López Jm

Bone Turnover and Density in Healthy Women During Breastfeeding and After Weaning

To investigate the changes in maternal bone density and turnover associated with lactation we ran a longitudinal study in fully breastfeeding women (age 26.3±4.1 years, mean±SD) at the first (stage I, n=30) and sixth (stage II, n=25) months postpartum and 6 months after weaning (stage III, n=20), and in a contemporary control group of non-nursing women. At each time point bone density, serum calcium, phosphorus, alkaline phosphatases, parathyroid hormone (PTH), osteocalcin, follicle stimulating hormone (FSH), estradiol (E2), prolactin (PRL) urinary hydroxyproline and creatinine (OH-P/Cr) were measured in both groups. The daily calcium intake of nursing women (1479±590 mg/day at stage I) was higher than in non-nursing women (536±231 mg/day at stage I). Biochemical markers of bone turnover were higher (p<0.05) in nursing than in non-nursing women at stages I and II, while in stage III only OH-P/Cr was elevated. The lumbar spine (L2–4) bone mineral density was similar in the two groups at the beginning of the study (1.148 ±0.111 g/cm2 in nursing women vs 1.211±0.102 g/cm2 in non-nursing women; p=0.06), but it was lower in nursing women at stage II (1.144±0. 110g/cm2vs 1.216±0.095 g/cm2 respectively; p<0.05). Right femoral neck bone density decreased by 3% between stages I and II in nursing women but did not differ from values in non-nursing women (0.947±0.110 vs 0.973±0.108 in stage I and 0.918±0.114 vs 0.975±0.098 in stage II respectively; ps<0.05, ANOVA). After weaning, lumbar spine and femoral neck bone density increased by 6% and 8% respectively (p<0.05, ANOVA). No correlation was found between changes in bone turnover markers or bone density and parity, frequency and duration of nursing episodes, body weight, body mass index, and plasma PRL, E2 and PTH levels. We conclude that in nursing women with a daily calcium intake at the recommended dietary allowance (>1200 mg/day), full breastfeeding extending over 6 months is characterized by increased maternal bone turnover and a transient bone loss which normalizes after weaning.

Primary hyperparathyroidism: changes on biochemical and hormonal profile related to pregnancy.

A woman with mild asymptomatic hypercalcemia due to primary hyperparathyroidism became pregnant and her serum calcium normalized while her hypophosphatemia worsered. The PTH was low normal, but her urinary cAMP was elevated. In the second trimester of pregnancy a parathyroid adenoma was removed. After surgery, a transient hypocalcemia that normalized ten days later, a partial recovery of hypophosphatemia, and a 40% reduction of the elevated urinary cAMP excretion were observed. Pregnancy continued uneventful and a normal newborn was delivered. This case demonstrates the diagnostic difficulties posed by primary hyperparathyroidism during pregnancy, derived from inapparent changes in serum calcium and PTH. However, phosphorus and urinary cAMP deviations are significant constituting the basis for a correct diagnosis.

Utilidad de la PTH intraoperatoria como predictor de curación quirúrgica en hiperparatiroidismo primario

Serum PTH was measuredto all patients operated for PHPT between 2003 and 2008, before and five and ten minutes after theexcision of the parathyroid gland causing the disease. The criteria for complete cure were a normalserum calcium at 24 hours and 6 months after surgery and the pathological confirmation ofparathyroid gland excision.

Bioactive GH‐like immunoglobulins G in active acromegaly: response to long‐term treatment with bromocriptine

In acromegaly, certain forms of circulating immuno reactlve hGH are not true 6H but IgGs which possess G H biological activity (bioactive G H‐like IgGs). In this study, we tested the effect of bromocriptine on circulating bioactive G H‐like IgGs In an acromegalic woman. Increasing doses of oral bromocriptine (2.5, 5.0 and 7.5mg/day) were administered (for 2, 8 and 6 months respectively). TRH tests were performed before treatment and at the end of treatment with each dose. The patient was without detectable pituitary or extra‐pituitary tumour by magnetic resonance imaging. Her serum contained bioactive G H‐like IgGs equivalent to 240mU/l of hGH and elevated insulin‐like growth factor I (IGF‐I; 9500 U/l). Basal hGH was 12.8 μ/l and Increased to 220mU/l 15 min after TRH (200 μg, l.v.). In addition, in the basal samples of each test we measured total IgGs (radial immunodiffusion), bioactive GH‐like IgGs (isolated by Sephadex and protein A affinity chromatography and assayed using the Nb2 cell assay) and IGF‐I(RIA). Bromocriptine treatment gradually reduced serum levels of bioactive GH‐like IgGs and IGF‐I, with significant falls observed first at 10 months of treatment. Bioactive GH‐like IgGs were 240, 240, 36‐0 and <0.124mU/l and IGF‐I levels were 9500,8700,4000 and 3100 U/l at 0,2,10 and 16 months of treatment, respectively. In contrast, IR‐hGH response to TRH decreased after 2 months of treatment to 89 mU/l and to 49.2 mU/l at the end of the study while basal IR‐hGH remained between 13 and 8‐4 mU/l. Basal PRL fell to almost undetectable levels. Bromocriptine treatment decreased the G H response to TRH and the serum concentration of bioactive G H‐like IgGs and IGF‐I. The striking similarity between the pattern of decrease of serum bioactive GH‐like IgGs and IGF‐I supports the presence of an immuno component in our patients acromegaly

Carcinoma familiar del tiroides no medular (CFTNM): características de presentación en 17 casos

Retrospective analysis of medical records of patients with thyroid carcinoma. An index case wasdefined as a subject with the diagnosis of differentiated thyroid carcinoma with one or morefirst degree relatives with the same type of cancer. Seventeen such patients were identified andwere compared with 352 subjects with PTC.

Autoimmune thyroid disease in the puerperium. Predictive value of thyroid enlargement and related hormonal changes occurring during pregnancy

The incidence of goiter detected during pregnancy and its significance as an indicator of autoimmune thyroid disease after delivery was investigated in a sample of 707 pregnant women (81% in their 2nd trimester of gestation). Goiter was detected in 106 subjects (15%). Blood T4, T3, TSH, free T4 index (FT4I), antimicrosomal antibodies (AMA) and urinary iodine excretion were measured in these women and in a control group of gravidas without goiter. These measurements were repeated at 1 and 3 months after delivery. Compared with controls during pregnancy, subjects with goiter had lower FT4I values (11.0 ± 2.8 vs 9.0 ± 1.8; p < 0.01) and higher TSH values (2.9 ± 0.6 μU/ml vs 4.2 ± 2.1 μU/ml; p < 0.01). In contrast, T4, T3, AMA and urinary iodine excretion values were similar in both groups. In subjects with goiter FT4I values increased over pregnancy levels at 1 month (11.2 ± 2.0; p < 0.05) and 3 months (14.0 ± 3.0; p < 0.05) after delivery; in 29% a biochemical hyperthyroidism (FT4I > 13.5) was detected. During the same period TSH values decreased significantly (1 month: 1.9 ± 0.7 μU/ml; p < 0.05; 3 months: 2.7 ± 3.0 μU/ml; p < 0.05). Frequency of positive AMA increased from 8.6% during pregnancy up to 32.1% in the post-delivery period (p < 0.01). In the control group no variation in the FT4I, TSH or AMA were observed after delivery. These results indicate that goiter during pregnancy is common in Chilean gravidas and that it has predictive value for the appearance of autoimmune thyroid disease after delivery.

Genetic analysis and effect of triiodothyronine and prednisone trial on bone turnover in a patient with craniotubular hyperostosis

Craniotubular hyperostosis are a group of high bone mass disorders related to mutations in the LRP5 and SOST genes, although other causative genes remain to be identified. Little is known about the bone turnover and the response to T3 or glucocorticoids in these patients. We describe a patient with craniotubular hyperostosis, including mutation analyses of the LRP5, SOST, DKK1 and KRM1 genes. We also studied bone turnover and bone mineral density (BMD), before and after a trial with T3 (75 microg/d for 28 weeks) and T3 and prednisone (T3 100 microg/d for 2 weeks, followed by 10 weeks on prednisone 10 mg/d, and a final 2 weeks period off of medicactions, completing 3 cycles in 42 weeks. Mutation analysis of the complete coding region and flanking highly conserved sequences of SOST, evaluation of the presence of the 52-kb deletion associated with Van Buchem disease in Dutch patients and mutation analysis of exons 2-4 of LRP5, and the coding regions of DKK1 and KRM1 did not reveal any disease-causing mutations. A baseline 5 to 7 fold increase in osteocalcin and in deoxypiridinoline was detected. After 4 weeks on 75 microg/d of T3, osteocalcin decreased 36%, but at week 28, it returned to basal. Deoxypiridinoline did not change. After the first cycle on T3 and prednisone, osteocalcin decreased 72%, and at the end of the third cycle it remained 44% below basal value. Deoxypiridinoline was stable and high during the three cycles; no changes in BMD were observed. As we failed to identify any disease-causing mutations in our patient with craniotubular hyperostosis, we suggest that another gene must be involved in the pathogenesis of his condition. This study provides additional data about the high bone turnover described in craniotubular hyperostosis, and also suggests an abnormal response to T3 excess in this condition.