Unusually High Prolactin Level for Medication-induced Hyperprolactinemia: a Case Report İlaca Bağlı Hiperprolaktinemi Için Alışılmadık Derecede Yüksek Prolaktin Değeri: Vaka Sunumu

Hyperprolactinemia has a number of etiologies, including physiological , pathological and pharmacological causes. Hyperprolactinemia is frequently associated with the use of certain medications. Patients using medications known to cause hyperprolactinemia generally develop a mild form of the condition, and the prolactin level rarely exceeds 100 ng/mL in these cases. We report a case of a 43-year-old woman with an extremely high prolactin level in medication-induced hyperprolactinemia caused by a combination of an antipsychotic (sulpirid) and an antidepressant (paroxetine). Özet Hiperprolaktineminin fizyolojik, patolojik ve farmakolojik bir çok nedeni mevcuttur. Hiperprolaktinemi belirli ilaçların kullanımı ile sıklıkla ilişkilidir. Ancak ilaca bağlı hiperprolaktinemi genellikle hafif yükselmelere neden olup nadiren 100 ng/mL değerinin üstüne çıkar. Bu vaka sunumunda, 43 yaşında bayan bir hastada antipisikotik (sül-pirid) ve antidepresan (paroksetin) kombinasyonuna bağlı gelişen, ilaca bağlı hiperprolaktinemi için oldukça yüksek kabul edilecek de-ğerlerde, bir hiperprolaktinemi olgusu rapor edildi.


Introduction
Prolactin is a protein produced in the lactotroph cells of the anterior pituitary gland.Secretion is pulsatile and increases with sleep, stress, pregnancy and chest wall stimulation or trauma.Prolactin production can be stimulated by the hypothalamic peptides, thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP).Normal fasting values are generally less than 25 ng/mL, depending on the individual laboratory.
Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis.It is necessary to determine the cause in confirmed cases of hyperprolactinemia.Determination of the cause involves a careful history and examination, laboratory tests and diagnostic imaging of the sella turcica.Pathological hyperprolactinemia is defined as a consistently elevated serum prolactin level in cases in which the physiological causes of prolactin hypersecretion mentioned above have been excluded.Pathological causes include lactotroph adenomas, other hypothalamic and pitu-itary disorders, pregnancy, medication use, hypothyroidism, chest wall injury, and chronic renal failure.A number of drugs may cause hyperprolactinemia.Pharmacological agents that inhibit dopamine synthesis or action, such as L-methyldopa, antiemetics or antipsychotics, frequently cause increased serum prolactin.The magnitude of the elevation varies with the drug.Most prolactin concentrations lie between the upper limits of normal and 100 ng/mL, the level at which there is the largest differential diagnosis.

Case Report
A 43-year-old woman was referred to the endocrinology clinic for investigation of her clinical presentation of mastalgia.She had been taking paroxetine (20 mg once a day) and sulpirid (50 mg twice a day) for 15 days for the treatment of depression.
In our clinic, the physical and neurological examinations of the patient were normal.The complete blood count values were as follows: white blood cell count 4,600/mm 3 , hemo-globin 13.3 g/dL, hematocrit 42.1% and platelets 193000/ μL.The basic serum levels of the biochemical parameters were as follows: sodium 136 mmol/L, potassium 3.9 mmol/L, blood urea nitrogen 10.8 mg/dL, creatinine 0.6 mg/dL, blood glucose 82 mg/dL, albumin 4.1 g/dL, total protein 6.9 g/dL, total bilirubin 0.25 mg/dL, calcium 8.1 mg/dL, and phosphorus 3.3 mg/ dL.The hormonal parameters were as follows: TSH 1.14 uIU/ mL, IGF-1 130 ng/mL, and GH 0.076 ng/mL.The urinalysis was normal.The analyzed prolactin levels were 311 ng/mL and 376 ng/mL.The patient's pituitary MRI was normal (Figure 1, 2).She was not pregnant, and she denied having any other precipitating factor for hyperprolactinemia.
Medication-induced hyperprolactinemia was suspected, and after psychiatric consultation, paroxetine and sulpirid were stopped.After 15 days, her prolactin level was 11 ng/mL.After withdrawing the medications, her symptoms resolved, and the diagnosis of medication-induced hyperprolactinemia was confirmed.

Discussion
Hyperprolactinemia is defined as a serum prolactin level above the normal range (25 ng/mL in premenopausal women and 15 ng/mL in men and postmenopausal women) [1].
Hyperprolactinemia is a very common condition frequently associated with the use of certain medications [2][3][4].The investigation of hyperprolactinemia in people using antipsychotic medications is complicated because of the well-known association between medications and hyperprolactinaemia [4].In patients taking medications known to cause hyperprolactinemia, it is critical to establish that the medication is the cause and that the cause is not a structural lesion in the hypothalamic/pituitary area.
Hyperprolactinemia induced by medication should return to normal after the withdrawal of the offending drug.It would be reasonable to arrange further investigation if the prolactin is elevated above 150 ng/mL or does not return to normal after the withdrawal of the offending drug, at which point the likelihood of a prolactinoma would be increased significantly.
To our knowledge, a prolactin level above 350 ng/mL caused by a drug is extremely rare.A serum prolactin level above 250 ng/mL is typically due to a prolactinoma, particularly a macroadenoma instead of a microadenoma [1,7].In conclusion although no specific test can assist in determining the etiology of hyperprolactinemia, a prolactinoma is likely if the prolactin level is greater than 250 ng/mL.In cases of patients using medications known to cause the hyperprolactinemia, medication-induced hyperprolactinemia must be considered.