Thyroid-Stimulating Hormone Stimulation Tests in the Bottlenose Dolphin (Tursiops truncatus)

Stimulation of the thyroid with thyroid-stimulating hormone (TSH) is a potentially useful diagnostic of thyroid dysfunction, but little is known about the response of the thyroid to TSH stimulation in bottlenose dolphins (Tursiops truncatus). To better characterize the response of the dolphin thyroid to TSH stimulation, five adult dolphins participated in a TSH stimulation study. Dolphins voluntarily beached onto a padded mat and were given a 1.5 mg intramuscular injection of human recombinant TSH. Blood samples collected the day prior, at multiple intervals the day of, and daily for three days after the injection were analyzed via radioimmunoassay for free and total triiodothyronine (fT3 and tT3), and free and total thyroxine (fT4 and tT4). Significant increases in circulating fT3, fT4, and tT4 were observed with peaks occurring for all hormones the day after the TSH injection; maximal increases were 44%, 47%, and 23% for each hormone, respectively. Temporal patterns in the hormones potentially reflected feedback mechanisms countering the surge in fT3 following stimulation. Though recombinant human TSH was effective at stimulating hormone release, it is likely that use of dolphin or dolphin-derived TSH would enhance the clinical utility of the stimulation test, as would the development of antibodies specific to dolphin TSH.

No difference in the outcome of metastatic thyroid cancer patients when using recombinant or endogenous TSH

Objective: At present, recombinant TSH cannot be used for the treatment of metastatic differentiated thyroid cancer patients. The aim of this study was to evaluate if the type of TSH stimulation, recombinant or endogenous, had an impact on the outcome of these patients. Design and methods: We compared the outcome of two propensity score-matched groups of metastatic patients, stimulated by either only recombinant TSH (n = 43) or only endogenous TSH (n = 34). Results: As expected from the matching procedure, the clinical–pathological features and the cumulative 131-I activities administered to the two groups were very similar. After 4 years of follow-up, 4% of patients were cured, 3% had biochemical disease and 93% had structural disease. However, 91% of patients obtained a clinical benefit from this therapy in terms of stabilization of the disease or complete remission or partial response. When considering the two groups separately, we did not find any difference in their outcome. When considering the response to 131-I therapy of the single type of metastases, 8% of lymph node metastases and 8% of lung metastases disappeared but none of the bone metastases. The response to 131-I therapy of the single type of metastases was similar when we looked at the two groups separately. Conclusions: This study shows (i) an overall clinical benefit of the 131-I therapy, since the majority of patients remained affected but with a stable disease, and (ii) that the preparation with either recombinant or endogenous TSH has no impact on the 131-I therapy efficacy and the outcome of our two groups of patients.

Malignant struma ovarii with a robust response to radioactive iodine

Summary Struma ovarii is a rare, usually benign ovarian tumour with malignancy occurring in <5% of cases. Metastases, particularly seeding to bone, are extremely rare. Presentation is variable but often features local pain and/or ascites and hyperthyroidism may occur. It is not established how to best treat and follow patients with extensive disease. Case reports of radioiodine (I131) ablative therapy following thyroidectomy have shown reduced recurrence. We describe the case of a 33-year-old woman who presented with bone pain and was diagnosed with skeletal metastases with features of follicular thyroid carcinoma. However, thyroid pathology was benign. She recalled that 5 years prior, an ovarian teratoma was excised, classified at that time as a dermoid cyst. Retrospective review of this pathology confirmed struma ovarii without obvious malignant features. The patient was found to have widespread metastases to bone and viscera and her thyroglobulin was >3000 µg/L following recombinant TSH administration prior to her first dose of I131. At 25 months following radioiodine treatment, she is in remission with an undetectable thyroglobulin and clear I131 surveillance scans. This case demonstrates an unusual presentation of malignant struma ovarii together with challenges of predicting metastatic disease, and demonstrates a successful radioiodine regimen inducing remission. Learning points: Malignant transformation of struma ovarii (MSO) is extremely rare and even rarer are metastatic deposits in bone and viscera. MSO can be difficult to predict by initial ovarian pathology, analogous to the difficulty in some cases of differentiating between follicular thyroid adenoma and carcinoma. No consensus exists on the management for post operative treatment of MSO; however, in this case, three doses of 6Gbq radioiodine therapy over a short time period eliminated metastases to viscera and bone. Patients should continue to have TSH suppression for ~5 years. Monitoring thyroglobulin levels can predict recurrence.

A Novel Antigonadotropic Role of Thyroid Stimulating Hormone on Leydig Cell-Derived Mouse Leydig Tumor Cells-1 Line

Subclinical hypothyroid men characterized by a rise in only thyroid stimulating hormone (TSH) levels, and normal thyroid hormone levels showed a fall in their serum progesterone and testosterone levels. This suggested a role of TSH in regulating Leydig cell steroidogenesis. Therefore, we investigated the direct role of TSH on steroid production and secretion using a mouse Leydig tumor cell line-1 (MLTC-1). MLTC-1 cells were treated with different doses of TSH isolated from porcine pituitary as well as recombinant TSH. Steroid secretion was measured by radioimmunoassay (RIA). The mRNA levels of steroidogenic enzymes were quantitated by real-time polymerase chain reaction (RT-PCR), whereas the corresponding protein levels were determined by western blot. In MLTC-1 cells, pituitary TSH as well as recombinant TSH inhibited progesterone and testosterone secretion in a dose-dependent manner. The inhibitory action of TSH on steroid secretion was unique and not mimicked by other anterior pituitary hormones including follicle stimulating hormone and adrenocorticotropic hormone. Recombinant TSH showed no effect on steroidogenic acute regulatory protein and CYP11A1, the enzymes catalyzing the nonsteroidogenic and steroidogenic rate-limiting steps of steroid synthesis, respectively. Recombinant TSH was shown to inhibit steroidogenesis in MLTC-1 cells by inhibiting the 3-β hydroxy steroid dehydrogenase mRNA and protein levels, the enzyme that catalyzes the conversion of pregnenolone to progesterone. This inhibitory effect of TSH is probably direct as both mRNA and protein of the TSH receptor were shown to be present in the MLTC-1 cells.