Iatrogenic Cushing's Syndrome Following Intra-Articular Triamcinolone Injection in an HIV-Infected Patient on Cobicistat Presenting as a Pulmonary Embolism: Case Report and Literature Review.

BACKGROUND: Iatrogenic Cushing's syndrome (ICS) typically develops after long-term exposure to corticosteroids, but it can occur after a single dose in patients treated with cobicistat or ritonavir for HIV. We present a patient who developed ICS due to the interaction between cobicistat and triamcinolone, a review of the literature, and what to our knowledge is the first case of ICS presenting as a pulmonary embolism. CASE PRESENTATION: A 55-year old male with a past medical history of human immunodeficiency virus, undetectable for 15 years and currently on elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, received 2 intra-articular injections of triamcinolone one month apart for a Baker's cyst in his right knee. He used nasal fluticasone for 9 days in-between the injections. After his second knee injection, he developed easy bruising and friable skin. Over the coming months, he experienced weight gain and Cushingoid facies. Four months after the knee injections he developed a pulmonary embolism and deep vein thrombosis treated with warfarin. The Cushingoid facies prompted an evaluation and diagnosis of ICS along with hypothalamic pituitary adrenal axis suppression. CONCLUSION: This case demonstrates the need to monitor patients on pharmacological boosters with any exposure to corticosteroids, whether it be injected, inhaled, topical, oral or intravenous, as it can lead to profound adrenal suppression and ICS.

Neuroendocrine thymic carcinoma metastatic to the parathyroid gland that was reimplanted into the forearm in patient with multiple endocrine neoplasia type 1 syndrome: a challenging management dilemma.

OBJECTIVE: To describe a unique case of a metastatic thymic carcinoma to the hyperplastic parathyroid gland and to present a challenging management dilemma. METHODS: Our patient is 60-year-old, intellectually disabled man with history of the multiple endocrine neoplasia type 1 (MEN1) syndrome, a surgery in 1985 for hypercalcemia with removal of one parathyroid gland, surgery in 2007 with findings of extensively necrotic well differentiated neuroendocrine carcinoma (carcinoid tumor) of the thymus. In 2012, he presented with persistent hypercalcemia (calcium level 11.7 mg/dL [range, 8.6-10.2]), and a parathyroid hormone (PTH) level of 225 pg/mL (range, 15-65 pg/mL). He underwent a repeat neck exploration with removal of 2 small inferior and a large left superior 4.5 × 2.5 × 1.5 cm parathyroid glands, all of which showed hyperplasia on intraoperative frozen section. A small portion of the superior gland was reimplanted into the patient's forearm. Final pathology showed the presence of a focus of neuroendocrine tumor within the left superior parathyroid gland with immunostain identical to the thymic carcinoma. His postoperative PTH level was 14 pg/mL and calcium 8.5 mg/dL. A positron emission tomography-computed tomography (PET-CT) and octreotide scans revealed an extensive metastatic disease within the lung, mediastinum, and bones. RESULTS: We decided to leave a portion of the reimplanted parathyroid gland with possible metastatic thymic carcinoid in his forearm because of the presence a widespread metastatic disease and his intellectual disability that would result in noncompliance with calcium replacement in case of permanent hypocalcemia. CONCLUSION: Metastatic thymic carcinoma to the parathyroid gland has never been reported in the literature. We have described the first case and presented a challenging management dilemma.

Elevated circulating IGF-I promotes mammary gland development and proliferation.

Animal studies have shown that IGF-I is essential for mammary gland development. Previous studies have suggested that local IGF-I rather than circulating IGF-I is the major mediator of mammary gland development. In the present study we used the hepatic IGF-I transgenic (HIT) and IGF-I knockout/HIT (KO-HIT) mouse models to examine the effects of enhanced circulating IGF-I on mammary development in the presence and absence of local IGF-I. HIT mice express the rat IGF-I transgene under the transthyretin promoter in the liver and have elevated circulating IGF-I and normal tissue IGF-I levels. The KO-HIT mice have no tissue IGF-I and increased circulating IGF-I. Analysis of mammary gland development reveals a greater degree of complexity in HIT mice as compared to control and KO-HIT mice, which demonstrate similar degrees of mammary gland complexity. Immunohistochemical evaluation of glands of HIT mice also suggests an enhanced degree of proliferation of the mammary gland, whereas KO-HIT mice exhibit mammary gland proliferation similar to control mice. In addition, HIT mice have a higher percentage of proliferating myoepithelial and luminal cells than control mice, whereas KO-HIT mice have an equivalent percentage of proliferating myoepithelial and luminal cells as control mice. Thus, our findings show that elevated circulating IGF-I levels are sufficient to promote normal pubertal mammary epithelial development. However, HIT mice demonstrate more pronounced mammary gland development when compared to control and KO-HIT mice. This suggests that both local and endocrine IGF-I play roles in mammary gland development and that elevated circulating IGF-I accelerates mammary epithelial proliferation.

Insulin-mediated acceleration of breast cancer development and progression in a nonobese model of type 2 diabetes.

Epidemiologic studies suggest that type 2 diabetes (T2D) increases breast cancer risk and mortality, but there is limited experimental evidence supporting this association. Moreover, there has not been any definition of a pathophysiological pathway that diabetes may use to promote tumorigenesis. In the present study, we used the MKR mouse model of T2D to investigate molecular mechanisms that link T2D to breast cancer development and progression. MKR mice harbor a transgene encoding a dominant-negative, kinase-dead human insulin-like growth factor-I receptor (IGF-IR) that is expressed exclusively in skeletal muscle, where it acts to inactivate endogenous insulin receptor (IR) and IGF-IR. Although lean female MKR mice are insulin resistant and glucose intolerant, displaying accelerated mammary gland development and enhanced phosphorylation of IR/IGF-IR and Akt in mammary tissue, in the context of three different mouse models of breast cancer, these metabolic abnormalities were found to accelerate the development of hyperplastic precancerous lesions. Normal or malignant mammary tissue isolated from these mice exhibited increased phosphorylation of IR/IGF-IR and Akt, whereas extracellular signal-regulated kinase 1/2 phosphorylation was largely unaffected. Tumor-promoting effects of T2D in the models were reversed by pharmacological blockade of IR/IGF-IR signaling by the small-molecule tyrosine kinase inhibitor BMS-536924. Our findings offer compelling experimental evidence that T2D accelerates mammary gland development and carcinogenesis,and that the IR and/or the IGF-IR are major mediators of these effects.

The role of endocrine insulin-like growth factor-I and insulin in breast cancer.

Epidemiologic studies demonstrate that breast cancer is the most common type of cancer diagnosed in women and is a significant cause of morbidity and mortality. While there are many risk factors known to be associated with increased breast cancer risk, this review will focus specifically on circulating IGF-I, hyperinsulinemia, and type 2 diabetes. Their effects on promoting breast cancer development, progression, and adverse outcomes have been demonstrated in both animal and human studies, suggesting that the IGF system is a potential target for breast cancer therapy. In addition, in the clinical setting, emphasizing metabolic risk modifications to patients including weight loss, dietary changes, and diabetes control may also play an important role in breast cancer risk reduction.

Insulin resistance as the underlying cause for the metabolic syndrome.

Classically, the metabolic syndrome is characterized as group of pathologies including visceral obesity, hypertension, dyslipidemia, and impaired glucose tolerance. It is now realized that insulin resistance plays a principal role in initiating and perpetuating the pathologic manifestations of the metabolic syndrome. A more in-depth understanding of the basic pathophysiologic mechanisms underlying insulin resistance may aid clinicians in treating and possibly delaying or even preventing the onset of the metabolic syndrome and its complications. This article outlines how abnormal insulin signaling and secretion, impaired glucose disposal, lipotoxicity, and proinflammatory cytokines exacerbate insulin resistance and result in the perturbations of the metabolic syndrome.

Appropriateness of the Ilfeld Psychiatric Symptom Index as a screening tool for depressive symptomatology in persons with spinal cord injury.

BACKGROUND: Depressive symptomatology is seen in some persons with spinal cord injury (SCI). Identification of a depressed mood can assist clinicians in early treatment. The Ilfeld Psychiatric Symptom Index (Ilfeld PSI) is a screening tool that assesses a range of symptoms: depression, cognitive disturbance, anxiety, and anger. The purpose of this study was to compare the efficacy of the Ilfeld PSI to the Zung Self-Rating Depression Scale (Zung SRS) in persons with chronic SCI. DESIGN: This was a case-control study. METHODS: A total of 59 subjects completed the study: 20 persons with tetraplegia, 19 with paraplegia, and 20 age-matched able-bodied controls. The total scores for both measures were analyzed using Pearson correlation, analysis of variance, and chi-square tests. RESULTS: The Zung SRS total scores correlated with the Ilfeld PSI subscales and index scores. When using the traditional cutoff scores, there was a low level of agreement between scales. The Ilfeld PSI classified 79% of the SCI group and 75% of controls as depressed. In contrast, 8% of the SCI group and none of the controls met criteria for depression using the Zung SRS. CONCLUSIONS: The Ilfeld PSI screens for a broad range of symptoms; however, it poorly discriminates somatic symptoms unrelated to depression. Therefore, the Ilfeld PSI may not be a useful instrument for persons with SCI.