Overview
Definition:
Hyperprolactinemia is an endocrine disorder characterized by elevated levels of prolactin in the blood
In adolescents, it can stem from various causes, including physiological states, medications, pituitary adenomas (prolactinomas), and macroprolactinemia.
Epidemiology:
The prevalence of hyperprolactinemia in adolescents is not precisely defined but is considered a significant cause of menstrual irregularities in females and may contribute to delayed puberty or hypogonadism in males
Pituitary adenomas account for a substantial proportion of pathological hyperprolactinemia.
Clinical Significance:
Understanding the causes of hyperprolactinemia in teens is crucial for timely diagnosis and management, preventing long-term consequences such as infertility, bone density loss, and potential tumor growth
Differentiating between functional causes, macroprolactin, and pituitary adenomas dictates specific treatment strategies.
Clinical Presentation
Symptoms:
In adolescent females: Oligomenorrhea or amenorrhea
Galactorrhea (milky nipple discharge)
Irregular menstrual cycles
Infertility
Decreased libido
Headache or visual disturbances (suggestive of a large pituitary mass)
In adolescent males: Decreased libido
Erectile dysfunction
Gynecomastia
Galactorrhea
Infertility
Less commonly, mass effect symptoms like headache or visual field defects.
Signs:
Physical examination may reveal galactorrhea
In females, signs of hypogonadism like delayed sexual maturation or scanty pubic/axillary hair
In males, gynecomastia or signs of hypogonadism
Neurological signs such as visual field deficits (bitemporal hemianopia) or papilledema may be present with large pituitary adenomas.
Diagnostic Criteria:
Persistent serum prolactin levels >20-25 ng/mL (or >500 mIU/L) in the absence of physiological causes (pregnancy, lactation, stress) are generally considered diagnostic
Confirmation requires repeat measurement
Differentiating macroprolactin often involves specific assays.
Diagnostic Approach
History Taking:
Detailed menstrual history (onset, regularity, duration)
History of galactorrhea
Sexual history and concerns
Use of medications (antipsychotics, antidepressants, antihypertensives, opioids, estrogens)
History of head trauma or radiation
Symptoms of hypogonadism (delayed puberty, decreased libido)
Symptoms of pituitary mass effect (headache, visual changes)
Family history of endocrine disorders or pituitary tumors.
Physical Examination:
Thorough general physical examination
Assessment of pubertal development (Tanner staging)
Examination of breasts for galactorrhea
Neurological examination focusing on visual fields and cranial nerves
Palpation of thyroid gland.
Investigations:
Serum prolactin levels (fasting, in the morning, after rest)
Multiple measurements may be needed
Assay type is critical: standard prolactin assay vs
macroprolactin assay
Thyroid-stimulating hormone (TSH) to rule out hypothyroidism
Pregnancy test (hCG) in females
Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (in females), and testosterone (in males) to assess gonadal function
Magnetic Resonance Imaging (MRI) of the pituitary gland with and without contrast to detect pituitary adenomas, especially if prolactin levels are significantly elevated (>100 ng/mL) or there are symptoms of mass effect
Macroprolactin measurement if standard prolactin is elevated and no clear cause is found.
Differential Diagnosis:
Physiological hyperprolactinemia (pregnancy, lactation, stress, sleep)
Medications (dopamine antagonists, certain antidepressants, estrogens)
Hypothyroidism
Chronic renal failure
Pituitary stalk compression
Polycystic ovary syndrome (PCOS) can have mild prolactin elevation
Macroprolactinemia (monomer prolactin is normal, but total prolactin is high due to binding to IgG antibodies)
Pituitary adenoma (prolactinoma).
Management
Initial Management:
Address any reversible causes first, such as discontinuing causative medications or treating hypothyroidism
If physiological causes are identified, manage accordingly
For unexplained persistent hyperprolactinemia, further investigation for macroprolactin or pituitary adenoma is necessary.
Medical Management:
For prolactinomas: Dopamine agonists are the first-line treatment
Bromocriptine (initially 1.25-2.5 mg orally at bedtime, increasing as tolerated to 5-10 mg/day divided into 2-3 doses) or Cabergoline (initially 0.25-0.5 mg orally twice weekly, may increase to 1 mg twice weekly)
Goal is to normalize prolactin levels, reduce tumor size, and restore gonadal function
For macroprolactinemia: Usually asymptomatic and does not require treatment
If symptoms are present (e.g., menstrual irregularities), dopamine agonists can be tried but are often less effective than for prolactinomas
Careful follow-up of prolactin levels is important.
Surgical Management:
Surgical management is indicated for macroprolactinomas that are resistant to medical therapy, rapidly growing, cause significant mass effect (visual field defects, cranial nerve palsies), or are associated with apoplexy
Transsphenoidal surgery is the preferred approach
For non-prolactin adenomas causing hyperprolactinemia (rare), surgery may also be considered
Surgery is not indicated for macroprolactinemia itself.
Supportive Care:
Monitoring of prolactin levels, menstrual cycles, gonadal function, and bone mineral density
Counseling regarding fertility and management of hypogonadism
Regular ophthalmological evaluation if a large pituitary adenoma is present
Psychological support for adolescents experiencing body image issues or concerns related to their condition.
Complications
Early Complications:
For prolactinomas: Rapid tumor growth, pituitary apoplexy (sudden severe headache, visual loss, cranial nerve palsies), visual field defects, hypopituitarism.
Late Complications:
For untreated or inadequately treated prolactinomas: Infertility, osteoporosis, increased risk of fractures due to hypogonadism
Recurrence after surgery or treatment
For macroprolactinemia: Generally minimal, unless symptoms are severe and persistent.
Prevention Strategies:
Early identification and treatment of hyperprolactinemia
Regular follow-up to monitor treatment efficacy and detect recurrence
Ensuring adequate calcium and vitamin D intake and monitoring bone density in patients with prolonged hypogonadism
Judicious use of medications known to cause hyperprolactinemia.
Prognosis
Factors Affecting Prognosis:
Tumor size and invasiveness for prolactinomas
Responsiveness to dopamine agonist therapy
Adherence to treatment
Age of diagnosis
Presence of other endocrine deficiencies.
Outcomes:
Most prolactinomas respond well to medical management, leading to normalization of prolactin levels, tumor shrinkage, and restoration of gonadal function
Long-term remission is achievable in a significant proportion of patients
Macroprolactinemia, if asymptomatic, has an excellent prognosis and typically requires no intervention.
Follow Up:
Patients with prolactinomas require lifelong follow-up, including regular assessment of prolactin levels, pituitary imaging (especially in the first few years of treatment), and monitoring for symptoms of hypogonadism and bone health
Follow-up for macroprolactinemia is guided by the presence of symptoms and the need for treatment.
Key Points
Exam Focus:
Differentiate macroprolactinemia from true prolactinomas
Key medical treatments (bromocriptine, cabergoline) and indications for surgery in prolactinomas
Significance of prolactin levels and appropriate interpretation
Management of hypogonadism and osteoporosis in hyperprolactinemic teens.
Clinical Pearls:
Always check TSH and consider pregnancy in any adolescent female with elevated prolactin
Consider macroprolactin in patients with significantly elevated prolactin but minimal symptoms or signs of a pituitary mass
Dopamine agonists are highly effective for prolactinomas and often lead to tumor shrinkage.
Common Mistakes:
Over-reliance on a single high prolactin reading without considering physiological causes or medications
Inadequate workup for pituitary adenoma when prolactin levels are markedly elevated
Treating asymptomatic macroprolactinemia
Failure to monitor for long-term complications like osteoporosis.