Pituitary Abscess Causing Hypopituitarism in a Patient With Acquired Immunodeficiency Syndrome.

Background/Objective: Pituitary abscess is an uncommon infectious process, comprising <1% of pituitary pathology; however, it can be challenging to diagnose and treat. Case Report: A 46-year-old woman with acquired immunodeficiency syndrome (AIDS) presented with headaches, nausea, and visual disturbances. Imaging revealed a sellar mass with peripheral wall enhancement. She was found to have panhypopituitarism. A diagnosis of pituitary abscess was made based on the patient's presentation and imaging results. She was started on broad-spectrum antibiotics, corticosteroids, and thyroid hormone, with improvement of her symptoms and imaging results. Surgery was not performed given the patient's immunocompromised state and improvement with medical therapy. Discussion: Infection spread from neighboring structures is a common cause of pituitary abscess, and such infections can occur after surgery or head trauma. Pituitary abscesses can be difficult to distinguish from other lesions; however, rim enhancement is one of the classic findings. Pituitary dysfunction is common, with secondary adrenal insufficiency and diabetes insipidus being the most common hormonal deficiencies found. In addition to antibiotic therapy, the transsphenoidal debridement approach has been the most common route of treatment. Conclusion: We present a case of pituitary abscess in a patient with AIDS, which likely developed after the patient sustained head trauma. Our patient presented with evidence of panhypopituitarism, requiring emergency treatment. Antibiotic therapy alone was used for treatment. She had to complete a 6-week course of a broad-spectrum antibiotic regimen because the culprit organism could not be identified. Given her posttreatment imaging studies, pituitary function recovery was unlikely because the pituitary gland was completely compromised.

Aggressive Papillary Thyroid Carcinoma Presenting with Metastasis to the Pancreas.

Papillary thyroid cancer is the most common type of thyroid cancer. Aggressive forms tend to metastasize to the lungs and bones, but the abdomen is a rare site of metastasis. We present a 46-year-old male patient who presented with a neck mass associated with shortness of breath and hemoptysis. He was found to have a large thyroid mass on imaging. He underwent a total thyroidectomy with bilateral neck dissection, with pathology showing a multifocal tall cell variant of papillary thyroid carcinoma with lymphovascular invasion in both thyroid lobes. Due to recurrent findings of residual thyroid tissue on whole-body scan imaging, the patient underwent radioactive iodine ablation therapy twice, with poor response to therapy, suggested by persistently elevated thyroglobulin levels. However, the residual tissue responded to external beam radiation. After the initial response to radiation, thyroglobulin was noted to have increased again, prompting a PET-CT after administration of recombinant TSH. PET showed a focal area of increased uptake in the head of the pancreas. The patient underwent the Whipple procedure for resection of the metastasis. Pathology showed papillary thyroid carcinoma with strong and diffuse staining for TTF-1 and thyroglobulin. The patient was started on lenvatinib in the postoperative period and is currently tolerating treatment well with evidence of decreasing thyroglobulin levels. Intra-abdominal metastasis from a thyroid malignancy source is quite rare and can be challenging as far as diagnosis and treatment. Surgical resection can be curative and can be followed by radioactive iodine ablation therapy if cancer cells show avidity. Tyrosine kinase inhibitors can be used in refractory disease. New research is being conducted on new agents that can reverse the resistance to radioactive iodine therapy.

Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease.

Thyroid hormones (TH) have a cardinal role in the development of the central nervous system during embryogenesis and early infancy. However, the TH-responsive genes in the developing brain cease to respond to TH in adulthood. Nevertheless, thyroid dysfunction in adults is commonly associated with a host of cognitive and psychiatric problems. Cognitive decline, dysphoria, and depression are common manifestations of overt hypothyroidism while hyperthyroidism can cause agitation, acute psychosis, and apathy, especially in older people. Whereas levothyroxine treatment can reverse dementia in the setting of hypothyroidism, the effect of levothyroxine on depressive symptoms in subjects with subclinical hypothyroidism is controversial. The use of supraphysiologic doses of TH to treat depression refractory to antidepressant remains a viable therapeutic tool with the caveat that excessive doses of thyroid hormone to treat depression may have potentially damaging effects on other organ systems. The present communication describes the pathophysiology of neuropsychiatric manifestations of thyroid disease, including changes in neurotransmission, alterations in neuronal or glial cell gene expression, blood-brain barrier dysfunction, increased risk of cerebrovascular disease, and occasionally cerebral inflammatory disease in the context of autoimmune thyroid disease. Elucidating the molecular mechanisms of TH effect on cerebral tissue will help identify novel therapeutic targets for managing people with neuropsychiatric disorders.

Insulin mimetic effect of D-allulose on apolipoprotein A-I gene.

Several nutrients modulate the transcriptional activity of the apolipoprotein A-I (apo A-I) gene. To determine the influence of rare sugars on apo A-I expression in hepatic (HepG2) and intestinal derived (Caco-2) cell lines, apo A-I, albumin, and SP1 were quantified with enzyme immunoassay and Western blots while mRNA levels were quantified with real-time polymerase chain reaction. The promoter activity was measured using transient transfection assays with plasmids containing various segments and mutations in the promoter. D-allulose and D-tagatose, increased apo A-I concentration in culture media while D-sorbose and D-allose did not have any measurable effects. D-allulose did not increase apo A-I levels in Caco-2 cells. These changes paralleled the increased mRNA levels and promoter activity. D-allulose-response was mapped at the insulin response core element (IRCE). Mutation of the IRCE decreased the ability of D-allulose and insulin to activate the promoter. Treatment of HepG2 cells, but not Caco-2 cells, with D-alluose and insulin increased SP1 expression relative to control cells. D-allulose augmented the expression and IRCE binding of SP1, an essential transcription factor for the insulin on apo A-I promoter activity. D-allulose can modulate some insulin-responsive genes and may have anti-atherogenic properties, in part due to increasing apo A-I production. PRACTICAL APPLICATIONS: Coronary artery disease (CAD) is the number one cause of mortality in industrialized countries. A risk factor associated with CAD is low high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) concentrations in plasma. Thus, novel therapeutic agents or nutrients that upregulate apo A-I production should be identified. D-allulose and D-tagatose are used as sweeteners and may have favorable effects on insulin resistance and diabetes. This study shows that D-allulose and D-tagatose increases apo A-I production through increased transcription factor SP1-binding to insulin response element of the promoter. These sweeteners modulate some insulin responsive genes, increase the production of apo-A-I, and therefore may have anti-atherogenic properties.

Differential effects of cyclooxygenase-2 (COX-2) inhibitors on endoplasmic reticulum (ER) stress in human coronary artery endothelial cells.

Selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was pulled off the market because of its association with increased risk of adverse cardiovascular effects. The precise underlying mechanism for the differential effects of COX-2 inhibitors on cardiovascular risk is not known. Since endoplasmic reticulum (ER) stress is implicated in atherogenesis, we examined the effects of COX-2 inhibitors on ER stress in primary human coronary artery endothelial cells (HCAEC), human umbilical vein endothelial cells (HUVEC), and human pulmonary artery endothelial cells (HPAEC). ER stress was measured in HCAEC treated with either tunicamycin (TM) or high-concentrations (27.5 mM) of dextrose (HD) using the secreted alkaline phosphatase (ES-TRAP) assay. Markers of the unfolded protein response (UPR) such as activating transcription factor 6 (ATF6), glucose-regulated protein 78 (GRP78), inositol-requiring enzyme 1α (IRE1α), phospho-IRE1α, protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), and phospho-PERK were measured by Western blot. Treatment of HCAEC with TM and HD decreased secreted alkaline phosphatase activity indicating increased ER stress. Treatment of cells exposed to TM or HD with celecoxib, meloxicam, ibuprofen, and acetylsalicylic acid, but not rofecoxib, resulted in a dose-dependent decrease in ER stress. High-dextrose and TM increased IRE1α and PERK phosphorylation and ATF6 and GRP78 expression. Treatment with celecoxib, but not rofecoxib, inhibited these markers of the UPR. Treatment with selective COX-2 inhibitors, with the exception of rofecoxib, suppressed ER stress as measured with both alkaline phosphatase activity assays and markers for the UPR. The inability of rofecoxib to inhibit ER stress, unlike the other cyclooxygenase inhibitors tested, may have contributed to its unfavorable effects on cardiovascular outcomes.

Clavicular Metastasis as an Initial Presentation of Papillary Thyroid Cancer.

OBJECTIVE: We present the case of a 44-year-old man with a large neck mass to highlight the unique presentation of papillary thyroid carcinoma (PTC) metastatic to the clavicle. METHODS: We reviewed the medical record for a detailed history and physical examination findings. Our radiology colleagues examined the diagnostic imaging studies performed. The pathology team reviewed the neck mass biopsy and the confirmatory surgical pathology after total resection of the mass. RESULTS: A 44-year-old man presented with an enlarging neck mass. Initial X-rays revealed a large soft tissue density mass that extended to the midline of the right clavicle. A neck ultrasound established a 5.4 × 3.6 cm mass with increased vascularity and calcification extending from the thyroid. A CT scan noted the extension of the mass into the adjacent sternoclavicular junction with osteolysis of the middle third of the clavicle and the superior aspect of the sternal body. Fine-needle aspiration revealed a thyroid neoplasm with follicular features and positive immunostaining consistent with thyroid carcinoma. The patient underwent a composite resection of the tumor, including a segmental osteotomy of approximately two-thirds of the medial clavicle. The pathology report confirmed PTC with extrathyroidal extension and clavicle involvement (staged pT4a pN0), with further genomic findings showing positive KRAS mutation. CONCLUSION: Clavicular metastasis from differentiated thyroid cancer is rare. While the prognosis is generally favorable, various factors, including age greater than 45 years, poor differentiation, follicular thyroid carcinoma, Hurthle cell variant, and extrapulmonary metastasis, have typically been associated with poorer cancer-specific survival.

Severe recurrent hypoglycaemia in a patient with aggressive melanoma.

We present a case of hypoglycemia in a young patient without diabetes mellitus who presented initially with enlarging neck mass and weight loss, and was found to have aggressive melanoma with metastasis to multiple organs and diffuse lymphadenopathy. He had presented to the emergency room two times with neuroglycopenic symptoms that required admission and intravenous dextrose continuously. Evaluation of hypoglycemia included C-peptide, insulin levels, insulin-like growth factor (IGF) -I and -II, and ß- hydroxybutyrate. Insulin levels were suppressed appropriately during hypoglycemia, however, IGF-II:IGF-I ratio was high, suggesting non-islet tumour induced hypoglycemia. The presence of IGF-II produced by large tumors results in a low hepatic glucose output and increased uptake by skeletal muscle, resulting in hypoglycemia especially in a patient with extremely low appetite such as our patient. Treating the culprit malignancy leads to resolution of hypoglycemia, but corticosteroids have been used to suppress IGF-II levels and alleviate symptoms.

Kaposi sarcoma with musculoskeletal manifestations in a well-controlled HIV patient.

We present here a case of relapsed HIV-related Kaposi Sarcoma (KS), manifesting as a plantar ulcer with underlying bone involvement in a patient with well-controlled HIV. Radiographic and magnetic resonance imaging of the patient's right foot showed bone destruction suggestive of osteomyelitis. However, when a bone biopsy was done, this was consistent with KS, without any signs of bone infection. Patient was initially diagnosed with KS four years prior. He was successfully treated at the time with doxorubicin, radiation therapy, and began HIV therapy. At the time of the KS recurrence, his HIV viral load was undetectable and his CD4 count was over 900 cells/uL (CD4 percentage of 42%). Musculoskeletal (MSK) involvement in KS is a rare manifestation of this disease. The argest series of skeletal KS in people living with HIV by Papanastasopoulos at el. showed a prevalence of only 1.1%. The radiological features of MSK-KS are generally lytic osseous lesions, but presentations may differ. Bone biopsy remains the gold standard for diagnosis, as many other infectious and neoplastic processes can mimic MSK-KS radiographically. In the era of highly active antiretroviral therapy, people living with HIV who are diagnosed with MSK-KS appear to have a substantially improved survival rate than previously described.