TS is a thirty-two year-old female who presented to her gynecologist with a history of headaches and associated amenorrhea and galactorrhea. Her work-up included a prolactin level, which was elevated at 75 ng/dl (Normal 5-20). The patient was advised that she may have a pituitary microadenoma and was referred to an endocrinologist, after obtaining a Magnetic Resonance Imaging (MRI) study which showed a pituitary tumor. As part of her treatment plan she was started on Bromocriptine at 2.5 mg twice a day. To inform her about other treatment options she was referred to the Neuroendocrine Clinic.

On further evaluation, the patient reported a history of carpal tunnel syndrome. She also admitted to having a sensation of tightness in her extremities but no significant change in her shoe or ring size. She reported having difficulty with her breathing and her husband complained that she has recently started snoring. Also, she was recently diagnosed with elevated blood sugar levels and was started on an oral hypoglycemic.

Laboratory and Radiologic Studies:
Because of these signs and symptoms we obtained a growth hormone and insulin growth factor-1 (IGF-1or Somatomedin C) levels as part of a complete pituitary hormonal work-up. Her cortisol and adrenocorticotropin hormone (ACTH) levels were within normal range. The LH and FSH levels were slightly decreased. Her repeated prolactin level was 65 ng/dl. The growth hormone (GH) level was 4 ng/dl (Normal = 0.0-0.5), and the IGF-1 level was elevated at 820 (Normal = 114-492). The MRI study was consistent with a pituitary adenoma.

Discussion:
This patient was diagnosed and treated as a case of a hyperprolactinemia secondary to a prolactin secreting pituitary adenoma. Although this is the most common clinical scenario it is important to differentiate patients with hyperprolactinemia secondary to prolactinoma from hyperprolactinemia secondary to the mass effect of a pituitary tumor other than a prolactinoma.

Hyperprolactinemia secondary to a prolactinoma usually presents with a prolactin level, which is more than 150 ng/dl. The prolactin level in this case made us suspect that this patient’s hyperprolactinemia was secondary to the loss of the hypothalamic inhibition, which occurs as a result of compression of the pituitary stalk. This is described as "the stalk effect".

Hyperprolactinemia can be caused by a number of drugs in addition to pituitary adenomas. The enclosed table shows several etiologic factors that can cause hyperprolactinemia. They include several of the most commonly used drugs. It is important to recognize that incidental non-functioning pituitary adenomas are not uncomon in the general population. This means that a patient on Prozac who has an incidental microadrenoma on a brain MRI (see star on image below) could easily be misdiagnosed as a case of prolactin secreting pituitary adenoma. In such a case the treatment options are different and should focus on changing the medication.

In this presented case the hyperprolactinemia was most likely secondary to "the stalk effect" from a growth hormone producing pituitary adenoma, and not from a prolactin producing adenoma. This fact changes the treatment plan. The treatment of GH producing pituitary adenoma is surgical excision, usually through the transnasal transsphenoidal approach.

Growth hormone levels could very well be within normal in growth hormone producing pituitary adenomas, but IGF-I (Somatomedin C) levels are elevated. In this case the growth hormone production has not been long enough to cause significant acral and physical changes of acromegaly. One other possibility to keep in mind is that some pituitary adenomas are capable of producing more than one hormone, such as growth hormone and prolactin, at the same time.

In patients who present with hyperprolactinemia, a detailed history of all the possible side effects of dysfunction related to the other pituitary hormones should carefully be evaluated. There should always be a good correlation between prolactin levels and its etiology before a definitive treatment plan is established.

Causes of Hyperprolactinemia

Ali F. Krisht, M.D. is an assistant professor in the Department of Neurosurgery at UAMS Medical Center.
He graduated with a medical degree from the American University of Beirut, School of Medicine. He did his neurosurgical training at Emory University School of Medicine in Atlanta, Georgia.
Dr. Krisht is the Director of the Neuroendocrine Clinic and has special expertise in cerebrovascular disorders. He is also the Chief of Service in the Department of Neurosurgery at John L. McClellan Memorial Veterans Hospital.
He has several ongoing research projects with the main focus on cerebrovascular diseases and pituitary disorders. He is involved in professional and public education and is frequently invited to meetings and workshops to give presentations both at the national and international level.
For more information or to make a referral to Dr. Krisht, call 501/296-1463.