Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum total testosterone, total 17 beta-estradiol, LH, FSH, and PRL concentrations were measured by RIA in 59 homosexual men infected with the human immunodeficiency virus (32 clinically healthy antibody-positive men (HH+), 20 men with acquired immune deficiency syndrome (AIDS), and 7 men with AIDS-related complex (ARC). The results were compared with those of 26 antibody-negative homosexual men (HH-) who served as controls. The mean serum total testosterone concentration was significantly lower in the men with AIDS [414 +/- 230 (+/- SD) ng/dL (14.5 +/- 8.0)] than in the HH- men [550 +/- 172 ng/dL (19.0 +/- 6.0 nmol/L); P less than 0.05]. The mean serum LH level was significantly higher in the men with AIDS (26 +/- 14 vs. 14 +/- 4 IU/L in HH- men; P less than 0.01) and slightly but significantly higher in the men with ARC (19 +/- 8 IU/L; 0.10 greater than P greater than 0.05). Serum FSH also was significantly higher in the men with AIDS (P less than 0.05). Serum PRL was significantly higher in the men with ARC (10 +/- 2 micrograms/L; P less than 0.05) and AIDS (16 +/- 10 micrograms/L; P less than 0.001) than in the HH- men (8 +/- 3 micrograms/L). Serum sex hormone-binding globulin levels were similar in HH- men and men with AIDS as were serum T responses to hCG administration for 2 days. These results suggest that alterations of the hypothalamic-pituitary-gonadal axis indicative of primary hypogonadism accompany human immunodeficiency virus infection in homosexual men.
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PMID:Changes in the hypothalamic-pituitary-gonadal axis in human immunodeficiency virus-infected homosexual men. 249 26

Physicians who think epidemiologically are rare. A method is suggested for detecting their aptitude early in their career when help may be offered to make the most of their special talent. Clusters geographically or in families may provide clues to cancer etiology. Clusters have been systematically thought by mapping cancer mortality in the US and independently in China. Case-control studies have revealed environmental exposure responsible for some of the clusters. Clusters noted by alert clinicians or other astute observers have revealed most of the known environmental causes of human cancers. Genetic influence in carcinogenesis has been identified by studies of peculiar cancer occurrence, such as familial aggregation, multiple primary cancer or the occurrence of cancer with other diseases as, for example, congenital malformations and immunodeficiency disorders. Ethnic differences in cancer occurrence may be revealing. Thus, in Japan there is low frequency of B-cell lymphoma but high frequency of certain autoimmune diseases, as if inherent protection against one predisposes the other. As a rule of thumb, the occurrence of three rare observations is not likely to be due to chance. Examples include ideal carcinoma in three persons with cystic fibrosis of the pancreas who survived to about 30 years of age, and the occurrence in Klinefelter's syndrome of germ cell tumor of the pineal--a neoplasm that has an unusually high frequency in Japan. Finally, the history of discoveries concerning cancer etiology, an aspect of what Comroe has called "research on research", can point the way to new discoveries in the future.
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PMID:Nakahara memorial lecture. Rare events and cancer epidemiology. 333 98

Gonadal, adrenal, and thyroid functions were evaluated in 70 men seropositive for human immunodeficiency virus (HIV) infection, clinically categorized as asymptomatic (n = 19), AIDS-related complex (ARC) (n = 9), or acquired immunodeficiency syndrome (AIDS) (n = 42). Twenty of 40 men (50 percent) with AIDS were hypogonadal. Mean serum testosterone concentrations in both ARC (292 +/- 70 ng/dl) and AIDS (401 +/- 30 ng/dl) men were significantly less than in asymptomatic (567 +/- 49 ng/dl) or normal men (608 +/- 121 ng/dl). Of these hypogonadal men, 18 of 24 (75 percent) had hypogonadotropic hypogonadism. Seven of eight hypogonadal men (88 percent) had a normal gonadotropin response to gonadotropin-releasing hormone administration. Hypogonadism correlated with lymphocyte depletion and weight loss. Adrenal cortisol reserve, evaluated by adrenocorticotropin stimulation, was normal in 36 of 39 patients (92 percent) with AIDS. Indices of thyroid function were normal with the exception of one ARC man with a low free thyroxine index. In conclusion, hypogonadism is common in men with HIV infection and may be the first or most sensitive endocrine abnormality.
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PMID:Endocrine disorders in men infected with human immunodeficiency virus. 334 69

A 54-year-old man of Persian origin presented to our department with a 1-year history of ulcers on the right leg that had been unresponsive to numerous topical treatments, accompanied by lymphedema of the right leg. Medical history included hypergonadotropic hypogonadism, which had not been further investigated. He was treated for 20 years with testosterone IM once monthly, which he stopped a year before the current hospitalization for unclear reasons. The patient reported no congenital lymphedema. Physical examination revealed two deep skin ulcers (Figure 1) on the right leg measuring 10 cm in diameter with raised irregular inflammatory borders and a boggy, necrotic base discharging a purulent hemorrhagic exudate. Bilateral leg pitting edema and right lymphangitis with lymphadenitis were noted. He had low head hair implantment, sparse hair on the body and head, hyperpigmentation on both legs, onychodystrophia of the toenails (mainly the large toe and less prominent on the other toes), which was atrophic lichen-planus-like in appearance and needed no trimming (Figure 2), normal hand nails, oral thrush, and angular cheilitis. Other physical findings were gynecomastia, pectus excavatum, small and firm testicles, long extremities, asymmetrical goiter, systolic murmur 2/6 in left sternal border, and slow and inappropriate behavior. The patient's temperature on admission was 39 degrees C. Blood cultures were negative for bacterial growth. Results of laboratory investigations included hemoglobin (11.2 g/dL), hematocrit (26.8%), normal mean corpuscular volume and mean corpuscular hemoglobin volume, and red blood cell distribution width (16%). Blood smear showed spherocytes, slight hypochromia, anisocytosis, macrocytosis, and microcytosis. Blood chemistry values were taken for iron (4 micro g/dL [normal range 40-150 micro g/dL]), transferrin (193 mg/dL [normal range 220-400 mg/dL]), ferritin (1128 ng/mL [normal range 14-160 ng/mL]), transferrin saturation (1.5% [normal range 20%-55%]), serum folate (within normal limits), and vitamin B12 (within normal limits). Direct Coombs' test equaled positive 2 + IgG. All these values indicated anemia of chronic diseases combined with hemolytic anemia. Further blood work-up tested antinuclear antibody (positive <1:80 homogeneous pattern), rheumatoid factors (143 IU/mL [positive >8.5 IU/mL]), C-reactive protein (286 mg/L [normal range 0-5 mg/L]), anticardiolipin IgM antibody (9.0 monophosphoryl lipid U/mL [normal range 0-7.00 MPL U/mL]) and antithrombin III activity (135% [normal range 74%-114%]). Results of other blood tests were within normal limits or negative, including lupus anticoagulant, beta2 glycoprotein, anticardiolipin IgG Ab, anti-ss DNA Ab, C3, C4, anti-RO, anti-LA, anti-SC-70, anti-SM Ab, P-ANCA, C-ANCA, TSH, FT4, anti-T microsomal, antithyroglobulin, protein C activity, protein S free, cryoglobulins, serum immunoelectrophoresis, VDRL, hepatitis C antibodies, hepatitis B antigen, and human immunodeficiency virus. Endocrinological work-up examined luteinizing hormone (22.9 mIU/mL [normal range for adult men 0.8-6 mIU/mL]), follicle stimulating hormone (49.7 mIU/mL [normal range for adult men 1-11 mIU/mL]), testosterone (0.24 ng/mL [normal range for adult men 2.5-8.0 ng/mL]), bioavailable testosterone (0.02 ng/mL [normal range for adult men >0.6 ng/mL]), and percent bioavailable test (8.1% [normal value >20%]). These results indicate hypergonadotropic hypogonadism. Plasminogen activator inhibitor 1 was 6 U (normal value 5-20 U/mL). Karyotyping performed by G-banding technique revealed a 47 XXY karyotype, which is diagnostic of Klinefelter's syndrome. Doppler ultrasound of the leg ulcers disclosed partial thrombus in the distal right femoral vein. X-rays and bone scan displayed osteomyelitis along the right tibia. Histological examination of a 4-mm punch biopsy from the ulcer border revealed hyperkeratosis, acanthosis, hypergranulosis, and mixed inflammatory infiltrate containing eosinophils compatible with chronic ulcer. Multiple vessels were seen, compatible with a healing process. Direct immunofluorescence of the biopsy revealed granular IgM in the dermo-epidermal junction. Indirect immunofluorescence was negative. Thyroid function tests showed normal thyroid stimulating hormone and free throxine4. Multinodular goiter was seen on thyroid scan and ultrasound. Thyroid fine needle aspiration was compatible with multinodular goiter (normal follicular cells, free colloid, macrophages with pigment). IV treatment with amoxicillin-clavulanic acid 1 g t.i.d. was administered for 2 weeks, with a decrease in temperature and normalization of the leukocyte level. Oral antibiotic treatment with amoxicillin-clavulanic acid was continued for 10 more days, followed by 25 days of ciprofloxacin for the osteomyelitis. Local treatment included saline soakings followed by application of Promogran (Johnson & Johnson, New Brunswick, NJ) and Kaltostat (ConvaTec Ltd., a Bristol-Myers Squibb Company, New York, NY) with slight improvement. At the same time, the patient was treated with warfarin sodium due to deep vein thrombosis under international normalized ratio 2-3. The patient was treated with IM testosterone once monthly for 1 year, which resulted in a reduction in the diameter and depth of the leg ulcers (Figure 3). Blood tests were not performed for follow-up of the immune state.
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PMID:Klinefelter's syndrome presenting with leg ulcers. 1536 65

WAS is a rare X-linked recessive disorder characterized by primary progressive T cell immunodeficiency, impaired antipolysaccharide antibody response, thrombocytopenia with small platelet, and eczematoid dermatitis. Untreated patients with typical WAS have poor prognosis with the major causes of death being infection, bleeding, lymphoproliferative disorders, and malignancy. Due to the increased risk of infectious and hemorrhagic episodes the best results with HSCT are achieved in patients less than five yr of age and are recommended as early as possible. Here, we report a three-yr-old boy with WAS who underwent UCB and BMT from his genotypically identical brother with Klinefelter syndrome.
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PMID:Hematopoietic stem cell transplantation from a donor with Klinefelter syndrome for Wiskott-Aldrich syndrome. 1853

Properdin is an initiator and stabilizer of the alternative complement activation pathway (AP). Deficiency of properdin is a rare X-linked condition characterized by increased susceptibility to infection with Neisseria meningitidis associated with a high mortality rate. We report properdin deficiency in a large Pakistani family. The index cases were found by screening for immunodeficiency due to a history of recurrent infections. This revealed absent AP activity, but normal classical and lectin pathway activity. Sequencing of the properdin gene (PFC) revealed a novel frameshift mutation. When all available relatives (n=24) were screened for the mutation, four affected males, four female carriers and a male heterozygous carrier were identified. He was subsequently diagnosed with Klinefelter syndrome. A questionnaire revealed a striking association between properdin deficiency and recurrent otitis media (P=0.0012), as well as recurrent pneumonia (P=0.0017). This study is the first to show a significant association between properdin deficiency and recurrent infections.
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PMID:Properdin deficiency associated with recurrent otitis media and pneumonia, and identification of male carrier with Klinefelter syndrome. 1932 43

Bruton's agammaglobulinemia is a rare X-linked humoral immunodeficiency manifesting with recurrent bacterial infections early in life. Klinefelter's syndrome caused by an additional X chromosome is the most common sex chromosome disorder. A previously unreported association of these two conditions is described here.
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PMID:X-Linked agammaglobulinemia in a child with Klinefelter's syndrome. 2447 49

Androgen deficiency occurs frequently in men with human immunodeficiency virus (HIV) infection. Antiretroviral treatments had reduced the prevalence of male hypogonadism. The pathogenesis of testosterone (T) deficiency in HIV is multifactorial. Several mechanisms have been proposed; among them, drugs, fat redistribution, and a poor health status could explain the mechanism leading to gonadotropins inhibition and hypogonadotropic hypogonadism. The diagnosis of hypogonadism in HIV-infected men should be made based on clinical symptoms and a specific workup including T measurement. The interpretation of the results of biochemical testing is more difficult in men with HIV due to several confounding factors. T treatment should be offered to HIV-infected men with documented clinical hypogonadism and symptoms, especially if they are losing lean mass.
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PMID:Hypogonadism in the HIV-infected man. 2516 63

Oral thrush is considered as the opportunistic infection, which is caused by fungus Candida albicans. Various kinds of immunodeficiency diseases, such as HIV infection, immunosuppressive therapy, use of broad-spectrum antibiotics, and invasive surgical procedures such as solid organ or bone marrow transplantation, lead to increased susceptibility to fungal infections, but persistent and refractory thrush, with typical clinical signs of oral fungal infection and without any other sign of immunodeficiencies, has not been reported so far. We describe a case of persistent and refractory thrush with Klinefelter syndrome (47, XXY) as the unusual cause.
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PMID:Persistent and refractory thrush with unknown cause. 2567 17

Background: Primary antibody deficiencies (PADs) and anterior pituitary dysfunction are both rare conditions. However, recent studies have remarkably reported the occurrence of anterior pituitary dysfunction in PAD patients. Methods: In this cross-sectional, single-center study we evaluated the prevalence of endocrine disorders in adult PAD patients. Our study focused on common variable immunodeficiency (CVID), immunoglobulin G (IgG) subclass deficiency (IgGSD), and specific anti-polysaccharide antibody deficiency (SPAD). We assessed hormone levels, performed provocative tests and genetic testing in a subset of patients by direct sequencing of the nuclear factor kappa beta subunit 2 (NFKB2) gene and primary immunodeficiency (PID) gene panel testing by whole exome sequencing (WES). Results: Our results demonstrated that one out of 24 IgGSD/SPAD patients had secondary hypothyroidism and three out of 9 men with IgGSD/SPAD had secondary hypogonadism. Premature ovarian failure was observed in four out of 9 women with CVID and primary testicular failure in one out of 15 men with CVID. In two out of 26 CVID patients we found partial adrenal insufficiency (AI) and in one out of 18 patients with IgGSD/SPAD secondary AI was found. Moreover, in one out of 23 patients with CVID and in two out of 17 patients with IgGSD/SPAD severe growth hormone deficiency (GHD) was found, while one patient with IgGSD/SPAD showed mild GHD. Combined endocrine disorders were detected in two women with CVID (either partial secondary AI or autoimmune thyroiditis with primary hypogonadism) and in three men with IgGSD/SPAD (two with either mild GHD or secondary hypothyroidism combined with secondary hypogonadism, and one man with secondary AI and severe GHD). Genetic testing in a subset of patients did not reveal pathogenic variants in NFKB2 or other known PID-associated genes. Conclusion: This is the first study to describe a high prevalence of both anterior pituitary and end-organ endocrine dysfunction in adult PAD patients. As these endocrine disorders may cause considerable health burden, assessment of endocrine axes should be considered in PAD patients.
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PMID:Endocrine Disorders Are Prominent Clinical Features in Patients With Primary Antibody Deficiencies. 3154 81


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