Treatment with somatostatin analogs and chemoembolization of liver metastases for severe hypoglycemia in malignant insulinomas.

BACKGROUND: Preventing hypoglycemia is of vital importance and a major challenge in patients with severe symptomatic hypoglycemia related to malignant unresectable insulinomas, but there is no consensus treatment. PATIENTS: Five patients with malignant unresectable insulinomas were referred to our department for severe hypoglycemia. At referral the five patients were dependent on iv infusion of glucose solution. Patient 1 had a locally invasive 5-cm insulinoma, patients 2, 3 and 4 had multiple liver metastases and patient 5 had a 2.5-cm pancreatic tumor with multiple liver and lung metastases. Before referral to our department, 4/5 patients had been administered systemic chemotherapy and 3/5 therapeutic doses of radiolabeled octreotide without any benefit on blood glucose levels. Octreoscan scintigraphy was positive in 4 patients (patients 1-4). Diazoxide alone or combined with glucocorticoids had failed to control hypoglycemia. Continuous sc administration of octreotide (up to 1500 µg/day) resulted in normalization of blood glucose levels in patient 1. Chemoembolization of liver metastases normalized blood glucose levels in patient 2, minimized hypoglycemia in patients 3 and 4, and normalized blood glucose levels in patient 5 when followed by subcutaneous administration of octreotide (2000 µg/day). Chemoembolization had to be repeated four times in patient 3 to control blood glucose levels. CONCLUSION: Chemoembolization of liver metastases and high-dose octreotide in responsive patients (alone or combined with chemoembolization) can control severe hypoglycemia in patients with symptomatic malignant unresectable insulinomas; the efficacy of octreotide can be improved after chemoembolization of liver metastases.

[Pituitary carcinomas and aggressive adenomas: an overview and new therapeutic options]. / Carcinomes et adénomes hypophysaires agressifs : mise au point et nouvelles options thérapeutiques.

Pituitary carcinomas are a rare disease with an estimated prevalence around 0.2 % of the pituitary tumours. They are defined by the presence of intra or extra-cranial metastases but initially they can share the same features as aggressive pituitary adenomas. Indeed there are some indicators that help to differentiate adenomas and carcinomas such as histological findings and immunohistochemical characteristics. Usually in carcinomas, mitotic activity is higher, proliferative index Ki-67 is higher, p53 expression is positive and microvascular density is mostly increased. The majority of carcinomas are prolactin or ACTH-secreting tumors. Dopamine and somatostatin-receptor agonists are not as effective as for the treatment of adenomas. Carcinomas require often repeated surgery and radiotherapy fail to control the tumor. Conventional chemotherapy is poorly effective, but recent case reports with the alkylating agent temozolomide have provided better results at least in the short term. The effects of temozolomide are reversed by the enzyme MGMT and the treatment's response can be predicted by the study of MGMT's expression : tumours lacking MGMT are especially sensitive to temozolomide.

Pituitary apoplexy and idiopathic thrombocytopenic purpura: a new case and review of the literature.

Pituitary apoplexy can occur as a complication of idiopathic thrombocytopenic purpura. We report here a new case of such association. A male patient aged 59 years, complaining of decreased libido for one year, was referred to the emergency department for purpura and severe thrombocytopenia (4000 platelets/mm3). 24 hours after the cutaneous rash the patient presented with clinical symptoms of bilateral cavernous sinus compression comprising ptosis, bilateral ophtalmoplegia and right supraorbital hypoesthesia. Cranial CT scan showed an enlarged sella and a pituitary mass with signs of intrapituitary haemorrhage. Hormonal evaluation showed hyperprolactinemia (50 ng/mL) and hypopituitarism, and the patient needed substitution with hydrocortisone and levothyroxine. Immunoglobulins and corticosteroids were given to the patient to treat thrombocytopenia, then worsening of neurological and ophtalmological symptoms led to pituitary surgery. Histopathological examination found necrotical pituitary tissue. Immunostaining with an anti-prolactin antibody was positive in several groups of cells. Neurological symptoms subsided and thrombocytopenia was corrected by treatment. In conclusion, we report a case of pituitary apoplexy due to severe thrombocytopenia occurring as a complication of a preexisting macroprolactinoma.