The Grapes of Wrath

1. The Grapes of Wrath Eric Larson, MD, FACP Sanford School of Medicine

2. Presentation • 49 year old woman presented with a chief complaint of “I think I may be hypothyroid”

3. History of Present Illness • Three month history of: • Abnormal periods • Malaise • Abdominal bloating • Constipation

4. HPI, continued • Two home pregnancy tests were negative • Evaluated by gynecology 3 months prior and given trial of progesterone which precipitated weight gain, hot flashes and increased irregular bleeding • Constipation worsening

5. HPI, continued • Gastroenterology evaluation 2 months prior to presentation recommended laxative and follow-up

6. Past Medical History • DVT post-pregnancy • Adenomatous colon polyps • Anxiety • Migraines • Laparotomy for ovarian cysts, remote

7. Medications • Aspirin 81 mg daily • Multivitamin daily

8. Family History • Father– coronary artery disease • Mother – hypertension, arthritis • Sister – asthma

9. Social History • Non-smoker • Non-drinker • Married • Employed, college educated

10. Review of Systems • Negative except as already discussed

11. Physical Examination • Weight 149 lbs (unchanged) • BP 130/80 • Pulse 76 • Respirations 18

12. PE, continued • Heart – regular, no murmurs • Lungs – Clear • Abdomen – midline abdominal fullness up to umbilicus • Exam otherwise unremarkable

13. Laboratory Evaluation • Complete blood count – normal • Comprehensive metabolic panel – sodium 134 otherwise normal • TSH < 0.02 and FT4 – 1.6 • Quantative beta HCG > 200,000

14. Pelvic Ultrasound

15. CT Scan

16. Pathology • Complete hydatidiform mole • No invasion • Fully excised

17. Follow-up • Serial quantative beta-HCG demonstrated rapid (6 months) and sustained normalization • While the patient was clinically euthyroid she was biochemically hyperthyroid. This resolved without treatment over the next year. • The patient is doing well 5 years post diagnosis

18. Points for the Internist • Why were the patients initial pregnancy tests negative? • Why was the patient biochemically hyperthyroid with resolution post-operatively?

19. Hook Effect • Usual pregnancy testing on either serum or urine utilizes two antibodies against beta-hCG. • Both antibodies must be bound to the same beta-hCG glycoprotein forming a “sandwich” to show positive results • Massive amounts of beta-hCG will fill all antibody sites and not allow “sandwich” formation resulting in false negative results

20. Hook Effect, continued • Dilution of samples will result in increasing positivity • Has been documented with other immunoassays such as PSA, RPR, Ca-125

21. Why Hyperthyroid? • Likely due to thyrotrophic effect of beta-hCG (similar to TSH) • Massive amounts of beta-hCG usually required to cause thyrotoxicosis (our patient was clinically euthyroid) • Some effect on TSH noted in normal pregnancy

22. Thank You

23. References • Fignon A, Guilloteau D, Lansac J, Besnard JC. Hook effect in immunoradiometric assay for human chorionic gonadotropine as a marker for trophoblastic disease. Eu J of Ob Gyn Rep Bio. 1995;61:183-184. • Hendrickson R, Opheim GL, Saltroe E. Incomplete mole with a false-low level fo human chroionicgonadotropin and hyperthyroidism. ActaObstetGynecol Scand. 2004;633-635. • Levavi H, et al. “Hook Effect” in complete hydatidiform molar pregnancy: A falsely low level of beta-hCG. Obstet Gynecol. 1993;82:720-721. • Pang YP, Rajesh H, Tan LK. Molar pregnancy with false negative urine hCG: the hook effect. Singapore Med J. 2010;51(3):e58-e61. • Walkington L, Webster J, Hancock BW, Everard J, Coleman RE. Hyperthyroidism and human chorionic gonadotrophin production in gestational trophoblasticdisease. Br J Cancer. 2011;104:1665-1669.