Primary amenorrhoea with ulcerative colitis

HOSP # WARD
CONSULTANT   DOB/AGE 15 y girl

Abnormal Result

This patient was discussed at a combined Endocrinology / Chemical Pathology meeting.

Total bilirubin: 281 umol/L

Presenting Complaint

The patient was a candidate for a liver transplant, but was referred to the endocrinology department for the short stature and primary amenorrhoea prior to surgery.

History

She was diagnosed with ulcerative colitis in 2016 (@ 12y age) and primary sclerosing cholangitis. Breast development started in 2018 (@14 years), but no menstrual cycles started ever since.

She has one younger sister which is well currently at 4 y age.

Birth weight was 3.8 kg.

Medication

Patient was receiving steroids and sulfasalazine intermittently.

For portal hypertension she is also receiving furosemide and spironolactone

Vitamin D supplements are also given

Examination

Height (114cm) for age: <3rd percentile

Weight 35 kg

Breasts well developed – Tanner IV,

No armpit hair growth, parse pubic hair – Tanner II

Laboratory Investigations

Test Result
Total bili (umol/L)   281 H
Conj bili (umol/L)   246 H
ALT (U/L)    58 H
AST (U/L)   151 H
ALP (U/L)   524 H
GGT (U/L)    65 H
TSH mIU/ml  1,74  
Free T4 (pmol/L)  16,4  
Free T3 (pmol/L)   2,8 L
FSH (IU/L)   8,2  
LH (IU/L)   6,2  
E2 (pmol/L   462  
Prog (nmol/L)   0.9  
Prolactin (ug/L)  15,4  
INR 2.09
IGF-1 (ug/L) 107.8 – 541.5
Tanner stages:
Boys Girls
Stage I 63 – 271 ug/L 71 – 394 ug/L
Stage II 114 – 411 ug/L 122 – 508 ug/L
Stage III 166 – 510 ug/L 164 – 545 ug/L
Stage IV 170 – 456 ug/L 174 – 480 ug/L
Stage V 161 – 384 ug/L 169 – 400 ug/L
23.5
Table 1 – Results

Other Investigations

Histology (Colonoscopy)

MICROSCOPIC:
Right, transverse and left colon:
Sections show large bowel type mucosa with maintained crypt architecture with no cryptitis or crypt abscess formation noted. No significant increased intra epithelial lymphocytes or subepithelial collagen deposition is present. The lamina propria shows normal inflammatory cells with no giant cells, granulomas, infective organisms, viral inclusions, epithelial atypia or malignancy identified. Colon mucosa morphologically within normal limits

Rectum:
Sections show large bowel mucosa with preserved crypt architecture and increased chronic inflammation in the lamina propria. Active inflammation is absent. There is no evidence of granulomas, viral inclusions, parasites or dysplasia. Non-specific increase in chronic inflammation in the lamina propria.

The other proposed additional examination is a pubic ultrasound to evaluate the ovaries, fallopian tubes and uterus.

It was also proposed that IGF binding protein 3 be measured, as low levels may yield IGF-1 shorter biologically active.

Final Diagnosis

Primary amenorrhoea most likely due to a physiological delay. Although the pelvic ultrasound hasn’t been done at the time of writing, the low IGF-1 likely indicates a low growth due to chronic systemic disease – see other possible aetiologies below.

Take Home Message

Amenorrhea can be a condition resulting from dysfunction of the hypothalamus, pituitary, ovaries, uterus, or vagina.

The most common aetiologies include:

  • Gonadal dysgenesis, including Turner syndrome – 43%
  • Müllerian agenesis (absence of vagina, sometimes with absence of uterus) – 15%
  • Physiological delay of puberty (constitutional delay of puberty, chronic systemic disease, acute illness) – 14%
  • Polycystic ovary syndrome (PCOS) – 7%
  • Isolated gonadotropin-releasing hormone (GnRH) deficiency – 5% (possible selection bias)
  • Transverse vaginal septum – 3%
  • Weight loss/anorexia nervosa – 2%
  • Hypopituitarism – 2%



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: