Epiphyseal (pineal) hypertension and migraine






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Azad Jafarov was born in Azerbaijan. He completed his primary education,
secondary and high schools in Azerbaijan. In 1995 he came to Turkey to
attend Faculty of Medicine in Training and Research Hospital at Trakya
University. Now he is an intern doctor at this university in Turkey.
The purpose of his preference for Faculty of Medicine is to produce or
create new idea which will be beneficial for all human beings in the World
of Medicine.
While he was attending the 3rd and 4th classes, he has had some interesting


If a person is said to suffer from hypertension, this expression means that the average arterial pressure of that person is above the level which is accepted as normal. The increase in blood pressure is an interesting health problem for three resons; it is frequently seen, its effects are sometimes destructive and its symptoms are not recognizable even in the laters phases of the clinical course. Its effects are common and seen in all organs and it is determined as the only and most important factor of risk for especially both the coronary heart attacks and the cerebrovascular diseases. Also, it may cause direct congestive heart failure and renal inadequacy. There is not a threshold value, high level of which can be regarded as hypertensive and low level, safe for individuals, women and men. Infact, this value increases gradually as the destructive effects of the blood pressure increases. Therefore, hypertension should be determined subjectively, in a way. Several people agree with the idea that the basic criterion of the diastolic pressure is always to be above 90 mmHg. That the systolic pressure is always 140 mmHg is defined as hypertension, but the clinical results of this, are different from diastolic hypertension for some reasons. When these criteria are considered to be base, the ratio of people suffering from hypertension to the general population is found to be 25% in a comprehensive scanning program. However, the systolic and the diastolic values which are regarded as limit for adults, are considered as 160/95. Even with these values, the frequency rate is frighteningly found to be 18% during this program above. Despite the fact that hypertension tends to be much more severe for young adults, the frequency of hypertension increases with age.

Approximately 90% of hypertension is idiopathic and it is specifically seen as primary (essential) hypertension. 10% of the rest is secondary for most renal diseases and coarctation of the renal artery (renovascular hypertension) which is generally caused by an atheroma plaque. Secondary hypertension develops as a results of primary aldosteronism at a low rate, and some surrenal disorders such as Cushing’s syndrome and feochromositoma.


  • Primary (essential) HT
  • Secondary HT
  • HT resulting from paranchymatous nephritis
  • HT resulting from renovascular diseases
  • HT resulting from hyperparathyroidism
  • HT resulting from adrenal or hypophyseal Cushing’s syndrome
  • HT resulting from primary aldosteronism
  • HT resulting from congenital adrenal hyperplasia
  • HT resulting from feochromasitoma
  • HT resulting from toxemia of pregnancy
  • HT resulting from aortic coarctation developing in the superior part of the body
  • Toxic HT (Toxication of lead, cadmium and other agents)
  • HT resulting from the increase of the endocranial pressure
  • HT resulting from the use of birth control pills

In addition to those mentioned above, I think, there is another different HT. This is the Epiphyseal HT which develops itself scientifically and logically. This type of HT is explained below:


The pineal gland, which weighs 0.10 - 0.18 in human beings, is in the sulcus between the colliculi superior and it is composed of cellular lobules which are seperated from each other by means of a connective tissue septum. It consist of two types of cells which are called pinealocyte and neuroglia. It develops calcification which varies in degree with age. In radiologic studies, the determination of calcification is regarded as the sign of that the pineal is in its postpubertal period. The activation of the pineal gland continues during the life time inspite of the calcification. The pineal gland develops vascularization in vital scales. It is said to be second after the kidneys with its value of 4 ml/min/g in respect to blood flow. -That it is vascularized so much after kidneys means it has a vital importance in the organism.

The continuty of the endocrinous function of the pineal gland depends on neural innervation on a great scale. Therefore it is regarded as a neuroendocrinous organ. That the sensorial knowledge concerning light and darkness of the environment by eyes plays an important role in the secretion of melatonin from the pineal gland. Generally, light decreases the secretion of melatonin, on the contrary darkness increases it. Therefore, melatonin is called the hormone of darkness. In healthy people, melatonin is secreted more at nights. Generally, the secretion of melatonin begins between the hours 21:00 and 22:00 and it decreases between the hours 07:00 and 09:00. In adults, its average maximum levels in plasma are between 50-70 pg/ml. Its maximum concentration in plasma is observed between the hours 02:00 and 04:00. -It is proved that the ilnesses become more serious at nights as a result of the increase in the tonus of the vagus. That the concentration of melatonin increases at 2 A.M. gives us a clue about the necessity of research and thinking about this subject. -For human beings, 1000-2500 lx light causes decrease in the secretion of melatonin.

Melatonin is released in the general circulation. As soon it is exposed to darkness, its secretion increases and the secretion stops in the light.

The concentration of melatonin in the blood varies according to the age. It reaches its maximum level in the blood at nearly eighth age and it obviously begins to decrease in the period of puberty. An increase in the level of melatonin has been observed in some cases where puberty is delayed. Melatonin level of the blood continuously decreases after puberty. That the secretion of melatonin, which is high in sick males who lacks GnRH, arrives at its normal level with a testosterone treatment is proved to regulate the secretion of melatonin by the fact that the gonadal steroids probably affect the spesific receptors those available in the pineal gland. -That’s to say, it puts the fact forward that epiphysis has a great effect on the development of the organism and the protection of the mutual balance of hormons of the endocrine glands.

Also, seasonal differences are very effective on the secretion of melatonin. In months of winter and summer, the levels of plasma melatonin are higher when they are compared with the ones in months of spring and fall.

The continuity of the rhythm of melatonin in human beings depends on the availability of the sympathetic innervation of the tractus retinohypothalamicus and the pineal. If the tractus retinohypothamicus is sectioned, it results in the disorder of the circadien cycle. During the degenerative sympathetic neuropathies, the rhythm of melatonin is lost. For example; in the peripheric diabetic neuropathy with sympathetic degeneration and when the cervical cords is sectioned, the rhythm of melatonin is lost.

Among the substances which are biologically active in the pineal the biological amins (norepinephrine, serotonin, histamine, melatonin and other indolamins, dopamine and octapamine) and peptides (TRH, LHRH, somathostatine and vasotocin which is the analogue of oxytocin) might be included. Also, the pineal has a protein named as inhibitor neurotransmitter GABA and epiphysin which resembles neurofusin. Also, some peptides which have not been identified yet, it may result in some gonodotrophin inhibitor effects on the pineal. -As it is understood from what we have said, the substances prepared by the epiphysis help the protection of the compensatory ability of the human organism and the protection of the resistance of the organism against diseases.

Melatonin, which is the main hormone secreted from the pineal, is a derivative of an indole. The synthesis of indolamin occurs in the pinealocyte. Tryptophan is transformed into 5-hydroxytrypophan (5- HTP) by hydroxylasis, and 5-HTP is transformed into serotonin (5-HT) by means of aromatic amino acid decarboxylasis (dopa decarboxylasis), Serotonin is transformed into N-acetyl serotonin by means of serotonin N-acetyl transferasis (NAT) and lastly N-acetyl serotonin is transformed into melatonin by the enzyme of hydroxyindole-O-methyltransferasis (HIOMT).

The production of melatonin is under adrenergic control. The increase in the synthesis of melatonin from the pineal gland in the dark is possible with the secretion of NE(norepinephrine) from the postganglionic nerve endings which are in the pineal gland.NE accelerates NAT and so the synthesis of melatonin by increasing the production of c-AMP affecting the main 1 receptors which are in the pinealocyte membrane. 1 receptors are in the pinealocytes and they play a role which increases the stimulation during the regulation of the pineal function. It has been determined that the activities of NAT and HYOMT enzymes, which play a role during the transformation of serotonin into melatonin, are higher in human pineal gland at night. The changes in the content of NAT are dramatical and they increases 25-100 fold after a few minutes when the environment is darkened. They also cause beta-adrenergic blockers and light enzyme activity to decrease quickly (half life 3.5 minutes).

In my opinion, in the cases in which I have arrived at a conclusion of epiphyseal hypertension, the transformation of serotonin into melatonin is disordered and concentration of serotonin has increased in the peripheric circulation. This is impossible in several ways:

  1. NAT enzyme has decreased. That is, a part of serotonin is transformed into melatonin but the concentration of serotonin is high.
  2. NAT enzyme is normal but the pineal gland hyperplasia or the syntesis of serotonin has increased for another reason. Perhaps, NAT which is at its normal level might not be transforming all the serotonin into melatonin.
  3. There is not a NAT enzyme or an auto-antibody has been produced.
  4. There are not 1 receptors in the pineal gland or an auto-antibody has been produced. Therefore, NE, NAT and so the melatonin perform its synthesis.
  5. The production of melatonin which depends on the sympathetic nerve degeneration might not be performed.
  6. There may be a disorder in getting tryptophan.

As a conclusion, Epiphyseal Hypertension develops as a result of the high rate of serotonin. Serotonin directly constricts the vessel walls (of skin, kidney, stomach, uterus, brain, placenta vessel walls and umblical vessels) excluding the ones in the skeletal muscles. During the constriction of vessels by 5-HT, the direct effect of vessel smooth muscles generally plays a role depending on their activation of 5-HT1 and/or 5-HT2 receptors. During the constriction of vessels by serotonin, secondarily, its potentialization or “amplification” of the effects of the endogenous vasoconstrictor substances such as angiotensin II, PGF2, adrenaline, noradrenaline play a role, too. (It is also said that serotonin is synthesized in the pineal paranchimal cells and taken by the sympathetic nerve endings in the gland). -As we mentioned above NE plays a role during the transformation serotonin into melatonin. In case of absence or inadequacy of NAT, NE increases more as serotonin can not be transformed into melatonin. This results in an increase in tension.

Renal vessel walls are very sensitive to serotonin; they cause severe vasoconstriction which may cause necrose in the renal tissues of the animals used in experiments. They also form antidiuresis decreasing the speed of glomerular filtration. Renal vasoconstriction effect is generally mediated by receptors like 5-HT1. -As it is understood, long-term vasoconstriction of the renal vessel walls may be regarded as one of the causes of Goldblatt hypertension.

The direct effect of serotonin on the heart is not obvious in the in vivo experiments. Serotonin may stimulate the heart with an indirect effect of increasing the secretion of cathecolamines from medulloadrenal as well as it may make the heart beat speed slow down with the effect of Bezold-Jarisch. But, in an isolated heart, serotonin cause obvious pozitive chronothrop and inothrop effects. That these effects are partially direct and they partially stimulate the adrenergic nerve endings in the heart, helps us determine that the receptors, which play a role in positive inothrop and chronothrop effects in human beings, are 5-HT4 in the myocardium.

As we all understand from the knowledge above, serotonin, which increases as a result of an epiphyseal disorder, have the arterial pressure increased in direct and indirect ways. We can give examples for its indirect increase of arterial pressure such as its having the vessel walls become sensitive to endogenous vasoconstrictors and also its constricting the renal vessel walls.

Besides hypertension, its effects on the heart are worrisome in these patients. Its direct or indirect effect on the heart is so frightening as resulting in heart failure for the patient. The superfluity of serotonin in the blood can decrease the nourishment of the heart with a constriting effect as well as increasing the tension with the effect of vasoconstriction in vessels all over the body. The effect of the superfluity of serotonin in the blood become obvious through a sequence of symptoms. Thus, the tension may increase in such patients provided that it does not increase so much (160-180 systolik). Heart beat sometimes increases and it may be deemed as heart failure. Pains stem from on specific points at the level of heart. Such patients are very excited and they always feel frightened and quite restless. This restlessness may be stemming from the fact that serotonin can not be transformed into melatonin. The basic point of this hypertension is that it has the characteristics mentioned above although it it doesn’t increase too mush.


The serotonin secreted by epiphysis may scientifically and logically be said to play a role in etiopathogenesis of migraine. As it is known, there are two hypothesis about the etiopathogenesis of migraine, which have not been proved yet. The first one is that the cause of pain stemming from migraine is the inadequate blood flow in the capillary as a result of the folded precapillary arteriovenous shunts and of the discharge of serotonin from the tissue and thrombosits which lie at the cerebral vessel walls nourished by the carotid arteria. Secondly, the migraine fit stems from the local inflammation resulting from the proinflammatory peptides released from the trigominovascular afferent nerve endings according to the hypothesis on the neurogenic inflammation of the pathogenesis of migraine. -In addition, I claim a hypothesis which is appropriate for the clinic of migraine. I support the thesis that migraine occurs as a result of the increase in the concentration of serotonin in epiphyseal disorders. Because, patients suffering from migraine prefer relaxing in dark and quiet atmosphere. During this period, a great part of serotonin in the epiphysis is transformed into melatonin and serotonin in the periphery decreases partially. This decrease, in the concentration of serotonin in the periphery relaxes the patient and results in a partial recovery of the pain. This type of patients generally suffer from photophobia.

At the beginning phase of migraine, both extracranial and intracranial vessels are contracted. This contraction takes 5-45 minutes and then vasodilatation begins.

In my opinion, the first vasoconstriction occurs as a result of the combination of serotonin with some cerebrovascular receptors such as 5-HT2 and 5-HT1. However, 5-HT1D receptors aremore than the others in Central Nervous System(CNS) vessels and then vasodilatation occurs as a result of the combination of serotonin to these receptors with the increase in concentration of serotonin. As it is mentioned in the first hypothesis, it results in the unfolding of the shunts. The vasodilatator effect of serotonin partially depends on the release of EDRF (nitricoxide) through 5-HT1D receptors from the endothelium.

The effect mechanism of partial agonists of serotonin like Metiserjid which is used in the treatment of migraine has not been obvious up till now. I think, these medicine prevents vasodilatation by clinging to 5-HT1D receptors before serotonin has clung to them, that is at the beginning of the attack. These preparatives has no effect when they are used after the attack begins.

Consequently; Migraine is not a neurologic disease, but it occurs depending on the incrase of serotonin as a result of an epiphyseal disorder. I think, this is the epiphyseal hypertension which we mentioned about when describing the characteristics of patients suffering from migraine. Perhaps, the patient suffering from epiphyseal hypertension may not have migraine, but they probably suffer from a slight headache.


  1. If the clinical sympthoms, which are mentioned above, are seen in patients whose tension is not so high, the examination of epiphysis and the measurement of the amount of serotonin in the blood may play an important role while lightening the etiopatogenesis phase of the disease both scientifically and logikally.
  2. In such patients the measurement of the enzymes which transforms serotonin into melatonin in the blood may lighten our topic.
  3. At the same time, the measurement of the enzymes which transforms serotonin into melatonin in the blood on patients who are suffering from migraine, will be useful for the treatment of this disease.
  4. I think, what we all mentioned up to now will be helpful for the correct treatment and suitable medicine for the diseases and the patients suffering from them.


  1. Tÿbbi fizyoloji - Guyton & Hall
  2. Temel patoloji - Kumar. Cotran. Robins
  3. Temel iç hastalÿklarÿ - Ÿliçin. Únal. Biberoõlu. Akalÿn. Suleymanlar.
  4. Tÿbbi Farmakoloji - Oõuz Kayaalp
  5. Farmakoloji ders kitabÿ - Türk Farmakoloji Derneõi
  6. Endokrinoloji ve Metabolizma hastalÿklarÿ kurs kitabÿ 1997 Ankara
  7. Nõroloji - Ÿstanbul Üniversitesi Cerrahpata Tÿp Fakültesi Nõroloji Anabilim dalÿ
  8. Farmakoloji Ders Notlarÿ - Dr. Arif Nihat Dursun
  9. Patoloji - Arthur S.Schneider. Philip A.Szanto

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