Pituitary Disorders Flashcards
1
Q
Pituitary tumors (minority) cause clinical problems due to:
A
- uncontrolled secretion of pituitary hormones.
- local compression effects.
- inadequate production of hormones by the remaining normal pituitary (i.e. hypopituitarism).
2
Q
Tumors may be:
A
- Small = micro-adenomas <10mm diameter
- Large = macro-adenomas >10mm diameter
3
Q
Name some Local compression effects of a pituitary tumor
A
- Bitemporal hemianopia (optic chiasm)
- Diplopia & CN III, IV & VI palsies
- Headache
- Increase prolactin (PRL) levels due to loss of dopaminergic inhibitory control.
- If very large = altered hypothalamic control of appetite, thirst & somnolence.
4
Q
Many hormones are released in either by a _______ or a _________ pattern & are regulated by feedback systems.
A
pulsatile, circadian
5
Q
Pituitary tumors are a relatively common incidental finding in the general population, only a minority cause clinical problems due to:
A
- uncontrolled secretion of pituitary hormones
- due to local compression effects
- hypopituitarism = inadequate production of hormones by the remaining normal pituitary
6
Q
The vast majority of tumors are?
A
Benign
7
Q
Tumors may be
A
- small = microadenomas <10mm diameter
- large = macroadenomas >10mm diameter
8
Q
Local compression effects of Pituitary tumors
A
- failure of pituitary gland function
- bitemporal hemianopia (lateral vision loss - optic chiasm)
- diplopia (double vision - optic nerves)
- CN III, IV & VI palsies
- increase prolactin (PRL) levels
- headache
- if very large = can alter the hypothalamic control of appetite, thirst & somnolence (strong desire for sleep)
9
Q
Uncontrolled hormone release occurs with tumors arising from the 5 types of cells:
A
- corticotroph cells = ACTH excess = Cushing’s syndrome.
- somatotroph cells = hGH excess = Acromegaly (adults) or Gigantism (kids)
- lactotrophs = PRL excess = Prolactinoma
- thyrotrophs = rarely hyperthyroidism = TSH-releasing tumors
- gonadotroph = rare LH or FSH excess = ovarian hyperstimulation & testicular enlargement.
10
Q
Uncontrolled hormone release occurs with tumors arising from the 5 types of cells:
A
- corticotroph cells = ACTH excess = Cushing’s syndrome.
- somatotroph cells = hGH excess = Acromegaly (adults) or Gigantism (kids)
- lactotrophs = PRL excess = Prolactinoma
- thyrotrophs = rarely hyperthyroidism = TSH-releasing tumors
- gonadotroph = rare LH or FSH excess = ovarian hyperstimulation & testicular enlargement.
11
Q
Some common pituitary tumors cause no apparent hormone excess & are referred to as ______________ tumors.
A
non-functioning tumors
12
Q
Investigations of Pituitary tumor
A
- MRI of the pituitary = superior to CT because it readily shows any significant pituitary mass. Microadenomas are very common on MRI (10%) = pituitary incidentalomas
- visual field = Goldmann perimetry & using red pin for clinical assessment. Common defects = upper temporal quadrantanopia & bitemporal hemianopia.
13
Q
The aim of therapy for pituitary tumors is to: (4)
A
(1) Reduce tumor bulk & relieve pressure on local structures.
(2) Restore excess hormone secretion to normal levels
(3) Eliminate associated co-morbidities & increased mortality resulting from hormone excess.
(4) Preserve or restore pituitary function.
14
Q
Treatment of pituitary tumors includes:
- dependent on the etiology of the pituitary mass.
A
- surgery
- radiotherapy
- medical therapy
15
Q
Post-operative radiotherapy is used if?
A
Significant tumor bulk remains after surgery or the underlying disease is still active.
16
Q
Radiotherapy results in?
A
Decline of residual pituitary function over many years & must be monitored.
17
Q
Surgery is only required if the pituitary tumor is large enough to?
(2)
A
- cause anatomical effects
- secretion of excess hormones. Small tumors producing no significant symptoms, pressure or endocrine effects may be observed.
18
Q
Surgery for pituitary tumor is via the _______ route, which is usually the treatment of choice.
A
trans-sphenoidal route
19
Q
Very large pituitary tumors are usually done through the ______ _______ route for surgery.
A
open trans-cranial (usually trans-frontal) route
20
Q
Radiotherapy
A
- done by conventional linear accelerators or newer stereotactic techniques.
- conventional regimen = involves a dose of 45Gy.
- postoperative radiotherapy is used when the tumor bulk remains after surgery or the underlying disease is still active.
- results in gradual decline or residual pituitary function over many years & must be monitored.
21
Q
Medical therapy for pituitary tumor
A
- Somatostatin analogs and/or dopamine agonists (can shrink specific tumor types)
22
Q
________ _________ are the most common mass lesion of the pituitary (90%)
A
Pituitary adenomas
23
Q
Craniopharyngioma
A
- 1-2%
- usually cystic hypothalamic tumor
- arises from Rathke’s pouch
- most common pituitary tumor in children
- may present at any age
24
Q
Uncommon tumors include
A
- meningiomas
- gliomas
- chondromas
- germinomas
- pinealomas
25
Occasionally PRL & ACTH-secreting tumors present in an ________ manner which may?
aggressive manner which may require chemotherapy in addition to conventional treatment.
26
Metastases occasionally present as apparent pituitary tumors, typically accompanied by?
headache & diabetes insipidus
27
Panhypopituitarism
deficiency of all anterior pituitary hormones
28
Panhypopituitarism is most commonly caused by:
(3)
- pituitary tumors
- surgery
- radiotherapy
29
ADH will only be significantly affected if?
the hypothalamus is involved or if there is an infiltrative/inflammatory process.
30
Causes of Hypopituitarism (7)
1. Congenital = isolated deficiency of pituitary hormones (e.g. Kallmann's syndrome), POU1F1 mutations.
2. Infective = basal meningitis, encephalitis, syphilis.
3. Vascular = pituitary apoplexy (infarction of the pituitary), Sheehan's syndrome, carotid artery aneurysm.
4. Immunological = autoimmune hypophysitis, pituitary antibodies.
5. Neoplastic = pituitary or hypothalamic tumor, craniopharyngioma, meningioma, lymphoma.
6. Traumatic = skull fractures through base, surgery (especially transfrontal), perinatal trauma.
7. Infiltrations = sarcoidosis, langerhans' cell histiocytosis, hypophysitis = postpartum, giant cell.
31
PROP1 gene
Provides instructions for making a protein that helps control the activity of many other genes.
32
POU1F1 gene
Regulates the expression of several genes involved in pituitary development & hormone expression.
33
Mutations in the PROP1 & POU1Fi genes
Prevents differentiation of anterior pituitary cells leading to deficiencies of hormones.
differentiation - process of cells, tissues & organs acquiring specialized features.
34
Symptoms of deficiency of a pituitary-stimulating hormone are the _______ as those of primary deficiency of the peripheral endocrine gland.
- Example
same
- Example = TSH deficiency & primary hypothyroidism cause similar symptoms due to lack of thyroid hormone secretion.
35
Treatment for Hypopituitarism
- steroid & thyroid hormones are given as oral replacement drugs
- androgens & estrogens for symptomatic control
- LH & FSH analogs are used if fertility is desired.
- GH therapy should be given to the growing child under appropriate specialist supervision.
36
2 warnings necessary for the treatment of hypopituitarism
1. Thyroid replacement should not commence until normal glucocorticoid function has been demonstrated or replacement steroid therapy is initiated.
- may precipitate an adrenal crisis
2. Glucocorticoid deficiency masks impaired urine concentrating ability.
- Diabetes insipidus is apparent after steroid replacement.
37
Symptoms for Acromegaly
- Head & neck = changes in facial appearance, headaches, visual deterioration, deep voice, goitre.
- General = weight gain, breathlessness, excessive sweating, joint pain, muscular weakness.
38
Signs of Acromegaly
- Facial = prominent supraorbital ridge, prognathism (protruding jaw), interdental separation, large tongue, visual field defects.
- Hands = space-like hands & feet
- General = hirsutism (thick hair growth on different body parts), thick greasy skin.
39
Investigations for Acromegaly
(7)
1. GH levels
2. Glucose tolerance test
3. IGF-1 levels
4. Visual field examination
5. MRI scan pituitary
6. Pituitary function
7. Prolactin levels
40
GH levels - Acromegaly
- a detectable value alone is non-diagnostic
- normal adult levels < 0.5 microg/L (except during stress or a GH pulse)
41
Glucose tolerance test - Acromegaly
- is diagnostic if there is no suppression of Gh
- about 25% of acromegalics have a positive diabetic glucose tolerance test
42
IGF-1 levels - Acromegaly
- are almost always increased in acromegaly
- a normal IGF-1 + a random GH <1 microg/L may be taken to exclude acromegaly if the diagnosis is clinically unlikely.
43
Management of Acromegaly
- indication & aim
- Treatment is indicated in all except the elderly or those with minimal abnormalities.
- Aim = to achieve a mean GH level <2.5 microg/L not always normal BUT considered a safe GH level. Also to have a normal IGF-1 level.
44
Management of Acromegaly
(3)
1. Surgery
- trans-sphenoidal surgery is the appropriate 1st-line therapy.
- transfrontal surgery is rarely required except for massive macroadenomas.
2. Pituitary Radiotherapy
- normally used after pituitary surgery fails to normalize GH levels.
- combined with a somatostatin analog, dopamine agonist, or GH antagonist because of the slow biochemical response to radiotherapy.
3. Medical Therapy
45
Medical therapy - Acromegaly
3 receptor targets
1. Pituitary somatostatin receptors
- Octreotide & Lanreotide = monthly depot injections (slow release)
2. Dopamine (D2) receptors
- can be given to shrink tumors prior to definitive therapy OR to control symptoms & persisting GH secretion.
- given alone, they reduce GH to safe levels in only a minority of cases but are useful for mild residual disease or in combination with somatostatin analogs.
- bromocriptine 10-60mg daily
3. GH receptors antagonists
- Pegvisomant = genetically modified analog of GH
- it doesn't decrease GH levels or tumor size but normalizes IGF-1 levels (90%).
- daily injection
46
Prolactin (PRL) stimulates _______ ______ but also inhibits ______ _______. It is under tonic ________ inhibition.
milk secretion, gonadal activity, dopamine.
47
Causes of Hyperprolactinemia
(3)
1. Physiological
- pregnancy, lactation, stress, sleep, exercise & coitus.
2. Pathological
- prolactinoma, co-secretion of prolactin in tumors causing acromegaly, PCOS, primary hypothyroidism, idiopathic hyperprolactinemia.
3. Drug-induced
- estrogens (contraceptive pill), dopamine antagonists, antidepressants (SSRIs), antiemetics (metoclopramide).
48
In the presence of a pituitary mass on MRI, the level of PRL helps determine whether the mass is a...
- prolactinoma
- non-functioning pituitary tumor
49
Strongly suggestive of a Prolactinoma
>5000 mU/L + macroadenoma
>2000 mU/L + microadenoma (or no radiological abnormality)
- Macroprolactinoma >10mm in diameter
- Microprolactinoma <10mm in diameter
- Mesoadenomas approx. 10mm
50
Treatment for Hyperprolactinemia
- goals?
- reduce the size of the tumor
- treat galactorrhea
- reverse hypogonadism = avoid the long-term effects.
