WEEK 1 Endocrine

(SENIN)
Headache
An intracranial headache results from the dilation of arterial blood vessels at the base of
the brain caused by a temporary increase in blood supply. An intracranial headache may result as a
consequence of a fever, a “hangover,” a severe and sudden attack of high blood pressure, or
an inflammation or hemorrhage affecting the arteries and their adjacent meningeal tissues (as
during meningitis or a cerebral hemorrhage). One can also occur if a tumour displaces tissues inside
the skull. Intracranial headaches often begin abruptly; they usually occur on awaking or at night, and
pain usually changes with a change in posture.
Extracranial headaches may be caused by dilation and distension of the extracranial arteries that
supply the surface tissues of the head or sustained contraction of the skeletal muscles of the face,
scalp, and neck. Excess fatigue, neck problems, and eyestrain can all cause extracranial headaches.

An acute headache is one that has been present for hours or days, a subacute headache for days or
weeks, and a chronic headache for months or years

Anatomy
Hypothalamus
Location: dienchepalon (caudorostral to thalamus)

Hypothalamus functions:

 releasing hormones

 regulating body temperature

 maintaining daily physiological cycles

 controlling appetite

 managing of sexual behavior

  regulating emotional responses

Pituitary
Location: hypophysial fossa (floor of sella turcica)
Physiology
POSTERIOR PITUITARY

The posterior pituitary is actually an extension of the neurons of the paraventricular and
supraoptic nuclei of the hypothalamus.

. Neurosecretory cells in the hypothalamus release oxytocin (OT) or ADH into the posterior lobe of
the pituitary gland. These hormones are stored or released into the blood via the capillary plexus.

The posterior pituitary gland does not produce hormones, but rather stores in herring bodies
and secretes hormones produced by the hypothalamus. The paraventricular nuclei produce the
hormone oxytocin, whereas the supraoptic nuclei produce ADH. These hormones travel
along the axons into storage sites in the axon terminals of the posterior pituitary. In response
to signals from the same hypothalamic neurons, the hormones are released from the axon
terminals into the posterior pituitary capillaries to the bloodstream

ANTERIOR PITUITARY

Recall that the posterior pituitary does not synthesize hormones, but merely stores them. In
contrast, the anterior pituitary does manufacture hormones. However, the secretion of
hormones from the anterior pituitary is regulated by two classes of hormones. These
hormones—secreted by the hypothalamus—are the releasing hormones that stimulate the
secretion of hormones from the anterior pituitary and the inhibiting hormones that inhibit
secretion.

Hypothalamic hormones are secreted by neurons, but enter the anterior pituitary through
blood vessels. Within the infundibulum is a bridge of capillaries that connects the
hypothalamus to the anterior pituitary. This network, called the hypophyseal portal system,
allows hypothalamic hormones to be transported to the anterior pituitary without first
entering the systemic circulation. The system originates from the superior hypophyseal
artery, which branches off the carotid arteries and transports blood to the hypothalamus. The
branches of the superior hypophyseal artery form the hypophyseal portal. Hypothalamic
releasing and inhibiting hormones travel through a primary capillary plexus to the portal
veins, which carry them into the anterior pituitary. Hormones produced by the anterior
pituitary (in response to releasing hormones) enter a secondary capillary plexus, and from
there drain into the circulation.

Anterior Pituitary. The anterior pituitary manufactures seven hormones. The hypothalamus produces
separate hormones that stimulate or inhibit hormone production in the anterior pituitary. Hormones
from the hypothalamus reach the anterior pituitary via the hypophyseal portal system.
The anterior pituitary produces seven hormones. These are the growth hormone (GH),
thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-
stimulating hormone (FSH), luteinizing hormone (LH), beta endorphin, and prolactin. Of the
hormones of the anterior pituitary, TSH, ACTH, FSH, and LH are collectively referred to as
tropic hormones (trope- = “turning”) because they turn on or off the function of other
endocrine glands.

Pineal

Location:  epithalamus between the two hemispheres tucked in the groove of the thalamus join. This
gland develops from brain section diencephalon and located behind the third cerebral ventricle
Physiology: light stimulates action potential to the superchiasmatic nucleus to stimulate the superior
cervical ganglion produce norepinephrine to the receptors of the pinealocytes in the pineal gland to
produce melatonin. In darkness, more NE is produced thus more melatonin is produced. Increased
melatonin attached to the receptors of the SCN to reset biological clock.

Acromegaly (in adults) & Gigantism (in children)

Symptoms
- Excessive growth in height
- Rapid weight gain
- macrocephaly
- Soft tissue growth (hands & feet)
- Organ growth
- Cause: pituitary adenoma, hypothalamic tumour, McCune Albright syndrome

Hypothalamus – Ant. Pituitary: hypothalamo-hypophyseal portal system

Hypothalamus – post. Pituitary: extension of supraoptic and paraventricular nuclei

CO 3/WO 4

Pituitary Hormones
Pituitary Chemical
Associated hormones Effect
lobe class
Anterior Growth hormone (GH) Protein Promotes growth of body tissues
Promotes milk production from
Anterior Prolactin (PRL) Peptide
mammary glands
Thyroid-stimulating hormone Stimulates thyroid hormone
Anterior Glycoprotein
(TSH) release from thyroid
Adrenocorticotropic hormone Stimulates hormone release by
Anterior Peptide
(ACTH) adrenal cortex
Follicle-stimulating hormone Stimulates gamete production in
Anterior Glycoprotein
(FSH) gonads
Stimulates androgen production
Anterior Luteinizing hormone (LH) Glycoprotein
by gonads
Stimulates water reabsorption by
Posterior Antidiuretic hormone (ADH) Peptide
kidneys
Stimulates uterine contractions
Posterior Oxytocin Peptide
during childbirth

WO 5

Hypothalamic hormones

 Stimulatory

- Thyrotropin (TRH) -> ant. Pituitary produce TSH -> thyroid produce thyroid
hormones -> negative feedback to pituitary to produce less TSH

- Corticotropin (CRH) -> ant. Pituitary produce adenocorticotropic hormone

(ACTH) -> adrenal produce cortisol-> negative feedback to pituitary to
produce less CRH
 - Gonadotropin (GnRH) -> ant. Pituitary produce FSH/LH-> testes/ovary sex
hormones-> negative feedback to pituitary to produce less GnRH

*ovulation make positive feedback to ant. pituitary

- Growth hormone (GHRH) -> ant. Pituitary produce GH-> makes long bones
grow

 Inhibitory

- GHIH:

- Prolactin inhibiting factor (dopamine): keeps being produced kecuali lagi

nyusu

CO 4

Growth Hormone (somatotropin)

- Produced by somatotroph

- Released in pulsatile manner

- Stimuli: hypoglcemia, exercise, puberty

- Negative feedback:

 Increased GHRH in blood

 Somatomedins made by liver, muscle, bones

 Increased GHRH in blood + Somatomedins: signal hypothalamus to produce

somatostatin

CO 5

Growth:

 Direct: stimulation of cellular metabolism

- In adipose: lypolisis

- Liver: gluconeogenesis & gycogenolysis

 - Increase insulin resitance

 Indirect: stimulates release of somatomedin C (insulin-like growth factor 1)

- Promotes cell metabolism

- Prevents cell death

- Increase cell division

In muscle: stimulate AA intake -> protein production ->muscle growth

In bone: acts on epiphyseal cartilage -> stimulate osteoblast & chondrocyte -> boost growth

VISUAL PATHWAY

Within the middle cranial fossa, the optic nerves from each eye unite to form the optic
chiasm. At the chiasm, fibres from the nasal (medial) half of each retina cross over to the
contralateral optic tract, while fibres from the temporal (lateral) halves remain ipsilateral:
 Left optic tract – contains fibres from the left temporal (lateral) retina, and the right
nasal (medial) retina.
 Right optic tract – contains fibres from the right temporal retina, and the left nasal
retina.

Each optic tract travels to its corresponding cerebral hemisphere to reach the lateral
geniculate nucleus (LGN)

(RABU)

Hyperprolactinemia

In women: galactorrhea (increase milk production), anovulatory amenorrhea (absence of

ovulation & menstruration)

In men: gynecomastia, erectile dysfuntion

Increased GH = acromegaly/gigantism

Pituitary adenomas can be divided into 2 categories based on size:

 Microadenomas are tumors that are smaller than 1 centimeter (cm) across. Because
these tumors are small, they rarely damage the rest of the pituitary or nearby tissues.
But they can cause symptoms if they make too much of a certain hormone. Many
people actually have small adenomas that are never found because they don't grow
large enough or make enough hormones to cause a problem.
  Macroadenomas are tumors 1 cm across or larger. Macroadenomas can affect a
person’s health in 2 ways. First, they can cause symptoms if they make too much of a
certain hormone. Second, they can cause symptoms by pressing on normal parts of the
pituitary or on nearby nerves, such as the optic nerves. Symptoms: headache,
bitemporal hemianopia, double vision, hypopituitarism, pituitary apoplexy
Functional versus non-functional adenoma

Functional adenomas: Most of the pituitary adenomas that are found make excess
hormones. The hormones can be detected by blood tests or by tests of the tumor when it is
removed with surgery. Based on these results, pituitary adenomas are classified as:

 Lactotroph adenomas make prolactin and account for about 4 out of 10 pituitary

tumors.
 Somatotroph adenomas make growth hormones and make up about 2 in 10 pituitary
tumors.
 Corticotroph adenomas make ACTH and account for about 1 in 10 pituitary tumors.
 Gonadotroph adenomas make LH and FSH and are very rare.
 Thyrotroph adenomas make TSH and are very rare.
 Plurihormonal adenomas make more than one hormone.

Non-functional adenomas: Pituitary adenomas that don’t make excess hormones are

called non-functional adenomas or null cell adenomas. They account for about 3 in 10 of all
pituitary tumors that are found. They are usually found as macroadenomas, causing
symptoms because of their size as they press on nearby structures.

If tumour grows superiorly -> press on optic chiasm

If tumour grows laterally -> press nerves in cavernous sinus -> cavernous sinus syndrome

Craniopharyngioma

Craniopharyngiomas are benign, slow-growing tumors that originate from epithelial remnants
of the Rathke pouch at the junction of the infundibulum and the pituitary gland.

Meningioma: tumor of meninges

Intrasellar: adenoma, craniopharyngioma, kista rhathke

Parasellar: meningioma, aneurysm, carcinoma

Suprasellar: craniopharyngioma, adenoma, meningioma

Pituitary Adenoma
Epidemiology

Frequency

United States

Pituitary tumors represent anywhere between 10% and 15% of all intracranial tumors.

Incidental pituitary tumors are found in approximately 10% of autopsies.

The incidence of acromegaly is approximately 3 per million. Acromegaly has no sex

predilection.

Pathophysiology

Multiple oncogene abnormalities may be involved in pituitary tumorgenesis. G-protein

abnormalities, ras gene mutations, p53 gene deletions, mutations, and rearrangements, and
the association of pituitary tumors with the syndrome of multiple endocrine neoplasia have
been described and are involved in the development of adenomas in the pituitary gland. The
pituitary tumor transforming gene-1 (PTTG-1) is a newly discovered oncogene that serves as
a marker of malignancy grades in several endocrine malignancies; this gene is known to
regulate the cellular mitosis process and forced expression of this gene induces tumor
formation in nude mice. PTTG-1 is overexpressed in pituitary tumors.

Recent work suggests that pituitary tumorigenesis is more heterogenous than formerly
thought. Nonfunctioning adenomas are associated with hypermethylation of p16
prolactinomas, and corticotropin-secreting tumors express galectin-3 (Gal-3), a gene involved
in cell growth and apoptosis. Inhibition of Gal-3 may serve as a molecular therapeutic target.
Mutations of the aryl hydrocarbon-interacting protein gene (AIP) may be present in some
cases of familial gigantism and acromegaly, as well as other pituitary tumor types.

Most of these tumors are benign, but certain factors involved in the genesis of the tumor may
determine its rate of growth and aggressiveness. For instance, the presence of p53 correlates
with more aggressive tumor behavior.

Clinical manifestations are due to the local effect of the mass and distant endocrine
manifestations that can affect a variety of organ systems. These effects are due to lack or
excess of a given stimulating hormone on the target organ. Pituitary adenomas, with a few
exceptions, are not under the control of hypothalamic releasing factors.

Hormonal deficiencies - Clinical effects

Growth hormone deficiency

  Adults - Increased rate of cardiovascular disease, obesity, reduced muscle strength
and exercise capacity, and increased cholesterol

 Infants - Hypoglycemia

 Children - Decreased height and growth rate

Gonadotrophin deficiency

 Men - Diminished libido and impotence; testes shrink in size, but spermatogenesis
generally preserved

 Women - Diminished libido and dyspareunia; breast atrophy in chronic deficiency

 Children - Delayed or frank absence of puberty

 Adolescent girls - Present similarly to adult women

Thyrotropin deficiency - Malaise, weight gain, lack of energy, cold intolerance, and
constipation

Corticotrophin deficiency

 Unlike primary adrenal insufficiency, mineralocorticoid function (which is dependent

on the angiotensin-renin axis) not affected; deficiency limited to glucocorticoids and
adrenal androgens

 Initially, symptoms nonspecific (eg, weight loss, lack of energy, malaise); severe
adrenal insufficiency may present as a medical emergency

Hormonal overproduction - Clinical effects

Prolactin

 Hypogonadism, if hyperprolactinemia sustained

 Women - Amenorrhea, galactorrhea, and infertility

 Men - Decreased libido, impotence, and rarely galactorrhea

Growth hormone

 Children and adolescents - pituitary gigantism

 Adults - Acromegaly

Cushing disease

 Weight gain, centripetal obesity, moon facies, violet striae, easy bruisability, proximal
myopathy, and psychiatric changes
  Other possible effects - Arterial hypertension, diabetes, cataracts, glaucoma, and
osteoporosis

Treatment

Microadenomas

- Complete Transsphenoidal surgery

- <1ng/ml GH morning after surgery

- Normal serum IGF-1 after 12 weeks

Macroadenomas

- Partial surgery

- Medical therapy: somatostatin analog, GH receptor antagonist

- Radiotherapy

Natural course: buta

Prognosis

The outlook depends on the size and type of adenoma you have. When treatment destroys the
tumor, most patients who have benign adenomas can return to full, normal lives. Adenomas
can recur, which means you will need treatment again. About 18% of patients with non-
functioning adenomas and 25% of those with prolactinomas, the most common type of
hormone-releasing adenomas, will need more treatment at some point. In some cases,
adenoma treatment results in low hormone levels, and you have to take hormone medicines to
replace what you have lost.

X-ray

Sella turcica membesar

MRI