Assessment of pituitary function post pituitary surgery

1

• Assessment of pituitary function post pituitary
  surgery
• Rola Zamel, R5

2

• Outline
• Cases
• Our current approach
• Preoperative evaluation
• Postoperative evaluation
• Conclusion

3

• Case 1
• Mr.AB
• 45 YOM
• Presents with symptoms consistent with VF defect
• MRI pituitary tumor 1.5 cm
• Hormone evaluation Normal

4

• Case 2
• Mr.CD
• 45 YOM
• Presents with symptoms consistent with VF defect
• MRI pituitary tumor 3.0 cm
• Preoperative hormone evaluation
• IGF-1 low
• LH/ FSH/ S.testosterone low
• TSH 2.5 FT4 9 FT3 2
• AM cortisol 50 ACTH low
• PRL 35

5

• Protocol for managing patients after pituitary
  surgery
• Pre-operative
• Solucortef 50-100 mg on call to the OR
• (Some like to give Decadron 4mg IV as well
  check with consultant)
• Post-operative
• Solucortef 50-100mg IV q6-8h
• - decrease by 25-50 each day when over major
  stress until down to 30 mg per day
• - switch to equivalent dose of oral
  hydrocortisone and if stable gradually decrease
  to
• 20 mg per day
• - daily serum electrolytes and osmolality and
  urine osmolality
• - IO hourly - call if gt200/hr for 3 consecutive
  hours or
• gt300/hr for 2 consecutive hours or
• gt400/hr for 1 hour
• - if output exceeds one of above calculate total
  IO and if output exceeds intake order
• serum electrolytes and osmolality and consider
  giving ddAVP intranasally or IV
• - if serum Na gt150 or osmoality gt300 and urine
  output gt200 give ddAVP
• On discharge
• Give patient OHIP lab order form from
  Endocrinologist responsible for continuing care
  for

6

• Current Practice here
• Patient receives stress dosing peri-operatively
• Hydrocortisone tapered to 20 mg OD (AM) only
• 8 AM cortisol level (48 hrs after last HC dose)
• cortisol lt 100 ? pit-adrenal insufficiency
• Cortisol gt 500 (550) ? sufficient function
• Cortisol 100-500 unsure need stimulation test
• Stimulation tests can be
• Insulin tolerance test
• ACTH stimulation test
• (CRH test)

7

• Preoperative assessment of pituitary function
• A minimum set of pre-operative endocrine tests
  should include
• 1- Electrolytes
• 2- IGF-1
• 3- LH/FSH, Estradiol / testosterone
• 4- TSH, FT3,FT4
• 5- AM (8-9) Cortisol
• 6- Prolactin

8

• Interpretation of serum prolactin levels
• A- high PRL
• 1- R/O 2nd causes of high prolactin
• Eg. Pregnancy, PRL- elevating drugs, primary
  hypothyroidism, PCOS
• 2- if PRL gt200 mcg/l is diagnostic of
  macroprolactinoma
• 3- lt80 mcg/l in macroprolactinoma indicates
  disconnection

9

• 4- R/O the hook effect and macroprolactin
• B- Low PRL
• Acquired PRL deficiency in a patient not
  taking PRL lowering medication is associated with
  severe hypopituitarism and reduced IGF-1 levels

10

• HPA
• Precaution
• 1- Patient on glucocorticoids
• 2- Patients on E2, need to hold E2 6 weeks prior
  to the test

11

• Several tests are available to help predict
  whether the HPA is able to respond to a
  significant stress
• 1- Basal cortisol
• Should be measured 8-9 AM since HPA activity is
  maximal at this time
• If am cortisol lt100nmol/l replacement should
  start
• If gt450 nmol/l adrenal insufficiency is unlikely

12

• 100 lt am cortisollt 450, then a provocative test
• ITT
• Glucagon stimulation test
• ACTH stimulation test ( iv 250 mcg)
• CRH test ( not recommended)

13

• GH IGF-1 axis
• IGF1
• GH provocative tests
• the gold standard is ITT
• Arginine-GHRH test

14

• Hypothalamus pituitary thyroid axis
• TSH, Free T4
• NTI can cause a pattern of low T4, N/?/? TSH
• Hypothalamus-pituitary-gonadal function
• Gonadotropins/sex steroids ( E2 and AM
  testosterone)

15

• DI
• Uncommon preoperatively in setting of pituitary
  adenoma
• Occurs commonly in Craniopharyngioma or other
  hypothalamic pathology
• S.Na, Osmol, U.Osmol

16

• Postoperative assessment of the patient after
  transsphenoidal pituitary surgery
• Early post-operative period ( 1st few weeks post
  OR)
• 1-Neurosurgical monitoring for
• - disturbances in vision or neurological
  function
• - CSF leak (drainage of clear fluid from the
  nose, especially on bending over)
• - meningitis periop ABs was shown to reduce
  incidence
• - Nasal packs are removed 1224 h after surgery

17

• 2-Monitoring for water imbalances
• DI
• Can occur at any time, peaks in the 1st 48h
• - Monitoring of thirst (craving for cold
  liquids), volume status
• - Ins/outs
• - specific gravities
• - daily serum electrolyte measurements

18

• Diagnostic criteria Urine specific gravity lt
  1.005 and urine volume gt 250 cc/hr for 2-3 hours
• Indications for desmopressin therapy Patient
  unable to maintain adequate oral fluid intake,
  urine output gtgt fluid intake, hypernatremia

19

• SIADH
• Peaks in the 7th postoperative day
• Home monitoring of fluid intake and urine output
  after discharge in patients with DI
  postoperatively
• Measure serum sodium emergently if symptoms of
  hyponatremia (headache, nausea and vomiting,
  mental status changes or seizure)

20

• Measurement of serum sodium one week after
  surgery in all patients (isolated hypoNa after TS
  was reported)
• Fluid restriction ( 800cc/d depending on
  severity of hyponatremia)

21

• 3-What about Ant pituitary deficiency?
• The development of new pituitary hormone
  deficiencies after TS is uncommon when performed
  by an experienced pituitary surgeon

22

• Predictors of hypopituitarism post TS
• 1-When the surgical procedure is more extensive,
  hemorrhage or necrosis within the tumor are seen
• 2- DIthe likelihood of postoperative AI was
  found to be increased four-fold in patients who
  had post-operative DI
• 3-Type of pituitary lesion non-pituitary lesions
  such as craniopharyngiomas are more likely to be
  accompanied by hypopituitarism or DI

23

• 3-Pituitaryadrenal axis assessment
• No RCTs
• Various strategies exist for ensuring the
  integrity of this axis

24

• 1- IV HC 100 mg at time of surgery, this dose is
  tapered quickly over two to three days
• 2- dexamethasone at doses of 2 mg at the time of
  surgery and 1 mg bid on postoperative day 1
  Postoperative assessment of the patient after
  transsphenoidal pituitary surgery (Ausiello J et
  al. Pituitary 2008)

25

• 3- Some recommend administering these to patients
  with preoperative hypopituitarism but withholding
  them in those with normal preoperative
  pituitaryadrenal function peak cortisol
  gt496.8 nmol/l (18 µg/dl) post 250 µg cosyntropin
  stimulation in whom only selective adenomectomy
  is planned Inder WJ, Hunt PJ (2002)
  Glucocorticoid replacement in pituitary surgery
  guidelines for perioperative assessment and
  management. J Clin Endocrinol Metab

26
Inder WJ, Hunt PJ (2002) Glucocorticoid
replacement in pituitary surgery guidelines for
perioperative assessment and management. J Clin
Endocrinol Metab
27

• Prior to hospital discharge after TS each patient
  needs an assessment of pituitaryadrenal axis
  integrity
• The 250 µg CST is not the test of choice for
  early post-operative assessment of
  pituitary-adrenal function because of its
  inability to detect recent onset secondary AI
• ITT not be clinically appropriate within the
  first few days after surgery

28

• AM postoperative cortisol
• the accuracy of this test for the prediction of
  secondary AI has been investigated

29

• How early after surgery one may safely assess
  patients for adequacy of adrenal function?
• Immediate postoperative cortisol levels
  accurately predict postoperative
  hypothalamicpituitaryadrenal axis function
  after transsphenoidal surgery for pituitary
  tumors . Pituitary March 26,2010
• Goal
• to examine the ability of a normal preoperative
  ACTH stimulation test to predict an adequate
  postoperative stress response and normal HPA axis
  function. Results of preop CST was compared to
  immediate post op DOS S.cortisol and late post op
  CST

30

• A prospective study
• 100 patients ( pituitary adenoma (n  99) or a
  Rathkes cleft cyst (n  1) who underwent
  transsphenoidal surgery by a single neurosurgeon
  between October 2006 and March 2009)
• Cleveland Clinic

31

• Exclusion criteria
• 1- Patients undergoing surgery for Cushings
  disease
• 2- patients who chronically received daily
  corticosteroids prior to surgery
• 3- patients who did not have a preoperative
  ACTH stimulation test or who failed to follow up
  appropriately for postoperative testing
• 4- patients who failed preoperative ACTH
  stimulation test

32

• Method
• - All patients were tested preoperatively with a
  modified low-dose (25 µg) CST to evaluate HPA
  axis function.
• - Serum total cortisol levels were assayed at 0,
  30 and 60 min post injection. An adequate and
  sufficient response was defined as an absolute
  cortisol level of 18 µg/dL (496.8 nmol/l) at
  either t 30 or t 60.

33

• Patients with normal pre-operative HPA axis
  function did not receive glucocorticoid coverage
  during pituitary surgery
• All patients had
• S.cortisol immediately post op,
• modified low-dose CST at 46 weeks
  postoperatively
• F/U at 3 months, one year , and then at one
  year intervals thereafter. Laboratory assays of
  HPA axis function were performed at these visits
  if clinical symptoms suggestive of
  hypocortisolemia were present, with a mean
  follow-up of 22 months

34

• Results
• In patients in whom adequate pre-operative
  adrenal function is demonstrated, an immediate
  postoperative cortisol level 15 µg/dL has a
  similar or greater ability to predict normal
  postoperative HPA axis function as does
  determination of cortisol levels on POD1 or later
  

35

• In most centers, therefore, cortisol levels are
  measured the morning of the 2nd or 3rd
  postoperative day, 24 h after the last dose of
  peri-operative hydrocortisone coverage
• 1- AM cortisol levels gt17 µg/dl (460 nmol/L) do
  not require replacement on discharge
• 2- level lt10 ug/dl ( 270nmol/L) require
• 3- AM cortisol levels between 10 and 17
  debatable, some argue that these patients should
  receive further therapy, some Rx if symptoms of
  AI, some Rx if DI or complicated surgery

36

• In most centers morning cortisol levels are
  reassessed 1 week postoperatively, 24 h after the
  most recent dose of hydrocortisone
• ..
• Despite the many studies on this question, there
  is still disagreement regarding the morning
  cortisol level that best predicts normal HPA axis
  function in stressed and unstressed situations so
  some centers treat all postoperative patients
  with oral glucocorticoid therapy on discharge and
  continue this until at least the first
  postoperative visit

37

• Other anterior pituitary hormone assessments
• One report suggests measuring FT4 one week
  postoperatively in patients with
• 1- other abnormalities of pituitary function
  2- unknown preoperative thyroid function
• 3- pituitary apoplexy

38

• In patients with prolactinomas, who may undergo
  TS because they are resistant to or intolerant of
  dopamine agonists, early measurement of prolactin
  levels can be undertaken as low levels may
  portend a better surgical outcome
• Assessment of growth hormone and gonadotropins
  is reserved for a later postoperative visit

39

• Late postoperative phase
• new hypopituitarism is very rare after TS in
  patients with intact pituitary function
  preoperatively.
• In general, most cases of new hypopituitarism are
  detected very early post-operatively and almost
  always within the first 3 months

40

• - In one retrospective study of 71 patients 32
  developed AI but none developed AI after 3 months
  post OR. Adrenocortical insufficiency after
  pituitary surgery an audit of the reliability of
  the conventional short synacthen test Clin
  Endocrinol (Oxf). 2005 Nov63(5)499-505.

41

• Assessment of the pituitaryadrenal axis
• 1-Measure morning cortisol at first postoperative
  visit 24-hrs after glucocorticoid dose if on
  therapy)
• 2-Assess cortisol level and clinical status
• If AM cortisol lt100 nmol/L ( 3.7) likely to
  remain ACTH deficient, but late recovery was
  documented
• Some recommend D/C steroid if am.cortisol
  gt10 and no other hypopituitarism, others use gt18

42

• 3-Consider further testing of pituitary-adrenal
  function
• 1- ITT ( the gold standard for assessing HPA)
• Normal response gt500 nm
• 2- Cosyntropin stimulation test (250 µg) (CST can
  be used 4 weeks post OR)
• Normal response gt550 nm
• 3- Glucagon stimulation test
• The recommended dose is 1 mg IM
• Adequate response is gt500nm
• 4- CRH test
• Is not recommended as it is inferior to 8AM
  s.cortisol for assessing HPA in pituitary disease
• It doesnt provided further info in the group
  with intermediate cortisol level 200-400nM

43

• Optimal timing of the tests to assess HPA is
  controversial
• Some recommend s.cortisol at d 7
• and definitive testing 7-14 days
• then review in clinic at 3-4 weeks
• - Other approach is to perform definitive test
  between 4-6 weeks post op

44

• Thyroid axis
• Thyroid function can be assessed by measuring
  free thyroxine levels at the first postoperative
  visit, again some time within the first few
  months after surgery and on a yearly basis
  thereafter

45

• Pituitarygonadal axes
• In premenopausal women gonadal function can be
  assessed based on menstrual history and
  gonadotropin and estradiol levels if necessary
• Male
• 1- Assess for symptoms of hypogonadism
• 2- gonadotropin levels, and a morning total
  testosterone. A free testosterone may be
  necessary in patients at risk for abnormal SHBG
  levels (elderly, obese, thyroid illness or other
  significant comorbidities)

46

• Growth hormone axis
• The optimal time postoperatively to assess for
  and begin GHD therapy is not yet established
• Method
• 1- ITT
• 2- arginine/GHRH test

47

• Radiologic evaluation
• MRI 3 months post op
• Then q1yr X 5 yrs
• Then can lengthen interval if stable

48

• Long term monitoring with assessments of visual,
  neurological and pituitary function coupled with
  pituitary imaging is necessary for all patients
  who have undergone surgery, irrespective of the
  hormone status of their tumors.

49

• Assessments in patients with hormone secreting
  pituitary tumors
• 1- ACTH secreting tumors
• a- administer stress glucocorticoids and taper to
  about twice replacement doses postoperatively
• b- Other approach is to withhold peri-operative
  and early postoperative glucocorticoids until
  remission or persistent disease is documented.
  S.cortisol q6 h and monitor for signs and
  symptoms of AI
• If cortisol lt55.2 nmol/l (2 µg/dl) and
  patients have symptoms, remission is achieved and
  replacement glucocorticoids are begun

50

• GH-secreting tumors
• Preliminary assessment of recovery
• Can be done by measuring GH level on the 3rd
  postoperative day. The lower the GH level, the
  better the evidence for remission

51

• Conclusion
• Do we need to change our protocol?

52

• References
• 1-Preoperative assessment for pituitary
  surgery.Pereira O, Bevan JS.Pituitary.
  200811(4)347-51. Review.
• 2-Postoperative assessment of the patient after
  transsphenoidal pituitary surgery Ausiello et
  alPituitary. 200811(4)391-401.
• 3-Immediate postoperative cortisol levels
  accurately predict postoperative
  hypothalamicpituitaryadrenal axis function
  after transsphenoidal surgery for pituitary
  tumors . Pituitary March 26,2010
• 4-Glucocorticoid replacement in pituitary
  surgery guidelines for perioperative assessment
  and management. Inder WJ, Hunt PJ.
• J Clin Endocrinol Metab. 2002 Jun87(6)2745-50.
  Review.
• 5-Adrenocortical insufficiency after pituitary
  surgery an audit of the reliability of the
  conventional short synacthen test. Clin
  Endocrinol (Oxf). 2005 Nov63(5)499-505.