Subclinical hypothyroidism and conception in a woman with primary infertility

Hypothyroidism is the most common endocrinological problem affecting women who present with ovulatory dysfunction resulting in infertility.It’s milder form, subclinical hypothyroidism (SH) characterized by mildly elevated thyroid stimulating hormone levels and normal free thyroxine levels, may also contribute to disturbed reproductive function. We report a case highlighting the beneficial effects of levothyroxine replacement therapy in women with subclinical hypothyroidsm presenting with infertility

Tuberculosis of the sella masquerading as pituitary adenoma

Tuberculosis of the central nervous system is an ominous consequence of disseminated tuberculosis which usually manifests as meningitis, an abscess or rarely as a tuberculoma. Though infrequent, intracranial tuberculomas especially within the sella, are notorious for simulating as pituitary tumors, by jeopardising pituitary hormonal function and exerting compressive effects on adjacent intracranial structures. However, a prompt evaluation can help tackle this diagnostic challenge with timely institution of anti-tuberculosis treatment, (ATT). Although in rare instances surgery may be a favourable option especially for managing extensive intrasellar masses, ATT usually facilitates resolution of such lesions. Long term hormonal replacement therapy may be required for established endocrine dysfunction

Wpływ badań oceniających bezpieczeństwo sercowo-naczyniowe na wybór preparatu insuliny w leczeniu cukrzycy typu 2: opinia ekspertów

Wstęp: Niniejszą opinię ekspertów opracowano w celu omówienia epidemiologii i patofizjologii chorób układu sercowo-naczyniowego (CVD) u chorych na cukrzycę typu 2 (T2DM), wyjaśnienia różnych zagadnień statystycznych i niuansów w interpretacji wyników badań oceniających bezpieczeństwo sercowo-naczyniowe (CVOT) ze szczególnym zaakcentowaniem badań typu CVOT dotyczących insulinoterapii i ich wpływu badań na wybór preparatów insuliny w codziennej praktyce klinicznej. Metody: Grupa ekspertów krytycznie przeanalizowała opublikowane dane z badań obserwacyjnych, badań klinicznych z randomizacją, metaanaliz i badań CVOT dotyczących bezpieczeństwa stosowania preparatów insuliny w odniesieniu do układu sercowo-naczyniowego i uzgodniła serię opinii popartych dostępnymi dowodami naukowymi i oceną kliniczną ekspertów. Wyniki: Wielu chorych na T2DM charakteryzuje się wysokim ryzykiem CVD i zgonu sercowo-naczyniowego, które częściowo wynika z czynników ryzyka związanychz insulinoopornością i hiperglikemią. W ciągu ostatniej dekady badania CVOT stały się integralną częścią procesu rejestracji leków przeciwcukrzycowych przez Amerykańską Agencję ds. Żywności i Leków (FDA). Większość obecnie stosowanych preparatów insulinowych, poza kilkoma opracowanymi w ostatnich latach insulinami, dopuszczono do obrotu długo przed wprowadzeniem tego wymogu rejestracyjnego, a zatem nie poddano ich rygorystycznym badaniom CVOT. Istnieje wiele danych obserwacyjnych dotyczących sercowo-naczyniowego bezpieczeństwa stosowania preparatów insuliny. Dane te są często niejednoznaczne, a czasami — sprzeczne. W tym kontekście należy zauważyć, że badania CVOT dwóch analogów insuliny bazowej — insuliny glargine ocenianej w badaniu Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia Trial (ORIGIN) i insuliny degludec ocenianej w badaniu Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes Trial (DEVOTE) — wykazały długoterminowe bezpieczeństwo sercowo-naczyniowe ich stosowania. Badanie DEVOTE dostarczyło dodatkowych danych o bezpieczeństwie, wskazujących, że stosowanie insuliny degludec wiązało się z mniejszą liczbą epizodów ciężkiej hipoglikemii niż stosowanie insuliny glargine. Wnioski: W niniejszej pracy dokonano krytycznej analizy dwóch badań CVOT oceniających analogi insuliny bazowej w połączeniu z ogólnym przeglądem meto-dologicznych i interpretacyjnych aspektów badań typu CVOT. Omówiono długoterminowe bezpieczeństwo sercowo-naczyniowe stosowania analogów insuliny bazowej. Za główną lukę badawczą w tej dziedzinie uznano brak badań CVOT z mieszankami insulin ludzkich i analogów insulinowych

History of growth hormone therapy

Although the importance of the pituitary gland for growth was recognized in late 19 th century, Growth hormone (GH) therapy was made available for severely GH-deficient children and adolescents only in late 1950s. Use of GH for other conditions was limited because of the limited supply of human pituitary-derived hormone. With unlimited availability of recombinant human GH (rhGH), the scenario of GH treatment has been changed enormously. Currently there is ever increasing list of indications of GH treatment in children, adolescents, and adults

Developmental origins of adult diseases

There is considerable evidence for the fact that early life environment in human beings are associated with future development of various metabolic diseases. Fetal programming and perinatal events appear to exert effects on later life that are independent of environmental risk factors in adults. Our understanding of the underlying mechanisms are limited and remains unclear. However several animal models and epidemiological studies have shown this association, and it is assumed secondary to the penalties of developmental plasticity. In this review, we amalgamate facts from several disciplines to support this hypothesis

Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant

Berardinelli Seip congenital lipodystrophy (BSCL) is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age

Russell Silver syndrome: a perspective on growth and the influence of growth hormone therapy

A 6 years male child was referred to our Endocrinology clinic with complaints of failure to thrive and he displayed the characteristic features of Russell Silver Syndrome which included short stature, relative macrocephaly, triangular facies and bilateral clinodactyly. He had a birth weight of 2.14 kg and an expected target height of 170 cm. He was subjected to a hormonal analysis which revealed a normal thyroid profile, but low serum markers of growth namely IGF-1=68 ng/ml (52-297 ng/ml) and basal growth hormone (GH) (1.5 μg/l). No defects were detected on MRI of the sella. Therefore a growth hormone stimulation test with Clonidine was performed which confirmed complete GH deficiency (at 0 min=0.16 μg/l, 60 min=0.27 μg/l, 120 min=4.73 μg/l). He was commenced on rhGH therapy at 8 years of age (height=102 cm, SDS=-4.53), due to financial restraints. Following initiation of GH therapy (1.5 IU/day) for 19 months, a height gain of 15 cm was obtained (Height=117 cm, SDS=-3.05). Bone age at 9 yr. was between 7-8 years

The impact of cardiovascular outcome trials on the choice of insulins in the management of type 2 diabetes mellitus: An expert review

Introduction. This expert review aims to address the epidemiology and pathophysiology of cardiovascular disease (CVD) in persons with type 2 diabetes mellitus (T2DM), help understand the various statistical considerations and interpretational nuances of cardiovascular outcome trials (CVOTs) in general, and discuss in particular, the CVOTs with insulins, and their impact on the choice of insulins in day-to-day clinical practice. Material and methods. The expert panel critically analysed published data from observational studies, randomized clinical trials, meta-analyses and CVOTs regarding cardiovascular (CV) safety of insulin preparations, and agreed on a series of consensus statements supported by available scientific evidence and the collective clinical judgement of the experts. Results. A proportion of persons with T2DM have a high risk of CVD and CV mortality, which is partly contributed by insulin resistance-related, and hyperglycaemiarelated, risk factors. Over the past decade, CVOTs have become an integral part of the drug approval process of anti-diabetic therapies by the United States Food and Drug Administration (FDA). Most insulin preparations in use today, barring a few modern insulins, were introduced much before this regulatory requirement was put in place, and hence, have not undergone rigorous CVOTs. There is a large body of observational data concerning the CV safety of insulin preparations, which are often confusing and, at times, contradictory. In this background, it is reassuring to note that CVOTs of two basal insulin analogues, namely insulin glargine, studied in the Basal Insulin and Cardiovascular and Other Outcomes in Dysglycaemia Trial (ORIGIN), and insulin degludec, studied in the Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes Trial (DEVOTE), established their long-term CV safety. The DEVOTE trial provided additional safety data reporting fewer severe hypoglycaemic events with insulin degludec in comparison to insulin glargine. Conclusions. This review critically analyses the two CVOTs of basal insulin analogues, in tandem with a general review of the methodological and interpretational aspects of CVOTs in general. The long-term CV safety of analogue basal insulins is discussed. The lack of CVOTs with prandial and pre-mixed insulins, either human or analogue, was identified as the main research gap in this area.Introduction. This expert review aims to address the epidemiology and pathophysiology of cardiovascular disease (CVD) in persons with type 2 diabetes mellitus (T2DM), help understand the various statistical considerations and interpretational nuances of cardiovascular outcome trials (CVOTs) in general, and discuss in particular, the CVOTs with insulins, and their impact on the choice of insulins in day-to-day clinical practice. Material and methods. The expert panel critically analysed published data from observational studies, randomized clinical trials, meta-analyses and CVOTs regarding cardiovascular (CV) safety of insulin preparations, and agreed on a series of consensus statements supported by available scientific evidence and the collective clinical judgement of the experts. Results. A proportion of persons with T2DM have a high risk of CVD and CV mortality, which is partly contributed by insulin resistance-related, and hyperglycaemiarelated, risk factors. Over the past decade, CVOTs have become an integral part of the drug approval process of anti-diabetic therapies by the United States Food and Drug Administration (FDA). Most insulin preparations in use today, barring a few modern insulins, were introduced much before this regulatory requirement was put in place, and hence, have not undergone rigorous CVOTs. There is a large body of observational data concerning the CV safety of insulin preparations, which are often confusing and, at times, contradictory. In this background, it is reassuring to note that CVOTs of two basal insulin analogues, namely insulin glargine, studied in the Basal Insulin and Cardiovascular and Other Outcomes in Dysglycaemia Trial (ORIGIN), and insulin degludec, studied in the Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes Trial (DEVOTE), established their long-term CV safety. The DEVOTE trial provided additional safety data reporting fewer severe hypoglycaemic events with insulin degludec in comparison to insulin glargine. Conclusions. This review critically analyses the two CVOTs of basal insulin analogues, in tandem with a general review of the methodological and interpretational aspects of CVOTs in general. The long-term CV safety of analogue basal insulins is discussed. The lack of CVOTs with prandial and pre-mixed insulins, either human or analogue, was identified as the main research gap in this area

The 1 μg cosyntropin test in normal individuals: A reappraisal

Background: The 1μg cosyntropin test has some advantages over the 250μg test as a test of adrenal function. One of the concerns regarding the 1 μg test includes stability of the cosyntropin when reconstituted and stored. Classically the 5 th percentile responses to cosyntropin in normal individuals have been used to define a normal response. Recent studies have shown that these normative values should be determined for individual assays. Materials and Methods: We performed a 1μg cosyntropin test using reconstituted and refrigerated (4-8° C) cosyntropin in saline solution in 49 non pregnant adults who were apparently healthy and had no exposure to exogenous glucocorticoids. The cosyntropin solution was stored for up to 60 days following reconstitution. We analysed the data for any association between duration of cosyntropin solution storage and the cortisol responses to cosyntropin administration. Results: The mean ± SD cortisol level at baseline, 30 and 60 min were-12.19 ± 3 μg/dl, 20.72 ± 2.63 μg/dl, 16.86 ± 3.33 μg/dl. The 5 th percentile cortisol response at 30 min was 16.5 μg/dl (16.33 μg/dl rounded off). The correlation coefficients between number of days of cosyntropin solution storage and the cortisol responses at 30 and 60 min were (Spear mans rho = 0.06,-0.24 respectively) (P = 0.69 and 0.41). There were no differences in cortisol values whether the storage was for less than 30 days or more than 30 days (mean difference 0.25 μg/dl P = 0.44). Conclusion: The 5 th percentile normative values determined for our assay is lower than what is currently being used clinically and in research publications. Prolonged refrigerated storage of cosyntropin solution does not affect the validity of the 1 μg cosyntropin test