Hypopituitarism & Hyperpituitarism

Hypopituitarism & Hyperpituitarism

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

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4. The hypothalamic-pituitary axesThe hypothalamic-pituitary axes

5. HYPOTHALAMUS AND HYPOTHALAMUS AND
PITUITARY GLANDPITUITARY GLAND
HYPOPHYSISHYPOPHYSIS
ANTERIOR ANTERIOR
LOBELOBE
INTERMEDIATE INTERMEDIATE
LOBELOBE
POSTERIOR POSTERIOR
LOBELOBE
MelanotropinMelanotropin
ADH ADH
(vasopresin)(vasopresin)
OxytocinOxytocin
Basophile cellsBasophile cells
EosinophilicEosinophilic
cellscells Chromophobes Chromophobes
cellscells
ACTHACTH
TSHTSH
FSHFSH
ICSHICSH
TTHTTH
STGSTG
ProlactinProlactin

6. Hypothalamic releasing hormonesHypothalamic releasing hormones
Hypothalamic releasing hormone Effect on pituitaryEffect on pituitary
Corticotropin releasing Corticotropin releasing
hormone (CRH)hormone (CRH)
Stimulates ACTH secretionStimulates ACTH secretion
Thyrotropin releasing Thyrotropin releasing
hormone (TRH)hormone (TRH)
Stimulates TSH and Stimulates TSH and
Prolactin secretionProlactin secretion
Growth hormone releasing Growth hormone releasing
hormone (GHRH)hormone (GHRH)
Stimulates GH secretionStimulates GH secretion
SomatostatinSomatostatin Inhibits GH (and other Inhibits GH (and other
hormone) secretionhormone) secretion
Gonadotropin releasing Gonadotropin releasing
hormone (GnRH)hormone (GnRH)
Stimulates LH and FSH Stimulates LH and FSH
secretionsecretion
Prolactin releasing Prolactin releasing
hormone (PRH)hormone (PRH)
Stimulates PRL secretionStimulates PRL secretion
Prolactin inhibiting Prolactin 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 Stimulating Thyroid Stimulating
HormoneHormone (TSH) (TSH)
causes the thyroid gland to causes the thyroid gland to
produce and release thyroid produce and release thyroid
hormoneshormones
Growth HormoneGrowth Hormone (GH) (GH) regulates growth and metabolism regulates growth and metabolism
Adrenocorticotropic Adrenocorticotropic
Hormone (ACTH) Hormone (ACTH)
triggers the adrenals to release triggers the adrenals to release
the hormone cortisolthe hormone cortisol
Luteinizing Hormone (LH)Luteinizing Hormone (LH) menstrul cycle and reproduction menstrul cycle and reproduction
Follicle Stimulating Follicle Stimulating
Hormone (FSH) Hormone (FSH)
in the ovary stimulates the growth in the ovary stimulates the growth
of immature of immature Graatian folliclesGraatian follicles
to maturation. to maturation.
In men enhances the production In men enhances the production
of androgen-bilding protein by the of androgen-bilding protein by the
Sertoli cellsSertoli cells of the testes and is of the testes and is
critical for spermatogenesis critical for spermatogenesis
stimulates production of breast stimulates production of breast
milk and is necessary for normal milk and is necessary for normal
milk production during milk production during
breast feeding breast feedingProlactinProlactin (PRL) (PRL)

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

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

10. HypopituitarismHypopituitarism
is loss of function in an endocrine gland due to failure of is loss of function in an endocrine gland due to failure of
the pituitary gland to secrete hormones which the pituitary gland to secrete hormones which
stimulate that gland's function. stimulate that gland's function.
PanhypopituitarismPanhypopituitarism
This condition represents the loss of This 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 pituitary is also known as complete pituitary
failure.failure.
The terms Reye syndrome, Sheehan’s and The terms Reye syndrome, Sheehan’s and
Simmond’sSimmond’s syndromesyndrome refers to necrosis of the refers to necrosis of the
pituitary during the postpartum period. pituitary during the postpartum period.
Only the difference in Only the difference in Simmond’s syndromeSimmond’s syndrome is that is that
although it is very similar medical condition can take although it is very similar medical condition can take
place in both males and females and it is independent place 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,
apoplexy apoplexy
 Iatrogenic Iatrogenic - Radiation, surgery, withholding previous - Radiation, surgery, withholding previous
chronic glucocorticoid replacement chronic 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,
hemochromatosis hemochromatosis
InfectionsInfections - - Tuberculosis, syphilis, meningitis Tuberculosis, 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, Postpartum Simmond’s disease, Postpartum
pituitary necrosis, Postpartum ishemic necrosis of pituitary necrosis, Postpartum ishemic necrosis of
the anterior pituitary, Postpartum the anterior pituitary, Postpartum
panhypopituitarismpanhypopituitarism
Sheehan’s syndromeSheehan’s syndrome, or , or necrosis of the necrosis of the
pituitary glandpituitary gland, is a rare complication of , is a rare complication of
postpartum hemorrhage initially postpartum hemorrhage initially
described in 1937described in 1937. .
Sheehan’s syndrome was named when the Sheehan’s syndrome was named when the
English pathologist English pathologist Harold Leeming Harold Leeming
Sheehan (1900-1988)Sheehan (1900-1988) reviewed and reviewed and
described the syndrome.described the syndrome.
Polish physician Polish physician Leon Konrad Glinski (1870-Leon Konrad Glinski (1870-
1918)1918) counts for the other name, counts for the other name, Glinski Glinski
Simmon’s syndrome.Simmon’s syndrome.

13. Laboratory diagnostic of Laboratory 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)
TT
44 (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 hormone Serum 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 of Standard therapy of
Sheehan’s syndromeSheehan’s syndrome
Hormone replacement medications may Hormone replacement medications may
include:include:
Corticosteroids Corticosteroids 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 and testosterone in men and
estrogen or a combination of estrogen and estrogen or a combination of estrogen and
progesterone in womenprogesterone in women

15. Glucocorticoids Glucocorticoids used in adrenal insufficiency: used in adrenal insufficiency:
HydrocortisoneHydrocortisone 20-30 mg/d PO divided bid 20-30 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/c 6-125 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 doses 180 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/week 0.3 mg/kg/week
Testosterone Testosterone - - 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 cycle repeat cycle
Treatment of Sheehan’s syndromeTreatment of Sheehan’s syndrome

16. PITUITARY NANISMPITUITARY NANISM
HYPOPHYSIAL MICROSOMIA, HYPOPHYSIAL HYPOPHYSIAL MICROSOMIA, HYPOPHYSIAL
NANOCORMIANANOCORMIA
it is a genetic disease caused by it is a genetic disease caused by
absolute or relative deficiency of STH absolute or relative deficiency of STH
in the organism. in the organism.
The sudden growth inhibition is marked The 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 by First 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 the is 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 adult resulting in less than normal adult
stature.stature.
Abnormally short stature. Abnormally short stature.
The average adult height of The average adult height of male male and and female female
dwarfismdwarfism sufferers are sufferers are 130130 cmcm and and 120 cm120 cm
respectively. respectively.
Also known as Also known as nanismnanism..

18. Etiology and pathogenesisEtiology and pathogenesis
pituitary nanism pituitary nanism
Congenital Congenital
insufficiencyinsufficiency
autosomal – recessiveautosomal – recessive
inheritance inheritance
(idiopathic forms)(idiopathic forms)
Acquired insufficiencyAcquired insufficiency
pituitary tumorpituitary tumor
craniopharyngiomacraniopharyngioma
injury of the pituitary injury of the pituitary
sarcoidosissarcoidosis
toxoplasmosistoxoplasmosis
infectioninfection
vascular pathologyvascular pathology
PeripheralPeripheral
resistance resistance
of GHof GH
Growth deceleration and differentiation of skeleton Growth deceleration and differentiation of skeleton
Absolute Absolute
deficiency ofdeficiency of
GH GH
Relative Relative
deficiency ofdeficiency of
GHGH

19. Classification of pituitary dwarfismClassification of pituitary dwarfism
Organic: Organic:
traumatrauma
neoplasmsneoplasms
infection infection
Idiopatic:Idiopatic:
primary primary
secondarysecondary
due to hypothalamic due to hypothalamic
deficiencydeficiency
Panhypopituitarism Panhypopituitarism
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 instances in other instances
a hereditary basis cannot be established) a hereditary basis cannot be established)

20. PhysicalPhysical
Children Children
The standing height The standing height
standard deviation score standard deviation score
is usually below -2 is usually below -2
Growth velocity is below the Growth velocity is below the
10-25 th percentile, 10-25 th percentile,
which reflects growth which reflects growth
decelerationdeceleration
Increased subcutaneous fat Increased subcutaneous fat
is present, especially is present, especially
around the trunkaround the trunk
The face is immature, with a The face is immature, with a
prominent forehead and prominent forehead and
depressed midfacial depressed midfacial
developmentdevelopment
Dentition is delayedDentition is delayed
The average age of pubertal The average age of pubertal
onset is delayed in both onset is delayed in both
boys and girlsboys and girls
Adults
Reduced lean body mass Reduced lean body mass
and increased weight, with and increased weight, with
body fat mass body fat mass
predominantly in the predominantly in the
abdominal region abdominal region
Thin and dry skin Thin and dry skin
Cool peripheries Cool peripheries
Poor venous access Poor venous access
Reduced muscle mass and Reduced muscle mass and
strength and reduced strength and reduced
exercise performance exercise performance
Depressed affect Depressed affect
Labile emotions Labile 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 cm Girl , 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 the is 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 form First, 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 as also known as
neurogenic, central, or cranial DI is the result of partial or neurogenic, 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 renal is 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 polyuric is a polyuric
syndrome secondary to excess fluid intake. Though structural syndrome secondary to excess fluid intake. Though structural
abnormalities may be the cause, it is generally a manifestation abnormalities may be the cause, it is generally a manifestation
of primary polydipsia, psychiatric disease, or secondary of 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
Idiopathic Idiopathic
Secondary/Secondary/
acquiredacquired
Trauma:Trauma:
Head injury Head injury
Post surgeryPost surgery
(transcranial, (transcranial,
transphenoidal)transphenoidal)
Tumour:Tumour:
CraniopharyngiomCraniopharyngiom
Germ cell tumoursGerm cell tumours
MetastasesMetastases
Pituitary Pituitary
macroadenoma macroadenoma
Inflammatory:Inflammatory:
Granulonulomas Granulonulomas
SarcoidosisSarcoidosis
HistiocytosisHistiocytosis
Infection Infection
Infundibulo-Infundibulo-
neurohypophysitisneurohypophysitis
Guillaine-Barre Guillaine-Barre
SyndromeSyndrome
AutoimmuneAutoimmune
Vascular:Vascular:
AneurysmAneurysm
Infarction Infarction
Sheehan's Sheehan's
syndromesyndrome
Sickle cell diseaseSickle cell disease
PregnancyPregnancy
(associated with vasopressinase) (associated with vasopressinase)
Nephrogenic DI Nephrogenic DI
Dipsogenic DI Dipsogenic DI
CompulsiveCompulsive
water drinkingwater drinking
AssociatedAssociated
with affective with affective
disordersdisorders
Structural/Structural/
organic organic
hypothalamic hypothalamic
diseasedisease::
Sarcoid
Tumours involving
hypothalamus
Head injury
Tuberculous
meningitis
PrimaryPrimary
SecondarySecondary
Genetic:Genetic:
X-linked recessive X-linked recessive
Autosomal recessive Autosomal recessive
Autosomal dominantAutosomal dominant
Idiopathic:Idiopathic:
Chronic renal disease Chronic renal disease
Metabolic disease Metabolic disease
Drug induced Drug induced
Osmotic diuretics Osmotic diuretics
Systemic disorders Systemic disorders
PregnancyPregnancy

26. Diabetes insipidus (DI)Diabetes insipidus (DI)
HYPOTHALAMIC DIHYPOTHALAMIC DI NEPHROGENIC (RENAL)NEPHROGENIC (RENAL)
DIDI
absolute deficiency of absolute deficiency of
antidiuretic hormoneantidiuretic hormone
genetic pathology of genetic pathology of
ADH receptors, ADH receptors,
it inherits it 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 during damage 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 nodes sarcoidosis (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 thirst excessive thirst

excessive urine production (up to a dozen or more excessive urine production (up to a dozen or more
quarts a day) of diluted, colorless urine quarts a day) of diluted, colorless urine

dehydration dehydration

dry hands dry 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 imbalance electrolyte 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 defects Structural or functional defects
in ADH receptors or aquaporinsin ADH receptors or aquaporins
OnsetOnset
·congenital defect of congenital defect of
hypothalamus or pituitary hypothalamus or pituitary
·acquired acquired
·congenital defect of receptors congenital defect of receptors
or aquaporins or aquaporins
·acquired acquired
CausesCauses trauma or disease of pituitary or trauma or disease of pituitary or
hypothalamushypothalamus
trauma or disease of the kidneytrauma or disease of the kidney
Signs & Signs &
TestsTests
polyuria polyuria
·polydispsia polydispsia
·electrolyte imbalance electrolyte imbalance
·possible dehydration possible dehydration
·low ADH levels low ADH levels
·urinalysis low specific gravity urinalysis low specific gravity
polyuria polyuria
·polydispsia polydispsia
·electrolyte imbalance electrolyte imbalance
·possible dehydration possible dehydration
·low ADH levels low ADH levels
·urinalysis low specific gravity urinalysis low specific gravity
DiagnosisDiagnosis ·rule out other causes rule out other causes
·imagery of pituitary and imagery of pituitary and
hypothalamus hypothalamus
·water deprivation test water deprivation test
·ADH trial ADH trial
·rule out other causes rule out other causes
·rule out CDI rule out CDI
TreatmentTreatment desmopressin desmopressin oral chlorothiazide oral chlorothiazide
·chloropropamide chloropropamide
·NSAIDs NSAIDs
·restrict salt restrict salt
PrognosisPrognosis variable variable
·not life-threatening if treated not life-threatening if treated
and fluid intake maintained and fluid intake maintained
congenital NDI--chronic congenital NDI--chronic
·acquired NDI--variable acquired NDI--variable

30. Treatment of Diabetes InsipidusTreatment of Diabetes Insipidus
Central DI: Central DI:
long-acting VPlong-acting VP analogue DDAVP: analogue DDAVP:
intranasal spray intranasal spray H-DesmopressinH-Desmopressin single dose single dose
consists of consists of 10 mcg10 mcg of Desmopressin acetate of Desmopressin acetate
(5-100 mcg daily), (5-100 mcg daily),
AdiupressinAdiupressin («Ameda Pharma», India) is used («Ameda Pharma», India) is used
intranasal intranasal 2–8 gutters2–8 gutters (10-40 mcg) (10-40 mcg) a day. a day.
Antidiuretic effect shows Antidiuretic effect shows in an hourin an hour, , maximal action maximal 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).
Oral Oral Minirin Minirin is used by is used by 100–200 mcg a 100–200 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 hydrochlorothiazide hydrochlorothiazide 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 mg Clozapine 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’s Itsenko-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 outside Extends outside
the sellathe sella
Presents often withPresents often with
chiasmal compressionchiasmal compression
syndromesyndrome

34. Causes of acromegalyCauses of acromegaly
SOMATOTROPH ADENOMAS SOMATOTROPH ADENOMAS
Eosinophilic pituitary adenoma
Pituitary tumors: microadenomas (pituitary microadenomas (pituitary
tumors less than 1 cm in size); tumors less than 1 cm in size);
macroadenomas (pituitary tumors greater macroadenomas (pituitary tumors greater
than 1cm)than 1cm)

Nonpituitary tumors: Nonpituitary tumors: by tumors of the by tumors of the
pancreas, lungs, and other parts of the brain pancreas, 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 decreased Erectile 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
A A – Arthralgias/ – Arthralgias/
ArthritisArthritis
B B – BP raised– BP raised
CC – Carpal – Carpal
TunnelTunnel
DD – Diabetes – Diabetes
E E – 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 showed It 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 teeth Separation of the teeth
on the lower jaw on 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 precisely The 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 are The patient slides into the machine andspinning magnets are
used to create an image of the pituitary gland and the surrounding tissue used 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 patient of 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 enlargement In the cefalometric radiograms, an enlargement
in the sella tursica and prognathism in 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

Cardiomyopathy Cardiomyopathy

Congestive heart failureCongestive heart failure

ArrhythmiasArrhythmias

HypertensionHypertension
Respiratory:Respiratory:

KyphosisKyphosis

Obstructive sleep apneaObstructive sleep apnea
Metabolic:Metabolic:

Diabetes mellitus/IGTDiabetes mellitus/IGT

Hyperlipidemia Hyperlipidemia
Neurologic:Neurologic:
Carpal Tunnel syndromeCarpal Tunnel syndrome
Stroke Stroke
Neoplastic: Neoplastic:
Coorectal Coorectal
Breast and prostate - Breast and prostate -
uncertainuncertain
Musculoskeletal: Musculoskeletal:
Degenerative Degenerative
arthropathy arthropathy
Calcific discopathy, Calcific discopathy,
pyrophosphate pyrophosphate
arthropathyarthropathy

44. Treatment of acromegalyTreatment of acromegaly
Somatostatin analogues (SSAs):Somatostatin analogues (SSAs):
Octreotide Octreotide ((SandostatinSandostatin)) and lanreotide and lanreotide ((Somatuline Somatuline
DepotDepot)) 50 mcg s/c tid; can increase to 500 mcg tid; doses 50 mcg s/c tid; can increase to 500 mcg tid; doses
of 300-600 mcg/day or higher seldom result in additional of 300-600 mcg/day or higher seldom result in additional
benefit.benefit. LanreotideLanreotide is given as a long-acting is given as a long-acting
subcutaneous injection once a month. subcutaneous injection once a month.
Dopamine agonists: Dopamine agonists:
Bromocriptine Bromocriptine (Parlodel)(Parlodel) 20-30 mg PO qd (10-60 20-30 mg PO qd (10-60
mg/day) mg/day) in divided doses. Safety not demonstrated at in divided doses. Safety not demonstrated at
>100 mg/d. >100 mg/d.
Cabergoline Cabergoline (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.
Pegvisomant Pegvisomant (Somavert)(Somavert) 40 mg s/c40 mg s/c
10 mg s/c qd initially; may increase or decrease q 4 – 6 10 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 with Acromegaly is traditionally treated with transsphenoidal transsphenoidal
pituitary surgery and adenoma removalpituitary surgery and adenoma removal

Endonasal Transphenoidal surgeryEndonasal Transphenoidal surgery

Septal Pushover/Direct Sphenoidotomy Septal Pushover/Direct Sphenoidotomy

Endoscopic approachEndoscopic approach
Radio-therapyRadio-therapy
Conventional radiation therapy Conventional radiation therapy this type of radiation is this type of radiation is
usually given every weekday over four to six weeks. It may take usually given every weekday over four to six weeks. It may take
five to 10 years or more for your growth hormone levels to five to 10 years or more for your growth hormone levels to
return to normal return to normal
Stereotactic radiosurgeryStereotactic radiosurgery Radiation can also be given Radiation can also be given
stereotactically, with precisely focused, intense beams aimed at stereotactically, with precisely focused, intense beams aimed at
a tumor from multiple directions. This strategy can deliver a a tumor from multiple directions. This strategy can deliver a
high dose of radiation to tumor cells while limiting the amount of high dose of radiation to tumor cells while limiting the amount of
radiation to nearby normal tissues radiation to nearby normal tissues
Current stereotactic technologies deliver radiation with a Current 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 the is a disease, which is manifested by the
bilateral hyperplasia of adrenal glands, bilateral hyperplasia of adrenal glands,
increased secretion of ACTH and hormones increased secretion of ACTH and hormones
of adrenal cortex.of adrenal cortex.
First, the disease was described by the First, the disease was described by the
Russian Russian neuropatolologist N.M. Icsenko neuropatolologist N.M. Icsenko
in 1924in 1924. . In 1932In 1932 the same symptom was the same symptom was
described by the American described by the American neurosurgeon neurosurgeon
Harvey Cushing.Harvey Cushing.

47. Icsenko-Cushing’s disease and Icsenko-Cushing’s disease and
Icsenko-Cushing’s syndrome Icsenko-Cushing’s syndrome
Icsenko-Cushing’s syndromeIcsenko-Cushing’s syndrome
is a syndrome due to excess cortisol is a syndrome due to excess cortisol
from pituitary, adrenal or other sources from 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 pituitary is hypercortisolism due to excess pituitary
secretion of ACTH (about 70% of cases of secretion of ACTH (about 70% of cases of
endogenous Icsenko-Cushing’s endogenous 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 fungal Cutaneous fungal
infectionsinfections
HyperpigmentationHyperpigmentation
Oligo- or amenorrheaOligo- or amenorrhea
Hirsutism and Virilization Hirsutism 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 or Glucose intolerance or
steroid diabetessteroid diabetes
HypokalemiaHypokalemia
ThromboembolismThromboembolism
DepressionDepression
InfectionInfection
GlaucomaGlaucoma

50. Progressive Obesity of Progressive Obesity of
Icsenko-Cushing’s Disease Icsenko-Cushing’s Disease
Age 6Age 6 Age 7 Age 7 Age 8 Age 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 are Occur 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 and local mass effect: headache, visual disturbances and
panhypopituitarism:panhypopituitarism: hypogonadism, hypothyroidism, hypogonadism, hypothyroidism,
hypoadrenalismhypoadrenalism
most consist of chromophobic cells or intensely most consist of chromophobic cells or intensely
eosinophilic cellseosinophilic cells

53. GigantismGigantism
or or giantismgiantism, (from , (from GreekGreek gigasgigas, , gigantasgigantas " "
giantgiant") is a condition characterized by ") is a condition characterized by
excessive height growth and bigness excessive height growth and bigness
significantly above significantly above average heightaverage height. .
Height is Height 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 Defen Yao Defen

55. Features of acromegaly/gigantism. Features of acromegaly/gigantism.
A 22-year-old man with gigantism due to excess growth hormone is A 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 activate Increased activate
of leptin receptors of leptin receptors
in hypothalamusin hypothalamus
HyperleptinemiaHyperleptinemia
in plasma in plasma
Adipose depotAdipose depot
Increased Increased
fat accumulation fat accumulation
High level ofHigh level of
leptin synthesisleptin synthesis
Increased food intakeIncreased food intake
reduced energy consumption reduced energy consumption

59. HYPOTHALAMIC SYNDROMEHYPOTHALAMIC SYNDROME
Autonomic-vascular form Autonomic-vascular form
Sympatho-adrenaline crisisSympatho-adrenaline crisis:
Increasing pressureIncreasing pressure
TachycardiaTachycardia
Cardiac respirationCardiac respiration
Pallor Pallor
FearFear
TremblingTrembling
Agitation Agitation
Vago-insular crisis:Vago-insular crisis:
HypotentionHypotention
BradycardiaBradycardia
SweatingSweating
Heat sensationHeat sensation
Redness of the face Redness of the face
Neuroendocrine formNeuroendocrine form
Violations of water-salt metabolismViolations of water-salt metabolism
Disturbance of thermoregulationDisturbance of thermoregulation
Oligo- or amenorrhea Oligo- or amenorrhea
Obesity Obesity
Hypertension Hypertension
Neurotrophic formNeurotrophic form
Change the color of the skinChange the color of the skin
NarrowNarrow
Bright device Bright device
Dryness and rash Dryness and rash
on the skin on 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/m 1% - 1,0 g i/m
PiroksanPiroksan 0.015 1 tablet 3 times/day 3 weeks 0.015 1 tablet 3 times/day 3 weeks
DopehitDopehit 0.25 1 tablet 3 times/day 3 weeks 0.25 1 tablet 3 times/day 3 weeks
Vago-insular crisis:Vago-insular crisis:
Atropine sulfateAtropine sulfate 1% - 1,0 s/c 1% - 1,0 s/c
Extract of belladonnaExtract of belladonna 0.015 1 tablet 3 times/day 3 weeks 0.015 1 tablet 3 times/day 3 weeks
Nootropics: Nootropics:
Lutsetam Lutsetam 800 mg 2 times/day 3 weeks800 mg 2 times/day 3 weeks
Symptomatic therapy:Symptomatic therapy:
ATP ATP 1.0 g i/m (10 days)1.0 g i/m (10 days)
Glutamic acidGlutamic acid 0.25 3 times/ day 3 weeks 0.25 3 times/ day 3 weeks
Dehydration therapy:Dehydration therapy:
Hypothiasid Hypothiasid 50 – 100 mg/day50 – 100 mg/day
MgSO4 MgSO4 25 % solution i/m 10 – 15 times 25 % solution i/m 10 – 15 times
Physiotherapy:Physiotherapy:
Galvanizing hypothalamic nuclesGalvanizing hypothalamic nucles 10 days to 15 minutes 10 days to 15 minutes
Hypocaloric diet:Hypocaloric diet: 1000-1500 kcal/day1000-1500 kcal/day