1.

Embryology + Anatomy + Histology + Blood supply

a. Hypothalamus 
- Developing brain kebagi jadi 3 sections yaitu prosencephalon (forebrain), mesenchepalon
(midbrain), rhombecephalon (hindbrain)
- Prosencephalon akan jadi telenchepalon (future cortex and basal ganglia) dan
diaencephalon (will evolve into the optic cup, thalamus, hypothalamus, and mammilary
bodies)

Internal carotid Internal carotid artery C4

artery C6 Segment Segment (meningohypophyseal
trunk)

- Blood supply: Circle of Willis

 Anteromedial branches  anterior cerebral artery and anterior communicating artery
(preoptic, supraoptic, rostral porstion of lateral hypotalamic area)
 Postero medial branches  posterior communicating artery
(tuberal region, mammiliary, cuadal portion of hypotalamic area)
 Thalamoperforating branches from posterior cerebral artery
(posterior n)

b. Pituitary
- A part of the stomedeum’s roof (Buccal promordium) will grow cranialy forming Rathke’s
pouch with a stalk called Rathke’s stalk
- A part of the dienchephalon’s floor (cranial promordium) will grow caudally forming pars
nervosa with a stalk called infundibulum
- The anterior wall of Rathke’s pouch will
be thickened forming pars distalis while
the thinner posterior wall will form pars
intermedia
- The pars nervosa will adhere to pars
intermedia forming the posterior lobe ,
pars distalis with pars tuberalis will form
anterior lobe
 - The Rathke’s stalk degenerates

c. Pineal gland
- Develops from neuroectoderm of posterior portion of roof of dienchepalon, remains
attached to brain by a short stalk (week 7-8)
- Blood supply: choroidal branches of the posterior cerebral artery
2. Topography of hypothalamus and pituitary
- Hypothalamus
 Inferior to thalamus
 Posterior to optic chiasm, bordered on the sides by the temporal lobes and optic tracts
- Pituitary  di sellae turcica
 Anterior lobe
i. Pars anterior
ii. Pars intermedia
iii. Pars tuberalis
 Posterior lobe
i. Pars nervosa
3. Hypothalamo-hypophysial tract: sistem syaraf yang menghubungkan hypothalamus dengan
posterior hypophysis (supraoptic nucleus + paraventricular nucleus)
Hypothalamohypophysial portal system: sistem perdarahan yang bertugas untuk sekresi dan
menghambat hormone dari hypothalamus ke posterior hypophysis
4. Hormones:
 Growth Hormone  Somatotropin
Peptide hormone  somatotropic cells of anterior pituitary
Regulate tissue growth
Effect  cell metabolism stimulation, growth, division
DIRECT
Increase fatty acids (stimulates adipose tissue lipolysis)
Increase blood glucose level (Stimulates gluconeogenesis, glycogenolysis in liver,
increase tissue insulin resistance)
INDIRECT
Insulin-like effects through insulin-like growth factors  (IGF 1)
Stimulate cell growth , division, differentiation, reduce apoptosis
Protein Stimulate amino acid, protein uptake, protein synthesis, decrease protein
breakdown
Epiphyseal plates, cartilage  stimulates bone osteoblast activity, cartilage chondrocyte
activity  increased linear growth
 TSH (thyroid stimulating hormone)  thyrotropin
Glycoprotein hormone  pituitary gland
Stimulating thyroid gland growth, thyroid hormone synthesis and release
Effect  stimulates in all steps in thyroid gland hormone synthesis, secretion
Trophic effect  increase growth of thyroid gland
 ACTH (adrenocorticotropic hormone)
Secreted by anterior pituitary corticotropic cells
Stimulating adrenocortical cells of zona fasciculata of the adrenal cortex to secrete
glucocorticoids (primarily cortisol)
i. Anti-inflammatory effect
ii. Increase blood glucose level
iii. Increase fat and protein breakdown
 Prolactin
Secreted by Anterior Pituitary
Lactogenesis
Metabolism
Immune system regulation
Pancreatic development
 FSH (gonadotropin)
Secreted by gonadotropic cells of anterior pituitary
Glycoprotein hormone
Maintains development, growth, and pubertal maturation, and reproductive processes
of the body
 LH (lutropin)
Secreted by gonadotropic cells in the anterior pituitary
Female  ovulation, development of corpus luteum
Males  LH called interstitial cell stimulating hormone  stimulate leydig’s cell to
produce testosterone
 Vasopressin  ADH/arginine vasopressin/argipressin
Peptide hormone
Synthesized di hypothalamus
Increases the amount of solute-free water reabsorbed back into the circulation from the
filtrate in the kidney tubules of the nephrons
Increases peripheral vascular resistance and BP  constricts arteriole
Social behavior, sexual motivation, pair bonding, maternal responses to stress
 Oxytocin
Peptide hormone
Synthesized di hypothalamus
Uterine contraction, milk ejection
5. Hypothalamus-pituitary axis  hubungan hypothalamus and pituitary gland (anterior posterior)
untuk secrete hormone biasanya lewat hypophyseal portal system (paracrine signal)
Ex:
- Hypothalamus secrete Gonadotropin-releasing hormone buat signal anterior pituitary
untuk secrete FSH dan LH dan mereka akan disalurkan ke gonads (testis/ovaries) agar
mereka produksi hormon
- Kalau di posterior pituitary, dia cuman store hormone yang diproduksi hypothalamus (ADH,
oxytocin)  collecting duct and uterine contraction
6. Acute headache  hours-days
Sub-acute  days-weeks
Chronic  months-years
A headache occurs when any of the pain-sensitive structures in the head and neck are
stimulated.
Primary and Secondary
It is thought that these headaches are due to an increased sensitivity to pain due to the release
of vasoactive neuropeptides like substance-P and calcitonin gene-related peptides.
7. Melatonin and Circadian Cycle
Melatonin  secreted by pineal gland
Function: regulates wake-sleep cycle, anti-oxidant, immune system
How Melatonin affects Circadian Cycle
Jadi cahaya dari luar ke pupil habis itu ke retina, di retina ada IPRG-cells (intrinsically
photosensitive retinal ganglion cells) yang berguna untuk synchronization tubuh dengan
circadian cycle (sleep-wake)
Pada saat ada cahaya, IPRG cells akan depolarize yang akan leads to inhibition of endocrine
functions of pineal gland  no melatonin secretion
 Pada saat tidak ada cahaya, IPRG cells akan repolarize yang akan induce melatonin secretion
Melatonin ini bersifat circadian alerting system dimana dia akan mengurangi aktivitas di cerebral
cortex (thinking, wakefullness, learning) and drives circadian rhytm to dark cycle
Cahaya akan inhibit melatonin secretion

8. Pituitary hormone secretion disorders

Pituitary adenoma  hormone-secreting cells becomes neoplastic
Overproduction of
- Acromegaly/gigantism  growth hormone
- Cushing syndrome  ACTH
- Galactorrhea + amenorrhea + infertility  Prolactin
- Low libido (erectile dysfunction) + gynecomastia (male)  prolactin
Paling sering  Lactotroph adenoma/prolactinoma

Underproduction of

- Diabetes insipidus  vasopressin

- Hypopituitarism  multiple hormones

Etiology of Pituitary adenoma

- Sporadic
- Mutation of PRKA1A gene  loss function of negative regulatory unit of protein kinase A 
increased cAMP activity increase hormone
- Mutation of AIP gene

Classification of Pituirary adenoma

- Benign/malignant
- Basophilic (TSH, LH, FSH, ACTH)/eosinophilic (prolactin, GH)
- Microadenoma (< 1 cm)/macroadenoma (> 1 cm)
- Functioning (hormone secreting)/non-functioning (non-hormone secreting)

Diagnosis

- Check hormone yang diproduksi hypophysis (cortisol, gonads, rolactine, TSH, GH)
- Biopsy

Treatment

- Surgery  transsphenoidal adenomectomy (medication tidak berhasil 

radiotheraphy/drugs atau menggangu penglihatan)
- Radiotheraphy (untuk partial adenomectomy  mencegah perbesaran tumor&maintain
hormone) ex: stereostatic radiosurgery
- Drugs  (Somatostatin analog, dopamine agonist, growth hormone receptor antagonist)

Follow Up

- MRI  melihat apakah ada reccurent

- Hormonal theraphy
9. Natural history of Pituitary tumor
- Heart failure
- Diabetes insipidus
- Diabetes mellitus
- GI carcinoma
10. Suprasellar  anterior of sellae turcica
Intasellar  di dalam diaphragma sellar
Parasellar  cavernous sinuses, hypothalamus, suprasellar cistern, ventral inferior third
ventricle
11. Diabetes Insipidus
Tipe:
a. Dispogenic/Psychogenic Polydipsia  konsumsi cairan terlalu banyak  konsentrasi darah
berkurang  ADH berkurang  polyuria
b. Gestational  pada ibu mengandung akibat vasopreinasse yang dihasilkan placenta
melawan ADH
c. Central/neurogenic  masalah di hypothalamus/hypophysis (kerusakan hypothalamus,
osmosreceptor, supraoptic nucleus  trauma, ischemic, pituitary tumor) yang
menyebabkan produksi ADH terganggu dan menyebabkan jumlah ADH dalam darah
berkurang  vasokonstriksi berkurang + aquaporin-2 berkurang
d. Nephrogenic  kerusakan pada ginjal yang membuat ginjal resisten ADH (akibat obat-
obatan atau congenital defect)

Classification:

a. Complete/absolut  absence of ADH

b. Incomplete/relative  presence of ADH

Symptoms:

a. Polyuria (<3 L/day)

b. Thirsty  dehydration
c. Low blood pressure
d. Fatigue, nausea
12. Gigantism  pas childhood karena over secretion of GH, bertambah tinggi akibat ephyphysela
plate yang masih berkembang (akibat tumor, keturunan)
Acromegaly  pas adulthood juga karena over secretion of GH, biasanya pada saat ini
ephyphyseal plate sudah berhenti untuk tumbuh (akibat tumor, keturunan)
Gigantism dapat berlanjut ke acromegaly pada saat epiphyseal plate sudah tidak berkembang
13. Drugs for hormone disorder
- Somatostain analogs  binds to GHIH/SS receptor di hypothalamus  inhibit GH dengan
cara menghambat kerja anterior hypophysis
- Dopamine agonist  bind to D1/D2 receptor  activates G-protein  inhibit adenyl cyclase
 prevent ATP from activating cAMP  protein kinase A ga aktif  no GH
- GH receptor agonist  binds to GHRH receptor  GHRH cannot bind  no stimulus for
anterior hypophysis  no GH