Cancer predisposition syndromes are entities determined especially by germinal pathogenic variants, with most of them autosomal dominantly inherited. The risk of a form of cancer is variable throughout life and affects various organs, including the thyroid. Knowing the heterogeneous clinical picture and the existing genotype–phenotype correlations in some forms of thyroid cancer associated with these syndromes is important for adequate and early management of patients and families. This review synthesizes the current knowledge on genes and proteins involved in cancer predisposition syndromes with thyroid cancer and the phenomena of heterogeneity (locus, allelic, mutational, and clinical).

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.

Children diagnosticated with idiopathic short stature (ISS) are probably, in most cases, underdiagnosticated. The genetic causes of ISS may be mutations of genes involved in local regulation of the growth plate or genes involved in the GH-IGF1 axis physiology. We present a kindred of five children evaluated for short stature or low normal stature, initially diagnosticated as idiopathic short stature, familial short stature, or being small for gestational age. Clinical signs suggestive of SHOX deletion screening in a child with short stature are low arm span/height ratio, increased sitting height/height ratio, BMI > 50% percentile, Madelung deformity, cubitus valgus, bowing and shortening of the forearm, dislocation of the ulna (at the elbow), and the appearance of muscular hypertrophy. Radiological characteristics suggestive of SHOX deficiency are triangularisation of the distal radial epiphysis, an enlarged diaphysis of the radius plus bowing of the radius, the convexity of the distal radial metaphysis, short fourth and fifth metacarpals, pyramidalization of the carpal row. Treatment with rGH is approved for children with SHOX gene deficiency and short stature. This kindred is an example that familial short stature, idiopathic short stature, and short stature due to a small gestational age are not final diagnoses. Complex investigations are necessary to identify the precise cause, leading to optimal clinical management. Treatment with rGH is an option for some of them; for others, it has no therapeutic response and, in some cases, is even harmful.

Personalized diagnosis can save unnecessary thyroid surgeries, in cases of indeterminate thyroid nodules, when clinicians tend to aggressively treat all these patients. Personalized diagnosis benefits from a combination of imagery and molecular biomarkers, as well as artificial intelligence algorithms, which are used more and more in our timeline. Functional imaging diagnosis such as SPECT, PET, or fused images (SPECT/CT, PET/CT, PET/MRI), is exploited at maximum in thyroid nodules, with a long history in the past and a bright future with many suitable radiotracers that could properly contribute to diagnosing malignancy in thyroid nodules. In this way, patients will be spared surgery complications, and apparently more expensive diagnostic workouts will financially compensate each patient and also the healthcare system. In this review we will summarize essential available diagnostic tools for malignant and benignant thyroid nodules, beginning with functional imaging, molecular analysis, and combinations of these two and other future strategies, including AI or NIS targeted gene therapy for thyroid carcinoma diagnosis and treatment as well.

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.

Primary aldosteronism is one of the most common causes of secondary hypertension. This condition is characterized by autonomous hypersecretion of aldosterone which produces sodium retention and potassium excretion, resulting in high blood pressure and potential hypokalemia. Transient postoperative hyporeninemic hypoaldosteronism with an increased risk of hyperkalemia may occur in some patients. We report the case of a 63-year-old patient with persistent hypokalemia, periodic paralysis, and refractory hypertension who was diagnosed with primary hyperaldosteronism due to elevated aldosterone, undetectable plasmatic renin concentration, and the presence of a left adrenal mass. One month after the surgery, the patient was admitted with signs of severe hyperkalemia (8 mmol/L) and worsened renal function, thus requiring hemodialysis. Fluid resuscitation, loop diuretic, and sodium bicarbonate treatment decreased his potassium. Zona glomerulosa insufficiency was confirmed by hormonal tests which exposed low aldosterone–renin axis. The fludrocortisone treatment was initiated and maintained, with consequent potassium and creatinine stabilization. Old age, long duration of hypertension, impaired renal function, severe hypokalemia before surgery, and large size of the aldosterone-producing adenoma are important risk factors for serious potassium imbalance after removal of the adenoma. We have to consider monitoring the patients after surgery for primary hyperaldosteronism in order to prevent severe hyperkalemia; therefore, postoperative immediate follow-up (arterial pressure, potassium, and renal function) is mandatory.