Skull Base and Pituitary Surgery

Question 1

A 45-year-old man presents with sudden onsent headache, nausea, vomiting and visual disturbance. On examination he is apyrexial, hypotensive, and tachycardic but does not have neck stiffness or photophobia. Visual fields appear to be constricted on confrontation. CT head is abnormal therefore MRI is done. Which one of the following is appropriate acute management?
a. Dexamethasone
b. Formal visual field tests
c. Pituitary profile and start empirical intravenous hydrocortisone
d. Lumbar puncture
e. Transsphenoidal surgery

Answer 1

c. Pituitary profile and start empirical intravenous hydrocortisone

Pituitary apoplexy is characterized by sudden onset
headache, nausea, vomiting, with or without acute
visual disturbance and cranial nerve palsy (2nd,
3rd, 4th, 6th) due to pituitary hemorrhage and/
or infarction. Precipitating factors in those with
or without an underlying pituitary tumor include
hypertension, major surgery, dynamic testing of
pituitary function, anticoagulation/coagulopathy,
estrogen therapy, dopamine receptor agonist initiation/withdrawal, radiotherapy, pregnancy and
head trauma. Assessment should focus on history
and examination findings consistent with preexisting pituitary dysfunction. Anterior pituitary
function tests (FT4, TSH, IGF-1, random cortisol, prolactin, growth hormone, FSH/LH, and
testosterone in men or estradiol in women) should
be checked urgently but those with hemodynamic
instability (i.e. Addisonian crisis) should be started
on empirical hydrocortisone. Indications for
empirical steroid therapy in patients with pituitary
apoplexy are hemodynamic instability, altered
consciousness level, reduced visual acuity and
severe visual field defects. Patients who do not fulfill the criteria for urgent empirical steroid therapy
should be considered for treatment with steroids, if
their 0900 serum cortisol is less than 550 nmol/L;
The majority of the patients (nearly 80%) will have
deficiency of one or more anterior pituitary hormones at presentation. As most of the patients have
underlying macroadenomas, partial hypopituitarism would be expected to have been present the majority even before the apoplectic episode.
Clinically, the most crucial deficit is that of adrenocorticotroph hormone (ACTH) in up to 70%
of the patients. Thyrotrophin and gonadotrophin
deficiencies are observed in 50% and 75% of the
patients, respectively. Hyponatremia has been
reported in up to 40% of the patients because of
either the syndrome of inappropriate antidiuretic
hormone secretion or hypocortisolism. Patients
with pituitary apoplexy who have low serum prolactin (PRL) levels at presentation have the highest
intrasellar pressure and are the least likely to
recover from hypopituitarism after decompressive
surgery. Formal visual fields assessment, using
Humphrey visual field analyzer or Goldmann
perimeter must be undertaken when the patient
is clinically stable, preferably within 24 h of the
suspected diagnosis. MRI of the pituitary is
required to confirm the diagnosis. Hemorrhage
appears hyperintense on non-enhanced T1W
images and, in the acute stage, hyperdense on
CT and may rarely contain a fluid level (as in this
case) with evidence of optic chiasm being stretched
across the top of the mass. Patients with pituitary
apoplexy who are without any neuro-ophthalmic
signs or mild and stable signs can be considered
for conservative management with careful monitoring. In patients with reduced visual acuity or
defective visual fields, formal assessment of visual
fields and acuity should be performed every day
until a clear trend of improvement is observed.
Indications for urgent neurosurgical decompression include deteriorating level of consciousness,
severely reduced visual acuity, severe/persistent/ worsening visual field defect. Ocular paresis
because of involvement of III, IV or VI cranial
nerves in cavernous sinus in the absence of visual
field defects or reduced visual acuity is not in itself
an indication for immediate surgery. Resolution
will typically occur within days or weeks with
conservative management. Surgery should be
performed preferably within the first 7 days of onset
of symptoms by an experienced pituitary surgeon

Pituitary apoplexy is characterized by sudden onset headache, nausea, vomiting, with or without acute visual disturbance and cranial nerve palsy (2nd, 3rd, 4th, 6th) due to pituitary hemorrhage and/ or infarction. Precipitating factors in those with or without an underlying pituitary tumor include hypertension, major surgery, dynamic testing of pituitary function, anticoagulation/coagulopathy, estrogen therapy, dopamine receptor agonist initiation/withdrawal, radiotherapy, pregnancy and head trauma. Assessment should focus on history and examination findings consistent with pre- existing pituitary dysfunction. Anterior pituitary function tests (FT4, TSH, IGF-1, random cortisol, prolactin, growth hormone, FSH/LH, and testosterone in men or estradiol in women) should be checked urgently but those with hemodynamic instability (i.e. Addisonian crisis) should be started on empirical hydrocortisone. Indications for empirical steroid therapy in patients with pituitary apoplexy are hemodynamic instability, altered consciousness level, reduced visual acuity and severe visual field defects. Patients who do not fulfill the criteria for urgent empirical steroid therapy should be considered for treatment with steroids, if their 09 00 serum cortisol is less than 550 nmol/L; The majority of the patients (nearly 80%) will have deficiency of one or more anterior pituitary hormones at presentation. As most of the patients have underlying macroadenomas, partial hypopituitarism would be expected to have been present in the majority even before the apoplectic episode. Clinically, the most crucial deficit is that of adrenocorticotroph hormone (ACTH) in up to 70% of the patients. Thyrotrophin and gonadotrophin deficiencies are observed in 50% and 75% of the patients, respectively. Hyponatremia has been reported in up to 40% of the patients because of either the syndrome of inappropriate antidiuretic hormone secretion or hypocortisolism. Patients with pituitary apoplexy who have low serum prolactin (PRL) levels at presentation have the highest intrasellar pressure and are the least likely to recover from hypopituitarism after decompressive surgery. Formal visual fields assessment, using Humphrey visual field analyzer or Goldmann perimeter must be undertaken when the patient is clinically stable, preferably within 24 h of the suspected diagnosis. MRI of the pituitary is required to confirm the diagnosis. Hemorrhage appears hyperintense on non-enhanced T1W images and, in the acute stage, hyperdense on CT and may rarely contain a fluid level (as in this case) with evidence of optic chiasm being stretched across the top of the mass. Patients with pituitary apoplexy who are without any neuro-ophthalmic signs or mild and stable signs can be considered for conservative management with careful moni- toring. In patients with reduced visual acuity or defective visual fields, formal assessment of visual fields and acuity should be performed every day until a clear trend of improvement is observed. Indications for urgent neurosurgical decompression include deteriorating level of consciousness, severely reduced visual acuity, severe/persistent/worsening visual field defect. Ocular paresis because of involvement of III, IV or VI cranial nerves in cavernous sinus in the absence of visual field defects or reduced visual acuity is not in itself an indication for immediate surgery. Resolution will typically occur within days or weeks with conservative management. Surgery should be performed preferably within the first 7 days of onset of symptoms by an experienced pituitary surgeon.
FURTHER READING Rajasekaran S, Vanderpump M, Baldeweg S, Drake W, Reddy N, Lanyon M, Markey A, Plant G, Powell M, Sinha S, Wass J. UK guidelines for the management of pituitary apoplexy. Clin Endocrinol (Oxf) 2011;74(1):9-20.

Question 2

A 64-year-old male presented with severe headache and visual disturbance. Plain CT imaging revealed a sellar mass but no other acute abnormality. Contrast imaging was performed (below). Which one of the following is the most important next management step?
a. Pituitary profile
b. Formal visual field assessment
c. Image guided biopsy
d. Lumbar puncture
e. ICP monitoring

Answer 2

d. Lumbar puncture

Imaging above is a CT angiogram demonstrating a
giant ICA aneurysm expanding the sella. The most
important next step is to clarify the likelihood that
it has ruptured, and if so the patient will need to be
started on subarachnoid hemorrhage treatment
and the aneurysm secured. Options include lumbar
puncture (though many would avoid this given the
risk of aneurysm rupture) or assessing hemosiderin
on MRI. Others may argue that given the history
and the size of the aneurysm, treatment should
be performed expediently as in aneurysmal subarachnoid hemorrhage patients.

Imaging above is a CT angiogram demonstrating a giant ICA aneurysm expanding the sella. The most important next step is to clarify the likelihood that it has ruptured, and if so the patient will need to be started on subarachnoid hemorrhage treatment and the aneurysm secured. Options include lumbar puncture (though many would avoid this given the risk of aneurysm rupture) or assessing hemosiderin on MRI. Others may argue that given the history and the size of the aneurysm, treatment should be performed expediently as in aneurysmal subarachnoid hemorrhage patients.

Question 3

A 57-year-old undergoes elective transsphenoidal surgery for a non-functioning macroadenoma compressing the optic chiasm. Recovery was uneventful and routine bloods on postoperative day 1 were normal, and endocrine profile showed FT4 12 pmol/L (11.5-22), TSH 0.9 mU/L (0.35-5.5) and 9 am cortisol 154 nmol/L. Which one of the following statements regarding further management is LEAST accurate?
a. If thyroid function tests are normal on day 3 or 4 a further assessment should take place at 4-8 weeks
b.Evening steroid dose should not be omitted
if checking 9 am cortisol
c. If day 2 postoperative 9 am cortisol >550 nmol/L does not require steroid replacement
d. If day 2 postoperative 9 am cortisol 400550 nmol/L requires hydrocortisone only during severe illness
e. If day 2 postoperative 9 am cortisol <400 nmol/L does requires regular oral hydrocortisone

Answer 3

b.Evening steroid dose should not be omitted
if checking 9 am cortisol

If preoperative steroid reserve adequate or
unknown:
* Check 9 am serum cortisol on day 2 and on
day 3 after surgery, in patients with no
evidence of cortisol deficiency before operation. If already on hydrocortisone replacement, omit the evening dose for the
previous day before checking.
In patients without Cushing’s disease (9 am cortisol: >550 nmol/L no requirement for hydrocortisone, 400-550 nmol/L hydrocortisone only
during severe illness or stress, <400 nmol/L start
regular oral hydrocortisone).
If preoperative steroid reserve deficient:
* In patients with proven cortisol deficiency
before surgery, continue hydrocortisoneand consider changing over to maintenance
dosage when stable. These patients will
need further assessment at 4-8 weeks with
anterior hormone profile and short
synacthen test to determine whether they
will need long-term steroids;
* FT4 and TSH should be assessed on day 3
or day 4 and thyroid hormone replacement
should be considered if deficient.
* If FT4 and TSH normal further assessment
should take place at 4-8 weeks

If preoperative steroid reserve adequate or unknown:
* Check 9 am serum cortisol on day 2 and on day 3 after surgery, in patients with no evidence of cortisol deficiency before operation. If already on hydrocortisone replacement, omit the evening dose for the previous day before checking.
In patients without Cushing’s disease (9 am cortisol: >550 nmol/L no requirement for hydrocortisone, 400-550 nmol/L hydrocortisone only during severe illness or stress, <400 nmol/L start regular oral hydrocortisone). If preoperative steroid reserve deficient:
* In patients with proven cortisol deficiency before surgery, continue hydrocortisone and consider changing over to maintenance dosage when stable. These patients will need further assessment at 4-8 weeks with anterior hormone profile and short synacthen test to determine whether they will need long-term steroids;
* FT4 and TSH should be assessed on day 3 or day 4 and thyroid hormone replacement should be considered if deficient.
* If FT4 and TSH normal further assessment should take place at 4-8 weeks.
FURTHER READING Rajasekaran S, Vanderpump M, Baldeweg S, Drake W, Reddy N, Lanyon M, Markey A, Plant G, Powell M, Sinha S, Wass J. UK guidelines for the management of pituitary apoplexy. Clin Endocrinol (Oxf) 2011;74(1):9-20.

Question 4

A 65-year-old man undergoes transsphenoidal surgery for a non-functioning macroadenoma. Postoperatively on day 1 the nurses notice he is passing large volumes of dilute urine via his catheter. Which one of the following criteria is LEAST suggestive of diabetes insipidus?
a. Urine specific gravity <1.003 or osmolality <200 mOsmol/kg
b. Urine output >250 ml/h for 2 consecutive hours
c. Serum sodium normal or raised
d. Primary adrenal insufficiency
e. Inability to concentrate urine to >300 mOsmol/L in the presence of clinical dehydration

Answer 4

d. Primary adrenal insufficiency

Diabetes insipidus cannot occur in primary adrenal insufficiency (hypocortisolism/hypoaldosteronism) because mineralocorticoid activity is
required for kidneys to produce free water

Diabetes insipidus cannot occur in primary adrenal insufficiency (hypocortisolism/hypoaldosteronism) because mineralocorticoid activity is required for kidneys to produce free water.

Question 5

A 17-year-old female presents with an 8 month history of secondary amenorrhea. More recently she has noticed that she is more thirsty and is passing large volumes of urine. Her examination is otherwise unremarkable. Routine blood tests are normal and endocrine profile shows: FSH 5.5 U/L (follicular 0.5-5, mid-cycle 8-33, luteal 2-8), LH 2.8 U/L (follicular 3-12, mid-cycle 20-80, luteal 3-16), estradiol 32 pmol/L (follicular 17-260, luteal 180-1100), prolactin 990 mU/L (60-620), 9 am cortisol 400 nmol/L, fasting blood glucose 5.5 mmol/L, serum calcium 2.35 mmol/ L (2.2-2.6). Water deprivation test: serum osmolality 300 mOsmol/kg, urine 200 mOsmol/kg at 6 h, post-DDAVP urine osmolality 800 mOsmol/kg. MRI head is shown. Which one of the following would you perform next?
a. Serum and CSF HCG and AFP
b. Ultrasound pelvis/ovaries
c. Insulin tolerance test
d. Short synacthen test
e. Visual field tests

Answer 5

a. Serum and CSF HCG and AFP

Water deprivation test involves serial 2 hourly measurement of serum and urine osmolality (and body
weight) over a water deprivation period of 6-8 h—if
serum osmolality>290 and urine<300 by the endit
is suggestive of DI and DDAVP is given. If kidneys
are functioning normally, DDAVP should cause a
rise in urine osmolality to>750 suggesting a cranial
(failure of posterior pituitary vasopressin secretion,
as in this case) cause for the DI. This case describes
an adolescent presenting with a hypopituitarism
including cranial diabetes insipidus, with an homogeneously enhancing suprasellar mass and smaller
enhancing pineal cyst.The main concernis of a germinoma (synchronous suprasellar and pineal) given
her age andimaging, rather thanlymphocytic hypophysitis which presents later although the two may
be difficult to distinguish. MRI of the whole spine
with contrast should also be performed given these
findings. In a small proportion of germinomas,
there may be non-germinomatous elements secreting BHCG or AFP hence serum and CSF should be
checked urgently. If these are both negative biopsy
should be performed to confirm a diagnosis of germinoma and start radiotherapy with or without
chemotherapy

Water deprivation test involves serial 2 hourly measurement of serum and urine osmolality (and body weight) over a water deprivation period of 6-8 h—if serum osmolality>290 and urine<300by the end it is suggestive of DI and DDAVP is given. If kidneys are functioning normally, DDAVP should cause a rise in urine osmolality to>750 suggesting a cranial (failure of posterior pituitary vasopressin secretion, as in this case) cause for the DI. This case describes an adolescent presenting with a hypopituitarism including cranial diabetes insipidus, with an homogeneously enhancing suprasellar mass and smaller enhancing pineal cyst. The main concern is of a germinoma (synchronous suprasellar and pineal) given her age and imaging, rather than lymphocytic hypophysitis which presents later although the two may be difficult to distinguish. MRI of the whole spine with contrast should also be performed given these findings. In a small proportion of germinomas, there may be non-germinomatous elements secreting BHCG or AFP hence serum and CSF should be checked urgently. If these are both negative biopsy should be performed to confirm a diagnosis of germinoma and start radiotherapy with or without chemotherapy.

Question 6

A 33-year-old female who presents with a several week history of headache, extreme fatigue and malaise. She gave birth to her first child 2 months ago via vaginal delivery. Examination was unremarkable. Routine bloods were normal, and endocrine profile showed: Prolactin 801 mU/L (100-550), FT4 10 pmol/L (11.5-22), TSH 0.1 mU/L (0.35-5.5). Short synacthen test: 0 h cortisol 55 nmol/L, 30 min cortisol 155 nmol/L. MRI is shown. Which one of the following is most likely?
a. Lymphocytic hypophysitis
b. Sheehan’s syndrome
c. Non-functioning adenoma
d. Langerhans cell histiocytosis
e. Sarcoidosis

Answer 6

a. Lymphocytic hypophysitis

The clinical picture is that of anterior pituitary
pathology with early involvement/impairment of
corticotrophs (short synacthen test suggesting
adrenal insufficiency; normally increase should be
>200 nmol/L and 30 min value >600 nmol/L)
and thyrotrophs (low TSH). This is in contrast to
non-functioning pituitary adenomas where there
is usually early involvement of gonadotrophs.
Lymphocytic hypophysitis is most commonly
seen during pregnancy or postpartum period and
represents an inflammatory/autoimmune process
affecting the pituitary gland and the pituitary stalk
(infundibulum). Presentation is with pituitary
failure such as lethargy, amenorrhea, diabetes
insipidus and visual disturbance (if there is optic
chiasm compression). MRI may show a homogeneously enhancing sellar/infundibular mass and
T1WI may even show loss of posterior pituitary
bright spot (normally present due to vasopressin
storage) in cranial diabetes insipidus. Where there
is a high clinical suspicion (e.g. postpartum, other
autoimmune conditions, ipilimumab use, absence
of serum markers for sarcoidosis) treatment with
steroids and supportive therapy can be initiated.
However, if the picture is uncertain or no response
to steroids biopsy should be performed as it is the
only way to make the diagnosis.

The clinical picture is that of anterior pituitary pathology with early involvement/impairment of corticotrophs (short synacthen test suggesting adrenal insufficiency; normally increase should be >200 nmol/L and 30 min value >600 nmol/L) and thyrotrophs (low TSH). This is in contrast to non-functioning pituitary adenomas where there is usually early involvement of gonadotrophs. Lymphocytic hypophysitis is most commonly seen during pregnancy or postpartum period and represents an inflammatory/autoimmune process affecting the pituitary gland and the pituitary stalk (infundibulum). Presentation is with pituitary failure such as lethargy, amenorrhea, diabetes insipidus and visual disturbance (if there is optic chiasm compression). MRI may show a homogeneously enhancing sellar/infundibular mass and T1WI may even show loss of posterior pituitary bright spot (normally present due to vasopressin storage) in cranial diabetes insipidus. Where there is a high clinical suspicion (e.g. postpartum, other autoimmune conditions, ipilimumab use, absence of serum markers for sarcoidosis) treatment with steroids and supportive therapy can be initiated. However, if the picture is uncertain or no response to steroids biopsy should be performed as it is the only way to make the diagnosis.

Question 7

A 48-year-old male presents with low mood, malaise and reduced exercise tolerance. He has a past history of IHD and a non-functioning pituitary adenoma resected 5 years ago resulting in partial anterior hypopituitarism. He is normally on thyroxine and hydrocortisone replacement therapy. On examination his BMI is 39 kg/m 2 and shows central adiposity. His endocrine tests show 9 am cortisol 410 nmol/L, IGF-1 8 nmol/L (16-118), FT4 16 pmol/L (11.5-22) and TSH 0.03 mU/L (0.35-5.5). Which one of the following is most appropriate to confirm the diagnosis?
a. Growth hormone levels
b. GHRH-arginine stimulation test
c. IGF-binding protein 3 measurement
d. Insulin tolerance test
e. Water deprivation test

Answer 7

b. GHRH-arginine stimulation test

The clinical features of growth hormone deficiency are nonspecific and include lethargy, low
mood, poor quality of life, loss of muscle mass
and central adiposity. GH is normally secreted
in a pulsatile fashion (5 per 24 h) hence random
measurement of levels is not helpful. A low IGF-1 level may be present in 60-70% of patients with
GH deficiency, and may suggest the need for
dynamic tests of GH secretion. Equally, a low
IGF-1 in the presence of 3 or more other anterior
pituitary hormone deficiencies in an otherwise
healthy individual is a strong predictor of GH deficiency and treatment should be considered without dynamic testing. Contraindications to GH
therapy is active malignancy (other than pituitary).
If dynamic testing is required, the gold standard is
insulin tolerance test (ITT) where insulin administration should provoke a rise in GH (peak level
<10 mU/L or <3 μg/L is suggestive of severe
GH deficiency). However, ITT is contraindicated
in those with IHD and epilepsy due to the risks
associated with hypoglycemia and may give a false
result in obese patients. In this situation, other
dynamic tests include GNRH-arginine stimulation and glucagon stimulation test which have a
higher sensitivity than IGFBP-3 levels.

The clinical features of growth hormone deficiency are nonspecific and include lethargy, low mood, poor quality of life, loss of muscle mass and central adiposity. GH is normally secreted in a pulsatile fashion (5 per 24 h) hence random measurement of levels is not helpful. A low IGF- 1 level may be present in 60-70% of patients with GH deficiency, and may suggest the need for dynamic tests of GH secretion. Equally, a low IGF-1 in the presence of 3 or more other anterior pituitary hormone deficiencies in an otherwise healthy individual is a strong predictor of GH deficiency and treatment should be considered without dynamic testing. Contraindications to GH therapy is active malignancy (other than pituitary). If dynamic testing is required, the gold standard is insulin tolerance test (ITT) where insulin administration should provoke a rise in GH (peak level <10 mU/L or <3 μg/L is suggestive of severe GH deficiency). However, ITT is contraindicated in those with IHD and epilepsy due to the risks associated with hypoglycemia and may give a false result in obese patients. In this situation, other dynamic tests include GNRH-arginine stimulation and glucagon stimulation test which have a higher sensitivity than IGFBP-3 levels.

Question 8

A 56-year-old presents with a 2-month history of headache and visual disturbance. Confrontation testing revealed a bitemporal hemianopia. Routine bloods were normal and endocrine profile is: FT4 pmol/L 8.5 (11.5-22), TSH 0.5 mU/L (0.35-5.5), FSH 1.0 U/L (1.4-18.1), LH 2.5 U/L (3-8), prolactin 900 mU/L (45-375), testosterone 3.5 nmol/L (8.4-28.7), 9 am cortisol 405 nmol/L. MRI is shown. Which one of the following is most likely?
a. Non-functioning adenoma
b. Thyrotropinoma
c. GH-secreting pituitary adenoma
d. Prolactinoma
e. Cushing’s disease

Answer 8

a. Non-functioning adenoma

Pituitary adenomas are the most common neoplasms in the sellar region and comprise
10-15% of all primary brain tumors. They are
classified as microadenomas (<10 mm) and
macroadenomas (>10 mm). Furthermore, they
may be non-functional pituitary adenomas
(clinically not hormonally active) or functional
(clinically showing signs of hormone excess).
Non-functional adenomas account for 15-30%
of pituitary adenomas and show gonadotroph
(FSH, LH) deficiency in 80%, followed by
somatotrophy (GH secretion) deficiency, and
later thyrotrophs (TSH) and corticotrophs
(ACTH) deficiency in 20-50%. Gonadotrophs
are the commonest primary cell type involved
in NFPA. As such, patients tend to present with
hypogonadotrophic hypogonadism early, and
features of GH deficiency, secondary hypothyroidism and secondary adrenal insufficiency later on. Hypogonadotrophic hypogonadism is characterized by Large NFSs compress the pituitary
stalk, causing impairment of dopamine transport
to the lactotrophs and a slight rise in prolactin
secretions above normal (but prolactinoma is
usually associated with levels >200 mU/L).
Macroadenomas of either type (functional or
non-functional) may present with mass effect on
adjacent structures (e.g. chiasmal compression) or
pituitary apoplexy. MRI with and without contrast
is the imaging modality of choice. Management of
nonfunctioning pituitary adenoma is with elective
transsphenoidal surgery if there is evidence of optic
chiasm compression (as in this case with suprasellar
extension)—otherwise endocrine, ophthalmologic
and imaging surveillance is appropriate

Pituitary adenomas are the most common neoplasms in the sellar region and comprise 10-15% of all primary brain tumors. They are classified as microadenomas (<10 mm) and macroadenomas (>10 mm). Furthermore, they may be non-functional pituitary adenomas (clinically not hormonally active) or functional (clinically showing signs of hormone excess). Non-functional adenomas account for 15-30% of pituitary adenomas and show gonadotroph (FSH, LH) deficiency in 80%, followed by somatotrophy (GH secretion) deficiency, and later thyrotrophs (TSH) and corticotrophs (ACTH) deficiency in 20-50%. Gonadotrophs are the commonest primary cell type involved in NFPA. As such, patients tend to present with hypogonadotrophic hypogonadism early, and features of GH deficiency, secondary hypothyroidism and secondary adrenal insufficiency later on. Hypogonadotrophic hypogonadism is characterized by Large NFSs compress the pituitary stalk, causing impairment of dopamine transport to the lactotrophs and a slight rise in prolactin secretions above normal (but prolactinoma is usually associated with levels >200 mU/L). Macroadenomas of either type (functional or non-functional) may present with mass effect on adjacent structures (e.g. chiasmal compression) or pituitary apoplexy. MRI with and without contrast is the imaging modality of choice. Management of nonfunctioning pituitary adenoma is with elective transsphenoidal surgery if there is evidence of optic chiasm compression (as in this case with suprasellar extension)—otherwise endocrine, ophthalmologic and imaging surveillance is appropriate.

Question 9

A 50-year-old male presents with a 12 month history of reduced libido and lethargy. On examination there were mild left sided 3rd and 6th nerve palsies. Routine bloods were normal and endocrine profile showed: FT4 8 pmol/L (11.5-22), TSH 0.4 mU/L (0.355.5), FSH 2.2 U/L (1.4-18.1), LH 3.5 U/L (3-8), testosterone 6.8 nmol/L (8.4-28.7), IGF-1 35 nmol/L (16-118), prolactin 880 mU/L (45-375). MRI is shown. Which one of the following is most appropriate next?
a. Stereotactic radiosurgery
b. Transsphenoidal debulking followed by stereotactic radiosurgery
c. Cabergoline
d. Somatostatin
e. Petrous sinus sampling

Answer 9

b. Transsphenoidal debulking followed by stereotactic radiosurgery

There is extensive cavernous sinus involvement
hence transsphenoidal surgery alone is unlikely to
be sufficient (but will decompress/separate tumour
mass from optic nerve), and given the features of a
non-functional pituitary adenoma stereotactic
radiosurgery is the appropriate next action as medical therapy is unlikely to be of benefit.

There is extensive cavernous sinus involvement hence transsphenoidal surgery alone is unlikely to be sufficient (but will decompress/separate tumour mass from optic nerve), and given the features of a non-functional pituitary adenoma stereotactic radiosurgery is the appropriate next action as medical therapy is unlikely to be of benefit.

Question 10

Which one of the following statements regarding diagnosis and management of prolactinomas is LEAST accurate?
a. Prolactinomas are managed medically with dopamine receptor agonists
b. Hook effect describes spuriously high prolactin levels due to macroprolactin complexes
c. Compression of the pituitary stalk can cause a mildly raised prolactin
d. Prolactin levels in a prolactinoma are usually >2000 mU/L
e. Hypothyroidism may result in hyperprolactinemia

Answer 10

b. Hook effect describes spuriously high prolactin levels due to macroprolactin complexes

Prolactinomas are the most common secreting
pituitary adenomas and tend to arise laterally
within the anterior lobe of the pituitary gland.
They may depress the floor of the sella turcica
or expand one side of the gland, causing a subtle
upwardly convex bulge and contralateral
displacement of the infundibulum. Hyperprolactinemia in men interferes with sperm production
(infertility) and testosterone production (lethargy, reduced libido, reduced muscle mass),
galactorrhea, loss of pubic/axillary hair, and
erectile dysfunction (and small gonads in prepubertal boys). In females, hypeprolactinemia
reduces estradiol production and this causes
irregular menstrual cycles, amenorrhea, galactorrhea and premature menopausal symptoms
(does not cause similar symptoms in postmenopausal women). Blood tests show prolactin levels >2000 mU/L (note that hypothyroidism may
also cause hyperprolactinemia). Macroprolactin
with its longer half-life and biological inert
nature needs to be measured, and may cause a
spuriously high prolactin level. Equally, depending on the assay used, if prolactin levels are truly
very high they may saturate the assay giving a
near-normal result (Hook effect). Estrogen containing oral contraceptives can stimulate lactotrophs and cause hyperprolactinemia. The
primary treatment of prolactin-secreting microadenomas is medical and the role of imaging in
cases of hyperprolactinemia is to assess size and
any chiasmal compression. Bromocriptine and
cabergoline are both safe options for females
in the reproductive age group presenting with
a microprolactinoma if they are planning a pregnancy in the near future, and have not been
associated with fetal malformation. The therapy
can be stopped once pregnancy is confirmed.
Dopamine agonists reduce prolactin levels and
induce ovulation, hence females started on them
are possibly at higher risk of pregnancy and
should be given advice regarding contraception
at initiation if they do not wish to become pregnant. Management of prolactinomas during
pregnancy is challenging as prolactin measurements are unreliable. There is <5% chance of
microprolactinoma regrowth and 15-40%
chance of macroprolactinoma regrowth during
pregnancy. As such, patients need to be kept
under close surveillance with periodic formal
visual field assessments. Imaging in other secreting pituitary adenomas (TSH, GH, ACTH) is
also important to localize the exact position of
the tumor for surgical treatment. In particular,
given the high morbidity of Cushing’s disease
if no lesion is found on MRI then inferior petrosal and/or cavernous sinus venous sampling may
be necessary to grossly lateralize an adenoma for
surgery.

Prolactinomas are the most common secreting pituitary adenomas and tend to arise laterally within the anterior lobe of the pituitary gland. They may depress the floor of the sella turcica or expand one side of the gland, causing a subtle upwardly convex bulge and contralateral displacement of the infundibulum. Hyperprolactinemia in men interferes with sperm production (infertility) and testosterone production (lethargy, reduced libido, reduced muscle mass), galactorrhea, loss of pubic/axillary hair, and erectile dysfunction (and small gonads in pre- pubertal boys). In females, hypeprolactinemia reduces estradiol production and this causes irregular menstrual cycles, amenorrhea, galactorrhea and premature menopausal symptoms (does not cause similar symptoms in postmeno- pausal women). Blood tests show prolactin levels >2000 mU/L (note that hypothyroidism may also cause hyperprolactinemia). Macroprolactin with its longer half-life and biological inert nature needs to be measured, and may cause a spuriously high prolactin level. Equally, depending on the assay used, if prolactin levels are truly very high they may saturate the assay giving a near-normal result (Hook effect). Estrogen containing oral contraceptives can stimulate lactotrophs and cause hyperprolactinemia. The primary treatment of prolactin-secreting microadenomas is medical and the role of imaging in cases of hyperprolactinemia is to assess size and any chiasmal compression. Bromocriptine and cabergoline are both safe options for females in the reproductive age group presenting with a microprolactinoma if they are planning a preg- nancy in the near future, and have not been associated with fetal malformation. The therapy can be stopped once pregnancy is confirmed. Dopamine agonists reduce prolactin levels and induce ovulation, hence females started on them are possibly at higher risk of pregnancy and should be given advice regarding contraception at initiation if they do not wish to become pregnant. Management of prolactinomas during pregnancy is challenging as prolactin measurements are unreliable. There is <5% chance of microprolactinoma regrowth and 15-40% chance of macroprolactinoma regrowth during pregnancy. As such, patients need to be kept under close surveillance with periodic formal visual field assessments. Imaging in other secreting pituitary adenomas (TSH, GH, ACTH) is also important to localize the exact position of the tumor for surgical treatment. In particular, given the high morbidity of Cushing’s disease if no lesion is found on MRI then inferior petrosal and/or cavernous sinus venous sampling may be necessary to grossly lateralize an adenoma for surgery.

Question 11

Which one of the following statements regarding management of incidentally found pituitary adenomas (except prolactinomas) is most accurate?
a. Anterior pituitary hormone profile should only be performed if the patient is symptomatic
b. MRI surveillance for lesions <10 mm and >10 mm is the same
c. Indications for surgery include secreting tumours
d. Macroincidentalomas should be reimaged at 12 months
e. Formal visual field testing should be performed as a baseline

Answer 11

c. Indications for surgery include secreting tumours

Due to improvements in imaging there has been a
rise in the number of incidental pituitary adenomas discovered on cranial imaging with rates of 5-
30% for those <10 mm (microincidentaloma)
and 0.1-0.25% for those >10 mm in size (macroincidentaloma). They should be investigated for
subclinical disease even if asymptomatic including endocrinological history and examination,
anterior pituitary profile, MRI pituitary (if lesion
found on CT) and, if clinical visual field defect or
evidence of chiasmal comtpression on imaging,
formal visual field testing. If all results are normal,
microincidentalomas should be rescanned at 1 year then every 1-2 years for the first 3 years
then less frequently after that. Macroincidentalomas should be rescanned at 6 months then at least
yearly for the first 3 years. Repeat anterior pituitary hormone profile should only be performed if
symptomatic or MRI changes are seen. Indications for surgery include visual field deficit, optic
nerve/chiasm compression, ophthalmoplegia,
pituitary apoplexy with severely reduced visual
acuity or field defect, and evidence of secreting
tumor (e.g. Acromegaly, Cushing’s disease).

Due to improvements in imaging there has been a rise in the number of incidental pituitary adenomas discovered on cranial imaging with rates of 530% for those <10 mm (microincidentaloma) and 0.1-0.25% for those >10 mm in size (macroincidentaloma). They should be investigated for subclinical disease even if asymptomatic including endocrinological history and examination, anterior pituitary profile, MRI pituitary (if lesion found on CT) and, if clinical visual field defect or evidence of chiasmal compression on imaging, formal visual field testing. If all results are normal, microincidentalomas should be rescanned at 1 year then every 1-2 years for the first 3 years then less frequently after that. Macroincidentalomas should be rescanned at 6 months then at least yearly for the first 3 years. Repeat anterior pituitary hormone profile should only be performed if symptomatic or MRI changes are seen. Indications for surgery include visual field deficit, optic nerve/chiasm compression, ophthalmoplegia, pituitary apoplexy with severely reduced visual acuity or field defect, and evidence of secreting tumor (e.g. Acromegaly, Cushing’s disease). FURTHER READING Freda PU, Beckers AM, Katznelson L. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011;96(4):894-904.

Question 12

Which one of the following statements regarding medical management of secreting pituitary adenomas is LEAST accurate?
a. Octreotide used in patients with acromegaly
b. Cabergoline is a dopamine receptor antagonist
c. Bromocriptine is used in the treatment of prolactinoma
d. Pegvisomant is a GH receptor blocker and useful if somatostatin fails in acromegaly
e. Mitotane used for Cushing’s disease

Answer 12

b. Cabergoline is a dopamine receptor antagonist

Dopamine receptor agonists (e.g. bromocriptine,
cabergoline) augment physiological inhibition of
prolactin secretion. Octreotide is a somatostain
analog used in the treatment of acromegaly is
associated with the development of gallstones
and reduced gall bladder contractility, but causes
>2% tumor reduction in 75% of patients treated.
GI side effects are common, and glycemic
control also

Dopamine receptor agonists (e.g. bromocriptine, cabergoline) augment physiological inhibition of prolactin secretion. Octreotide is a somatostain analog used in the treatment of acromegaly is associated with the development of gallstones and reduced gall bladder contractility, but causes >2% tumor reduction in 75% of patients treated. GI side effects are common, and glycemic control also.

Question 13

A 36-year-old patient with Cushing’s syndrome but normal ACTH levels is referred. There is no visual compromise. Pituitary MRI shows a 3 mm hypodense area in the lateral aspect of the pituitary gland. Which one of the following is the next appropriate management?
a. Laparoscopic adrenalectomy
b. Transsphenoidal surgery
c. Inferior petrosal sinus sampling
d. High-dose dexamethasone test
e. Start octreotide

Answer 13

c. Inferior petrosal sinus sampling

This finding is nonspecific and occurs in up to
10% of healthy people. It may or may not be
related to Cushing syndrome. The odds are good
that the patient has a pituitary tumor, but the MRI
findings do not prove this. The MRI is diagnostic
only if it shows a large tumor. One option is to proceed directly to pituitary surgery because a patient
with abnormal MRI findings has a 90% chance of
having an ACTH-secreting pituitary tumor. To
achieve more diagnostic certainty, one has to perform bilateral simultaneous inferior petrosal sinus
sampling (IPSS) for ACTH levels. Catheters are
advanced through the femoral veins into the inferior petrosal sinuses, which drain the pituitary
gland, and blood samples are obtained for ACTH
levels. If ACTH levels in the petrosal sinuses are
significantly higher than those in peripheral samples, the pituitary gland is the source of excessive
ACTH. If there is no gradient between petrosal
sinus and peripheral levels of ACTH, the patient
probably has a carcinoid tumor somewhere. The
accuracy of the test is further increased if ACTH
responses to injection of exogenous CRH are measured. If sinus sampling is positive for a gradient
transsphenoidal surgery (TSS) should be scheduled with an experienced neurosurgeon who omfortable examining the pituitary for small adenomas. ACTH levels from the right and left petrosal sinuses obtained during the sampling study may
tell the neurosurgeon in which side of the pituitary
gland the tumor is likely to be found, but this
information is not 100% accurate. If IPSS shows
no gradient in ACTH levels, start the search for
a carcinoid tumor (e.g. lung, adrenal, GI) and
treatment as appropriate.

This finding is nonspecific and occurs in up to 10% of healthy people. It may or may not be related to Cushing syndrome. The odds are good that the patient has a pituitary tumor, but the MRI findings do not prove this. The MRI is diagnostic only if it shows a large tumor. One option is to proceed directly to pituitary surgery because a patient with abnormal MRI findings has a 90% chance of having an ACTH-secreting pituitary tumor. To achieve more diagnostic certainty, one has to perform bilateral simultaneous inferior petrosal sinus sampling (IPSS) for ACTH levels. Catheters are advanced through the femoral veins into the inferior petrosal sinuses, which drain the pituitary gland, and blood samples are obtained for ACTH levels. If ACTH levels in the petrosal sinuses are significantly higher than those in peripheral samples, the pituitary gland is the source of excessive ACTH. If there is no gradient between petrosal sinus and peripheral levels of ACTH, the patient probably has a carcinoid tumor somewhere. The accuracy of the test is further increased if ACTH responses to injection of exogenous CRH are measured. If sinus sampling is positive for a gradient transsphenoidal surgery (TSS) should be sched- uled with an experienced neurosurgeon who is comfortable examining the pituitary for small adenomas. ACTH levels from the right and left petrosal sinuses obtained during the sampling study may tell the neurosurgeon in which side of the pituitary gland the tumor is likely to be found, but this information is not 100% accurate. If IPSS shows no gradient in ACTH levels, start the search for a carcinoid tumor (e.g. lung, adrenal, GI) and treatment as appropriate. FURTHER READING Samuels MH. Cushing syndrome. In: McDermott MT (Ed.), Endocrine secrets. Saunders, Elsevier, 2013.

Question 14

Which one of the following statements regarding Cushing’s disease is most accurate?
a. It is often due to ACTH-secreting pituitary adenoma
b. Primary management is surgical resection of the tumor
c. High-dose dexamethasone suppression test is able to lateralize the side of ACTH-secreting microadenoma within the pituitary gland
d. It may be caused by ectopic ACTH producing tumors
e. Can cause amenorrhea in females and infertility in males

Answer 14

e. Can cause amenorrhea in females and infertility in males

ushing’s syndrome (hypercortisolism) can present in children and young adults with an
increase in body weight, central obesity and
growth retardation. In adults, it is associated
with mood facies, proximal myopathy, bruising,
abdominal striae, oligomenorrhea/amenorrhea
in females, impotence in males, infertility, hirsutism, hypertension and diabetes. Adrenal
tumors are commoner in children under 10
(neuroblastoma) causing ACTH-independent
Cushing’s syndrome with signs of virilization.
Cushing’s disease due to ACTH-secreting pituitary tumor is commoner in older children and
adults. In adults, ectopic ACTH production
due to lung cancer or carcinoid/neuroendocrine
tumor can also occur. Initial screening tests such
as 24 h urinary cortisol collection, 9 am and midnight cortisol (loss of diurnal variation; remains
high), and overnight (low-dose) dexamethasone
suppression test help confirm the diagnosis of
hypercortisolism. Second line localization tests
aim to differentiate hypercortisolism based on
whether it is secondary to increased ACTH
secretion (e.g. ACTH-secreting pituitary tumor
or ectopic/carcinoid tumor) or not (e.g. adrenal
tumor). Third line tests aim to differentiate location of ACTH-dependent hypercortisolism as
pituitary (reduces ACTH/cortisol production
in response to high-dose dexamethasone; gradient on petrosal sinus sampling) or ectopic tumor
(no reduction in ACTH/cortisol secretion in
response to high-dose dexamethasone; cortisol
rise if CRH stimulation test; no cortisol rise on
CRH stimulation; no gradient on petrosal sinus
sampling).

Cushing’s syndrome (hypercortisolism) can present in children and young adults with an increase in body weight, central obesity and growth retardation. In adults, it is associated with mood facies, proximal myopathy, bruising, abdominal striae, oligomenorrhea/amenorrhea in females, impotence in males, infertility, hirsutism, hypertension and diabetes. Adrenal tumors are commoner in children under 10 (neuroblastoma) causing ACTH-independent Cushing’s syndrome with signs of virilization. Cushing’s disease due to ACTH-secreting pituitary tumor is commoner in older children and adults. In adults, ectopic ACTH production due to lung cancer or carcinoid/neuroendocrine tumor can also occur. Initial screening tests such as 24 h urinary cortisol collection, 9 am and midnight cortisol (loss of diurnal variation; remains high), and overnight (low-dose) dexamethasone suppression test help confirm the diagnosis of hypercortisolism. Second line localization tests aim to differentiate hypercortisolism based on whether it is secondary to increased ACTH secretion (e.g. ACTH-secreting pituitary tumor or ectopic/carcinoid tumor) or not (e.g. adrenal tumor). Third line tests aim to differentiate location of ACTH-dependent hypercortisolism as pituitary (reduces ACTH/cortisol production in response to high-dose dexamethasone; gradient on petrosal sinus sampling) or ectopic tumor (no reduction in ACTH/cortisol secretion in response to high-dose dexamethasone; cortisol rise if CRH stimulation test; no cortisol rise on CRH stimulation; no gradient on petrosal sinus sampling).

Question 15

Which one of the following would be most appropriate treatment following failure of transsphenoidal surgery to treat Cushing’s disease?
a. Surveillance imaging
b. Repeat transsphenoidal surgery
c. Cabergoline
d. Octreotide
e. Bilateral adrenalectomy

Answer 15

b. Repeat transsphenoidal surgery

Patients with inadequately treated Cushing’s syndrome have a markedly increased mortality rate
(four- to fivefold above the normal rate), usually rom cardiovascular disease or infections. Hypertension, impaired glucose tolerance, dyslipidemia, and visceral obesity all contribute to the
excess risk for cardiovascular mortality. This
excess mortality normalizes with adequate therapy. If TSS does not cure a patient with Cushing’s
disease, alternative therapies must be tried
because patients with inadequately treated hypercortisolism have increased morbidity and mortality rates. Of the various options after failed
surgery, none is ideal. Patients may require repeat
pituitary surgery, radiation therapy, medical therapy to block adrenal cortisol secretion (e.g. ketoconazole, metyrapone, mitotane, or etomidate),
centrally acting agents that suppress ACTH
secretion, and glucocorticoid receptor blocker
(mifepristone). Bilateral adrenalectomy can be
safely performed via a laparoscopic approach,
with low morbidity in experienced hands. However, this procedure leads to lifelong adrenal
insufficiency and dependence on exogenous glucocorticoids and mineralocorticoids. The other
main drawback is the development of Nelson syndrome in up to 30% of patients after adrenalectomy. Nelson syndrome is the appearance,
sometimes years after adrenalectomy, of an
aggressive corticotroph pituitary tumor.

Patients with inadequately treated Cushing’s syndrome have a markedly increased mortality rate (four- to fivefold above the normal rate), usually from cardiovascular disease or infections. Hypertension, impaired glucose tolerance, dyslipidemia, and visceral obesity all contribute to the excess risk for cardiovascular mortality. This excess mortality normalizes with adequate therapy. If TSS does not cure a patient with Cushing’s disease, alternative therapies must be tried because patients with inadequately treated hypercortisolism have increased morbidity and mortality rates. Of the various options after failed surgery, none is ideal. Patients may require repeat pituitary surgery, radiation therapy, medical therapy to block adrenal cortisol secretion (e.g. ketoconazole, metyrapone, mitotane, or etomidate), centrally acting agents that suppress ACTH secretion, and glucocorticoid receptor blocker (mifepristone). Bilateral adrenalectomy can be safely performed via a laparoscopic approach, with low morbidity in experienced hands. However, this procedure leads to lifelong adrenal insufficiency and dependence on exogenous glucocorticoids and mineralocorticoids. The other main drawback is the development of Nelson syndrome in up to 30% of patients after adrenalectomy. Nelson syndrome is the appearance, sometimes years after adrenalectomy, of an aggressive corticotroph pituitary tumor.

Question 16

A 43-year-old female presents with coarse facial appearance, macroglossia and large hands and feet. She has also been experiencing worse glycemic control on a background of type II diabetes mellitus. Routine bloods are normal and endocrine profile shows: IGF-1 102 nmol/L (16-118), prolactin 610 mU/L (45-375), FT4 12.5 pmol/L (11.5-22), and TSH 1.5 mU/L (0.35-4.5). Which one of the following would you perform to confirm your biochemical diagnosis?
a. Oral glucose tolerance test
b. Insulin tolerance test
c. Short synacthen test
d. Dexamethasone suppression test
e. Domperidone test

Answer 16

a. Oral glucose tolerance test

Acromegaly is due to excess secretion of GH/
IGF-1 and results in coarsening of facial features,
increased ring/shoe size, prognathism, macroglossia, widely spaced teeth, enlargement of the
extremities and increased sweating. Due to pulsatile release of GH, serum GH levels are rarely
helpful—the main test should be random IGF-1
serum level which is useful in diagnosis and monitoring of subsequent treatment. However, a normal IGF-1 level does not exclude acromegaly and
an oral glucose tolerance test (OGTT) with measurements of GH remains the gold standard. Failure of oral glucose administration to suppress GH
level below 1 ng/mL (or higher sensitivity if
<0.4 ng/mL cutoff) is supportive of a diagnosis
of acromegaly. In those suspected to have acromegaly, MRI pituitary should be performed

Acromegaly is due to excess secretion of GH/ IGF-1 and results in coarsening of facial features, increased ring/shoe size, prognathism, macroglossia, widely spaced teeth, enlargement of the extremities and increased sweating. Due to pulsatile release of GH, serum GH levels are rarely helpful—the main test should be random IGF-1 serum level which is useful in diagnosis and monitoring of subsequent treatment. However, a nor- mal IGF-1 level does not exclude acromegaly and an oral glucose tolerance test (OGTT) with measurements of GH remains the gold standard. Failure of oral glucose administration to suppress GH level below 1 ng/mL (or higher sensitivity if <0.4 ng/mL cutoff) is supportive of a diagnosis of acromegaly. In those suspected to have acromegaly, MRI pituitary should be performed.

Question 17

Endoscopic view from within sphenoid sinus.
Which one of the following labels appropriately
identifies the opticocarotid recess?

Answer 17

E—Opticocarotid recess.

A—planum sphenoidale, B—chiasmatic groove
(CG), C—tuberculum sellae, D—optic nerve
prominence, E—opticocarotid recess, F—clival
recess, G—prominence of the internal carotid
artery
The panoramic view provided by the endoscope of the bony prominences and depressions
inside the sphenoid sinus allows one to see a sort of “fetal face,” where the forehead corresponds to
the planum sphenoidale, the eyes to the two opticocarotid recesses, the eyebrows to the two bony
protuberances covering the optic nerves, the nose
to the sellar floor, and the mouth to the clival
indentation, laterally limited by the two paraclival
carotid arteries, representing the cheeks.
Image with permission from Laws ER, Lanzino G (Eds.),
Transsphenoidal Surgery, Saunders, Elsevier, 2010

A—planum sphenoidale, B—chiasmatic groove (CG), C—tuberculum sellae, D—optic nerve prominence, E—opticocarotid recess, F—clival recess, G—prominence of the internal carotid artery The panoramic view provided by the endoscope of the bony prominences and depressions inside the sphenoid sinus allows one to see a sort of “fetal face,” where the forehead corresponds to the planum sphenoidale, the eyes to the two opticocarotid recesses, the eyebrows to the two bony protuberances covering the optic nerves, the nose to the sellar floor, and the mouth to the clival indentation, laterally limited by the two paraclival carotid arteries, representing the cheeks.

Question 18

A patient presents 7 days after transsphenoi- dal resection of pituitary adenoma with headache, neck stiffness, fever and clear fluid discharge from his nose. Which one of the following is the most appropriate management?
a. Endoscopic repair
b. External ventricular drain
c. Bed rest and lumbar puncture
d. Lumbar drain
e. Empirical antibiotics and CT head

Answer 18

e. Empirical antibiotics and CT head

CT head should be done initially to exclude
development of postoperative hydrocephalus
and exclude subdural hematoma formation from
intracranial hypotension due to CSF leak. In
patients who have a traumatic leak and normal
CSF pressure, conservative treatment consists
of bed rest with head of bed elevation and lumbar
drainage of CSF for 5-10 days. With conservative
management, there is a reported risk ranging
from 7% to 30% of ascending meningitis.
The incidence of spontaneous resolution with
conservative management is reported to be
70%. The general consensus among practicing
otolaryngologist is that antibiotics should not
be used for conservative management unless
there is a very large defect with comminuted bone
of the skull base as a simple CSF leak carries a 7%
infection rate (meningitis, intracranial abscess,
cellulitis/abscess, and osteomyelitis) and prophylactic antibiotics have not been shown to decrease
the risk of infection. After endoscopic repair,
antibiotics are generally recommended for 24-
48 h. This is done to cover possible contamination at the time of surgery in a non-sterile field
with concomitant sealing of the sterile to nonsterile flushing of an active leak. A reconstructive
ladder should be used to help determine the type
of repair performed. For simple, small (less than
1 cm) defects, a fat plug harvested from the earlobe or abdomen can be used to plug the defect.
The next option includes a simple overlay graft
harvested from the nasal floor mucosa, turbinate
mucosa, or nasal septum. If a more complex,
larger reconstruction is in order, a composite
(underlay and overlay) graft can be used consisting of an intracranial underlay of bone or cartilage from nasal septum, auricular cartilage or
turbinate bone, and an overlay graft of mucosa
(free or pedicled) as above. Local pedicled flaps
should include the nasoseptal flap, which is supplied by the posterior nasal septal artery, a terminal branch of the sphenopalatine artery.
Additional grafts that can be useful in larger
defects include temporal fascia or tensor fascia
lata grafts. These grafts are often bolstered in

CT head should be done initially to exclude development of postoperative hydrocephalus and exclude subdural hematoma formation from intracranial hypotension due to CSF leak. In patients who have a traumatic leak and normal CSF pressure, conservative treatment consists of bed rest with head of bed elevation and lumbar drainage of CSF for 5-10 days. With conservative management, there is a reported risk ranging from 7% to 30% of ascending meningitis. The incidence of spontaneous resolution with conservative management is reported to be 70%. The general consensus among practicing otolaryngologist is that antibiotics should not be used for conservative management unless there is a very large defect with comminuted bone of the skull base as a simple CSF leak carries a 7% infection rate (meningitis, intracranial abscess, cellulitis/abscess, and osteomyelitis) and prophylactic antibiotics have not been shown to decrease the risk of infection. After endoscopic repair, antibiotics are generally recommended for 2448 h. This is done to cover possible contamination at the time of surgery in a non-sterile field with concomitant sealing of the sterile to nonsterile flushing of an active leak. A reconstructive ladder should be used to help determine the type of repair performed. For simple, small (less than 1 cm) defects, a fat plug harvested from the earlobe or abdomen can be used to plug the defect. The next option includes a simple overlay graft harvested from the nasal floor mucosa, turbinate mucosa, or nasal septum. If a more complex, larger reconstruction is in order, a composite (underlay and overlay) graft can be used consisting of an intracranial underlay of bone or cartilage from nasal septum, auricular cartilage or turbinate bone, and an overlay graft of mucosa (free or pedicled) as above. Local pedicled flaps should include the nasoseptal flap, which is supplied by the posterior nasal septal artery, a terminal branch of the sphenopalatine artery. Additional grafts that can be useful in larger defects include temporal fascia or tensor fascia lata grafts. These grafts are often bolstered in the sinonasal cavity with abdominal fat, a nasoseptal flap or both. In complex situations of extensive defects or poor local tissue, such as in chemoradiated patients, a craniotomy with pericranial flap or free flap reconstruction of the skull base may be necessary. A multitude of studies over the past 20 years have shown high success rates of primary repair around 90%, and secondary repair around 97%. These success rates compare favorably to traditional craniotomy approaches with reported success rates between 70% and 80% that carry a higher morbidity profile. FURTHER READING Scholes MA. ENT Secrets, 4th ed. Elsevier, 2016.

Question 19

A 24-year-old female presents with a 3 year history of menstrual irregularities. Prior to this she had regular menstrual cycles. Examination was unremarkable. Routine bloods were normal, and endocrine profile showed: FSH 45 U/L (follicular 0.5-5, midcycle 8-33, luteal 2-8), LH 2.5 U/L (follicular 3-12, mid-cycle 20-80, luteal 3-15), estradiol 1332 pmol/L (follicular 17-260, luteal 180-1100), prolactin 604 mU/L (45-375). Ultrasound of pelvis shows bilateral enlarged and cystic ovaries. MRI shows a pituitary tumor without optic chiasm compression.

Sellar and parasellar lesions:
a. ACTH-secreting pituitary adenoma
b. Arachnoid cyst
c. Craniopharyngioma
d. Germinoma
e. GH-secreting pituitary adenoma
f. Gonadotropin-secreting adenoma
g. Hypothalamic hamartoma
h. Langerhans cell histiocytosis
i. Lymphocytic hypophysitis
j. Non-functioning pituitary adenoma
k. Optic pathway glioma
l. Prolactin-secreting pituitary adenoma
m. Thyrotropinoma

Answer 19

f. Gonadotropin-secreting adenoma

1—f, Gonadotropin-secreting adenoma. This a rare tumor presenting with ovarian cysts and menstrual abnormalities, high or normal estradiol and usually suppressed LH due to secretion of FSH by the pituitary adenoma. Treatment is surgery.

Question 20

A 49-year-old female presents with a 6 month history of palpitations, weight loss, increased sweating and shortness of breath. Her examination was unremarkable except for sinus tachycardia. Routine bloods were normal and TFTs showed: FT4 27 pmol/L (9-19), FT3 pmol/L (8 (2.6-5.7), TSH 7 (0.35-5.5). Further tests show alphasubunit to TSH ratio >1.

Sellar and parasellar lesions:
a. ACTH-secreting pituitary adenoma
b. Arachnoid cyst
c. Craniopharyngioma
d. Germinoma
e. GH-secreting pituitary adenoma
f. Gonadotropin-secreting adenoma
g. Hypothalamic hamartoma
h. Langerhans cell histiocytosis
i. Lymphocytic hypophysitis
j. Non-functioning pituitary adenoma
k. Optic pathway glioma
l. Prolactin-secreting pituitary adenoma
m. Thyrotropinoma

Answer 20

m. Thyrotropinoma

2—m, TSH-secreting tumor (thyrotropinoma, TSHoma). Inappropriately high or normal TSH in the presence of high free T3 and T4 levels is suggestive of either TSH-secreting tumor or thyroid hormone resistance syndromes. TSH-secreting tumors represent 0.5-1% of pituitary adeno- mas and present with features of thyrotoxicosis and goiter, and is distinguished from hormone resistance by its alpha-subunit to TSH ratio >1(if>5.7 is diagnostic), presence of pituitary adenoma on MRI, lack of TSH response to TRH stimulation testing and lack of a family history of thyroid problems. Surgery is the treatment of choice, but octreotide may be used in non-surgical candidates or surgical failure.

Question 21

A 9-year-old girl presents with bitemporal hemianopia and cafe-au-lait spots. Autoantibody screen in normal. MRI shows a lesion involving the chiasm and hypothalamus.

Sellar and parasellar lesions:
a. ACTH-secreting pituitary adenoma
b. Arachnoid cyst
c. Craniopharyngioma
d. Germinoma
e. GH-secreting pituitary adenoma
f. Gonadotropin-secreting adenoma
g. Hypothalamic hamartoma
h. Langerhans cell histiocytosis
i. Lymphocytic hypophysitis
j. Non-functioning pituitary adenoma
k. Optic pathway glioma
l. Prolactin-secreting pituitary adenoma
m. Thyrotropinoma

Answer 21

k. Optic pathway glioma

3—k, Optic pathway glioma. Increased association with NF-1.

Question 22

A 37-year-old male presents with abdominal pain, fatigue, hypotension and skin hyperpigmentation. Neither short or long synacthen tests show cortisol response.

Pituitary dysfunction:
a. Acromegaly
b. Conn’s syndrome
c. Cushing’s disease
d. Diabetes insipidus
e. Hyperprolactinemia
f. Hyperthyroidism
g. Hypothyroidism
h. Nelson’s syndrome
i. Panhypopituitarism
j. Pituitary apoplexy
k. Primary adrenal insufficiency (Addison’s disease)
l. Secondary adrenal insufficiency
m. Syndrome of inappropriate ADH
secretion

Answer 22

k. Primary adrenal insufficiency (Addison’s disease)

1—k, Primary adrenal insufficiency (Addison’s disease). Short synacthen tests can demonstrate adrenal insufficiency (lack of cortisol production in response to synthetic ACTH). Long synacthen tests differentiate between primary causes (e.g. adrenal infarction) which fail to respond even after several doses, compared to secondary causes (e.g. non-function- ing adenoma causing reduced ACTH release) which start to produce cortisol after several doses.

Question 23

A 57-year-old male undergoes transsphenoidal surgery for non-functioning adenoma. On day 2 postoperatively his serum sodium rises to 149 mmol/L and urine output is 300 ml/h for greater than 2 h despite previously normal fluid balance. Serum osmolality is 295 mOsmol/kg and urine osmolality is 105 mOsmol/kg.

Pituitary dysfunction:
a. Acromegaly
b. Conn’s syndrome
c. Cushing’s disease
d. Diabetes insipidus
e. Hyperprolactinemia
f. Hyperthyroidism
g. Hypothyroidism
h. Nelson’s syndrome
i. Panhypopituitarism
j. Pituitary apoplexy
k. Primary adrenal insufficiency (Addison’s
disease)
l. Secondary adrenal insufficiency
m. Syndrome of inappropriate ADH
secretion

Answer 23

d. Diabetes insipidus

Question 24

A 44-year-old on pituitary hormone replacement with bitemporal hemianopia and right ocular paresis. She was diagnosed with a brain tumor but had an operation on her abdomen to stop it causing symptoms.

Pituitary dysfunction:
a. Acromegaly
b. Conn’s syndrome
c. Cushing’s disease
d. Diabetes insipidus
e. Hyperprolactinemia
f. Hyperthyroidism
g. Hypothyroidism
h. Nelson’s syndrome
i. Panhypopituitarism
j. Pituitary apoplexy
k. Primary adrenal insufficiency (Addison’s
disease)
l. Secondary adrenal insufficiency
m. Syndrome of inappropriate ADH
secretion

Answer 24

h. Nelson’s syndrome

3—h, Nelson-Salassi syndrome. When bilateral adrenalectomy is performed for ACTHsecreting pituitary adenoma (Cushing’s disease) to treat the associated hypercortisolism, loss of negative cortisol feedback to hypothalamus causes increased secretion of corticotropin releasing hormone and growth of pituitary tumors. This was seen before the advent of transsphenoidal surgery and radiotherapy, when adrenalectomy was more commonly performed.

Question 25

Contains maxillary nerve (CNV2)

Answer 25

1—k, Foramen rotundum;

a—Lesser, greater wings of sphenoid bone, b—Carotid groove, c—Pituitary fossa, d—Foramen lacerum, e—Condylar fossa (mandibular), f—Facial hiatus, g—Temporal bone, h—Internal auditory meatus, i—Optic canal, j—Superior orbital Fissure, k—Foramen rotundum, l—Foramen ovale, m—Foramen spinosum, n—Foramen jugulare, o—Hypoglossal Canal.

Question 26

Contains greater petrosal nerve (VII) which joins with deep petrosal nerve to form vidian nerve (of the pterygoid canal).

Answer 26

2—d, Foramen lacerum,

a—Lesser, greater wings of sphenoid bone, b—Carotid groove, c—Pituitary fossa, d—Foramen lacerum, e—Condylar fossa (mandibular), f—Facial hiatus, g—Temporal bone, h—Internal auditory meatus, i—Optic canal, j—Superior orbital Fissure, k—Foramen rotundum, l—Foramen ovale, m—Foramen spinosum, n—Foramen jugulare, o—Hypoglossal Canal.

Question 27

Contains facial nerve (VII), vestibulocochlear (VIII)

Answer 27

2—h, Internal auditory meatus

a—Lesser, greater wings of sphenoid bone, b—Carotid groove, c—Pituitary fossa, d—Foramen lacerum, e—Condylar fossa (mandibular), f—Facial hiatus, g—Temporal bone, h—Internal auditory meatus, i—Optic canal, j—Superior orbital Fissure, k—Foramen rotundum, l—Foramen ovale, m—Foramen spinosum, n—Foramen jugulare, o—Hypoglossal Canal.

Question 28

Presigmoid approach that uses a mastoidectomy and skeletonization of the sigmoid sinus

Answer 28

1—f, Retrolabyrinthine;

Serviceablehearingincludesapuretoneaverage threshold better than 50 dB and/or speech discrimination greater than 50% (50/50 rule), and may favor the use of hearing-sparing approaches depending on tumor size and location (e.g. middle fossa, retrosigmoid, retrolabyrinthine). Use of other approaches sacrifices hearing, hence other criteria such as surgical exposure gained and risk of facial nerve injury become prime considerations.

Question 29

Includes drilling the posterior and superior external auditory canal and sacrificing middle ear structures and inner ear (cochlea), and rerouting the facial nerve to provide access to the anterior cerebellopontine angle, petrous apex, and ventral brainstem.

Answer 29

2—h, Transcochlear

Serviceablehearingincludesapuretoneaverage threshold better than 50 dB and/or speech discrimination greater than 50% (50/50 rule), and may favor the use of hearing-sparing approaches depending on tumor size and location (e.g. middle fossa, retrosigmoid, retrolabyrinthine). Use of other approaches sacrifices hearing, hence other criteria such as surgical exposure gained and risk of facial nerve injury become prime considerations.