[Factitious hyperthyroidism due to intake of herbal supplements for weight reduction]. / Hipertiroidismo facticio por ingesta de suplementos herbales para reducción de peso.

Factitious thyrotoxicosis is characterized by the intentional or accidental intake of excess thyroid hormones or their derivatives. We describe 6 cases of patients who developed thyrotoxicosis and adverse effects by weight-reducing herbal medicines. Currently there is a lot of publicity about supplements that "help to lose weight", which are over-the-counter and widely distributed in health food stores or online, which is why it is common to have patients who consume them, without many noticing their possible risks. If factitious hyperthyroidism is suspected, we should request thyroglobulin and anti-thyroglobulin tests, as well as a thyroid scan or uptake curve. To make the differential diagnosis between intake of thyroxine (T4) or triiodothyronine (T3) or its derivatives, we must request the measurement of T4 and T3. In case of ingestion of T4, T4 and T3 will be elevated, but in case of ingestion of triodothyronine or its derivatives, T4 will be decreased with elevated T3.

La tirotoxicosis facticia se caracteriza por la ingesta de un exceso de hormonas tiroideas o derivados de las mismas de forma intencional o accidental. Describimos 6 casos clínicos de pacientes que desarrollaron tirotoxicosis y efectos adversos con la ingesta de suplementos de herbales de venta libre para descenso de peso. Actualmente existe mucha publicidad sobre suplementos que "ayudan al descenso de peso", los cuales son de venta libre y distribuidos ampliamente en tiendas de dietéticas o por internet por lo cual es habitual tener pacientes que los consumen, sin que muchos reparen en sus posibles riesgos. En caso de sospechar un hipertiroidismo facticio debemos solicitar tiroglobulina y anticuerpos anti tiroglobulina así como centellograma tiroideo o curva de captación. Para realizar el diagnóstico diferencial entre ingesta de tiroxina (T4) o triiodotironina (T3) o sus derivados debemos solicitar medición de T4 y T3. En caso de ingesta de T4, la T4 y T3 se encontrarán elevadas, pero en caso de ingesta de triodotironina o sus derivados la T4 se encontrará descendida con una T3 elevada.

Hipertiroidismo facticio por ingesta de suplementos herbales para reducción de peso / Factitious hyperthyroidism due to intake of herbal supplements for weight reduction

Resumen La tirotoxicosis facticia se caracteriza por la ingesta de un exceso de hormonas tiroideas o derivados de las mismas de forma intencional o accidental. Describimos 6 casos clínicos de pacientes que desarrollaron tirotoxicosis y efectos adversos con la ingesta de suplementos de herbales de venta libre para descenso de peso. Actualmente existe mucha publicidad sobre suplementos que "ayudan al descenso de peso", los cuales son de venta libre y distribuidos ampliamente en tiendas de dietéticas o por internet por lo cual es habitual tener pacientes que los consumen, sin que muchos reparen en sus posibles riesgos. En caso de sospechar un hipertiroidismo facticio debemos solicitar tiroglobulina y anticuerpos anti tiroglobulina así como centellograma tiroideo o curva de captación. Para realizar el diagnóstico diferencial entre ingesta de tiroxina (T4) o triiodotironina (T3) o sus derivados debemos solicitar medición de T4 y T3. En caso de ingesta de T4, la T4 y T3 se encontrarán elevadas, pero en caso de ingesta de triodotironina o sus derivados la T4 se encontrará descendida con una T3 elevada.

Abstract Factitious thyrotoxicosis is characterized by the intentional or accidental intake of excess thyroid hormones or their derivatives. We describe 6 cases of patients who developed thyrotoxicosis and adverse effects by weight-reducing herbal medicines. Currently there is a lot of publicity about supplements that "help to lose weight", which are over-the-counter and widely distributed in health food stores or online, which is why it is com mon to have patients who consume them, without many noticing their possible risks. If factitious hyperthyroidism is suspected, we should request thyroglobulin and anti-thyroglobulin tests, as well as a thyroid scan or uptake curve. To make the differential diagnosis between intake of thyroxine (T4) or triiodothyronine (T3) or its deriva tives, we must request the measurement of T4 and T3. In case of ingestion of T4, T4 and T3 will be elevated, but in case of ingestion of triodothyronine or its derivatives, T4 will be decreased with elevated T3.

Displasia fibrosa ósea / Fibrous dysplasia of bone

La displasia fibrosa ósea es un trastorno no hereditario del desarrollo esquelético caracterizado por una proliferación anormal de fibroblastos y diferenciación deficiente de osteoblastos que conduce a un reemplazo del tejido óseo esponjoso por tejido conectivo fibroso. Es producida por una mutación somática activadora del gen GNAS1 que induce una activación y proliferación de células mesenquimales indiferenciadas con formación de tejido fibroso y trabéculas óseas anómalas. Existen formas monostóticas, poliostóticas y craneofaciales con diversos grados de dolor, deformidades y fracturas óseas, aunque muchos casos son asintomáticos. En ocasiones se producen quistes óseos aneurismáticos, hemorragias, compromisos neurológicos y raramente osteosarcomas. Algunos casos se asocian a síndrome de McCune-Albright, síndrome de Mazabraud y a osteomalacia por hipofosfatemia por pérdida tubular renal inducida por el FGF23 producido por el tejido displásico. Los hallazgos en las radiografías convencionales son característicos, aunque variables y de carácter evolutivo. La gammagrafía ósea es la técnica de imagen con mayor sensibilidad para determinar la extensión de la enfermedad. El diagnóstico diferencial incluye múltiples lesiones óseas de características similares y en raras ocasiones se requiere biopsia ósea o estudio genético para confirmarlo. No existe un consenso unánime acerca del abordaje terapéutico de estos pacientes, razón por la cual es necesario un enfoque multidisciplinario. La conducta puede ser expectante o quirúrgica según el tipo de lesiones y es importante el manejo del dolor y de las endocrinopatías asociadas. La mayor experiencia publicada se refiere al uso de bifosfonatos y, más recientemente, denosumab. Los tratamientos actuales son insuficientes para modificar el curso de la enfermedad y es necesario el desarrollo de nuevas moléculas que actúen específicamente en el gen GNAS1 o sobre las células mesenquimales afectadas. (AU)

Fibrous dysplasia of bone is a noninherited developmental anomaly of bone characterized by abnormal proliferation of fibroblasts and differentiation of osteoblasts that cause a replacement of trabeculous bone by fibrous connective tissue. It is caused by a somatic mutation in the GNAS1 gene, which induces an undifferentiated mesenquimal cells activation and proliferation with formation of fibrous tissue and abnormal osseous trabeculae. There are monostotic, polyostotic and craniofacial variants with different grades of bone pain, deformities and fractures, although many cases remain asymptomatic. Aneurysmal bone cysts, bleeding, neurological compromise and infrequently osteosarcoma are possible complications. Some cases are associated to McCune-Albright syndrome, Mazabraud syndrome or hypophosphatemia and osteomalacia due to to renal tubular loss induced by FGF23 produced by dysplastic tissue. The findings on conventional radiography are characteristic although variable and evlolve with time. Bone scintigraphy is the most sensitive technique to evaluate the extent of disease. Differential diagnosis include several osseous lesions of similar appearance and, in some cases, bone biopsy or genetic testing may be necessary. Today, there is no consensus regarding the therapeutic approach for these patients and it is necessary a multidisciplinary medical team. Watchful waiting or surgical interventions can be indicated, depending on the type of bone lesions. Bone pain and associated endocrinopathies management are very important. Most published experience refers to the use of bisphosphonates and, more recently, denosumab. Current treatments are insufficient to modify the natural curse of the disease and therefore, new molecules with specific action on GNAS1 gene or affected mesenchymal cells are necessary. (AU)

Recommended vitamin D levels in the general population. / Recomendaciones de vitamina D para la población general.

OBJECTIVE: To provide recommendations based on evidence on the management of vitaminD deficiency in the general population. PARTICIPANTS: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. METHODS: Recommendations were formulated using the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the term VitaminD and the name of each issue. Papers in English and Spanish with publication date before 17 March 2016 were included. Recommendations were jointly discussed by the Working Group. CONCLUSIONS: This document summarizes the data about vitaminD deficiency in terms of prevalence, etiology, screening indications, adequate levels and effects of supplementation on bone and non-skeletal health outcomes.

Tumour-induced osteomalacia: An emergent paraneoplastic syndrome.

Endocrine paraneoplastic syndromes are distant manifestations of some tumours. An uncommon but increasingly reported form is tumour-induced osteomalacia, a hypophosphatemic disorder associated to fibroblast growth factor 23 (FGF-23) secretion by tumours. The main biochemical manifestations of this disorder include hypophosphatemia, inappropriately low or normal tubular reabsorption of phosphate, low serum calcitriol levels, increased serum alkaline phosphatase levels, and elevated or normal serum FGF-23 levels. These tumours, usually small, benign, slow growing and difficult to discover, are mainly localized in soft tissues of the limbs. Histologically, phosphaturic mesenchymal tumours of the mixed connective tissue type are most common. Various imaging techniques have been suggested with variable results. Treatment of choice is total surgical resection of the tumour. Medical treatment includes oral phosphorus and calcitriol supplements, octreotide, cinacalcet, and monoclonal antibodies.

[Update of recommendations for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology]. / Actualización de las recomendaciones para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales. Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN.

OBJECTIVE: To update previous recommendations developed by the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition for the evaluation and treatment of osteoporosis associated to different endocrine and nutritional diseases. PARTICIPANTS: Members of the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition. METHODS: Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date between 18 October 2011 and 30 October 2014 were included. The recommendations were discussed and approved by all members of the Working Group. CONCLUSIONS: This update summarizes the new data regarding evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions.

Bone turnover markers in patients with prostate carcinoma: influence of sex steroids levels.

There are limited data about bone turnover markers (BTM) in androgen deprivation therapy (ADT)-treated prostate cancer (PCa) patients, and the relationship between sex steroids, bone mass, and BTM has not been explored. Our objective was to analyze the influence of sex steroids levels on BTM in patients with PCa treated with or without ADT. We performed a cross-sectional study including 83 subjects with PCa (54% with ADT). BTM, bone mineral density (BMD), and sex steroids were determined. BTM were inversely related to serum level of estrogens. Tartrate-specific acid phosphatase (TRAP-5b) showed a negative correlation with free estradiol (Free E) (r = -0.274, p = 0.014) and Bio E (r = -0.256, p = 0.022) that remained after adjustment for age: Free E (ß = -0.241, p = 0.03) and Bio E (ß = -0.213, p = 0.063). Bone-specific alkaline phosphatase (BSAP) concentrations were inversely related to Free E (r = -0.281, p = 0.011, age-adjusted ß = -0.256, p = 0.024). There was a negative correlation between osteocalcin (OC) levels and Free E (r = -0.195, p = 0.082; age-adjusted ß = -0.203, p = 0.076) and Bio E (r = -0.215, p = 0.054; age-adjusted ß = -0.240, p = 0.039). BTM and androgens were inversely related to TRAP-5b: total testosterone (total T) (r = -0.238, p = 0.033), Free T (r = -0.309, p = 0.05), and Bio T (r = -0.310, p = 0.05), but these correlations disappeared after age-adjustment. We did not find any relationship between BMD at different locations and sex steroids. In conclusion, in patients with PCa, estrogen levels influence bone resorption and bone formation whereas androgens may exert actions only in bone resorption. These results suggest that estradiol is the main sex steroid that regulates bone metabolism in males with prostate carcinoma.

[Treatment effect of breast cancer and prostate cancer on bone]. / Efecto del tratamiento del carcinoma de mama y del carcinoma de próstata sobre la masa ósea.

Aromatase inhibitors are used in the treatment of breast cancer and androgen deprivation therapy is used in prostate cancer. Both of them induce bone loss and increase fracture incidence. Early detection is important for patients with increased risk of osteoporotic fractures. In this article we review the available treatments and their indication to prevent the onset of osteoporosis and osteoporotic fractures in this patient group.

Serum osteoprotegerin and sex steroid levels in patients with prostate cancer.

The relationship between sex steroids and osteoprotegerin (OPG) in patients with prostate cancer is not well established. Our aim was to evaluate serum OPG levels in patients with prostate cancer and its relationship with sex steroids, bone mineral density, bone turnover markers, and fractures. We performed a cross-sectional study including 91 patients with prostate cancer. We determined: bone mineral density by dual-energy x-ray absorptiometry, bone turnover markers, serum levels of sex steroids and osteoprotegerin, and prevalent radiographic vertebral fractures. Serum OPG levels were higher in patients with vertebral fractures (8.02 ± 2.0 vs 4.91 ± 0.28 pmol/L; P < .05). OPG level and the duration of hormonal therapy were related (r = 0.299, P = .004), but this association did not persist after adjustment for age. In patients without androgen deprivation therapy, serum OPG levels were correlated with the levels of total testosterone (r = 0.508, P = .001) and bioavailable testosterone (r = 0.311, P = .037). In patients receiving androgen deprivation therapy, serum OPG levels were correlated with levels of total estradiol (r = 0.199, P = .18), bioavailable estradiol (r = 0.37, P = .009), and free estradiol (r = 0.349, P = .016). In conclusion, in patients with prostate cancer treated with androgen deprivation therapy, serum OPG levels were correlated with the levels of total estradiol, bioavailable estradiol, and free estradiol. Our hypothesis is that in patients with androgen deprivation therapy, the higher relative estrogen levels could stimulate OPG production in response to the higher resorption state. Future prospective studies are needed to clarify the role of OPG in androgen deprivation therapy-mediated bone loss.

An unusual association of neuroendocrine tumors in MEN 1A.

Multiple Endocrine Neoplasia type 1 is an autonomic dominant disease with a high degree of penetrance. It is characterized by combinations of over 20 different endocrine and nonendocrine tumors. A 25-year-old woman was referred for 1 year-evolution amenorrhea and bilateral galactorrhea. She also had fasting hypoglycaemia and hypercalcemia, and she was diagnosed of Multiple Endocrine Neoplasia type 1A. Resection of three parathyroid glands was performed showing hyperplasia of principal cells. Post-parathyroidectomy serum levels of calcium and intact PTH were normal but 3 years later serum calcium levels rose again. A 99mTc-sestamibi scan showed increased uptake in the low right area compatible with adenoma. After biochemical test showing probable insulinoma, somatostatin receptor scintigraphy showed a focal captation in head and body of pancreas. MRI found two nodules in the same localization. An antral gastrectomy, total pancreatoduodenectomy, colecistectomy and truncal vagotomy was performed and histopathologic examination revealed a combination of neuroendocrine tumors: gastrinomas, somastotinomas, glucagonomas and insulinomas. After surgery she started with tingling in fingers, toes and lips, and calcium levels was 5.9 mg/dl and PTH intact 3 pg/ml. A new 99m Tc-sestamibi scan showed no captation and cervical ultrasonography was normal. Now, 2 years later, she continues with normal calcium and i-PTH levels. This report represents an unusual case of MEN 1A with association of insulinomas, gastrinomas glucagonomas and somatostatinomas in the same patient.

Serum 25 OH vitamin D concentrations and calcium intake are low in patients with prostate cancer.

OBJECTIVE: To evaluate dietary calcium intake (DCI) and vitamin D serum concentrations in patients with prostate cancer. METHODS: We conducted a cross-sectional study including 91 subjects with prostate cancer. We determined DCI by a questionnaire, 25 OH vitamin D levels and bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA). RESULTS: According to current guidelines (1000 mg/day), calcium intake was low in patients with prostate cancer (394±201 mg/day). Twenty-two percent (20) of patients had adequate levels of vitamin D, whereas 29.7% (27) of patients were vitamin D deficient and 48.3% (44) were classified as vitamin D insufficiency. Vitamin D levels were not different in patients with or without androgen-deprivation therapy. There were no correlation between DCI, 25 OH vitamin and BMD. CONCLUSIONS: In summary, in our group of prostate cancer patients DCI was low and vitamin D deficiency is highly prevalent. Although this is a common condition in other populations, in this group of patients especially prone to osteoporosis could have more relevance. Additional research is needed to establish the consequences of low calcium intake and vitamin D deficiency in prostate cancer patients.

[Secondary hyperparathyroidism in advanced prostate cancer]. / Hiperparatiroidismo secundario en el cáncer de próstata avanzado.

BACKGROUND AND OBJECTIVE: High parathyroid hormone (PTH) concentrations are associated with increased bone resorption and bone matrix degradation. Some studies show elevated PTH concentrations and hypocalcemia in patients with advanced prostate carcinoma, although the pathophysiological significance of these findings is not well defined. MATERIALS AND METHODS: We performed a retrospective study of 60 patients diagnosed with advanced prostate cancer (44 nonmetastatic and 16 metastatic) treated with androgen deprivation. In all patients, PTH, calcium, phosphorus, 25 (OH) vitamin D and prostate-specific antigen (PSA) were determined. Bone scintigraphy had previously been performed. RESULTS: In patients with bone metastases, mean concentrations were as follows: calcium 9.19 mg/dl, phosphorus 3.47 mg/dl, 25 (OH) vitamin D 13.85 ng/ml, PTH 66.8 pg/ml and total PSA 101.27 ng/ml. For those without bone metastases, the results were calcium 9.39 mg/dl, phosphorus 3.38 mg/dl, 25 (OH) vitamin D 20.50 ng/ml, PTH 52.23 pg/ml and total PSA 2.52 ng/ml. PTH levels were significantly higher in patients with prostate cancer and bone metastases than in those without metastases (p=0.03). Vitamin D levels were also significantly lower in this group (p=0.03). There were no differences in other values. CONCLUSIONS: The present study found increased PTH concentrations in patients with advanced prostate cancer. This finding could be useful to predict disease progression.

[Hypophosphatasia: new therapeutic approaches]. / Hipofosfatasia: nuevas perspectivas terapéuticas.

Hypophosphatasia is a rare inborn error of metabolism characterized by a deficiency of tissue non-specific alkaline phosphatase (bone, liver and kidney) which leads to abnormal mineralization of skeletal and dental tissues. There are several forms of hypophosphatasia with wide variations in severity ranging from high-mortality neonatal presentation to mild forms in adults associated with fragility fractures and osteomalacia. The biochemical diagnosis is based on measurement of low levels of serum alkaline phophatase and increased serum or urine concentrations of phosphoethalnolamine, pyridoxal 5'-phosphate and inorganic pyrophosphate. To date, therapy has been quite heterogeneous with quite limited outcomes. The recent progress in research leads to new therapeutic approaches for this complex disease. The administration of parathyroid hormone in adult hypophosphatasia and enzyme replacement therapy using a novel soluble recombinant form of human alkaline phosphatase for severe forms of hypophosphatasia are currently the most promising approaches.