Coincidence or Causality: Parathyroid Carcinoma in Chronic Kidney Disease-Case Report and Literature Review.

Parathyroid carcinoma (PC) associated with primary hyperparathyroidism (PHPT) has been well investigated in recent years. Data regarding PC evolution in secondary hyperparathyroidism (SHPT) due to chronic kidney disease (CKD) are, however, scarce. Most features that raise the suspicion of PC in PHPT are part of the usual SHPT evolution in CKD, mirroring the natural changes undergone by the parathyroid glands. Therefore, pre-surgically establishing the malignant or benign character of the lesions is cumbersome. We present two cases of PC in end-stage renal disease, one of which was bilateral, diagnosed after total parathyroidectomy in a high-volume parathyroid surgery center. A literature review of the data was also performed. A systematic search of the PubMed/MEDLINE database until January 2024 identified 42 cases of PC associated with SHPT. Understanding the PC features in CKD might improve associated bone and mineral disease management, and reduce the risk of metastasis, parathyromatosis, or recurrence. Irradiation, prolonged immunosuppression, long dialysis vintage, and genotype may predispose to the malignant transformation of chronically stimulated parathyroids. Despite postsurgical diagnosis, favorable outcomes occurred when distant metastases were absent, even without "en bloc" resection. Further research is warranted to delineate specific diagnostic and therapeutic approaches tailored to this particular patient subpopulation.

Drugs Associated with Adverse Effects in Vulnerable Groups of Patients.

In recent years, a series of recommendations have been issued regarding the administration of drugs because of awareness of the serious side effects associated with certain classes of drugs, especially in vulnerable patients. Taking into account the obligation of the continuous improvement of professionals in the medical fields and the fact that we are in the midst of a "malpractice accusations pandemic", through this work, we propose to carry out a "radiography" of the scientific literature regarding adverse effects that may occur as a result of the interaction of drugs with the physiopathological particularities of patients. The literature reports various cases regarding different classes of drugs administration associated with adverse effects in the elderly people, such as fluoroquinolones, which can cause torsade de pointes or tendinopathy, or diuretics, which can cause hypokalemia followed by torsade de pointes and cardiorespiratory arrest. Also, children are more prone to the development of adverse reactions due to their physiological particularities, while for pregnant women, some drugs can interfere with the normal development of the fetus, and for psychiatric patients, the use of neuroleptics can cause agranulocytosis. Considering the physiopathological particularities of each patient, the drug doses must be adjusted or even completely removed from the treatment scheme, thus requiring the mandatory active participation both of clinician pharmacists and specialists in the activity of medical-pharmaceutical analysis laboratories within the structure of hospitals.

Preptin: A New Bone Metabolic Parameter?

Preptin is a 34-aminoacid peptide derived from the E-peptide of pro-insulin-like growth factor 2 (pro-IGF2) that is co-secreted with insulin and upregulates glucose-mediated insulin secretion. High serum preptin levels were described in conditions associated with insulin resistance, such as polycystic ovary syndrome and type 2 diabetes mellitus (T2M). Insulin and also IGF2 are known to be anabolic bone hormones. The "sweet bone" in T2M usually associates increased density, but altered microarchitecture. Therefore, preptin was proposed to be one of the energy regulatory hormones that positively impacts bone health. Experimental data demonstrate a beneficial impact of preptin upon the osteoblasts. Preptin also appears to regulate osteocalcin secretion, which in turn regulates insulin sensitivity. Preptin is greatly influenced by the glucose tolerance status and the level of physical exercise, both influencing the bone mass. Clinical studies describe low serum preptin concentrations in osteoporosis in both men and women, therefore opening the way towards considering preptin a potential bone anabolic therapy. The current review addresses the relationship between preptin and bone mass and metabolism in the experimental and clinical setting, also considering the effects of preptin on carbohydrate metabolism and the pancreatic-bone loop.

Pituitary hypoplasia and growth hormone deficiency in a patient with Coffin-Siris syndrome and severe short stature: case report and literature review.

Coffin-Siris syndrome (CSS) is a rare genetic disorder caused by the haploinsufficiency of one of the various genes that are part of the Brahma/BRG1-associated factor (BAF) complex. The BAF complex is one of the chromatin remodeling complexes, involved in embryonic and neural development, and various gene mutations are associated with cognitive impairment. CSS has a highly variable genotype and phenotype expression, thus lacking standardized criteria for diagnosis. It is generally accepted to associate 5th digit/nail hypoplasia, intellectual disability (ID)/developmental delay and specific coarse facial features. CSS patients usually display miscellaneous cardiac, genitourinary and central nervous system (CNS) anomalies. Many patients also associate intrauterine growth restriction, failure to thrive and short stature, with several cases demonstrating growth hormone deficiency (GHD). We report the case of a 4-year-old girl with severe short stature (-3.2 standard deviations) due to pituitary hypoplasia and GHD that associated hypoplastic distal phalanx of the 5th digit in the hands and feet, severe ID, coarse facial features (bushy eyebrows, bulbous nose, flat nasal bridge, dental anomalies, thick lips, dental anomalies, bilateral epicanthal fold) and CNS anomalies (agenesis of the corpus callosum and bilateral hippocampal atrophy), thus meeting clinical criteria for the diagnosis of CSS. Karyotype was 46,XX. The patient was started on GH replacement therapy, with favorable outcomes. Current practical knowledge regarding CSS diagnosis and management from the endocrinological point of view is also reviewed.

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).

Coexistent papillary thyroid carcinoma diagnosed in surgically treated patients for primary versus secondary hyperparathyroidism: same incidence, different characteristics.

BACKGROUND: The coexistence of hyperparathyroidism and thyroid cancer presents important diagnostic and management challenges. With minimally invasive parathyroid surgery trending, preoperative thyroid imaging becomes more important as concomitant thyroid and parathyroid lesions are reported. The aim of the study was to evaluate the rate of thyroid cancer in patients operated for either primary (PHPT) or secondary hyperparathyroidism (SHPT). METHODS: Our retrospective study included PHPT and SHPT patients submitted to parathyroidectomy and, when indicated, concomitant thyroid surgery between 2010 and 2017. RESULTS: Parathyroidectomy was performed in 217 patients: 140 (64.5%) for PHPT and 77 (35.5%) for SHPT. Concomitant thyroid surgery was performed in 75 patients with PHPT (53.6%), and 19 papillary thyroid carcinomas (PTC) were found, accounting for 13.6% from all cases with PHPT and 25.3% from PHPT cases with concomitant thyroid surgery. Thirty-one of operated SHPT patients (40.3%) also underwent thyroid surgery and 9 PTC cases were diagnosed (11.7% of all SHPT patients and 29% of patients with concomitant thyroid surgery). We found differences between PHPT and SHPT patients (p < 0.001) with respect to age (54.6 ± 13y versus 48.8 ± 12y), female-to-male ratio (8:1 versus ~ 1:1), surgical technique (single gland parathyroidectomy in 82.8% PHPT cases; versus subtotal parathyroidectomy in 85.7% SHPT cases) and presurgical PTH (357.51 ± 38.11 pg/ml versus 1020 ± 161.38 pg/ml). Morphopathological particularities, TNM classification and multifocality incidence of PTC were similar in the two groups. All PTC from patients with SHPT were thyroid microcarcinomas (TMC, i.e. tumors with a diameter smaller than 1 cm), whereas seven out of the 19 cases with PTC and PHPT were larger than 1 cm. CONCLUSIONS: PTC was frequently and similarly associated with both PHPT and SHPT irrespective of presurgical PTH levels. Thyroid tumors above 1 cm were found only in patients with PHPT. Investigators should focus also on associated thyroid nodular pathology in patients with PHPT.