Pineal Calcification Research Articles

Is postmenopausal osteoporosis related to pineal gland functions?

There is currently considerable interest in the pathogenesis of postmenopausal osteoporosis, which is the most common metabolic bone disease. Osteoporosis affects approximately 20 million persons in the United States, 90% of whom are postmenopausal women. Although there is evidence that estrogen deficiency is an important contributory factor, the pathogenesis of osteoporosis is multifactorial and presently poorly understood. There is evidence that pineal melatonin is an anti-aging hormone and that the menopause is associated with a substantial decline in melatonin secretion and an increased rate of pineal calcification. Animal data indicate that pineal melatonin is involved in the regulation of calcium and phosphorus metabolism by stimulating the activity of the parathyroid glands and by inhibiting calcitonin release and inhibiting prostaglandin synthesis. Hence, the pineal gland may function as a "fine tuner" of calcium homeostasis. In the following communication, we propose that the fall of melatonin plasma levels during the early stage of menopause may be an important contributory factor in the development of postmenopausal osteoporosis. Consequently, plasma melatonin levels taken in the early menopause could be used as an indicator or perhaps as a marker for susceptibility to postmenopausal osteoporosis. Moreover, light therapy, administration of oral melatonin (2.5 mg at night) or agents which induce a sustained release of melatonin secretion such as 5-methoxypsoralen, could be useful agents in the prophylaxis and treatment of postmenopausal osteoporosis. Finally, since application of external artificial magnetic fields has been shown to synchronize melatonin secretion in experimental animals and humans, we propose that treatment with artificial magnetic fields may be beneficial for postmenopausal osteoporosis.

FACTORS INFLUENCING URINARY 6‐SULPHATOXYMELATONIN, A MAJOR MELATONIN METABOLITE, IN NORMAL HUMAN SUBJECTS

6-Sulphatoxymelatonin (aMT6s) has been measured, by a direct radioimmunoassay, in urine from 130 normal volunteers aged 2-80 years. Its relationship to a number of physiological parameters has been assessed. Total urinary excretion of aMT6s did not vary in a group of 40 children aged 2-20 years (24 boys and 16 girls) except when expressed as a function of body weight. In this case, total aMT6s excretion over 24 h decreased as a function of age. In 90 adult volunteers (44 men and 46 women) aged 20-80 years, there was an age-related decline in total 24 h aMT6s excretion with significantly lower values in elderly subjects. In this same adult group no relationships were found between total aMT6s excretion and body weight or height. No sex differences were found either in the 2-20 years or the 20-80 years groups. Pineal calcification was assessed by lateral skull X-ray in 26 adult volunteers (17 men and 9 women) aged 20-50 years. No significant differences in aMT6s excretion were found as a function of pineal calcification. In 16 of these subjects plasma melatonin and aMT6s also showed no relationship to pineal calcification. These studies confirm the usefulness of aMT6s as an index of melatonin secretion in normal volunteers.

The Relationship of Pineal Calcification to Subtypes of Tardive Dyskinesia in Bipolar Patients

Recent studies have suggested that bipolar patients may be at high risk for developing tardive dyskinesia (TD) if exposed to chronic neuroleptic therapy. It has been suggested that reduced melatonin secretion may favor the development of TD in bipolar and schizoaffective patients. Since pinealectomized rats have been reported to develop increased incidence and severity of abnormal chewing movements, and as depression is associated with reduced melatonin secretion, the increased risk of TD in bipolar patients may be associated with diminished melatonin secretion. Evidence suggestive of an inverse correlation between pineal calcification and reduced melatonin secretion, led me to study the relationship between pineal calcification on CT scan and the severity of axial (truncal) and limb and orofacial dyskinesias in bipolar patients with TD. The incidence of pathologically enlarged pineal calcifications (i.e., greater than 1 cm in diameter) in the bipolar patients was 25 times greater than the reported incidence in the literature among nonpsychiatric patients. In addition, there was a significant difference in scores of axial dyskinesias between patients with pineal calcification of less than 1 cm in diameter compared to those with pineal calcification of greater than 1 cm in diameter (F = 3.24; p = .04, one-way ANOVA). There was no significant association between scores of limb and orofacial dyskinesias and pineal calcification. These findings suggest a meaningful association between the presence of enlarged pineal calcification, and axial dyskinesias in bipolar patients. Further studies using direct plasma melatonin measurements are required to more precisely define the association between TD and melatonin secretion in bipolar patients.

The Relationship Between Ect Nonresponsiveness and Calcification of the Pineal Gland in Bipolar Patients

It has been suggested recently that the therapeutic effects of electroconvulsive therapy (ECT) may be mediated in part through stimulation of pineal melatonin secretion. If melatonin does mediate the antidepressant effects of ECT and depression itself is associated in some patients with reduced melatonin secretion, patients with reduced melatonin secretion could respond less readily to ECT. There is evidence to suggest an inverse relationship between melatonin secretion and the degree of pineal calcification. Specifically, heavy pineal calcifications in animals have been reported to be associated with reduced plasma melatonin levels. In this study, an investigation was conducted to establish more precisely the relationship between the clinical response to ECT in 17 bipolar patients and the degrees of pineal calcification present on CT scan. There was a significant association between ECT nonresponsiveness and the presence of pathologically enlarged pineal calcification (i.e., greater than 1 cm in diameter) (p.01). In addition, there was a significant difference in ECT responsiveness in patients without pineal calcification compared to those with pathologically enlarged pineal calcification (F = 6.10; p = .01, one-way ANOVA). These findings indicate an association between enlarged pineal calcification and ECT nonresponsiveness and suggest that reduced melatonin secretion may be associated with ECT nonresponsiveness. An enlarged pineal calcification could be a useful radiological marker of ECT nonresponsiveness and administration of melatonin precursors (i.e., L-tryptophan; 5-HTP) and its cofactors (i.e., pyridoxine, folate) as well as melatonin-release enhancing agents (i.e., 5-methoxypsoralen) prior to ECT might augment its antidepressant effects in bipolar patients.

The association of pineal calcification with drug-induced dystonic movements

There is evidence that reduced melatonin secretion is associated with the pathophysiology of neuroleptic-induced movement disorders including tardive dyskinesia and Parkinsonism. It has been recently reported that pinealectomized rats developed increased incidence and severity of spontaneous chewing movements compared to normal controls. Increased chewing movements in rats has been suggested to reflect acute drug-induced dystonias in humans. To investigate the relationship between melatonin secretion and the pathophysiology of neuroleptic-induced dystonic movements, the presence and size of pineal calcification (PC) on CT scan was studied in relation to the severity of dystonic movements in 34 neuroleptic-treated chronic schizophrenic patients. The incidence of pathologically enlarged PC (greater than 1 cm in diameter) in the schizophrenic patients was 8-9 times greater than the incidence reported in the literature among nonpsychiatric patients. In addition, there were significant differences (p less than .0001) between the severity of dystonic movements in patients with no PC and those with pathologically enlarged PC, and between the severity of the dystonic movements in patients with PC of less than 1 cm and those with PC of greater than 1 cm diameter. These findings indicate an association between the pathophysiology of neuroleptic-induced dystonic movements and the presence of enlarged PCs and suggest that disturbances of melatonin secretion is associated with the emergence of neuroleptic-induced dystonic movements in schizophrenic patients. Further studies using direct measurements of plasma melatonin levels are required more precisely to confirm the association between pineal melatonin secretion and the pathophysiology of drug-induced dystonic movement disorders.

Pineal calcification and subtypes of tardive dyskinesia

There is evidence that reduced melatonin secretion is associated with the pathophysiology of tardive dyskinesia (TD). To investigate the relationship between melatonin secretion and TD, I evaluated scores of subtypes of TD with CT scan measurements of pineal calcification (PC) size in 77 chronic institutionalized schizophrenic and bipolar patients. There was a significantly greater incidence of pathologically enlarged calcified pineal glands (greater than 1 cm in diameter) in the patients (18.1%) compared to the reported incidence in the literature in nonpsychiatric subjects (1%). In addition, there was a significant association between scores of limb-axial (but not orofacial) dyskinesias and the presence of pathologically enlarged PC (p less than 0.05). These findings support the notion that the pathophysiology of orofacial dyskinesias may be distinct from limb-axial dyskinesias. In addition, since it is possible that a pathologically enlarged calcified pineal gland is associated with reduced melatonin secretion, these findings add further support to implicate decreased melatonin secretion in the pathophysiology of TD. Further studies using direct measurements of plasma melatonin levels are required to define more precisely the relationship between TD and melatonin secretion.

The Relationship of Pineal Calcification to Tardive Dyskinesia

Click to increase image sizeClick to decrease image sizeKey Words: pineal calcificationmelatonintardive dyskinesia

A radiologic study by CT scan of pineal size in cancer patients: correlation to melatonin blood levels.

Alterations in size of the pineal body and melatonin secretion have been observed in cancer patients. The present study was carried out to evaluate pineal dimensions in a group of cancer patients and their relation to melatonin blood levels. The study included 70 oncologic patients. As controls, 41 patients with acute or chronic disease other than cancer entered the study. Melatonin serum levels were measured by radioimmunoassay on venous blood samples collected at 9:00 a.m. Pineal size was determined by brain CT scan, by considering the product of the two longest perpendicular diameters, multiplied by the thickness of the stratum. The volume of the pineal body was found to be enlarged in 12/70 (17%) cancer patients, and its mean value was significantly higher than that observed in controls. Melatonin levels were also significantly higher in oncologic patients than in controls. However, there was no correlation between melatonin levels and pineal size in cancer patients. Finally, cancer patients did not show a higher degree of pineal calcifications than controls. The clinical significance of pineal enlargement in cancer patients remains to be understood.

CT of pineal region tumors.

The computed tomographic (CT) features of pineal region tumors were analyzed in 60 histologically proven tumors. This is the largest reported series of histologically verified pineal region tumors studied with CT. The tumors were classified as germ-cell tumors, glial tumors, pineal parenchymal tumors, and meningiomas. Preenhancement germinomas revealed characteristically high-density areas with calcification; uniform enhancement was seen after injection of contrast material. When present, pineal calcification was engulfed by the tumor. Teratomas, present only in male patients, revealed areas of mixed densities (e.g., calcification and fatty areas) and did not show significant contrast enhancement. Spontaneous intraventricular rupture was noted in one case. Unlike other tumors, the original pineal calcification could be recognized in two-thirds of glioma cases and was displaced anteriorly and superiorly in most. Gliomas were hypodense to isodense on precontrast scans and enhanced in a nodular and a ring fashion. Benign pineal parenchymal tumors showed iso- to hyperdense areas with nodular enhancement after injection of contrast material. Pineoblastomas were well defined hyperdense masses without calcification on precontrast scans. After injection of contrast material, they showed well defined enhancement with occasional small, central lucencies. Meningiomas were hyperdense in most cases, uniformly enhanced in a homogeneous fashion, and showed a tentorial attachment.

Incidence of pineal calcification in the first 18 years of life

There are sparse or contradictory data on frequency and pathological significance of pineal calcifications in childhood. This is particularly so for children younger than 6 years of age. We therefore looked for pineal gland calcifications in 1044 consecutive a.p. and lateral skull films. Pineal calcification was diagnosed, if accepted by both authors, and if the calcified spot fitted into at least 2 of 4 localisation methods. 80 patients with pineal calcifications were detected using this method. In 40 of these patients CCT confirmed the calcification. The frequency of pineal calcification was 3% in the first 12 months of life rising gradually to 7.1% in children of 10 years of age. From 10 years onwards, there is a marked increase of frequency of calcifications of the pineal gland up to 33% in the group of children of 18 years of age. In contrast to some statements in literature, pineal calcifications seem to be physiological in a limited percentage even below the age of 6 years.

Pineal gland calcification and defective sense of direction.

Calcification of the pineal gland is shown to be closely related to defective sense of direction. In a tricentre prospective study of 750 patients lateral skull radiographs showed that 394 had calcified pineal glands. Sense of direction was assessed by subjective questioning and objective testing and the results noted on a scale of 0-10 (where 10 equals perfect sense of direction). The average score for the 394 patients with pineal gland calcification was 3.7 (range 0-8), whereas the 356 patients without pineal gland calcification had an average score of 7.6 (range 2-10). This difference was highly significant (p less than 0.01). A smaller parallel study in pigeons showed that pineal calcification also leads to a reduction in homing abilities. The findings suggested that the pineal gland plays an important part in directional sense and that damage to the gland, as indicated by calcification, causes defective sense of direction - perhaps by altering the intrinsic intracranial electromagnetic environment and thus affecting the magnetite response mechanism.

Isodense Epidermoid Cyst in the Pineal Region

A 69-year-old male was admitted complaining of gait disturbances and diplopia, 2.5 years after an episode of serous meningitis. Neurological examination on admission disclosed Parinaud's sign, unsteady gait and dysdiadochokinesis on the left side. A striking finding on the computerized tomography (CT) was the left to right shift of the posterior portion of the third ventricle without visualization of the quadrigeminal and ambient cisterns, which were almost completely occupied by an isodense mass accompanied by high dense flecks and a low dense part. Enhanced CT showed positive enhancement in the vicinity of the pineal calcification. By the suboccipital supracerebellar approach, an encapsulated mass containing brownish yellow fluid was subtotally removed and a histological examination of it revealed epidermoid tissue and hemosiderin deposits in the solid portion. Few reports of isodense epidermoid cysts have so far been found in the literature giving a full explanation for this unusual CT attenuation value. Based on the clinical course and histology of this case, the pathogenesis of the unusual density is discussed along the following lines: The mixture of the low dense factor due to cholesterin and the high dense factor due to prior bleeding is believed to result in the isodense attenuation value in the liquid portion. Also, in the solid part, a microscopically mixed texture of deposited hemosiderin and cholesterin clefts in the inflammatory granulomatous tissue could explain its density on the CT scan.

Clinical and computed tomographic correlations of pineal neoplasms

Ten patients with pineal neoplasms were evaluated by CT. Germinomas appear as hyperdense lesions in the posterior third ventricular region on plain scan and show homogeneous enhancement which sometimes extends to the anterior third and lateral periventricular region. The pineal gland usually appears normal. Tumors originating from pineal cell cause abnormal pineal calcification and appear as iso or hypodense masses with heterogeneous calcification on plain scan. They usually show heterogeneous enhancement. Based upon CT findings differentiation of the varied types tumors of pineal region or differentiation from astrocytomas is not usually possible.

Age-related incidence of pineal calcification detected by computed tomography.

The age-related incidence of detectable pineal calcification in 725 patients (age range, newborn-20 yrs) suggests that there is a relationship between calcification and the hormonal role played by the pineal gland in the regulation of sexual development. Pineal calcification (demonstrated by computed tomography (CT) on 8-mm-thick sections) in patients less than 6 years old should be looked upon with suspicion, and follow-up CT should be considered to exclude the possible development of a pineal neoplasm.

Pineal Tumors

The clinical presentations, findings of neuroradiological examinations, laboratory findings, pathological diagnoses, methods of treatment, and results of follow-up of 43 cases of pineal tumor collected at the Nagoya University Hospital from 1958 to 1979 are reviewed. The definitions of calcification of the pineal body and of pineal tumor are given. There is a significant difference in the incidence of calcification of the pineal body between pineal teratomas and pineal germinomas. Although there is a 100% rate of calcification of the pineal body in cases of pineal germinoma, the rate is very low in cases of pineal teratoma; calcification appears in only a small percentage of the cases of teratoma mixed with germinoma or embryonal carcinoma, or both. In male patients with suprasellar germinoma, there is a high frequency of an associated pineal calcification. No pineal calcification is seen in cases of basal ganglia germinoma. The computed tomographic (CT) findings of pineal teratoma and germinoma are characteristic. CT scanning is superior for early diagnosis of suprasellar and basal ganglia germinomas.

Pineal calcification on computed tomography

Pineal calcification on computed tomography

ROLE OF PINEAL GLAND IN ÆTIOLOGY AND TREATMENT OF BREAST CANCER

The hypothesis that diminished function of the pineal gland may promote the development of breast cancer in human beings is suggested by the relation between breast cancer and prolonged œstrogen excess, and by the observation that the pineal secretion, melatonin, inhibits ovarian œstrogen production, pituitary gonadotrophin production, and sexual development and maturation. The hypothesis is supported by the following points. (1) Pineal calcification is commonest in countries with high rates of breast cancer and lowest in areas with a low incidence; the incidences of pineal calcification and of breast cancer are moderate among the black population in the United States. (2) Chlorpromazine raises serum-melatonin; there are reports that psychiatric patients taking chlorpromazine have a lower incidence of breast cancer. (3) Although information is lacking on breast cancer, the pineal and melatonin may influence tumour induction and growth in experimental animals. (4) The demonstration of a melatonin receptor in human ovary suggests a direct influence of this hormone on the ovarian function, and possibly œstrogen production. (5) Impaired pineal secretion is believed to be an important factor triggering puberty (early menarche is a risk factor for breast cancer).

Distribution of calcification within the pineal gland.

The distribution of calcification in the normal pineal gland was investigated by a macroradiographic in vitro technique. The centre of calcification in 72 out of 73 glands studied was within 2 mm of the mid-line of the gland. In one gland it lay 2.6 mm from the mid-line. These findings explain the accepted normal limits for pineal calcification on the standard semi-axial projection of the skull of up to 2 mm to either side of the mid-line and the occasional measurement in excess of this in normal subjects.

The Ultrastructure of the Gerbil Pineal Gland Under Normal and Experimental Conditions

Multilayered concretions (corpora arenacea), which have been found in the pineal gland of numerous species, may be indicative of the intensity of the secretory processes of the pineal gland. Concretions in the pineal gland of the gerbil (Meriones unguiculatus) occur by the age of 2 months and are a consistent feature in the adult animal. We feel the gerbil pineal provides a good system for examining pineal calcification under controlled conditions.The ultrastructure of the pineal gland of the gerbil was examined in 1 to 18 month old gerbils which had been maintained in a controlled light environment (LD 14:10). Other gerbils used for this study had been maintained either in constant light environment, had been superior cervical ganglionectomized, or had been blinded by bilateral optic enucleation.

Calcified inclusions in the superficial pineal gland of the mongolian gerbil<i>, Meriones unguiculatu</i><i>s</i>

A histological and histochemical study of the pineal gland of neonatal, juvenile and adult gerbils is described. Calcified inclusions appear within pinealocytes in the superficial pineal about the third week of age, and the incidence of inclusions increased with age until, by the eleventh week, they are found in all animals. The inclusions contain an organic matrix composed of a carbohydrate, probably an acid mucopolysaccharide, complexed to protein. Calcification does not occur in the deep pineal. The data are interpreted to indicate that the formation of calcified inclusions is a normal process within the gerbil pineal. The similarity of the process of calcification in the gerbil and in the human pineal suggests that the gerbil may be an animal of choice for the controlled study of the phenomenon of pineal calcification.