Pineal gland - Epiphysis

Table of contents of this page:

1 Where in the brain
2 Other names for the pineal gland
3 Connections with other brain areas and the pineal gland
4 Structure of the pineal gland
5 Function of the pineal gland

• 6 Biological clock and sleep-wake rhythm
• 7 Sexual development
• 8 Inhibits the development of tumors
• 9 Serotonin function

10 Diseases of the pineal gland

• Congenital malformations, atrophy, poor functioning (dystrophic changes) and tissue damage with death of
  the cells (necrobiotic changes)
  
• 11 Blood supply disorders
• 12 Inflammations
• 13 Parasitic processes
• 14 Tumors of the pineal gland
• 15 Specific complaints of increased pressure
  • Hydrocephalus
  • Other complaints
    
• 16 Pineal gland cyst / pinealis cyst
• 17 Pineocytoma or pinealocytoma
• 18 Pineal parenchymal tumors with intermediate differentiation
• 19 Pineoblastoma
• 20 Papillary tumor of the pineal region

1 Where in the brain?

The pineal gland (epiphysis) is located deep in the brain, between the two hemispheres of the brain and just below the posterior end of the brainbeam (the corpus callosum). It is the outgrowth of the roof of the third ventricle of the brain. The pineal gland is part of the epithalamic region in the midbrain (diencephalon).

The midbrain (diencephalon) also includes the following brain structures:

• thalamus
• hypothalamus
• pituitary gland
• third ventricle of the brain 

2 Other names for the pineal gland

• glandula pinealis
• corpus pineale 
• epiphysis
• epiphysis cerebri

3 Connections with other brain areas

The pineal gland has close connections with the
hypothalamus, an important control center in the brain and connected to various parts of the midbrain and to endocrine glands and other organs. Together with the pituitary gland, among other things, it constitutes the entire system that regulates the gonads and the growth of the body. The pineal gland has an inhibitory influence on the thyroid gland.

4 Structure

The pineal gland has a flattened cone shape with lobes. It resembles a young pine cone. It is approximately 6-10 millimeters long and 506 millimeters wide.

Size and weight change with age.
In the first year of life there is quite an enormous growth from 7 milligrams to 100 milligrams.

At about the age of ten, the weight doubles to approximately 200 milligrams.

The pineal gland then becomes smaller again (atrophy) as it grows older, which can sometimes lead to tumor formation. An average adult human has a pineal gland of 120 milligrams.

5 What is the fuction of the pineal gland?

The pineal gland secretes hormones and neurotransmitters. Therefore it belongs to the endocrine system. The following hormones and neurotransmitters are secreted by the pineal gland. 

• the hormone melatonin, which regulates the day-night rhythm and plays a role in sexual maturation and different biological rhythms. Melatonin production is stimulated by darkness and inhibited by light.
• adrenoglomerulotropin, which stimulates aldosterone secretion by the adrenal glands, which in turn plays a role in regulating blood pressure. A second factor, also from the pineal gland, inhibits the production of aldosterone as well as that of cortisol.
• carrier proteins (neurophysins), which probably play a role in transport to the axon terminals).
• vasoactive intestinal polypeptide (VIP) is a neurotransmitter but also acts as a blood-borne hormone. VIP participates in the regulation of several important bodily functions. It affects the blood vessels of the intestines by regulating blood flow.
• neurotransmitters, such as serotonin. About 15% of serotonin comes from the pineal gland. This hormone regulates the psycho-emotional state of a person. It relieves stress, regulates smooth muscle tension and is produced during the day. A lack of this hormone can cause depression and phobias.
• other hormones such as penialin, of which it is not yet entirely clear what role they play. Penialin is known to be involved in deregulation of blood glucose levels (hypoglycemic factor).
• substances that regulate the metabolism of minerals (phosphorus, calcium, potassium and magnesium).

6 Biological clock and sleep-wake rhythm

The pineal gland produces the hormone melatonin, which is very important for the sleep-wake rhythm. The human biological clock is located in the suprachiasmatic nucleus (SCN), which lies just behind the optic nerve. Certain light-sensitive nerve cells in the retina (retina) sense light and send a signal via the sympathetic nerve pathway to the suprachiasmatic nucleus (SCN), which stimulates the pineal gland to produce the hormone melatonin.
Melatonin production is stimulated when it gets dark and is inhibited by light. Melatonin is a serotonin-derived hormone that regulates sleep patterns in both day-night rhythm (circadian cycle) and seasonal cycles.

Light stimuli inhibit melatonin production. In the dark, inhibitory neural influences disappear and pineal gland activity increases.
This also explains why people with a clouded retina or glaucoma can experience sleep disorders. They may not receive enough daylight during the day, which inhibits the production of melatonin and disrupts the sleep-wake rhythm.
Melatonin was discovered in 1958 by A.V. Lerner. He also proved that the pineal gland is a true endocrine gland, because melatonin is released into the bloodstream.
The pineal gland is the only organ that has the enzyme oxyindole-O-methyltransferase (OIOMT), which is necessary for the production of melatonin (indole-N-acetyl-5-methoxytryptamine). Approximately 30 µg of melatonin is produced in the pineal gland per day, three quarters of which are produced after midnight until the early morning hours. This has consequences for people who live and work a lot in artificial light or who work night shifts, because the production of melatonin is then disrupted, resulting in insomnia complaints. Depression, high blood pressure, obesity, diabetes (type 2 diabetes) are also associated with a melatonin deficiency.
In Alzheimer's disease and other dementia conditions, the suprachiasmatic nucleus (SCN) is damaged, which means that it does not properly control the pineal gland and less melatonin is produced.

In Alzheimer's patients, a clearly noticeable reduced melatonin concentration is noticeable. This is accompanied by a disturbed sleep-wake rhythm. If people with Alzheimer's disease spend more time in real daylight (two hours of bright light for at least four weeks) during the day, and taking melatonin in tablet form can improve the disturbed sleep-wake rhythm.

Blue light affects the sleep-wake rhythm. In order to be able to read what is on the screen of your tablet, computer, smartphone and television during the brightest moments of a day, these devices continuously emit blue light. Blue light is also found in LED lamps. That blue light imitates sunlight, daylight, which can disrupt the human biological clock. Blue light prevents the production of this sleep hormone.

7 Sexual development

The pineal gland also appears to influence sexual development. Melatonin is responsible for the menstrual cycle in women. Melatonin and serotonin appear to have an inhibitory effect on the formation of two sex hormones, FSH (follicle-stimulating hormone) and LH (luteinizing hormone), which are produced in the anterior pituitary gland. This is called an antigonadotropic effect.
In animals, research has been conducted into what happens when the pineal gland is removed. There was an increase in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the blood and body growth increased. If a person or animal has to live in continuous darkness, the production of growth hormone (GH) decreases
pituitary gland decreases significantly. The removal of the pineal gland removes this darkness and as a result growth hormone is produced again in the pituitary gland.
​

8 Inhibits the development of tumors

The hormones of the pineal gland have an important function. These hormones inhibit growth hormone. They also inhibit unwanted, uncontrollable growth of cells. That is what we call cancer.

With age, it is common for calcium-containing particles to be deposited in the pineal gland.

9 Function of Serotonin

Serotonin is a neurotransmitter of the pineal gland with a predominantly inhibitory function.

It calms you down and is therefore the counterpart of the neurotransmitters adrenaline, dopamine and endorphins that cause action.
Serotonin affects a person's mood and emotion. It helps relieve stress. It regulates the tension of smooth muscles and plays a role in the processing of pain stimuli.

Serotonin helps deal with various forms of anxiety, obsessive thoughts, aggressiveness, etc.

Unlike melatonin, serotonin is produced during the day.

In the event of a shortage of serotonin, the activating neurotransmitters gain the upper hand and various syndromes can arise, such as depression, phobias and more complex psychological disorders.

10 Diseases of the pineal gland

1. Congenital malformations with a deficiency of pineal gland hormones often shows premature sexual development in children.

a. incomplete development (hypoplasia)
b. developmental delay (agenesis)

2. Shriveling (atrophy) of the pineal gland is rare. This is usually due to the pressure of a tumor on the gland itself or in the adjacent brain areas or from the pressure on the gland that has a hydrocephalus.

3. Poor functioning (dystrophic changes) of the pineal gland can occur in case off:

a. infectious diseases
b. liver necrosis
c. phosphorus poisoning
d. leukemia

4. Tissue damage with cell death (necrobiotic changes) of the pineal gland can occur in case off:

a. acute infections
b. eclampsia

5. Blood supply disorders

6. Inflammations

7. Parasitic processes

8. Tumors of the pineal gland

11 Blood supply disorders

• Bleeding in the tissue of the pineal gland can occur at any age. There are several possible causes of bleeding:
  • trauma
  • high bloodpressure
  • arteriosclerosis
  • aneurysm due to congenital vascular abnormalities
  • infection
  • increased bleeding tendency (hemorrhagic diathesis)
• A blood clot in the blood vessels (infarction) can occur as a result of arteriosclerosis.
• An accumulation of blood in the pineal gland (hyperemia). This can occur as a result of acute infections, but also due to too much thyroid hormone in the blood (thyrotoxicosis) and due to abnormally high blood pressure in the lung blood vessels (pulmonary hypertension).

12 Inflammations

If there are inflammatory processes anywhere in the head, they can also affect the pineal gland, for example brain abscess, meningitis  and blood poisoning (sepsis).

13 Parasitic processes

If the doctor suspects that there is a process in the pineal gland involving a parasite, he will first think of echinococcosis.

The echinococcus granulosus is a small tapeworm (also called fox tapeworm) in the small intestine of dogs and canines such as foxes. Fox tapeworm eggs are released into the environment through feces and can enter the human body through food or drink.

Where dogs are used to herd livestock, echinococcosis appears to occur quite often among the farmers involved. There is also a relationship with direct contact with foxes and eating unwashed forest fruits. The parasite can invade brain tissue and form cysts that are prone to growth. A cyst due to echinococcosis has a dense capsule through which medications cannot penetrate, so such a cyst is surgically removed.

14 Tumors of the pineal gland

'Tumor' can indicate both benign and malignant neoplasms.
Pineal gland tumors (pineal tumor or pinealoma) can be either benign or malignant.
Pineal gland tumors are given a grade between 1 and 4 according to how fast they grow, with grade 1 being the slowest growing and grade 4 the most aggressive.

Large tumors require surgical treatment often followed by radiation or chemotherapy.
The pineal gland tumors can also be classified into four groups based on the origin of their cells.

1. Tumors of pineal cell origin (called pineal parenchymal tumors; pineoblastoma and pineocytoma)

2. tumors of germ cell origin (germimoma / germ cell tumors; mature teratomas, benign teratomas, teratocarcinoma, embryonic carcinomas, yolk sac (endodermal sinus tumor), choriocarcinoma and mixed germ cell tumors with features of the aforementioned, glial tumors and meningiomas).
3. Tumors of other cell origin
4. Cysts (fluid-filled cavity).

Tumors in the pineal gland area are germ cell tumors (germimoma) in half of the cases. They also become pinealomas or atypical pineal teratomas. Half of it comes from the pineal gland itself. The other half is located above the Turkish saddle (suprasellar) or lies on the base of the skull (parasellar).
Sometimes it is a metastasis of a tumor elsewhere in the body due to growth through the third ventricle wall or through the cerebrospinal fluid (CSF) from the pineal gland (secondary tumor). Germ cell tumors (germimoma) are very sensitive to radiation (radiotherapy).
Growths of the glandular tissue of the pineal gland (gliosis) occur in 15% of people.
Proportionally, three times as many men are affected by a pineal gland tumor than women. The symptoms of pineal gland tumors depend on the pressure they place on the surrounding tissues, such as pressure on the optic nerve (increased eye pressure).
A tumor in the pineal gland can accelerate or delay puberty.
Precocious puberty (pubertas praecox) occurs in a small percentage of pineal gland tumors. It is caused by pressure on the hypothalamic control center or by decreased production of melatonin.
It can lead to macrogenitosomia praecox
also called the Pellizzi syndrome, characterized by the development of sexual characteristics in youth, with extreme growth in height and of the sexual organs, but without maturation of the sexual organs.

There is often a correlation between a less functioning
hypothalamus and pituitary gland: hypothalamic-pituitary dysfunction.
The names of various growths of the pineal gland according to the WHO grading:

• pineal gland cyst or pinealis cyst - benign
• pineocytoma or pinealocytoma - Grade I
• pineal parenchymal tumors - Grade II+ III
• pineoblastoma/pinealoblastoma - Grade IV
• papillary tumor - Grade II + III

Tumors located in the brain do not have much room to grow.

The skull cannot expand, it is a closed whole containing the brain, cerebral fluid and blood. When a tumor grows, it causes an increase in pressure within the skull and this can put pressure on brain tissue (increased brain pressure), which can manifest itself as:

• headache
• nausea
• vomiting
• drowsiness and sleepiness
• reduced consciousness
• dizziness
• epileptic attacks
• problems with vision
• symptoms of failure of arms and/or legs
• disturbed coordination of movements
• speech disorders
• hydrocephalus
• behavioral changes

15 Specific complaints of increased pressure

15 a Hydrocephalus
By pressure forward, a thin tube filled with cerebrospinal fluid, called the aqueduct of Sylvius (aquaductus cerebri), may be obducted, causing an increased brain pressure and hydrocephalus to develop. The Aqueduct of Silvius is part of a system of corridors and brain cavities filled with cerebrospinal fluid that is connected to the spinal cord.

Complaints may include:

• headache; nagging headache throughout the head, sometimes migraine-like headache
• vomiting
• drowsiness and drowsiness
• reduced consciousness
• swelling of the optic nerve

The image below clearly shows the corridor system with the brain cavities. The aqueduct of Sylvius is the thin tube that runs from top to bottom between the upper cerebral cavities and the fourth (lower) cerebral cavity.

15 b Other complaints of increased pressure

Pressure backwards towards the brain stem

By pressure backwards (caudally) towards the brainstem on the tegmentum (which is also called the 'carpet' of the midbrain) there are problems controlling eye movements.

This can cause the following complaints:

• Problems with eye movement (Parinaud syndrome):
  • vertical gaze palsy (the patient cannot look up or down)
  • inability to look at the nose with both eyes (convergence)
  • certain type of rapid eye movement or nystagmus
  • retraction of the upper eyelid (in 40% of these patients)
• Absence of the pupillary response to light
• The eyes remain at the bottom of the eye socket and are unable to look up (setting sun symptom) 

Pressure sideways to thalamus

With pressure to the side (lateral) towards the thalamus
there may be abnormalities in the visual field (hemianopsia).

Ingrowth into the hypothalamus

Ingrowth into the hypothalamus can result in disruption of growth hormone (GH) production. Sometimes a change in body temperature regulation (thermoregulation), abnormal appetite/gluttony (hyperphagia) or anorexia. However, this is rare.

Pressure on the pituitary gland

Pressure on the pituitary gland can cause diabetes insipidus. It is caused by the fact that the antidiuretic hormone ADH cannot be produced properly in the pituitary gland. This causes urine production to increase and the body to lose too much fluid.

Pressure on the cerebellum

Pressure on the cerebellum can cause gait disturbance, uncoordinated movements (ataxia).

Shifted from the midline

The pineal gland can be displaced from the midline in the skull for various reasons. If the pineal gland is calcified, this can be clearly seen on X-rays.

16 Pineal cyst - Benign

The best known is the pineal gland cyst. This is a fluid-filled cavity that can occur in children and adults. Most pineal gland cysts do not cause any symptoms even if they grow millimeters and do not become malignant. They are often discovered by chance because a scan of the head is made for another reason. An MRI check can show whether the cyst is growing.
If the cyst does cause complaints, the following complaints may occur:

• headache complaints; melatonin tablets can sometimes help.
• disruption of hormones
• hydrocephalus
• increased cerebral pressure

Sometimes the cyst grows and presses on the aqueduct of Sylvius (aqueductus cerebri), causing it to become blocked, causing headaches and increased cerebral pressure and hydrocephalus.

17 Pineocytoma or pinealocytoma Grade I

A pineocytoma or pinealocytoma is a benign slow-growing tumor that originates from the large cells of the pineal parenchyma.
A pineocytoma belongs to the pineal parenchymal tumors, but it is the least aggressive form.

WHO class grade I with a good prognosis.

Possible complaints are:

• Parinaud's syndrome
• Eye movement abnormalities; difficulty looking up or down (vertical gaze palsy)
• Certain type of rapid uncontrolled eye movement eye twitches: nystagmus (convergence-retraction nystagmus)
• Pupil disorders (the patient cannot look up or down)
• Inability to look at the nose with both eyes (convergence)
• Headache
• Hydrocephalus
• Increased brain pressure
• Nausea and vomiting
• Balance problems
• Incontinence
• Cognitive problems
• Memory problems
• Mood swings
• Sometimes difficulty walking and hearing problems
  

18 Pineal parenchymal tumors with mixed differentiation Grade II + III

The parenchymal cells in a tumor (neoplasm) are generally cells that continuously duplicate and give rise to a 'clone' of cells (monoclonal), but they can also transmit a change to the new cells (undergo differentiation) and thus forming a mixed tumor. These tumors fall under the WHO classification of grade 2 + 3
Possible complaints are:

• headache
• nausea
• vomiting
• drowsiness and sleepiness
• reduced consciousness
• dizziness
• epileptic attacks
• problems with vision
• symptoms of failure of arms and/or legs
• disturbed coordination of movements
• speech disorders
• hydrocephalus
• behavioral changes

Both pineocytomas (the benign form) and pinealoblastomas (the malignant form) are tumors that arise from the cells of the pineal parenchyma. The pinealoblastomas arise from the small parenchyma cells and the pineocytomas from the large parenchyma cells.

19 Pinealoblastoma / Pineoblastoma Grade IV

A pineoblastoma or pinealo blastoma arises from the precursor cells that are already present in the embryo; the small cells of the pineal parenchyma.
According to the WHO classification, this tumor is grade IV and is very aggressive. Pineoblastoma is seen more often in boys than in girls and manifests itself on average around the age of twenty.
This type of cancer is often seen in combination with a retinal tumor, retinoblastoma or eye cancer. Hereditary retinal blastoma can be associated with both benign and malignant brain abnormalities and is usually discovered before the age of five. It is therefore advisable to screen children in whom a retinal blastoma has been discovered for pineal gland cancer.
Specific to pineoblastoma is that it can spread to the spinal cord and spinal cord, causing pain in the back. Complaints gradually worsen.

Possible complaints are:

Very common:

• Headache

Common:

• Rapid neurological deterioration
• Increased brain pressure
• Cognitive disorders
• Behavioral changes
• Memory problems

Less common:

• Eye problems like 
  • Short-term blindness of one eye / inability to see in one eye (amaurosis fugax)
    
  • Problems turning the eyes toward the nose, which is necessary for near vision (convergence disorder)
    
  • Swelling of the optic nerve (papilledema)
    
  • Progressive visual field loss
    
  • Reduced acuity of vision
    
  • Retinal tumor/eye cancer (retinoblastoma)
    
• Epileptic attacks
  
• Decreased nerve function with reduced and altered sensation (sensory neuropathy)
  
• Paralysis
  
• Calcification in the median plane of the brain (midline brain calcification)
  

Seldom:

• Drowsiness, dullness, lethargy
  
• Decreased consciousness, confusion

20 Papillary tumor of the pineal region Grade II + III

Papillary tumor of the pineal region (PTPR) is a very rare formation of uncoordinated rapidly growing new tissue (neoplasm) in the pineal region.
This tumor probably arises from specialized ependymocytes. These cells form a membrane around the system of the brain cavities (ventricles). The cerebrospinal fluid in the cerebral cavities is also produced by ependymocytes.
The complaints are variable. Possible complaints are:

Very common:

• Headache
  
• Hydrocephalus
  
• Increased brain pressure
  
• Nausea and vomiting
  
• Double vision (diplopia)
  
• Memory problems

Common:

• Abnormality of the eyelid
  
• Visual field loss
  
• Nystagmus (rapid uncontrollable eye movements)
  
• Periods with coordination disorder and balance disorder (ataxia)
  
• Cognitive disorders
  
• Increased content of cerebrospinal fluid protein
  

Sometimes difficulty walking and hearing problems.