Thursday, February 26, 2009

Metoclopramide-Induced Gynecomastia


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This site will stay online as an archived source, but will no longer be updated.
For active posts on these cases and new cases go to www.pallimed.com. 


By Gordon J. Wood, MD
Originally posted at the Institute to Enhance Palliative Care, University of Pittsburgh Medical Center
Vol 9, No. 1 - January 2009
Case

Mr BT is a 57 year old man with stage IV laryngeal squamous cell carcinoma, status post radiation and chemotherapy who is now thought to have no evidence of metastases or recurrence. He was followed in a palliative care clinic for chronic musculoskeletal pain and was referred to a new palliative care physician when his prior physician left the practice. Upon presentation to the new physician, the patient complained mainly of painful gynecomastia (excessive growth of breasts in a male) without galactorrhea (spontaneous flow of milk from the nipple) for the past several months. Besides some unrelated knee pain, his examination was remarkable only for bilateral tender gynecomastia. He had not undergone any endocrinological lab studies and a recent PET/CT of the head/neck/chest/abdomen/pelvis was unremarkable. Upon review of his medications, the only possible culprit was metoclopramide which had been started approximately one year prior for nausea. The nausea had since resolved but he was still taking the medication since it was prescribed on a scheduled basis. The metoclopramide was discontinued and several labs were ordered in consultation with endocrinology including testosterone, prolactin, TSH, free T4, FSH, LH, estradiol and HCG. Lab workup was largely unrevealing although most, including the prolactin level, were drawn after the metoclopramide was discontinued. Over the several months following metoclopramide discontinuation the patient’s gynecomastia resolved without any recurrence of his nausea.

Discussion
Male with severe gynecomastia(Not the patient in this case) Gynecomastia Image via Wikipedia

This case, although relatively simple, is important for two major reasons. First, it reminds us of a rare but significant side effect of a medicine commonly used in Palliative Care. Second, and perhaps more importantly, it highlights the dangers of polypharmacy in the Palliative Care setting.

Metoclopramide is a Dopamine type 2 (D2) receptor antagonist and is used as an antiemetic and prokinetic agent. In addition to these effects, it also reliably increases prolactin levels through its action on the D2 receptor. Dopamine normally inhibits pituitary secretion of prolactin. Metoclopramide administration blocks this inhibition resulting in increased prolactin levels.1 This effect has been used as both a research tool and as a clinical test. Symptomatic gynecomastia from elevated prolactin in patients taking metoclopramide, however, is rare, although it has been reported.2 Galactorrhea has also been reported. In fact, metoclopramide has been used to augment lactation in breast-feeding women.3 Upon serologic testing, prolactin levels will generally be elevated in metoclopramideinduced gynecomastia. Discontinuation of the drug generally results in resolution of the symptoms.

Since metoclopramide is generally considered a first line antiemetic and is frequently used in clinical Palliative Care practice, this case serves as useful reminder of this rare but significant side effect. The equally or more important message from this case, however, is the need for careful medication management in this vulnerable population.4 Going back to Cicely Saunders, one of the guiding principles of Palliative Care is the scheduled administration of medications to provide continuous symptom control. Recent literature reinforces this concept in the management of nausea and vomiting.5 In addition, it is suggested to not only use scheduled antiemetics but to add second and third antiemetics as needed instead of stopping one and starting another. While this method has been shown to provide effective relief of symptoms, it can expose the patient to a high risk of side effects if the practitioner fails to taper the medications after the emetic impulse has resolved. This patient had no recurrence of his nausea with discontinuation of his metoclopramide, suggesting that he could have been spared the development of gynecomastia if the metoclopramide had been tapered earlier.

This case also reinforces one of the most basic but important principles in medicine: symptoms which emerge after initiation of a medication are most likely caused by that medication. Because of the serious and progressive nature of the illnesses encountered in Palliative Care, it can be easy to assume that all clinical deterioration is due to worsening of the underlying disease. This case reminds us of the importance of a solid understanding of medication adverse effects and the need for a constant vigilance for these outcomes. Fortunately for Mr BT, the culprit medication was discovered and the symptoms resolved with discontinuation, thereby allowing him to get back to enjoying his life after what appears to be a very successful initial treatment of his serious underlying cancer.

References:
1. Macullum RW, Sowers JR, Hershman JM, Sturdevant RAL. Metoclopramide stimulates prolactin secretion in man. J Clin Endocrinol Metab. 1976;43:1148-1152.

2. Madani S, Tolia V. Gynecomastia with metoclopramide use in pediatric patients. J Clin Gastroenterol. 1997;24:79-81.

3. Ehrenkranz RA, Ackerman BA. Metoclopramide effect on faltering milk production by mothers of premature infants. Pediatrics. 1986;78:614-620.

4. Bernard SA, Bruera E. Drug interactions in palliative care. J Clin Oncol. 2000;18:1780-1799.

5. Wood GJ, Shega JW, Lynch B, Von Roenn JH. Management of intractable nausea and vomiting at the end of life: “I was feeling nauseous all of the time…nothing was working”. JAMA. 20087;298:1196-1207
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Thursday, February 26, 2009 by Christian Sinclair ·

Thursday, February 12, 2009

Huntington’s Disease:
How Can Palliative Care Help?

Pallimed Case Conferences (cases.pallimed.org) is closed to comments and new posts as of April 25, 2013.
This site will stay online as an archived source, but will no longer be updated.
For active posts on these cases and new cases go to www.pallimed.com. 

By Mamta Bhatnagar, MD
Vol 8, No. 11 - December 2008
(Original PDF)
Case

A 43-year-old woman, WM was diagnosed with Huntington’s Disease (HD) in September 1996. In 1997 WM stopped working due to disability related to her disease progression. Since 2004 she was living at a skilled nursing facility where her care had been stable until 4 weeks prior when her choreiform movements intensified, her oral intake declined, and she was unable to rest or sleep due to incessant body movements. Several medication changes at the nursing facility were unsuccessful and she was transferred to an inpatient hospice unit for end-of-life care. On exam the patient appeared younger than her stated age and cachectic. She was non-ambulatory. She had flailing involuntary movements of her arms and legs, which made a comprehensive physical examination difficult. Her speech was unintelligible and skin on her arms and legs showed bruises and open wounds that she sustained when she hit any furniture around her. The patient’s husband and power of attorney’s primary goal was to control her movements and allow her to rest.
George Huntington (1850-1916), American physician.
Dr. Huntington via Wikipedia

Brief overview of Huntington’s disease

HD is a neurodegenerative disorder that is inherited in an autosomal dominant fashion so that each child of an affected patient has a 50% chance of developing the disease. Most patients develop symptoms in their forties and fifties. Symptoms are usually a triad of motor, cognitive, and psychiatric issues. The motor symptoms involve impairment in voluntary movements and appearance of involuntary movements called chorea (hence the name Huntington’s chorea). Impairment in voluntary movements results in loss of manual dexterity, slurred speech, swallowing difficulties, problems with balance, and falls. The motor symptoms worsen in the middle stages followed by rigidity in the late stages of the illness. Cognitive symptoms manifest in the patient’s inability to perform complex tasks with loss of speed and flexibility, progressing to global impairment in the later stages of the disease. Psychiatric symptoms most commonly include depression. Patients may also manifest irritability, anxiety, agitation, impulsivity, apathy, social withdrawal, and obsessiveness.

Treatment

Medications do not alter the progression of HD. Patients are vulnerable to cognitive side effects of pharmacologic therapy. Motor symptoms are usually managed using either neuroleptic agents such as haloperidol and/or benzodiazepines. There are no medications to treat swallowing difficulties or rigidity that occurs later in the disease. Depression is treated with serotonin specific reuptake inhibitors such as sertraline and paroxetine. The mainstay of therapy for HD remains non-pharmacologic management. Padding of furniture and weights on wrists and ankles will help reduce injuries and the amplitude of involuntary movements respectively. As swallowing difficulties progress, the food consistency can be softened and pureed. Eating is usually supervised, and the patient is given time to eat with no distractions. Caregivers should be trained in Heimlich maneuver. Cognitive impairment and difficulties in communication can be eased by giving the patient time to answer and asking closed-ended questions. Establishing routines around the patient and activities that adjust to his or her cognitive level help to decrease anxiety and allow cognitive stimulation. Identifying and avoiding triggers for emotional outbursts and providing family and caregiver supports are measures to help manage behavioral manifestations of the disease.

Survival

Average survival time after diagnosis is 15 to 20 years. Disease course is variable, and every patient is unique, which makes prognostication difficult.

Back to the Case

Initial attempts to sit the patient in a padded wheelchair and feed her proved unsuccessful. A trial of phenobarbital was initiated to allow her to rest and monitor response. All furniture was removed from her room. Several mattresses were placed on the floor and padding was applied to the walls. Over the course of 3-4 days the patient’s movements subsided, and she was able to stay awake. Her appetite improved, and she drank shakes. Feeding times were unique; one staff member would hold WM in her lap while the other would feed her. Over a period of 2 weeks, WM thrived. Although she was incontinent for bowel and bladder, she would call out to the nursing staff when she needed care. Her room was decorated with her favorite sport team jerseys and family photos. Her husband visited daily and was able to participate in feeding times, and together they watched sports events on TV. WM’s only medications were oral fluoxetine, laxatives, antacids and phenobarbital. While we initiated our treatment plan to relieve distress and attempted palliative sedation therapy as a means to relieve what appeared to be refractory symptoms at the end of life, the patient’s response was so dramatic that we now planned for her care for the next several weeks at a nursing facility. Our objective was to achieve a smooth transition for WM, and we encouraged nursing facility staff to visit the hospice unit and witness her personal care and feeding. The patient was eventually transferred and has continued to be stable at the nursing facility. She has not required any medication adjustments.

References:
1. Aubeeluck A, Wilson E. Huntington's disease. Part 1: essential background and management. Br J Nurs. 2008;17(3):146-51.
2. Rosenblatt A, Ranen NG, Nance MA, Paulsen JS. A Physician's Guide to the Management of Huntington's Disease. Second Edition. Huntington's Disease Society of America 1999.
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Thursday, February 12, 2009 by Christian Sinclair ·