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International Journal of Molecular... Feb 2024A 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... (Review)
Review
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 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 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 pathogenic variants and parafibromin expression are yet to be explored. Currently, the heterogeneous expression of parafibromin status and, the wide spectrum of 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.
Topics: Male; Female; Humans; Young Adult; Adult; Parathyroid Neoplasms; Jaw Neoplasms; Hyperparathyroidism; Fibroma; Transcription Factors; Tumor Suppressor Proteins; Adenoma
PubMed: 38396977
DOI: 10.3390/ijms25042301 -
Indian Journal of Endocrinology and... 2023Primary hyperparathyroidism (PHPT) is rarely associated with the occurrence of acute or chronic pancreatitis, requiring complex perioperative management. This study...
BACKGROUND
Primary hyperparathyroidism (PHPT) is rarely associated with the occurrence of acute or chronic pancreatitis, requiring complex perioperative management. This study aimed to assess the prevalence and disease characteristics of pancreatitis in PHPT.
MATERIALS AND METHODS
This study is a clinicopathological analysis of the medical records of patients who were diagnosed with PHPT with pancreatitis between 1989 and 2021 in the Endocrine Surgery department, SGPGI, Lucknow.
RESULTS
Out of 548 PHPT cases, 44 (8.03%) were found to be associated with pancreatitis. The mean age was 33.57 years (15-65 years); 5 were ≤20 years, while 26 were ≤30 years of age. There were 27 males and 17 females. Twenty-one cases were of acute (11 acute, nine recurrent acute, one acute on chronic), whereas 23 were of chronic pancreatitis (six chronic calcific pancreatitis). The major clinical presentation of PHPT with pancreatitis was abdominal pain (65.91%). The mean number of attacks per patient in recurrent acute pancreatitis was two. Mean PTH levels were 68.19 pmol/L. The mean tumor size (in the largest dimension) was 2.79 ± 1.4 cm while the mean tumor weight was 4.91 g. Nephrolithiasis was associated with 25 cases. An association with multiple endocrine neoplasia type 1 syndrome was seen in one case. The final histopathological diagnosis was parathyroid carcinoma in two, hyperplasia in three, and parathyroid adenoma in 39 cases. Normocalcemia was seen in 27.2%, hypercalcemic crisis in 15.9%, and 25% of patients required semi-emergency parathyroidectomy. The outcome was favorable in all, as none had any further attacks of pancreatitis.
CONCLUSION
In our study, the prevalence of pancreatitis in PHPT cases was 8.03%. The majority of patients were young. Normocalcemia was seen in 12 patients, so even if calcium levels are normal, PHPT should be suspected in young patients with pancreatitis. Parathyroidectomy resulted in the complete resolution of symptoms of pancreatitis in all 44 patients.
PubMed: 38371176
DOI: 10.4103/ijem.ijem_169_23 -
Journal of Family Medicine and Primary... Dec 2023Multiple endocrine neoplasia (MEN) are tumors that involve two or more endocrine glands. It can also involve other organs and tissues as well. Out of the four types of...
Multiple endocrine neoplasia (MEN) are tumors that involve two or more endocrine glands. It can also involve other organs and tissues as well. Out of the four types of MEN type 2 is the most common. In MEN type 2 or type 3, paraganglioma is rare, but in our case, medullary thyroid carcinoma (MTC), hyperparathyroidism, and pheochromocytoma were associated with the paraganglioma.
PubMed: 38361883
DOI: 10.4103/jfmpc.jfmpc_328_23 -
Endocrine Jun 2024Cowden syndrome (CS) is a rare genetic condition due to the various germline mutations in the phosphatase and tensin homologue on chromosome ten (PTEN) tumour suppressor...
Cowden syndrome (CS) is a rare genetic condition due to the various germline mutations in the phosphatase and tensin homologue on chromosome ten (PTEN) tumour suppressor gene. As a result, CS is characterised by an increased risk of developing various benign and malignant tumours, such as thyroid, breast, endometrial and urogenital neoplasms, as well as gastrointestinal tract tumours. However, the neuroendocrine tumour association with CS is not elucidated yet. We present a case of a 46-year-old male patient diagnosed with testicular seminoma and follicular thyroid cancer in his medical history. Our patient met the clinical diagnostic criteria of Cowden syndrome. Genetic analysis established the clinical diagnosis; a known heterozygous PTEN mutation was detected [PTEN (LRG_311t1)c.388 C > T (p.Arg130Ter)]. Incidentally, he was also seen with multiple pulmonary lesions during his oncological follow-up. A video-assisted thoracoscopic left lingula wedge resection and later resections from the right lung were performed. Histological findings revealed typical pulmonary carcinoid tumours and smaller tumorlets. Somatostatin receptor SPECT-CT, F-FDG-PET-CT and F-FDOPA-PET-CT scans and endoscopy procedures could not identify any primary tumours in other locations. Our patient is the first published case of Cowden syndrome, associated with multifocal pulmonary carcinoids. Besides multiple endocrine neoplasia type 1, we propose Cowden syndrome as another hereditary condition predisposing to multiple pulmonary tumorlets and carcinoid tumours.
Topics: Humans; Hamartoma Syndrome, Multiple; Middle Aged; Male; Carcinoid Tumor; Bronchial Neoplasms; PTEN Phosphohydrolase
PubMed: 38353885
DOI: 10.1007/s12020-024-03693-8 -
Annales D'endocrinologie Apr 2024RET gain-of-function mutations are the most common drivers in medullary thyroid carcinoma, while RET fusions are identified in 5-10% of papillary thyroid carcinomas.... (Review)
Review
RET gain-of-function mutations are the most common drivers in medullary thyroid carcinoma, while RET fusions are identified in 5-10% of papillary thyroid carcinomas. Thus, RET plays a major role in the tumorigenesis of thyroid neoplasia, making it a valuable therapeutic target. Over a decade ago, multikinase inhibitors (MKIs) were first shown to have variable degrees of anti-RET activity. Despite some clinical efficacy in RET-altered thyroid cancers, significant off-target activity of MKIs led to marked toxicities limiting their use. More recently, two potent, highly selective RET inhibitors, selpercatinib and pralsetinib, were shown to have notable efficacy in RET-altered cancers, associated with more tolerable side effect profiles than those of MKIs. However, these treatments are non-curative, and emerging evidence suggests that patients who progress on therapy acquire mutations conferring drug resistance. Thus, the quest for a more definitive treatment for advanced, RET-altered thyroid cancers continues. This year we celebrate the 30 anniversary of the association of germline mutations of the RET proto-oncogene with the multiple endocrine neoplasia (MEN) type 2 syndromes. In this timely review, we summarize the current state-of-the-art treatment strategies for RET-altered thyroid cancers, their limitations, as well as future therapeutic avenues.
Topics: Humans; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms; Carcinoma, Neuroendocrine; Mutation; Germ-Line Mutation; Multiple Endocrine Neoplasia Type 2a; Protein Kinase Inhibitors
PubMed: 38342224
DOI: 10.1016/j.ando.2024.02.001 -
Cancers Jan 2024The clinical manifestation of multiple endocrine neoplasia type 2 (MEN2) in terms of developing medullary thyroid cancer (MTC), pheochromocytoma (PCC), and/or primary...
The clinical manifestation of multiple endocrine neoplasia type 2 (MEN2) in terms of developing medullary thyroid cancer (MTC), pheochromocytoma (PCC), and/or primary hyperparathyroidism (PHPT) is related to the respective pathogenic variant of the proto-oncogene. The aim of this study is to retrospectively analyze the individual, genotype-dependent clinical manifestations of a large cohort of MEN2 patients. By comparing their clinical profile with currently existing evidence-based knowledge, an optimal therapy and prevention strategy in terms of prophylactic thyroidectomy and clinical follow-up could be ensured. This is a retrospective single-center study of 158 MEN2 patients who were diagnosed and/or surgically treated at a tertiary referral care center between 1990 and 2022. All participants were categorized according to their pathogenic variant of the proto-oncogene. Subsequently, the clinical manifestation of the disease and its time of occurrence was documented. Our analysis showed results in line with existing studies, except for a considerably lower-than-predicted occurrence of PCC in patients with V804M/L mutations. This study supports the current recommendation regarding the pathogenic variant-dependent management of this rare cancer-associated syndrome.
PubMed: 38339246
DOI: 10.3390/cancers16030494 -
International Journal of Molecular... Feb 2024Several genetic investigations were conducted to identify germline and somatic mutations in somatotropinomas, a subtype of pituitary tumors. To our knowledge, we report...
Several genetic investigations were conducted to identify germline and somatic mutations in somatotropinomas, a subtype of pituitary tumors. To our knowledge, we report the first acromegaly patient carrying a pathogenic variant: c.2410G>A (rs79658334), p.Val804Met. Alongside the fact that the patient's father and daughter carried the same variant, we investigated the clinical significance of this variant in the context of somatotropinomas and other endocrine tumors, reviewing the mutations' oncogenic mechanisms. The aim was to search for new targets to precisely manage and treat acromegaly. Our case describes a new phenotype associated with the pathogenic variant, represented by aggressive acromegaly, and suggests consideration for mutation screening if NGS for well-established PitNET-associated gene mutations renders negative.
Topics: Humans; Acromegaly; Germ-Line Mutation; Multiple Endocrine Neoplasia Type 2a; Mutation; Phenotype; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms
PubMed: 38339173
DOI: 10.3390/ijms25031895 -
International Journal of Molecular... Jan 2024() and () are two long noncoding RNAs upregulated in multiple cancers, marking these RNAs as therapeutic targets. While traditional small-molecule and antisense-based...
() and () are two long noncoding RNAs upregulated in multiple cancers, marking these RNAs as therapeutic targets. While traditional small-molecule and antisense-based approaches are effective, we report a locked nucleic acid (LNA)-based approach that targets the and triple helices, structures comprised of a U-rich internal stem-loop and an A-rich tract. Two LNA oligonucleotides resembling the A-rich tract (i.e., AGCA) were examined: an LNA (L15) and a phosphorothioate LNA (PS-L15). L15 binds tighter than PS-L15 to the and stem loops, although both L15 and PS-L15 enable RNA•LNA-RNA triple-helix formation. Based on UV thermal denaturation assays, both LNAs selectively stabilize the Hoogsteen interface by 5-13 °C more than the Watson-Crick interface. Furthermore, we show that L15 and PS-L15 displace the A-rich tract from the and stem loop and methyltransferase-like protein 16 (METTL16) from the METTL16- triple-helix complex. Human colorectal carcinoma (HCT116) cells transfected with LNAs have 2-fold less and . This LNA-based approach represents a potential therapeutic strategy for the dual targeting of and .
Topics: Humans; Methyltransferases; Nucleic Acid Conformation; Oligonucleotides; RNA, Long Noncoding
PubMed: 38338910
DOI: 10.3390/ijms25031630 -
International Journal of Hyperthermia :... 2024Multiple endocrine neoplasia type 1 (MEN1), a rare tumor syndrome, is inherited in an autosomal dominant pattern, mainly manifested as primary hyperparathyroidism...
Multiple endocrine neoplasia type 1 (MEN1), a rare tumor syndrome, is inherited in an autosomal dominant pattern, mainly manifested as primary hyperparathyroidism (PHPT). Surgery is preferred for patients with MEN1 and PHPT. Thermal ablation has been widely applied for PHPT but rarely for postoperative recurrent PHPT in MEN1 patients. Based on a series of cases, we aimed to investigate the clinical efficacy and safety of ultrasound-guided percutaneous microwave ablation in the treatment of MEN1 patients with postoperative recurrence of PHPT.
Topics: Humans; Hyperparathyroidism, Primary; Microwaves; Multiple Endocrine Neoplasia Type 1; Parathyroidectomy; Treatment Outcome
PubMed: 38314667
DOI: 10.1080/02656736.2024.2308056 -
Problemy Endokrinologii Jun 2023Multiple endocrine neoplasia type 2B (MEN 2B) is a rare variant of hereditary tumor syndromes caused by germinal mutations in the proto-oncogene RET. One of the...
Multiple endocrine neoplasia type 2B (MEN 2B) is a rare variant of hereditary tumor syndromes caused by germinal mutations in the proto-oncogene RET. One of the components of the syndrome is multiple neurinomas, the early detection of which is not always given due attention. We present a description of the case of MEN 2B, manifested in the first months of life by intestinal ganglioneuromatosis. The disease presented with chronic constipation, including episodes of intestinal obstruction that required repeated surgical interventions. MEN 2B was suspected at the age of 15. At the time of diagnosis, an increase in serum calcitonin levels was noted (1041 pg/ml, norm <9.5 pg/ml), and a node in the thyroid gland was also determined (1,3*1,0*1,2 see, TIRADS 5), subsequently verified as a neoplasm of C-cells. By DNA analysis, a pathogenic variant p.Met918Thr, typical for MEN2 B, was detected in the RET gene. No signs of pheochromocytoma were found at the time of investigation. The patient underwent a thyroidectomy with lymphadenectomy. The difficulties of early diagnosis of sporadic cases of MEN 2B due to the nonspecificity of gastrointestinal manifestations of the disease are discussed.
Topics: Humans; Multiple Endocrine Neoplasia Type 2b; Thyroid Neoplasms; Ganglioneuroma; Pheochromocytoma; Adrenal Gland Neoplasms
PubMed: 38312000
DOI: 10.14341/probl13302