Calcifediol: a review of its pharmacological characteristics and clinical use in correcting vitamin D deficiency.

BACKGROUND: In addition to the role of vitamin D in bone mineralization, calcium and phosphate homeostasis, and skeletal health, evidence suggests an association between vitamin D deficiency and a wide range of chronic conditions. This is of clinical concern given the substantial global prevalence of vitamin D deficiency. Vitamin D deficiency has traditionally been treated with vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol). Calcifediol (25-hydroxyvitamin D3) has recently become available more widely. METHODS: By means of targeted literature searches of PubMed, this narrative review overviews the physiological functions and metabolic pathways of vitamin D, examines the differences between calcifediol and vitamin D3, and highlights clinical trials conducted with calcifediol in patients with bone disease or other conditions. RESULTS: For supplemental use in the healthy population, calcifediol can be used at doses of up to 10 µg per day for children ≥ 11 years and adults and up to 5 µg/day in children 3-10 years. For therapeutic use of calcifediol under medical supervision, the dose, frequency and duration of treatment is determined according to serum 25(OH)D concentrations, condition, type of patient and comorbidities. Calcifediol differs pharmacokinetically from vitamin D3 in several ways. It is independent of hepatic 25-hydroxylation and thus is one step closer in the metabolic pathway to active vitamin D. At comparable doses to vitamin D3, calcifediol achieves target serum 25(OH)D concentrations more rapidly and in contrast to vitamin D3, it has a predictable and linear dose-response curve irrespective of baseline serum 25(OH)D concentrations. The intestinal absorption of calcifediol is relatively preserved in patients with fat malabsorption and it is more hydrophilic than vitamin D3 and thus is less prone to sequestration in adipose tissue. CONCLUSION: Calcifediol is suitable for use in all patients with vitamin D deficiency and may be preferable to vitamin D3 for patients with obesity, liver disease, malabsorption and those who require a rapid increase in 25(OH)D concentrations.

Evidence based Latin American Guidelines of clinical practice on prevention, diagnosis, management and treatment of glucocorticoid induced osteoporosis. A 2022 update : This manuscript has been produced under the auspices of the Committee of National Societies (CNS) and the Committee of Scientific Advisors (CSA) of the International Osteoporosis Foundation (IOF).

Guidelines and recommendations developed and endorsed by the International Osteoporosis Foundation (IOF) are intended to provide guidance for particular pattern of practice for physicians who usually prescribe glucocorticoid (GC) therapy, and not to dictate the care of a particular patient. Adherence to the recommendations within this guideline is voluntary and the ultimate determination regarding their application should be made by the physician in light of each patient's circumstances. Guidelines and recommendations are intended to promote a desirable outcome but cannot guarantee any specific outcome. This guideline and its recommendations are not intended to dictate payment, reimbursement or insurance decisions. Guidelines and recommendations are subjected to periodic revisions as a consequence of the evolution of medicine, technology and clinical practice. A panel of Latin American (LATAM) experts specialized in osteoporosis with recognized clinical experience in managing patients with glucocorticoid-induced osteoporosis (GIO) met to produce evidence-based LATAM recommendations for the diagnosis and management of GIO. These guidelines are particularly intended to general practitioners and primary care physicians who prescribe GC treatments in LATAM to guide their daily clinical practice in terms of evaluation, prevention and treatment of GIO. These recommendations were based on systematic literature review using MEDLINE, EMBASE, SCOPUS and COCHRANE Library database during the period from 2012 to 2021. Randomized clinical trials (RCT), systematic reviews of RCT, controlled observational studies, guidelines and consensus were considered. Based on the review and expert opinion the panel members voted recommendations during two successive rounds of voting by panel members. Agreements for each statement were considered if a concordance of at least 70% was achieved following Delphi methodology. Grading of recommendations was made according to the Oxford Centre for the Evidence-based Medicine (EBM) criteria. Among five GIO guidelines and consensus initially identified, two of them (American College of Rheumatology 2017 and the Brazilian Guidelines 2021) were selected for comparison considering the latter as the most current guides in the LATAM region. Based on this methodology fifty statements were issued. All of them but four (1.20, 1.21, 1.23 and 4.2) attained agreement.

[An update on parathyroid carcinoma]. / Puesta al día: carcinoma paratiroideo.

Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.

Puesta al día: carcinoma paratiroideo / An update on parathyroid carcinoma

Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.

Salud ósea en pacientes sometidos a trasplante de precursores hematopoyéticos: un nuevo problema a considerar / Vitamin D and parathyroid hormone levels and bone mineral density in patients undergoing hematopoietic cell transplantation

Background: Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk of developing osteoporosis. Aim: To determine the frequency and severity of Vitamin D deficiency, secondary hyperparathyroidism and low bone mass in patients undergoing HCT. Patients and Methods: Analysis of the database of patients undergoing HCT in our institution in the 2010-2015 period. We searched for patients with measurements of 25-OH vitamin D (25OHD), parathyroid hormone (PTH) and bone densitometry by double beam X ray absorptiometry (DXA) prior and up to one year after HCT. Results: Ninety patients were included, 53 were evaluated prior to HCT and 37 after HCT. They represent 73% of all patients undergoing HCT in the period. Median 25OHD was 12 ng/ml (range 4-41.4). Ninety seven percent of patients had levels considered insufficient and 85% compatible with deficiency. Median PTH was 60.5 pg/ml (range 21-186). Forty five percent of patients had secondary hyperparathyroidism. DXA was performed in 65 patients (prior to HCT in 54 and after HCT in 11). Of these, 11% had had a low bone mineral density. Conclusions: Patients undergoing HCT have a high risk of vitamin D deficiency, secondary hyperparathyroidism and low bone mineral density.

Early pregnancy thyroid hormone reference ranges in Chilean women: the influence of body mass index.

OBJECTIVE: Thyroid dysfunction and obesity during pregnancy have been associated with negative neonatal and obstetric outcomes. Thyroid hormone reference ranges have not been established for the pregnant Hispanic population. This study defines thyroid hormone reference ranges during early pregnancy in Chilean women and evaluates associations of body mass index (BMI) with thyroid function. DESIGN, PATIENTS, MEASUREMENTS: This is a prospective observational study of 720 healthy Chilean women attending their first prenatal consultation at an outpatient clinic. Thyroid function [TSH, Free T4, Total T4 and antithyroid peroxidase antibodies (TPOAb)] and BMI were assessed at 8·8 ± 2·4 weeks of gestational age. RESULTS: Median, 2·5th percentile (p2·5), and 97·5th percentile (p97·5) TSH values were higher, while median, p2·5, and p97·5 free T4 values were lower in obese patients compared with normal weight patients. Obesity was associated with a median TSH 16% higher (P = 0·035) and a median free T4 6·5% lower (P < 0·01) than values from patients with normal weight. BMI had a small, but statistically significant effect on TSH (P = 0·04) and free T4 (P < 0·01) when adjusted by maternal age, TPO antibodies, parity, sex of the newborn, gestational age and smoking. In all TPOAb (-) patients, median (p2·5-p.97·5) TSH was 1·96 mIU/l (0·11-5·96 mIU/l) and median (p2·5-p.97·5) free T4 was 14·54 pmol/l (11·1 - 19·02 pmol/l). Applying these reference limits, we found a prevalence of overt and subclinical hypothyroidism of 0·9% and 3·05% respectively. CONCLUSIONS: TSH distributes at higher values and free T4 at lower values in obese pregnant women compared to normal weight pregnant women. Thyroid hormone reference ranges derived from Chilean patients with negative TPOAb are different from the fixed internationally proposed reference ranges and may be used in the Hispanic population.

[Vitamin D and parathyroid hormone levels and bone mineral density in patients undergoing hematopoietic cell transplantation]. / Salud ósea en pacientes sometidos a trasplante de precursores hematopoyéticos: un nuevo problema a considerar.

BACKGROUND: Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk of developing osteoporosis. AIM: To determine the frequency and severity of Vitamin D deficiency, secondary hyperparathyroidism and low bone mass in patients undergoing HCT. PATIENTS AND METHODS: Analysis of the database of patients undergoing HCT in our institution in the 2010-2015 period. We searched for patients with measurements of 25-OH vitamin D (25OHD), parathyroid hormone (PTH) and bone densitometry by double beam X ray absorptiometry (DXA) prior and up to one year after HCT. RESULTS: Ninety patients were included, 53 were evaluated prior to HCT and 37 after HCT. They represent 73% of all patients undergoing HCT in the period. Median 25OHD was 12 ng/ml (range 4-41.4). Ninety seven percent of patients had levels considered insufficient and 85% compatible with deficiency. Median PTH was 60.5 pg/ml (range 21-186). Forty five percent of patients had secondary hyperparathyroidism. DXA was performed in 65 patients (prior to HCT in 54 and after HCT in 11). Of these, 11% had had a low bone mineral density. CONCLUSIONS: Patients undergoing HCT have a high risk of vitamin D deficiency, secondary hyperparathyroidism and low bone mineral density.

Hemangioma capilar lobulado asociado a hiperplasia de células de Leydig testicular en adulto añoso: presentación de un caso / Testicular capillary hemangioma and Leydig cell hyperplasia in an elderly patient: A case report

La combinación de hemangioma capilar (HC) lobulado testicular con hiperplasia de células de Leydig es excepcional. Presentamos un caso en un varón de 72 años, con antecedente de seminoma testicular izquierdo hace 34 años, que consultó por asimetría mamaria. El estudio ultrasónico testicular mostró en el testículo derecho una lesión sólida, hipoecogénica, de 0,6 cm, con flujo vascular central y periférico. Los niveles de β-HCG, LH, estradiol y testosterona fueron normales. Mediante cirugía conservadora, con enucleación de la lesión, y biopsia intraoperatoria se confirmó la benignidad de la lesión. De acuerdo con lo revisado en la literatura, el presente caso sería el primer HC asociado a hiperplasia de células de Leydig en un adulto mayor (AU)

Lobulated capillary hemangioma with Leydig cell hyperplasia in the same nodule is exceptional. We report a case of a 72 year old male presenting with mammary asymmetry. Thirty seven years previously he had had a left sided testicular seminoma. Testicular ultrasonography of the right testicle revealed a 0.6 cm hypoecogenic nodule, which was solid with central and peripheral vascular flux. Beta-HCG, LH, estradiol and total testosterone levels were normal. Enucleation of the lesion was performed and an intraoperatory biopsy confirmed a benign lesion. The definitive diagnosis was lobulated capillary hemangioma with Leydig cell hyperplasia. To our knowledge, this is the first case reported in an adult (AU)

[From macro to micro thyroid carcinoma: records of a clinical hospital from 1991 to 2010]. / Del macro al microcarcinoma tiroideo: cambios en las características de presentación del cáncer de tiroides en un centro universitario chileno en 20 años.

BACKGROUND: The prevalence of thyroid cancer has increased, particularly in nodules smaller than 10 mm, probably due to the growing use of routine thyroid ultrasound. There is controversy about the biological behavior of micro carcinomas and the relevance of their early detection. AIM: To characterize the clinical presentation of thyroid cancer over 20 years in an University medical center and to evaluate the differences between macro and micro carcinomas. PATIENTS AND METHODS: We reviewed 1547 surgical biopsy records of thyroid cancer in our institution obtained between 1991 and 2010. RESULTS: We observed a sustained increase in the rate of thyroidectomies for thyroid cancer (per 1000 surgical procedures) in the study period. Papillary, follicular, mixed, medullary and anaplastic carcinomas were observed in 95, 3, 2, 0.5 and 0.1% of biopsies, respectively. The incidence of tumors of less than 10 mm (micro carcinoma) also increased. Those findings were associated with a significant decrease in tumor aggressiveness, determined by a low frequency of surgical margin involvement of thyroid capsule, perithyroid tissue invasion, vascular permeation and lymph node metastases. CONCLUSIONS: The increased prevalence of thyroid cancer, especially of micro carcinomas, may reflect the greater use of diagnostic ultrasound or represent a real change in the biological behavior of this disease and our data suggest that further studies are needed to know the impact of early treatment in the outcome of those patients because of the real less histologic agressiveness of micro carcinomas.

Del macro al microcarcinoma tiroideo: cambios en las características de presentación del cáncer de tiroides en un centro universitario chileno en 20 años / From macro to micro thyroid carcinoma: records of a clinical hospital from 1991 to 2010

Background: The prevalence of thyroid cancer has increased, particularly in nodules smaller than 10 mm, probably due to the growing use of routine thyroid ultrasound. There is controversy about the biological behavior of micro carcinomas and the relevance of their early detection. Aim: To characterize the clinical presentation of thyroid cancer over 20 years in an University medical center and to evaluate the differences between macro and micro carcinomas. Patients and Methods: We reviewed 1547 surgical biopsy records of thyroid cancer in our institution obtained between 1991 and 2010. Results: We observed a sustained increase in the rate of thyroidectomies for thyroid cancer (per 1000 surgical procedures) in the study period. Papillary, follicular, mixed, medullary and anaplastic carcinomas were observed in 95, 3, 2, 0.5 and 0.1% of biopsies, respectively. The incidence of tumors of less than 10 mm (micro carcinoma) also increased. Those findings were associated with a significant decrease in tumor aggressiveness, determined by a low frequency of surgical margin involvement of thyroid capsule, perithyroid tissue invasion, vascular permeation and lymph node metastases. Conclusions: The increased prevalence of thyroid cancer, especially of micro carcinomas, may reflect the greater use of diagnostic ultrasound or represent a real change in the biological behavior of this disease and our data suggest that further studies are needed to know the impact of early treatment in the outcome of those patients because of the real less histologic agressiveness of micro carcinomas.

An ultrasound model to discriminate the risk of thyroid carcinoma.

RATIONALE AND OBJECTIVES: Thyroid nodules are common on ultrasonographic examination and are mostly benign. Ultrasound characteristics may help discriminate thyroid carcinoma (TC) from benign nodules. The aims of this study were to identify ultrasonographic characteristics associated with TC and to validate a previously proposed model based on the presence of three ultrasonographic characteristics. MATERIALS AND METHODS: From a protocolized prospective registry of 1108 fine needle aspiration biopsies performed during a 16-month period at an ambulatory center, the ultrasonographic characteristics of TC and non-TC biopsies were compared. Adjusted odds ratios (ORs) and likelihood ratios for TC were estimated for eight combinations of three previously identified characteristics (microcalcifications, hypoechogenicity, and irregular borders). RESULTS: Microcalcifications (OR, 6.6; 95% confidence interval [CI], 4.4-9.9), hypoechogenicity (OR, 4.7; 95% CI, 2.8-8.0), and irregular borders (OR, 4.3; 95% CI, 2.8-6.5) were independently associated with TC. When added to a logistic regression model, the three ultrasonographic characteristics remained statistically significant. In the absence of these three features, the likelihood ratio for TC was 0.1 (95% CI, 0.0-0.2), while in their simultaneous presence, the likelihood ratio was 11 (95% CI, 6.6-19.0). CONCLUSIONS: The absence or simultaneous presence of three simple ultrasonographic characteristics generates a large change of pretest probability of TC and could avoid unnecessary fine needle aspiration biopsy.

Utilidad de la PTH intraoperatoria como predictor de curación quirúrgica en hiperparatiroidismo primario / Usefulness of intraoperative parathormone measurement to predict surgical cure in primary hyperparathyroidism

Background: The aim of the surgical treatment of primary hyperparathyroidism (PHPT) is to achieve its complete cure, evidenced by normal serum calcium in the postoperative period. Measurement of intraoperative serum parathormone (PTH) can be useful to predict complete cure of the disease. Aim: To assess the usefulness of intraoperative PTH measurement to predict complete cure of PHPT Material and methods: Serum PTH was measured to all patients operated for PHPT between 2003 and 2008, before and five and ten minutes after the excision of the parathyroid gland causing the disease. The criteria for complete cure were normal serum calcium at 24 hours and 6 months after surgery and the pathological confirmation of parathyroid gland excision. Results: Eighty-eight operated patients, aged 58±15 years (72 females) were studied. Sixty four percent were asymptomatic and their preoperative serum calcium was 11.6± 1.2 mg/dl. A normal serum calcium was achieved in 86 patients (98 percent) at 24 hours and 50 of 52 patients followed for six months (96 percent). The pathological study disclosed an adenoma in 69 (78 percent), and multiglandular disease in 16 (18 percent), a parathyroid cancer in one and a normal gland in one patient. Intraoperative PTH predicted early and definitive cure in 97 percent and 100 percent of patients with a single adenoma, respectively. Among patients with multiglandular disease, the predictive figures were 94 percent and 100 percent, respectively. Conclusions: Intraoperative PTH measurement efficiently predicts early and definitive surgical cure of PHPT.

[An ultrasound score to predict the presence of papillary thyroid carcinoma. Preliminary report]. / Diseño de una escala ecográfica predictora de malignidad en nódulos tiroideos: comunicación preliminar.

BACKGROUND: Thyroid nodules are common and associated to a low risk of malignancy. Their clinical assessment usually includes a fine needle aspiration biopsy (FNAB). AIM: To identify ultrasonographic characteristics associated to papillary thyroid carcinoma (PTC) and generate a score that predicts the risk of PTC. MATERIAL AND METHODS: Retrospective review of all fine needle aspiration biopsies of the thyroid performed in a lapse of two years. Biopsies that were conclusive for PTC were selected and compared with an equal amount of randomly selected biopsies that disclosed a benign diagnosis. RESULTS: One hundred twenty two biopsies of a total of 1,498 were conclusive for PTC. Univariate analysis showed associations with PTC for the presence of micro-calcifications (Odds ratio (OR) 49.2: 95% confidence intervals (CI) 18.7-140.9), solid predominance (OR 25.1; 95% CI 6-220), hypoechogenicity (OR 23.5, 95% CI 6.5-122.6), irregular borders (OR 17, 95% CI 7.2-42.9), lymph node involvement (OR 12.3, 95% CI2.7-112), central vascularization (OR 12.2, 95% CI 4.8-33.3), local invasion and hyperechogenicity (OR 0.2; CI 95% CI 0.03-0.6). Multivariate analysis disclosed microcalcifications (OR 28.1; CI 95% 8.9-89), hypoechogenicity (OR 9.4; 95% CI 1.5-59.5) and irregular borders (OR 4.7; CI 95% 1.5-15) as the variables independently associated with the presence of PTC. The prevalence of PTC in the presence of the three variables was 97.6% (Likelihood ratio (LR) 45) and 5.4% in their absence (LR 0.06). CONCLUSIONS: This scale predicts the presence or absence of PTC using simple ultrasound characteristics.

Diseño de una escala ecográfica predictora de malignidad en nódulos tiroideos: Comunicación preliminar / An ultrasound score to predict the presence of papillary thyroid carcinoma: Preliminary report

Background: Thyroid nodules are common and associated to a low risk of malignancy. Their clinical assessment usually includes a fine neddle aspiration biopsy (FNAB). Aim To identify ultrasonographic characteristics associated to papillary thyroid carcinoma (PTC) and generate a score that predicts the risk of PTC. Material and methods: Retrospective review of all fine needle aspiration biopsies of the thyroid performed in a lapse of two years. Biopsies that were conclusive for PTC were selected and compared with an equal amount of randomly selected biopsies that disclosed a benign diagnosis. Results: One hundred twenty two biopsies of a total of 1,498 were conclusive for PTC. Univariate analysis showed associations with PTC for the presence of micro-calcifications (Odds ratio (OR) 49.2: 95 percent confidence intervals (CI) 18.7-140.9), solid predominance (OR 25.1; 95 percent CI 6-220), hypoechogenicity (OR 23.5, 95 percent CI 6.5-122.6), irregular borders (OR 17, 95 percent CI 7.2-42.9), lymph node involvement (OR 12.3, 95 percent CI2.7-112), central vascularization (OR 12.2, 95 percent CI 4.8-33.3), local invasion and hyperechogenicity (OR 0.2; CI95 percent CI 0.03-0.6). Multivariate analysis disclosed microcalcifications (OR 28.1; CI 95 percent 8.9-89), hypoechogenicity (OR 9.4; 95 percent CI 1.5-59.5) and irregular borders (OR 4.7; CI 95 percent 1.5-15) as the variables independently associated with the presence of PTC. The prevalence of PTC in the presence of the three variables was 97.6 percent (Likelihood ratio (LR) 45) and 5.4 percent in their absence (LR 0.06). Conclusions: This scale predicts the presence or absence of PTC using simple ultrasound characteristics.

Psicofármacos y función gonadal / Psychotropic drugs and gonadal function

Psychotropic medications have a series of neurobiological effects which may be related to adverse effects. The endocrinological side effects may affect prolactin and thyroid, parathyroid and antidiuretic hormones. They may also influence the appearance of metabolic syndrome, gonadal and sexual problems. There disturbances must be borne in mind to prevent or detect them on time,since they may affect the compliance with the treatment. This revision focuses on the relationship between psychotropic drugs, antidepressants, mood stabilizers and gonadal function. As a general recommendation, patients using these medications should be monitored for menstrual and fertility disturbances, weight change, hirsutism, galactorrhea and changes in libido and sexual life.

[Usefulness of intraoperative parathormone measurement to predict surgical cure in primary hyperparathyroidism]. / Utilidad de la PTH intraoperatoria como predictor de curación quirúrgica en hiperparatiroidismo primario.

BACKGROUND: The aim of the surgical treatment of primary hyperparathyroidism (PHPT) is to achieve its complete cure, evidenced by normal serum calcium in the postoperative period. Measurement of intraoperative serum parathormone (PTH) can be useful to predict complete cure of the disease. AIM: To assess the usefulness of intraoperative PTH measurement to predict complete cure of PHPT. MATERIAL AND METHODS: Serum PTH was measured to all patients operated for PHPT between 2003 and 2008, before and five and ten minutes after the excision of the parathyroid gland causing the disease. The criteria for complete cure were normal serum calcium at 24 hours and 6 months after surgery and the pathological confirmation of parathyroid gland excision. RESULTS: Eighty-eight operated patients, aged 58+/-15 years (72 females) were studied. Sixty four percent were asymptomatic and their preoperative serum calcium was 11.6+/- 1.2 mg/dl. A normal serum calcium was achieved in 86 patients (98%) at 24 hours and 50 of 52 patients followed for six months (96%). The pathological study disclosed an adenoma in 69 (78%), and multiglandular disease in 16 (18%), a parathyroid cancer in one and a normal gland in one patient. Intraoperative PTH predicted early and definitive cure in 97% and 100% of patients with a single adenoma, respectively. Among patients with multiglandular disease, the predictive figures were 94% and 100%, respectively. CONCLUSIONS: Intraoperative PTH measurement efficiently predicts early and definitive surgical cure of PHPT.

[Pathological characteristics of thyroid microcarcinoma. A review of 402 biopsies]. / Características de presentación del microcarcinoma papilar del tiroides. Experiencia retrospectiva de los últimos 12 años.

BACKGROUND: Thyroid microcarcinoma is a tumor of 10 mm or less, that should have a low risk of mortality. However, a subgroup of these carcinomas is as aggressive as bigger tumors. AIM: To describe the pathological presentation of these tumors, and compare them with larger tumors. MATERIAL AND METHODS: All pathological samples of thyroid carcinoma that were obtained between 1992 and 2003, were studied. In all biopsies, the pathological type, tumor size, the focal or multifocal character, the presence of lymph node involvement and the presence of lymphocytic thyroiditis or thyroid hyperplasia, were recorded. RESULTS: One hundred eighteen microcarcinomas and 284 larger tumors were studied. The mean age of patients with microcarcinoma and larger tumors was 42.7+/-14 and 49.3+/-16 years respectively (p <0,001) and 83% were female, without gender differences between tumor types. Mean size of microcarcinomas was 8.6 mm and 116 (98%) were papillary carcinomas. Of these, 109 (94%) were well differentiated and seven (6%) were moderately differentiated. Thirty six (31%) were multifocal and in 10 (8,6%), there was lymph node involvement. The mean size of larger tumors was 23.8 mm and 241 (85%) were papillary carcinomas. Of these, 200 (83%) were well differentiated, and 41 (17%) were moderately differentiated. Eighty five (35%) were multifocal and in 44 (18%) there was lymph node involvement. The prevalence of thyroiditis and hyperplasia was significantly higher among microcarcinomas than in larger tumors (15 and 2.5%, respectively, p <0.001, for the former; 32.4 and 1.7%, respectively, p <0.001, for the latter). CONCLUSIONS: In this series, one third of microcarcinomas were multifocal and 10% had lymph node involvement. Therefore, the aggressiveness of these tumors is higher than what is reported in the literature and they should be treated with total thyroidectomy.

Novel intronic mutation of MEN1 gene causing familial isolated primary hyperparathyroidism.

Primary hyperparathyroidism may occur as part of hereditary syndromes, including multiple endocrine neoplasia types 1 and 2A (MEN1 and MEN2A), hyperparathyroidism-jaw tumor syndrome, and the familial isolated hyperparathyroidism (FIHP). It is unclear whether FIHP corresponds to a different genetic entity or a variant of MEN1 (or hyperparathyroidism-jaw tumor syndrome). We report a patient and 11 family members with FIHP in whom we identified a heterozygous G-to-A mutation at nucleotide 7361 of tumor suppressor MEN1 gene. This mutation is located in the first base of intron 9 (IVS9 + 1 G>A). All the family members with hyperparathyroidism were heterozygous for the intronic mutation. In vitro studies were performed in COS cells transfected with minigenes carrying the coding regions spanning exon-intron 9 and 10 with the mutant and the wild-type sequences. RT-PCR analyses showed an abnormal mRNA of greater size (829 bp) in the mutated MEN1 gene than the normal transcript (629 bp). The longer PCR product includes the exon 9, the unspliced intron 9, and part of exon 10. RT-PCR of MEN1 mRNA from patient's blood confirmed the existence of unspliced intron 9 in mature mRNA. In summary, we report a case of FIHP associated with a new intronic heterozygous germline mutation (IVS9 + 1 G>A) of MEN1 gene. This mutation produces an aberrant splicing of mRNA that could lead to a truncated protein, without activity, explaining the clinical picture of this patient and his family.