Recovery of parathyroid function in patients with thyroid cancer treated by total thyroidectomy: An analysis of 685 patients with hypoparathyroidism at discharge of surgery.

OBJECTIVE: We aimed to study the predictive factors for recovery of parathyroid function in hypoparathyroid patients after total thyroidectomy for thyroid cancer. METHODS: We designed a retrospective, multicentre and nation-wide analysis of patients with total thyroidectomy who were seen in twenty endocrinology departments from January to March 2018. We selected patients with histologically proven thyroid cancer and retrieved information related to surgical procedure and thyroid cancer features. Survival analysis and Cox regression analysis were used to study the relationship between these variables and the recovery of parathyroid function. RESULTS: From 685 patients with hypoparathyroidism at discharge of surgery, 495 (72.3%) recovered parathyroid function over time. Kaplan-Meier analysis showed that this recovery was significantly related to the presence of specialized surgical team (P<0.001), identification of parathyroid glands at surgery (P<0.001), papillary histopathology (P=0.040), and higher levels of postoperative calcium (Ca) (P<0.001) and parathyroid hormone (PTH) (P<0.001). Subjects with gross extrathyroidal extension (P=0.040), lymph node metastases (P=0.004), and surgical re-intervention after initial surgery (P=0.024) exhibited a significant risk of persistence of hypoparathyroidism. Multivariate Cox regression analysis showed that the significant and independent factors for recovery of parathyroid function were postoperative concentrations of Ca (P=0.038) and PTH (P=0.049). The presence of lymph node metastases was a negative predictor of recuperation of parathyroid function (P=0.042) in this analysis. CONCLUSION: In patients with thyroid cancer, recovery of parathyroid function after total thyroidectomy was directly related to postoperative Ca and PTH concentrations, and inversely related to lymph node metastases.

Late Recovery of Parathyroid Function After Total Thyroidectomy: A Case-Control Study.

The clinical characteristics of patients with postoperative hypoparathyroidism who recover parathyroid function more than 12 months after surgery have not been studied. We aimed to evaluate whether the intensity of replacement therapy with calcium and calcitriol is related to the late recovery of parathyroid function. We compared the demographic, surgical, pathological, and analytical features of two groups of patients: cases, i. e., late recovery patients (those who recover parathyroid function>1 year after thyroidectomy, n=40), and controls, i. e., patients with permanent hypoparathyroidism (n=260). Replacement therapy with calcium and calcitriol was evaluated at discharge of surgery, 3-6 months, 12 months, and last visit. No significant differences were found in clinical, surgical, pathological, or analytical characteristics between cases and controls. The proportion of cases who required treatment with calcium plus calcitriol at 12 months was significantly lower than that found in controls (p<0.001). Furthermore, daily calcium and calcitriol doses in controls were significantly higher than those in cases at 3-6 months (p=0.014 and p=0.004, respectively) and at 12 months (p<0.001 and p=0.043, respectively). In several models of logistic regression analysis therapy with calcium and calcitriol at 12 months was negatively related to late recovery of parathyroid function. Although delayed recuperation of parathyroid function after total thyroidectomy is uncommon (13%), follow-up beyond 12 months is necessary in patients with postoperative hypoparathyroidism, especially in those whose needs of treatment with Ca and calcitriol are reducing over time.

Permanent postoperative hypoparathyroidism: an analysis of prevalence and predictive factors for adequacy of control in a cohort of 260 patients.

BACKGROUND: Recent guidelines for the treatment of hypoparathyroidism emphasize the need for long-term disease control, avoiding symptoms and hypocalcaemia. Our aim has been to analyze the prevalence of poor disease control in a national cohort of patients with hypoparathyroidism, as well as to evaluate predictive variables of inadequate disease control. METHODS: From a nation-wide observational study including a cohort of 1792 patients undergoing total thyroidectomy, we selected 260 subjects [207 women and 53 men, aged (mean ± SD) 47.2±14.8 years] diagnosed with permanent hypoparathyroidism. In every patient demographic data and details on surgical procedure, histopathology, calcium (Ca) metabolism, and therapy with Ca and calcitriol were retrospectively collected. A patient was considered not adequately controlled (NAC) if presented symptoms of hypocalcemia or biochemical data showing low serum Ca levels or high urinary Ca excretion. RESULTS: Two hundred and twenty-one (85.0%) patients were adequately controlled (AC) and 39 (15.0%) were NAC. Comparison between AC and NAC patients did not show any significant difference in demographic, surgical, and pathological features. Rate of hospitalization during follow-up was significantly higher among NAC patients in comparison with AC patients (35.9% vs. 10.9%, P<0.001). Dose of oral Ca and calcitriol were also significantly higher in NAC subjects. In a subgroup of 129 patients with serum parathyroid hormone (PTH) levels available, we found that NAC patients exhibited significantly lower postoperative PTH concentrations than AC patients [median (interquartile range) 3 (1.9-7.8) vs. 6.9 (3.0-11) pg/mL; P=0.009]. CONCLUSIONS: In a nation-wide cohort of 260 subjects with definitive hypoparathyroidism, 15% of them had poor disease control. These patients required higher doses of oral Ca and calcitriol, had higher rate of hospitalization during follow-up and showed lower PTH concentrations in the postoperative period.

Diagnosis and treatment of thyroid nodules in Spain. Results of a national survey. / Diagnóstico y tratamiento del nódulo tiroideo en España. Resultados de una encuesta nacional.

INTRODUCTION: Thyroid nodule (TN) is a common reason for consultation in daily practice. The purpose of this study was to evaluate the diagnosis and treatment of TNs in our environment and to assess the current status regarding the existence and structure of high-resolution TN clinics. MATERIAL AND METHODS: Members of the Spanish Society of Endocrinology and Nutrition were invited in 2018 to participate in an online survey on the diagnostic and therapeutic processes of TN. RESULTS: A total of 211 valid surveys were received. Of all respondents, 30.8% stated that there were high-resolution TN clinics in their environment, with the endocrinologist being the main person responsible for performing ultrasonography (87.7%) and fine needle aspiration (FNA) (69.2%). For ultrasound classification of TNs, 32.7% used the ATA criteria, 32.2% the TI-RADS criteria, and 22.7% no classification. In situ verification of sample suitability was performed in 35.5% of the cases, and molecular analysis in 8.1%. With regard to clinical discharge, 65.4% would consider it after 5 years of follow-up and with a benign FNA. In the event of a Bethesda III result, 50.2% of respondents would repeat FNA and 35.5% would opt for surgery; if a Bethesda IV result was found, 95.8% would opt for surgery. CONCLUSIONS: High-resolution TN clinics are structures increasingly implemented in our environment where the endocrinologist is the main person responsible for performing ultrasonography and FNA. The standard clinical practice in our specialty is consistent with most recommendations concerning clinical practice guidelines for TNs.

Diagnosis, treatment, and management of gestational hypothyroidism. The TIROGEST study.

INTRODUCTION: There is no agreement on the procedures to be used for diagnosis and treatment of gestational thyroid dysfunction. Controversy still exists on the normal range of thyroid-stimulating hormone (TSH) levels and use of gestational hypothyroidism (GH) screening. The aim of this study was to assess diagnosis and treatment of thyroid dysfunction during pregnancy in a group of Spanish hospitals. STUDY DESIGN: This was a retrospective, multicenter study in pregnant females with GH attending Spanish healthcare centers from March 2013 to July 2014. Variables analyzed included diagnosis criteria for GH (availability of universal screening for gestational thyroid disorders and TSH reference values (RVs) by trimester of pregnancy): risk factors for GH, iodine intake from food or supplementation, gestational age (at diagnosis/treatment) and l-thyroxine treatment. RESULTS: Fourteen centers participated in the study. Universal screening was performed in only half of the centers, and only 14% had their own TSH RVs. Overall, 257 pregnant women were enrolled, 53.7% with hypothyroidism (HT) diagnosed before pregnancy (pre-GH) and 46.3% with HT diagnosed during pregnancy (intra-GH). A comparison of intra-GH and pre-GH women showed that intra-GH women made their first visit later (59.7% vs. 75.4% respectively before week 12, p=0.007) and had more frequently high TSH levels (>2.5µIU/ml) during the first trimester (94.4% vs. 67.0% respectively, p<0.001). CONCLUSIONS: Our results suggest that GH may be underdiagnosed or inadequately diagnosed in most healthcare centers. These findings suggest the need of improving the current practice in Spain.

Prevalence and risk factors for hypoparathyroidism following total thyroidectomy in Spain: a multicentric and nation-wide retrospective analysis.

PURPOSE: The prevalence of postoperative hypoparathyroidism has been studied in registries and in surgical series with highly variable and imprecise results. However, the frequency of this hormonal deficiency in the clinical practice of endocrinologists is not known with accuracy. We aimed to assess the prevalence and risk factors of hypoparathyroidism in patients undergoing total thyroidectomy in Spain. METHODS: We designed a retrospective, multicentre and nation-wide protocol including all patients with total thyroidectomy who were seen in the endocrinology clinic of the participant centers from January to March 2018. Prevalence of hypoparathyroidism was evaluated at discharge of surgery, 3-6 months after surgery, 12 months after surgery and at last visit. Twenty hospitals participated in the study. RESULTS: Of 1792 patients undergoing total thyroidectomy, 866 (48.3%) developed postoperative hypoparathyroidism at discharge of surgery. Most of them recover parathyroid function over time. Prevalence of hypoparathyroidism at 3-6 months, 12 months and at last visit was 22.9%, 16.7% and 14.5%, respectively. The risk of developing definitive hypoparathyroidism was related to the presence of parathyroid tissue at histology, lymph node dissection, and two-stage thyroidectomy. Patients with thyroid cancer, with higher postoperative calcium levels and treated by expert surgical teams exhibited lower risk of developing permanent hypoparathyroidism. CONCLUSIONS: Although most patients with postsurgical hypoparathyroidism recover parathyroid function, the prevalence of permanent disease in clinical practice is non negligible (14.5%). Postoperative calcium, extent and timing of surgery, the presence of cancer, expert surgical team, and parathyroid tissue at histology are predictors of permanent hypoparathyroidism.

Frequent and Rare HABP2 Variants Are Not Associated with Increased Susceptibility to Familial Nonmedullary Thyroid Carcinoma in the Spanish Population.

BACKGROUND/AIMS: A genomic HABP2 variant was proposed to be responsible for familial nonmedullary thyroid carcinoma (FNMTC). However, its involvement has been questioned in subsequent studies. We aimed to identify genetic HABP2 mutations in a series of FNMTC patients and investigate their involvement in the disease. METHODS: HABP2 was sequenced from 6 index patients. Presence of the variants was investigated in all members of one family. Somatic BRAF and RAS "hotspot" mutations were investigated by the IdyllaTM BRAF Mutation Test and/or Sanger sequencing. RESULTS: Two HABP2 variants (p.E393Q and p.G534E) were identified in the index patient from one family with papillary thyroid carcinoma (PTC) (follicular variant). The prevalence of p.E393Q in Spanish control alleles was 0.5% and that of p.G534E was 5.1%. However, neither change cosegregated with the phenotype in 3 affected members and 5 healthy members of the kindred. Interestingly, all 3 members affected by PTC harbored the p.V600E somatic mutation in BRAF. CONCLUSIONS: The variant G534E is prevalent in the Spanish population (5.1%); however, p.E393Q is rare (< 1%) and none cosegregated with the FNMTC phenotype. The presence of the noninheritable V600E BRAF mutation in this family supports Knudson's "double-hit" hypothesis for cancer development and suggests the involvement of more than 1 gene in the clinical expression of FNMTC.

Cost of clinical management of acromegaly in Spain.

INTRODUCTION AND BACKGROUND: The cost of the therapeutic management of acromegaly depends on the selection of resources used, surgery and/or pharmacological treatment, by the specialist responsible for treatment, related to the characteristics of the patient and tumour. The objective of this work is to evaluate these costs for an illness that is rare but that is associated with a high morbidity in the context of routine clinical practice. METHODS: This was an epidemiological, prospective, naturalistic, multicentre study in Spain, in which 38 endocrinologists participated. Adult patients with acromegaly and a pituitary microadenoma or macroadenoma were included in the study. Patients were assigned, according to first-line treatment, to the following two groups: surgery first-line group (surgery in the 6 months before inclusion or during the follow-up period) and pharmaceutical first-line group (treatment with somatostatin analogues [SAs] for at least 6 months and with or without surgery after starting treatment with SAs). Data were collected during routine visits made during a follow-up period of 2 years. All resources were estimated at 2009 prices (€) and adjusted according to the Spanish consumer price index in 2010. RESULTS: Seventy-four patients were included, the majority of them with macroadenoma (70%). Eighty-eight percent of patients were treated surgically (76% as a first-line treatment), while 12% of patients received only SAs. Treatment with SAs was used at some point in the study by 85% of patients. The mean annual total cost of acromegaly is €9668 per patient (€9223 for the surgery group and €11,054 for the pharmaceutical group). Seventy-one percent of the direct cost of the disease corresponds to treatment with SAs. The cost of a patient treated only with surgery is €2501 on an annual basis, versus €9745 for a patient receiving only pharmacological treatment. In cases where a combination of both types of treatment is required, the annual total cost ranges from €10,866 to €12,364. CONCLUSION: The annual direct cost per patients of acromegaly in Spain is €9668. Even though surgery is the preferred option for treatment for a great number of patients, SAs must be added to the treatment regimen of the majority of such patients. The costs associated with this treatment are greater than the cost of treatment with SAs alone.

Coincidental diagnosis of an occult hilar steroid cell tumor of the ovary and a cortisol-secreting adrenal adenoma in a 49-year-old woman with severe hyperandrogenism.

OBJECTIVE: To report an exceptional association between an occult ovarian steroid cell tumor and a cortisol-secreting adrenal adenoma. DESIGN: Case report. SETTING: Endocrinology and nutrition unit at a general hospital in Spain. PATIENT(S): A 49-year-old woman who presented with persistence of severe hyperandrogenism after removal of a left adrenal adenoma. INTERVENTION(S): An endocrine study evaluating serum androgens, adrenal function, and tumor markers was ordered. Transvaginal sonography was done to rule out an ovarian tumor. Finally, a selective catheterization of ovarian veins allowed the correct diagnosis. MAIN OUTCOME MEASURE(S): Clinical and endocrine description of the patient and preoperative localization of the source of T secretion. RESULT(S): After adrenal surgery, urinary free cortisol levels decreased to normal values, but serum T remained within the tumoral range (3.04 ng/mL). Selective catheterization of ovarian veins revealed a gradient of T concentration in the right ovary. After bilateral annexectomy, a microscopic steroid cell tumor of hilar type was found in the right ovary. Serum T fell within the normal range, and hirsutism progressively improved. CONCLUSION(S): This unusual association between an occult-virilizing ovarian steroid cell tumor and a cortisol-secreting adrenal adenoma illustrates the value of an accurate preoperative workup in women with severe hyperandrogenism.