Complete and sustained remission of hypercortisolism with pasireotide treatment of an adrenocorticotropic hormone (ACTH)-secreting thoracic neuroendocrine tumor: an n-of-1 trial.

N-of-1 trials can serve as useful tools in managing rare disease. We describe a patient presenting with a typical clinical picture of Cushing's Syndrome (CS). Further testing was diagnostic of ectopic Adrenocorticotropic Hormone (ACTH) secretion, but its origin remained occult. The patient was offered treatment with daily pasireotide at very low doses (300 mg bid), which resulted in clinical and biochemical control for a period of 5 years, when a pulmonary typical carcinoid was diagnosed and dissected. During the pharmacological treatment period, pasireotide was tentatively discontinued twice, with immediate flare of symptoms and biochemical markers, followed by remission after drug reinitiation. This is the first report of clinical and biochemical remission of an ectopic CS (ECS) with pasireotide used as first line treatment, in a low-grade lung carcinoid, for a prolonged period of 5 years. In conclusion, the burden of high morbidity caused by hypercortisolism can be effectively mitigated with appropriate pharmacological treatment, in patients with occult tumors. Pasireotide may lead to complete and sustained remission of hypercortisolism, until surgical therapy is feasible. The expression of SSTR2 from typical carcinoids may be critical in allowing the use of very low drug doses for achieving disease control, while minimizing the risk of adverse events.

Thyroid dysfunction and non-alcoholic fatty liver disease.

Thyroid hormones are crucial for hepatic lipid and glucose metabolism. Non-alcoholic fatty liver disease (NAFLD), a very common and potentially serious disease of modern society, shares common clinical features with hypothyroidism, such as obesity, insulin resistance and dyslipidemia. Furthermore, in certain studies, increased prevalence of hypothyroidism was observed in patients with NAFLD. However, whether there is a linear relationship between thyroid hormone levels, including values within or in proximity to the reference range and NAFLD incidence and severity remains a contradictory subject in the literature. On the other hand, attempts to treat NAFLD with thyromimetic drugs remain at an early stage. In this review, data derived from observational studies along with evidence on possible treatment with thyroid hormone analogues are presented.

Unusual case of Cowden-like syndrome, neck paraganglioma, and pituitary adenoma.

BACKGROUND: Pituitary tumors, paragangliomas, and Cowden syndrome do not usually occur together. METHODS: The synchronous presentation of papillary thyroid carcinoma and neck paraganglioma was revealed in a 43-year-old woman who had been diagnosed with a microprolactinoma one decade before and now presented with a constellation of characteristics that are components of Cowden syndrome, specifically macrocephaly, multiple skin papules, fibrocystic mammary disease, and uterine leiomyofibroma. RESULTS: Germline mutation analysis of phosphatase and tensin homolog (PTEN), succinate dehydrogenase subunit B (SDHB), succinate dehydrogenase subunit C (SDHC), and succinate dehydrogenase subunit D (SDHD) was performed with revelation of 3 polymorphic sites in introns 1, 4, and 8 of the PTEN gene and 1 polymorphic site in exon 1 of the SDHB gene, but absence of known pathogenic mutations. CONCLUSION: The coexistence of Cowden-like syndrome, neck paraganglioma, and pituitary adenoma is described for the first time, and could represent a novel genetic syndrome with an as yet unidentified common genetic basis.

Amelioration of cardiovascular risk factors with partial biochemical control of acromegaly.

OBJECTIVE: Complete remission of acromegaly is associated with favourable changes in cardiovascular risk parameters. We evaluated the effects of suboptimal therapy on haemodynamic, metabolic, inflammatory and coagulation cardiovascular risk indices. DESIGN AND METHODS: Eighteen acromegalic patients on somatostatin analogues, with incomplete biochemical control, were evaluated at diagnosis and 6 months after treatment and compared to 15 healthy age- and body mass index (BMI)-matched controls. Measurements of blood pressure, GH, IGF-I, glucose, insulin, glycated haemoglobin (HbA1c), lipids, apolipoprotein A1 (apoA1), apoB, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA) and circulating thrombomodulin were performed in all study participants, followed by an oral glucose tolerance test (OGTT). Insulin sensitivity (IS) was expressed by the Matsuda index (OGTT(ISI)). RESULTS: Partial control of acromegaly resulted in a significant reduction in systolic and diastolic blood pressure, glucose, insulin, HbA1c, total (T-C) and low density lipoprotein cholesterol (LDL-C) and triglyceride levels, and a significant increase in apoA1, high density lipoprotein cholesterol (HDL-C) and OGTT(ISI) compared to pretreatment levels. Plasma fibrinogen and PAI-1 levels fell significantly [respectively (mean +/- SEM), 11.04 +/- 0.41 vs. 10.12 +/- 0.34 micromol/l, P = 0.003 and 9.6 +/- 1.97 vs. 6.55 +/- 1.89 microg/l, P < 0.001]. However, a marked reduction in tPA [median (IQR) 5.1 (2.5-15) vs. 3.4 (2.4-8.6) microg/l, P = 0.031] and an increase in hs-CRP [median (IQR) 0.05 (0.03-0.11) vs. 0.1 (0.06-0.23) mg/l, P < 0.001] were also noted. On treatment, acromegalic patients were comparable to controls, except for OGTT(ISI), lipoprotein(a) [Lp(a)], fibrinogen and tPA and HDL-C levels. Thrombomodulin and apoB levels were not affected by treatment. CONCLUSIONS: Partial control in disease activity following somatostatin analogues results in significant improvement in a considerable number of cardiovascular risk markers in acromegaly.