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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperprolactinemia and prolactinoma in patients with long-term primary hypothyroidism have been recognized for decades. We report a case of 57-year-old female patient with lingual thyroid and cretinism who had a high serum prolactin level (greater than 200 ng/ml) and a pituitary tumor with suprasellar and parasellar extension. The tumor regressed to a size undetectable by CT scan after 2 years of thyroid hormone replacement therapy, but complete normalization of the hyperprolactinemia required additional bromocriptine therapy. This patient showed generalized short metacarpal and phalangeal bones, calcification of the basal ganglia and dentate nuclei bilaterally, and subcutaneous calcification at both gluteal regions, while serum calcium, phosphorus and c-PTH levels were all normal. Thus in addition to short stature, brachydactyly, a round face, and obesity, which are related to hypothyroidism, she also presented features uniquely mimicking the Albright's hereditary osteodystrophy seen in patients with pseudohypoparathyroidism and pseudopseudohypoparathyroidism. Since she had no family history of pseudohypoparathyroidism and had a normal level of Gs alpha protein on the membrane of the red blood cells, there is no evidence of pseudopseudohypoparathyroidism. The cause of the ectopic calcification remains unknown.
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PMID:Intracranial calcification and brachydactyly mimicking Albright's hereditary osteodystrophy in an adult patient with lingual thyroid and prolactinoma-like lesion. 167 15

The manifestations of endocrine derangements in the musculoskeletal system in infancy and childhood are disturbances in growth and maturation and in adulthood are disturbances in maintenance and metabolism. Hypercortisolism during skeletal immaturity suppresses growth. In the adult, hypercortisolism leads to osteoporosis, osteonecrosis, and muscle wasting. Deficiency of growth hormone during skeletal development results in short stature. An excess of growth hormone in a skeletally immature individual results in gigantism, an excess in a skeletally mature individual results in acromegaly. Patients with gigantism have extreme height with normal body proportions. Musculoskeletal manifestations of acromegaly include soft-tissue thickening, vertebral body enlargement, characteristic hand and foot changes, and enthesal bony proliferation. Hyperthyroidism causes catabolism of protein and loss of connective tissue, which manifest as muscle wasting. Deficient levels of thyroid hormone cause defects in growth and development. Severe growth retardation from congenital hypothyroidism is rare because neonatal screening recognizes the disorder and leads to early treatment. The skeletal manifestation of hypergonadism in children is precocious growth and early skeletal maturation. Although the initial precocious growth spurt results in a tall child, early closure of the growth plates results in a short adult. Hypogonadism in the prepubertal child results in delayed adolescence and delayed skeletal maturation. Diabetes mellitus in childhood results in decreased growth, a phenomenon presumed to be secondary to nutritional abnormalities. Generalized osteoporosis and short stature are common. In the adult, generalized osteoporosis may accompany insulin-dependent diabetes mellitus if obesity is absent. Calcification of interdigital arteries of the foot is common in diabetics and uncommon in other conditions. Additional skeletal manifestations relate to complications of diabetes such as peripheral neuropathy and diabetic foot disease.
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PMID:Radiologic manifestations in the musculoskeletal system of miscellaneous endocrine disorders. 198 24

Growth charts of five children with Prader-Labhart-Willi syndrome were examined. Clinical diagnosis was based on usual features of this condition. These included hypotonia in infancy, obesity, mental retardation, short stature, undescended testes in boys and typical physical features. Extensive investigations have failed to reveal pathognomonic abnormalities in this syndrome. Obesity and failure to thrive, beginning in early infancy and increasing with age is a precocious and typical feature. This pattern helps to early diagnosis. Only congenital hypothyroidism could show a similar pattern.
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PMID:[Body growth in the early diagnosis of Prader-Labhart-Willi syndrome]. 687 76

Central hypothyroidism (CH) is a rare cause of hypothyroidism, generally due to either pituitary or hypothalamic defects. On the basis of its etiology, it is possible to distinguish acquired and hereditary forms. Hereditary CH can be isolated or associated with combined pituitary hormone deficiency (CPHD). In the former case, alterations of only two genes, TSHbeta and the TRH receptor, have so far been described as responsible for the disorder. In hereditary CH associated with CPHD, inactivating mutations of different pituitary transcription factors (HESX1, PROP-1, POU1F1) have been found involved in the pathogenesis of the disease. Finally, an association between CH and severe obesity has been described in patients with leptin receptor (Leptin-R) mutations. The clinical consequences of CH in adult life vary greatly depending on the etiology, the severity of the thyroid impairment, the extent of the associated hormone deficiencies, and the age of the patient at the time of the onset of the disease. In general, acquired CH is less severe than the congenital form because of the constitutive activity of the wild-type TSH-receptor. Symptoms and signs of thyroid insufficiency are usually milder than those of primary hypothyroidism, and goiter is always absent. In CPHD, most patients have other endocrine manifestations of the disease (growth failure, delayed puberty, adrenal insufficiency, diabetes insipidus) that lead them to seek medical attention before the hypothyroidism becomes severe. Early diagnosis of the congenital form by neonatal screening for hypothyroidism is strongly recommended in order to avoid cretinism. Replacement therapy with L-thyroxine administration has to be established as soon as possible.
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PMID:Central hypothyroidism: consequences in adult life. 1196 21

Molecular diagnostic techniques provide an unsurpassed opportunity to understand the pathophysiological basis of endocrine disorders. Diseases have been associated with mutations in almost every gene known to have a role in either the production or secretion of a hormone or the mediators of hormone signalling. Even though most of these mutations are rare and account for only a small fraction of endocrine diseases, molecular diagnostics offers a valuable tool for the clinician in these cases. The most common endocrine disorders such as autoimmune thyroiditis, type 2 diabetes mellitus, osteoporosis, growth disorders, and obesity have all major genetic components, but these are mostly unknown. In this review the clinical implications of molecular diagnostics are illustrated for some endocrine diseases: congenital adrenal hyperplasia, congenital hypothyroidism, thyroid hormone resistance, familial hypocalciuric hypercalcaemia, growth hormone deficiency and resistance, and monogenic obesity. Improved diagnostic specificity has direct implications for treatment and follow up in these syndromes. Molecular diagnostics in endocrine tumours and diabetes are presented in two other articles in this series.
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PMID:[Molecular diagnostics in endocrine diseases]. 1647 3

We describe in two brothers an apparently novel syndrome comprising obesity, congenital hypothyroidism, neonatal colitis, cardiac biventricular hypertrophy, craniosynostosis, and developmental delay. The first brother presented with neonatal colitis and congenital hypothyroidism and died at age 5 weeks of fulminant colitis. The second brother presented neonatally with the same condition, but survived and subsequently developed severe obesity, sagittal and coronal synostosis, and developmental delay. Both pregnancies had been complicated by hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Exhaustive genetic and metabolic investigations have failed to provide a unifying pathogenesis. This unique combination of manifestations appears to represent a new syndrome with probable autosomal recessive or X-linked recessive inheritance.
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PMID:Obesity, hypothyroidism, craniosynostosis, cardiac hypertrophy, colitis, and developmental delay: a novel syndrome. 1716 33

An earlier adiposity rebound, suggestive of adult obesity, has been reported in children with congenital hypothyroidism. We undertook this study to evaluate the effect of congenital hypothyroidism on: 1) the timing of adiposity rebound, 2) the long-term prognosis of BMI status, and 3) the factors potentially affecting adiposity in subjects with congenital hypothyroidism. We found that in children with congenital hypothyroidism the BMI values were higher during the first years of life compared to normal population, but subsequently normalized. After the initial rise of BMI, the decline (nadir) and subsequent rise (adiposity rebound), usually occurring in normal children at an age greater than 30 months, was less evident in our group of children with congenital hypothyroidism. The severity of hypothyroidism affected BMI values at 6 and 12, but not at 36 months of age. In conclusion, in children with congenital hypothyroidism, 1) the high BMI values in early childhood normalize in adolescence, and 2) the normally expected BMI fluctuations during the first years of life are attenuated. These findings constitute indirect evidence that thyroid function during fetal and neonatal life affects BMI status during the first years of life.
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PMID:Obesity and attenuated adiposity rebound in children with congenital hypothyroidism. Normalization of BMI values in adolescents. 1761 7

Recent reports of the World Health Organization show iodine deficiency to be a worldwide occurring health problem. As iodine status is based on median urinary iodine excretion, even in countries regarded as iodine sufficient, a considerable part of the population may be iodine deficient. Iodine is a key element in the synthesis of thyroid hormones and as a consequence, severe iodine deficiency results in hypothyroidism, goiter, and cretinism with the well known biochemical alterations. However, it is also known that iodine deficiency may give rise to clinical symptoms of hypothyroidism without abnormality of thyroid hormone values. This led us to the hypothesis that iodine deficiency may give rise to subtle impairment of thyroid function leading to clinical syndromes resembling hypothyroidism or diseases that have been associated with the occurrence of hypothyroidism. We describe several clinical conditions possibly linked to iodine deficiency, a connection that has not been made thus far. In this paper we will focus on the relationship between iodine deficiency and obesity, attention deficit hyperactivity disorder (ADHD), psychiatric disorders, fibromyalgia, and malignancies.
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PMID:Iodine deficiency, more than cretinism and goiter. 1870 93

Various inactivating mutations in guanine nucleotide-binding protein, alpha-stimulating activity polypeptide1 (GNAS1) gene have been described with poor phenotype correlation. Pseudohypoparathyroidism type 1a (PHP1a) results from an inactivating mutation in the GNAS1 gene. Hormone resistance occurs not only to parathyroid hormone (PTH), but typically also to other hormones which signal via G protein coupled receptors including thyroid stimulating hormone (TSH), gonadotropins, and growth hormone releasing hormone. In addition, the phenotype of Albright hereditary osteodystrophy (AHO) is observed, which may include short stature, round facies, brachydactyly, obesity, ectopic soft tissue or dermal ossification (osteoma cutis) and psychomotor retardation with variable expression. We present a 2-year-old boy with PHP 1A who initially presented at age 3 weeks with congenital hypothyroidism. By 17 months of age, he manifested osteoma cutis, psychomotor retardation, obesity, brachydactyly and resistance to PTH with normocalcemia and mild hyperphosphatemia. Genetic analysis revealed a novel mutation in exon 13 of GNAS1 in our patient. This mutation, c.1100_1101insA, resulted in a frameshift and premature truncation of bases downstream. This mutation was also found in the mother of this patient who was also noted to have short stature, obesity, brachydactyly and non progressive osteoma cutis, but no hormone resistance.We report a novel heterozygous mutation causing PHP1A with PTH and TSH resistance and AHO which has not been described previously. PHP1A is also a rare presentation of congenital hypothyroidism.
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PMID:A novel mutation causing pseudohypoparathyroidism 1A with congenital hypothyroidism and osteoma cutis. 2127 2

Pseudohypoparathyroidism (PHP) is a group of disorders characterized by end-organ resistance to the parathyroid hormone (PTH). PHP type 1A includes multihormone resistance syndrome, Albright's hereditary osteodystrophy, and obesity and is caused by mutations in GNAS exon 1 through 13. PHP type 1B (PHP1B), caused by epigenetic changes in the GNAS locus, was initially described as an isolated resistance to PTH. Epigenetic changes in GNAS have also been reported in patients who display mild Albright's hereditary osteodystrophy or mild thyroid-stimulating hormone (TSH) resistance without mutation of GNAS. Here we report a case of PHP caused by epigenetic changes in GNAS in a patient with congenital hypothyroidism. The patient was referred for a positive newborn screening for hypothyroidism (TSH 50 mIU/L). She exhibited severe clinical features of congenital hypothyroidism. The thyroid was in place, and etiologic explorations were negative. TSH was normalized under L-thyroxin, and the symptoms disappeared, except for a macroglossia. In childhood, PHP was suspected in addition to elevated PTH, obesity, brachydactyly, and a rounded face. Sequencing, methylation analysis, and large deletion research were performed in GNAS. No genetic mutations were found. Methylation analysis revealed a broad epigenetic defect without deletion in GNAS consistent with sporadic PHP1B. The multilocus methylation analysis were negative. This finding expands the known onsets of PHP1B and emphasizes the need for a new PHP classification system. This case report has important consequences for the etiologic diagnosis of congenital hypothyroidism because it adds a new cause of the disease.
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PMID:Case report of GNAS epigenetic defect revealed by a congenital hypothyroidism. 2580 48


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