Loss of Efficacy of Pasireotide After its Re-Administration: is There a Reason Why?

Pasireotide is a recently approved medical treatment for persistent or recurrent Cushing's disease (CD). However, an escape from the initial successful response has not yet been described. A 42-year-old female presented with several symptoms indicative of hypercortisolism. Biochemical evaluation and imaging were consistent with CD due to a pituitary adenoma. Surgical excision of the adenoma was unsuccessful and gamma-knife radiosurgery was followed. Our patient remained hypercortisolemic thus treatment with pasireotide (900 mg subcutaneously twice daily) was decided. Biochemical and clinical remission was noted shortly thereafter. Moderate adverse events led to dose reduction to 600 mg subcutaneously twice daily. The patient remained in remission for 6 months, when treatment was discontinued due to cholecystitis. One month after cholecystectomy, pasireotide was restarted with no clinical or biochemical benefit that time. Pasireotide is an effective medical treatment for CD. Nevertheless, a loss of its initial efficacy may rarely be described.

Treatment compliance and severe adverse events limit the use of tyrosine kinase inhibitors in refractory thyroid cancer.

OBJECTIVE: The aim of the present study was to assess patient compliance with tyrosine kinase inhibitor (TKI) treatment used for refractory and progressive thyroid cancer, in addition to the efficacy and serious adverse events associated with these agents. METHODS: We retrospectively analyzed data from adult patients with metastatic differentiated or medullary thyroid cancer unresponsive to conventional treatment and treated with TKIs. Patients received treatment until disease progression or onset of serious adverse events, or until they expressed an intention to stop treatment. RESULTS: Twenty-four patients received TKIs. The median duration of treatment was four (range: 1-19) cycles. The most frequent adverse events were fatigue, nausea, diarrhea, hypertension, and stomatitis, and the most severe were nasal bleeding, diarrhea, heart failure, rhabdomyolysis, renal failure, QT prolongation, neutropenia, and severe fatigue. Dose reduction was required in eight patients, while five decided to terminate TKI therapy because adverse events impaired their everyday activities. During therapy, two patients showed a partial response and three showed stable disease. The lungs were the metastatic sites favoring a response to treatment. CONCLUSION: Patient selection and meticulous pretreatment education are necessary in order to ensure adherence with TKI therapy. If adverse events appear, dose reduction or temporary treatment interruption may be offered because some adverse events resolve with continuation of treatment. In the event of serious adverse events, treatment discontinuation is necessary.

PREGO (presentation of Graves' orbitopathy) study: changes in referral patterns to European Group On Graves' Orbitopathy (EUGOGO) centres over the period from 2000 to 2012.

BACKGROUND/AIMS: The epidemiology of Graves' orbitopathy (GO) may be changing. The aim of the study was to identify trends in presentation of GO to tertiary centres and initial management over time. METHODS: Prospective observational study of European Group On Graves' Orbitopathy (EUGOGO) centres. All new referrals with a diagnosis of GO over a 4-month period in 2012 were included. Clinical and demographic characteristics, referral timelines and initial decisions about management were recorded. The data were compared with a similar EUGOGO survey performed in 2000. RESULTS: The demographic characteristics of 269 patients studied in 2012 were similar to those collected in the year 2000, including smoking rates (40.0% vs 40.2%). Mild (60.5% vs 41.2%, p<0.01) and inactive GO (63.2% vs 39.9%, p<0.01) were more prevalent in 2012. The times from diagnosis of thyroid disease to being seen in EUGOGO centres (6 vs 16 months) and from first symptoms of GO (9 vs 16 months) or from diagnosis of GO (6 vs 12 months) to first consultation in EUGOGO centres were shorter in 2012 (p<0.01). The initial management plans for GO were no different except surgical treatments for patients with mild inactive disease were more frequently offered in the 2012 cohort than in 2000 (27.3% vs 17%, p<0.05), and selenium supplements were offered only in the 2012 cohort (21.2% vs 0%, p<0.01). CONCLUSIONS: These findings suggest that the clinical manifestations of patients with GO may be changing over time in Europe.

Diagnosis of Graves' orbitopathy (DiaGO): results of a pilot study to assess the utility of an office tool for practicing endocrinologists.

CONTEXT: In active Graves' orbitopathy (GO), treatment can improve the final cosmetic and visual outcome. Diagnostic delay results in significant morbidity and increases patient dissatisfaction. However, it can be challenging for endocrinologists to recognize GO and decide who should be referred for ophthalmic care. OBJECTIVE: DiaGO, a clinical assessment tool, was developed for use in patients with Graves' disease (GD). The tool is designed to alert clinicians to the possibility of GO and prompt early ophthalmic assessment. DESIGN AND SETTING: A 20-point assessment tool was devised and tested on 104 GD patients: 27 "positive controls" with GO and 77 people with GD attending endocrine clinics over 17 months. Those scoring positively in endocrine clinics were referred for ophthalmic assessment. Both the appropriateness of the referral and subsequent treatment were assessed. RESULTS: Eighty-eight of the 104 patients (85%) were female (mean age, 48.5 y; range, 18-76 y). All 27 "controls" scored positively. Of the 77 people evaluated with GD, 27 (35%) scored above the threshold for referral and GO was confirmed in 24/26 (92%) who attended for specialist ophthalmic assessment. Twelve of these 24 (50%) were offered specific treatment following ophthalmology review. CONCLUSIONS: The timely diagnosis of GO is important because early intervention in active disease can improve prognosis. DiaGO alerts clinicians to the possibility of GO and prompts referral to specialist ophthalmic care. It is quick and easy to use and does not require specialist ophthalmic skills. Overall, half of those referred after use of DiaGO were offered specific treatment, suggesting its use might significantly improve the management of patients.

Thyroglossal duct cyst carcinomas: is there a need for thyroidectomy?

OBJECTIVE: Thyroglossal duct cyst (TGDC) carcinoma is a rare entity and its management is controversial. The aim of this retrospective study was to: (a) identify patients with TGDC carcinoma followed up in our clinic and (b) study specific characteristics of the disease and their association with thyroid carcinoma. DESIGN: Medical files of patients with TGDC carcinoma were reviewed and tumour characteristics, lymph node metastases, treatment and follow-up were evaluated. RESULTS: A total of 6 patients, 4 females and 2 males, mean age 39.3 years (median 33.5), were treated for papillary thyroid carcinoma arising in a TGDC. Carcinoma of the thyroid gland was found simultaneously in 4 of these patients, while in one patient thyroid carcinoma developed 10 years after the diagnosis of TGDC carcinoma. A variable clinical picture and presentation was recorded. The most aggressive manifestation of the disease in terms of local infiltration, local recurrence and lymph node metastases was observed in our youngest patients. CONCLUSIONS: Long-term follow-up is necessary for patients with thyroid carcinoma arising in a TGDC. In view of the frequent co-existence of thyroid cancer in these patients, we would recommend detailed thyroid evaluation and, eventually, total thyroidectomy at initial diagnosis of TGDC carcinoma.

Parathyroid involvement in thyroid cancer: an unforeseen event.

BACKGROUND: Parathyroid metastatic disease from thyroid cancer has not been studied extensively, mainly due to the need for parathyroid preservation during thyroid surgery. METHODS: We reviewed files from 1,770 patients with thyroid cancer followed up in our department and 10 patients with parathyroid metastases (0.5%) were identified. Patient and tumor characteristics were recorded. RESULTS: Six out of ten patients had metastases from papillary thyroid cancer, three from follicular thyroid cancer and one from anaplastic thyroid cancer. In nine patients parathyroid infiltration from thyroid cancer was found in direct contact with the thyroid cancer, and in one patient metastatic foci were observed not in continuity with the thyroid cancer. CONCLUSIONS: Parathyroid involvement, although infrequent, may occur in thyroid cancer independently of patient age and tumor size. The clinical significance of such event is not clear. The influence on disease outcome remains to be elucidated.

99mTc pertechnetate thyroid scan leads to serendipitous detection of metastatic thyroid cancer.

99mTc pertechnetate is considered insensitive in detecting thyroid carcinoma metastases. We report the case of a 71-year-old male patient, in whom metastasis of an unknown thyroid cancer was diagnosed incidentally on a routine 99mTc pertechnetate scan, performed for the assessment of nodular thyroid disease. Marked tracer accumulation was unexpectedly noted on the left frontal region, where a palpable, painless, soft tissue mass was present. Surgical excision of the mass revealed metastatic poorly differentiated thyroid carcinoma synchronous to soft tissue and adjacent bone.