A case of amenorrhoea in a 17-year old female

HOSP # MRN94883340 WARD Paeds Endocrine Clinic
CONSULTANT   Jody Rusch / Ariane Spitaels DOB/AGE 17 year female

Abnormal Result

Prolactin 51.1 ug/L

Monomeric Prolactin 36.2 ug/L

Presenting Complaint

Amenorrhoea (more details unknown)

History

The patient presented with a tempoparietal tumour and had received two episodes of radiotherapy – was asked by the oncologists to be reviewed by the Endocrinologists.

Mother stopped epilim (reason unknown)

Patient currently has amenorrhoea (unknown whether it is primary or secondary)

Examination

Residual right hemiplegia

Unfortunately no other facts about the physical examination are known

Laboratory Investigations

  • Normal TFT:
    • TSH 1.7 mIU/L (0.51 – 4.3)
    • Free T4 16.2 (12.6 – 21.0)
  • Cort 11am 330 nmol/L
  • FSH 3.8 IU/L
  • LH 2.4 IU/L
  • E3 106 pmol/L
  • Prol 51.1 ug/L
  • Monomeric Prolactin 36.2 ug/L
  • Recovery: 70.8%

Other Investigations

Proposed investigations:

  • Pregnancy test (most common cause of amenorrhoea)
  • Ovarian ultrasound to exclude early-onset PCOS (which may become a diagnosis of exclusion)
  • History about prior amenorrhoea
  • Brain MRI to visualize pathology in the cranium

Final Diagnosis

Hyperprolactinemia – likely causing amenorrhoea – cause yet to be determined

Take Home Message

Hyperprolactinemia is perhaps one of the most common problems in clinical endocrinology. It relates with various aetiologies (see below), the clarification of which requires careful history taking and clinical assessment. Analytical issues (presence of macroprolactin or of the hook effect) need to be taken into account when interpreting the prolactin values. Medications and sellar/parasellar masses (prolactin secreting or acting through “stalk effect”) are the most common causes of pathological hyperprolactinaemia. Hypogonadism and galactorrhoea are well-recognized manifestations of prolactin excess, although its implications on bone health, metabolism and immune system are also expanding. Treatment mainly aims at restoration and maintenance of normal gonadal function/fertility, and prevention of osteoporosis; further specific management strategies depend on the underlying cause.

The main physiological causes of hyperprolactinemia:

  • Ovulation
  • Pregnancy
  • Breastfeeding
  • Stress
  • Exercise
  • Nipple stimulation or chest wall injury

Pathological

  • Prolactin-secreting pituitary adenoma
  • “Stalk-effect” from sellar / parasellar lesions
  • Renal failure
  • Liver cirrhosis
  • Primary hypothyroidism
  • Polycystic Ovarian Syndrome
  • Seizures

Pharmacological

  • Antipsychotics / neuroleptics
  • Antidepressants
  • Antiemetics
  • Opioids
  • Antihypertensives

It is clear in this case that the history is quite important in any patient in whom hyperprolactinemia is detected, since a vast array of causes exist.

For an excellent review on prolactin: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947286/

For another case of high prolactin see:




Rapidly decreasing Prolactin result

HOSP # WARD Endocrinology Clinic
CONSULTANT John Stanfliet   DOB/AGE 36 y Female

Abnormal Result

A low prolactin result was obtained in a patient in whom a macroadenoma was suspected:

Prolactin: 1.3 mIU/L

Presenting Complaint

The patient presented with headache and decreased visual acuity (more specifically peripherally).

History

There were bilateral galactorrhoea, amenorrhoea, and as noted above, headache and visual disturbances.

The patient had received Cabergoline (a dopamine receptor agonist on D2 receptors) for the past 4 months.

Examination

As above

Laboratory Investigations

Date Prolactin (mIU/L)
02/2019 106 (Recovery of 80% following PEG precipitation)
05/2019 135
06/2019 85
08/2019 1.3 (1.59 with a 1:10 dilution; 3.94 with a 1:50 dilution)
Prolactin Results

Other Investigations

MRI Head was booked for the following week. Interestingly, even in prolactin secreting tumours, the correlation between tumour size and prolactin level is limited. MRI head remains a vital investigation.

Final Diagnosis

An Introduction to Sellar Masses (Chapter 10) - Clinical Neuroendocrinology
Pituitary Macroadenoma

Take Home Message

During pregnancy the concentration of prolactin rises under the influence of elevated estrogen and progesterone production. The stimulating action of prolactin on the mammary gland leads post partum to lactation. Hyperprolactinemia (in men and women) is the main cause of fertility disorders. The determination of prolactin is utilized in the diagnosis of anovular cycles, hyperprolactinemic amenorrhea and galactorrhea, gynecomastia and azoo-spermia. Prolactin is also determined when breast cancer and pituitary tumors are suspected. As in this case, a pituitary tumour was suspected, hence the repeated prolactin results.

As was noted in another short case, our assay on the Roche platform does measure all forms of prolactin, and when a high result is obtained (above the gender-specific reference range) it is recommended to measure the recovery after PEG precipitation.

Figure 1

Dr. John Stanfliet (pathologist at Pathcare) repied to the above case with very valuable comments:

  • We use Beckman Coulter DxI, an immunoassay that is not affected by macroprolactin (I’ve include an article that shows this).
  • Even in prolactin secreting tumours, the correlation between tumour size and prolactin level is limited.  MRI head remains a vital investigation.
  • Some prolactin secreting tumours also secrete other pituitary hormones such as growth hormone.
  • I would ascribe the reduction in PRL to the Carbegoline and wonder whether the dose has been increased.
  • Dr. Pete Berman would often suggest a mixing study: find a sample with high PRL, mix it 50/50 with this sample, and measure it to see whether there is some interferant in this sample.