Oncologic manifestations of Klinefelter syndrome.

Klinefelter syndrome (47,XXY) has a prevalence of approximately 1 in 500 males. It is a condition characterized by an extra X chromosome and is an underdiagnosed clinical entity. Inactivation of genes enables their escape from regulatory mechanisms, which can result in such classic physical manifestations as hypogonadism, gynecomastia, infertility, and various hormonal and physical abnormalities. While the endocrine manifestations of 47,XXY are well-known, the oncologic manifestations have received less attention. An association between cancer and 47,XXY has not as yet been clearly defined, with variability noted in the prevalence of different malignancies in 47,XXY patients. The mechanisms underlying these altered oncologic risks are still under debate. Some of the proposed explanations include hormone imbalance, developmental malfunctions, and failed DNA repair mechanisms. However, the recognition of the oncological associations linked to 47,XXY could be helpful. Screening measures in certain malignancies may enable an earlier diagnosis of 47,XXY and the implementation of more customized care in 47,XXY and the mosaic variants.. The data for this review was compiled from relevant PubMed articles published within the last three decades and organized based on cancer type.

Recurrent thyrotoxicosis following near-total thyroidectomy.

Total thyroidectomy for hyperthyroidism is usually curative. We report the unusual recurrence of thyrotoxicosis following a near-total thyroidectomy. The patient, a 27-year-old woman, elected to have a total thyroidectomy and began levothyroxine after the procedure. Approximately 2 years later, recurrent thyrotoxicosis was evident off levothyroxine. Vascularized thyroid tissue was noted on ultrasound, and a radioactive iodine scan indicated increased uptake in the right thyroid region. She began antithyroid medication and was subsequently treated with radioactive iodine once a euthyroid state was achieved. We discuss the implications of this rare scenario-recurrence of thyrotoxicosis after near-total thyroidectomy.

Hypothyroidism following gastric sleeve surgery resolved by ingesting crushed thyroxine tablets.

Bariatric procedures for weight loss have increased in the past few decades. Levothyroxine malabsorption has been reported following gastric bypass; however, few studies have addressed this issue after gastric sleeve procedures. Levothyroxine dosing is usually weight based and administered at approximately 1.6 µg/kg body weight. Absorption occurs mainly in the jejunum and upper ileum, which can be altered by gastric pH, other drugs, food, and other factors. We present a 35-year-old woman with longstanding iatrogenic hypothyroidism treated with thyroxine, whose thyroid-stimulating hormone level rose following a gastric sleeve procedure despite taking levothyroxine daily.

Resolution of hypercalcemia in primary hyperparathyroidism with vitamin D replacement.

Vitamin D deficiency is common in patients with primary hyperparathyroidism. We present a case of primary hyperparathyroidism with a positive parathyroid scan and history of nephrolithiasis. The patient had normal albumin and renal function but was vitamin D deficient. After treatment with vitamin D for 13 months, her parathyroid hormone values declined in parallel with the elevation in vitamin D. Although her total calcium normalized, her ionized calcium remained elevated throughout treatment. We believe vitamin D deficiency should be carefully monitored in primary hyperparathyroidism.

Hypervitaminosis D without toxicity.

Vitamin D deficiency is highly prevalent and there are an increasing number of reports of vitamin D toxicity, mostly related to the misuse of over-the-counter supplements. We report a case with marked hypervitaminosis D (25(OH)D 196 ng/mL) without clinical or biochemical toxicity and normal serum calcium, phosphorus, and 1,25(OH)2D levels. The decline and normalization of the patient's 25(OH)D and urine calcium after cessation of supplements indicated that these supplements were the likely etiology of her hypervitaminosis D. Over-the-counter medications would benefit from regulation by the Food and Drug Administration to prevent incidental toxicity, as seen in our patient.

Ocular Manifestations of von Hippel-Lindau Disease.

In this review article, we aimed to analyze the available data on the ocular manifestations of von Hippel-Lindau (VHL) disease. In this disease, the VHL protein becomes inactivated by germline mutations of the VHL tumor suppressor gene on chromosome 3p25-26, resulting in an overproduction of VEGF in non-hypoxic conditions. Ocular manifestations are expected in roughly half of VHL patients. Retinal capillary hemangioblastomas (RCHs) are the most commonly observed tumors in VHL and are often the initial manifestation of the disease. Ablative therapy, surgical resection, and pharmacotherapy have been implemented to control tumors. Left untreated, RCHs will often enlarge, emphasizing the importance of early diagnosis and treatment to preserve vision. Complications of enlarging peripheral or optic nerve tumors may be severe. Large RCHs may disrupt normal retinal architecture, eventually leading to exudative retinal detachment. Rarely, non-retinal manifestations, such as neovascularization of the iris or cornea, may progress to neovascular glaucoma and vision loss. Ablative therapy of larger tumors carries increasing risks and offers limited success, often necessitating surgical resection. Because this life-threatening disease is not routinely encountered in clinical practice, clinicians will benefit from our review which brings awareness to the ocular presentation of VHL and lifelong screening recommendations for diagnosed patients.

Secondary adrenal insufficiency induced by long-term use of opioid analgesics.

The effects of long-term use of opioid analgesics on the hypothalamic-pituitary-adrenal axis are not well recognized. We report a 41-year-old woman on chronic opioid therapy hospitalized for cardiovascular collapse following a right stellate ganglion nerve block. She developed severe hypotension after the procedure. Morning cortisol was low. The results from the cosyntropin test were consistent with secondary adrenal insufficiency. Her secondary adrenal insufficiency was likely due to long-term use of opioid analgesics for pain in the absence of other etiologies.

Glycemic Disturbances in Pheochromocytoma and Paraganglioma.

In this review article, we aimed to analyze the available data on pheochromocytomas and paragangliomas as it pertains to their not as well-recognized association with significant glycemic abnormalities in the preoperative, perioperative, and postoperative settings as well as how they should be managed clinically. Pheochromocytomas are rare adrenal tumors that account for about 0.1% of hypertension. Paragangliomas, on the other hand, are even less common and have fewer clinical manifestations. Both types of tumors may have unusual modes of presentation which can challenge even the most experienced clinicians and are easy to overlook, resulting in post-mortem diagnosis. We wish to draw further attention to the life-threatening effects on glucose and insulin homeostasis that can occur in the form of hyperglycemic and hypoglycemic states. Hyperglycemia is a result of a glucose intolerant state created in the setting of catecholamine excess, which can present in the form of resistant diabetes, diabetic ketoacidosis (DKA), or even hyperglycemic hyperosmolar states (HHS). In many reported cases, these abnormalities resolve with resection of the tumor. However, past clinicians have also described a state of "reactive hypoglycemia" that can occur following tumor resection, further emphasizing the need for very close perioperative and postoperative monitoring. Severe hypoglycemia may also occur with inherited diseases linked to pheochromocytoma such as von Hippel-Lindau (VHL) disease as well as predominantly epinephrine-producing tumors, given some of the dramatic downstream effects of alpha and beta adrenoceptor agonization. While much of the data remains anecdotal, clinicians will benefit from the awareness of the protean manifestations of these tumors and the varied and lesser-known effects on glucose and insulin homeostasis.

Shifting cervical lymphadenopathy in Hashimoto's disease.

Hashimoto's disease typically presents with hypothyroidism due to lymphocytic infiltration of the thyroid. Cervical lymphadenopathy has rarely been reported in Hashimoto's disease. We report the unusual association of shifting cervical lymphadenopathy with Hashimoto's disease.

Clomiphene for hypogonadism complicated by polycythemia.

Male hypogonadism is associated with poor sexual function. Testosterone therapy via the intramuscular route is the preferred treatment but is associated with secondary polycythemia. We report a patient in whom clomiphene citrate improved hypogonadal symptoms and restored normal free testosterone levels. Clomiphene is inexpensive and can be given orally in secondary hypogonadism. Clomiphene citrate is a promising alternative in patients who develop secondary polycythemia with testosterone.

Transient T3 toxicosis associated with Hashimoto's disease.

In its early course, Hashimoto's disease may present as thyrotoxicosis (Hashitoxicosis). This usually manifests as elevated free T4 and suppressed thyroid-stimulating hormone (TSH). We report the unusual occurrence of an elevated T3 level in a patient with Hashimoto's disease. A 27-year-old woman presented with an incidental finding of elevated free T3 levels, normal free T4 levels, and low TSH levels, which were confirmed with follow-up testing. Her only medication was a birth control pill. There was no family history of thyroid disease. Physical examination was normal. She tested positive for thyroid peroxidase and thyroglobulin antibodies. Thyroid heterogeneity was noted on ultrasound. Two months later, her TSH, free T3, and free T4 were normal and remained normal on subsequent testing. No treatment was administered due to spontaneous resolution of her T3 toxicosis. This case highlights a novel presentation of T3 toxicosis in the setting of Hashimoto's disease with spontaneous resolution.

The Association of Unreported Sleep Disturbances and Systemic Inflammation: Findings from the 2005-2008 NHANES.

BACKGROUND/OBJECTIVE: Sleep apnea is associated with elevated inflammatory markers. A subgroup of patients never report sleep disturbances to their physician. The inflammatory status of this subgroup is not known. The present study aims to evaluate two inflammatory markers, C-reactive protein (CRP) and red cell distribution width (RDW), in those with unreported sleep disturbances and compares these findings to those with and without reported sleep disorders. We also investigate the utility of RDW as an inflammatory marker in sleep disorders. METHODS: Sample includes 9,901 noninstitutionalized, civilian, nonpregnant adults from the 2005-2008 National Health and Nutrition Examination Survey, a nationally representative, cross-sectional U.S. study. Sleep questionnaire and laboratory data were used to compare inflammatory markers (CRP and RDW) in five subgroups of individuals: reporting physician-diagnosed sleep apnea, reporting another physician-diagnosed sleep disorder, reported sleep disturbance to physician with no resulting diagnosis, unreported sleep disturbance (poor sleep quality not reported to physician), and no diagnosed sleep disorder or sleep disturbance. RESULTS: Individuals with unreported sleep disturbance had significantly higher odds of elevated RDW (>13.6%) when compared to those without a sleep disturbance in adjusted models (OR=1.33). Those with unreported sleep disturbance had significantly higher odds of elevated CRP levels (>1 mg/L) than those without sleep disturbances (OR 1.34), although the association was not significant when adjusted for obesity and other controls. CONCLUSION: Self-identified unreported sleep disturbances are associated with significantly higher odds of elevated RDW than those without sleep disturbances. RDW may serve as a valuable indicator in identifying individuals at higher risk for sleep apnea and other sleep disorders.

The Role of Sex Hormones in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelination disorder with an immune-mediated pathophysiology that affects the central nervous system (CNS). Like other autoimmune conditions, it has a predilection for female gender. This suggests a gender bias and a possible hormonal association. Inflammation and demyelination are hallmarks of MS. Oligodendrocytes are the myelinating cells of the CNS and these continue to be generated by oligodendrocyte precursor cells (OPCs). The process of remyelination represents a major form of plasticity in the developing adult CNS. Remyelination does occur in MS, but the process is largely inadequate and/or incomplete. Current treatment strategies primarily focus on reducing inflammation or immunosuppression, but there is a need for more extensive research on re-myelination as a possible mechanism of treatment. Previous studies have shown that pregnancy leads to an increase in OPC proliferation, oligodendrocyte generation and the number of myelinated axons in the maternal CNS. Studies have also suggested that this remyelination is possibly mediated by estriol. Sex hormones in particular have been shown to have an immuno-protective effect in TH1-driven autoimmunity diseases. The aim of our article is to review the available research on sex hormone-specific immune modulatory effects, assess its remyelination potential in MS, and suggest a future path for more extensive research on sex hormone as a target for therapeutics in MS.