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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Demonstration of the long-term efficacy of GH replacement in GH-deficient adults has depended on a combination of single-centre studies and data from large multinational databases, which, by virtue of their size, are likely to detect rare adverse events and also permit analysis of mortality rates. The Pharmacia International Metabolic Surveillance (KIMS) study (a pharmacoepidemiological survey of the safety and efficacy of GH replacement in adults, sponsored by Pharmacia) is currently the largest database, with information on over 8000 patients from a total of 27 countries. Abundant epidemiological evidence confirms that hypopituitarism is associated with premature mortality, with an increase in cardiovascular and cerebrovascular disease as a primary underlying cause. Central adiposity, hyperlipidaemia, insulin resistance, and diabetes mellitus are common in adults with hypopituitarism. GH replacement is associated with improvements in central fat mass and mean reductions in serum total and low-density lipoprotein cholesterol which may be additive to those achieved with hydroxymethylglutaryl-coenzyme A reductase inhibitors. These beneficial effects are maintained for at least 2 Years after initiation of therapy, as are reductions in central adiposity, with similar benefits seen in men and women when the GH dose is titrated to achieve a serum IGF-I between the median and the upper end of the age-related reference range. Fasting plasma glucose and glycated haemoglobin increase, usually within the reference range, during prolonged GH replacement, but do not tend to rise further above baseline in subjects with pre-existing impaired glucose tolerance. Bone remodelling increases during GH replacement therapy, but indices tend to return to baseline within 5 Years of commencing treatment. Bone mineral density increases in men whereas, in women, improvement is limited to stabilisation of bone density. Data from the KIMS study demonstrate that prolonged GH replacement is associated with a reduction in the number of patients requiring assistance with daily living and a significant reduction in sick leave and hospital admissions. GH replacement therapy improves psychological well-being, particularly in those patients with the greatest deficit prior to treatment, with improvement maintained beyond 6 Months of therapy and sustained during long-term follow-up. Data from the KIMS population show that there is no increase in the overall occurrence of de novo neoplasia or the rate of regrowth of primary pituitary tumours. There is an apparent increase in intracranial neoplasia, which may be an artefact of comparing a surveillance population with general population data. Unlike mortality in untreated hypopituitary GH-deficient patients, mortality in the KIMS study is currently similar to that predicted for the normal population.
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PMID:Long-term experience with GH replacement therapy: efficacy and safety. 1267 Feb 95

Dermatologists may commonly see skin lesions that reflect an underlying endocrine disorder. Identifying the endocrinopathy is very important, so that patients can receive corrective rather than symptomatic treatment. Skin diseases with underlying endocrine pathology include: thyrotoxicosis; hypothyroidism; Cushing syndrome; Addison disease; acromegaly; hyperandrogenism; hypopituitarism; primary hyperparathyroidism; hypoparathyroidism; pseudohypoparathyroidism and manifestations of diabetes mellitus. Thyrotoxicosis may lead to multiple cutaneous manifestations, including hair loss, pretibial myxedema, onycholysis and acropachy. In patients with hypothyroidism, there is hair loss, the skin is cold and pale, with myxedematous changes, mainly in the hands and in the periorbital region. The striking features of Cushing syndrome are centripetal obesity, moon facies, buffalo hump, supraclavicular fat pads, and abdominal striae. In Addison disease, the skin is hyperpigmented, mostly on the face, neck and back of the hands. Virtually all patients with acromegaly have acral and soft tissue overgrowth, with characteristic findings, like macrognathia and enlarged hands and feet. The skin is thickened, and facial features are coarser. Conditions leading to hyperandrogenism in females present as acne, hirsutism and signs of virilization (temporal balding, clitoromegaly).A prominent feature of hypopituitarism is a pallor of the skin with a yellowish tinge. The skin is also thinner, resulting in fine wrinkling around the eyes and mouth, making the patient look older. Primary hyperparathyroidism is rarely associated with pruritus and chronic urticaria. In hypoparathyroidism, the skin is dry, scaly and puffy. Nails become brittle and hair is coarse and sparse. Pseudohypoparathyroidism may have a special somatic phenotype known as Albright osteodystrophy. This consists of short stature, short neck, brachydactyly and subcutaneous calcifications. Some of the cutaneous manifestations of diabetes mellitus include necrobiosis lipoidica diabeticorum, diabetic dermopathy, scleredema adultorum and acanthosis nigricans.
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PMID:Cutaneous manifestations of endocrine disorders: a guide for dermatologists. 1268 37

We report two cases of pituitary germinomas in two young men aged 13 and 21, revealed by insipidus diabetes associated with visual field defects or hypopituitarism. Neuroimaging of the first case was initially normal, then showed an infiltration of the stalk; the lesion of the second case appeared as a nodular thickening of the stalk and subsequently a pituitary infiltration. Histologically they mimicked lymphocytic infundibulo-neuro-hypophysitis (LINH) or lymphocytic hypophysitis (LH), the large tumoral clear cells being out-numbered by the heavy inflammatory stroma or mistaken for macrophages. Only the immuno-staining by placental alkaline phosphatase led to the diagnosis. In these tumours, immunostaining positive for CD-117 and negative for CD30, confirmed the diagnosis and should allow the distinction of pituitary germinoma from other germ cell tumours as recently described in the testis, and may have a therapeutic interest.
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PMID:[Pituitary germinoma and lymphocytic hypophysitis: a pitfall. Report of two cases]. 1459

Studies of acromegaly have shown a doubling of mortality compared with the general population. With the development of new modalities of treatment, it has become important to identify prognostic factors relating to mortality. Between 1964 and 2000, 208 acromegalic patients were followed for a mean of 13 yr at Auckland Hospital. Treatment was by surgery or radionuclide pituitary implantation, and all except 27 patients received pituitary radiation. Over the duration of the study, 72 patients died at a mean age of 61 +/- 12.8 yr. Those dying were significantly older at diagnosis, had a higher prevalence of hypertension and diabetes, and were more likely to have hypopituitarism. The observed to expected mortality ratio (O/E ratio) fell from 2.6 (95% confidence interval, 1.9-3.6) in those with last follow-up GH greater than 5 microg/liter to 2.5 (1.6-3.8), 1.6 (0.9-3), and 1.1 (0.5-2.1) for those with GH less than 5, less than 2, and less than 1 microg/liter, respectively (P < 0.001). Serum IGF-I, expressed as an SD score, was significantly associated with mortality, with O/E mortality ratios of 3.5 (95% confidence interval, 2.8-4.2) for those with an SD score greater than 2, 1.6 (0.6-2.6) for those with an SD score less than 2 (normal or low levels), and 1.0 (0.1-3) for those with an SD score less than zero. When assessed by multivariate analysis, last serum GH (P < 0.001), age, duration of symptoms before diagnosis (P < 0.03), and hypertension (P < 0.04) were independent predictors of survival. If IGF-I was substituted for GH, then survival was independently related to last IGF-I SD score (P < 0.02), indicating that GH and IGF-I act equivalently as predictors of mortality. These findings indicate that reduction of GH to less than 1 microg/liter or normalization of serum IGF-I reduces mortality to expected levels.
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PMID:Factors influencing mortality in acromegaly. 1553 56

A 47-year-old man presented with severe clinical hypoglycaemia. He had long-standing insulin-dependent diabetes with previously good glycaemic control. Intense headaches and vomiting initiated hospitalization. A brain computed tomography (CT) scan was normal, and a lumbar puncture showed elevated cerebrospinal fluid (CSF) protein [0.67 g/L; normal range (NR) 0.15-0.45 g/L], suggesting resolving viral meningitis. Routine thyroid function tests were abnormal (free thyroxine 10.6 pmol/L, NR 9-22.5 pmol/L; thyroid-stimulating hormone 0.16 mU/L, NR 0.35-5 mU/L). In the absence of evident thyroid therapy, the laboratory policy required an urgent cortisol assay to be added; this was very abnormal (42 nmol/L), suggesting hypopituitarism. Later analysis showed that concentrations of gonadotrophins and adrenocorticotrophin were low. An urgent pituitary magnetic resonance imaging scan revealed an unsuspected pituitary tumour with recent haemorrhage (pituitary apoplexy). The patient was given intravenous hydrocortisone and then stabilized on oral hydrocortisone, thyroxine and mesterolone. He made a full recovery and the hypoglycaemia resolved. The normal brain CT scan was falsely reassuring and the CSF protein was not due to viral meningitis but to haemorrhage into the pituitary tumour. If laboratory policy had not required the urgent cortisol assay be added, the diagnosis of hypopituitarism would have been delayed or even missed altogether. This could have led to the death of the patient.
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PMID:The role of the biochemistry department in the diagnosis of pituitary apoplexy. 1502 11

Patients with hypopituitarism develop a phenotype similar to metabolic syndrome with central obesity and diabetes. Similarly, patients with hypothalamic damage may develop central obesity, insulin resistance, and hyperphagia. We sought to examine the clinical associations between hypopituitarism, hypothalamic dysfunction, and nonalcoholic fatty liver disease (NAFLD). A case series of patients seen at our institution with diagnoses of hypopituitarism, hypothalamic obesity, or craniopharyngioma and NAFLD was undertaken. Clinical, laboratory, and liver biopsy features were reviewed. Twenty-one patients were identified. NAFLD was diagnosed 6.4 +/- 7.5 years (median 3 years) after the diagnosis of hypothalamic/pituitary dysfunction. Mean gain in body mass index (BMI) between diagnoses of hypothalamic/pituitary disease and NAFLD was 11.3 +/- 8.9 kg/m(2) at an average yearly rate of 2.2 +/- 2.2 kg/m(2). The majority of patients developed elevated glucose levels and dyslipidemia by time of diagnosis of NAFLD. Of the 10 patients biopsied, six were cirrhotic, two had nonalcoholic steatohepatitis (NASH) with fibrosis, and two had simple steatosis. Long-term follow-up of 66 +/- 33 months (range 12-120) was available for 18 patients. Two required liver transplantation. Six patients died, two from liver related causes. In conclusion, patients with hypothalamic and/or pituitary disease are at risk of excessive weight gain, impaired glucose tolerance, and dyslipidemia with subsequent development of NAFLD. This group has a high prevalence of cirrhosis placing them at risk for liver-related death. The novel evidence that hypothalamic/pituitary dysfunction may be accompanied by progressive NAFLD has important implications for the work-up and management of patients with hypothalamic/pituitary disease.
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PMID:Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction. 1505 93

Normal ageing is associated with a decline in spontaneous growth hormone (GH) secretion, and although elderly hypopituitary adults demonstrate an increase in total and central fat compared with age-matched controls and are distinguishable from control subjects in terms of GH responsiveness on dynamic testing, there are few data available on the response to GH replacement in older subjects. We have studied the baseline characteristics of 295 patients (173 males and 122 females) aged >65 years of age who began GH replacement therapy at the time of entry into the KIMS program (Pfizer International Metabolic Database) and the effects of GH replacement in 125 patients who completed at least 12 months of GH replacement therapy. Data were compared with those of 2469 (1249 males and 1220 females) patients aged <65 years with adult-onset GH deficiency (GHD). The patients were selected using strict criteria in accordance with the recommendations from the Growth Hormone Research Society. There was a higher proportion of pituitary adenoma relative to craniopharyngioma in the older age group (P<0.001), but there was no difference between groups in the degree of hypopituitarism (number of additional hormone deficiencies). Blood pressure, cholesterol and low-density lipoprotein (LDL) cholesterol levels were positively correlated with age, and older patients had a predictably higher prevalence of diabetes mellitus, coronary heart disease, stroke and history of hypertension. Quality of life (Assessment of Growth Hormone Deficiency in Adults (AGHDA) score) was impaired in both groups before the start of GH therapy. GH replacement doses were lower in older patients with GHD as compared with patients <65 years old. After 12 months of GH replacement, significant improvements were evident in waist circumference, waist/hip ratio, lean body mass, diastolic blood pressure, total and LDL cholesterol levels and AGHDA scores in patients aged <65 years. Similar significant reductions were evidenced in patients >65 years old compared with those observed in younger patients. The total number of adverse events was similar in younger and older patients with GHD. However, younger patients had more fluid retention-related adverse events such as headache, oedema and arthralgia; whereas, older patients with GHD had more adverse events related to glucose metabolism, cardiovascular events and neoplasms. These data indicate a positive benefit from GH replacement in older patients with hypopituitarism - particularly in relation to quality of life - using a lower dose of GH for replacement and with appropriate age-related safety controls.
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PMID:Aspects of growth hormone deficiency and replacement in elderly hypopituitary adults. 1513 78

A 70-year-old man was seen in a hospital consultation for evaluation of cellulitis of the left arm. The patient had multiple medical problems, including advanced liver disease due to alcohol, diabetes mellitus, congestive heart failure, atrial fibrillation, chronic renal in sufficiency, and hypopituitarism requiring steroid replacement. Most recently, he was admitted to the intensive care unit, where he required intubation and mechanical ventilation support following respiratory failure secondary to pneumonia. At that time, an attempt was also made to place an arterial line in the left radial artery. The patient had multiple areas of ecchymosis on both arms. A large bulla was found on the lateral aspect of the left wrist several days after the attempted arterial line placement. Subsequently, the lesion drained serosanguineous fluid, and, during the next 2 days, it ulcerated with necrosis extending around the wrist and to the elbow. He was started on ampicillin/sulbactam and clindamycin for presumed necrotizing fasciitis. The surgical service performed a very limited debridement,which was partially limited by his coagulopathy from liver disease. The initial tissue culture was positive only for Enterococcus faecium. At the time of the consultation, his temperature was 95' F (35 degrees C), pulse 82 bpm, respirations 16 BPM, and blood pressure 101/56 mmHg. He was awake but not oriented or responsive. His cardiopulmonary exam was unremarkable. Abdominal exam disclosed ascites. His extremities were all grossly edematous with multiple ecchymoses. His left forearm had a circumferential area of ecchymosis and necrosis with macerated margins, sparing only the lateral ulnar epicondyle, and involving deeper structures of subcutaneous fat and muscle(Figures 1-2 showing evolution of the lesion in a period of 1 week). Small tissue clippings were taken from the edge of the lesion and placed on culture plates. By the next morning, the patient's tissue culture grew a mold, later identified as Rhizopus. Amphotericin B was initiated. Surgical intervention (wide debridement with potential conversion to amputation of the left arm) was considered to offer little benefit in view of the patient's multiple and severe comorbidities and his poor prognosis. Amphotericin B was then stopped; the patient died within a week from his multiple medical complications. The family refused an autopsy.
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PMID:Cutaneous zygomycosis following attempted radial artery cannulation. 1553 83

In this study, the central technique of in vitro culture has been used to further investigate whether LH/FSH-expressing, but clinically "functionless" pituitary adenomas are gonadotropinomas or whether their hormone secretion is due to transdifferentiation events. 664 "functionless" pituitary adenomas were examined for hormone secretion by in vitro culture and for hormone content by immunostaining. The results were correlated with the clinical findings. 40 % of the tumours (n = 263) secreted at least one of the gonadotropins alone, 8 % (n = 53) exhibited various patterns of anterior pituitary hormones, whilst the remaining 52 % of tumours were not associated with any hormone. In the secretory tumours, immunostaining revealed only a few scattered hormone-containing cells (5 to 15 %). Mild hyperprolactinaemia was observed in some cases, presumably because of pressure effects of the tumours. The majority of the patients suffered clear cut hypopituitarism (p < 0.05). Pre-operatively, gonadotropin hypersecretion was observed in 3 cases, but only one of these secreted hormones in culture. Interestingly, a higher proportion of tumours removed from patients with hypopituitarism showed secretory activity in vitro than those tumours removed from patients showing no hormonal dysfunction or hyperprolactinaemia. We conclude that the term "gonadotropinoma" to describe functionless pituitary tumours associated with LH and/or FSH secretion is a misnomer, because the presence of LH and/or FSH confirmed by in vitro methods in the present series is a result of only a few scattered cells. We suggest that primary pituitary tumour cells differentiate into a secretory type (transdifferentiation), possibly in response to altered serum hormone levels such as decreased steroids. Further work is required to identify the factors which trigger the altered cells' characteristics.
Exp Clin Endocrinol Diabetes 2005 Jun
PMID:Analysis of secretory, immunostaining and clinical characteristics of human "functionless" pituitary adenomas: transdifferentiation or gonadotropinomas? 1597 3

Wolfram syndrome (WFS) is an autosomal recessive disorder characterized by early onset diabetes mellitus, progressive optic atrophy, sensorineural deafness and diabetes insipidus. Affected individuals may also have renal tract abnormalities as well as neurogical and psychiatric syndromes. WFS1 encoding a transmembrane protein was identified as the gene responsible for WFS. We report herein a Japanese family, of which two members had this syndrome. In the WFS1 gene of these patients, we identified a novel mutation, a nine nucleotide insertion (AFF344-345ins). In addition, one of these patients had preclinical hypopituitarism, which is an unusual feature of WFS. As only the two family members homozygous for the mutation showed WFS, these data support the notion that this mutation is the cause of WFS.
Diabetes Res Clin Pract 2005 Aug
PMID:Identification of a novel WFS1 mutation (AFF344-345ins) in Japanese patients with Wolfram syndrome. 1600 63


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