Hypopituitarism & Hyperpituitarism

1. Hypothalamic - pituitaryHypothalamic - pituitary
disorders.disorders.
Hypopituitarism andHypopituitarism and
HyperpituitarismHyperpituitarism

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4. The hypothalamic-pituitary axesThe hypothalamic-pituitary axes

5. HYPOTHALAMUS ANDHYPOTHALAMUS AND
PITUITARY GLANDPITUITARY GLAND
HYPOPHYSISHYPOPHYSIS
ANTERIORANTERIOR
LOBELOBE
INTERMEDIATEINTERMEDIATE
LOBELOBE
POSTERIORPOSTERIOR
LOBELOBE
MelanotropinMelanotropin ADHADH
(vasopresin)(vasopresin)
OxytocinOxytocin
Basophile cellsBasophile cells
EosinophilicEosinophilic
cellscells ChromophobesChromophobes
cellscells
ACTHACTH
TSHTSH
FSHFSH
ICSHICSH
TTHTTH
STGSTG
ProlactinProlactin

6. Hypothalamic releasing hormonesHypothalamic releasing hormones
Hypothalamic releasing hormone Effect on pituitaryEffect on pituitary
Corticotropin releasingCorticotropin releasing
hormone (CRH)hormone (CRH)
Stimulates ACTH secretionStimulates ACTH secretion
Thyrotropin releasingThyrotropin releasing
hormone (TRH)hormone (TRH)
Stimulates TSH andStimulates TSH and
Prolactin secretionProlactin secretion
Growth hormone releasingGrowth hormone releasing
hormone (GHRH)hormone (GHRH)
Stimulates GH secretionStimulates GH secretion
SomatostatinSomatostatin Inhibits GH (and otherInhibits GH (and other
hormone) secretionhormone) secretion
Gonadotropin releasingGonadotropin releasing
hormone (GnRH)hormone (GnRH)
Stimulates LH and FSHStimulates LH and FSH
secretionsecretion
Prolactin releasingProlactin releasing
hormone (PRH)hormone (PRH)
Stimulates PRL secretionStimulates PRL secretion
Prolactin inhibitingProlactin inhibiting
hormone (dopamine)hormone (dopamine)
Inhibits PRL secretionInhibits PRL secretion

7. The hormones are secreted by the anterior pituitary:The hormones are secreted by the anterior pituitary:
HORMONEHORMONE FUNCTIONFUNCTION
Thyroid StimulatingThyroid Stimulating
HormoneHormone (TSH)(TSH)
causes the thyroid gland tocauses the thyroid gland to
produce and release thyroidproduce and release thyroid
hormoneshormones
Growth HormoneGrowth Hormone (GH)(GH) regulates growth and metabolismregulates growth and metabolism
AdrenocorticotropicAdrenocorticotropic
Hormone (ACTH)Hormone (ACTH)
triggers the adrenals to releasetriggers the adrenals to release
the hormone cortisolthe hormone cortisol
Luteinizing Hormone (LH)Luteinizing Hormone (LH) menstrul cycle and reproductionmenstrul cycle and reproduction
Follicle StimulatingFollicle Stimulating
Hormone (FSH)Hormone (FSH)
in the ovary stimulates the growthin the ovary stimulates the growth
of immatureof immature Graatian folliclesGraatian follicles
to maturation.to maturation.
In men enhances the productionIn men enhances the production
of androgen-bilding protein by theof androgen-bilding protein by the
Sertoli cellsSertoli cells of the testes and isof the testes and is
critical for spermatogenesiscritical for spermatogenesis
stimulates production of breaststimulates production of breast
milk and is necessary for normalmilk and is necessary for normal
milk production duringmilk production during
breast feedingbreast feedingProlactinProlactin (PRL)(PRL)

8. The hormones are secreted by theThe hormones are secreted by the
posterior pituitary:posterior pituitary:
HORMONEHORMONE FUNCTIONFUNCTION
stimulates contractions of the uterusstimulates contractions of the uterus
during labor and the ejection of milkduring labor and the ejection of milk
during breast-feedingduring breast-feeding
increases reabsorption of water intoincreases reabsorption of water into
the blood by the kidneys andthe blood by the kidneys and
therefore decreases urine productiontherefore decreases urine production
Intermediate lobeIntermediate lobe
producesproduces melanocyte – stimulating hormonemelanocyte – stimulating hormone (MSH)(MSH)
regulates the production of melanin, a dark pigment, byregulates the production of melanin, a dark pigment, by
melanocytes in the skinmelanocytes in the skin
OxytocinOxytocin
oror VasopressinVasopressin
AntidiureticAntidiuretic
HormoneHormone (ADH)(ADH)

9. DISORDERS OF PITUITARY GLANDDISORDERS OF PITUITARY GLAND
with the decreased function
HYPOPITUITARISMHYPOPITUITARISM
with the increased function
HYPERPITUITARISMHYPERPITUITARISM
Pituitary dwarfismPituitary dwarfism
(nanism)(nanism)
 Sheehan’sSheehan’s
syndromesyndrome
(Simmond’s desease)(Simmond’s desease)
 Diabetes insipidusDiabetes insipidus
AcromegalyAcromegaly
GigantismGigantism
Icsenko-CushingIcsenko-Cushing
diseasedisease
HyperprolactinaemiaHyperprolactinaemia

10. HypopituitarismHypopituitarism
is loss of function in an endocrine gland due to failure ofis loss of function in an endocrine gland due to failure of
the pituitary gland to secrete hormones whichthe pituitary gland to secrete hormones which
stimulate that gland's function.stimulate that gland's function.
PanhypopituitarismPanhypopituitarism
This condition represents the loss ofThis condition represents the loss of all hormonesall hormones
released by the anterior pituitary gland.released by the anterior pituitary gland.
PanhypopituitarismPanhypopituitarism is also known as complete pituitaryis also known as complete pituitary
failure.failure.
The terms Reye syndrome, Sheehan’s andThe terms Reye syndrome, Sheehan’s and
Simmond’sSimmond’s syndromesyndrome refers to necrosis of therefers to necrosis of the
pituitary during the postpartum period.pituitary during the postpartum period.
Only the difference inOnly the difference in Simmond’s syndromeSimmond’s syndrome is thatis that
although it is very similar medical condition can takealthough it is very similar medical condition can take
place in both males and females and it is independentplace in both males and females and it is independent
from the postpartum complications.from the postpartum complications.

11. Causes of hypopituitarismCauses of hypopituitarism
Ischemia and infarctionIschemia and infarction – Sheehan’s syndrome,– Sheehan’s syndrome,
apoplexyapoplexy
 IatrogenicIatrogenic - Radiation, surgery, withholding previous- Radiation, surgery, withholding previous
chronic glucocorticoid replacementchronic glucocorticoid replacement
 Trauma to the hypophysisTrauma to the hypophysis
TumorsTumors - Craniopharyngiomas, pituitary adenomas- Craniopharyngiomas, pituitary adenomas
Infiltrative processesInfiltrative processes - Sarcoidosis, histiocytosis X,- Sarcoidosis, histiocytosis X,
hemochromatosishemochromatosis
InfectionsInfections -- Tuberculosis, syphilis, meningitisTuberculosis, syphilis, meningitis
Empty sella syndromeEmpty sella syndrome
CongenitalCongenital – Kallmann’s syndrome– Kallmann’s syndrome
AutoimmuneAutoimmune - Lymphocytic hypophysitis- Lymphocytic hypophysitis

12. Sheehan’s syndromeSheehan’s syndrome
Synonyms:Synonyms: Simmond’s disease, PostpartumSimmond’s disease, Postpartum
pituitary necrosis, Postpartum ishemic necrosis ofpituitary necrosis, Postpartum ishemic necrosis of
the anterior pituitary, Postpartumthe anterior pituitary, Postpartum
panhypopituitarismpanhypopituitarism
Sheehan’s syndromeSheehan’s syndrome, or, or necrosis of thenecrosis of the
pituitary glandpituitary gland, is a rare complication of, is a rare complication of
postpartum hemorrhage initiallypostpartum hemorrhage initially
described in 1937described in 1937..
Sheehan’s syndrome was named when theSheehan’s syndrome was named when the
English pathologistEnglish pathologist Harold LeemingHarold Leeming
Sheehan (1900-1988)Sheehan (1900-1988) reviewed andreviewed and
described the syndrome.described the syndrome.
Polish physicianPolish physician Leon Konrad Glinski (1870-Leon Konrad Glinski (1870-
1918)1918) counts for the other name,counts for the other name, GlinskiGlinski
Simmon’s syndrome.Simmon’s syndrome.

13. Laboratory diagnostic ofLaboratory diagnostic of
Sheehan’s syndromeSheehan’s syndrome
• Blood tests:Blood tests:
 Serum thyroid stimulating hormoneSerum thyroid stimulating hormone (TSH):(TSH):
decreased (decreased (↓↓) or normal (N)) or normal (N)
 TT44 (thyroid hormone):(thyroid hormone): ↓↓
 Serum luteinizing hormoneSerum luteinizing hormone (LH):(LH): ↓ or N↓ or N
 Serum follicle stimulating hormoneSerum follicle stimulating hormone (FSH):(FSH): ↓ or N↓ or N
 Serum testosteroneSerum testosterone:: ↓↓
 Serum estradiolSerum estradiol (estrogen):(estrogen): ↓↓
 Serum cortisolSerum cortisol:: ↓↓
 Serum ACTHSerum ACTH:: ↓↓
 Serum growth hormoneSerum growth hormone (GH):(GH): ↓↓
• Bone x-rays of the hand:Bone x-rays of the hand:
• to determine bone ageto determine bone age

14. Standard therapy ofStandard therapy of
Sheehan’s syndromeSheehan’s syndrome
Hormone replacement medications mayHormone replacement medications may
include:include:
CorticosteroidsCorticosteroids are required if the ACTH-are required if the ACTH-
adrenal axis is impairedadrenal axis is impaired
Treat secondary hypothyroidismTreat secondary hypothyroidism --
LevothyroxineLevothyroxine
Sex hormones:Sex hormones: testosterone in men andtestosterone in men and
estrogen or a combination of estrogen andestrogen or a combination of estrogen and
progesterone in womenprogesterone in women

15. GlucocorticoidsGlucocorticoids used in adrenal insufficiency:used in adrenal insufficiency:
HydrocortisoneHydrocortisone 20-30 mg/d PO divided bid20-30 mg/d PO divided bid
(often 15 mg in the morning and 10 mg in the afternoon)(often 15 mg in the morning and 10 mg in the afternoon)
Thyroid hormonesThyroid hormones used in hypothyroidism:used in hypothyroidism:
LevothyroxineLevothyroxine 100-200 mcg/d p/o100-200 mcg/d p/o
Growth hormonesGrowth hormones used in the treatment of children:used in the treatment of children:
Somatropin (Humatrope, Genotropin)Somatropin (Humatrope, Genotropin) 6-125 mcg/kg/d s/c6-125 mcg/kg/d s/c
Pediatric dose:Pediatric dose: GenotropinGenotropin - 160-240 mcg/kg SC q week divided- 160-240 mcg/kg SC q week divided
in 6-7 dosesin 6-7 doses
Humatrope -Humatrope -180 mcg/kg IM/SC q week divided in 3-7 doses180 mcg/kg IM/SC q week divided in 3-7 doses
Sex hormonesSex hormones used in hypogonadism:used in hypogonadism:
Recombinant human GHRecombinant human GH (rhGH)(rhGH) by SC injection daily:by SC injection daily:
0.3 mg/kg/week0.3 mg/kg/week
TestosteroneTestosterone -- 50-400 mg i/m q 2-4 week50-400 mg i/m q 2-4 week
EstrogensEstrogens -- 0.3-0.625 mg/d p/o for 3 week; off 1 week,0.3-0.625 mg/d p/o for 3 week; off 1 week,
repeat cyclerepeat cycle
Treatment of Sheehan’s syndromeTreatment of Sheehan’s syndrome

16. PITUITARY NANISMPITUITARY NANISM
HYPOPHYSIAL MICROSOMIA, HYPOPHYSIALHYPOPHYSIAL MICROSOMIA, HYPOPHYSIAL
NANOCORMIANANOCORMIA
it is a genetic disease caused byit is a genetic disease caused by
absolute or relative deficiency of STHabsolute or relative deficiency of STH
in the organism.in the organism.
The sudden growth inhibition is markedThe sudden growth inhibition is marked
the age of 2-3 years in genetic nanism.the age of 2-3 years in genetic nanism.
First the disease was described byFirst the disease was described by
A. Paltuff in 1891.A. Paltuff in 1891.

17. Pituitary dwarfismPituitary dwarfism
is a condition in which the growth of theis a condition in which the growth of the
individual is very slow or delayed,individual is very slow or delayed,
resulting in less than normal adultresulting in less than normal adult
stature.stature.
Abnormally short stature.Abnormally short stature.
The average adult height ofThe average adult height of malemale andand femalefemale
dwarfismdwarfism sufferers aresufferers are 130130 cmcm andand 120 cm120 cm
respectively.respectively.
Also known asAlso known as nanismnanism..

18. Etiology and pathogenesisEtiology and pathogenesis
pituitary nanismpituitary nanism
CongenitalCongenital
insufficiencyinsufficiency
autosomal – recessiveautosomal – recessive
inheritanceinheritance
(idiopathic forms)(idiopathic forms)
Acquired insufficiencyAcquired insufficiency
pituitary tumorpituitary tumor
craniopharyngiomacraniopharyngioma
injury of the pituitaryinjury of the pituitary
sarcoidosissarcoidosis
toxoplasmosistoxoplasmosis
infectioninfection
vascular pathologyvascular pathology
PeripheralPeripheral
resistanceresistance
of GHof GH
Growth deceleration and differentiation of skeletonGrowth deceleration and differentiation of skeleton
AbsoluteAbsolute
deficiency ofdeficiency of
GHGH
RelativeRelative
deficiency ofdeficiency of
GHGH

19. Classification of pituitary dwarfismClassification of pituitary dwarfism
Organic:Organic:
traumatrauma
neoplasmsneoplasms
infectioninfection
Idiopatic:Idiopatic:
primaryprimary
secondarysecondary
due to hypothalamicdue to hypothalamic
deficiencydeficiency
PanhypopituitarismPanhypopituitarism
Isolated GH deficiencyIsolated GH deficiency
(may be hereditary and transmitted(may be hereditary and transmitted
as an autosomal recessive trait,as an autosomal recessive trait,
in other instancesin other instances
a hereditary basis cannot be established)a hereditary basis cannot be established)

20. PhysicalPhysical
ChildrenChildren
The standing heightThe standing height
standard deviation scorestandard deviation score
is usually below -2is usually below -2
Growth velocity is below theGrowth velocity is below the
10-25 th percentile,10-25 th percentile,
which reflects growthwhich reflects growth
decelerationdeceleration
Increased subcutaneous fatIncreased subcutaneous fat
is present, especiallyis present, especially
around the trunkaround the trunk
The face is immature, with aThe face is immature, with a
prominent forehead andprominent forehead and
depressed midfacialdepressed midfacial
developmentdevelopment
Dentition is delayedDentition is delayed
The average age of pubertalThe average age of pubertal
onset is delayed in bothonset is delayed in both
boys and girlsboys and girls
Adults
Reduced lean body massReduced lean body mass
and increased weight, withand increased weight, with
body fat massbody fat mass
predominantly in thepredominantly in the
abdominal regionabdominal region
Thin and dry skinThin and dry skin
Cool peripheriesCool peripheries
Poor venous accessPoor venous access
Reduced muscle mass andReduced muscle mass and
strength and reducedstrength and reduced
exercise performanceexercise performance
Depressed affectDepressed affect
Labile emotionsLabile emotions

21. S., 13 years old.
Height – 85 cm,
weight – 12 kg G., 3 years old.
Height – 68 cm,
weight – 7 kg.

22. Girl , 4 years old, her height -120 cmGirl , 4 years old, her height -120 cm

23. MEDICATIONMEDICATION
GenotropinGenotropin
NutropinNutropin
0.15 - 0.3
mg/kg/week
S/C initially
divide into equal doses to be
given daily or 6 times/week
as subcutaneous injections

24. Diabetes insipidus (DI)Diabetes insipidus (DI)
is a condition that results from insufficient production of theis a condition that results from insufficient production of the
antidiuretic hormone (ADH).antidiuretic hormone (ADH).
First, it was described by Thomas Willis in 1674. The family formFirst, it was described by Thomas Willis in 1674. The family form
of hypothalamic DI was described by Lacomb in 1841.of hypothalamic DI was described by Lacomb in 1841.
Hypothalamic Diabetes Insipidus (HDI)Hypothalamic Diabetes Insipidus (HDI) also known asalso known as
neurogenic, central, or cranial DI is the result of partial orneurogenic, central, or cranial DI is the result of partial or
complete lack of osmoregulated ADH secretion.complete lack of osmoregulated ADH secretion.
Nephrogenic Diabetes Insipidus (NDI)Nephrogenic Diabetes Insipidus (NDI) is due to renalis due to renal
resistance to the antidiuretic effects of ADH.resistance to the antidiuretic effects of ADH.
Dipsogenic Diabetes Insipidus (DDI)Dipsogenic Diabetes Insipidus (DDI) is a polyuricis a polyuric
syndrome secondary to excess fluid intake. Though structuralsyndrome secondary to excess fluid intake. Though structural
abnormalities may be the cause, it is generally a manifestationabnormalities may be the cause, it is generally a manifestation
of primary polydipsia, psychiatric disease, or secondaryof primary polydipsia, psychiatric disease, or secondary
to drug effects.to drug effects.

25. Classification of Diabetes Insipidus (DI)Classification of Diabetes Insipidus (DI)
Hypothalamic DIHypothalamic DI
PrimaryPrimary
Genetic:Genetic:
DIDMOAD (Wolfram)DIDMOAD (Wolfram)
syndromesyndrome
Autosomal dominantAutosomal dominant
Autosomal recessiveAutosomal recessive
DevelopmentalDevelopmental
syndromes:syndromes:
Septo-optic dysplasiaSepto-optic dysplasia
IdiopathicIdiopathic
Secondary/Secondary/
acquiredacquired
Trauma:Trauma:
Head injuryHead injury
Post surgeryPost surgery
(transcranial,(transcranial,
transphenoidal)transphenoidal)
Tumour:Tumour:
CraniopharyngiomCraniopharyngiom
Germ cell tumoursGerm cell tumours
MetastasesMetastases
PituitaryPituitary
macroadenomamacroadenoma
Inflammatory:Inflammatory:
GranulonulomasGranulonulomas
SarcoidosisSarcoidosis
HistiocytosisHistiocytosis
InfectionInfection
Infundibulo-Infundibulo-
neurohypophysitisneurohypophysitis
Guillaine-BarreGuillaine-Barre
SyndromeSyndrome
AutoimmuneAutoimmune
Vascular:Vascular:
AneurysmAneurysm
InfarctionInfarction
Sheehan'sSheehan's
syndromesyndrome
Sickle cell diseaseSickle cell disease
PregnancyPregnancy
(associated with vasopressinase)(associated with vasopressinase)
Nephrogenic DINephrogenic DI
Dipsogenic DIDipsogenic DI
CompulsiveCompulsive
water drinkingwater drinking
AssociatedAssociated
with affectivewith affective
disordersdisorders
Structural/Structural/
organicorganic
hypothalamichypothalamic
diseasedisease::
Sarcoid
Tumours involving
hypothalamus
Head injury
Tuberculous
meningitis
PrimaryPrimary
SecondarySecondary
Genetic:Genetic:
X-linked recessiveX-linked recessive
Autosomal recessiveAutosomal recessive
Autosomal dominantAutosomal dominant
Idiopathic:Idiopathic:
Chronic renal diseaseChronic renal disease
Metabolic diseaseMetabolic disease
Drug inducedDrug induced
Osmotic diureticsOsmotic diuretics
Systemic disordersSystemic disorders
PregnancyPregnancy

26. Diabetes insipidus (DI)Diabetes insipidus (DI)
HYPOTHALAMIC DIHYPOTHALAMIC DI NEPHROGENIC (RENAL)NEPHROGENIC (RENAL)
DIDI
absolute deficiency ofabsolute deficiency of
antidiuretic hormoneantidiuretic hormone
genetic pathology ofgenetic pathology of
ADH receptors,ADH receptors,
it inheritsit inherits
as recessive signas recessive sign
which linkedwhich linked
with sex (in male)with sex (in male)

27. Causes of DICauses of DI
 malfunctioning hypothalamusmalfunctioning hypothalamus
 malfunctioning pituitary glandmalfunctioning pituitary gland
 damage to hypothalamus or pituitary gland duringdamage to hypothalamus or pituitary gland during
surgerysurgery
 brain injurybrain injury
 tumortumor
 tuberculosistuberculosis
 blockage in the arteries leading to the brainblockage in the arteries leading to the brain
 encephalitisencephalitis
 meningitismeningitis
 sarcoidosis (a rare inflammation of the lymph nodessarcoidosis (a rare inflammation of the lymph nodes
and other tissuesand other tissues
throughout the body)throughout the body)

28. SYMPTOMS OF DIABETES INSIPIDUSSYMPTOMS OF DIABETES INSIPIDUS
 excessive thirstexcessive thirst
 excessive urine production (up to a dozen or moreexcessive urine production (up to a dozen or more
quarts a day) of diluted, colorless urinequarts a day) of diluted, colorless urine
 dehydrationdehydration
 dry handsdry hands
 constipation (due to "dry" bowels)constipation (due to "dry" bowels)
LABORATORY TESTS OF DI:LABORATORY TESTS OF DI:
 low ADH levelslow ADH levels
 electrolyte imbalanceelectrolyte imbalance
 polyuriapolyuria (> 3 litre)(> 3 litre)
 urinalysis shows a low specific gravityurinalysis shows a low specific gravity (< 1008)(< 1008)

29. NameName Central Diabetes InsipidusCentral Diabetes Insipidus Neprhogenic Diabetes InsipidusNeprhogenic Diabetes Insipidus
SituationSituation Lack of or insufficient ADHLack of or insufficient ADH Structural or functional defectsStructural or functional defects
in ADH receptors or aquaporinsin ADH receptors or aquaporins
OnsetOnset
•congenital defect ofcongenital defect of
hypothalamus or pituitaryhypothalamus or pituitary
•acquiredacquired
•congenital defect of receptorscongenital defect of receptors
or aquaporinsor aquaporins
•acquiredacquired
CausesCauses trauma or disease of pituitary ortrauma or disease of pituitary or
hypothalamushypothalamus
trauma or disease of the kidneytrauma or disease of the kidney
Signs &Signs &
TestsTests
polyuriapolyuria
•polydispsiapolydispsia
•electrolyte imbalanceelectrolyte imbalance
•possible dehydrationpossible dehydration
•low ADH levelslow ADH levels
•urinalysis low specific gravityurinalysis low specific gravity
polyuriapolyuria
•polydispsiapolydispsia
•electrolyte imbalanceelectrolyte imbalance
•possible dehydrationpossible dehydration
•low ADH levelslow ADH levels
•urinalysis low specific gravityurinalysis low specific gravity
DiagnosisDiagnosis •rule out other causesrule out other causes
•imagery of pituitary andimagery of pituitary and
hypothalamushypothalamus
•water deprivation testwater deprivation test
•ADH trialADH trial
•rule out other causesrule out other causes
•rule out CDIrule out CDI
TreatmentTreatment desmopressindesmopressin oral chlorothiazideoral chlorothiazide
•chloropropamidechloropropamide
•NSAIDsNSAIDs
•restrict saltrestrict salt
PrognosisPrognosis variablevariable
•not life-threatening if treatednot life-threatening if treated
and fluid intake maintainedand fluid intake maintained
congenital NDI--chroniccongenital NDI--chronic
•acquired NDI--variableacquired NDI--variable

30. Treatment of Diabetes InsipidusTreatment of Diabetes Insipidus
Central DI:Central DI:
long-acting VPlong-acting VP analogue DDAVP:analogue DDAVP:
intranasal sprayintranasal spray H-DesmopressinH-Desmopressin single dosesingle dose
consists ofconsists of 10 mcg10 mcg of Desmopressin acetateof Desmopressin acetate
(5-100 mcg daily),(5-100 mcg daily),
AdiupressinAdiupressin («Ameda Pharma», India) is used(«Ameda Pharma», India) is used
intranasalintranasal 2–8 gutters2–8 gutters (10-40 mcg)(10-40 mcg) a day.a day.
Antidiuretic effect showsAntidiuretic effect shows in an hourin an hour,, maximal actionmaximal action
1–5 hours1–5 hours,, effect longevity is 8–20 hourseffect longevity is 8–20 hours..
Parenteral injection (0.1-2.0 mcg daily).Parenteral injection (0.1-2.0 mcg daily).
OralOral MinirinMinirin is used byis used by 100–200 mcg a100–200 mcg a
dayday (1–3 tablets), in divided doses.(1–3 tablets), in divided doses.

31. Nephrogenic DI:Nephrogenic DI:
is usually treated withis usually treated with
thiazide diureticsthiazide diuretics hydrochlorothiazidehydrochlorothiazide 25 mg/day25 mg/day,,
which are among the class of "water pills“.which are among the class of "water pills“.
Non-steroidal anti-inflammatory drugs:Non-steroidal anti-inflammatory drugs:
Ibuprofen 200 mg/dayIbuprofen 200 mg/day.
Low salt dietLow salt diet ..
Dipsogenic DI:Dipsogenic DI:
Clozapine 100 mgClozapine 100 mg may reduce
polydipsia in those patients with refractory
schizophrenia on other dopamine antagonistsdopamine antagonists.
Reduced fluid intakefluid intake is the only rational treatment.
Treatment of Diabetes InsipidusTreatment of Diabetes Insipidus

32. HyperpituitarismHyperpituitarism
AcromegalyAcromegaly
GigantismGigantism
Itsenko-Cushing’sItsenko-Cushing’s
syndromesyndrome
 HyperprolactinaemiaHyperprolactinaemia

33. PITUITARY ADENOMAPITUITARY ADENOMA
MICROADENOMAMICROADENOMA MACROADENOMAMACROADENOMA
CATEGORIESCATEGORIES
Diameter = / < 10 mmDiameter = / < 10 mm
IntrasellarIntrasellar
Presents usually withPresents usually with
hormonal hypersecrationhormonal hypersecration
syndromesyndrome
Diameter > 10 mmDiameter > 10 mm
Extends outsideExtends outside
the sellathe sella
Presents often withPresents often with
chiasmal compressionchiasmal compression
syndromesyndrome

34. Causes of acromegalyCauses of acromegaly
SOMATOTROPH ADENOMASSOMATOTROPH ADENOMAS
 Eosinophilic pituitary adenoma
 Pituitary tumors: microadenomas (pituitarymicroadenomas (pituitary
tumors less than 1 cm in size);tumors less than 1 cm in size);
macroadenomas (pituitary tumors greatermacroadenomas (pituitary tumors greater
than 1cm)than 1cm)
 Nonpituitary tumors:Nonpituitary tumors: by tumors of theby tumors of the
pancreas, lungs, and other parts of the brainpancreas, lungs, and other parts of the brain

35. Symptoms of acromegalySymptoms of acromegaly
Facial change, acral enlargement, and soft-Facial change, acral enlargement, and soft-
tissue swellingtissue swelling
Excessive sweatingExcessive sweating
Acroparesthesiae/ carpal tunnel syndromeAcroparesthesiae/ carpal tunnel syndrome
Tiredness and lethargyTiredness and lethargy
HeadachesHeadaches
Oligo- or amenorrhea, infertilityOligo- or amenorrhea, infertility
Erectile dysfunction and/or decreasedErectile dysfunction and/or decreased
libidolibido
ArthropathyArthropathy
Impaired glucose tolerance/ diabetesImpaired glucose tolerance/ diabetes
GoiterGoiter
Ear, nose throat and dental problemsEar, nose throat and dental problems
Congestive cardiac failure/ arrythmiaCongestive cardiac failure/ arrythmia
HypertensionHypertension
Visual field defectsVisual field defects
AA – Arthralgias/– Arthralgias/
ArthritisArthritis
BB – BP raised– BP raised
CC – Carpal– Carpal
TunnelTunnel
DD – Diabetes– Diabetes
EE – Enlarged– Enlarged
OrgansOrgans
FF – Field defect– Field defect

37. It be showed largenessIt be showed largeness
in the size of nose, ears , lipsin the size of nose, ears , lips
It be showed largenessIt be showed largeness
in the size of tonguein the size of tongue
It be showedIt be showed
growth in handsgrowth in hands
Typical facies of acromegalyTypical facies of acromegaly

38. Typical facies of acromegalyTypical facies of acromegaly
Frontal bossingFrontal bossing
Thickening of the noseThickening of the nose
MacroglossiaMacroglossia
PrognathismPrognathism

39. Separation of the teethSeparation of the teeth
on the lower jawon the lower jaw

40. Image of a radiotherapy machine.Image of a radiotherapy machine.
The patient lies within a fixed mask that targets the radiation preciselyThe patient lies within a fixed mask that targets the radiation precisely
A magnetic resonance imaging (MRI) machine.A magnetic resonance imaging (MRI) machine.
The patient slides into the machine andspinning magnets areThe patient slides into the machine andspinning magnets are
used to create an image of the pituitary gland and the surrounding tissueused to create an image of the pituitary gland and the surrounding tissue

41. Typical Skull X-RayTypical Skull X-Ray
(Thickening of the Calvarium)(Thickening of the Calvarium)
of an Acromegalic patientof an Acromegalic patient
Lateral skull X-rayLateral skull X-ray
The bones of the skull are normal.The bones of the skull are normal.
Regular sella (arrow)Regular sella (arrow)

42. In the cefalometric radiograms, an enlargementIn the cefalometric radiograms, an enlargement
in the sella tursica and prognathismin the sella tursica and prognathism
and obliquity in angulus mandibula were observedand obliquity in angulus mandibula were observed

43. Complications of acromegalyComplications of acromegaly
Cardiovascular:Cardiovascular:
 Ischemic heart diseaseIschemic heart disease
 CardiomyopathyCardiomyopathy
 Congestive heart failureCongestive heart failure
 ArrhythmiasArrhythmias
 HypertensionHypertension
Respiratory:Respiratory:
 KyphosisKyphosis
 Obstructive sleep apneaObstructive sleep apnea
Metabolic:Metabolic:
 Diabetes mellitus/IGTDiabetes mellitus/IGT
 HyperlipidemiaHyperlipidemia
Neurologic:Neurologic:
Carpal Tunnel syndromeCarpal Tunnel syndrome
StrokeStroke
Neoplastic:Neoplastic:
CoorectalCoorectal
Breast and prostate -Breast and prostate -
uncertainuncertain
Musculoskeletal:Musculoskeletal:
DegenerativeDegenerative
arthropathyarthropathy
Calcific discopathy,Calcific discopathy,
pyrophosphatepyrophosphate
arthropathyarthropathy

44. Treatment of acromegalyTreatment of acromegaly
Somatostatin analogues (SSAs):Somatostatin analogues (SSAs):
OctreotideOctreotide ((SandostatinSandostatin)) and lanreotideand lanreotide ((SomatulineSomatuline
DepotDepot)) 50 mcg s/c tid; can increase to 500 mcg tid; doses50 mcg s/c tid; can increase to 500 mcg tid; doses
of 300-600 mcg/day or higher seldom result in additionalof 300-600 mcg/day or higher seldom result in additional
benefit.benefit. LanreotideLanreotide is given as a long-actingis given as a long-acting
subcutaneous injection once a month.subcutaneous injection once a month.
Dopamine agonists:Dopamine agonists:
BromocriptineBromocriptine (Parlodel)(Parlodel) 20-30 mg PO qd (10-6020-30 mg PO qd (10-60
mg/day)mg/day) in divided doses. Safety not demonstrated atin divided doses. Safety not demonstrated at
>100 mg/d.>100 mg/d.
CabergolineCabergoline (Dostinex)(Dostinex)
Growth hormone antagonistsGrowth hormone antagonists::
blocks the effect of growth hormone on body tissues.blocks the effect of growth hormone on body tissues.
PegvisomantPegvisomant (Somavert)(Somavert) 40 mg s/c40 mg s/c
10 mg s/c qd initially; may increase or decrease q 4 – 610 mg s/c qd initially; may increase or decrease q 4 – 6
week by 5-mg increments as determined by IGF-I levels;week by 5-mg increments as determined by IGF-I levels;
not to exceed 30 mg/d.not to exceed 30 mg/d.

45. SurgerySurgery
 Acromegaly is traditionally treated withAcromegaly is traditionally treated with transsphenoidaltranssphenoidal
pituitary surgery and adenoma removalpituitary surgery and adenoma removal
 Endonasal Transphenoidal surgeryEndonasal Transphenoidal surgery
 Septal Pushover/Direct SphenoidotomySeptal Pushover/Direct Sphenoidotomy
 Endoscopic approachEndoscopic approach
Radio-therapyRadio-therapy
Conventional radiation therapyConventional radiation therapy this type of radiation isthis type of radiation is
usually given every weekday over four to six weeks. It may takeusually given every weekday over four to six weeks. It may take
five to 10 years or more for your growth hormone levels tofive to 10 years or more for your growth hormone levels to
return to normalreturn to normal
Stereotactic radiosurgeryStereotactic radiosurgery Radiation can also be givenRadiation can also be given
stereotactically, with precisely focused, intense beams aimed atstereotactically, with precisely focused, intense beams aimed at
a tumor from multiple directions. This strategy can deliver aa tumor from multiple directions. This strategy can deliver a
high dose of radiation to tumor cells while limiting the amount ofhigh dose of radiation to tumor cells while limiting the amount of
radiation to nearby normal tissuesradiation to nearby normal tissues
Current stereotactic technologies deliver radiation with aCurrent stereotactic technologies deliver radiation with a
gamma knifegamma knife, a linear accelerator or a proton beam, a linear accelerator or a proton beam

46. Icsenko-Cushing’s diseaseIcsenko-Cushing’s disease
CORTICOTROPH ADENOMASCORTICOTROPH ADENOMAS
(small basophilic microadenomas that(small basophilic microadenomas that
secret ACTH)secret ACTH)
is a disease, which is manifested by theis a disease, which is manifested by the
bilateral hyperplasia of adrenal glands,bilateral hyperplasia of adrenal glands,
increased secretion of ACTH and hormonesincreased secretion of ACTH and hormones
of adrenal cortex.of adrenal cortex.
First, the disease was described by theFirst, the disease was described by the
RussianRussian neuropatolologist N.M. Icsenkoneuropatolologist N.M. Icsenko
in 1924in 1924.. In 1932In 1932 the same symptom wasthe same symptom was
described by the Americandescribed by the American neurosurgeonneurosurgeon
Harvey Cushing.Harvey Cushing.

47. Icsenko-Cushing’s disease andIcsenko-Cushing’s disease and
Icsenko-Cushing’s syndromeIcsenko-Cushing’s syndrome
Icsenko-Cushing’s syndromeIcsenko-Cushing’s syndrome
is a syndrome due to excess cortisolis a syndrome due to excess cortisol
from pituitary, adrenal or other sourcesfrom pituitary, adrenal or other sources
(exogenous glucocorticoids, ectopic(exogenous glucocorticoids, ectopic
ACTH, etc.)ACTH, etc.)
Icsenko-Cushing’s diseaseIcsenko-Cushing’s disease
is hypercortisolism due to excess pituitaryis hypercortisolism due to excess pituitary
secretion of ACTH (about 70% of cases ofsecretion of ACTH (about 70% of cases of
endogenous Icsenko-Cushing’sendogenous Icsenko-Cushing’s
syndrome)syndrome)

48. Icsenko-Cushing’s diseaseIcsenko-Cushing’s disease
Centripetal obesityCentripetal obesity
Moon faceMoon face
Buffalo humpBuffalo hump
Skin atrophySkin atrophy
Easily bruisedEasily bruised
StriaeStriae
Cutaneous fungalCutaneous fungal
infectionsinfections
HyperpigmentationHyperpigmentation
Oligo- or amenorrheaOligo- or amenorrhea
Hirsutism and VirilizationHirsutism and Virilization
with adrenal tumorswith adrenal tumors

49. Icsenko-Cushing’s diseaseIcsenko-Cushing’s disease
Proximal muscle wasting &Proximal muscle wasting &
weaknessweakness
OsteoporosisOsteoporosis
Glucose intolerance orGlucose intolerance or
steroid diabetessteroid diabetes
HypokalemiaHypokalemia
ThromboembolismThromboembolism
DepressionDepression
InfectionInfection
GlaucomaGlaucoma

50. Progressive Obesity ofProgressive Obesity of
Icsenko-Cushing’s DiseaseIcsenko-Cushing’s Disease
Age 6Age 6 Age 7Age 7 Age 8Age 8 Age 9Age 9 Age 11Age 11

51. TREATMENT OF ICSENKO-CUSHING DISEASETREATMENT OF ICSENKO-CUSHING DISEASE
ACTH-DependentACTH-Dependent
HypercortisolismHypercortisolism
Pituitary MRI Petrosal sinusPituitary MRI Petrosal sinus
ACTH samplingACTH sampling
ACTH-secreting pituitary adenomaACTH-secreting pituitary adenoma
Consider chest/Abd imagingConsider chest/Abd imaging
Ectopic ACTH excludedEctopic ACTH excluded
Transsphenoidal surgical resectionTranssphenoidal surgical resection
Biochemical cureBiochemical cure Persistent hypercortisolismPersistent hypercortisolism
PituitaryPituitary
irradiationirradiation
andand//oror
SteroidogenicSteroidogenic
inhibitorsinhibitors
ADRENALECTOMYADRENALECTOMY
Serial biochemical and MRISerial biochemical and MRI
evaluationevaluation
GlucocorticoidGlucocorticoid
replacement,replacement,
if neededif needed

52. GONADOTROPH ADENOMASGONADOTROPH ADENOMAS
 Majority produce FSH, some FSH and LH, rarely only LHMajority produce FSH, some FSH and LH, rarely only LH
 Occur in middle-aged men and women usually areOccur in middle-aged men and women usually are
macroadenomasmacroadenomas
 May cause amenorrhea or galactorrhea,May cause amenorrhea or galactorrhea, ↓ libido in men↓ libido in men
THYROTHROPH ADENOMASTHYROTHROPH ADENOMAS
 produce TSH►hyperthyroidismproduce TSH►hyperthyroidism
NON-SECRETORY ADENOMASNON-SECRETORY ADENOMAS
 in 4th decade of lifein 4th decade of life
 may grow to large size- macroadenomas 1 cmmay grow to large size- macroadenomas 1 cm
 local mass effect: headache, visual disturbances andlocal mass effect: headache, visual disturbances and
panhypopituitarism:panhypopituitarism: hypogonadism, hypothyroidism,hypogonadism, hypothyroidism,
hypoadrenalismhypoadrenalism
 most consist of chromophobic cells or intenselymost consist of chromophobic cells or intensely
eosinophilic cellseosinophilic cells

53. GigantismGigantism
oror giantismgiantism, (from, (from GreekGreek gigasgigas,, gigantasgigantas ""
giantgiant") is a condition characterized by") is a condition characterized by
excessive height growth and bignessexcessive height growth and bigness
significantly abovesignificantly above average heightaverage height..
Height isHeight is 2.25 - 2.402.25 - 2.40 metres.metres.

54. The world's tallest peopleThe world's tallest people
Leonid StadnikLeonid Stadnik, Ukraine, 258 cm, Ukraine, 258 cm
Alexander SizonenkoAlexander Sizonenko, Russia, 250 cm, Russia, 250 cm
Yunsay ChangYunsay Chang, China, 242 cm, China, 242 cm
Radhuan CharbybaRadhuan Charbyba, Tunis, 237 cm, Tunis, 237 cm
Bao Si ShunBao Si Shun, China, 236 cm, China, 236 cm
Nasir SoomroNasir Soomro, Pakistan 236 cm, Pakistan 236 cm
Besad HusseinBesad Hussein, Britain, 236 cm, Britain, 236 cm
Yao DefenYao Defen,, JapanJapan, 236 cm, 236 cm
Leonid StadnikLeonid Stadnik Alexander SizonenkoAlexander Sizonenko Bao Si ShunBao Si Shun
Yao DefenYao Defen

55. Features of acromegaly/gigantism.Features of acromegaly/gigantism.
A 22-year-old man with gigantism due to excess growth hormone isA 22-year-old man with gigantism due to excess growth hormone is
shown to the left of his identical twin.shown to the left of his identical twin.
The increased height and prognathism.The increased height and prognathism.
Enlarged hand and foot of the
affected twin are apparent.
Their clinical features
began to diverge at the age of
approximately 13 years.

56. HYPOTHALAMIC SYNDROMEHYPOTHALAMIC SYNDROME
 Obesity is not cushingoid (not central)Obesity is not cushingoid (not central)
 Striae (pink and not very large)Striae (pink and not very large)
 Hypertension (constant or permanent)Hypertension (constant or permanent)
 Glucose intoleranceGlucose intolerance

58. Increased activateIncreased activate
of leptin receptorsof leptin receptors
in hypothalamusin hypothalamus
HyperleptinemiaHyperleptinemia
in plasmain plasma
Adipose depotAdipose depot
IncreasedIncreased
fat accumulationfat accumulation
High level ofHigh level of
leptin synthesisleptin synthesis
Increased food intakeIncreased food intake
reduced energy consumptionreduced energy consumption

59. HYPOTHALAMIC SYNDROMEHYPOTHALAMIC SYNDROME
Autonomic-vascular formAutonomic-vascular form
Sympatho-adrenaline crisisSympatho-adrenaline crisis:
Increasing pressureIncreasing pressure
TachycardiaTachycardia
Cardiac respirationCardiac respiration
PallorPallor
FearFear
TremblingTrembling
AgitationAgitation
Vago-insular crisis:Vago-insular crisis:
HypotentionHypotention
BradycardiaBradycardia
SweatingSweating
Heat sensationHeat sensation
Redness of the faceRedness of the face
Neuroendocrine formNeuroendocrine form
Violations of water-salt metabolismViolations of water-salt metabolism
Disturbance of thermoregulationDisturbance of thermoregulation
Oligo- or amenorrheaOligo- or amenorrhea
ObesityObesity
HypertensionHypertension
Neurotrophic formNeurotrophic form
Change the color of the skinChange the color of the skin
NarrowNarrow
Bright deviceBright device
Dryness and rashDryness and rash
on the skinon the skin
Early graying and hair lossEarly graying and hair loss
Sleep Disorders and VitalitySleep Disorders and Vitality
The attack sleepiness in other moment
Cataplexy
Acoustic and color nightmarish dreams

60. Treatment of hypothalamic syndromeTreatment of hypothalamic syndrome
Sympatho-adrenaline crisis:Sympatho-adrenaline crisis:
PiroksanPiroksan 1% - 1,0 g i/m1% - 1,0 g i/m
PiroksanPiroksan 0.015 1 tablet 3 times/day 3 weeks0.015 1 tablet 3 times/day 3 weeks
DopehitDopehit 0.25 1 tablet 3 times/day 3 weeks0.25 1 tablet 3 times/day 3 weeks
Vago-insular crisis:Vago-insular crisis:
Atropine sulfateAtropine sulfate 1% - 1,0 s/c1% - 1,0 s/c
Extract of belladonnaExtract of belladonna 0.015 1 tablet 3 times/day 3 weeks0.015 1 tablet 3 times/day 3 weeks
Nootropics:Nootropics:
LutsetamLutsetam 800 mg 2 times/day 3 weeks800 mg 2 times/day 3 weeks
Symptomatic therapy:Symptomatic therapy:
ATPATP 1.0 g i/m (10 days)1.0 g i/m (10 days)
Glutamic acidGlutamic acid 0.25 3 times/ day 3 weeks0.25 3 times/ day 3 weeks
Dehydration therapy:Dehydration therapy:
HypothiasidHypothiasid 50 – 100 mg/day50 – 100 mg/day
MgSO4MgSO4 25 % solution i/m 10 – 15 times25 % solution i/m 10 – 15 times
Physiotherapy:Physiotherapy:
Galvanizing hypothalamic nuclesGalvanizing hypothalamic nucles 10 days to 15 minutes10 days to 15 minutes
Hypocaloric diet:Hypocaloric diet: 1000-1500 kcal/day1000-1500 kcal/day