Overview
Definition:
Hyperprolactinemia, defined as elevated serum prolactin levels, can be a significant side effect of antipsychotic medications, particularly those with potent dopamine D2 receptor antagonism
In pediatric patients, this can lead to a range of endocrine and potentially behavioral disruptions.
Epidemiology:
The incidence of hyperprolactinemia with antipsychotic use in children and adolescents varies widely depending on the specific agent, dose, and duration of treatment, but is generally higher than in adults
Rates of up to 50-70% have been reported with certain agents.
Clinical Significance:
Persistent hyperprolactinemia in pediatric populations can lead to delayed puberty, menstrual irregularities in girls, galactorrhea, reduced bone mineral density, and sexual dysfunction, impacting physical development and psychological well-being
Early recognition and management are crucial to mitigate long-term consequences.
Clinical Presentation
Symptoms:
In prepubertal children: Galactorrhea
In pubertal or postpubertal girls: Menstrual irregularities (oligomenorrhea, amenorrhea), galactorrhea
In pubertal or postpubertal boys: Gynecomastia, galactorrhea, decreased libido, erectile dysfunction
General symptoms may include headaches, visual disturbances (rare but serious, suggestive of pituitary adenoma), and emotional lability.
Signs:
Galactorrhea (milky nipple discharge) on breast or nipple expression
Gynecomastia (enlarged breast tissue) in males
Signs of delayed puberty or gonadal dysfunction
In rare cases, visual field defects if a significant prolactinoma develops.
Diagnostic Criteria:
Diagnosis is based on persistently elevated serum prolactin levels (typically >2-3 times the upper limit of normal for age and sex) in the context of antipsychotic use, with exclusion of other causes of hyperprolactinemia
Serial measurements may be necessary to confirm persistence.
Diagnostic Approach
History Taking:
Thorough medication history, including type of antipsychotic, dose, duration, and adherence
Inquire about menstrual history in girls, pubertal development in both sexes
Explore symptoms of galactorrhea, gynecomastia, headaches, visual changes, and sexual dysfunction
Assess for other potential causes of hyperprolactinemia (e.g., hypothyroidism, renal insufficiency, pituitary tumors).
Physical Examination:
Assess for signs of puberty according to Tanner staging
Examine breasts for galactorrhea and gynecomastia
Perform a basic neurological exam focusing on visual fields and cranial nerves
Evaluate for signs of hypothyroidism.
Investigations:
Serum prolactin levels: Measured typically in the morning after a period of rest
Levels >100-200 ng/mL are highly suggestive of a macroprolactinoma or significant drug effect
A single elevated prolactin level should be confirmed with repeat testing, especially if symptoms are mild
Other relevant investigations: Thyroid function tests (TSH, free T4) to rule out hypothyroidism
Beta-hCG in adolescent girls to rule out pregnancy
Renal function tests
Consider prolactinoma workup (MRI pituitary) if prolactin levels are very high, there are visual symptoms, or there is suspicion of an intrinsic pituitary issue.
Differential Diagnosis:
Physiological hyperprolactinemia (pregnancy, sleep, stress, lactation)
Pituitary adenoma (prolactinoma)
Hypothyroidism
Medications other than antipsychotics (e.g., certain antidepressants, antihypertensives)
Renal failure
Chest wall stimulation
Idiopathic hyperprolactinemia.
Management
Initial Management:
The cornerstone of management is to identify and address the underlying cause
If antipsychotic treatment is essential, strategies to mitigate hyperprolactinemia should be employed.
Medical Management:
1
Dose reduction or switching antipsychotics: If clinically feasible, reduce the dose of the offending antipsychotic or switch to an agent with a lower propensity to cause hyperprolactinemia (e.g., quetiapine, aripiprazole, ziprasidone are generally associated with lower risk than risperidone or paliperidone)
2
Pharmacological treatment of hyperprolactinemia: Dopamine agonists are the mainstay
Bromocriptine: Initial dose 1.25-2.5 mg daily, titrated up to 5-10 mg daily in divided doses
Cabergoline: More potent and longer-acting, typically 0.25-1 mg twice weekly, titrated as needed
These agents directly block prolactin release
Monitor prolactin levels and symptoms closely
Re-evaluation of antipsychotic necessity and dose should occur concurrently.
Surgical Management:
Surgical intervention is generally not indicated for antipsychotic-induced hyperprolactinemia
It is reserved for large, symptomatic pituitary adenomas causing mass effects (visual compromise, hypopituitarism) or for rare cases refractory to medical management in the context of intrinsic pituitary pathology, not drug side effects.
Supportive Care:
Regular monitoring of prolactin levels, endocrine function, and bone mineral density (e.g., DEXA scans if prolonged or severe)
Patient and family education regarding the potential side effects and management strategies
Counseling for associated sexual dysfunction or menstrual irregularities.
Complications
Early Complications:
Galactorrhea, menstrual irregularities, gynecomastia, decreased libido, headaches, visual disturbances (rare).
Late Complications:
Osteoporosis due to hypogonadism, infertility, potential for pituitary adenoma growth (though rare with drug-induced hyperprolactinemia unless an underlying adenoma exists), impaired growth and development, psychological distress.
Prevention Strategies:
Careful selection of antipsychotics with lower prolactin-elevating potential
Using the lowest effective dose
Regular monitoring of prolactin levels, especially in children at risk or on high doses
Prompt initiation of management strategies (dose adjustment, switching, or dopamine agonists) if hyperprolactinemia is detected.
Prognosis
Factors Affecting Prognosis:
The prognosis is generally good with appropriate management
Factors influencing outcome include the severity and duration of hyperprolactinemia, adherence to treatment, and the underlying psychiatric condition being treated
Reversibility of symptoms and normalization of prolactin levels are common.
Outcomes:
With timely intervention, symptoms such as galactorrhea, menstrual disturbances, and gynecomastia usually resolve
Normalization of gonadal function and improvement in bone mineral density can be achieved
However, long-term monitoring is essential to prevent recurrence or late complications.
Follow Up:
Regular follow-up with endocrinologists and psychiatrists is crucial
Prolactin levels should be monitored periodically (e.g., every 3-6 months initially, then as clinically indicated)
Bone density should be assessed in individuals with prolonged or severe hyperprolactinemia
Continue monitoring for psychiatric condition stability.
Key Points
Exam Focus:
Antipsychotics that commonly cause hyperprolactinemia (risperidone, paliperidone, haloperidol)
Agents with lower risk (quetiapine, aripiprazole)
Management options: Dose reduction, switching, dopamine agonists (bromocriptine, cabergoline)
Key investigations: Prolactin, TSH, MRI pituitary if indicated
Long-term risks: Osteoporosis, impaired growth.
Clinical Pearls:
Always consider drug-induced hyperprolactinemia in a child on antipsychotics presenting with galactorrhea, menstrual abnormalities, or gynecomastia
Differentiate from pituitary adenoma by history and prolactin levels
Dopamine agonists are highly effective but require careful titration and monitoring
Educate patients and families about potential side effects and management.
Common Mistakes:
Attributing symptoms solely to the psychiatric condition without considering medication side effects
Delaying diagnosis due to infrequent prolactin monitoring
Failing to consider other causes of hyperprolactinemia
Inadequate follow-up leading to complications like osteoporosis.