Prolactinoma and Pituitary Tumours Flashcards

1
Q

Prolactin

A

Prolactin is secreted by the anterior pituitary gland with release being controlled by a wide variety of physiological factors. Dopamine acts as the primary prolactin releasing inhibitory factor and hence dopamine agonists such as bromocriptine may be used to control galactorrhoea. It is important to differentiate the causes of galactorrhoea (due to the actions of prolactin on breast tissue) from those of gynaecomastia

Features of excess prolactin

men: impotence, loss of libido, galactorrhoea
women: amenorrhoea, galactorrhoea

NB Bromocriptine can be used to control galactorrhoea (dopamine acts as primary prolactin releasing inhibitory factor)

NB Prolactin is unique amongst the pituitary hormones in being tonically inhibited by the hypothalamus i.e. under CONTINUOUS inhibition

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2
Q

Causes of a Raised Prolactin

A
Causes of raised prolactin
prolactinoma
pregnancy
oestrogens
physiological: stress, exercise, sleep
acromegaly: 1/3 of patients
polycystic ovarian syndrome
primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)
Drug causes of raised prolactin
metoclopramide, domperidone
phenothiazines
haloperidol
very rare: SSRIs, opioids
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3
Q

Prolactinoma - Mx: Example Question

A

A 23-year-old woman attends a fertility clinic with her partner. She complains of oligomenorrhoea and galactorrhoea and has failed to get pregnant after 18 months of regular unprotected intercourse. Blood tests reveal a serum prolactin level of 6000 mIU/l (normal <500 mIU/l). A pituitary MRI is arranged which shows a microprolactinoma.

Which of the following is the best initial treatment?

	Octreotide
	> Bromocriptine
	Trans-sphenoidal hypophysectomy
	Pituitary radiotherapy
	Transfrontal hypophysectomy

This patient has a prolactinoma. In the majority of cases, symptomatic patients are treated medically with dopamine agonists (e.g. bromocriptine) which inhibit the release of prolactin from the pituitary gland. Surgery is performed for patients who cannot tolerate or fail to respond to medical therapy. A trans-sphenoidal approach is generally preferred unless there is a significant extra-pituitary extension. Radiotherapy is rarely performed and octreotide is a somatostatin analogue used in the treatment of acromegaly.

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4
Q

Pituitary Tumours

A

Pituitary tumours

Hormones secreted
prolactin- 35%
no obvious hormone, 'non-functioning', 'chromophobe' - 30%
growth hormone - 20%
prolactin and growth hormone - 7%
ACTH - 7%
others: TSH, LH, FSH - 1%
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5
Q

Pituitary Macroadenoma - Mx

A

A 27-year-old female presents with secondary amenorrhoea after stopping the oral contraceptive pill 6 months ago. She gets regular headaches and struggles to stand from seated or climb stairs.

On examination, milk could be expressed from the breasts and visual fields showed bilateral defects in the upper outer quadrants.

Prolactin	1080 mIU/L (NR<360)
FSH	0.1 IU/L (NR 1-11)
LH	0.2 IU/L (NR 20-75)
TSH	0.1 mIU/L (NR 0.3-6.0)
T4	8 pmol/L (NR 10-25)
9am cortisol	20 nmol/L (NR 140-700)

Pituitary MRI: 3cm pituitary mass with tenting of optic chiasm.

What is the next step in management?

	Bromocriptine
	Octreotide
	Stereotactic radiotherapy
	> Trans-sphenoidal surgery
	Transcranial hypophysectomy

This patient has a macroadenoma (>1cm) causing visual field defects. Trans-sphenoidal surgery is the first step in management. Raised prolactin can be secondary to blockage of the pituitary stalk with prevention of dopamine reaching the pituitary causing disinhibition of the lactotrophs.

Prolactin secreting macroadenomas secrete very high quantities and PRL is usually >6000mU/ml particularly with macro-prolactinomas (this is not the case making a prolactinoma unlikely). Prolactinomas are treated with dopamine agonists (bromocriptine, cabergoline) first-line. Octreotide is used to treat acromegaly.

Transcranial hypophysectomy is done for very large tumours that cant be removed via the trans-sphenoidal route.

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6
Q

Markedly Raised Prolactin - Ix: Example Question

A

A 42-year-old man is referred from his GP to the outpatient department with a loss of libido and impotence. He has a stressful job as a pharmaceutical representative and has a five-year pack year history. He consumes four pints of beer per night.

Blood tests reveal a prolactin of 3340 mU/l (<360), normal thyroid function tests, MCV 100 fl, testosterone low.

Which of the following would be the most appropriate investigation?

	Visual field testing
	Urine cortisol
	Pituitary dynamic function tests
	> MRI pituitary
	Anterior pituitary function testing

This patient has a prolactin result of over 3340 mU/l suggesting the most likely diagnosis is a prolactinoma. As the result is below 6000 mU/l would be suggestive of microprolactinoma as opposed to a macroprolactinoma. The most appropriate investigation would therefore be an MRI of the pituitary. On a side note, his raised MCV reinforces his history that he consumes too much alcohol.

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7
Q

Secondary Amenorrhoea and Prolactin : Example Question

A

A 29-year-old nulligravida woman attends her GP as she has not menstruated for 6 months. Menarche was at age 14. She had irregular periods from age 14-16, and then took oral hormonal contraception until last year when she got married. The patient does not know her family history as she is adopted. She is otherwise fit and well, enjoying running recreationally and eating healthy. She does not drink, smoke or use illicit drugs. Her vital signs are normal and body mass index is 22 kg/m².

Physical examination shows no abnormalities. Urine pregnancy test is negative.

Which of the following is the most appropriate screening test for this patient?

	Karyotype
	MRI of the pituitary
	Serum 17-hydroxyprogesterone
	> Serum prolactin
	Ultrasound of the pelvis

The patients presentation is consistent with secondary amenorrhoea. The first investigative step is normally to do a pregnancy test, which in this case is negative. There are no obvious explanations for secondary amenorrhoea from her presentation. Hence the next step is to obtain serum prolactin, TSH and FSH blood results (as this will help differentiate between the most common causes of secondary amenorrhoea following pregnancy: hyperprolactinaemia, thyroid dysfunction and premature ovarian failure respectively).

Choice 1: Premature ovarian insufficiency is characterised by elevated FSH and low oestradiol. A karyotype may be considered if Turner syndrome or fragile X syndrome is suspected, as these patients usually have ovarian dysfunction. However, this patient has no dysmorphic features or other co-morbidities to warrant karyotype evaluation.

Choice 2: An MRI of the pituitary should be performed in patients with persistently elevated prolactin (with or without galactorrhoea), unexplained headaches, bitemporal hemianopia or other concerning neurologic findings. It is not an appropriate screening test in this patient.

Choice 3: Serum 17-hydroxyprogesterone is elevated in non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, a condition that presents with hyperandrogenism in late childhood. This patient has no findings of androgen excess (e.g. male pattern hair distribution, severe acne).

Choice 5: An ultrasound may be indicated in patients with abnormal pelvic pain, pelvic organ enlargement or masses on examination, or signs of hyperandrogenism (e.g. polycystic ovarian syndrome, androgen tumour), none of which are seen in this patient.

Reference: http://cks.nice.org.uk/amenorrhoea#!scenario:1

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8
Q

Secondary Amenorrhoea

A

Ix:
Pregnancy test, serum prolactin, TSH and FSH blood results

Common causes of secondary amenorrhoea:

  • Pregnancy
  • Hyperprolactinaemia
  • Thyroid dysfunction
  • Premature ovarian failure
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9
Q

Prolactinoma Mx

A

< 6000mU/l = microprolactinoma
> 6000 mU/l = macroprolactinoma.

Prolactin secreting macroadenomas secrete very high quantities and PRL is usually >6000mU/ml particularly with macro-prolactinomas

Prolactinomas are treated with dopamine agonists (bromocriptine, cabergoline) first-line.

A macroadenoma (>1cm) causing visual field defects is not necessarily a prolactinoma.
Raised prolactin can be secondary to blockage of the pituitary stalk with prevention of dopamine reaching the pituitary causing disinhibition of the lactotrophs. 
- Trans-sphenoidal surgery is the first step in management.

Transcranial hypophysectomy is done for very large tumours that cant be removed via the trans-sphenoidal route.

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10
Q

Macroadenoma - Example Question

A

A 27-year-old female presents with secondary amenorrhoea after stopping the oral contraceptive pill 6 months ago. She gets regular headaches and struggles to stand from seated or climb stairs.

On examination, milk could be expressed from the breasts and visual fields showed bilateral defects in the upper outer quadrants.

Prolactin	1080 mIU/L (NR<360) 
FSH	0.1 IU/L (NR 1-11) 
LH	0.2 IU/L (NR 20-75) 
TSH	0.1 mIU/L (NR 0.3-6.0) 
T4	8 pmol/L (NR 10-25) 
9am cortisol	20 nmol/L (NR 140-700)

Pituitary MRI: 3cm pituitary mass with tenting of optic chiasm.

What is the next step in management?

Bromocriptine 
Octreotide 
Stereotactic radiotherapy 
> Trans-sphenoidal surgery 
Transcranial hypophysectomy

This patient has a macroadenoma (>1cm) causing visual field defects. Trans-sphenoidal surgery is the first step in management. Raised prolactin can be secondary to blockage of the pituitary stalk with prevention of dopamine reaching the pituitary causing disinhibition of the lactotrophs.

Prolactin secreting macroadenomas secrete very high quantities and PRL is usually >6000mU/ml particularly with macro-prolactinomas (this is not the case making a prolactinoma unlikely). Prolactinomas are treated with dopamine agonists (bromocriptine, cabergoline) first-line. Octreotide is used to treat acromegaly.

Transcranial hypophysectomy is done for very large tumours that cant be removed via the trans-sphenoidal route.

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11
Q

TSH Secreting Pituitary Tumour

A

A 55 year-old female presents to the outpatients department having been referred by her GP. She complains of fatigue, increased sweating and weight loss over the past four months. She also reports a loss of sex drive.

Examination reveals that she is pale and has a pulse rate of 121 per minute with a bounding pulse character. Her blood pressure is 118/79 mmHg and she has heart sounds 1 and 2 presents with no added sounds. On auscultation, her chest is clear and her abdomen is soft and non-tender with no organomegaly. She has a smooth goitre but has no signs of thyroid eye disease. Examination of her cranial nerves are normal.

The results of recent blood tests are as follows:

Hb	11.3 g/dl
Platelets	190 * 109/l
WBC	10.9 * 109/l
Na+	129 mmol/l
K+	4.3 mmol/l
Urea	7.9 mmol/l
Creatinine	94 µmol/l
ALP	155 u/l
Calcium	2.40 mmol/l
Albumin	40 g/L
TSH	11 mU/L
Free T4	41 pmol/L
Free T3	11 pmol/L

Which of the following is the most likely diagnosis?

	Grave's disease
	Thyroid cancer
	Surreptitious thyroxine ingestion
	De Quervain's thyroiditis
	> TSH secreting pituitary tumour

Biochemistry reveals elevated thyroid-stimulating hormone (TSH) with concurrent elevated thyroxine (T4) and tri-iodothyronine (T3). An elevated alkaline phosphatase (ALP) is consistent with thyrotoxicosis. Hyponatraemia suggests hypoadrenalism.

Taken with the symptoms, this patient has a likely diagnosis of a thyrotropinoma, which is a rare type of pituitary tumour accounting for approximately less than 1% of cases of pituitary tumours. 90% are macroadenomas.

Presentation is typically with features of thyrotoxicosis and include weight loss, sweating, fatigue and tachycardia. There may also be signs of hypopituitarism.

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12
Q

Pituitary Tumours

A

Pituitary tumours

Hormones secreted
prolactin- 35%
no obvious hormone, 'non-functioning', 'chromophobe' - 30%
growth hormone - 20%
prolactin and growth hormone - 7%
ACTH - 7%
others: TSH, LH, FSH - 1%
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13
Q

Panhypopituitarism - Example Question

A

A 52-year-old male presented with poor concentration, weight gain and tiredness for nine months duration. Three years ago he underwent resection of a pituitary tumour and was commenced on hydrocortisone 10 mg twice per day and thyroxine 150 g daily.

Examination reveals nothing significant.

Investigations show:

Serum free T4 12 pmol/L
Serum TSH < 0.05 mU/L
Serum testosterone 7.3 nmol/L (10-30)
IGF-1 8.9 nmol/L (10-35)

What is the most appropriate treatment for this patient?

	Reduce the dose of thyroxine
	Reduce the dose of hydrocortisone
	Increase the dose of hydrocortisone
	Testosterone injection
	> Growth hormone

This man with panhypopituitarism is receiving adequate replacement of hydrocortisone and thyroxine.

In panhypopituitarism the TSH is low so the thyroxine replacement is monitored by the free T4 which is within the normal range in this case.

Symptoms of weight gain, tiredness and poor concentration are typical of growth hormone deficiency which is further supported by the low IGF-1.

Indeed, this gentleman is also requiring testosterone replacement but this is not the best answer here.

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