Initiation of basal bolus insulin therapy.

Most practice guidelines recommend the use of longacting or pre-mixed insulin at the initiation of insulin therapy in type 2 diabetes, especially in patients not achieving glycaemic goals. Nonetheless, there are some specific indications where basal bolus insulin is the preferred regimen for insulin initiation. These include the "5S" situations - 'Severe' hyperglycaemia, 'Symptomatic' diabetes, 'Sick' diabetes (acute or chronic comorbidity), 'Special' situations (pregnancy, childhood, adolescence) and 'Secondary' diabetes (pancreatic, drug-induced, endocrine disorders). This review describes a practical approach to initiation and follow up of basal bolus insulin regimens.

The andro-accelerator hypothesis.

Testosterone levels are known to decline with advancing age. However, there are frequent reports of inappropriate social behaviour involving middle-aged men, suggestive of hyperandrogenic state. The andro-accelerator hypothesis seeks to explain this phenomenon. This states that external stimuli, both asexual and sexual in nature, can increase or accelerate testosterone production, by stimulating the hypothalamo-pituitary-testicular axis, and resetting this axis at a higher level. This article discusses the concepts of andro-conditioning due to endocrine disruptor stimuli or endocrine disruptor social content, explores the clinical and public health relevance of the andro-accelerator hypothesis, and calls for a focus on addressing androgen imbalance, achieving "androequanimity", rather than treating andropause as a disease.

A Comparison between Silent and Symptomatic Renal Stones in Primary Hyperparathyroidism.

BACKGROUND: Nephrolithiasis is a common complication of primary hyperparathyroidism (PHPT), and in a subgroup of patients stones are clinically silent. Patients with silent and symptomatic stones may differ biochemically. There is a scarcity of data available comparing patients with silent and symptomatic renal stones in PHPT. AIMS: To characterize patients with PHPT with nephrolithiais and to compare patients with silent and symptomatic stones. MATERIALS AND METHODS: We reviewed clinical data of 186 patients with PHPT managed at our center from January 1996 to December 2017. Silent renal stones were defined as ultrasonography finding of renal stones without symptoms. Symptomatic renal stones were defined as those with symptoms or a history of graveluria or any procedure for nephrolithiasis. A 5-mm diameter was set as the cut-off between micro- and macrolithiasis. We compared those with (n = 95) and without (n = 91) stones, and, among stone formers, those with symptoms (n = 66) and silent (n = 29) were compared. RESULTS: There was no significant difference between stone formers and nonstone formers with respect to biochemical parameters. Patients with silent renal stones had significantly lower serum calcium and higher phosphate, than those with symptomatic stones. Most (75%) patients with silent renal stones had microlithiais, while only a fifth (22%) with symptomatic renal stones had microlithiasis. CONCLUSION: Nephrolithiasis is a common complication of PHPT. Most patients with silent renal stones had microlithiasis and biochemical features of less severe disease. Patients with silent renal stones may represent early mild stage of PHPT.

Bone Mineral Density is Unaltered in Women with Polycystic Ovary Syndrome.

CONTEXT: The effects of endocrine aberrations associated with polycystic ovary syndrome (PCOS) on bone mineral density (BMD) in young women is a matter of debate. OBJECTIVES: To compare BMD in young women with PCOS to age and body mass index (BMI) matched controls and to elucidate its correlation to BMI, insulin resistance and serum testosterone. DESIGN AND METHODS: We recruited 60 women with PCOS aged 14-24 years, diagnosed based on Rotterdam 2003 criteria, and 58 age matched controls. BMD was measured by dual energy X-ray absorptiometry. In addition, these subjects underwent biochemical and hormonal analysis including oral glucose tolerance test, calculation of Homeostatic Model Assessment-Insulin Resistance Index, measurement of serum thyroxine, thyrotropin, prolactin, total testosterone, dehydroepiandrosterone sulfate, follicular phase luteinizing hormone and follicle stimulating hormone. RESULTS: There was no difference of BMD between women with PCOS and control women (1.103±0.08 vs 1.126±0.083 g/cm2; p=0.122). In subgroup analysis based on BMI, BMD in obese women with PCOS was significantly higher than their overweight and lean counterparts at lumbar spine (p<0.001), neck of femur (p=0.005) and total hip (p<0.001). BMD was not different at any site between oligomenorrheic and non-oligomenorrheic women with PCOS. It positively correlated with BMI, waist and hip circumference in women with PCOS. No correlation was found with HOMA-IR or Testosterone. CONCLUSIONS: BMI is the most important determinant of BMD in women with PCOS. BMD is not different between healthy young women and those with PCOS.

Usefulness of pre- and post-operative calcium and Vitamin D supplementation in prevention of hypocalcemia after total thyroidectomy: A randomized controlled trial.

BACKGROUND: Total thyroidectomy (TT) is a commonly performed surgery and postoperative hypocalcemia is a major detriment to early discharge. The aim of this randomized controlled trial was to ascertain the usefulness of routine pre- and post-operative calcium and Vitamin D supplementation in prevention of hypocalcemia after TT. MATERIALS AND METHODS: Sixty consecutive patients who underwent total or near TT from February 2013 to August 2014 were included in the study. They were randomly divided into two groups - Group 1 received oral calcium (500 mg every 6 h) and Vitamin D (calcitriol 0.25 mcg every 6 h) 7 days before and 7 days after the surgery; and Group 2 did not receive supplementation. Symptoms and signs of hypocalcemia were monitored. Calcium profile was measured pre- and post-operatively at 6, 12, 24, 48, 72 h, and on 30th day. Hypocalcemia after surgery was either symptomatic or laboratory documented. Serum calcium level ≤ 8.5 mg/dl was considered as laboratory hypocalcemia. RESULTS: Twelve patients from Group 2, and 3 patients from Group 1 developed symptomatic hypocalcemia (P < 0.01). Laboratory hypocalcemia within postoperative 24 h was comparable between two groups, but more patients of Group 2 compared to Group 1 developed hypocalcemia at 48 h (6 and 13, respectively; P = 0.04) and at 72 h after surgery (5 and 14, respectively; P = 0.01). Twenty-four hours postoperative serum calcium level was significantly associated with grade of goiter, preoperative calcium, and nature of thyroid disease (benign or malignant). On multiple linear regression analysis, preoperative serum calcium was only independent variable significantly associated with development of 24 h post-TT hypocalcemia. CONCLUSION: Routine pre- and post-TT calcium and Vitamin D supplementation can significantly reduce postoperative hypocalcemia.

Reversible thyrotroph hyperplasia with hyperprolactinemia: A rare presenting manifestation of primary hypothyroidism.

Pituitary thyrotroph hyperplasia with hyperprolactinemia has been described as a rare presentation of primary hypothyroidism. Premenopausal females with this disorder can present with features of hypothyroidism, menstrual disturbances, galactorrhea, and visual field defects because of enlarged pituitary. Here we describe a 32-year-old female presenting to her gynecologist primarily with galactorrhea and secondary amenorrhea. She was found to have raised serum prolactin, and MRI brain showed enlarged pituitary. She was referred for pituitary surgery when she came to us. Clinical examination and biochemistry were suggestive of primary hypothyroidism. She was prescribed levothyroxine replacement. At 6 weeks follow-up, serum prolactin came down to normal, galactorrhea subsided, and spontaneous menstrual cycles resumed. In 12 weeks, pituitary enlargement completely regressed and in another month after that, she conceived. Hence, primary hypothyroidism can present with thyrotroph hyperplasia, where correct diagnosis and levothyroxine therapy can prevent unnecessary pituitary surgery. Hyperprolactinemia in this setting is of no clinical significance.

Acute parvovirus b19 infection leading to severe aplastic anemia in a previously healthy adult female.

Human Parvovirus B19 has been linked to a variety of diseases. One of the most common complications is transient aplastic crisis in patients with chronic hemolytic anemia. Very few case reports have implicated this virus as a putative etiology behind hepatitis and severe aplastic anemia in immuno competent individuals. We report a case of severe aplastic anemia in a previously healthy adult female due to acute parvovirus B19 infection. Laboratory examination showed pancytopenia in peripheral blood and severe hypoplastic bone marrow on biopsy. Serological analysis (ELISA) revealed acute Parvovirus B19 infection. In the face of unavailable HLA matched bone marrow donor, immuno-supressive therapy was contemplated, but could not be given because of financial constraints. Pancytopenia persists till date, 4 months after the diagnosis, with the patient requiring repeated packed red cell and irradiated platelet transfusions. Thus, acute infection with this virus must be considered a cause of acquired aplastic anemia even in individuals without underlying disease.

Endocrine manipulations in cancer prostate: A review.

Prostate cancer is an androgen dependent condition where Dihydrotestosterone promotes the growth of the neoplastic tissue. Androgen deprivation has been the mainstay of therapy for this condition. This can be achieved by surgical or medical means. Types of medical regimens are intermittent maximal or sequential androgen blockade.

Nephrocalcinosis: a rare presenting manifestation of primary Sjögren's syndrome.

Renal involvement in primary Sjögren's syndrome (pSS) is not uncommon. Autoimmune tubulointerstitial disorders and distal renal tubular acidosis (dRTA) account for majority of the cases of renal involvement. While dRTA may precede the onset of sicca syndrome in pSS, nephrocalcinosis as a presenting manifestation of pSS is rare. Here, to emphasize the need for initiating investigations for pSS in any patient presenting with nephrocalcinosis due to dRTA, we report a 21-year-old woman presenting with nephrocalcinosis long before pSS was objectively diagnosed.

Nanosomal Amphotericin B is an efficacious alternative to Ambisome for fungal therapy.

Amphotericin B was formulated in lipids (Nanosomal Amphotericin B) without using any detergent or toxic organic solvents during the preparation. Electron microscopy and particle size determination of Nanosomal Amphotericin B showed a homogeneous population of nanosized particles below 100 nm. Hemolysis assay indicated that Nanosomal Amphotericin B causes significantly less lysis of red blood cells than Amphotericin B deoxycholate and was comparable to Ambisome. A maximum daily dose of Nanosomal Amphotericin B at 5 mg/kg in rabbits and 10 mg/kg in mice for 28 days showed no symptoms of toxicity, mortality or significant body weight reduction. Hematological and gross pathological analysis of tissues revealed no abnormalities attributable to the drug treatment. Nanosomal Amphotericin B and Ambisome were injected (iv) at 2 mg/kg consecutively for 5 days into mice infected with Aspergillus fumigatus. The treatment resulted in 90% survival with Nanosomal Amphotericin B and only 30% survival with Ambisome after 10 days of fungal infection. However, all of the 10 control mice which were not treated with Amphotericin B died within 5 days of fungal infection. Nanosomal Amphotericin B is safe, cost effective and provides an alternative option for treatment of fungal disease.

Polyoxyl 60 hydrogenated castor oil free nanosomal formulation of immunosuppressant Tacrolimus: pharmacokinetics, safety, and tolerability in rodents and humans.

OBJECTIVE: Develop Nanosomal formulation of Tacrolimus to provide safer alternative treatment for organ transplantation patients. Investigate safety, tolerability and pharmacokinetics of Nanosomal Tacrolimus formulation versus marketed Tacrolimus containing polyoxyl 60 hydrogenated castor oil (HCO-60) that causes side effects. METHODS: Nanosomal Tacrolimus was prepared in an aqueous system. The particle size was measured by Particle Sizing Systems and structure morphology was determined by freeze-fracture electron microscopy. Investigational safety studies were conducted in mice and rats. Safety and pharmacokinetics of Nanosomal Tacrolimus were also evaluated in healthy human subjects. RESULTS: The morphology of Nanosomal Tacrolimus showed a homogeneous population of nanosized particles with mean particle size of less than 100 nm. A 14 day consecutive administration of Nanosomal Tacrolimus up to 5 and 10mg/kg dose in rats and mice respectively, resulted in no mortality. Nanosomal Tacrolimus in human studies showed that it is safe and the pharmacokinetics profile is similar to the marketed HCO-60 based Tacrolimus. No significant change in peripheral blood lymphocyte percentage was noted in either mice or healthy human male subjects. CONCLUSIONS: Nanosomal Tacrolimus is well characterized product which provides a new treatment option. It contains no alcohol or surfactants like HCO-60. Thus, Nanosomal Tacrolimus presents a new and improved therapeutic approach for organ transplant patients compared to the marketed HCO-60 based Tacrolimus product.