Diary of an endocrine resident: Recollections from Post Graduate Institute of Medical Education and Research, Chandigarh.

Endocrinology is a relatively newer field in medicine but it has gained tremendous progress in the recent past and is currently one of the most cherished and sought after superspecialty subject. The journey is long and an average of 12 years is spent to complete a superspecialty training starting from Bachelor of Medicine, Bachelor of Surgery career. To get a seat in endocrinology in institutes like PGIMER, Chandigarh is difficult, the training is grueling and the final exit is tough but the vast clinical experience, research oriented teaching and the team work of the closely knit family of faculty members and resident colleagues had made these 3 years of our life as the most enjoyable years to be remembered forever.

Physiologically based pharmacokinetic modeling in drug discovery and development: a pharmaceutical industry perspective.

The application of physiologically based pharmacokinetic (PBPK) modeling has developed rapidly within the pharmaceutical industry and is becoming an integral part of drug discovery and development. In this study, we provide a cross pharmaceutical industry position on "how PBPK modeling can be applied in industry" focusing on the strategies for application of PBPK at different stages, an associated perspective on the confidence and challenges, as well as guidance on interacting with regulatory agencies and internal best practices.

Effect of saxagliptin on the pharmacokinetics of the active components of Ortho-Cyclen(®), a combined oral contraceptive containing ethinyl estradiol and norgestimate, in healthy women.

Saxagliptin (Onglyza™) is a dipeptidyl peptidase-4 (DPP4) inhibitor for treating type 2 diabetes mellitus. This open-label, randomized, two-way crossover study in 20 healthy female subjects investigated the effect of saxagliptin on the pharmacokinetics (PK) of the active components of a combined oral contraceptive (COC). Subjects received either COC (Ortho-Cyclen(®)) once daily (QD) for 21 days, then 5 mg saxagliptin QD + COC QD for 21 days, or vice versa. Coadministration of saxagliptin and COC did not alter the steady-state PK of the primary active oestrogen (ethinyl estradiol) or progestin (norelgestromin) COC components. The area under the concentration-time curve (AUC) and peak plasma concentration (Cmax) of an active metabolite of norelgestromin (norgestrel) were increased by 13 and 17%, respectively, a magnitude that was not considered clinically meaningful. Coadministration of saxagliptin and COC in this study was generally well-tolerated. Saxagliptin can be co-prescribed with an oestrogen/progestin combination for women taking oral contraceptive.

Adolescent acromegaly: clinical parameters and treatment outcome.

BACKGROUND: Adolescent acromegaly is a rare disorder and these patients present with tall stature/gigantism, tumor mass effects and menstrual irregularities. PATIENTS AND METHODS: 34 consecutive (26 males) patients having onset of disease prior to 21 years of age were included in this retrospective analysis. Their clinical features and treatment outcome were studied. RESULTS: Mean age and lag time at presentation were 21.6 +/- 3.9 years and 5.1 +/- 3.5 years respectively. Common presenting manifestations included acral enlargement, tumor mass effects and menstrual irregularities. Mean height at presentation was 174.6 +/- 13.7 cms (range: 150-210 cm) and one third had gigantism (height > or =97th percentile, WHO growth charts). Hypertension and glucose intolerance were seen in 15% and 23.5% respectively. Mean nadir GH after glucose load was 58.2 +/- 13.7 ng/ml and IGF -1 was 534.8 +/- 132.8 ng/ml. Half of the patients had concomitant hyperprolactinemia. Almost all (97%) had macroadenoma and anterior pituitary hormone deficiencies were frequent (75%). Patients with gigantism were younger (19.6 +/- 4.9 vs. 22.6 +/- 2.9 years; p = 0.001), had higher GH values (66.68 +/- 27.22 vs. 53.98 +/- 15.99 ng/ml; p = 0.04) and hypogonadism was more common (90.9% vs. 56.5%, p = 0.03) than those with normal stature. 32 patients (94.1%) were treated primarily with surgery, 7 (21.9%) received post operative radiotherapy. Mean duration of follow up was 33.1 +/- 10.1 months. Only 30% had nadir GH values of <1 ng/ml. CONCLUSION: One third of adolescent patients had acrogigantism. These patients were younger, had higher GH levels and concurrent hypogonadism was more common. Cure could be achieved only in about one third of the patients.

Hypophosphataemic rickets/osteomalacia: a descriptive analysis.

BACKGROUND & OBJECTIVES: Hypophosphataemic rickets/osteomalacia (HRO) is an uncommon metabolic bone disorder which affects all ages and either sex. It is characterized by low concentration of serum phosphate levels leading to impairment of mineralization of bone matrix with variable aetiology. We present clinical profile and treatment outcome of 17 patients of HRO. METHODS: Seventeen consecutive patients (8 were < 18 yr of age, with median age of presentation being 27.5 yr) of HRO who came to the department of Endocrinology in a tertiary care hospital in north India from January 2000 to December 2006 were included in the present study. Their aetiology, clinical features, biochemical parameters, radiographic features, treatment and outcome were analyzed. RESULTS: HRO was commoner in females (70.5%) with positive family history observed in 6 (35.3%) patients. Common presenting features were short stature (58.8%), backache (58.8%), bony deformities (58.8%), joint pain (52.9%), fractures (29.4%) and dental abnormalities (23.5%). Radiological abnormalities noted were generalized bony deformities (58.8%), fractures (29.4%), and pseudo fractures (17.6%). Mesenchymal tumours were localized in the pelvis in one patient and in the right jaw in another. The patients were treated with calcium (elemental calcium 1 g/d) and oral phosphate supplements (dose 30 - 50mg/kg/day in divided doses) along with active vitamin D supplements (dose 1 - 3 microg/day) and followed up for a mean of 2 yr. Two patients also received growth hormone (GH) therapy in the dose of 2U/day for 6 and 18 months respectively. Symptomatic well being was reported by all the patients and improvement was noted in the levels of phosphate (P<0.005) and alkaline phosphatase (P<0.05) after treatment. INTERPRETATION & CONCLUSIONS: A diagnosis of HRO should be considered in all patients presenting with short stature, deformities or musculoskeletal pains along with low serum phosphate with normal iPTH and 25--hydroxy vitamin D.

A child with suprasellar mass and ascites.

A 7-year-old child having short stature presented with headache and vomiting of 6 months' duration. MRI of the brain showed a sellar and suprasellar mass suggestive of craniopharyngioma with hydrocephalus. He underwent a right ventriculo-peritoneal (V-P) shunting followed by a subtotal resection of the tumour. A year later, he presented with progressive ascites and umbilical hernia. Systemic examination was unremarkable except for massive ascites. Ultrasound abdomen confirmed free-fluid in the peritoneal cavity and the ascitic fluid was transudative. Ventriculo-cysternography revealed a functional and patent V-P shunt. A diagnosis of cerebrospinal fluid ascites (shunt ascites) was made and he underwent ventriculo-atrial shunting. After treatment the patient improved with the gradual disappearance of ascites.

Osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare metabolic bone disorder characterized by increased bone fragility, low bone mass, recurrent fractures and numerous extra-osseus features. Many patients remain undiagnosed and unattended particularly in developed countries. Presently, medical management with bisphosphonates has changed the scenario. MATERIALS AND METHODS: Twenty consecutive patients of OI were enrolled over a period of four years. Their clinical features, radiology, and biochemical parameters and treatment outcome were analysed. RESULTS: Of the 20 patients, 16 (80%) were male and 4 (20%) were female. Mean age (SD) of the patients was 20.8 (13.8) years. All the patients had presented with fractures, the number of fractures per person varying from 1 to 20. Long bones were predominantly involved and thirteen (65%) had deformities of long bones. Ten (50%) had a positive family history of fractures after trivial traum. Eleven (55%) patients had dentiginous imperfecta (DI) and ten (50%) had blue sclerae at presentation. Impaired hearing was present in 1 patient only. Calcium profile was normal. Nine patients received pamidronate. Fracture frequency and pain decreased remarkably in these patients. CONCLUSION: Patients with OI presented late, predominantly with fracture of long bones, deformities and blue sclerae. Pamidronate therapy remarkably decreased fractures and pain in these patients.