenes C Spotty skin lesions J ) Adrenal cushing C Lean cushings J © Atrial oD) Pituitary C GH > Prolactin J Carey's triad > Gist + Pulmonary ‘Chondoma. + Paraganglioma. Nelson syndrome oo8-37 ACTH secreting macroadenoma_ Rapid progression due to loss of negative feedback Extreme hyperpigmentation Symptoms due 4o expanding Intrasellar mass lesion Transsphenoidal surgery Sheehan and its complications * Wringkling > due to GH deficiency Dryface / expressionless > due to hypothyroidism First Hormone to be lost > ¢h ‘Second Hormone > TSH COMPLICATIONS # # Adrenal Crisis > Hypotension * Severe Hyponatremia. * Severe osteoporosis, * weight loss SBitatiory opopiong ‘ctv spacePOSTERIOR PITUITARY Posterior pituitary [neurohypophyseal relation] 00:00:30 Hormones —> Hypothalamus * vasopressin | Via. stall, * oxytocin Stored in the Posterior pituitary Released when required Posterior pituitary — Cdown grousth from the Sloor of 3 ventricle] ADH / Vasopressin or Arginine Vasopressin (AVP) __ 00:01:40 Produced from Supraoptic nucleus or paraventricular nucleus of Hypothalamus Preproarginine vasopressin Neurohypophysin a Copeptin ADH Receptors + vivo vy vivid vive Blood vessels —> Vasoconstriction Plotelets — Aggregation Liver > alycogenolysis uterus, — Contraction Myocardium —> Hypertrophy Aetivospace vv): Anterior pituitary > TACTH release640 Endocrine 100 ‘System y, Vascular endothelium —> Release VWF — Platelet adhesion Kidney Function of ADH ADH doesn’t undergo glomerular filtration 4 From efferent arteriole it enters into Peritubular capillary plexus Binds at v, ie se&n af cells of Cortical collecting duet CPeelis] principal cells 4 fT came, ‘ t Pquaporins expression from Apical membrane CAquaporins stored in vesicle] t Rap, 4 “Reabsorb free water? Golute free) ‘Two types of water reabsorption 00:08: Obligatory woter reabsorption Facultative H,0 Reabsorbtion ~ Independent of ADH = Rets at proximal convoluted tubule = Aquaporins involved: AQP, Age. sone nay ~ Dependent on ADH = Acts at collecting duct = Aquaporins involved: AQP,100 Posterior 641 Pituitary Aquaporins 00:10:42 LA@ey AQP, | PCT a. AQP, Apical membrane 3. AQP AQP, | CO/L] Basolateral membrane of collecting duct 4. AQP, Inside vessels of collecting duct 'S. AQP, No Role in Kidney Glomerular Ritrate Normal: Serum osmolality a85-a90 mosm/ikg oF H,0 4 Osmolarity of the fitrate remains same after reabsorption in PCT Csr, osm -a8S-290] This phenomenon is called “ ts0 osmotic reabsorption? 4 At tip of loop of Henle (Sr.osm-laoomosm) a0 is reabsorbed in the thin deseending limb to reach maximum Altrate osm -1400 mosm This process is called “ Counter current muttiplication® 4 Lowest Ritrate Osmolality (so mosm] At OCT C.-.Through Thick Ascending limb — Lsolutes are reabsorbed] From So mosm 40 800-900 mosm/Kg, 4 Concentration gradient f by using ADH Factors required for ADH to function + |. medullary Interstitial Osmolalitu a. urea 3, Vasarecta. 4 Counter current exchange Active space642 Endocrine 100 System sorts ony Defence mechanism to prevent hyponatremia 00:18:55, Both Hypo and hypernatremia are the disorders of water metabolism Bod gucose BUN, Serum osmolality =axna + ——2—— + = ABS — 290 mosm/Kg oF H.0 Low osmolality = Low Na Low osmolality = Hyponatremia = "True Hyponatremia” WF Nia" low but Osmolality Normal or High = Pseudo — Hyponatremia High Na is never equal to High osmolality : Osmolality is Normal < a8S-290 mosm/kg “7. BDH evels are Kept below I ng/i 7 a80 — a8 mosm/Kg, ? a90 mosm/kg fon tt supra. optic. | osmoregulatory centre ‘ Free H,0 reabsorbtion t Thrist 4 ‘ Osmolality Normal free H.0 reabsorption ‘osmolality Normal High Na? = High Osmolality + in Neurosurgery cases : Patient with head injury or on ventilator, Pituitary apoplexy ADH not released > hypernatremia, otherwise hypernatremia, is rare Adipsic hypernatremia 02848 Disease of Hypothalamus — Damage to osmoregulatory, Centres of supraoptic nucelus100 Posterior 643 Pituitary Low Osm = Low Na* High Osm = High No” Normally ADH is 20 meg/L 's. Absence of pituitary, adrenal, thyroid, renal and liver disease644 Endocrine 100 System once ony IP free 4,0 reabsorbtion more —> Tendency for intravascular Volume — RAS(-) inhibited — Aldosterone | | urinary Na’ ff — Plrial Natriuretic Factor t T— So, urinary Na’= 7 20 meg/L Diabetes Insipidus [DI] 00.384 No ADH — Central DI Resistance to ADH — Peripheral or Nephrogenie 1 to ADH Polyurias C>somi/Kg/aahrs or asL/.aahrs] Solute diuresis water diuresis 1. Tubular injury Lo &. Mannitol 2. Urine dipstick —> “ve 3 Urine dipstick +ve 3, rine osm < S00 mosm For glucose 4. Urine specie gravity $ 1010 Causes for water diuresis 00:44:28 |. Central ot ; To differentiate &. Nephrogenic D1 > test 3. Psychogenie polydipsia ——" Water deprivation test 00:45:26 urine Osmolality Central D1 < aSO mosm Nephrogenic D1 250-450 mosm Pshycogenic 01 450-600 mosmat water deprivation 4.008m, la noon, Ceaseline urine osmolality _LOss oF 73% oF Repeat noted] body weight urine osmolality Stop the test urine osmolality Urine osmolality hhas inereased to more than stil ows &S0-700m0smn | CPsychogenic polydypsia] o * Cif urine osmolality still low ater Ianoon give Intranasal desmopression on $/¢ aqueous vasopressin and check at apm and 4pm for urine osmolality At 4 pm urine osm f by 7 So% —> Central DI Cin aes] Cia-4pm] Wurine osm f by < 10% —* Nephrogenic 0.1 Cin aes] urine osm f by 10 - So % — Partial central 01 Cin ates] Central D.I 00:50:44 Required Genetic Caz] \ Stalk effect DIDMOAD syndrome CWOLFRAM] - Pituitary adenoma Cmcc] diabetes inspidus CFunetional/Non — om functional] optic atrophy i = Infiltrast infiltrative peatness a Csareoidosis; LOH Autoimmune; Hemochromatosis] ~ Infection LT6; PCP; Toxoplasmosis, Histoplasmosis] ~ TraumaricCO SSSSfS“<$ 646 Endocrine 100 System N Pituitary infarction Leg: Sheehan; ADH deficiency rare] M Pregnancy Cvasopressinase] major symptoms: Polyuria The patient able to drink water 4 No hypernatremia, Nephrogenic DI [peripheral] 0054.08 \ Drugs Lithium Demeclocycline Cisplatin Aminoglycoside Foscarnet Amphotericin 6 WW Chronic tubulo interstitial disease CADH resistance] Couses: * a Autoimmune disease (Sjogren} Sarcoidosis] * 4 metabolic toa vn f uric Acid Huper oxaluria ~ chiemood mianey disease Reflux Nephropathy Mw Pregnancy IV Sickle cell Anaemia. FB eenetic causes, i * v, Receptor mutation CXL2] more common, + AGP, mutation CAR]— 100 Posterior 647 Pituitary ‘Treatment 1:00:06 Central 01: Intranasol desmopressin 10-a0g bd Partial DA + Aqueous $/C vasopressin or clofibrate or Carbamazepine Peripheral 0.1 + Lithium induced D1 ——> Amilrride or Triamterene Lithium [= feten Le exine enor w ct Peels Peel or w Other drug used Sor peripheral 0. —> Thiazide diuretios ction : Volume contraction T responsiveness of other parts of tubule ‘Active spaceSIADH v/s CSWS @ Causes For Hyponatremia post — head injury 1. SIRDH a. Cerebral salt wasting, syndrome Ccsws] (csws) Cerebral Salt Wasting Syndrome Dysautonomia © — type erain 1 Notriuretric Peptide cause B, reveptor damage Cendotheliumn] J J sa cells affected Natriuresis, J ond No RAS octivity sures J Salt and 4,0 wasting Present as Dehydration Hypovolemia. Hypovolemie Hyponatremia Occurs in I-a weeks after Head injury resolves in 3-4 weeks Normal uric acid levels cows SIROH 1. Polyuria No polyuria a, Hypovolemic hyponatremia | Euvolemic hyponatremia r Dehydration No dehydration i 4. Present after I-a weeks Presents immediately OF head injury after head injury 5. Treatment: Fluids CHydration] | > 48 hrs water restriction ©. normal uric acid levels Decreased uric acid levels‘WATER METABOLISM Hyponatremia and Hypernatremia 00:00:21 Hyponatremia Coisorders of H,0 metabolism] Recording to European care of intensive care unit, Serum Na < 1a0-las med/L are associated with symptoms, +. Cthere is no strict normal value for Na+ differs from person to person] us-ta0/ias med/L — &I symptoms, Anorexia, Nausea / vomiting, Cramps «ios meq/L — — mild neurological Agitation Confusion Dieziness Ataxia, Jeoncentration 100-105 meq/L. —> Serious neurological symptoms Cerebral edema, fier Cerebral edema — in hyponatremia- blood os- molality is low - water diffuses from high to low concentration (rom, capillaries into interstitium) step t) True vs Pseudo Hyponatremia Low osmolality High osmolality or Normal osmolality €9- Serum Na - 98, BUN- a8, blood glucose- 90 Blood guose guy —e tas ae ~ = +—+— axoat et as Serum Osmolality = aX Na+ = +S+10 = 199 mosr/kg/H,0 = True Hyponatremia. Actvospace650 Endocrine System 101 Pseudo hyponatremia Low Na; Osmolarity @ or f sed ©) Translocational Pseudo Hyponatremia, Certain solutes that easily cross From blood to cell membrane “ Ineffective solute” €g} Alcohol Certain solutes that cannot easily cross From blood to cell membrane remain in blood compartment; So, this tse os- molality of blood compartment} water From cell diffuses to blood: So, more water in blood results — Hyponatremia, These solutes are "effective solutes? 1. Glucose a. Mannitol 3. @lycine 4. maltose gq: Polyuria Cin om] f] ») methodology Flame spectro photo- metry, +o Measure No* Coidd T+ proteins| _ Te lipids -> + not This is also considered as “pseudo hyponatremia? lon sensitive electrodes CNew] This is not seen heress SS 101 Water 651 Metabolism Causes for pesudohyponatremia: 1, Glucose. ——— a. mannitol 3. Glycine 4.Moaltose ———! | By Translocation 5. f proteins — ce tipits —}? @yemethoddlegy Step 2: Evaluation of hyponatremia sere To assess whether Hypervolumeic | | euvolemie | | Hypovolemie Hypovolemic Hyponatremia, * CKO * Cirrhosis * Congestive Heart failure * Nephrotic sundrome Pathogenesis - Aldosterone < RAS < depleted Intra vascular volume ‘ absorb No* and H.0 (No* <0] 4 Hyponatremia, Treatment: “Loop Diuretics? athe space,BBE EGC aS ‘System Drug induced hyponatremia - thiazide or furosemide 00:14:35, Thiazide >? furosemide Thiazide: t resoonsiveness of other parts of tubules ‘ More H,0 and solute will be reabsorbed 4 Contribute to Medullary interstitial Osmolality 4 Medullary interstitial Osmolality will be Normal 4 @y ADH action free water reabsorbed 4 Hyponatremia. Furosemide: Potent diuretic exerete salt and water Wt exeretes more water than sodium Hypovolemic hyponatremia Non renal loss. Renal L Vomiting 1. Overuse of diuretics a. Diarrhea a. Reute tubular injury 3, 3" space loss 3, Renal tubular acidosis — Guns 4, Aldosterone insufficiency — Pancreatitis = Bhabdomyolysis, Cerebral salt wasting syndrome — Aso cause Hypovolemic 3 Hyponatremia 1 Euvotemic hyponatremia 001095 |. Cortisol insufficiency 2. Hypothyroidism 3. SIADHvor water Metabolism Criteria - SIADH 00:20:08 Five criteria: 1. | serum osmolality 4. Urine osmolality > serum osmolality 3. Clinical euvolemia. 4. T urine No* 5. Absence of pituitary, Adrenal, Renal © Thyroid; Liver disease Common couse SIADH — Head injury manifest with — Hyponatremia. ‘Treatment Hypovolemic Hyponatremia: Fluids are the mainstay tL of a Aud IMtusate Na — Serta, T.2w + 1 (Total body water) 154-100 0% x BW + 1 Body weight 60 kg) = SAxtoo A ot 3T (om of oud) AL of NS IS4 meq of Na = 1L Normal saime wll increases sodium by I-& meq/L Cmaxt 1s meo/t} Target correction => max — 8 meq/L / day S litres of Normal saline per day required Acte spsce vos