HypoparaNet: A Database of Chronic Hypoparathyroidism Based on Expert Medical-Surgical Centers in Italy.

Hypoparathyroidism is a rare disease characterized by low serum calcium levels and absent or deficient parathyroid hormone level. Regarding the epidemiology of chronic hypoparathyroidism, there are limited data in Italy and worldwide. Therefore, the purpose of this study was to build a unique database of patients with chronic hypoparathyroidism, derived from the databases of 16 referral centers for endocrinological diseases, affiliated with the Italian Society of Endocrinology, and four centers for endocrine surgery with expertise in hypoparathyroidism, to conduct an epidemiological analysis of chronic hypoparathyroidism in Italy. The study was approved by the Institutional Review Board. A total of 537 patients with chronic hypoparathyroidism were identified. The leading etiology was represented by postsurgical hypoparathyroidism (67.6%), followed by idiopathic hypoparathyroidism (14.6%), syndromic forms of genetic hypoparathyroidism (11%), forms of defective PTH action (5.2%), non-syndromic forms of genetic hypoparathyroidism (0.9%), and, finally, other forms of acquired hypoparathyroidism, due to infiltrative diseases, copper or iron overload, or ionizing radiation exposure (0.7%). This study represents one of the first large-scale epidemiological assessments of chronic hypoparathyroidism based on data collected at medical and/or surgical centers with expertise in hypoparathyroidism in Italy. Although the study presents some limitations, it introduces the possibility of a large-scale national survey, with the final aim of defining not only the prevalence of chronic hypoparathyroidism in Italy, but also standards for clinical and therapeutic approaches.

HER2 Analysis in Sporadic Thyroid Cancer of Follicular Cell Origin.

The Epidermal Growth Factor Receoptor (EGFR) family member human epidermal growth factor receptor 2 (HER2) is overexpressed in many human epithelial malignancies, representing a molecular target for specific anti-neoplastic drugs. Few data are available on HER2 status in differentiated thyroid cancer (DTC). The present study was aimed to investigate HER2 status in sporadic cancers of follicular cell origin to better clarify the role of this receptor in the stratification of thyroid cancer. By immunohistochemistry and fluorescence in-situ hybridization, HER2 expression was investigated in formalin-fixed paraffin-embedded surgical specimens from 90 DTC patients, 45 follicular (FTC) and 45 papillary (PTC) histotypes. No HER2 immunostaining was recorded in background thyroid tissue. By contrast, overall HER2 overexpression was found in 20/45 (44%) FTC and 8/45 (18%) PTC, with a significant difference between the two histotypes (p = 0.046). Five of the six patients who developed metastatic disease during a median nine-year follow-up had a HER2-positive tumor. Therefore, we suggest that HER2 expression may represent an additional aid to identify a subset of patients who are characterized by a worse prognosis and are potentially eligible for targeted therapy.

MTHFR C677T polymorphism, folate status and colon cancer risk in acromegalic patients.

BACKGROUND: Acromegalic patients have a higher risk of developing colorectal tumours (CRT). The common C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene is a well-documented CRT risk factor in the general population, but its role in acromegaly has never been examined. PURPOSE: We investigated the influence of MTHFR C677T polymorphism, folate status and other lifestyle, nutritional and disease-specific variables on CRT risk in acromegaly. METHODS: Clinical data were collected from 115 acromegalic patients (25 with active disease) who underwent a complete colonoscopy. C677T MTHFR genotype, homocysteine, vitamin B12, insulin growth factor and insulin levels, as well as metabolic variables were evaluated. RESULTS: Colorectal tumours were identified in 51 patients (3 adenocarcinomas). MTHFR C677T distribution was in the Hardy-Weinberg equilibrium and similar in patients with or without CRT. There was a correlation between patients with TT genotype and CRT occurrence (Spearman's test: P = 0.03), with an Odds Ratio (OR) of 1.32 (95% CI 0.522-3.362, P NS). A folate-MTHFR genotype interaction on CRT risk was found (P = 0.037): in the lower folate subgroup, TT patients showed a 2.4 higher OR for CRT (95% CI 0.484-11.891; P NS) than C-allele carriers. Smoking (P = 0.007), increased HbA1c levels (P = 0.021), dyslipidaemia (P = 0.049), acromegaly control (P = 0.057), and folate-MTHFR genotype interaction (P = 0.088) were associated with CRT at multivariate analysis. CONCLUSIONS: In this cohort of acromegalic patients, CRT risk is increased in 677TT MTHFR patients with low plasma folate levels. Smoking, high HbA1c levels, dyslipidaemia and disease activity were also associated with increased CRT risk.

Thyroid physiology in pregnancy.

OBJECTIVE: Various physiological changes occur in maternal thyroid economy during pregnancy. This review focuses on the events taking place during gestation that together strongly influence maternal thyroid function. METHODS: Scientific reports on maternal thyroid physiology in pregnancy. RESULTS: During the 1st trimester, human chorionic gonadotropin (hCG) induces a transient increase in free thyroxine (FT4) levels, which is mirrored by a lowering of thyroid-stimulating hormone (TSH) concentrations. Following this period, serum FT4 concentrations decrease of approximately 10 to 15%, and serum TSH values steadily return to normal. Also starting in early gestation, there is a marked increase in serum thyroxine-binding globulin (TBG) concentrations, which peak around midgestation and are maintained thereafter. This event, in turn, is responsible for a significant rise in total T4 and triiodothyronine (T3). Finally, significant modifications in the peripheral metabolism of maternal thyroid hormones occur, due to the expression and activity of placental types 2 and 3 iodothyronine deiodinases (D2 and D3, respectively). CONCLUSION: In line with these variations, both free thyroid hormone and TSH reference intervals change throughout pregnancy, and most scientific societies now recommend that method- and gestation-specific reference ranges be used for interpreting results in pregnancy.The maternal iodide pool reduces during pregnancy because of increased renal clearance of iodine and transfer of iodine to the feto-placental unit. This results in an additional requirement of iodine during pregnancy of ~100% as compared to nonpregnant adults. In accordance, the recommended iodine intake in pregnancy is 250 µg/day. A daily iodine intake below this threshold poses risks of various degrees of thyroid insufficiency for both the mother and the fetus.

Lack of association between autonomously functioning thyroid nodules and germline polymorphisms of the thyrotropin receptor and Gαs genes in a mild to moderate iodine-deficient Caucasian population.

BACKGROUND: Mutations of the thyrotropin receptor (TSHR) and/or Gαs gene have been found in a number of, but not all, autonomously functioning thyroid nodules (AFTNs). Recently, in a 15-year-old girl with a hyperfunctioning papillary thyroid carcinoma, we found two somatic and germline single nucleotide polymorphisms (SNPs): a SNP of the TSHR gene (exon 7, codon 187) and a SNP of Gαs gene (exon 8, codon 185). The same silent SNP of the TSHR gene had been reported in patients with AFTN or familial non-autoimmune hyperthyroidism. No further data about the prevalence of the two SNPs in AFTNs as well as in the general population are available in the literature. AIM: To clarify the possible role of these SNPs in predisposing to AFTN. METHODS: Germline DNA was extracted from blood leukocytes of 115 patients with AFTNs (43 males and 72 females, aged 31-85 years, mean ± SD = 64 ± 13) and 100 sex-matched healthy individuals from the same geographic area, which is marginally iodine deficient. The genotype distribution of the two SNPs was investigated by restriction fragment length polymorphism-polymerase chain reaction. RESULTS: The prevalence of the two SNPs in our study population was low and not different to that found in healthy individuals: 8 % of patients vs. 9 % of controls were heterozygous for the TSHR SNP and 4 % patients vs. 6 % controls were heterozygous for the Gαs SNP. One patient harbored both SNPs. CONCLUSIONS: These results suggest that these two SNPs do not confer susceptibility for the development of AFTN.

Serum interleukin-23 (IL-23) is increased in Hashimoto's thyroiditis.

Recent studies have demonstrated that T-helper 17 lymphocytes (Th17), which produce mostly IL-17, play a major role in several autoimmune diseases commonly thought to be Th1-related, including Hashimoto's thyroiditis (HT). IL-23, a member of the IL-12 cytokine family, is known to guide T cells toward the Th17 phenotype and its serum levels are increased in several autoimmune disease. Few data are available in the literature on IL-23 in HT. Using IL-23 Quantikine ELISA Kit (lower limit of detection 2.7 pg/mL) we analyzed the serum levels of IL-23 in 81 HT patients (75 females and 6 males, aged 14-70; mean age 39±17 years), and an age- and sex-matched group of 80 healthy persons. Both patients and controls did not receive any treatment. The positive detection rates of serum IL-23 were significantly higher in patients with HT: 56% of HT patients had detectable IL-23 in serum compared to 36% of healthy subjects (Chi χ² test, p=0.014). Moreover, HT patients had significantly higher serum concentrations of IL-23 (157.38 ± 17.92 pg/mL) in comparison with healthy controls (21.46 ± 5.4 pg/mL; p <0.0001). No significant correlation was found between serum levels of IL-23 and Tg-Ab or TPO-Ab levels, as well as with TSH values, in HT patients. In conclusion, serum IL-23 is increased in euthyroid and untreated HT patients, as compared to healthy subjects. Our data suggest that IL-23 would play a role in the pathogenesis of HT.

Role of pituitary dysfunction on cardiovascular risk in primary empty sella patients.

OBJECTIVE: Primary empty sella (PES) is a frequent anatomical condition rarely causing pituitary dysfunction. We assessed cardiovascular risk in a cohort of PES patients referred to Endocrine Units. DESIGN: The study was performed in three Italian tertiary referral centres. We evaluated pituitary function and cardiovascular risk, on the basis of lipid and glucose metabolism parameters and of Framingham score (FS), in 94 consecutive patients with PES diagnosis and in 94 gender, age and BMI matched controls. PATIENTS: Pituitary function was normal in 30 patients (group A), whereas a single or multiple pituitary hormone deficiency was demonstrated in 64 (group B). Growth hormone deficiency (GHD) was diagnosed in 56, central hypothyroidism in 35, hypogonadotropic hypogonadism in 32 and central hypoadrenalism in 24 cases. RESULTS: Framingham score was higher and glucose and lipid profile were worse in PES patients than in controls. Cardiovascular risk parameters were not different between group A and B. In group B, increased cardiovascular risk was associated with hypothyroidism and hypogonadism, but not with GHD. In group A, cardiovascular risk was higher and FT3 and FT4 levels were lower than in controls. Moreover, PES patients stratified for BMI showed a worse glucose and lipid profile and (in the overweight subgroup) higher FS than matched controls. CONCLUSIONS: Primary empty sella patients show increased cardiovascular risk, regardless of BMI. A worse lipid and glucose profile and higher FS were associated with secondary hypothyroidism, even subclinical, as well as hypogonadism.

Should aip gene screening be recommended in family members of FIPA patients with R16H variant?

Germline mutations of aryl-hydrocarbon-receptor interacting protein (AIP) are associated with pituitary adenoma predisposition. They occur in 20 % of familial isolated pituitary adenoma (FIPA) and in about 3-5 % of sporadic pituitary adenomas, especially in early onset somatotropinomas and prolactinomas. Our aim was to evaluate the clinical and genetic features of a large Italian FIPA family, where an AIP variant was identified. AIP direct sequencing from genomic DNA was carried out in 16 available family members. AIP R16H carriers also underwent magnetic resonance imaging and hormonal assessments. AIP mutations were also searched in 16 patients with sporadic growth hormone-secreting pituitary adenoma and in 6 unrelated patients in whom pituitary adenoma was excluded. We found an AIP R16H variation in two family members harbouring a pituitary adenoma and in 6 unaffected family members. No AIP mutation was found neither in growth hormone-secreting pituitary adenoma patients, nor in the unrelated patients without pituitary adenoma. We report a FIPA family harbouring an AIP R16H change, supporting the hypothesis that the latter represents a variant of unknown significance.

How to diagnose and manage Cushing's disease during pregnancy, when hypercortisolism is mild?

Diagnosis of mild Cushing's disease (CD) can be difficult in pregnant women, because its clinical and biochemical features can be erroneously interpreted as consequence of the gestation. Corticotropin releasing hormone (CRH) and desmopressin (DDAVP) tests are currently used to confirm CD, but data concerning adrenocorticotropic hormone (ACTH) response during pregnancy are lacking. A woman with mild cushingoid features was evaluated during the first trimester of gestation. Serum cortisol was normal at morning, but increased at midnight and incompletely suppressed by 1-mg dexamethasone overnight administration. Also 24-h urinary free cortisol levels were mildly elevated. She delivered vaginally a healthy newborn at the 39th week of an uneventful pregnancy. After delivery, an ACTH-secreting microadenoma was surgically removed. During the first trimester of gestation and after delivery, human CRH (h-CRH) and DDAVP-stimulated ACTH peaks were higher than those measured in 22 healthy premenopausal women. While the ACTH/h-CRH peak was intermediate between those measured in the healthy women and in 9 CD female patients, ACTH/DDAVP peak was in the range of CD patients and dramatically higher than those of healthy women. However, ACTH increase after h-CRH was significantly higher after delivery than during gestation (p < 0.003), while ACTH responses to DDAVP were similar. In pregnant women with mild cushingoid features, h-CRH and DDAVP tests are useful to confirm the diagnosis of CD. Mild hypercortisolism can be well tolerated, but cardiovascular and metabolic parameters should be monitored carefully.

Course of pregnancies in women with Cushing's disease treated by gamma-knife.

Data concerning pregnancy in women with Cushing's disease treated by gamma-knife (GK) are scanty. We present and discuss the course and outcome of five pregnancies in two women with Cushing's disease (CD), the first of whom was treated only by GK, and the second one treated by surgery, GK and ketoconazole. In the first patient, pregnancy was uneventful and full-term. During gestation, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were steady, and always in the normal range for healthy non-pregnant individuals. The newborn was healthy and normal-weight. In the second woman, two pregnancies, occurring 3 years after GK and few months after ketoconazole withdrawal, were interrupted by spontaneous abortion or placental disruption despite normal cortisol levels. This patient became again pregnant 3 years later and delivered vaginally a healthy full-term infant. Seven months after the delivery, the patient became pregnant again and at the 39th week of gestation delivered vaginally a healthy male. Hypoprolactinemia and/or central hypothyroidism occurred in both cases. In women with CD treated by GK, pregnancy can occur. However, pregnancy is at risk even when ACTH and cortisol levels are normalized by treatment. After GK, evaluation of pituitary function is mandatory due to the risk of hypopituitarism.

Maternal thyroid function in different conditions of iodine nutrition in pregnant women exposed to mild-moderate iodine deficiency: an observational study.

OBJECTIVE: We examined the effect of different conditions of nutritional iodine intake on maternal thyroid function throughout gestation in a cohort of healthy, anti-thyroid antibody-negative women from a mild-moderately iodine-deficient (ID) area. DESIGN: Observational cohort study. PATIENTS: The study included 168 women receiving prenatal preparations containing 150 µg of iodine from early pregnancy (150-I group); 105 women who had regularly used (>2 years) iodized salt prior to becoming pregnant (I-salt group); 160 women neither taking iodine supplements nor using iodized salt (no-I group). MEASUREMENTS: Maternal TSH, FT3 and FT4 were determined throughout gestation. RESULTS: Mean TSH concentrations were higher among the 150-I women than in the remaining two groups, and in a high proportion of them, TSH values were found to exceed the upper limit for gestational age. Conversely, the prevalence of low free-thyroxine levels in the 150-I women was similar to that observed in the I-salt women and markedly lower than that recorded for the no-I group. CONCLUSIONS: The regular use of iodine-containing supplements proved effective in reducing the risk of inappropriately low FT4 levels during pregnancy. The observed TSH increase in 150-I women may be because of a transient stunning effect on the thyroid gland, occurring as a result of the abrupt increase in daily iodine intake. Whilst the importance of gestational iodine supplementation is undisputed, we believe that in mild-moderately ID areas, women considering conception should be advised to take iodine supplementation for several months prior to pregnancy.

BRAFV600E mutation is associated with increased prevalence of contralateral lymph-node metastases in low and low-to-intermediate risk papillary thyroid cancer.

OBJECTIVE: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. Despite good prognosis being generally associated with PTC, persistent/recurrent disease can be observed in a not negligible number of patients. Accurate postoperative management can lead to a significant improvement of risk stratification/staging of PTC patients identifying those at higher risk of a more aggressive clinical course. Molecular tests were introduced at the beginning of the 2000s to improve PTC risk stratification. METHODS: We reviewed the records of 354/1185 patients affected by low or low-to-intermediate risk unilateral-PTC. In these patients, BRAFV600E mutation was looked for and 131-radioiodine therapy was performed 3 months after thyroid surgery. A radioiodine post-therapeutic imaging was obtained in all patients. RESULTS: BRAFV600E mutation was found in 170/354 PTC patients (female = 126). Forty-two out of 170 BRAFV600E mutation +ve patients (female = 27) had ipsilateral (n = 24) or contralateral (n = 18) loco-regional metastases at post-therapeutic imaging. Significant differences in terms of 2015 American Thyroid Association risk stratification, Hashimoto thyroiditis prevalence, tumor size, multifocality, disease staging and aggressive variant were observed between BRAFV600E mutation +ve and BRAFV600E mutation -ve patients (P ≤ 0.001;P = 0.001; P ≤ 0.001; P = 0.026; P ≤ 0.001; P ≤ 0.001). Interestingly, the prevalence of contralateral lymph-node metastases was significantly higher in BRAFV600E mutation +ve than BRAFV600E mutation -ve patients (18/42 vs. 2/22, respectively; P = 0.013). CONCLUSION: This study suggests that BRAFV600E mutation represents a significant risk factor for developing contralateral lymph-node metastases and confirms that BRAFV600E mutation is associated with more aggressive PTC features and a higher prevalence of metastatic disease also in low or low-to-intermediate-risk PTC patients.

Serum Levels of Soluble Receptor for Advanced Glycation End Products Are Reduced in Euthyroid Children with Newly Diagnosed Hashimoto's Thyroiditis: A Pilot Study.

OBJECTIVE: No data are available on advanced glycation end products (AGEs) and their soluble receptor (sRAGE) in pediatric patients with Hashimoto's thyroiditis (HT). The present study was aimed to simultaneously evaluate serum levels of sRAGE, AGEs, and advanced oxidation protein products (AOPPs) and investigate the relationships between these oxidative stress markers and clinical and biochemical parameters of thyroid function in euthyroid children with HT. DESIGN: This is a case-control study carried out in a single university hospital center. METHODS: We enrolled 19 newly diagnosed euthyroid HT pediatric patients (3 M, 16 F; median age 12.44 years, range 6.54-15.81 years) and 16 age-, sex-, and BMI-matched healthy controls (5 M, 11 F; median age 12.83 years, range 5.68-15.07 years). None was on levothyroxine treatment. The exclusion criteria were autoimmune, inflammatory, and infection comorbidities. Patients did not differ significantly from controls with regard to lipid or for anthropometric parameters. RESULTS: sRAGE levels were significantly lower in HT patients (median 414.30 pg/mL, range 307.30-850.30 pg/mL) than in controls (561.30, 273.20-1121.60 pg/mL; p = 0.034). No differences emerged between patients and controls with regard to serum AGEs (124.25 AU/g prot, 71.98-186.72 vs. 133.90, 94.06-200.78 AU/g prot, p = 0.707) and AOPPs (1.13 nmol/mL, 0.62-1.83 vs. 1.17, 0.76-1.42 nmol/mL, p = 0.545). CONCLUSIONS: sRAGE levels were decreased in euthyroid children/adolescents at the onset of HT, suggesting that autoimmunity per se seems to play an important role in such a reduction of sRAGE, irrespective of any functional alteration. Children and adolescents suffering from HT may exhibit increased susceptibility to oxidative damage, even when in euthyroid status.

Influence of Dietary Habits on Oxidative Stress Markers in Hashimoto's Thyroiditis.

Background: There is a growing awareness that nutritional habits may influence risk of several inflammatory and immune-mediated disorders, including autoimmune diseases, through various mechanisms. The aim of the present study was to investigate dietary habits and their relationship with redox homeostasis in the setting of thyroid autoimmunity. Materials and Methods: Two hundred subjects (173 females and 27 males; median age, 37 years) were enrolled. None were under any pharmacological treatment. Exclusion criteria were any infectious/inflammatory/autoimmune comorbidity, kidney failure, diabetes, and cancer. In each subject, serum thyrotropin (TSH), free thyroxine, antithyroid antibodies, and circulating oxidative stress markers were measured. A questionnaire on dietary habits, evaluating the intake frequencies of food groups and adherence to the Mediterranean diet, was submitted to each participant. Results: Among the 200 recruited subjects, 81 (71 females and 10 males) were diagnosed with euthyroid Hashimoto's thyroiditis (HT); the remaining 119 (102 females and 17 males) served as controls. In questionnaires, HT subjects reported higher intake frequencies of animal foods (meat, p = 0.0001; fish, p = 0.0001; dairy products, p = 0.004) compared with controls, who reported higher intake frequencies of plant foods (legumes, p = 0.001; fruits and vegetables, p = 0.030; nuts, p = 0.0005). The number of subjects who preferentially consumed poultry instead of red/processed meat was lower in HT subjects than in controls (p = 0.0141). In logistic regression analysis, meat consumption was associated with increased odds ratio of developing thyroid autoimmunity, while the Mediterranean diet traits were protective. In HT subjects, serum advanced glycation end products (markers of oxidative stress) were significantly higher (p = 0.0001) than in controls, while the activity of glutathione peroxidase and thioredoxin reductase, as well as total plasma antioxidant activity, were lower (p = 0.020, p = 0.023, and p = 0.002, respectively), indicating a condition of oxidative stress. Stepwise regression models demonstrated a significant dependence of oxidative stress parameters on consumption of animal foods, mainly meat. Conclusions: The present study suggests a protective effect of low intake of animal foods toward thyroid autoimmunity and a positive influence of such nutritional patterns on redox balance and potentially on oxidative stress-related disorders.

Maternal thyroid hormones are transcriptionally active during embryo-foetal development: results from a novel transgenic mouse model.

Even though several studies highlighted the role of maternal thyroid hormones (THs) during embryo-foetal development, direct evidence of their interaction with embryonic thyroid receptors (TRs) is still lacking. We generated a transgenic mouse model ubiquitously expressing a reporter gene tracing TH action during development. We engineered a construct (TRE2×) containing two TH-responsive elements controlling the expression of the LacZ reporter gene, which encodes ß-galactosidase (ß-gal). The specificity of the TRE2× activation by TH was evaluated in NIH3T3 cells by cotransfecting TRE2× along with TRs, retinoic or oestrogen receptors in the presence of their specific ligands. TRE2× transgene was microinjected into the zygotes, implanted in pseudopregnant BDF1 (a first-generation (F1) hybrid from a cross of C57BL/6 female and a DBA/2 male) mice and transgenic mouse models were developed. ß-gal expression was assayed in tissue sections of transgenic mouse embryos at different stages of development. In vitro, TRE2× transactivation was observed only following physiological T3 stimulation, mediated exclusively by TRs. In vivo, ß-gal staining, absent until embryonic day 9.5-10.5 (E9.5-E10.5), was observed as early as E11.5-E12.5 in different primordia (i.e. central nervous system, sense organs, intestine, etc.) of the TRE2× transgenic embryos, while the foetal thyroid function (FTF) was still inactive. Immunohistochemistry for TRs essentially colocalized with ß-gal staining. No ß-gal staining was detected in embryos of hypothyroid transgenic mice. Importantly, treatment with T3 in hypothyroid TRE2× transgenic mice rescued ß-gal expression. Our results provide in vivo direct evidence that during embryonic life and before the onset of FTF, maternal THs are transcriptionally active through the action of embryonic TRs. This model may have clinical relevance and may be employed to design end-point assays for new molecules affecting THs action.

Lymphocytic hypophysitis: differential diagnosis and effects of high-dose pulse steroids, followed by azathioprine, on the pituitary mass and endocrine abnormalities--report of a case and literature review.

We report on a man with a progressively increasing pituitary mass, as demonstrated by MRI. It produced neurological and ophthalmological symptoms, and, ultimately, hypopituitarism. MRI also showed enlargement of the pituitary stalk and a dural tail phenomenon. An increased titer of antipituitary antibodies (1:16) was detected in the serum. Pituitary biopsy showed autoimmune hypophysitis (AH). Neither methylprednisolone pulse therapy nor a subsequent treatment with azathioprine were successful in recovering pituitary function, or in inducing a significant reduction of the pituitary mass after an initial, transient clinical and neuroradiological improvement. Anterior pituitary function evaluation revealed persistent hypopituitarism. AH is a relatively rare condition, particularly in males, but it represents an emerging entity in the diagnostic management of pituitary masses. This case shows that response to appropriate therapy for hypophysitis may not be very favorable and confirms that diagnostic management of nonsecreting pituitary masses can be a challenge. Clinical, imaging, and laboratory findings are useful for suggesting the diagnosis, but pituitary biopsy may be necessary to confirm it.

Thyroid metastases from renal cell carcinoma: review of the literature.

The thyroid gland is a rare site of clinically detectable tumor metastasis and kidneys are frequently the site of the parent malignancy. In the present review on thyroid metastases from renal cell carcinoma, cases were searched on PubMed by entering the strings: "renal carcinoma [or "hypernephroma"] AND thyroid metastasis/metastases". Thus, we retrieved a total of 111 cases that were published between 1964 and 2007, a total that became 113 by adding two patients observed by us. The female to male ratio was 1.35:1. The primary renal cancer was almost always unilateral (90%) (with no significant side preference) and only rarely bilateral (9% in men, 4% in women), whereas bilaterality of thyroid metastases was relatively more frequent (28%). Thyroid metastasis from renal cancer was commonly single with a unique node that appears solid and hypoechoic at ultrasonography, approximately 9 years after nephrectomy. Concordance of lateralization was insignificantly greater for the right kidney/right thyroid lobe pattern (54%) than for the left kidney/left thyroid lobe pattern (40%), regardless of gender. Finally, survival was longer for women. Thyroid metastases, even if rare in the clinical practice, must be considered in the differential diagnosis of a thyroid nodule, particularly in patients who have a history of malignancies.