Hyperprolactinaemia is the most common endocrine disorder characterised by elevated serum prolactin (PRL). The cause of hyperprolactinaemia usually determines the course of treatment. This article presents a case of hyperprolactinaemia along with a discussion of its causes and management.

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Case presentation

The case

A 22-year-old woman was referred to the endocrine clinic with a 6-month history of secondary amenorrhoea with mild galactorrhea. She has previously been well and not on any medications. She denies any headache or visual disturbance.

On examination, her body mass index is 25 kg/m2. There were no features of hirsutism or any clinical signs suggestive of Cushing's syndrome.

Investigations

• Full blood count, renal and liver function test: normal
• FT4: 12.5 (8-18)
• TSH: 2.2 (0.3-4.5)
• Prolactin levels: 210 ng/ml

Diagnosis

The key point in history taking should be to rule out any physiological cause related to hyperprolactinaemia, in this case, pregnancy should be ruled out. The next thing we should ask this patient is her drug history whether she is on any antihypertensives, anti-depressants, Proton pump inhibitors, or anti-emetics to name a few which can result in hyperprolactinaemia by affecting the dopamine prolactin pathway. History to rule out pituitary causes, as this patient denies any headache and visual disturbance which rules out mass effect related to macroadenoma.

Treatment

This patient was initiated on cabergoline therapy (0.25 mg twice a week with gradual up-titration of the dose). The patient responded well to the cabergoline therapy. The first choice of therapy, in this case, is dopamine agonist as per guidelines for symptomatic patients.

The therapy with dopamine agonist was continued for at least 2 years with careful follow-up, therapy was tapered and discontinued in the patient as she no longer had elevated serum prolactin and a repeat MRI scan fails to show any visible tumour remnant.

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Discussion

Hyperprolactinaemia is one of the most common hypersecretion syndromes of the pituitary gland, with up to 40% of all pituitary tumours in both males and females. Prolactinoma is the commonest cause of serum prolactin >200 ng/ml. Other causes of hyperprolactinaemia are drug, hyperthyroidism, renal failure, pituitary stalk compression, and hypothalamic lesion.

Causes of physiological hyperprolactinaemia

• Pregnancy and lactation
• Sleep normalises with an hour of awakening
• Nipple stimulation
• Sexual orgasm
• Chest wall stimulation or trauma

Patient with mild to moderate hyperprolactinaemia (20-100 ng/ml)

• Drug-induced commonest cause (antipsychotics, anti-depressants, antihypertensive drugs like verapamil, labetalol and anticonvulsants, prokinetic agents like metoclopramide and domperidone)
• Primary hyperthyroidism
• Chronic renal failure
• Stalk compression syndrome

Pathogonomic features in female

1. Oligo amenorrhea.
2. Galactorrhea (80%), usually bilateral and spontaneous.
3. Galactorrhea is defined as the inappropriate discharge of milk-containing liquid from the breast, persisting even after 6 months of delivery or 6 months after discontinuation of breastfeeding. Mostly seen in hyperprolactinemic or premenopausal females.
4. Infertility is associated with decreased libido and mild hirsutism, weight gain. In the earliest effect infertility is seen without menstrual irregularity.
5. Bone loss occurs secondary to hyperprolactinaemia-mediated sex hormone attenuation.
6. Primary amenorrhoea when the onset is premenarchal.
7. Secondary oligomenorrhea when onset in postmenarcheal.

Clinical presentation in men

• Usually present late as macroprolactinoma
• Reduced libido
• Infertility
• Visual field compromise
• Hypogonadotropic hypogonadism (impotence, oligospermia, hypoandrogenemia)
• Galactorrhea is usually seen in the presence of gynecomastia

Clinical presentation due to mass effect includes

1. Headache
2. Visual field defects
3. Deficiency of other hormones
4. Hydrocephalus
5. Cerebral rhinorrhea

Evaluation of a case

1. Serum prolactin estimation basal level, fasting state.
2. MRI pituitary is to be done when prolactin > 100ng/ml.
3. USG / mammogram in cases of bloody galactorrhea.
4. Visual field examination if prolactin levels >200ng/ml.
5. To rule out secondary causes suspected drugs should be substituted and prolactin should be rechecked after 3 days. Rule out hypothyroidism, and chronic renal failure.

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Types of prolactinoma

Prolactinoma represents half of functioning pituitary tumours. The types of prolactinoma are as follows:

• Microdenoma < 10 mm which is usually intrasellar, with a 20:1 ratio in female to male
• Macroadenoma > 10 mm which may locally be invasive is with a 1:1 ratio
• Microprolactinoma > 100ng/ml
• Macroprolactinoma > 250ng/ml

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Management

1. The normalisation of prolactin level is the aim.
2. Therapeutic goals are to stop galactorrhea and to treat menstrual irregularities, libido and infertility.
3. To prevent loss of BMD due to hypogonadism.
4. Reduction in tumour size.
5. Assessment for macroprolactin levels in patients with asymptomatic hyperprolactinaemia.
6. For drug-induced hyperprolactinaemia stop the drug, if can’t be stopped start dopamine agonist along with it.
7. Discontinuation or substitution of an antipsychotic agent should not be undertaken without consulting the patient's physician. If the drug cannot be discontinued and the onset of the hyperprolactinaemia does not coincide with therapy initiation, as per recommendation a pituitary MRI should be done to differentiate between medication-induced hyperprolactinaemia and symptomatic hyperprolactinaemia due to a pituitary or hypothalamic mass.
8. For hypothyroidism replace with thyroxine, renal replacement in CRF.

Management of prolactinoma during pregnancy

1. As per recommendation, women with prolactinomas be instructed to discontinue dopamine agonist therapy as soon as they discover that they are pregnant.
2. In pregnant patients with prolactinomas, recommendations are against performing serum prolactin measurements during pregnancy.
3. Recommendations are against the use of routine pituitary MRI during pregnancy in patients with microadenomas or intrasellar macroadenomas unless there is clinical evidence for tumour growth such as visual field compromise.
4. As per recommendation women with macroprolactinomas who do not experience pituitary tumour shrinkage during dopamine agonist therapy or who cannot tolerate bromocriptine or cabergoline be counselled regarding the potential benefits of surgical resection before attempting pregnancy.
5. As per recommendation formal visual field assessment followed by MRI without gadolinium in pregnant women with prolactinomas who experience severe headaches and/or visual field changes.
6. As per recommendation, bromocriptine therapy should be used in patients who experience symptomatic growth of a prolactinoma during pregnancy.
7. Dopamine agonist therapy should be withheld until breastfeeding is completed.

Management of microprolactinoma

Progression to macroprolactinoma is rare, as per recommendations asymptomatic patients do not require treatment, for symptomatic cases dopamine agonist therapy is to be considered. Monitor with serum prolactin level, MRI should be repeated at intervals of 6-12 months. A reduction in prolactin doesn’t mean a reduction in tumour size.

Modes of therapy dopamine agonist therapy with either bromocriptine or cabergoline (suppresses PRL secretion, decreases PRL synthesis, decreases lactotrope cell proliferation).

1. Bromocriptine is short-acting and hence preferred when pregnancy is desired. It may be used during pregnancy when there is tumour growth. The dose is 0.623-1.25 at bedtime. The dose should be increased gradually to 1.25 mg every 2-3 days. Most patients require 2.5 mg tds, which may go up to 5-15mg/day.
2. Cabergoline is a long-acting dopamine agonist, 0.5-1.0 mg twice weekly. In microadenoma, it resolves galactorrhea in 90%, achieves normal prolactin levels, and resumes gonadal functions. In macroprolactinoma, cabergoline normalises prolactin levels and also shrinks tumours.

To monitor response to medical therapy following can be done:

1. After 1 month of treatment periodic measurement of prolactin to guide the clinician about the dose intensification to achieve the target levels.
2. Repeat MRI after 1 year and 3 months in case of macroprolactinomas where a patient presents with new symptoms like headache or visual disturbances even after starting the dopamine agonist.
3. Visual field examination in patients with macroadenomas.
4. Assessment and management of co-morbidities.

Surgery

Treatment for microprolactinoma may be withdrawn after 2 years once prolactin levels are normalised along with a decrease in the size of the tumour, the patient can be followed up with prolactin level at regular intervals along with MRI brain if the patient was diagnosed with macroprolactinoma or complains of symptoms related to the mass effect caused by the tumour.

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Hitesh Saraogi is a diabetologist, physician and an obesity specialist at Dhanvantari Hospital, Raj Nagar Extension, Ghaziabad.