“Beware, don't get hooked: A case report of a patient with complete hydatiform mole (CHM) presenting with falsely low serum beta hCG who
developed Ovarian Hyperstimulation Syndrome (OHSS) shortly after suction and evacuation”
Dr Stephen Bradford DRANZCOG*(5th year RANZCOG trainee), Dr Tan Yiap Loong MRCOG** & Dr Ganendra Raj Kader Ali Mohan MRCOG FRANZCOG**
. *Calvary hospital Canberra ACT Australia, **Sarawak General Hospital Kuching Sarawak Malaysia
To bring attention to rare manifestations that can be seen in
Complete Hydatiform Molar pregnancy
Methods
A case report, review of the literature and discussion
Discussion
The Treatment
Objectives
24/11 suction curettage performed under ultrasound guidance
EBL 2 L
HemoCue Hb70
Tamponade with a Foley’s catheter due to persistent bleeding
The Case
28 year old G0 presented to Sarawak General Hospital 15/11/2010
History:
12 weeks amenorrhea
Vaginal bleeding
Nausea and mild LIF pain
Denied ever having sexual intercourse
Methods
Examination:
PR 100-140 (reg), BP 110/60, Urine BHcg -ve
Goitre
Fundus = 20/40
PV bleeding, closed Cx
No other signs of hyperthyroidism
Investigations
Serology:
Prior to Curette
Foley’s insitu
Post OT
The patient was stable and admitted to the ICU intubated
following OT
Hypotensive 80/40
IV fluids (no inotropes were needed)
Hb 115, Plt 150
ELFT normal
TSH <0.01mIU/L
free T4 level 154 pmol/L
BHcg 719 U/L
6/24 Bedside ultrasound- free fluid in the abdomen
Differential diagnosis was uterine perforation
OT was booked immediately
Snow storm appearance
Mild bilateral increase in ovarian size to 4cms with multiple follicles

CXR NAD
The diagnostic dilemma
Hyperthyroidism
Gynaecological DDx
Molar pregnancy (see above for the low Bhcg level?)
Incomplete miscarriage
Miscarriage & fibroid
Benign polyp
Other….need tissue
Initial treatment
•Admission
•Propothyoruicil 100mg BD, Propanolol 40mg BD & lugol’s TDS
Then….
1. Serum is introduced to a detection kit that has
capture antibodies in solid state
•Whilst the T4 and Bhcg decreased
18/11 TSH <0.01 T4 66.87
19/11 Bhcg 659U/L
22/11 Bhcg 487 U/L
Out of frustration an MRI was arranged to help with the diagnosis
23/11 An MRI was performed
‘a large uterus with vesicular contents and a very thin uterine
wall with a possibility of invasion, likely mole..’
The Hook
•Again out of shear frustration the lab was contacted and asked to repeat
the Bhcg assay
•The results surprised the team but ultimately confirmed what the imaging
and high T4 had been suggesting2,656,450 IU/L
This is called the hook effect
2. Detection antibodies are then introduced
3. The ‘antigen’ (Bhcg) is thus ‘sandwiched’ between
the two antibodies
Return to OT
OT- 2cm mini-laporotomy
 ascitic fluid protein 24g/l, LDH 430 U/L
4. Excess serum is washed away and with it the
unbound detection antibodies
5. The quantity of the bound antigen is then
determined
Another unusual presentation in CHM
•Ovarian Hyper-Stimulation Syndrome (OHSS)
•Ovarian Hyper Stimulation Syndrome
• Incidence of 33% in ovulation induction(12)
• Can occur with clomiphene(13)
• Some genetic lines with abnormal FSH
receptors(13)
• Rarely described in GTD(4)
• Pathogenesis
•Due to over stimulation of the ovarian follicles
leading to massive elaboration of vasoactive
cytokines including Vascular Endothelial Growth
Factor (VEGF)(13)
•3rd spacing occurs due to endothelial
dysfunction
•Haemoconcentration, thrombosis, ascities,
effusion, ovarian torsion ensues
• Treatment is supportive
• Analgesia
• Fluid restriction
• Electrolyte modulation
• Thromboprophylaxis
• IV albumin
• Ascitic and effusion tap
• OT if ovarian torsion
•Persistent CHD
• The higher the Bhcg the more likely persistent disease
• Indeed Bhcg levels are scored in staging Molar disease
which instructs the type of chemo to be used in
persistence
• Logically, hyperthyroidism may be predictive
Recovery
Extubated next day (2 units PC given in total)
Discharged 30/11
Out patient department 6/12Bhcg 116819
 T4 9.23
U/S-ET 4mm, empty uterus, no ascites
20/12 rising Bhcg 193774 mIU/mL
Chemo was planned to start…. Pt lost to follow-up!!!!!!!
CONCLUSION
•
Discussion
•Over the next 9 days the uterus continued to increase to 24/40
www.PosterPresentations.com
Hyperthyroidism
• Hyperthyroidism has been well described in both pregnancy and
hydatiform mole(8,9)
• The incidence in normal pregnancy is about 1%(8)
• Incidence in CHD is unknown but is more likely the higher the
Bhcg
• Bhcg has 4000 times less affinity for TSH receptors(9)
• Thyroid hormone levels most be controlled prior to surgery as
there is a high risk of potentially fatal thyroid storm
• Plasmapheresis has been described as treatment in extreme
cases but more conventional treatment is the treatment used in
this case(9)
• The hook effect
• Bhcg is measured using a so called immunological
testing kit (1,2,3,10,11)
• The testing (described below) allows for
measurement via ELISA, radioisotope,
immunofluresence etc
•The team was expecting to find blood and a perforated uterus
Ultrasound
TEMPLATE DESIGN © 2008
•
Discussion
The hook effect and OHSS have both been described in the literature in
relation to molar pregnancy however we could not find both described in
one patient.(1,2,3,4) Additionally the patient had hyperthyroidism driven by
massive Bhcg and persistent Molar disease. Thus this case is indeed
unique!!
•Diagnosis of molar disease
•Diagnosis is made histologically with the aid of chromosomal studies
•Suspicion of molar disease is history, examination, Bhcg and
ultrasound
•In this case the Bhcg contradicted the ultrasound findings
•Interestingly, ultrasound alone has only a Sensitivity of 44% & a
specificity of 74%(5)
Mimics of CHD(6,7)
Adenmyomatous polyp
Hydropic placenta
•
The case is indeed a full house of the strange. Common things
happen commonly. However this case highlights important
albeit rare possibilities with CHD. The hook effect must be
thought of if the lab results don’t fit with the other
evidence, additionally the clinician must be vigilant that
OHSS may occur in CHD even immediately post evacuation.
The hook effect is when false low measurements occur
as a result of antigen super-saturation of both capture
and detection antibodies leading to a failure of
sandwiching(1,2,3,10)
Fernando et.al.(10) conducted experiments addressing
the hook effect and concluded that the hook effect is
potentially multifaceted and can occur due to
• Low affinity solid phase abs
• Inadequate washing
• Insufficient amounts of detection abs
• Excessive incubation time
• The hook effect can potentially occur in all
immunological testing and has been described in
• Prolactin, TSH, CA 125, 19.9, PSA(10)
• If suspected the hook effect can be ameliorated
against by dilution prior to testing
• The bottom line is that if CHD is suspected
the lab needs to know so steps such as
dilution and use of higher quality test kits can
be employed
References
(1)J Nodler J, K Kim, R Alvarez ‘Abnormally low hCG in a complete hydatidiform molar pregnancy: The hook effect’ Gynecologic Oncology
Reports 1 (2011) 6–7
(2)Pang Y P, Rajesh H, Tan L K ‘Molar pregnancy with false negative
urine hCG: the hook effect’ Singapore Med J 2010; 51(3) : e58
(3)R HENRIKSEN, G LISBET OPHEIM & E SALTRﾘE ‘Incomplete mole with a false-low level of human chorionic gonadotropin and
hyperthyroidism’ acta obstet gynecol scand ‘case reports’march 2004
(4)R Arora, Z Merhi, N Khulpateea, D Roth, & H Minkoff. Ovarian hyperstimulation syndrome after a molar pregnancy evacuation Fertility
and Sterility Vol. 90, No. 4, October 2008
(5)D. J. FOWLER, I. LINDSAY, M. J. SECKL and N. J. SEBIRE ‘Routine pre-evacuation ultrasound diagnosis of hydatidiform mole:
experience of more than 1000 cases from a regional referral center’ Ultrasound Obstet Gynecol 2006; 27: 56–60
(6)M. Furuhashi, Y. Miyabe, H. Oda‘Adenomyomatous polyp mimicking hydatidiform mole on ultrasonography’ Arch Gynecol Obstet (2000)
263:198–200
(7)K Jain ‘Gestational trophoblastic disease’ ultrasound quarterly 2005; 21(4):245-253
(8)L Walkington, J Webster, BW Hancock, J Everard and RE Coleman. ‘Hyperthyroidism and human chorionic gonadotrophin production in
gestational trophoblastic disease’ British Journal of Cancer (2011) 104, 1665 -1669
(9)E Adali, R Yildizhan, A Kolusari, M Kurdoglu, N Turan ‘The use of plasmapheresis for rapid hormonal control in severe hyperthyroidism
caused by a partial molar pregnancy’ Arch Gynecol Obstet (2009) 279:569-571
(10)S. A. Fernando & G. S. Wilson Multiple epitope interactions in the two-step sandwich immunoassay Journal of Immunological Methods,
151(1992)67-86
(11)http://en.wikipedia.org/wiki/ELISA
(12) THE MANAGEMENT OF OVARIAN HYPERSTIMULATION SYNDROME RCOG Green-top Guideline No. 5September 2006
(13) M. A. Fritz & L Sperroff Clinical Gyecologic Endocrinology and Infertility 8th ed. 2011 Lippincott Williams & Wilkins Philadelphia