Evidence of acute pancreatitis in a patient with radioresistant-differentiated thyroid cancer.

Peroxisome proliferator-activated receptor (PPAR) agonists are sometimes used in patients with radioiodine-resistant differentiated thyroid cancers in order to effect further differentiation of the tumor and increase the chance of therapeutic success with subsequent doses of radioiodine. PPAR agonists are reportedly protective of the pancreas and have been proposed as agents that might be useful in the prevention of pancreatitis. In this report, we describe a patient treated with the PPAR agonist rosiglitazone for thyroid cancer who showed imaging abnormalities on PET scan and biochemical evidence of acute pancreatitis. Despite evidence of acute pancreatitis, the etiology of which is unclear, the patient remained asymptomatic. It is speculated that the lack of symptoms in this patient was due to the suppression by rosiglitazone of proinflammatory cytokines.

Abnormalities in glucose metabolism in patients with schizophrenia treated with atypical antipsychotic medications.

The incidence of carbohydrate intolerance and overt diabetes is increased in patients with schizophrenia treated with the newer atypical antipsychotic agents. The precise mechanism for these abnormalities remains obscure. This review examines the potential interaction between atypical antipsychotic medications and several hormones known to influence appetite regulation and carbohydrate metabolism.

Thiazolidinediones and the preservation of beta-cell function, cellular proliferation and apoptosis.

The thiazolidinediones (TZDs) or glitazones are pharmaceutical agents that have profound effects on energy expenditure and conservation. They also exert significant anti-inflammatory effects and influence cell proliferation and cell death. The drugs are primarily used in clinical practice in the treatment of patients with type 2 diabetes mellitus, a disorder of insulin resistance that occurs when the pancreatic beta-cells are unable to produce adequate amounts of insulin to maintain euglycaemia. Loss of pancreatic beta-cell function in type 2 diabetes is progressive and often precedes overt diabetes by 10 years or more, as was shown by the United Kingdom Prospective Diabetes Study. Any therapeutic or preventive approach that would limit or reverse loss of beta-cell function in diabetes would have profound effects on the morbidity associated with this widespread disease. Evidence suggesting a potential role of TZDs in preserving beta-cell function in type 2 diabetes as well as the ability of these agents to exert anti-inflammatory and proapoptotic anticancer effects, and their ability to promote cellular proliferation in various organs is reviewed.

Enhanced radioiodine uptake in a patient with poorly differentiated papillary thyroid cancer after treatment with rosiglitazone.

The effect of pretreatment with the peroxisome proliferator-activated receptor (PPAR) agonist, rosiglitazone, on radioiodine uptake and serum thyroglobulin levels in a patient with radioiodine-resistant papillary thyroid cancer is described. Treatment with rosiglitazone resulted in enhanced radioiodine uptake in areas of presumed metastatic disease in the neck that were previously only faintly seen, and serum thyroglobulin fell from a pretreatment level of 41 ng/mL to less than 2 ng/mL.

Serum TNF-alpha in psoriasis after treatment with propylthiouracil, an antithyroid thioureylene.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) and its receptors play important roles in the development and persistence of psoriatic plaques. The antithyroid thioureylenes, propylthiouracil and methimazole, are effective in the treatment of patients with psoriasis with a significant number of patients showing clearing or near clearing of their lesions after a several weeks of treatment. METHODS: The present study examined the effect of treatment with propylthiouracil, given in a dose of 100 mg every 8 hours for 3 months, on the serum levels of TNF-alpha in 9 patients with plaque psoriasis. RESULTS: Propylthiouracil therapy did not result in a significant decline in serum TNF-alpha concentrations. CONCLUSIONS: The findings suggest that the therapeutic effect of propylthiouracil in psoriasis appears not to be related to any change in the concentration of TNF-alpha but occurs via an anti-proliferative mechanism as we have previously speculated.

Anti-thyroid thioureylenes in the treatment of psoriasis.

Psoriasis is a common skin disorder associated with significant morbidity. Many agents are used in the medical management of this debilitating condition with the newer anti-cytokine agents being the most recent addition to the pharmacological armamentarium to battle the disorder. Cost concerns are very important with the newer "biologic" treatments costing in excess of 10,000 US dollars annually. The need for cheaper, orally administered agents is therefore imperative. This paper addresses the potential role of anti-thyroid thioureylenes, propylthiouracil and methimazole, in the treatment of psoriasis and reviews the possible mechanism of action of these drugs in this disorder. It is hypothesized that the beneficial effect of anti-thyroid thioureylenes in psoriasis is linked to their effect as anti-proliferative agents as reflected by significant decrease in markers of cellular proliferation such as proliferative cell nuclear antigen in biopsy specimens after treatment with these drugs. Propylthiouracil has been shown to bind to the hepatic T 3 receptor and it is possible that propylthiouracil (6-n-propyl-2-thiouracil) binding to the ligand-binding site normally occupied by T 3 impairs transcription by inactivating the effect of T 3 as well as by squelching retinoic X receptor heterodimer formation with other receptors of the steroid receptor superfamily such as the peroxisome proliferator-activated receptor, retinoic acid receptor and vitamin D receptors.

Severe myopathy and psychosis in a patient with Cushing's disease macroadenoma.

Cushing's disease is most commonly caused by a corticotrope adenoma of the pituitary. Between 50 and 70% of patients with spontaneous hypercortisolism have ACTH-producing pituitary adenomas. The tumors are usually microadenomas with approximately 20% of patients with the disease showing no evidence of tumor on CT-scans or MR imaging of their pituitary glands. In contrast to patients with ectopic ACTH production, plasma ACTH concentrations in patients with spontaneous disease are generally within the normal range. We describe here a patient with a pituitary macroadenoma that showed evidence of necrosis on MRI. The patient had an atypical clinical presentation with plasma ACTH levels considerably higher than that seen in patients with non-ectopic ACTH-secretory syndrome, markedly elevated urine free cortisol, lack of phenotypical signs of hypercortisolism such as wide purplish striae, and whose most prominent and distressing symptom was severe myopathy that resulted in the patient becoming bed-ridden. Psychosis was another striking feature in this patient who during his hospital course developed multiple opportunistic infections that contributed to his demise.

CD1a expression in psoriatic skin following treatment with propylthiouracil, an antithyroid thioureylene.

BACKGROUND: The antithyroid thioureylenes, propylthiouracil (PTU) and methimazole (MMI), are effective in the treatment of patients with plaque psoriasis. The mechanism of action of the drugs in psoriasis is unknown. Since the drugs reduce circulating IL-12 levels in patients with Graves' hyperthyroidism, the effect of propylthiouracil on CD1a expression in psoriatic lesions was examined in biopsy samples of patients with plaque psoriasis. CD1a is a marker of differentiated skin antigen presenting cells (APC, Langerhans cells). Langerhans cells and skin monocyte/macrophages are the source of IL-12, a key cytokine involved in the events that lead to formation of the psoriatic plaque. METHODS: Biopsy specimens were obtained from six patients with plaque psoriasis who were treated with 300 mg propylthiouracil (PTU) daily for three months. Clinical response to PTU as assessed by PASI scores, histological changes after treatment, and CD1a expression in lesional skin before and after treatment were studied. RESULTS: Despite significant improvement in clinical and histological parameters the expression of CD1a staining cells in the epidermis did not decline with propylthiouracil treatment. CONCLUSIONS: It appears that the beneficial effect of propylthiouracil in psoriasis is mediated by mechanisms other than by depletion of skin antigen-presenting cells.

Effect of PTU on IL-12 and IL-10 in psoriasis.

Propylthiouracil (PTU), an antithyroid thioureylene with immunomodulatory properties, has been shown to be effective in the therapy of patients with plaque psoriasis. The mechanism of action of antithyroid thioureylenes in psoriasis remains unknown. Propylthiouracil is a commonly used agent in the treatment of patients with Graves' hyperthyroidism, a condition associated with elevated levels of interleukin-12 (IL-12), which fall significantly after propylthiouracil treatment. IL-12 is believed to play a pivotal role in the development of psoriasis. Production of IL-12 is modulated by the anti-inflammatory cytokine IL-10. The effect of PTU on IL-12 and IL-10 levels was, therefore, studied in twelve patients with plaque psoriasis. Treatment with 300 mg of PTU daily in divided doses for three months produced significant improvement of the PASI and histological scores in the patients. Serum IL-12 concentrations were undetectable at baseline and did not change with treatment. IL-10 concentrations were 1.39 +/- 1.49 pg/ml (mean +/- SD) at baseline, and showed no significant change after 2 weeks (1.63 +/- 1.61 pg/ml and 12 weeks 1.15 +/- 1.58 pg/ml of treatment with PTU. The data suggest that the clinical improvement with patients with psoriasis treated with PTU is not due to a fall in circulating IL-12 or a rise in IL-10 concentrations. Although the drug may have effects on lesional production of these cytokines this is not reflected in the circulating levels. It is speculated that the beneficial effect is likely mediated by an inhibitory effect on keratinocyte proliferation or promotion of apoptosis in these proliferated keratinocytes.