TUTOR GUIDE

ENDOCRINE & METABOLIC BLOCK

WEEK 3 : Pituitary & hypothalamus
HAGRID, the tall boy
Overall week objectives:
1. Describe the embryology, anatomy, histology and function of the hypothalamus, pituitary, and
pineal gland including their blood supply
2. Describe the topography of hypothalamus and pituitary and their correlation with the surrounding
structures
3. Describe the anatomic and functional relations of the pituitary gland with the hypothalamus
4. List the hormones secreted by anterior and posterior pituitary and describe the function and control
of each (GH, FSH, LH, TSH, ACTH, prolactine, vasopressin, oxytocin)
5. Describe hypothalmo-pituitary axis and feedback mechanism
6. Describe the hormone secreted by pineal gland and its correlation with circadian rhythms.
7. In histological slide, recognize the adeno and neurohypophysis; identify the principal cell types in
both. Relate the different cell types to hormone production.
8. Describe the patophysiology of disorders which caused by pituitary-hormone-secreting disorder
9. Describe the natural history of pituitary tumour and its classification
10. Describe correlation of clinical finding with hypothalamus-hypophysis disorders
Case Objective :
1. Describe the embryology, anatomy, histology and function of the pituitary gland
2. Describe the anatomic and functional relations of the pituitary gland with the hypothalamus
3. List the hormones secreted by anterior and posterior pituitary and describe the function and control
of each
4. Describe the role of Growth Hormone in growth and metabolism
5. Describe Growth-promoting action of GH on bones and tissue
6. Correlate clinical findings with abnormal secretion of GH and describe the natural history of
untreated acromegaly/gigantism
7. Describe the mechanism of action of drugs used in the management of pituitary disorders

THE TUTOR GUIDE MUST NEVER BE GIVEN TO STUDENTS

ADENOMA HYPOPHYSIS/PITUITARY ADENOMA

Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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Hipofisis merupakan kelenjar endokrin yang mendapat stimulus dari hypothalamus, terletak pada dasar
cranium pada sella tursika, , berukuran 15x10x6 mm, berat 600 mg, dan terdiri dari 2 lobus. Lobus anterior
(adenohipofisis) memproduksi 6 hormon penting (ACTH, GH, Prolaktin, TSH, LH dan FSH) dan lobus posterior
(neurohipofisis) mensekresi vasopressin dan oxytocin. Adenohipofisis merupakan bagian terbesar (2/3 bagian) dan
merupakan jenis tumor hipofisis (adenoma) yang paling sering terjadi.
Adenoma hipofisis menimbulkan masalah oleh karena 3 hal, yaitu akibat pendesakan ke jaringan sekitar,
akibat hipersekresi hormone tertentu ataupun hiposekresi akibat kompresi jaringan kelenjar yang normal. Menurut
fungsinya, tumor ini dapat diklasifikasikan menjadi 2:
1. Non-sekresi/non-fungsional; karena ketidakaktifan endokrinnya
2. Sekresi/fungsional (85-90%); memproduksi hormone-hormon tertentu secara berlebihan.
Peningkatan hormone prolaktin (prolaktinemia) menyebabkan gejala klinis galatorea, impotensi, infertility,
amenorrhea, ginekomasti. Peningkatan sekresi GH menyebabkan akromegali bila terjadi sesudah epifisis menutup
ataupun gigantisme yang terjadi sebelum epifisis menutup (sebelum usia 15 tahun). Gigantisme sangat jarang
terjadi dimana prevalensinya 3/1.000.000 penduduk, terjadi pembesaran tubuh yang simetris untuk semua tulang
dan jaringan lunaknya. Berbeda dengan akromegali dimana terjadi pembesaran tulang atau jaringan pada daerah
akral. Untuk diagnosis peningkatan sekresi GH akibat adenoma hipofisis dapat dilakukan tes toleransi glukosa oral
(TTGO). Pada kondisi normal, setelah pemberian glukosa oral akan terjadi penekanan sekresi GH. Jika setelah
pemberian glukosa kadar GH tidak turun dapat menkonfirmasi adanya adenoma hipofisis.
Seperti halnya tumor hipofisis, kraniofaringioma, meningioma dan aneurisma dapat menyebabkan
gangguan endokrin, namun umumnya berupa hipopituitarisme akibat penekanan hipofisis serta hiperprolaktinemia.
Sedangkan pada adenoma hipofisis terjadi peningkatan sekresi hormone.
Pemeriksaan penunjang untuk adenoma hipofisis diawali dengan foto polos kepala dimana dapat terlihat
pelebaran daerah sella, bahkan dapat terlihat destruksi dorsum sella. Bisa dilanjutkan dengan pemeriksaan CT scan
atau MRI kepala. Dilakukan pemeriksaan fungsi hormone dengan mengukur kadarnya di dalam darah. Yang
diperiksa biasanya adalah kadar kortisol, fungsi tiroid (TSH dan free tiroksin), fungsi gonad (FSH, LH, testosterone,
estradiol), GH, serta prolaktin.
Menurut ukurannya adenoma dibagi menjadi mikroadenoma jika diameternya <10 mm, dan makroadenoma
jika diameternya > 10 mm.
Prinsip tatalaksana pada adenoma hipofisis :
Menghambat hipersekresi
Mempertahankan fungsi normal hipofisis
Menghilangkan efek penekanan tumor
Indikasi operasi :
Mikroadenoma fungsional yang tidak membaik dengan terapi hormonal/radioterapi
Makroadenoma yang telah menimbulkan keluhan neurologis

Komplikasi pasca operasi :

Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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Diabetes insipidus
Panhipopituitarisme

Adenoma hipofisis dapat rekurens sebanyak 12-16% dalam 10 tahun setelah operasi. Sebaiknya dilakukan
pemeriksaan serial MRI setiap tahun untuk pemantauan. Angka kematian dapat diturunkan dengan meniadakan
penekanan massa tumor, dan mengurangi sekresi GH dengan obat-obatan yang menekan sekresi GH seperti
golongan dopamine agonis (bromocriptine), analog somatostatin (ocreotide) atau antagonis reseptor GH
(pegvisomant). Radioterapi diberikan jika pengangkatan tumor tidak dapat secara komplit, untuk mencegah
pembesaran sisa tumor atau mengontrol hipersekresi hormone atau jika terjadi kekambuhan tumor.

TUTORIAL 1

Page 1
Hagrid is a 16 years old student from SPH who present with his mother to the neurology clinic at
Siloam Hospital because of frontal headache and blurred vision for the past 2 months. He has otherwise
felt well. You are sitting at the desk when Hagrid and his mother walk into the room. (Please see the
photograph).

Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

Hagrid and his mother

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Questions:
1. What are Hagrids problems?
Frontal headache
Blurred vision
Tall stature
2. What are the possible causes for his problem?
Visual disorder
Growth hormone overproduction/endocrine disorder
Brain tumor
3. What is the possible mechanism of the causes?

Guiding questions:

Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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 What is the headache? How is the mechanism?

Nyeri kepala disebabkan adanya traksi, displacement, inflamasi, spasme vascular, atau distensi dari
struktur-struktur yang peka nyeri di daerah kepala (pain sensitive structures)
1. Intracranial Pain sensitive structure:
- Sinus venosus
- Arteri
- Lapisan duramater di basal cranium
- N. trigemninal (V), glosofaringeus (IX), vagus (X)
- Nucleus sensorik di thalamus
2. Extracranial Pain sensitive structure
- Periosteum
- Kulit kepala
- Jaringan subkutan
- Otot-otot kepala & otot-otot leher
- Arteri
- Saraf cervical 2-3
- Mata, telinga, mukosa hidung, gigi, sinus dan orofaring
Berdasarkan onsetnya, nyeri kepala dibedakan menjadi :

Akut : timbul mendadak

Mis. perdarahan subaracnoid akibat rupture aneurisma, stroke, meningitis, ensefalitis, Ocular disorder
(glaucoma)
Sub-akut : berlangsung dalam beberapa minggu sampai beberapa bulan
Mis. Tumor intracranial, meningitis, vasculitis
Kronis : berlangsung sampai bertahun-tahun
Mis : Migraine, tension headache, sinusitis, dental disease

What are the cause of blurred vision ?

Blurred vison atau vision impairment atau disturbances of vision adalah semua keluhan yang berhubungan
dengan gangguan penglihatan/visus. Dapat disebabkan karena :
Gangguan pada bola mata (mulai dari kornea, lensa, badan vitreus, retina, tekanan bola mata)
Gangguan pada otot-otot mata (ocular muscle)
Gangguan saraf cranial yang mempersarafi otot-otot mata
Gangguan pada sepanjang jalur visual (mulai dari nervus opticus, chiasma opticus, tractus opticus,
braintem, otak) atau pada jalur ocular-motoric di otak
Gangguan pada jalur visual dapat dibedakan menjadi:
1. Gangguan monocular
a. Amaurosis fugax/transient monocular blindness : gangguan penglihatan sesaat pada ssatu sisi
mata yang membaik kembali dalam 10-20 menit akibat oklusi sesaat arteri retina.
b. Optic neuritis : proses inflamasi pada saraf optikus.

Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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2. Gangguan binocular:
a. Papiledema
b. Lesi di chiasma optikum : tumor, trauma, aneurisma, penyakit demyelinating
c. Lesi retrochiasma : akibat adanya lesi di traktus optikus, lateral geniculate body, sampai korteks
oksipital

Tutorial 1
Page 2
Hagrid tells you that he has grown very quickly in the past 2 years. Two years ago, his height was
160 cm but has increased 20 cm in a year and increased another 30 cm this recent year. He has also
noted that his fingers became longer and enlarged in the past year and he now needs a very large pairs
of shoes (size 14).
He began having headache about 1 year ago and developed blurring of his vision in the past 2
months.
On examination, he is alert and cooperative; BP 120/70 mmHg, pulse 84 x/min, RR 16 x/min,
temperature 36,5 C. His body height is 210 cm and weight is 110 kg.
His general and neurological examination is normal except for decreased vision on confrontation
testing in both temporal fields.

Qustions:
1. How does the information help you?
Hagrid grown very fast, his hands and feet very large, it means abnormal. The possibility is he has
abnormality in Growth hormone.
2. How do you explain the findings in this case?
Hipersekresi GH yang terjadi pada masa anak-anak/remaja menimbulkan sindroma klinis GIGANTISM
(terjadi sebelum proses fusi dari epifisis tulang, sekitar usia 15 tahun), dimana pembesaran tubuhnya
simetris untuk semua tulang dan jaringan lunaknya. Jika terjadi pada usia dewasa (epifisis tulang telah
menutup) maka akan terjadi ACROMEGALY yaitu terjadi pembesaran jaringan lunak, kartilago,
tulang-tulang wajah menjadi prominent, tulang-tulang tangan dan kaki/bagian akral menjadi panjang,
kulit menjadi tebal dan kasar.

Growth Hormone diproduksi oleh kelenjar pituitary anterior (adenohypophysis) yang berlokasi di fossa
pituitary, disebelah posterior dari chiasma optikum. Pembesaran kelenjar pituitary akan menekan

Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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chiasma opticum menimbulkan keluhan blurred vision akibat gangguan lapang pandang berupa
hemianopia bitemporal.

Nyeri kepala terjadi akibat pertumbuhan tumor di daerah suprasella yang menyebabkan traksi atau
tarikan duramater pada diafragma sella yang dipersarafi oleh nervus trigeminus (N. V). Seiring dengan
pembesaran ukuran tumor, sakit kepala makin berat dan disertai muntah proyektil, hal ini dapat
menunjukkan adanya peningkatan tekanan intrakranial.

3. What further information do you need to understand this case?

Hormone level which secreted by pituitary (GH, FSH, LH, Prolactine, cortisol)
Radiology examination : plain radiograph, brain CT/MRI
Guiding Questions:
What is the mechanism of headache in this case ?
Gejala nyeri kepala merupakan efek kompresif paling dini dari tumor di daerah hipofisis dan sering tidak
spesifik. Biasanya bersifat bitemporal atau bifrontal atau keduanya. Nyeri kepala akibat tumor hipofisis
pada stadium awal disebabkan ekspansi tumor pada sella tursika dan tekanan terhadap diafragma sella
serta struktur duramater di sekitarnya yang dipersarafi oleh cabang pertama nervus V.
What is the Growth Hormone? Where is it reproduced? What is its function?
GH adalah hormon somatotropin yang disekresi oleh kelenjar pituitary anterior, bertanggungjawab dalam
proses pertumbuhan dan berperan dalam metabolism protein, lemak dan karbohidrat. Sekresi GH dikontrol
oleh GHRH (Growth Hormone-Releasing Hormone) dan GHIH (Growth Hormone-Inhibiting Hormone) yang
dikeluarkan oleh hipotalamus.
-------- siswa dituntun untuk mengetahui hipotalamus dan kelenjar pituitary secara embriologi, anatomi
(lokasi , struktur di sekitarnya) dan fungsional; (apa saja hormon-hormon yang diproduksi oleh hipotalamus
dan pituitary dan mengerti masing-masing fungsinya dalam metabolisme tubuh)
What is confrontation test? What is the function of this test?
Tes konfrontasi dilakukan untuk menilai lapang pandang (visual field) pasien . Tes ini dapat dilakukan
dengan :
1. Tes konfrontasi sederhana (dapat dilakukan bedside)
2. Alat Kampimetri

What is the clinical finding in this patient on confrontation test ?

Hemianopia bitemporal adalah gangguan lapang pandang pada kedua sisi temporal .

Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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TUTORIAL 2

Page 1
Laboratory examination showed the following result:
Hb : 13,2 g/dl
Ureum : 17 mg/dl
Ht : 43 %
Creatinin : 0,4 mg/dl
WBC : 8.000 /mm3
Random Blood Glucose : 153 g/dl
Platelet : 289.000 /mm3 SGOT : 16 U/L; SGPT: 9 U/L
Questions:
1. What is your interpretation of these test results?
There are normal results on laboratory examination except a slight increase on blood glucose.
2. What further information do you want?
Radioimaging (Plain Radiolographic, Brain CT/MRI)
Hormone level (FSH, LH, Prolactine, GH, Cortisol)

Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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TUTORIAL 2

Page 2
The imaging examination showed the following result:

Head MRI

Questions:
1. How do these results help you?
Skull X-ray showed balloning or widening of pituitary fossa
Head MRI showed a mass at pituitary fossa, enhancement with contrast, erode the floor of fossa
and compress the centre of chiasma opticum
2. What is now your probable diagnosis?
Mass/tumor at pituitary fossa which compress the chiasma opticum.
3. What further information do you want?
Hormone level (FSH, LH, Prolactine, GH, Cortisol)
Guiding questions:
What is the differential diagnosis for Suprasellar masses?
-

Pituitary adenoma
Craniopharyngioma
Optic nerve glioma/astrocytoma

Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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Meningioma suprasellar
Menigioma of the optic nerve sheath
Epidermoid/dermoid suprasellar

Semua tumor di daerah supraselar yang menekan jaras visual (nervus optikus, chiasma optikum atau
traktus optikus) akan menimbulkan keluhan gangguan visus.
Gangguan visual di daerah chiasma DD/
- Malformation and congenital anomalies : Encephalocele, Craniopharyngioma
- Masses
- Infection and inflammation : Meningitis, Chiasma arachnoiditis
- Vascular : Compression by aneurysm
- Other : Trauma, multiple sclerosis
Can you explain the anatomy structure and function of pituitary gland
Kelenjar hipofisis atau Pituitary gland merupakan kelenjar endokrin yang terletak pada dasar tengkorak dan
menempati sella tursika, berada dekat dengan chiasma opticum, berukuran 15x10x6 mm, berat 600 mg,
dan terdiri dari 2 bagian/lobus:
1. Anterior pituitary = Adenohypophysis, mensintesis hormone:
a. Corticotropes
- ACTH
b. Lactotropes
- Prolactin
c. Somatotropes
- GH
d. Thyrotropes
- Thyrotropin
e. Gonadotropes
- FSH, LH
2. Posterior pituitary= Neurohypohysis
a. Vasopressin
b. Oxytocin
Where is location of hypothalamus? What is the function of it?
Hipothalamus merupakan organ yang sangat kecil (0,3% dari total massa otak) namun merupakan bagian
yang sangat penting dalam system saraf pusat, tugasnya mengontrol system saraf otonom dan system
endokrin dan secara tidak langsung mengontrol homeostasis tubuh. Hipothalamus merupakan bagian dari
diencephalon, dibatasi oleh chiasma opticum sampai ke batas kaudal mammilary bodie. Terletak di bawah
thalamus, membentuk dasar dan bagian inferior dari dinding lateral dari ventrikel III. Hipothalamus
mengandung kumpulan neuron yang mensintesis releasing hormone yaitu:
Thyrotropin-releasing hormone (TRH)
Corticotropin-releasing hormone (CRH)
Gonadotropin-releasing hormone (GnRH)
Growth hormone-releasing hormone (GHRH)
Growth hormone-release inhibiting hormone (GHIH)
Prolactin-releasing factor (PRF)
Prolactin-inhibiting hormone (PIH)
Hormon-hormon ini disekresi ke anterior pituitary melalui hypothalamus-hypophyseal portal system.
Sekresi hormone ini dipengaruhi oleh :
- Emosi
- Status metabolik
----- Mahasiswa dituntun untuk mengerti tentang hypothalamus-hypophyseal portal system, termasuk
macam-macam nucleus di hipothalamus
Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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TUTORIAL 2

Page 3
Further laboratory results become available 1 week later :
TSH : 1,35 mU/L
(0,4 5,0 mIU/L)
FSH : 4,96 mIU/mL
(0,9 15 mIU/mL)
Prolactine : 63,15 ng/mL
(2 15 ng/mL)
GH : 48,0 ng/mL
(< 10 ng/mL)
Cortisol : 11 g/dL
(5 25 g/dL)
Questions:
1. What does this tell you about the cause of Hagrid,s problem ?
GH and prolactine were significantly increased.
2. How do you correlate this with the clinical features of the disease?
Hypersecretion of GH produces clinical syndrome: Gigantism or acromegaly
Hypersecretion of prolactine produces infertility, amenorrhoea, galactorrhoea
3. What is the natural course and prognosis of this condition?
Tumours of the pituitary gland constitute about 5-10% of intracranial tumours. They arise from the anterior
portion of the gland and are usually benign. The Classification can be made based on location, size,
hormone typed secreted, and pathologic features.
Clinical presentations are caused by endocrine effect (hormone hypersecretion or hyposecretion) and local
mass effect (headache, visual field defects)
4. What is the probable treatment for Hagrid?
Drug therapy
Operative
Radiotherapy
Guiding questions:
What are the classifications of pituitary tumor?
Berdasarkan anatomis tumor hipofisis terdiri dari 3 jenis :
1. Tumor intrasellar : adenoma, kraniofaringioma, kista celah Rathke
2. Tumor suprasellar : adenoma, kraniofaringioma, meningioma, kordoma, hamartoma
3. Tumor parasellar : meningioma, aneurisma, karsinoma metastasis
Berdasarkan ukurannya :
1. Microadenoma ; ukuran tumor < 10 mm
2. Macroadenoma; ukuran tumor 10 mm
Berdasarkan produksi hormone :
Prolactinoma 60%
GH hypersecretion tumour 20%
ACTH excess 10%
TSH, gonadotropine hypersecretion tumour jarang
Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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 Nonfuctional adenoma 10%

Find other classification .(based on grade or type or WHO classification)
TUTORIAL 3

Page 1
Then Hagrid undergo microsurgery by transphenoidal approach. The biopsy result shows the
following microscopic picture:

Questions:
1. How does this result say to you?
The tumour cell type is eosinophilic which is produces prolactine and GH. The basophilic cells produce
ACTH, TSH, FSH and LH.
Guiding question:
What are the pathologic classification of adenoma hypophysis ?
o Benign or malignant
o Chromophobic Non-functioning
o Basophilic Cushings
o Acidophilic/eosinophilic - Acromegaly
o Mixed

Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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TUTORIAL 3

Page 2
The pathology report results returned:
Microscopic examination revealed solid islands of tumor cells with round to oval nuclei and
moderately abundant eosinophilic cytoplasm. Histochemical staining was consistent with a Growth
Hormone producing adenoma.
One day following the surgery, Hagrid complains that he is very thirsty, drinking all the time and
has urination frequently. The urine volume was 8500 cc/24 hours; fluid balance was -6250 cc.
The laboratory results:
Serum sodium
Serum potassium
Serum chloride
plasma osmolality

: 155 meq/L (135 145 mEq/L )

: 3,7 meq/L (3,5 5 mEq/L )
: 133 meq/L (95 105 mEq/L)
: 321 mOsm/kg

Urine specific gravity

Urine osmolality
Urine sodium
Urine potassium
Urine Chloride

: 1, 001 (1,002 1,028)

: 210 mOsm/kg
: 18 (40-220 mmol/24h)
: 9 (25-125 mmol/24h)
: 27 (110-250 mmol/24h)

BUN
creatinine
Prolactine
GH

: 41 mg/dL
: 1.1 mg/dL
: 20,9 ng/mL
: 30 ng/mL

Questions:
1. What this information say to you?
Following the operation Hagrid gets diabetes insipidus. This complication occurs commonly after the
surgery. Symptoms include polyuria, excessive thirst, and polydipsia, with a 24-h urine output of > 50
mL/kg/day and urine osmolality that is less than that of serum (<300 mosmol/kg; specific gravity <
1,010). Laboratory signs including hypernatremia.
Following the operation level of GH and prolactine still slightly high.
2. What is the possible mechanism of the causes?
Diabetes insipidus is a disorder due to absolute or relative deficiency in the circulating level of ADH (arginine
vasopressin). Pituitary surgery is one of the causes of secondary central diabetes insipidus.

Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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3. What are the options for treatment for Hagrid?

For Diabetes insipidus: Mild cases require only adequate fluid intake. In more severe cases of central
diabetes insipidus should receive desmopressin acetate (DDAVP).
Bromocriptine and cabergolin, a dopamine agonist can suppres prolactine. Somastotatin analogs are useful
to suppress the level of GH.

EPILOGUE
Hagrid was encouraged to drink water as much as he could and was given DDAVP 0,2 ml twice
daily by nasal spray. His urinary volumes decreased after about 2 weeks, he was able to drink enough
without difficulty and the DDAVP was no longer needed. He was prescribed somatostatin analog 50 ug
3x daily and follow up Growth hormone levels were normal.

Endocrine block/Tutor guide/week3/Vivien Puspitasari, dr, SpS

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