Cardiovascular risk factors in adult patients with multisystem Langerhans-cell histiocytosis: evidence of glucose metabolism abnormalities.

BACKGROUND: Langerhans-cell histiocytosis (LCH) is a rare disease with features of chronic inflammation and it may also induce hypopituitarism, conditions associated with an increased risk of cardiovascular diseases. AIM: Cardiovascular and metabolic risk profile investigation in multisystem LCH patients with and without anterior pituitary deficiency. DESIGN: Prospective, observational study. METHODS: Fourteen adult patients with LCH, 7 with and 7 without anterior pituitary deficiency, and 42 controls matched for age, body mass index (BMI) and smoking. Cardiovascular risk factors were estimated in all subjects: glucose and lipid profile, mathematical indices of insulin resistance (IR), blood pressure, structural arterial and functional endothelial properties (intima-media thickness, brachial artery flow-mediated dilatation). Cardiovascular risk factors were estimated in the three groups studied; the effect of disease activity and/or treatment was also determined in patients with LCH. RESULTS: Ten patients had diabetes insipidus, and 7 anterior pituitary hormone deficiencies: 8 patients had active disease and 11 had received systemic treatment. No difference was observed between the study groups in vascular parameters, in lipid profile or in blood pressure. However, the insulin resistance index GIR was decreased in patients with LCH without anterior pituitary deficiency compared to controls (P = 0.033). Three patients had impaired glucose tolerance and one diabetes mellitus type 2. These patients were older and had active disease; there was no association with hypopituitarism and/or previous treatment. CONCLUSION: Adults patients with LCH have abnormalities of glucose metabolism that tend to occur in patients with active disease, and may be a consequence of the pro-inflammatory state.

Evolving radiological features of hypothalamo-pituitary lesions in adult patients with Langerhans cell histiocytosis (LCH).

Langerhans cell histiocytosis (LCH) is a rare, systemic disease caused by monoclonal expansion of dendritic cells that shows a particular predilection for the hypothalamic-pituitary system (HPS). We studied the function (anterior and posterior pituitary hormonal secretion) and morphology using magnetic resonance imaging (MRI) of the HPS in 17 adult patients (seven males, median age 35 years, range 18-59 years) with multisystem LCH. We also evaluated the evolution of structural HPS abnormalities in relation to pituitary function and response to treatment in 12 of these patients during a median follow-up period of 3.75 years (range 1.5-10 years). Of the 17 patients, 14 (82%) had abnormal HPS imaging, and 12 (70%) had more than one area involved. Lack of the bright spot of the posterior pituitary lobe was typically found in all patients with the diagnosis of diabetes insipidus (DI). Eight patients (47%) had infundibular enlargement, six (35%) pituitary infiltration, four (24%) partially or completely empty sella, three (18%) hypothalamic involvement, and two (12%) infundibular atrophy. DI was found in 16 patients (94%) and anterior pituitary hormonal deficiency (APHD) in 10 patients (59%); two patients had single (12%) and 8 (47%) multiple APHD. During the follow-up period there was improvement of the initially demonstrated HPS pathology in seven (47%) patients, and five (33%) of them had received at least one form of treatment. APHD and DI persisted in all patients except in one in whom established gonadotrophin deficiency recovered. In summary, DI and APHD are very common in patients with multisystem LCH and are almost always associated with abnormal HPS imaging.

Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues.

Neuroendocrine tumours (NETs) constitute a heterogeneous group of tumours that frequently express cell membrane-specific peptide receptors, such as somatostatin receptors (SSTRs), and of which gastroenteropancreatic (GEP), carcinoid and pancreatic islet cell tumours exhibit the highest expression of SSTRs. Radiolabelled receptor-binding somatostatin analogues (octreotide and lanreotide) act as vehicles to guide radioactivity to tissues expressing SSTRs, and can thus be used for their diagnosis and treatment. After the localization of NETs bearing SSTRs with (111)In-octreotide (OctreoScan), a number of radioisotopes with different physical properties have been used for their treatment. The administration of high doses of the Auger electron and gamma-emitter (111)In-diethylenetriaminepenta-acetic acid (DTPA)(0),octreotide in patients with metastatic tumours has been associated with considerable symptomatic improvement but relatively few and short-lived objective tumour responses. The use of another radiolabelled somatostatin analogue coupled with (90)Y, a pure beta-emitter, (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)(0),Tyr(3),octreotide ((90)Y-DOTATOC, OctreoTher), was associated with 10-30% objective tumour response rates, and appears to be particularly effective in larger tumours. (111)In- and (90)Y-DOTA-lanreotide has also been used for the treatment of NETs although its therapeutic efficacy is probably inferior to that of octreotide-based radiopharmaceuticals. More recently, treatment with (177)Lu-DOTA(0),Tyr(3)octreotate ((177)Lu-DOTATATE), which has a higher affinity for the SSTR subtype 2, resulted in approximately 30% complete or partial tumour responses; this radiopharmaceutical is particularly effective in smaller tumours. Furthermore, treatment using both (90)Y-DOTATOC and (177)Lu-DOTA(0),Tyr(3)octreotate seems promising, as the combination of these radiopharmaceuticals could be effective in tumours bearing both small and large lesions. Tumour regression is positively correlated with a high level of uptake on (111)In-octreotide scintigraphy, limited tumour mass and good performance status. In general, better responses have been obtained in GEP tumours than other NETs. The side effects of this form of therapy are relatively few and mild, particularly when kidney-protective agents are used. Treatment with radiolabelled somatostatin analogues presents a promising tool for the management of patients with inoperable or disseminated NETs, and particularly GEP tumours.

Treatment with oral biphosphonates can increase the sensitivity of sestamibi radionuclide imaging in patients with primary hyperparathyroidism.

The sensitivity of 99mTc-sestamibi scan in detecting parathyroid disease in primary hyperparathyroidism (PHP) is almost 90%, and therefore facilitates successful parathyroidectomy. To enhance the diagnostic accuracy of the procedure, we repeated imaging with 99mTc-sestamibi in 15 patients with PHP and an initially negative (11 patients) or weakly positive (four patients) 99mTc-sestamibi scan after the administration of 10 mg of oral alendronate for 2 months. Serum calcium, phosphate and parathormone (PTH) measurements were obtained at presentation and after 1 and 2 months' treatment with alendronate. Eight patients with an initially negative 99mTc-sestamibi scan demonstrated at least one area of uptake in the repeated scan. Six of these patients underwent surgery and obtained a biochemical cure; a single adenoma was found in four and hyperplasia in the remaining two. In all four patients with an initially weakly positive 99mTc-sestamibi scan, the repeated scan demonstrated enhanced uptake and also revealed further areas of uptake. Two of these patients underwent surgery with a biochemical cure; an adenoma was found in one and hyperplasia in another. Compared with baseline there was a significant increase in PTH but not in calcium or phosphate levels during treatment with alendronate. We suggest that, in patients with PHP and a negative or weakly positive initial 99mTc-sestamibi scan, administration of oral alendronate may be associated with a positive repeated 99mTc-sestamibi scan and can thus enhance the sensitivity of the procedure.