Insights into Hyperparathyroidism-Jaw Tumour Syndrome: From Endocrine Acumen to the Spectrum of CDC73 Gene and Parafibromin-Deficient Tumours.

A total of 1 out of 10 patients with primary hyperparathyroidism (PHP) presents an underlying genetic form, such as multiple endocrine neoplasia types 1, 2A, etc., as well as hyperparathyroidism-jaw tumour syndrome (HJT). We aimed to summarise the recent data, thus raising more awareness regarding HJT, from the clinical perspective of PHP in association with the challenges and pitfalls of CDC73 genetic testing and parafibromin staining. This narrative review included a sample-focused analysis from the past decade according to a PubMed search. We identified 17 original human studies (≥4 patients per article). The mean age at disease onset was between 20.8 and 39.5 years, while the largest study found that 71% of patients had HJT recognised before the age of 30. Males and females seemed to be equally affected, in contrast with sporadic PHP. PHP represented the central manifestation of HJT, occurring as the first manifestation in up to 85% of HJT cases. A biochemistry panel found a mean serum calcium level above the level of 12 mg/dL in PHP. PTH was elevated in HJT as well, with average values of at least 236.6 pg/mL. The most frequent pathological type in PHP was a parathyroid adenoma, but the incidence of a parathyroid carcinoma was much higher than in non-HJT cases (15% of all parathyroid tumours), with the diagnosis being established between the age of 15 and 37.5. In some families up to 85% of carriers suffered from a parathyroid carcinoma thus indicating that certain CDC73 pathogenic variants may harbour a higher risk. An important issue in HJT was represented by the parafibromin profile in the parathyroid tumours since in HJT both parathyroid adenomas and carcinomas might display a deficient immunoreactivity. Another frequent manifestation in HJT was ossifying fibromas of the jaw (affecting 5.4% to 50% of patients; the largest study found a prevalence of 15.4%). HJT was associated with a wide variety of kidney lesion (mostly: kidney cysts, with a prevalence of up to 75%, and renal tumours involved in 19% of patients). The risk of uterine lesions seemed increased in HJT, especially with concern to leiomyomas, adenofibromas, and adenomyosis. The underlying pathogenic mechanisms and the involvement of CDC73 pathogenic variants and parafibromin expression are yet to be explored. Currently, the heterogeneous expression of parafibromin status and, the wide spectrum of CDC73 mutations including the variety of clinical presentations in HJT, make it difficult to predict the phenotype based on the genotype. The central role of HJT-PHP is, however, the main clinical element, while the elevated risk of parathyroid carcinoma requires a special awareness.

FGF23 Beyond the Kidney: A New Bone Mass Regulator in the General Population.

Clinical studies investigating the relationship between fibroblast growth factor 23 (FGF23) and bone mass are controversial, especially in the healthy renal population. Our study is one of the forefronts investigating the relationship between FGF23 and bone mass parameters in the general population, according to age, sex, menopausal, and nutritional status. Cross-sectional study enrolling 123 volunteers between 20-80 years of age without primary osteoporosis under treatment nor secondary osteoporosis, where bone mass (bone mineral density-BMD, bone mineral content-BMC; assessed by Dual X-Ray Absorptiometry-DXA), body composition (DXA evaluation), and also the serum levels of FGF23, parathormone (PTH), 25(OH)D, bone resorption marker C-terminal telopeptide of type I collagen (CTx) and leptin were determined. FGF23 was negatively and independently associated with BMD and/or BMC in all groups. FGF23 contributed to up to 10% (p <0.05) of femoral neck BMD variance in postmenopausal women, but was not an accurate discriminator of normal versus low bone mass (AUC=0.622±0.076). FGF23 did not correlate with 25(OH)D, CTx, body weight, body composition parameters or leptin. FGF23 was independently associated with PTH in premenopausal women and men only. FGF23 was negatively associated with bone mass parameters in both sexes, but was not a fine discriminator between normal bone mass and osteopenia/osteoporosis. The mechanism through which FGF23 acts upon the bone seems independent of the nutritional status, requiring further investigation.

Incidence of transient and chronic hypoparathyroidism after total thyroidectomy - the experience of a tertiary center.

BACKGROUND: The most common cause of hypoparathyroidism (hypoPT) in adults is iatrogenic due to total thyroidectomy, while the ideal moment for considering it chronic is still under debate. Our study aims at reporting the prevalence of transient and permanent hypoPT following thyroid surgery in a tertiary surgical center, as well as serum Parathormone (PTH) variation up to 12 months after surgery stratified according to the type of thyroid disease. MATERIAL AND METHODS: 519 patients who underwent total thyroidectomy in a tertiary surgical center from 2018 to 2023 were analyzed. Postoperative hypoPT was defined as low PTH (less than 15 pg/ml) and/or hypocalcemia (albumin-corrected levels less than 8.5 mg/dl) on day 1 after surgery. Patients were considered to have permanent hypoPT if they had not recovered completely within 1 year after total thyroidectomy. PTH levels were compared according to the underlying thyroid disease. RESULTS: 140 patients (26.97%) had postoperative hypoPT. Twenty-two patients (4.23%) were considered to have permanent hypoPT 12 months after surgery. Approximately half of the patients recovered between 3 months and 12 months after surgery. HypoPT thyroiditis patients had higher PTH levels 3 months after surgery compared to papillary/follicular cancer and multinodular goiter, respectively, and all recovered 1 year after surgery. Papillary/follicular carcinoma was associated with a 29.4% rate of transient and 8.5% rate of chronic hypoPT, respectively. CONCLUSION: Most patients without incidental parathyroidectomy that still develop postoperative hypoPT will eventually recover; nevertheless, it can take up to 1 year for full resolution. Measuring serum PTH 3 months postoperative may be of interest.

Morphology and one immunohistochemical marker are enough for diagnosis of primary thyroid angiosarcoma.

Primary thyroid angiosarcoma is a very rare and extremely aggressive mesenchymal malignant neoplasm showing morphological and immunophenotypic evidence of endothelial cell differentiation. Early diagnosis of this tumor along with radical thyroidectomy followed by postoperative radiotherapy and chemotherapy are essential for adequate management of the patient. Currently available data on diagnosis and treatment options of this neoplasm are limited because it is a rare disease in endocrine organs. Raising awareness regarding its diagnosis can help to optimize the treatment and to improve the survival of the patient. We present the case of a 72-year-old female patient with multiple comorbidities who addressed to the hospital with obstructive respiratory symptoms: dyspnea, wheezing and hoarseness. The investigations, both clinical and paraclinical, identified a local invasive cervical mass located mainly in the left thyroid lobe, whose immunohistochemical examination confirmed primary thyroid angiosarcoma. Although this type of neoplasm is described mainly in the Alpine regions, it can appear in lower altitude regions and this tumor needs to be differentiated from a high-grade neoplasm (anaplastic thyroid carcinoma).

FGF23 and primary hyperparathyroidism: is there a link?

INTRODUCTION: Data regarding the role of fibroblast growth factor 23 (FGF23) in primary hyperparathyroidism (PHPT) are scarce and discordant. Our study aimed to evaluate the prognostic impact of FGF23 upon the clinical and biochemical evolution of PHPT. MATERIAL AND METHODS: Forty-two patients with ages between 30 and 80 years, diagnosed with PHPT caused by a sporadic, solitary parathyroid adenoma, and referred to surgery (minimally invasive parathyroidectomy) were prospectively included in the study. Serum levels of FGF23, PTH, 25(OH)D3, calcium (Ca), phosphate (P), total procollagen type 1 N-terminal propeptide, and C-terminal telopeptide of type I collagen were determined at baseline (preoperatory), one day after surgery, and in 13 patients also prospectively at three, six, and 12 months. Bone mineral density (BMD) was also evaluated before surgery in all patients and 12 months after surgery in the 13 followed up patients. RESULTS: In the 42 PHPT patients with D hypovitaminosis (mean 25(OH)D3 levels of 16.2 ± 1.5 ng/mL), preoperatory serum FGF23 concentration was within the normal range (75.55 ± 3.39 pg/mL) and remained unchanged one day post operation (81.69 ± 4.67 pg/mL, p = non-significant). The 13 patients followed prospectively for up to 12 months after surgery also showed unmodified FGF23 levels (80.9 ± 11.03 pg/mL, p = non-significant), despite PTH and Ca normalisation and vitamin D replenishment. Preoperatory FGF23 negatively correlated with PTH (r = -0.37, p = 0.038), but not with 25(OH)D3, Ca, P, bone mass, or metabolism markers. CONCLUSIONS: In PHPT, correlations between FGF23 and PTH seem rather an epiphenomenon. Therefore, we think that FGF23 evaluation and dynamics are not informative regarding PHPT severity. (Endokrynol Pol 2020; 71 (4): 306-312).

Leptin and adiponectin dynamics at patients with rectal neoplasm - Gender differences.

BACKGROUND: Numerous studies associate adipokines with colorectal malignancy, but few data deal with patients suffering exclusively of rectal carcinoma (RC). AIMS: We evaluated leptin and adiponectin levels in RC patients compared to healthy population and their dynamics after surgery. MATERIAL AND METHODS: Serum leptin and adiponectin were evaluated before surgery in 59 RC consecutive patients (38 males and 21 females), and in age and weight matched healthy controls. Measurements were repeated at 24, 72 hours and 7 days after surgery. RESULTS: Adipokine levels were higher in women. Controls had higher leptin (32.±4.34 vs 9.51±1.73 ng/ml in women and 11±2.66 vs 2.54±0.39 ng/ml in men, p = 0.00048 and 0.0032) and lower adiponectin (9±0.64 vs 11.85±1.02 µg/ml in women and 7.39±0.51 vs 8.5±0.62 µg/ml in men, p = 0.017 and 0.019) than RC patients. Surgery caused an increase of leptin from 5.11±0.8 to 18.7±2.42 ng/ml, p = 6.85 x 10¨8, and a decrease of adiponectin from 9.71±0.58 to 7.87±0.47 µg/ml, p = 1.4 x 10¨10 for all RC patients and returned thereafter to the initial range at 7 days. Adipokines were correlated with body weight (BW). The significance of correlation persisted after surgery only in males, but disappeared in females. Adipokines were not modified by tumor position, presurgical chemoradiotherapy or surgical technique. Women with RC experiencing weight loss had higher adiponectin than women without weight modifications (p<0.05 at all time points). CONCLUSIONS: Adipokine levels of patients with RC differ from the healthy population, possibly reflecting an adaptation to disease. Adipokine modifications after surgery may be related to acute surgical stress. Whether leptin and adiponectin directly interact is not clear. Women have higher adipokine levels, more so after significant weight loss, but the strength of their correlation with BW decreases after surgery. These data suggest gender differences in the adipokine profile of RC patients which may find clinical applications.