DISEASES OF THE Pituitary Gland
The pituitary gland is a bean-sized gland located at the base of the brain, just behind the nasal root, inside a bone structure called the sella turcica. It is responsible for managing our endocrine system like an orchestra conductor. The pituitary gland consists of two lobes, anterior (adenohypophysis) and posterior (neurohypophysis). While 6 different hormones named TSH, ACTH, GH, LH, FSH and Prolactin are synthesized from the anterior pituitary gland, two different hormones named ADH and Oxytocin are synthesized from the posterior pituitary gland. Diseases affecting the pituitary gland may result in excess or incomplete synthesis of one or more of these hormones, and in this case, complaints about the related hormone occur. Again, since the pituitary gland is located at the base of our brain, a disease that occurs here may affect the parts of our brain adjacent to the gland, causing neurological findings such as headache, vision problems, etc. We can roughly list the diseases related to the pituitary gland as follows.
Prolactinoma (Prolactin)
Acromegaly (GH)
Cushing’s Disease (ACTH)
TSHOMA (TSH)
Hypopitutarism
Craniopharyngioma
Diabetes Insipidus
Pituitary incidentilomas
1- PROLAKTINOMA:
Prolactin is secreted from the pituitary gland and its task is to ensure the production of milk from the breast (breast) in women. milk hormone) is a hormone. The normal value of prolactin hormone is <25ng/ml in women and 20 ng/ml in men. The presence of prolactin above these values is called Hyperprolactinemia. Many different reasons such as pregnancy, pituitary adenomas, drugs (depression drugs, birth control pills, etc.), hypothyroidism, liver diseases, kidney diseases, tight clothing and stress, etc. can increase the prolactin hormone value. If the Prolactin hormone is elevated due to an adenoma (benign mass) formed in the Pituitary gland, this situation is called Prolactinoma.
While high prolactin hormone causes symptoms such as menstrual irregularity, galactorrhea (milk from the breast), increased hair growth and infertility in women, the only finding in men is usually sexual dysfunction and infertility. Neurological findings such as headache and vision problems may occur in both sexes, depending on the adenoma in the brain.
Prolactin hormone level should be checked first in people with the above complaints. If the prolactin hormone is high, the use of drugs that may cause hormone elevation should be questioned in the second stage. Then, liver, kidney and thyroid functions should be evaluated with blood tests. Pregnancy must be ruled out in female patients. If no explanation can be found as a result of the tests, pituitary MRI examinations should be performed and it should be checked whether there is an adenoma in the pituitary gland.
The diagnosis of patients with elevated prolactin levels and adenoma detected in Pituitary MRI is Prolactinoma. After this stage, patients should be questioned about other pituitary hormone disorders and necessary pituitary function tests should be performed.
The first treatment option in diagnosed patients, except for some specific conditions, is drug therapy. In the vast majority of cases, the disease is effectively treated with Dopamine Agonist (Bromocriptine-Cabergoline) drugs. Rarely, Neurosurgery (Transsphenoidal adenoctomy) and Radiotherapy (gamma knife-cyber knife) are needed.
2- ACROMEGALY (GIANT DISEASE):
It is a very rare disease that occurs as a result of uncontrolled growth hormone synthesis due to adenoma secreting GH (Growth Hormone) in the pituitary gland. In acromegalic patients, the disease is often diagnosed late, as clinical symptoms and changes occur gradually over years.
In acromegalic patients, enlargement of the hands and feet, coarsening of the face, increase in the head circumference develops gradually over years. Patients complain that their shoe size is getting bigger, their rings are small, and their hats are not on their heads. Again, when patients look at their photographs taken years ago, they see that their face shapes have undergone a serious change. Apart from these direct effects of growth hormone, there are also systems that it indirectly affects and disrupts. Diseases affecting many different systems such as diabetes, hypertension, Coronary artery disease, heart failure, arrhythmia, sleep apnea syndrome, joint problems, secondary cancers occur in acromegalic patients in the long term, and if the patients are not treated, they mostly die due to heart diseases at an early age.
Basal GH and IGF-1 (somatomedin C) are checked in suspected individuals. If basal GH and IGF-1 are outside the target values, then the patient’s Pituitary MRI and OGTT-GH suppression test are performed. If GH values are not suppressed appropriately in OGTT and pituitary adenoma is detected in MRI, the diagnosis of Acromegaly is made.
Since acromegaly is a disease that causes a serious increase in mortality (death) and morbidity (disease), patients diagnosed must be treated. The first choice in the treatment is the surgical removal of the pituitary adenoma by an experienced pituitary surgeon. For this, mostly the Transsphenoidal (inserted through the nose) surgery is preferred. The chance of cure after surgical treatment varies between 50-80% on average. As the size of the adenoma decreases, the chance of cure increases.
Due to the possibility of recurrence of pituitary insufficiency and acromegaly that may develop after surgery, patients must be under endocrinology follow-up after surgery. In patients with recurrence, drug therapy is mostly preferred as a second treatment. For this purpose, drugs such as Somatostatin analogs (octreotide, Lanreotide), GH receptor blocker (pegvisomant) and Dopamine agonist (cabergoline) can be used alone or in combination. Radiotherapy (Gamma knife-Cyber Knife) treatment can be used together with drug therapy or alone in suitable patients.
3- CUSHING’S DISEASE:
ACTH hormone is the hormone that is synthesized from the pituitary gland and controls the synthesis of the hormone Cortisol, also called stress hormone, by stimulating the adrenal glands. The metabolic effects caused by the high level of Cortisol hormone due to ACTH-producing adenomas in the pituitary is called Cushing’s Disease. If the cause of the high level of Cortisol hormone originates from outside the Pituitary gland (adrenal gland, ectopic ACTH production, external cortisone intake), this situation is called Cushing’s Syndrome.
A number of clinical features occur due to increased Cortisol production in people with Cushing’s Disease. It affects many systems in the long term, such as obesity (especially fat storage in the upper part of the body), red face color, moonshine, thinning of the skin, increased hair growth, sexual dysfunction, menstrual irregularity, muscle weakness, osteoporosis, hypertension, diabetes, and depression. opens.
People with suspicious findings should definitely be examined for Cushing’s. The first thing to do is a Physical Examination by an experienced Endocrinologist. Because Cushing’s disease has very specific examination findings. In the second stage, tests (such as 81 mg dexamethasone suppression test, 24-hour urine cortisol excretion, midnight cortisol) are performed. In those with abnormal results in these tests, confirmation tests are performed in the second stage. After these tests, in patients with detected endogenous cortisol elevation, tests called localization tests are started to find the source of this elevation. At this stage, tests such as ACTH level, Pituitary MRI imaging, high-dose dexamethasone suppression test, CRH test, inferior petrosal sinus sampling are used.
After all these tests and examinations, the first treatment option for those diagnosed with Cushing’s Disease originating from pituitary adenoma is surgery. A pituitary adenoma should be removed by an experienced pituitary surgeon. The chance of cure after surgery is between 50-80%. The smaller the size of the adenoma at the time of diagnosis, the higher the chance of success of the surgery. If recurrence is observed after the first surgery, second surgery and/or radiotherapy treatments are preferred in appropriate cases. Treatment with drugs that block cortisol production is generally not preferred except in very specific situations.
4- TSHOMA:
It is a disease that occurs due to TSH producing adenoma in the pituitary gland. It is quite rare. Depending on the TSH produced, in these patients, while fT4 and fT3 are high, the TSH level is found to be inappropriately high or within the normal range. Patients may also have symptoms of hyperthyroidism (palpitations, sweating, weight loss, irritability, etc.) due to high thyroid hormone levels. Again, depending on the TSH stimulus, the thyroid gland of the patients enlarges and leads to the formation of goiter. The disease is most common in the 30-40s. Sometimes the adenoma in the pituitary secretes other pituitary hormones along with TSH. Acromegaly and hyperthyroidism are seen together most frequently due to the synthesis of growth hormone (GH) and TSH together. Pituitary adenomas that occur in this disease are usually Macroadenomas (>10 mm in diameter). For this reason, headache and vision problems can be seen in patients with TSHOMA
In patients presenting with hyperthyroidism symptoms, TSHOMA is suspected in patients who present with hyperthyroidism symptoms while fT4 and fT3 are high, but TSH is not suppressed. In this case, TSH alpha subunit test and T3 suppression test are performed. If the tests are compatible with TSHOMA, MRI imaging of the Pituitary Gland is performed and adenoma is detected.
The primary treatment of TSHOMA is surgery. However, since the majority of cases are macroadenomas, the chance of cure with surgical treatment alone is 35-40%. Radiotherapy is often added to the treatment to increase the chance of cure. In recent years, very successful results have been obtained with Somatostatin receptor analogs (Octreotid, Lantreotide) used for treatment, therefore, drug therapy may prevent surgical treatment in the following years.
5- HYPOPITUITARISM (Hypophysis Insufficiency):
The clinical picture that occurs as a result of insufficient production of one or more pituitary hormones is called Hypopituitarism. If there is a deficiency of all pituitary hormones, this condition is called Panhypopituitarism. Hypopituitarism may occur as a result of damage to the pituitary gland due to many different reasons such as genetic, infective, trauma, malignancy, vascular, drugs, pituitary adenomas, etc. In pituitary gland damage, growth (GH) and reproductive (LH-FSH) hormones are usually the first affected hormones, while ACTH (Cortisol) and TSH (Thyroid) hormones are affected last. Clinical symptoms occur due to insufficient hormone or hormones in hypopituitarism.
In GH (growth hormone) deficiency, growth and development retardation occurs in children, while symptoms such as weakness, decrease in muscle mass, increase in belly fat, bone resorption are seen in adults.
Reproductive Hormones (Gonodotropins) (LH-FSH) stimulate the ovaries in women and the testicles in men, thereby providing estrogen and egg formation in women and testosterone and sperm in men. In the deficiency of gonadotropins, menstrual irregularity, breast reduction, osteoporosis, sexual reluctance and infertility are seen in women, while symptoms such as sexual reluctance, erectile dysfunction, sperm reduction, weakness, decrease in muscle mass, shrinkage in testicles, decrease in beard and armpit hair are seen in men.
In TSH (Thyroid stimulating hormone) deficiency, the thyroid gland cannot be stimulated and a picture called central hypothyroidism occurs. Although all the findings here are the same as those seen in classical hypothyroidism (low thyroid hormone), laboratory tests show low fT3 and fT4, and TSH hormone, which should normally increase, is low or in the normal range.
If ACTH hormone deficiency develops, the adrenal glands (adrenal glands) cannot be stimulated and the production of Cortisol (Stress hormone) hormone produced from there decreases. The hormone cortisol is a vital hormone for our body, and its deficiency causes serious symptoms that threaten our lives. The most common of these are symptoms such as weakness, low blood pressure, abdominal pain, nausea, vomiting, and low sugar. When a person with cortisol deficiency (adrenal insufficiency) encounters any stress factor (infection, trauma, surgery, etc.), the body has difficulty fighting it, and even anesthesia for simple infection or surgery can lead to death.
The first test to be done in people with suspected hypopituitarism is to look at the pituitary hormones together with the last hormones synthesized by these hormones from the target glands.
GH with IGF1
LH- FSH with Esrodiol in Females Testosterone in Man
TSH with fT4 and fT3
ACTH with Cortisol
Prolactin
Diagnosis is made by simultaneous low levels of both pituitary and target gland hormones. After these first tests, various dynamic endocrine tests are used for diagnosis in necessary cases.
Which hormone or hormones are deficient in the treatment, their replacement is given. For this purpose, hormones such as Thyroid hormone, Growth hormone (Somatropin), Testosterone, Estrogen, Progesterone, Hydrocortisone and Desmopressin are used in required amounts.
6- CRANIOPHARYNGIOMA:
The pituitary gland originates embryonally from a tissue called Rathke’s sac. Very rarely (1-2 people per million) in some people, it originates from the residues of this sac and usually develops in the upper part of the pituitary gland in the brain, mostly in cystic character, containing calcifications (petrification) and can reach quite large sizes, most of which are benign. tumors are called Craniopharyngiomas.
Hypopituitarism findings may cause many different symptoms such as vision problems, headache, excessive urination, excessive water drinking, increase or decrease in appetite, depression and growth and development retardation in children, depending on the compression effect of the mass.
In suspected patients, the diagnosis is made by seeing a typical mass located on the pituitary gland and containing calcification by MRI or Tomography imaging. In these patients, pituitary hormones should also be evaluated in terms of hypopituitarim. Other brain tumors should be considered in the differential diagnosis. However, because of the very typical appearance of craniopharyngiomas, diagnosis is usually easy.
The treatment in diagnosed patients is surgical removal of the mass. It can be used in radiotherapy when needed. Patients diagnosed with pituitary insufficiency before and after surgery should be followed up with an appropriate dose of hormone replacement therapy.
7- DIABETES INSIPITUS:
The disease that occurs as a result of insufficient synthesis of ADH (Antidiuretic Hormone) hormone, which is synthesized in the Hypothalamus located above the pituitary gland and stored in the posterior (Neurohypophysis) lobe of the pituitary gland due to various reasons. It is called Diabetes Insipidus. The task of the hormone ADH is to keep water from our kidneys according to the needs of our body and accordingly to adjust the amount and concentration of urine. ADH production may decrease and Diabetes Insipidus may occur due to many different reasons such as Surgery, Trauma, Infection, Tumor, Bleeding, Medicines and genetic causes affecting the hypothalamus and/or pituitary region.
Due to the inability to retain water in the kidneys, typically in the disease, patients urinate a lot and therefore drink a lot of water. Depending on the severity of the disease, these people can make 20 liters of urine a day and drink water at this rate. As long as the patients can reach the water, there is usually no serious problem, but if the patients cannot reach the water somehow, it leads to serious complications that can result in death.
For diagnosis, blood and urine osmolarity tests are first checked. Water Restriction and AVP tests are used for definitive diagnosis in suspicious patients. It is often unnecessary and unreliable to look at the ADH hormone level for diagnosis.
Desmopressin (Minirin tb / Nasal spray) is used in the treatment of patients diagnosed with Central Diabetes Insipidus.
8- Pituitary Incidentilomas:
Pituitary adenomas detected incidentally in people who underwent brain imaging (MRI or Tomography) for another reason are called incidentilomas. If the adenomas are larger than 1 cm in size, they are classified as macroadenoma, and if they are small, they are classified as microadenomas. On the other hand, if adenomas produce one or more pituitary hormones, they are called functional adenoma, and if they do not, they are called non-functional adenomas.
Pituitary Incidentilomas do not cause clinical symptoms since they are mostly in the form of Nonfunctional Microadenomas. Especially macroadenomas and functional incidentillomas cause clinical symptoms. These symptoms include symptoms related to the related pituitary hormone disorder and pressure symptoms (vision impairment, headache, etc.).
Whether pituitary indentilomas cause symptoms or not, function tests should be performed by an Endocrinology specialist at the time of diagnosis. Pituitary incidentillomas that do not cause symptoms do not require treatment. They are followed for the possibility of growth and their growth potential is extremely low during follow-up. In symptomatic incidentilomas, the appropriate treatment method is applied according to the diagnosis to be made as a result of the tests to be performed.
