1 Hyperprolactinaemia An Unusual Case Dianne Wright Specialist Nurse in Endocrinology

2 Bradford Royal Infirmary

3 History 64 year old Asian lady Primary Hypothyroidism Hypertension Vitamin D Deficiency End stage renal failure on dialysis [diagnosed December 2005] Refused to go on transplant list

4 Treatment Renal dialysis Levothyroxine 125 mcg OD [primary hypothyroidism] Calcium Carbonate tablets 1.25gm TDS Alfacalcidol 0.25 mg OD Folic Acid 5mg OD Ezetimibe 10mg OD Vitamin B Co-Strong 2 tablets OD Quinine Bisulphate 300mg OD Lactulose 15mls BD

5 History of presenting complaint November 2006 – frontal headaches, dizzy spells & 1 episode of collapse CT [no contrast]: 2 small foci of calcification in frontal lobe ? due to small meningioma. Repeat CT recommended with contrast for confirmation of diagnosis.

6 January CT with contrast: Incidental finding of a lesion Compatible with small right parafalcine meningioma Abnormal patchily enhanced mass within an enlarged pituitary fossa, the mass extending inferiorly, eroding into the right side of the clivus. Erosion of right side of the posterior clinoid process & abnormal soft tissue extending into the right cavernous sinus. No suprasellar extension into prepontine cistern. Appearances of probable pituitary macroadenoma & not meningioma. MRI recommended.

7 MRI head / Pituitary January 2007 Small parafalcine meningioma in right parietal region. Pituitary fossa NOT enlarged. Enhancing pituitary tissue within the fossa & pituitary stalk, deviating to the left of midline. Appearances suggest expansile lesion within the clivus, NOT a pituitary macroadenoma which has eroded into the clivus. ? clival chordoma, ? plasmocytoma, ? metastasis. Biopsy of the clivus is recommended.

8 MRI head / Pituitary January 2007 Sagittal view Coronal view Fig1a: Coronal view of the head

9 Referral Referred by Bradford renal team to LGI for neuro assessment. Endocrinology not involved at this stage as did not particularly suggest pituitary problem.

10 Progress 11, 13, 15 June renal dialysis at LGI 11 th June 2007 – Transphenoidal Pituitary biopsy at LGI 2 days post surgery became dizzy! Unable to assess cortisol reserve. Commenced on hydro 20 / 10 mg Prolactin not checked pre surgery.

11 Progress LGI - Prolactin checked pre dialysis [after TS biopsy] – 516,890 miul/L An in-house analysis revealed prolactin to be exclusively of the monomeric form. Further analysis of the serum confirmed prolactin to be of monomeric form and both macroprolactin and big prolactin accounted for only 3% of the total.

12 Referral to Bradford Endocrine Team 16 th June 2007 Referral by telephone from endocrine LGI to myself. Formal written referral from medics never sent. GP discharge copy requested to use as our referral. Discussed with endocrine consultant in Bradford. Endocrine tests & appointment TBA.

13 Biopsy Results June 2007 Transphenoidal biopsy of clivus region showed pituitary adenoma. Histology – showed presence of clusters of neoplastic cells that were strongly + for synaptophysin, chromagranin and prolactin. The ACTH, TSH, FSH and LH stains were negative. A histological diagnosis of pituitary macroadenoma (prolactinoma) was made.

14 13 th August 2007 Short Synacthen Test [off hydrocortisone]: 0 mins 459 nmol/L 30 mins 503 nmol/L Hydrocortisone discontinued. Prolactin > 467,030 miu/L Macroprolactin, heterophilic antibody interference investigated & not found. Very unusual result, ? cause, advised repeat.

15 13 th August 2007 FT pmol/L TSH 4.3 miul/L IGF nmol/? [10-28] Oestradiol <40 pmol /L FSH 7.8 iu/L LH 0.4 iu/L FSH & LH inappropriately low. May represent the effects of raised prolactin or gonadatrophin deficiency.

16 23 rd August 2007 Renal dialysis potentially can cause rise in prolactin: Pre dialysis prolactin – >1,952,555 miu/L Post dialysis prolactin – >2,213,600 miu/L Interesting case! Awaiting endocrine appointment date to fit in with dialysis. Consultant Endocrinologist kept up to date.

17 Initial Endocrine Clinic Appointment – October 2007 Very well Off hydrocortisone for 7 weeks – random cortisol rechecked 4 week ago – satisfactory result No headaches No visual disturbances Visual fields normal to confrontation [DNA for formal visual fields test] Never experienced galactorrhoea Menses stopped approx 50 yrs

18 Initial Endocrine Clinic Appointment – October 2007 Formal GHD test never carried out as patient well Large prolactin secreting benign tumour Can potentially be shrunk with cabergoline Risk in shrinking lesion, any fibrosis & tethering can lead to traction & potentially cause more problems e.g. [haemorrhage, headaches, damage to pituitary function Discussion with patient. NOT treated with cabergoline as she is well Repeat pituitary MRI TBA – November 2007

19 MRI Pituitary with Contrast November 2007 No appreciable change in appearance within the clivus, pituitary fossa or para/supra sellar region. No obvious increase in size of lesion eroding the clivus which has turned out to be a prolactinoma. No change in parafalcine meningioma. Development of right posterior temporal lacunar infarct.

20 Where are we now? DNA endocrine appointment February 2008 February prolactin >294,900 miu/L April 2008 – Tel call to patient by endocrine nurse – well, no headaches, no visual disturbances Endocrine clinic - July 2008 – well Prolactin - >21,200 miu/L Pituitary function normal Repeat MRI suggested – patient not keen – delayed until next year Cabergoline not commenced due to risks as patient stable

21 Hyperprolactinaemia Hyperprolactinaemia is relatively common, but levels are seldom >1,000,000. Interestingly patient is asymptomatic. Although initial presentation [collapse, dizziness, frontal headaches] could be attributed to prolactinoma, the symptoms were not persistent, & fluctuating prolactin levels without changes in symptoms, would support the view of alternative diagnosis.

22 Would you have done anything differently? Thank You

23 Contact: Dianne Wright Specialist Nurse in Endocrinology RGN BSc[Hons] / Pager: