Prolactinomas and diabetes insipidus (DI) result from the incorrect production of hormones within the pituitary gland. Diabetes insipidus is not to be confused with the more commonly known diabetes mellitus (types 1 and 2): diabetes inspidus is caused by the lack of vasopressin/ADH as opposed to the lack of insulin.
What are prolactinomas?
These types of tumours affect the levels of the hormone prolactin: this hormone influences fertility in both sexes and the menstrual cycle of women in their child bearing years. Prolactinomas are the most common type of pituitary adenoma that is diagnosed.
How are prolactinomas diagnosed?
In order to determine the presence of prolactin within a laboratory setting, the pituitary is first biopsied and then put under immunohistochemical (IHC) tests and examined with a microscope. What IHC tests do are detect certain antigens (proteins) in a cell by the use of antibodies which are tagged.
These antibodies attach to the antigens via a ‘lock and key’ mechanism and under the microscope, the areas with positive Ag-Ab (antigen-antibody) lock are coloured. The results are correlated with the high levels of prolactin in the blood (otherwise known as hyperprolactinemia).
Is there a certain age group that this tumour affects?
They can affect both men and women, but they are most often diagnosed at an early stage in women of child-bearing years. This is because of the lack of a monthly period that can result without another obvious reason such as pregnancy or being severely underweight. In males and post-menopausal women, the tumours can get bigger because the symptoms of prolactinomas are relatively stable.
What are the symptoms of prolactinoma?
There are four symptoms of prolactioma:
- Lack of a monthly period (amenorrhea)
- Lack of libido or sex drive
- Galactorrhea (milk flowing from the breasts inappropriately i.e. without a baby present)
What else can trigger hyperprolactinaemia?
Prolactinomas are not the sole reason for high prolactin levels: the other conditions not related to prolactinomas that can trigger hyperprolactinaemia include:
- Hormone replacement therapy
- Renal failure
- Reserpine (dopamine inhibiting drug)
- Hypothalamic lesions
What is vasopressin and what is it responsible for?
Vasopressin is also known as ADH or anti-diuretic hormone, and it is produced in the hypothalamus and secreted by the posterior pituitary gland. It is classified as a a cyclic nonapeptide, and it is mainly responsible for the balance of water in the human body i.e. to regulate the amount of water taken in versus the amount of water secreted in sweat, urine and stool. Specifically, it targets the kidneys and attaches to the ascending loop of Henle and the collecting ducts to help retain extra water when it is leaking out too fast. Vasopressin also plays a role in the process of blood clotting by aiding in both von Willebrand factor and factor VII (7) release. The flow chart below shows the normal process that involves vasopressin:
What are diuretics?
Diuretics are substances which oppose the effects of anti-diuretic hormone. A well-known example of a substance which is a diuretic is caffeine. Diuretics dilute the urine by allowing more water to escape through the kidney and ultimately leave the body. If it is left unchecked, diuretics can lead to dehydration.
What are the symptoms of diabetes inspidus?
Diabetes inspidus (DI) can appear similar to diabetes mellitus (DM) because of its symptoms of polydipsia (excessive drinking of fluids) and polyuria (excessive urine production). To differentiate between the two, the tolerance of glucose must be checked.
What is a glucose tolerance test?
A glucose tolerance test or GTT involves two blood tests taken on the same day and the glucose level being checked on both. A patient who has fasted overnight comes in and has their blood drawn in a grey tube, and their fasting glucose is measured. Sugar water is then given to the patient to drink and a subsequent blood test is taken two hours later. This is designed to check how efficient the body is at metabolizing sugar: in DI the levels remain within normal limits because the pancreas is unaffected, but in DM the glucose levels remain high and do not fall back down because the pancreatic cells that control insulin are destroyed.
What can cause DI?
Around a third of patients have DI for an unknown reason: however, there are several things that can lead to diabetes insipidus, which include:
- Autoimmunity to vasopressin-secreting neurons
- CNS or pituitary tumours
- Diseases affecting pituitary stalk function
If the GTT comes up normal, how then is DI diagnosed?
The amount of time between the symptoms arising and diagnosis of DI can vary significantly, depending on the severity of the vasopressin deficiency. If the case is severe, it can easily confirmed, however in milder cases it is important to eliminate all other factors via a water deprivation test.
How does a water deprivation test work?
Like the name suggests, the patient is deprived of water over several hours and blood is drawn a few times over that period, spun through a centrifuge and the serum volume is compared to see how well the patient is able to conserve their fluids. This result is sometimes correlated with a prescription of vasopressin: if the results end up normal due to the effect of the medication, then DI is the definitive diagnosis.