ACTH-secreting metastatic prostate cancer with neuroendocrine differentiation.

Cushing's syndrome (CS) due to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) can result from a variety of tumours and rarely from those of prostatic origin. We present a male patient in his early 60s with ACTH-secreting metastatic prostate adenocarcinoma with neuroendocrine differentiation (ICD-O code 8574/3) years after prostatectomy and androgen-deprivation therapy, initially presenting with Cushingoid features. After open radical prostatectomy and bilateral orchiectomy for disease recurrence, the patient was found to have metastatic liver and bone lesions highly suggestive of metastatic prostatic cancer. About 10% of cells on liver biopsy expressed ACTH, a finding consistent with EAS as the cause of CS. His stay was complicated with multiple infections and ultimate death. Hence, we report a case of metastatic prostate adenocarcinoma with neuroendocrine differentiation who presented with CS. We also emphasize the importance of adequate and timely treatment.

Bilateral biochemically silent pheochromocytoma, not silent after all.

Pheochromocytoma is a sympathetic paraganglioma originating from the chromaffin cells. They are bilateral in 10% of cases and occur as a part of a MEN 2A or 2B syndromes. This is a case of bilateral asymptomatic pheochromocytomas diagnosed incidentally on imaging in a woman being investigated for secondary infertility. Laboratory tests were negative. Whole body FDG scan showed avid uptake of the tracer by both adrenal masses, but none in the thyroid. Hypertensive crisis occurred during right adrenalectomy on an unprepared patient in spite of clamping the adrenal vein, which raises the need for alpha-adrenergic blockade for patients undergoing adrenalectomy.

Adaptation of child oral health education leaflets for Arabic migrants in Australia: a qualitative study.

BACKGROUND: The purpose of this study was to gain an in-depth understanding of Arabic-speaking mothers views on the usefulness of existing oral health education leaflets aimed at young children and also to record their views on the tailored versions of these leaflets. METHODS: This qualitative study was nested within a large ongoing birth cohort study in South Western Sydney, Australia. Arabic-speaking mothers (n = 19) with young children were purposively selected and approached for a semi-structured interview. Two original English leaflets giving advice on young children's oral health were sent to mother's prior to the interview. On the day of interview, mothers were given simplified-English and Arabic versions of both the leaflets and were asked to compare the three versions. Interviews were audio-recorded, subsequently transcribed verbatim and analysed by thematic analysis. Ethical approval was obtained from Human Research Ethics Committees of the former Sydney South West Area Health Service, University of Sydney and Western Sydney University. RESULTS: Mothers reported that simplified English together with the Arabic version of the leaflets were useful sources of information. Although many mothers favoured the simplified version over original English leaflets, the majority favoured the leaflets in Arabic. Ideally, a "dual Arabic - simplified English leaflet" was preferred. The understanding of key health messages was optimised through a simple layout and visual images. CONCLUSIONS: There is a need to tailor oral health education leaflets for Arabic-speaking migrants. Producers of dental leaflets should also consider a "dual Arabic - simplified English leaflet" to improve oral health knowledge of Arabic-speaking migrants. The use of simple layout and pictures assists Arabic-speaking migrants to understand the content of dental leaflets.

The use of statins in people at risk of developing diabetes mellitus: evidence and guidance for clinical practice.

Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these claims and provides practical guidance for primary care physicians on the use of statins in people with or at risk of developing T2D. Overall, evidence suggests that the benefits of statins for the reduction of CV risk far outweigh the risk of developing T2D, especially in individuals with higher CV risk. To reduce the risk of developing T2D, physicians should assess all patients for T2D risk prior to starting statin therapy, educate patients about their risks, and encourage risk-reduction through lifestyle changes. Whether some statins are more diabetogenic than others requires further study. Statin-treated patients at high risk of developing T2D should regularly be monitored for changes in blood glucose or HbA1c levels, and the risk of conversion from pre-diabetes to T2D should be reduced by intensifying lifestyle changes. Should a patient develop T2D during statin treatment, physicians should continue with statin therapy and manage T2D in accordance with relevant national guidelines.

Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment.

Tyrosine kinase inhibitors (TKI) belong to a new class of molecular multitargeted anticancer therapy which targets different growth factor receptors and hence attenuates cancer cell survival and growth. Since their introduction as adjunct treatment for renal cell carcinoma and gastrointestinal stromal tumors (GIST), a number of reports have demonstrated that TKI can induce thyroid dysfunction which was especially more common with sunitinib maleate. Many mechanisms with respect to this adverse effect of tyrosine kinase inhibitors have been proposed including their induction of thyroiditis, capillary regression in the thyroid gland, antithyroid peroxidase antibody production, and their ability to decrease iodine uptake by the thyroid gland. Of interest is the observation that TKI-induced thyroid dysfunction may actually be protective as it was shown to improve overall survival, and it was suggested that it may have a prognostic value. Followup on thyroid function tests while patients are maintained on tyrosine kinase inhibitor is strongly recommended. When thyroid dysfunction occurs, appropriate treatment should be individualized depending on patients symptoms and thyroid stimulating hormone level.

Role of Gut-Related Peptides and Other Hormones in the Amelioration of Type 2 Diabetes after Roux-en-Y Gastric Bypass Surgery.

Bariatric surgery is currently the most effective and durable therapy for obesity. Roux-en-Y gastric bypass surgery, the most commonly performed procedure worldwide, causes substantial weight loss and improvement in several comorbidities associated with obesity, especially type 2 diabetes. Several mechanisms are proposed to explain the improvement in glucose metabolism after RYGB surgery: the caloric restriction and weight loss per se, the improvement in insulin resistance and beta cell function, and finally the alterations in the various gastrointestinal hormones and adipokines that have been shown to play an important role in glucose homeostasis. However, the timing, exact changes of these hormones, and the relative importance of these changes in the metabolic improvement postbariatric surgery remain to be further clarified. This paper reviews the various changes post-RYGB in adipokines and gut peptides in subjects with T2D.

Parathyromatosis: a rare yet problematic etiology of recurrent and persistent hyperparathyroidism.

Recurrent or persistent hyperparathyroidism is an uncommon yet challenging clinical problem, and parathyromatosis is one of its very rare causes. In this minireview, we review causes of recurrent hyperparathyroidism and all cases of parathyromatosis available in the literature. The clinical course of a case of parathyromatosis with the longest follow-up (1977-2011) is described. Similar cases reported between 1975 and the present are reviewed and analyzed to characterize the clinical presentation, course, and management of this rare condition. Parathyromatosis, which is benign parathyroid tissue seeding, has been detailed in 35 patients in the English literature. The majority were female subjects, with end-stage renal disease, in their fifth to sixth decade of life. In most cases, the diagnosis was made intraoperatively; and the condition was often refractory to surgery. A calcimimetic agent was used in 5 cases with end-stage renal disease; serum calcium and/or parathyroid hormone levels decreased in 4 subjects, but only one was reported to experience increments in bone density. Medical management combining a calcimimetic with a bisphosphonate may therefore be a preferred alternative.

25-hydroxyvitamin D assay variations and impact on clinical decision making.

CONTEXT: Laboratories are increasingly shifting to new automated 25-hydroxyvitamin D (25-OHD) assays, with subsequent variability in results. OBJECTIVE/SETTING: We describe the experience at our center with such a shift and illustrate its clinical implications. METHODS: 25-OHD levels were measured in 494 patients using Immunodiagnostic Systems RIA (IDS-RIA) and DiaSorin Liaison assays. Sources of variability between the assays were investigated in a subset of 83 samples, retested in the reference laboratory in the United States, and by reviewing the performance reports issued by the International Vitamin D External Quality Assessment Scheme, DEQAS. 25-OHD cut-points for target levels were used to compare the two assays. RESULTS: 25-OHD concentrations were significantly lower when measured with Liaison as compared to IDS-RIA: mean bias was -5 ng/ml, range was -38.1 to 18.7 ng/ml, P<0.001; the absolute bias was independent of 25-OHD value. Interassay variability was also detected in values obtained in the reference laboratory and in DEQAS reports. Using 20 ng/ml as the target 25-OHD level, 52% of patients required treatment when tested by Liaison, as opposed to 36% by IDS-RIA (P<0.001). Using 30 ng/ml as the desirable level, the proportions were 79 and 64%, respectively (P<0.001). The two assays agreed in only 41-68% of subjects, proportions that depended on criteria used to define agreement. CONCLUSION: A change in 25-OHD assays has a significant impact on results, patient classification, and treatment recommendations. Such variability cannot be ignored when deriving and applying vitamin D guidelines. It also renders universal assay standardization a pressing call.

Nonmydriatic retinal image review at time of endocrinology visit results in short-term HbA1c reduction in poorly controlled patients with diabetic retinopathy.

OBJECTIVES: The objective of this study was to evaluate the effect of discussing retinal findings following nonmydriatic retinal imaging during an endocrinology visit on subsequent HbA1c in poorly controlled diabetic patients with diabetic retinopathy (DR). MATERIALS AND METHODS: During a visit to an endocrinologist, patients with DR and documented HbA1c ≥ 8.0% within the preceding month were assigned to either addition of nonmydriatic imaging and discussion of retinal findings or standard endocrinology evaluation alone. Ophthalmology care was otherwise the same in both groups. Changes in HbA1c were evaluated 3 months later. RESULTS: One hundred thirteen (94%) of the original 120 subjects completed the study. The mean HbA1c change in the retinal imaging group was a decline of 1.35%, whereas the control group had a 0.26% increase. Controlling for gender, age, duration of diabetes, presence of hypertension, and use of insulin, the difference between groups was significant (p<0.0003). CONCLUSIONS: Nonmydriatic imaging and discussion of retinal findings during an endocrinologist visit may contribute, at least in the short term, to improved glycemic control in patients with DR and elevated HbA1c.

Outcome of thyroid associated ophthalmopathy treated by radiation therapy.

Thyroid associated orbitopathy is a common manifestation of Graves disease. Many options can be considered for treatment. In this case series, we reviewed the medical records of 17 patients who received radiation therapy (RT) for GO in a tertiary care center between 1997 and 2007. All patients received 20 Gy to both orbits and 12 of them (71%) had already received one or more trials of steroid therapy prior to RT. After a median follow-up of 2 years, a subjective improvement in exophthalmos and vision was reported by all patients at the end of RT but only 3 patients reported a decrease in their diplopia immediately after therapy. Symptoms continued to improve with time in many patients: 22% had complete reversal of their symptoms and signs, and the remaining 78% had partial improvement. Two patients developed recurrent signs and symptoms, both of them were smokers who continued to smoke after treatment. About 60-65% of patients responded favorably to RT alone which increased to 87-97% when RT is combined with steroids. No patients developed late toxicity during the follow-up period. We conclude that RT is an effective treatment option in GO even in patients who failed previous treatment with steroids or surgical decompression. Based on our own clinical experiences and the literature data, the combination of RT and intravenous corticosteroid administration may improve the response rate.

Antiphospholipid syndrome: endocrinologic manifestations and organ involvement.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic tendency that affects most organ systems in the human body. In this report, we present a review of the endocrinologic manifestations associated with APS by evaluating the medical literature from 1968 to 2009 using MEDLINE and these keywords: APS, antiphospholipid syndrome, antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant, anti ß-2 glycoprotein I, pituitary, adrenal, thyroid, parathyroid, ovary, testes, diabetes mellitus, and diabetes insipidus. Adrenal insufficiency was found to be the most common endocrine manifestation associated with APS. Autoimmune thyroid disease was associated with increased titers of antiphospholipid antibodies (aPL) without any APS clinical manifestations. In addition, hypopituitarism and Sheehan syndrome are increasingly being reported in association with aPL. Data regarding the prevalence and significance of aPL in diabetic patients remains uncertain. Finally, only a few cases of ovarian and testicular derangements have been reported. APS should be considered in any patient with adrenal insufficiency even in the absence of other thrombotic manifestations. It is also advisable to assess aPL in the sera of patients presenting with pituitary insufficiency. Further studies are needed to clarify the relationship between aPL and thyroid disorders and diabetes mellitus.

Thyroid cancer in Lebanese children and adolescents: a 15-year experience at a single institution.

BACKGROUND AND AIM: Thyroid carcinomas are rare in childhood and adolescence. Management of this entity remains controversial. The aim of this study is to review our experience with multidisciplinary management of papillary thyroid cancer in the pediatric population at a tertiary care specialized medical center in Lebanon. PROCEDURE: The medical records of all patients with thyroid cancer younger than 20 years who presented to our center between January 1991 and January 2006 were reviewed. RESULTS: Thirteen patients with papillary thyroid carcinoma (PTC) were identified. No patient had previous exposure to ionizing radiation. The mean age at diagnosis was 14.5 years. There were 8 females; all patients presented with a cervical mass. Ten patients underwent total thyroidectomy and three subtotal thyroidectomy. Eight patients (61.5%) had regional lymph node metastases, only one of whom (7.6%) had lung metastases. All received radioactive "131I" ablation postsurgical excision. Five (38.5%) had recurrences and needed multiple surgeries and/or "131I" ablation. At a median follow-up time of 8.3 years all patients are disease free. CONCLUSION: Pediatric thyroid cancer in Lebanon is a rare tumor that presents mainly as a primary malignancy. The main clinical presentation is a cervical mass with locoregional lymph nodes metastasis. The mainstay of therapy is total thyroidectomy with lymph node dissection when indicated and radioactive "131I" ablation. Despite recurrences the prognosis is excellent.

Prevalence and determinants of retinopathy in a cohort of Lebanese type II diabetic patients.

OBJECTIVE: Our aim was to determine the prevalence and the risk factors for diabetic retinopathy (DR) in a cohort of type II diabetic patients in Lebanon. DESIGN: Prospective observational cohort study. PARTICIPANTS: Five hundred consecutive patients with type II diabetes mellitus followed at the American University of Beirut Medical Center diabetes clinic were enrolled in the study. METHODS: All patients 18 years or older with diabetes mellitus who did not have gestational diabetes and who were able to complete the laboratory data and the retinal examination were invited to participate in the study; they were followed up for a period of 3 years. RESULTS: DR was present in 175 patients (35%), 130 (26%), and 45 (9%) having nonproliferative and proliferative DR, respectively. Clinically significant macular edema was present in 42 patients (8%). Microvascular and macrovascular diabetic complications, duration of disease, glycemic control, presence of hypertension (p < 0.003), systolic blood pressure (p = 0.04), and insulin use (p < 0.001) were individually significantly associated with a higher prevalence of DR on bivariate analysis. However, on multivariate regression analysis, only glycosylated hemoglobin >7% (odds ratio [OR] 2.81, 95% CI 1.06-7.43, p = 0.038), duration of diabetes (per 10 years, OR 9.0, 95% CI 4.0-20.0, p < 0.001), macroalbuminuria (OR 2.6, 95% CI 1.14-5.96 p = 0.023), and systolic blood pressure (per 10 mm Hg, OR 1.27, 95% CI 1.0-1.56, p = 0.037) were independent risk factors for DR. CONCLUSIONS: The elevated prevalence of DR in type II diabetic patients with high risk profiles calls for early medical intervention and education about DR and its identified controllable risk factors.

An unusual case of autonomous hyperparathyroidism in a patient with X-linked hypophosphatemic rickets and Kallmann syndrome.

We are reporting an unusual patient who presented to our medical center at 18 years of age for evaluation of disabling bilateral lower extremity deformity and delayed puberty. Extensive clinical, laboratory, and radiologic evaluation confirmed the coexistence of 2 X-linked inherited disorders, X-linked hypophosphatemic rickets (XLH) and Kallmann syndrome (KS). Treatment with oral phosphate and calcitriol along with intramuscular testosterone injections was initiated. Despite a dramatic response, the course of treatment was complicated by secondary hyperparathyroidism and, 13 years later, by the development of an autonomous parathyroid adenoma that was surgically resected. Furthermore, the coexistence of XLH and KS has not been reported before. We believe that the proximity of the KAL-1 gene (Xp 22.3), involved in the pathogenesis of KS, to the phosphate regulating endopeptidase on the X chromosome gene (Xp 22.1-22.2), involved in XLH, might be responsible for this association.

Prevalence and determinants of albuminuria in a cohort of diabetic patients in Lebanon.

BACKGROUND AND OBJECTIVES: Few data are available on the extent of albuminuria in diabetic populations in the Middle East generally and in Lebanon specifically. We conducted this study to determine the prevalence of albuminuria and its major risk factors in a cohort of diabetic patients in Lebanon. PATIENTS AND METHODS: Diabetic patients followed in the outpatient department at the American University of Beirut Medical Center (AUBMC) were included in a prospective observational study. AUBMC is a tertiary referral center and the outpatient department typically handles patients of low socioeconomic status with advanced disease. Patients were classified according to their urinary albumin-to-creatinine ratio (ACR) as having normoalbuminuria (ACR<30 mg/g creatinine), microalbuminuria (ACR=30 to <300 mg/g creatinine), or macroalbuminuria (ACR > or =300 mg/g creatinine). The three groups were compared to analyze the association between albuminuria and its risk factors. In addition, independent predictors of albuminuria were determined using multivariate logistic regression and presented as an odds ratio. RESULTS: Microalbuminuria and macroalbuminuria were present in 33.3% and 12.7% of 222 patients (mean age 56.4 years, mean deviation of diabetes 8.6 years, 58.7% women, 43.8% obese), respectively. Factors significantly associated with microalbuminuria included glycemic control, insulin use, and total and LDL cholesterol. Those associated with macroalbuminuria included in addition to glycemic control and insulin use, duration of diabetes, hypertension, elevated mean arterial pressure (MAP), and presence of neuropathy, retinopathy and peripheral vascular disease by bivariate analysis. Only glycemic control was an independent risk factor for both in addition to MAP and retinopathy for macroalbuminuria by multivariate analysis. CONCLUSION: Albuminuria is highly prevalent among this cohort of diabetic patients in Lebanon. Both glycemic control and blood pressure need to be better targeted in its management.

The association of Hashimoto disease and Congo red negative amyloidosis.

Systemic amyloidosis which is characterized by extracellular deposition of monoclonal immunoglobulin light chains in various organs may be difficult to diagnose at an early stage, especially when the Congo red stain is negative. We describe herein a case of Congo red negative primary amyloidosis associated with Hashimoto thyroiditis. The patient presented with multiple organ involvement suggestive of amyloidosis including heart failure, renal failure, and macroglossia. Serum and urine immunofixation studies were positive for monoclonal chains. Even though a biopsy taken from the enlarged tongue of the patient was negative when stained with Congo red, electron microscopy showed ultrastructural features of amyloid deposition. In conclusion, we are reporting a rare case of primary amyloidosis with a negative Congo red stain associated with Hashimoto thyroiditis.

Marked hypocalcemia after tocolytic magnesium sulphate therapy.

Symptomatic hypocalcemia has been reported infrequently in association with magnesium sulfate (MgSO (4)) tocolytic therapy. We report a 38-year-old woman who presented in preterm labor at 24 3/7 weeks. Twenty hours after starting MgSO (4), she developed chest pain. Studies revealed therapeutic serum Mg level, total serum calcium (Ca) = 5.5 mg/dL, 24-hour urine Ca = 763.9 mg, and low serum uric acid and phosphate levels. All studies corrected day 1 postpartum; urine Ca level corrected on day 2. Even short courses of MgSO (4) can result in severe hypocalcemia, raising the question of whether Ca levels should be routinely monitored.

Papillary carcinoma arising in a thyroglossal duct cyst; two case reports and review of the literature.

We present in this report two cases of papillary carcinoma arising in a thyroglossal duct cyst. The first case was a 32-year-old female patient who presented with a neck mass of 5 years' duration that had recently increased in size. The patient was otherwise asymptomatic. The second patient was a 41-year-old male patient who presented with a submental mass that had been growing over the previous several months. Associated symptoms included local symptoms such as dysphagia and hoarseness and general symptoms such as fatigue and weight loss. Pathological examination revealed the presence of papillary carcinoma in the mass with presence of focus of papillary carcinoma in the thyroid bed in both cases. Periosseous invasion of the hyoid bone and involvement of the submandibular lymph nodes were observed in the second patient. The patients underwent total thyroidectomy with lymph node dissection followed by radioactive iodine therapy and are currently on thyroxin replacement.