Hormonal Disharmony—A Rare Case of Catamenial Cyclical Vomiting Syndrome

Abstract

Cyclic vomiting syndrome (CVS) is a rare and enfeebling neuroendocrine disorder mostly seen in children. It is characterized by recurrent episodes of nausea and vomiting with interepisodic normal periods. There are various triggers for an episode among which menstruation is one critical trigger. A majority of childhood-onset CVS attain remission by teenage or before puberty. There is neurophysiological evidence to associate cyclical vomiting with migraine. It is also supported clinically by the presence of aura and photophobia. The fluctuation in estrogen and progesterone levels during the menstrual cycle is proposed to be the pathophysiological basis of catamenial CVS, which is shared by catamenial migraine. The diagnosis of cyclical vomiting is essentially clinical. Management comprises of acute stage followed by chronic stage. The acute management is targeted to abort the current episode and correct the fluid and electrolyte imbalance. Sumatriptan is found to be effective in the termination of an acute episode. Intravenous fluid and electrolyte replacement are critical. The second step is planning a prophylactic treatment strategy to prevent further episodes. Tricyclic antidepressants are extensively used and are found to be effective. Considering the background of hormonal fluctuation in catamenial cyclical vomiting, hormone replacement therapy with oral and transdermal patches has been attempted with positive results. Any chronic vomiting with inconclusive findings in investigations must raise suspicion regarding CVS. Early identification and treatment considerably improve the quality of life.

Background

Cyclic vomiting syndrome (CVS) is a neuroendocrine disorder seen in children. It is characterized by recurrent episodes of nausea and vomiting with interepisodic normal periods. The childhood-onset disorder extending into adulthood or disorder occurring in adults is not unusual. ¹ However, the characteristics of the disorder vary among different age groups. There are various triggers for an event among which menstruation is one critical trigger. There is very little literature on catamenial CVS. Here, we present a rare case of chronic cyclical vomiting with episodes occurring in relation to the menstrual cycle.

Case Report

A 40-year-old female, married with two children, was brought by her husband to the emergency department with complaints of excessive vomiting, reduced appetite, and extreme fatigue for three days. She had about 10–12 episodes of vomiting per day, more in the daytime. She complained of nausea and giddiness persisting throughout the day. A general examination revealed severe dehydration, low blood pressure, and tachycardia. The patient was hospitalized and central venous access was secured with the help of an anesthetist as the peripheral lines were inaccessible. Routine baseline investigations were done, which revealed hypoglycemia, hyponatremia, hypokalemia, and positive urine ketones. Her thyroid function test and hemoglobin A1c (HbA1c) were within normal limits. Opinion was sought from general physician immediately after admission for fluid and electrolyte imbalance and the correction was started. She was started on intravenous proton-pump inhibitors, antiemetics, and levosulpiride to reduce the nausea and vomiting. In a further interview, she had a history of similar episodes of severe vomiting every month which was associated with her menstrual cycle for about 32 years. She attained menarche at the age of 8 and her first episode of vomiting occurred after the second cycle of menstruation. Episodes start at around day 18 of the cycle and resolve around day 23, in a 30-day menstrual cycle. She recovers about five days prior to the menses. She had regular cycles and her pregnancies were uneventful. She had visited the emergency department multiple times and had been treated by clinicians from various faculties of medicine with no improvement. The patient had been given trials of amitriptyline (up to 100 mg/day), escitalopram (up to 15 mg/day), sertraline (up to 100 mg/day), amisulpride (up to 100 mg/day), and various antiemetics in the past for adequate duration but she denied improvement with any of them. Currently, she was subjected to a hormonal assay during her symptomatic period (D20), which revealed increased prolactin and reduced progesterone levels. Follicle-stimulating hormone and luteinizing hormone were in the upper limit of the normal range. Gynecologist opinion was taken and was suggested to be treated symptomatically as her menstrual cycles were regular. Hormone replacement therapy was suggested if she failed to respond to the symptomatic management. She did not have associated headaches, visual disturbances, abdominal discomfort, loose stools, or fever. She, however, reported severe anticipatory anxiety and low mood prior to every episode. Over the years, she restricted herself from traveling to places and participating in social events. She became house-borne for the past five years. She managed to do household chores during her asymptomatic period. The emetic phase was grossly disabling and she required assistance for personal care. There were no significant triggers like psychosocial stressors. She did not have any preexisting medical or surgical history. Magnetic resonance imaging of the brain and ultrasound of the abdomen and pelvis were reported to be normal. A clinical diagnosis of CVS with a catamenial pattern was made. Considering the failed attempts with tricyclic antidepressants in the past, the patient was started on sumatriptan 50 mg/day. She had resolution of symptoms after about three days. There was a dramatic improvement in the following cycle when she reported only nausea and no vomiting. After the third cycle, she became completely asymptomatic. She experienced the first symptom-free menstrual cycle after 32 years.

Discussion

Our patient had her first symptom at the age of 8, following menarche and the episodes were consistent every month since then. Despite the severity of the episodes, the diagnosis was delayed for about 32 years. The symptoms became more severe and distressing as the years progressed. It has been recorded that the duration of illness at the time of diagnosis can be as late as 43 years. ² The tendency of the patients to report to the emergency unit or other faculties of medicine and the possibility of diverse clinical entities to present with vomiting can substantially delay the diagnosis of CVS.

CVS is a rare and enfeebling disorder, with a prevalence of 2% among children. The average age of onset in childhood is five years ¹ and a majority of childhood-onset CVS (61%) attain remission by teenage ³ or before puberty, ⁴ which was not the case with our patient.

Fleishner et al. divided each cycle into four phases: (a) interepisodic—the asymptomatic period; (b) prodromal phase—marked by aura-like symptoms, including anxiety, abdominal discomfort, or fatigue; (c) hyperemesis phase—characterized by severe nausea and vomiting; and (d) recovery phase—vomiting stops and the general physical condition improves. The duration of each phase varies among individual patients. ²

There is neurophysiological evidence to associate cyclical vomiting with migraine. It is also supported clinically by the presence of aura and photophobia. ⁵ About 40% of the patients with CVS reported to have migraine, and 28% had a family history of migraine. ¹ It is noteworthy that there was no history of migraine in our patient or her family.

Menstruation has an established association with CVS. The prevalence of catamenial CVS is around 13% in postmenarcheal girls. The fluctuation in estrogen and progesterone levels during the menstrual cycle is proposed to be the pathophysiological basis of catamenial CVS, which is shared by catamenial migraine.^2,6 Our patient had onset of vomiting in the luteal phase and the follicular phase was mostly asymptomatic.

The diagnosis of cyclical vomiting is essentially clinical, as there is no gold standard diagnostic test. A detailed history and evaluation to rule out other organic causes of vomiting pave the way to the diagnosis.^1,6

The management of CVS can be divided into two stages. The first stage is acute management, which is targeted to abort the current episode and correct the fluid and electrolyte imbalance. Sumatriptan is effective in the termination of an acute episode. ¹ Intravenous fluid and electrolyte replacement are critical. ⁷ Any potential triggers like psychosocial stressors, anxiety, sleep disturbances, and diet modification must be identified. The second step is planning a prophylactic treatment strategy to prevent further episodes. Tricyclic antidepressants are extensively used and are found to be effective. ⁸ However, our patient did not respond well to tricyclic antidepressants. Hasler et al. have suggested mirtazapine and olanzapine as a prophylactic therapy option and ketamine as abortive therapy. ⁹ However, there was no literature on the efficacy of other antidepressants. Other agents used are antiepileptics and antimigraine drugs.^1,10 Considering the background of hormonal fluctuation in catamenial cyclical vomiting, hormone replacement therapy with oral and transdermal patches has been attempted with positive results.^5,11 Patino et al. reported a case of a 22-year-old nulliparous female with catamenial CVS, who responded well to progestin-only oral contraceptives. ¹¹ Other adjuvant pharmacological agents with some efficiency include beta-blockers, antiemetics, 5-HT antagonists, H1 blockers, and smooth muscle relaxants.^7,10

Conclusion

Catamenial CVS in adults is a rare and highly disabling clinical entity. Association with menstruation usually goes unnoticed because any physical or psychological symptom occurring in relation to menstruation is deemed to be within limits of normalcy. Any chronic vomiting with inconclusive findings in investigations must raise suspicion regarding CVS. The dramatic resolution of highly distressing symptoms with specific treatment strategies highlights the need for early diagnosis and treatment, so as to restore the quality of life at the earliest.