Search

Androgen replacement therapy has been reported to have a beneficial effect in patients with Klinefelter's syndrome or perforating plantar ulcers. We report the case of a 55-year-old man with a 35-year history of leg ulcers and venous insufficiency. His leg ulcers healed 4 months after a management scheme including vascular rehabilitation (intermittent pressure therapy, ankle mobilization, multiple layer compression bands on the lower limbs), skin grafts and foam sclerotherapy of the great saphenous vein. The ulcers recurred 1 month later. This recurrence and the unusually young age for development of venous leg ulcers led to a search for a rare cause. The diagnosis of anterior pituitary failure was established. Sclerotherapy and androgen replacement therapy led to complete healing without recurrence at the 1-year follow-up visit. A link between androgen deficiency and fibrinolysis, protein synthesis deficiency, inflammation and trophicity is well documented in the literature. A search for hypogonadism may be useful in young patients presenting a longstanding history of leg ulcers or in patients with suspected andropause irrespective of age., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Context: Germline mutations in SDHx genes cause hereditary paraganglioma., Objective: The aim of the study was to assess the indications for succinate dehydrogenase (SDH) genetic testing in a prospective study., Design: A total of 445 patients with head and neck and/or thoracic-abdominal or pelvic paragangliomas were recruited over 5 yr in 20 referral centers. In addition to classical direct sequencing of the SDHB, SDHC, and SDHD genes, two methods for detecting large genomic deletions or duplications were used, quantitative multiplex PCR of short fluorescent fragments (QMPSF) and multiplex ligation-dependent probe amplification (MLPA)., Results: A large variety of SDH germline mutations were found by direct sequencing in 220 patients and by QMPSF and MLPA in 22 patients (9.1%): 130 in SDHD, 96 in SDHB, and 16 in SDHC. Mutation carriers were younger and more frequently had multiple or malignant paraganglioma than patients without mutations. A head and neck paraganglioma was present in 97.7% of the SDHD and 87.5% of the SDHC mutation carriers, but in only 42.7% of the SDHB carriers. A thoracic-abdominal or pelvic location was present in 63.5% of the SDHB, 16.1% of the SDHD, and in 12.5% of the SDHC mutation carriers. Multiple paragangliomas were diagnosed in 66.9% of the SDHD mutation carriers. A malignant paraganglioma was documented in 37.5% of the SDHB, 3.1% of the SDHD, and none of the SDHC mutation carriers., Conclusions: SDH genetic testing, including tests for large genomic deletions, is indicated in all patients with head and neck and/or thoracic-abdominal or pelvic paraganglioma and can be targeted according to clinical criteria.

Self-monitoring of blood glucose (SMBG) is well acknowledged in type 1 diabetes mellitus (DM). However, although its use is widely recommended in some developed countries, with a significant economical cost, SMBG remains questionable in type 2 DM because its efficacy is not demonstrated by high-quality randomized controlled trials. Type 2 diabetes is an heterogenous disease and its natural history covers several decades. Although type 2 DM represents an important risk of microvascular and cardiovascular complications, it remains asymptomatic for a long time with often a very poor metabolic control and low drug compliance. Treatment of type 2 diabetes varies during these decades, changes in lifestyle at the very beginning, then using oral drugs without risk to develop hypoglycemia (metformin, glitazones, alpha-glucosidases inhibitors) and/or insulin secreting drugs (sulfonylureas or glinides) with potential hypoglycemic risks. At every stage, SMBG could sensitize the patient and possibly could improve glycemias and compliance. SMBG must be adapted to provide informations representing a very useful, motivating and pedagogic tool. Obviously SMBG, in non-insulin-treated type 2 DM, targets other objectives when compared to its use in type 1 DM requiring adapted educational programs to avoid its uselessness and depression of the patient. In insulin treated type 2 DM patients, with a bed time regimen, SMBG represents both a major tool for adjusting the insulin and oral hypoglycemic drugs doses and a comprehensive instrument for controlling and understanding the disease. Thus SMBG is a logical tool for the management of a large proportion of type 2 DM patients but it requires to be proposed in structured counseling educational programs adapted to the psychological and social profile of the patients. These programs must be evaluated by randomized controlled trials.

Accumulating data have provided evidence that 1 alpha,25 dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] is involved in brain function. Thus, the nuclear receptor for 1,25-(OH)(2)D(3) has been localized in neurons and glial cells. Genes encoding the enzymes involved in the metabolism of this hormone are also expressed in brain cells. The reported biological effects of 1,25-(OH)(2)D(3) in the nervous system include the biosynthesis of neurotrophic factors and at least one enzyme involved in neurotransmitter synthesis. 1,25-(OH)(2)D(3) can also inhibit the synthesis of inducible nitric oxide synthase and increase glutathione levels, suggesting a role for the hormone in brain detoxification pathways. Neuroprotective and immunomodulatory effects of this hormone have been described in several experimental models, indicating the potential value of 1,25-(OH)(2)D(3) pharmacological analogs in neurodegenerative and neuroimmune diseases. In addition, 1,25-(OH)(2)D(3) induces glioma cell death, making the hormone of potential interest in the management of brain tumors. These results reveal previously unsuspected roles for 1,25-(OH)(2)D(3) in brain function and suggest possible areas of future research.

Objectives: A prospective longitudinal study was conducted to investigate the influence of prolonged suppressive L-thyroxin therapy on bone density and biochemical markers of bone remodeling., Patients and Methods: Seventy-one patients (including 28 menopaused women) taking long-term L-T4 for thyroid carcinoma were divided into 3 groups according to their TSH level: low (TSH < 0.04 mlU/l), moderate (0.04 TSH < or = 0.10 mlU/l) and high (TSH > 0.10 mlU/l). Bone density was measured in lumbar vertebrae annually for a mean 4.5 years. Bone metabolism markers were measured over a 4 year period. Bone density measurements of the femur were also obtained for 2 years in 16 menopaused women., Results: Lumbar bone density did not decline whatever the TSH level or the duration of L-T4 treatment. Likewise for menopaused women without substitution estroprogesterone therapy. Over the 4 years, biochemical markers of bone formation, including bone alkaline phosphatases and osteocalcin, or of bone resorption, including urinary hydroxyprolin, did not vary. In addition, in menopaused women, femoral bone density was not significantly lowered over the 2 years follow-up. No lumbar or femoral osteopenia was observed in these patients taking L-thyroxin, even for those with complete TSH blockade. Biochemical markers did not demonstrate a significant acceleration of bone turnover during prolonged administration of L-T4 at suppressive levels.

The aim of our study was to assess the ability of routine calcitonin (CT) measurement to improve the preoperative diagnosis of medullary thyroid carcinoma (MTC) in nodular thyroid diseases. We systematically determined basal CT in 1167 patients before thyroid surgery and performed a pentagastrin (Pg) CT stimulation test in 121 of these patients whose basal CT level was normal. Sixteen MTC (1.37%) were found on histopathological examination of surgical specimens: 14 in the 34 patients (41.1%) with abnormal basal CT levels and 2 in the 1133 patients with normal basal CT levels (0.17%). An abnormal increase in Pg-stimulated CT was observed in 7 of the 121 patients tested and was related to microscopic MTC in 2 cases. Among 1167 thyroidectomized patients with nodular thyroid diseases, the prevalence of MTC was 1.37% and reached 41.1% when the basal CT level was abnormal (3% of the patients). CT evaluation detected MTC, whereas other procedures, such as fine needle aspiration cytology, failed, thus allowing early radical surgery. CT measurement should thus become a routine part of the diagnostic evaluation of nodular thyroid diseases.

In the multiple endocrine neoplasia (MEN) type 2A and in the familial medullary thyroid carcinoma (FMTC), the recent development of genetic testing has provided new methods of identifying disease gene carriers. The use of sensitive immunoradiometric calcitonin (CT) assays led us to evaluate reference ranges of plasma CT responses after pentagastrin in healthy subjects in order to discuss the place of pentagastrin testing in the management of hereditary MTC. Basal and pentagastrin-stimulated CT concentrations were measured in 71 healthy volunteers--aged 20-67 years--and 76 genetically unaffected members of families with hereditary MTC--aged 4-61 years. In healthy subjects, CT peak values were below 30 ng/l in 68 cases and below 50 ng/l in 3 cases. In the genetically unaffected patients, CT peak values were below 15 ng/l in young patients and below 30 ng/l in patients older than 19 year excepted 5 men with stimulated CT levels ranging from 36.5 to 52 ng/l. In 2 of these 5, thyroidectomy revealed C-cell hyperplasia. Borderline test results are not sufficient to establish diagnosis of MTC and in these familial syndromes, management has to be based on the results of genetic testing. However, the determination of the upper normal limit for stimulated CT concentrations in young patients (< 15 ng/l) may help to identify the optimal moment for surgery.

We first compared the analytical performances in terms of precision of two different generation thyrotropin (TSH) assays: Amerlite TSH-60 Assay (K2-TSH) versus Berilux hTSH (B3-TSH) and Kodak Amerlite TSH-30 Ultrasensitive Assay (K3-TSH). Then, we compared the clinical performances in 69 thyrotropin-suppressed patients with thyroid cancer and in 17 other patients referred for newly diagnosed hyperthyroidism. All the patients were given 200 micrograms of Protirelin IV for TRH testing. At the analytical level, the functional detection limit (FDL) was 0.006, 0.017, and 0.04 mU/l for B3-, K3-, and K2-TSH, respectively. At the clinical level of the 17 hyperthyroid patients, 52.9% displayed a positive TRH test with B3, 5.9% with K3, and 11.8% with K2; besides, 29.4% had a basal TSH detectable value with B3, 5.9% with K3, and 11.8% with K2. Among the patients receiving suppressive therapy: 1) 95.6%, 49.3%, and 50.7% showed a detectable TSH response to TRH, with B3-TSH, K2-TSH, and K3-TSH, respectively, and 2) only 5.8% had undetectable basal TSH values with Berilux hTSH, versus 84% with K2 and 89.8% with K3. Considering our findings, we first conclude that third generation TSH assays (having a functional sensitivity limit between 0.01 and 0.02 mU/l) can be useful for monitoring patients on thyroxine suppressive therapy, so as to distinguish partial from more complete thyrotropin suppression. Secondly, even though K3 has a FDL consistent with a third generation TSH assay, it appears less clinically sensitive than B3. Yet, no current assay can thoroughly ascertain a state of overtreatment. Finally, it is important to routinely determine the FDL, which can vary from one kit to the other, within one generation of TSH assays. Indeed, B3 with a FDL at 0.006 mU/l is more useful for monitoring LT4-suppressed patients for thyroid cancer than K3 whose FDL is 0.017 mU/l.

Amiodarone is a widely-used anti-arythmic drug that induces an iodine overload and, in 1 to 23% of the patients, a thyrotoxicosis. In a few cases, the thyrotoxicosis may be refractory to conventional pharmacological therapy, thus leading to thyroidectomy. We report the thyroid gland pathology in 5 thyroidectomies that were performed for uncontrolled thyrotoxicosis, induced by amiodarone (4 cases) and by Colchimax, another iodine-rich drug (1 case). Two cases have been studied by electron microscopy. Pathologic findings were: [1] colloid transformation of the parenchyma, [2] areas of follicular disruption with numerous foamy macrophages in the colloid, [3] regenerative areas and [4] a moderate T lymphocytic infiltration. No lysosomal lamellar inclusion body was found by electron microscopy. These lesions may be rather specific of an iodine toxicity. The pathogeny is still misunderstood, and probably complex. It may essentially involve toxic mechanisms, as well as immunologic or allergic mechanisms.

Since the first description by Wolfe et al of C-cell hyperplasia (CCH) in asymptomatic relatives of patients suffering from a medullary thyroid carcinoma (MTC), several investigators have described CCH associated with a chronic lymphocytic thyroiditis (CLT) not within the context of MTC or multiple endocrine neoplasia (MEN). We report the study of C-cell density in 112 cases of CLT on retrospective surgical material to determine the frequency of the association between CCH and CLT. The cases of CLT were compared with 19 normal thyroid glands obtained at necropsy. C cells, immunoreactive with a polyclonal anti-calcitonin (CT) antibody, were counted at high magnification (X400) and the number of low-power magnification (X100) microscopic fields (LPFs) containing at least 50 C cells per slide was assessed. Image analysis was performed to determine the C-cell density expressed in number of C cells/cm2. C-cell hyperplasia was defined by the following criteria: C-cell density > 40 cells/cm2 and the presence of at least three LPFs containing more than 50 C cells. Twenty percent of the cases of CLT showed a CCH thus defined, and four of them had an elevated serum CT level. Statistical analysis showed no clinical or biological correlation with the presence of CCH. However, the frequency of CCH was higher if a follicular cell carcinoma was associated with CLT. This study confirms a pathological association between CCH and CLT, provides new criteria for the definition of CCH on surgical pathology material, and reports four cases with an elevated serum CT level not within the context of MTC or MEN.