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Endocrine > Non-Functioning Pituitary Tumours (NFPA) and Incidentaloma > Flashcards

Non-Functioning Pituitary Tumours (NFPA) and Incidentaloma Flashcards

1
Q

What is pituitary adenoma?
How do classify pituitary adenoma?

A

Pituitary Adenoma
Benign monoclonal neoplasm of anterior pituitary cells.
More than 90% incidentalomas are microadenoma
80-100 cases per 100,000 persons

Classification
1. Cell origin: gonadotroph, lactotroph, somatotroph, corticotroph, thyrotroph
2. Size: microadenoma < 1cm, macroadenoma > 1cm, giant > 4cm
3. Hormonal overproduction
- Functioning: acromegaly, Cushing, prolactinoma
- Non-functioning: absent of hormonal excess, mostly gonadotroph in origin, but inefficient synthesis

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2
Q

What are the differential diagnosis of sellar mass?

A
  1. Pituitary adenomas
  2. Rest cell tumours (Rathke’s cleft cyst, cranipharyngioma)
  3. Arachnoid cyst
  4. Mesenchymal/stromal (meningioma, chordomas)
  5. Neuronal/paraneuronal (gangliocytoma, neuroblastoma)
  6. Hypophysitis
  7. Posterior pituitary
  8. Germ cell tumours
  9. Metastasis
  10. Pseudotumour (hypothyroidism, puberty, pregnancy)
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3
Q

Natural course of NFPA

A

Growth of 10-13% for microadenomas; 30-40% for macroadenomas over 8 years
Growth very slow rates (1-2mm/year)
Incidence of pituitary apoplexy 1.1 per 100 patient-years (macro), 0.4 per 100 patient-years (micro)

Expansion of intrasellar mass
1. Compresses intrasellar pituitary tissue
2. Invades dorsally through dura, lifting optic chiasm
3. Laterally to cavernous sinuses
4. Bony erosion
5. Brain compression

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4
Q

What are the common presentation for NFPA?

A
  1. 50-60 years old, slight male predominance
  2. Asymptomatic, detected incidentally (<10%)

Most tumours are macroadenoma >80% on detection - with tumour compressive effect

  1. Headache - stretching of dural membrane, intrasellar pressure, trigeminal pain
  2. Vision defect - optic chiasm compression
    - Superior temporal -> + inferior -> + bitemporal hemianopia
  3. Pituitary hormone deficiency
    - FSH, LH and GH (>50%)
    - Thyroid, adrenal hormone (< 30%)
  4. Ophthalmoplegia/diplopia - CN3/4/6/5 compression (cavernous sinus invasion)
  5. Pituitary apoplexy
  6. Cerebrospinal leak/rhinorrhoea - sphenoid bone and sinus extension
  7. Stroke (ICA occlusion)
  8. Seizure (temporal lobe involvement)
  9. Intracranial hypertension, hydrocephalus - compression of foramen of Monro
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5
Q

What is pituitary apoplexy?
How does pituitary apoplexy present?

A

Haemorrhage or infarct of pituitary gland

Syndrome of:
1. Headache
2. Visual deficit
3. Ophthalmoplegia
4. AMS
5. Haemodynamic instability
6. Adrenal insufficiency (75%)
7. hypothyroidism (50%)

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6
Q

Types of NFPA

A
  1. Gonadotrophs (80%) - stain positive LH-b, FSH-b, SF-1
  2. Null cell tumours - negative immunoreactivity
  3. Silent adenomas - no stigmata of hormonal excess
  4. Plurihormonal tumours
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7
Q

Are silent or plurihormonal pituitary tumours significant?

A

Yes - aggressive behaviour, high degree of invasiveness, high recurrence

Refractory to standard treatment, requires repeat resection +/- radiation.

May progress to function-apparent disease

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8
Q

Heritable pituitary adenomas

A

Most adenomas are not heritable

< 5% NFPA hereditary - MEN 1, MEN-4, familial isolated aenomas, succinate dehydrogenase mutations

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9
Q

Evaluation of pituitary adenoma or incidentaloma

A
  1. History and examination
    - Tumour compressive effects
    - Hormonal excess or deficient
  2. Pituitary hormone testing
    - 8am cortisol, ACTH, prolactin, GH, IGF-1, TSH, fT4, LH, FSH, testosterone, estradiol
    - DHEA-S for central adrenal insufficiency
  3. MRI pituitary gland (or CT pituitary gland if contraindicated)
  4. Formal visual field testing
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10
Q

Why does NFPA have elevated prolactin?

At what levels of elevated prolactin does it indicate functioning prolactinoma?

A

Prolactin secretions negative regulation by hypothalamic dopamine via pituitary stalk
- Stalk compression from large tumour impairs dopamine delivery -> loss of regulation increases prolactin level

Usually elevated range of 100-150ng/mL (2000-3500mIU/L)

Macroprolactinomas > 500ng/mL (>10,000mIU/L)

When indistinguishable, can trial dopamine antagonist (cabergoline)
- NFPA with stalk effect hyperprolactinaemia turns undetectable, but tumour does not shrink even months after treatment

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11
Q

Treatment of NFPA

A
  1. Trans-sphenoidal surgery

Indications
- Visual field deficit, vision loss, ophthalmoplegia
- Compression of optic apparatus
- Endocrine dysfunction
- Pituitary apoplexy
- Refractory headache
- Other neurological deficits

  1. Radiotherapy
    - In small adenomas
    - adjuvant therapy for incomplete resected tumors.
  2. Rarely used - temozolomide
    Only in very aggressive and malignant tumour

Other treatment are ineffective

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12
Q

NFPA Follow up criteria

A
  1. Interval MRI imaging
    - 6 monthly x2
    - Annually x5
    - 2-5 yearly if asymptomatic over prolonged period
  2. If significant interval growth for hormonal re-evaluation
  3. TSS if develop indications (complications)
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13
Q

TSS Recovery

A
  1. Hormonal function
    - Maintains normal hormonal function (90%)
    - Normalisation of hormonal abnormalities (15-30%)
    - New onset pituitary deficiency (5-7%)
  2. Headache - 70% relief
  3. Vision recovery - 50% recovery, 30% partial, 20% non recovery
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14
Q

Radiation therapy for NFPA

A

> 90% progression-free survival rates at 10 years

Choices
1. Conventional radiation
2. Stereotactic radiosurgery (gamma knife) - comparable efficacy, lower hypopituitarism rate

Criteria
Small adenomas (<3mm) with at least 5mm from optic chiasm (to prevent radiotherapy nerve toxicity)

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15
Q

Complications post-surgery

A
  1. Fluid and sodium balance abnormalities
    - Triphasic DI-SIADH-DI
    - Or other cycles of DI +/- SIADH
  2. Adrenal insufficiency
  3. Pituitary hormone insufficiency
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16
Q

Describe triphasic DI-SIADH-DI post-operative complication

A
  1. Transient DI
    - Impaired ADH secretions POD 1-2
    - High volume, diluted UO (>250mL/hour or > 3L/day)
  2. SIADH
    - POD 5-10
  3. Possible permanent DI
    - Exhaustion of ADH stores
    - Permanent destruction >85% of hypothalamic ADH neurons
17
Q

What are the possible causes of post-operative polyuria?

A
  1. Fluid excretion from perioperative fluid administration
  2. Central DI
  3. Osmotic diuresis (glycosuria)
  4. GH salt and water mobilisation (GH-secreting tumour)
18
Q

Management of post-operative polyuria

A

Mild: fluid replacement
Severe: desmopressin (DDAVP) 0.5-1 mcg once and PRN

19
Q

Management of post-operative SIADH?

A

Nadir sodium levels occur most commonly between POD 5 to 9

  1. Fluid restriction 1-1.5L/day
  2. Routine serum sodium check
  3. Severe hyponatraemia/complications - hypertonic saline
  4. Refractory: tolvaptan, conivaptan

Correction limited to < 10-12 mmol/L
(or even lower at < 8 mmol/L) - hypokalaemia, liver disease, alcoholism, poor nutrition

20
Q

Criteria for SIADH

A
  1. Serum sodium < 135
  2. Serum osmolality < 275
  3. Urine osmolality > 100
  4. Urinary sodium > 40
  5. Euvolaemic
  6. Normal renal function
21
Q

Pattern of hormonal loss post-surgery

A

GH, LH, FSH >TSH, ACTH > PRL
Rarely posterior deficiency (ADH, oxytocin)

22
Q

How common is pituitary carcinoma?
How to suspect pituitary carcinoma?

A

Extremely rare (<0.2%), usually from longstanding recurrent invasive prolactinoma and ACTH-secreting macroadenoma

Suspect pituitary carcinoma if imaging shows:
1. Non-contiguous with primary sellar tumour
2. Spread to distant sites - LN, spine, bone, liver

23
Q

What malignancies frequently metastasize to pituitary gland?

A
  1. Breast (40%)
  2. Lung (25%)
  3. Prostate (5%)
  4. Renal (5%)
  5. Melanoma (3%)
  6. Thyroid (3%)
  7. Colon (3%)
  8. Unknown primary (3%)
24
Q

Long term management of pituitary insufficiency post-surgery

A
25
Q

Criteria for DI

A
  1. Polyuria - UO > 800mL over 4 hours or > 500mL over 1 hour
  2. Hypernatraemia > 145 or hyperosmollity > 295
  3. Inappropriately dilut urine (uOsm < 200 or uOsm < sOsm, urine SG < 1.005))

Endocrine (4 decks)

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