Introduction
Choriocarcinoma is a malignant disease arising from the placenta and trophoblastic villi. Gestational trophoblastic neoplasia (GTN) occur in 1 : 40,000 pregnancies and are more common in South East Asia as compared to Europe and North America.
Invasive mole and Choriocarcinoma are the most common GTN, producing high levels of HCG and are known to be responsive to chemotherapy.
HCG is used as a marker for diagnosis, monitoring the therapy and follow up of these patients. HCG is a glycoprotein produced by placenta and has an intrinsic thyroid stimulating activity. 1 Structural resemblance of TSH and HCG causes release of Thyroxine from the thyroid gland.
The first case of Hydatidiform mole and Thyrotoxicosis was reported in 1955 by Tisne and colleagues. 2
Since then several cases of Gestational trophoblastic disease induced Hyperthyroidism have been reported in literature. 3, 4, 5, 6, 7, 8
Case Presentation
A 25 year old female, diagnosed case of GTN (Choriocarcinoma) was admitted to our tertiary cancer care centre for chemotherapy and supportive care.
Case history
Patient was G2P0A1 (Obstretic score). She had history of one abortion more than a year back. No other details were available. She presented to us with complaints of pain in abdomen, bleeding per vaginum (PV) and breathlessness.
Radiological investigations
Revealed extensive bilateral metastatic nodules in lung Parenchyma (Figure 1).
PET CT revealed hypermetabolic, heterogeneously enhancing solid cystic mass lesion involving the uterus and cervix. (Site of primary malignancy) (Figure 1).
Blood Investigations revealed: (Table 3)
Serum Beta-HCG level was 6,88,748 mIu/ml (Normal range: 0 to 10 mIu/ml).
Thyroid function tests showed Serum T3 to be 6.30 nmol/l (Normal range: 0.92 to 2.33 nmol/l).
Serum T4 was 975 nmol/l (Normal range: 62 to 120 nmol/l).
Serum TSH was less than 0.25 uIu/ml (Normal range: 0.25 to 5.00 uIu/ml).
Other Haematological and Biochemical parameters like Complete Blood Count(CBC), Kidney function tests (KFT) and liver function tests (LFT) were all within normal limits.
Diagnosis
Table 1
Prognostic scoring indexfor GTN (NCCN guidelines version 3.2020).
Table 2
BurchWartofsky point scale.
Patients Score 35 –Impending thyroid storm (Table 2)
Final Diagnosis: Gestational trophoblastic neoplasm (Chorio carcinoma, High Risk FIGO grade III).
(Table 1) with pulmonary metastases and hyperthyroidism (Impending Thyroid storm) ( Table 2).
Treatment aspect
Chemotherapy was started: EMACO Day 1 and Day 8, 6 cycles.
Patient had Biochemical as well as Clinical Hyperthyroidism. Burch- Wartofsky score for patient was 35 which indicated impending thyroid storm. (Table 2)
Patient was put on Neomercazol 5 mg BD. Other supportive care was initiated.
Patients Beta-HCG levels were monitored weekly. There was marked decline in serum BHCG levels. At one month, Beta-HCG was 711 mIu/ml and Thyroid function normalized. T3 was 2.0 nmol/l, T4 was 101 nmol/l and TSH was 1.80 uIu/ml. (Table 3)
Patient’s Anti thyroid medication i.e Neomercazol was stopped. Patient was monitored on monthly basis for serum B HCG levels. At one year follow up, Patients Beta-HCG level was 0.3 mIu/ml.
Patient was Euthyroid without any anti thyroid medication and doing well.
Table 3
Summary of HCG, TFT measurements.
Discussion
Choriocarcinoma is the most aggressive form of GTN, characterized by vascular invasion and wide spread metastases. The most common metastatic sites are lung (80 % ), vagina ( 30 % ) brain ( 10 % ) and liver ( 10 % ). 9
The pathophysiology of thyroid disease in GTN is related to the secretion of HCG from the trophoblastic tissue. The effect of HCG on thyroid gland is thought to occur due to molecular mimicry between HCG and TSH.
The two known mechanisms are increased thyrotropic activity by HCG and structural resemblance with TSH causing release of thyroxine from thyroid gland. 10
Cave and colleagues11 examined serum from patients with metastatic choriocarcinoma. By using gel filtration, a single peak coinciding with HCG was demonstrated. This suggested that the thyrotropin of choriocarcinoma was HCG. The similarity in structure between HCG and TSH can cause cross reactivity of each receptor.
Various studies have shown prevalence of hyperthyroidism with high levels of HCG. Lockwood et al. found suppressed TSH in 100 % specimen with HCG concentration > 40,000 Iu/l. 12 Glinoer estimated that any increase 10,000 Iu/l for HCG will be followed by increase in FT4 by
ng/dl and reduction in TSH by 0.1 mIu/ml. 13, 14, 15
Although there is no precise threshold at which HCG causes Thyrotoxicosis, thyroid function should be measured in all patients with HCG > 50,000 Iu/L regardless of the cause of elevation. 16, 17
Choriocarcinoma is sensitive to chemotherapy and choice of regimen is based on WHO (World Health Organisation)Prognostic Scoring System and the International Federation of Gynecology and Obstetrics( FIGO) anatomic staging system.
In patients having Biochemical and Clinical Hyperthyroidism, Burch- Wartofsky score should be assessed for presence of Thyroid storm and treatment should be initiated accordingly. Unless there are symptoms of severe thyrotoxicosis, treatment of hyperthyroidism is not needed, as chemotherapy for Choriocarcinoma should effectively bring down the HCG levels alleviating the hyperthyroidism.
Conclusion
Choriocarcinoma is not only associated with Hyperthyroidism , but also can induce thyroid storm.
GTD induced thyroid storm should be considered in any female of child bearing age with signs and symptoms of Thyrotoxicosis.
High levels of HCG are directly proportional to the clinical manifestation of Hyperthyroidism.
Thyroid function must be measured in all patients with HCG levels > 50,000Iu/L.
In patients having Biochemical and clinical hyperthyroidism, Burch- Wartofsky score should be assessed for presence of Thyroid storm and treatment should be initiated accordingly.
Unless there are symptoms of severe thyrotoxicosis, Treatment of hyperthyroidism is not initiated.
Thyroid function is expected to return to normal once the HCG levels come down.
Awareness of this condition is important for diagnosis and treatment of GTD.
GTD induced thyroid storm should be considered in any female of child bearing age with signs and symptoms of thyrotoxicosis.
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