P-698 Pituitary functioning gonadotroph adenomas (FGA)-induced ovarian hyperstimulation syndrome (OHSS): results from tertiary neuroendocrine centres in the UK
Authors: Papanikolaou N , Coulden A , Parker N , Lee S , Kelly C , Anderson R , Rees A , Cox J , Dhillo W , Meeran K , Al-Memar M , Karavitaki N , Jayasena C 
Published: June 2022

Abstract

Study question
There are no published series of OHSS due to FGA. What FGA features should clinicians look for during OHSS, and what treatments are effective?

Summary answer
FGA tumour size is always &gt;10mm. Other pituitary hormones may be deficient. Surgical resection of FGA is an effective treatment for OHSS.

What is known already
Pituitary adenomas affect 1:1000 adults and are classified as functioning or non-functioning. Non-functioning pituitary adenomas do not secrete hormones, but most commonly stain histologically gonadotroph cells. Functional pituitary adenomas secrete hormones such as prolactin causing prolactinoma. However, it is rare for a pituitary tumour to cause clinical features of excessive gonadotrophins (functioning gonadotroph adenoma; FGA).
Single case reports, but no case series, have been published on the presentation of FGA-induced OHSS in women.
Surgical excision of adenomas has been reported to cause remission of symptoms, though systematic data are lacking owing to rarity of these tumours.

Study design, size, duration
National case series from tertiary neuroendocrine units in England, Wales and Scotland.

Participants/materials, setting, methods
Eight high-volume pituitary endocrine tertiary units within England, Wales and Scotland audited their records for any cases of FGA-induced OHSS; only seven patients have been identified to date. In all cases, there had been no recent exposure to assisted reproductive technologies (ART) or drugs known to induce OHSS including gonadotrophins or selective oestrogen receptor modulators (SERMS).

Main results and the role of chance
Seven cases of FGA were identified with mean age 31.6 years (range 16-48) at diagnosis. Two-of-seven women presented acutely unwell with abdominal pain, distention and palpable mass requiring oophorectomy for ovarian torsion/ruptured ovarian cyst. The remaining five women presented with abdominal pain (n = 2), thyrotoxicosis (n = 1), menstrual irregularities/galactorrhoea (n = 1) and visual disturbances (n = 1). All women experienced intermittent pelvic pain during medical attendance. Pelvic ultrasound demonstrated enlarged multiseptated ovaries (volume ranging 27-442cm3). Ascites was noted in one woman. Six women had visual field defects due to optic chiasm compression on formal assessment. Median FSH was 26.10 u/L (8.3-33), but LH was &lt;2.5 u/L in all cases. Estradiol (E2) far exceeded the reference range in 5/7 women (2990 to &gt; 18000pmol/L);E2 was at the upper limit of normal in the remaining 2/7 women (960-1450pmol/L). Hyperprolactinaemia, hyperthyroidism and other pituitary hormones deficiency were noted in 6/7, 1/7 and 4/7 women respectively. All FGAs were macroadenomas with diameters ranging 16-48mm. Two patients were administered a somatostatin analogue prior to surgery, but FSH, E2 and tumour size did not change. Transsphenoidal surgery was performed in 6/7 women, and always improved symptomatic and biochemical features of OHSS; however, residual FGA tumour was present post-operatively in all cases studied.

Limitations, reasons for caution
It is possible that some ‘non-functioning’ gonadotroph adenomas cause subclinical problems including menstrual irregularity and mild OHSS which were never diagnosed.
We have insufficient data to determine the prognosis for future pregnancy after FGA-induced OHSS.
This study utilised historical case-notes, so some data is missing.

Wider implications of the findings
The ‘spontaneous’ presentation of OHSS may be confusing for clinicians. We report that FGA is an important cause of spontaneous OHSS which has well-defined biochemical and radiological characteristics, which may be treated effectively in the short-to-medium with pituitary surgery. Results of this study may provide greater awareness of FGA-induced OHSS.

Trial registration number
N/A