Advances in the management of parathyroid carcinoma.

Parathyroid carcinoma (PCA) is a rare malignancy accounting for approximately 1% of all patients with primary hyperparathyroidism. It is characterised by excessive parathyroid hormone (PTH) production. This manuscript reviews recent advances in the management of parathyroid carcinoma, focusing on molecular insights, diagnostic modalities, surgical innovations, adjuvant therapies, and emerging targeted treatments.

Pre-clinical phaeochromocytoma and paraganglioma models: Cell lines, animal models, and a human primary culture model.

While the establishment of human phaeochromocytoma and paraganglioma (PPGL) cell lines has proven to be particularly difficult over several decades of research, there are other reliable pre-clinical PPGL models currently available. This review provides a summary of these models, together with our recently established personalised drug screening platform using patient-derived PPGL primary cultures. Such currently available PPGL models include murine and rat PPGL cell lines, of which only one cell line (PC12) is publicly accessible through a cell repository, and PPGL animal models, of which the patient-derived xenograft models are promising but complex to establish.

Beware of epistaxis: fatal pseudoaneurysm rupture 30 years after treatment of acromegaly.

We present a fatal complication of treatment in a patient with early-onset acromegaly, treated with two transsphenoidal operations, radiotherapy, radiosurgery and pegvisomant. He was diagnosed in his 30s, and controlled from his 40s, with stable residual tumour within the left cavernous sinus. In his 60s, 30 years after surgery/radiotherapy and 14 years after radiosurgery, he developed recurrent episodes of mild epistaxis.

Opposing Effects of Cannabidiol in Patient-derived Neuroendocrine Tumor, Pheochromocytoma/Paraganglioma Primary Cultures.

Context: Treatment options for advanced neuroendocrine tumors (NETs), pheochromocytomas and paragangliomas (PPGLs) are still limited. In recent years, antitumor effects of cannabinoids have been reported; however, there are only very limited data available in NETs or PPGLs.

Objective: Investigation of the effects of cannabidiol (CBD) on patient-derived human NET/PPGL primary cultures and on NET/PPGL cell lines.

What We Know about and What Is New in Primary Aldosteronism.

Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, is seen in 5-10% of hypertensive patients, with its prevalence contingent upon the severity of the hypertension. The principal aetiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone-producing adenomas (APAs), while the less frequent causes include unilateral hyperplasia, familial hyperaldosteronism (FH) types I-IV, aldosterone-producing carcinoma, and ectopic aldosterone synthesis. This condition, characterised by excessive aldosterone secretion, leads to augmented sodium and water reabsorption alongside potassium loss, culminating in distinct clinical hallmarks: elevated aldosterone levels, suppressed renin levels, and hypertension.

The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinoma.

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex. Whilst surgery is the preferred treatment, adjunctive therapy with mitotane may be offered post-surgically to minimise the risk of recurrence or, in the absence of surgery, to attenuate progression.

Aim: The objective was to evaluate the effects of mitotane treatment on serum protein concentrations in patients treated for ACC with mitotane therapy and compare this to patients with other adrenal neoplasms and a normal pregnant cohort.

PD-L1 and HIF-2α Upregulation in Head and Neck Paragangliomas after Embolization.

Hypoxia activates pathways associated with tumor progression, metastatic spread, and alterations in the immune microenvironment leading to an immunosuppressive phenotype. In particular, the upregulation of PD-L1, a target for therapy with checkpoint inhibitors, is well-studied in several tumors. However, the relationship between hypoxia and PD-L1 regulation in pheochromocytomas and paragangliomas (PPGL), and especially in paragangliomas treated with embolization, is still largely unexplored.

Impact of the PI3K-alpha inhibitor alpelisib on everolimus resistance and somatostatin receptor expression in an orthotopic pancreatic NEC xenograft mouse model.

The mechanistic target of rapamycin complex 1 (mTORC1) inhibitor everolimus is one of the few approved therapies for locally advanced and metastatic neuroendocrine tumours (NETs). However, after initial disease stabilisation, most patients develop resistance within 1 year. Our aim was to overcome resistance to everolimus by additional treatment with the PI3K-alpha inhibitor alpelisib in an everolimus-resistant orthotopic pancreatic neuroendocrine carcinoma xenograft mouse model.

Primary Pituitary Carcinoids Do Not Exist: A Reappraisal in the Era of Pituitary Neuroendocrine Tumours.

The World Health Organization classification of pituitary tumours, published in 2022, supported a change in the terminology from "pituitary adenoma" to "pituitary neuroendocrine tumour" (PitNET). The neuroendocrine cells represent an integral part of the diffuse neuroendocrine system, including, among others, thyroid C cells, the parathyroid chief cells, and the anterior pituitary. Normal and neoplastic adenohypophyseal neuroendocrine cells have light microscopic, ultrastructural features and an immunoprofile compatible with the neuroendocrine cells and neuroendocrine tumours from other organs.

Tolvaptan for the treatment of the syndrome of inappropriate antidiuresis (SIAD).

The syndrome of inappropriate antidiuresis (SIAD), the commonest cause of hyponatraemia, is associated with significant morbidity and mortality. Tolvaptan, an oral vasopressin V2-receptor antagonist, leads through aquaresis to an increase in serum sodium concentration and is the only medication licenced in Europe for the treatment of euvolaemic hyponatraemia. Randomised controlled trials have shown that tolvaptan is highly efficacious in correcting SIAD-related hyponatraemia.

New developments and concepts in the diagnosis and management of diabetes insipidus (AVP-deficiency and resistance).

Diabetes insipidus (DI) is a disorder characterised by the excretion of large amounts of hypotonic urine, with a prevalence of 1 per 25,000 population. Central DI (CDI), better now referred to as arginine vasopressin (AVP)-deficiency, is the most common form of DI resulting from deficiency of the hormone AVP from the pituitary. The less common nephrogenic DI (NDI) or AVP-resistance develops secondary to AVP resistance in the kidneys.

Diagnosis and management of parathyroid carcinoma: a state-of-the-art review.

Parathyroid carcinoma is one of the least common endocrine malignancies and accounts for approximately 1% of all patients with primary hyperparathyroidism. A systematic review of peer-reviewed literature published between January 2000 and March 2022 via Medline, Embase, Cochrane Central Register of Controlled Trials, EudraCT, ClinicalTrials.gov, CINAHL and SCOPUS was conducted.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): Prevalence, clinicopathological characteristics and survival outcome in a cohort of 311 patients with well-differentiated lung neuroendocrine tumours.

Introduction: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is considered to be a rare condition associated with lung neuroendocrine tumours (NET), and its natural history is poorly described. We aimed to assess the prevalence and clinicopathologic characteristics of DIPNECH in the lung NET population, and to investigate predictors of time-to-progression (TTP) and overall survival (OS).

Methods: We retrospectively identified patients diagnosed with DIPNECH between April 2005 and December 2020.

Distinguishing Cushing's disease from the ectopic ACTH syndrome: Needles in a haystack or hiding in plain sight?

In the context of ACTH-dependent Cushing's syndrome, ectopic ACTH secretion from a neuroendocrine tumour is not uncommon, and needs to be carefully differentiated from pituitary-dependent Cushing's syndrome, Cushing's disease, in order to optimise therapy. Some cases may be quite obvious, while in others the diagnosis may be difficult to confirm and the source of ACTH problematic, as many clinical and biochemical tests may overlap with Cushing's disease. Imaging is essential, but needs to be interpreted in the light of both anatomical as well as functional imaging modalities.

Targeted Therapies in Pheochromocytoma and Paraganglioma.

Molecular targeted therapy plays an increasingly important role in the treatment of metastatic pheochromocytomas and paragangliomas (PPGLs), which are rare tumors but remain difficult to treat. This mini-review provides an overview of established molecular targeted therapies in present use, and perspectives on those currently under development and evaluation in clinical trials. Recently published research articles, guidelines, and expert views on molecular targeted therapies in PPGLs are systematically reviewed and summarized.

Ockham's Razor for a Retinal Lesion and Acromegaly and Breaking the Vicious Circle.

Acromegaly due to ectopic secretion of growth hormone-releasing hormone (GHRH) is rare. Treatment consists of surgical removal of the primary tumor, cytostatic therapy, "cold" or radioactive somatostatin analogue treatment, and medical therapy for acromegaly, if needed. A 53 year-old female had an ocular lesion noted on a routine optician visit, originally considered to be an ocular melanoma.

Biochemical discrepancies in the evaluation of the somatotroph axis: Elevated GH or IGF-1 levels do not always diagnose acromegaly.

The most frequent diagnosis underlying the finding of an elevated growth hormone (GH) and insulin-like growth factor-1 (IGF-1) is acromegaly due to a GH-secreting pituitary tumour. However, GH and IGF-1 levels can be discordant in patients with acromegaly due to early or partially treated disease, or there might be another cause of high GH or high IGF-1 unrelated to acromegaly, such as pre-analytical and technical pitfalls, physiological circumstances and pathological conditions. High GH and normal or low serum IGF-1, or alternatively, normal GH with elevated serum IGF-1, should be carefully assessed to avoid misinterpreting the activity of acromegaly or misdiagnosing a patient with acromegaly.

Metastatic medullary thyroid carcinoma: a new way forward.

Medullary thyroid carcinoma (MTC) is a rare malignancy comprising 1-2% of all thyroid cancers in the United States. Approximately 20% of cases are familial, secondary to a germline RET mutation, while the remaining 80% are sporadic and also harbour a somatic RET mutation in more than half of all cases. Up to 15-20% of patients will present with distant metastatic disease, and retrospective series report a 10-year survival of 10-40% from time of first metastasis.