Disorders of the pineal gland can occur due to aging, traumatic, and developmental conditions. Examples include pineal tumors, craniopharyngiomas; injuries affecting the sympathetic innervation of the pineal gland; and rare congenital disorders. Conditions that affect the pineal gland alter melatonin secretion and disrupt the circadian cycle.
As humans age, the pineal gland begins to calcify, which increases with advanced age. Calcification of the pineal gland may correlate with the age-related decline in melatonin production and fragmented sleep-wake patterns in the elderly. Also, some studies have found that the degree of calcification is higher in individuals with Alzheimer disease.
Tumors of the pineal gland are uncommon, constituting approximately three percent of brain tumors. Of the types of tumors that can form in the pineal region, germ cell tumors are the most frequent. They are more common in children aged 1 to 12 years and those assigned males at birth. Pineal gland tumors can lead to hydrocephalus, a condition resulting in the buildup of cerebrospinal fluid in the brain. Hydrocephalus presents with headaches, lethargy, and other signs of increased intracranial pressure, such as blurred vision, vomiting, changes in behavior, and weakness with moving or talking. The majority of individuals with pineal tumors have Parinaud syndrome. This neurological condition makes it difficult for the individual to look upwards due to pressure on the pretectal region of the brain (i.e., the dorsal aspect of the upper midbrain).
Another type of tumor affecting the pineal gland is craniopharyngiomas, rare, benign brain tumors that form near the pituitary gland and the hypothalamus. Craniopharyngiomas can occur at any age, but it occurs most often in children aged 5 to 14 and older adults aged 50 to 74. It is usually made of part solid mass and part fluid-filled cysts. As these cysts grow, the intracranial pressure increases, which can cause headaches, nausea, and vomiting. They may also extend to compress the pituitary gland and lead to hormonal dysfunction. Furthermore, it can compress other nearby structures, such as the optic chiasm, where the two optic nerves partially cross, resulting in visual deficits.
The pineal gland receives innervation from the hypothalamus via the spinal cord and the superior cervical ganglion. If a spinal cord injury occurs, the circuits that influence the basal production of pineal gland hormones may be disrupted. This results in tetraplegia, the inability to voluntarily move the upper and lower body parts. There may also be an absence in the pineal production of melatonin, which results in sleep disorders, poor quality of life, increased oxidative stress, and the loss of anti-inflammatory and neuroprotective effects.
Lastly, an example of a congenital pineal gland disorder includes pineal agenesis, or failure of the pineal gland to develop. This has been linked to mutations in the paired box gene 6 (PAX6), which leads to pineal gland abnormalities and other brain and eye abnormalities. PAX6 is responsible for cortical developmental processes, including cellular proliferation, neuronal migration, and axonal guidance. The extent to which pineal agenesis affects human growth and development has not yet been explored extensively. Additional neurological, endocrine, and sleep studies may help provide further insight into the effects on normal human growth and development.
Magnetic resonance imaging (MRI) is the most useful initial study to identify tumors and other pineal gland abnormalities and delineate their relationship to adjacent structures. For example, if a pineal tumor grows and extends into the third ventricle, it can block the flow of the cerebrospinal fluid and cause obstructive hydrocephalus, which can be seen on MRI. Computed tomography (CT) scans can also detect pineal abnormalities. Pineal region tumors usually appear as a solid mass that brightens with contrast. Additionally, CT can detect calcification of the pineal gland due to increased age.
Treatment of pineal gland tumors and craniopharyngiomas is surgery, if possible. Surgery aims to biopsy and obtain tissue to determine the tumor type and whether it is cancerous. The surgeon will typically remove as much tumor as possible without causing additional symptoms for the individual. Treatments after surgery may include radiation and chemotherapy. Treatment for pineal gland disorders due to injury and chemotherapy.
