Graves orbitopathy: update on diagnosis and therapy.

Graves orbitopathy (GO) is an autoimmune disorder representing the most frequent extrathyroidal manifestation of Graves disease. It is rare, with an age-adjusted incidence of approximately 16.0 cases per 100,000 population per year in women and 2.9 cases per 100,000 population per year in men. GO is an inflammatory process characterized by edema and inflammation of the extraocular muscles and an increase in orbital connective tissue and fat. Despite recent progress in the understanding of its pathogenesis, GO often remains a major diagnostic and therapeutic challenge. It has become increasingly important to classify patients into categories based on disease activity at initial presentation. A Hertel exophthalmometer measurement of >2 mm above normal for race usually categorizes a patient as having moderate-to-severe GO. Encouraging smoking cessation and achieving euthyroidism in the individual patient are important. Simple treatment measures such as lubricants for lid retraction, nocturnal ointments for incomplete eye closure, prisms in diplopia, or botulinum toxin injections for upper-lid retraction can be effective in mild cases of GO. Glucocorticoids, orbital radiotherapy, and decompression/rehabilitative surgery are generally indicated for moderate-to-severe GO and for sight-threatening optic neuropathy. Future therapies, including rituximab aimed at treating the molecular and immunological basis of GO, are under investigation and hold promise for the future.

The various faces of autoimmune endocrinopathies: non-tumoral hypergastrinemia in a patient with lymphocytic colitis and chronic autoimmune gastritis.

Serum gastrin levels exceeding 1000pg/ml (normal, <100) usually raise the suspicion for a neuroendocrine tumor (NET) that secretes gastrin. Rarely, such elevated gastrin levels are seen in patients with pernicious anemia which most commonly is associated with autoimmune gastritis (AG). AG can occur concomitantly with other autoimmune disorders including lymphocytic colitis (LC). Gastrin stimulates enterochromaffin-like cells which increase histamine secretion. Histamine excess can cause diarrhea as can bacterial overgrowth or LC. We present a 57-year-old woman with diarrhea, sporadic epigastric pain, and bloating. She also had a history of interstitial cystitis and took pentosan polysulfate and cetirizine. She had no history of ulcers, renal impairment or carcinoid syndrome. Fasting serum gastrin was 1846pg/ml. Esophagoduodenal gastroscopy and biopsies revealed chronic gastritis and a pH of 7 with low stomach acid. Serum gastrin and plasma chromogranin A were suggestive of a gastrinoma or NET. Pernicious anemia was unlikely. Imaging studies did not reveal any tumor. Random colonic biopsy was compatible with LC, possibly explaining her diarrhea, although we also considered excessive histamine from elevated gastrin, bacterial overgrowth, and pentosan polysulfate which can cause diarrhea and be misleading in this setting, pointing to the diagnosis of gastrinoma. At 4year follow-up in 2012, fasting serum gastrin was 1097pg/ml and the patient asymptomatic taking only cetirizine for nasal allergies. This case illustrates that diarrhea may be associated with very high serum gastrin levels in the setting of chronic gastritis, LC, and interstitial cystitis (pentosan use), without clear evidence for a gastrinoma or NET. If no history of ulcers or liver metastases is present in such cases, watchful observation rather than an extensive/invasive and costly search for a NET may be justified. Considering the various forms of polyglandular syndrome, this may represent a variant and we here provide an algorithm for working up such patients, while also reviewing literature on the intertwined relationship between the immune and endocrine systems.

A case of profound weight loss secondary to use of phentermine.

BACKGROUND: Obesity has become particularly prevalent in both the United States and worldwide. Mississippi continues to lead the nation in prevalence of obesity estimates. The proportion of morbidly obese subjects is increasing at a disproportionately greater rate and the burden of obesity and its complications are more prevalent among ethnic minorities. We present the unique case of a Choctaw lady with morbid obesity who has shown a profound response to pharmacotherapy with phentermine. METHODS: The clinical case history of the patient; a 34-year-old Choctaw lady with morbid obesity, hypertension, hyperlipidemia, and type 2 diabetes is presented, followed by discussion of issues relevant to impacting the obesity epidemic in Mississippi. RESULTS: A 34-year-old Choctaw lady with 1.5 year follow up was noted to have a peak initial body mass index (BMI) of 62.6 kg/m2 and weight of 176 kg. Since commencement of phentermine, initially at 15 mg daily and slowly up-titrated to 37.5 mg daily, she has lost over 23 kg (13% of baseline peak weight) with a current weight of 153 kg and BMI of 54.4 kg/m2. Accompanying the weight reduction has been sustained normal blood pressure and improvement in glycemic control. CONCLUSIONS: Phentermine is a viable and important adjunct in the medical approach to weight management in obese subjects. Its potential utility should be considered even among subjects with morbid obesity. Given its cost it could be a cost effective adjunct in comprehensive weight loss programs for Mississippi that may positively impact the ongoing obesity epidemic. There remains a need for more studies of phentermine to better define its place in obesity management.

Euthyroid Graves' orbitopathy and incidental papillary thyroid microcarcinoma.

UNLABELLED: Euthyroid Graves' orbitopathy (GO) combined with incidental papillary thyroid microcarcinoma has rarely been reported. CASE REPORT: A 61-year-old Caucasian woman initially presented with progressive fatigue, exophthalmos, and thyroid function tests within normal limits. She underwent thyroidectomy, was found to have two incidental papillary thyroid microcarcinomas, and received radioactive iodine ablation to eliminate thyroid antigen. In addition to following her eye disease, TSH-receptor antibodies, thyroid stimulating immunoglobulins, and serum thyroglobulin measurements were recorded, demonstrating no evidence of thyroid cancer at four-year follow-up. At first, she had mild GO, developing into moderate-to-severe GO, and at 4 years she had Hertel measurements of 20 mm in both eyes. CONCLUSION: This report underscores the difficulty of managing GO even when thyroid function is normal(ized) and thyroid antigen exposure has been minimized. In addition, it illustrates why antithyroidal antibodies should be considered in cases of concomitant papillary thyroid cancer, as thyroid cells can be stimulated not only by TSH but also by TSH-receptor stimulating antibodies.

What causes a prolactinoma to be aggressive or to become a pituitary carcinoma?

INTRODUCTION: Malignant prolactinoma is an exceedingly rare endocrine tumor and cannot be diagnosed on histological grounds alone. Similarly to other neuroendocrine tumors such as pheochromocytoma, the mitoses index, Ki-67, p53, and others are utilized in helping understand whether a tumor is benign or malignant or to better predict tumor behavior. We here present the unusual case of an unfortunate young man with an aggressive prolactinoma, the complications of which led to his premature death. CASE REPORT: A 25-year-old white man developed severe headaches, low energy, and decreased libido. A brain magnetic resonance imaging (MRI) showed a 4 x 3 x 2 cm pituitary tumor invading the left cavernous sinus. Laboratory findings revealed elevated prolactin (470 ng/mL) and adrenocorticotropic hormone (ACTH, 82 pg/ml) and decreased total testosterone (176 ng/dl). Visual fields showed superior quadrantanopia in the left eye. Transsphenoidal pituitary resection was undertaken. Pathology revealed a prolactinoma with atypical cells, diffuse p53 nuclear labeling, and a Ki-67 index of 23% (high). Postoperatively, prolactin remained elevated (725-891 ng/ml) and cabergoline was increased to 1 mg three times weekly, with serum prolactin further increasing to 3507 ng/ml five months postoperatively. Repeat MRI revealed extension of the tumor with optic chiasm compression and left orbit invasion. Because of acute left vision loss with ophthalmoplegia, an urgent left frontotemporal craniotomy and tumor resection were conducted. The Ki-67 index of the tumor was 24.8%, the mitotic figure immunostain phosphohistone-H3 positive. Sixty percent (60%) of tumor cells were positive for p53. Cabergoline was increased to 1 mg daily but prolactin remained elevated (770 ng/ml). The patient then underwent proton beam radiation to the area of concern involving the sella. Prolactin thereafter improved to 44 ng/ml. He then developed acute vision loss of the right eye with an MRI showing tumor in the right cavernous sinus. A 15 mm dural-based right temporal mass believed to be a metastasis was also noted. Following this scan, he was considered too high risk for debulking surgery and instead underwent gamma knife irradiation to the sella area. This shrank the right cavernous sinus tumor mass, while the right temporal mass increased in size. The patient developed blindness and left-sided weakness and required enteral feeding and tracheostomy after prolonged intubation. A trial of chemotherapy with temozolomide (350 mg daily for 5 days) near the end of his life was unsuccessful. He died on home hospice 31 months after his first surgery. CONCLUSION: Headaches, vision changes, and symptoms of androgen deficiency syndrome can be manifestations of an aggressive prolactinoma that might require surgery and additional medical therapy including cabergoline and temozolomide with an unpredictable time of survival.

Prevalence and cardiometabolic associations of the glucocorticoid receptor gene polymorphisms N363S and BclI in obese and non-obese black and white Mississippians.

OBJECTIVE: Polymorphisms (SNP) in the glucocorticoid receptor (GR) gene can alter sensitivity to glucocorticoids. Previous studies of the N363S and BclI SNP in the GR gene have shown a metabolic syndrome phenotype in mostly non-African populations. The obesity phenotype of African Americans (AA) seems to be more severe than that of Caucasians. DESIGN: We aimed to assess the prevalence of N363S and BclI in obese and non-obese Caucasian (n=26) and African (n=23) Mississippians (age: 23-63 years) to investigate associations with body composition (body mass index/BMI, waist-to-hip ratio), metabolic parameters (salivary cortisol, fasting glucose and insulin, hemoglobin A1C, fructosamine, HOMA-IR index), and psychological stress perception (blood pressure/BP, perceived stress scale/PSS). RESULTS: All subjects were homozygous for wildtype N363N. BclI polymorphism genotype frequencies among the 23 AA were: homozygous CC (57%), GG (4%), and heterozygous CG (39%), and among the 26 white women: homozygous CC (35%), GG (19%), and heterozygous CG (46%). Linear and logistic regression analyses including a parsimonious model identified BMI as a statistically significant parameter between the two ethnic groups (BMI was 3.13 kg/m2 higher in AA). Within the AA group, BMI, waist-to-hip ratio, log (HOMA-IR), PSS scores, BP, and hyperlipidemia showed no statistically significant relationships for the BclI polymorphism. PSS scores were 15.2 for AA vs. 14.7 for white women (normal mean: 14.7 vs. 12.8). CONCLUSION: Black Mississippians have a higher BMI than whites, which may be related to the presence of the BclI polymorphism and increased glucocorticoid sensitivity. Although more blacks (52%) than whites (38%) had elevated BP, PSS scores in both groups suggest that a high BMI is not regarded as abnormal or stressful. This might negatively impact behavior change regarding lifestyle modifications with increased physical activity and healthier food choices. Larger studies, particularly in African populations, are needed to better define metabolic and psychological characteristics in relation to the N363S and BclI GR gene polymorphisms.

[Is Widal syndrome always a severe disease?]. / Sindromul Widal este totdeauna o maladie severa?

CONTEXT: the Widal syndrome (WS) is known as the association of bronchial asthma to aspirin intolerance, nasal polyposis and/or allergic rhinitis, typical considered to have a difficult course. OBJECTIVES: finding the prevalence and severity of WS in general medical practice. VENUE: data bases from a private pneumology practice and the ambulatory of a pneumology clinic in Timisoara. PARTICIPANTS: 473 asthma patients, among which 41 (8.66%) matched the criteria for WS. There were 31 women (75.6%) and 10 men (24.39%). MAIN PARAMETERS EVALUATED: spirometry, ENT examination, skin allergy tests, serum IgE. RESULTS: most cases (22 pts., 53.65%) had mild to moderate asthma. Monitoring the cases for 4 years didn't show any worsening. The 19 severe cases (46.35%) had a progressive course, despite a complex treatment (anti-leukotrienes + systemic corticosteroids in high doses + long acting beta 2 agonists + long acting theophylline). The results don't match the classical description of WS, with a dominance of severe forms. CONCLUSIONS: in general medical practice WS has a frequency of 8.66% among asthmatic population, and the mild and moderate forms represent 53.65% and it seems they keep like that a long time.