From the Old, the Best: Parathyroidectomy in the Management of Soft-Tissue and Vascular Calcification in Patients with Chronic Renal Disease

Introduction. Bone mineral disease in patients with chronic kidney disease (CKD-MBD) is a clinical syndrome involving bone, biochemical changes, and extraosseous calcification. These complications increase morbidity and mortality. Prevalence reports are rare. Case Report. This case shows a young woman on peritoneal dialysis (PD) for 10 years with severe secondary hyperparathyroidism and soft-tissue calcifications in the hands, pelvis, and right knee, as well as severe vascular calcification, managed with calcimimetics without success. We decided to perform subtotal parathyroidectomy (STPTX). Three months after surgery, she had satisfactory evolution, despite notable hungry bone disease, without bone pain or functional limitation and almost no calcifications. Discussion. The benefit of hemodialysis has been shown with better volume management and improvement of calcium/phosphate products. STPTX allowed biochemical control and calcification improvement, with an evident better quality of life for our patient. Therapeutic alternatives need to be tailored to the patient’s characteristics in the calcimimetics era.

Multiple Endocrine Neoplasia Type 1 with Concomitant Existence of Malignant Insulinoma: A Rare Finding

Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome of autosomal dominant inheritance defined by co-occurrence of two or more tumors originating from the parathyroid gland, pancreatic islet cells, and/or anterior pituitary. Insulinoma which has an incidence of 0.4% is a rare pancreatic neuroendocrine tumor. Malignant insulinoma is extremely rare, while primary hyperparathyroidism is a common occurrence in MEN1. We present a case of MEN1 syndrome with 2.6 cm insulinoma in the pancreatic head and parathyroid adenoma in a 56-year-old female who presented with symptoms suggestive of hypoglycemia like multiple episodes of loss of consciousness for four years. Classical pancreaticoduodenectomy was carried out, and the postoperative period was uneventful. Later, subtotal parathyroidectomy was performed, which showed parathyroid adenoma. Patients presenting with features of hypoglycemia should be vigilantly assessed for the presence of a sinister pathology.

A Case of Intrathyroidal Parathyroid Carcinoma Accompanied by Contralateral Parathyroid Hyperplasia

Parathyroid carcinoma accounts for about 0.5%-5% of all parathyroid neoplasms. Very rarely, but if the intrathyroidal parathyroid gland is present, the carcinoma can arise in that developmental anomaly. It is very difficult to distinguish a thyroid nodule from an intrathyroidal parathyroid neoplasm with preoperative radiologic and cytologic evaluations. A 59-year-old male was initially evaluated as presenting a follicular thyroid neoplasm accompanied by hyperparathyroidism. He received hemi-thyroidectomy with central neck dissection and subtotal parathyroidectomy. The final pathology evaluation revealed intrathyroidal parathyroid carcinoma and hyperplasia of contralateral parathyroid glands. We report this very rare and unique clinical situation with a literature review.

The Usefulness of Intraoperative PTH as a Predictor for Successful Parathyroidectomy in Secondary Hyperparathyroidism

Introduction: Secondary hyperparathyroidism (SHPT) is a multisystemic syndrome that affects calcium and bone homeostasis in patients with chronic kidney disease (CKD). Despite medical treatment, 1–2% of patients require parathyroidectomy annually. The use of an intraoperative parathormone protocol (IOPTH) to predict cure is still in debate, due to the lack of standardized protocols, the use of different assays, and uneven PTH clearance. This study aimed to determine the diagnostic accuracy of an IOPTH in patients with SHPT for predicting successful surgery after parathyroidectomy.Methods: About 30 patients were enrolled. A prospective observational study (cohort) was performed in patients who were submitted to parathyroidectomy by an endocrine surgeon for SHPT. All were submitted to a bilateral neck exploration with a subtotal parathyroidectomy. Three IOPTH determinations were withdrawn: at anesthetic induction (PTH0), 15 min (PTH15), and 30 min (PTH30) after completion of gland resection. Another sample was taken 24 h after the procedure (PTH24), values <150 pg/mL defined a successful surgery, and patients were assigned to the success or failure group. IOPTH drop was analyzed to predict successful surgery with drops of 70 and 90% at 15 and 30 min, respectively.Results: A total of 26 patients were included, 19 patients were in the successful group. IOPTH showed a significant difference between groups in their absolute PTH15 and PTH30 values. A significant difference was also found in their PTH drop at 30 min (81 vs. 91%, p = 0.08). For predicting a successful surgery, having a PTH drop >90% at 30 min was the most significant factor [Odds Ratio (OR) 3.0 (1.5–4) IC 95%].Conclusions: This study points toward a stricter and staggered IOPTH protocol to predict a successful surgery. Our results suggest taking a PTH15 expecting a PTH drop of >90%. If this is not achieved, reexploration and a PTH30 sample are suggested to accurately predict success.

GHRH secretion from a pancreatic neuroendocrine tumor causing gigantism in a patient with MEN1

Summary A male patient with a germline mutation in MEN1 presented at the age of 18 with classical features of gigantism. Previously, he had undergone resection of an insulin-secreting pancreatic neuroendocrine tumour (pNET) at the age of 10 years and had subtotal parathyroidectomy due to primary hyperparathyroidism at the age of 15 years. He was found to have significantly elevated serum IGF-1, GH, GHRH and calcitonin levels. Pituitary MRI showed an overall bulky gland with a 3 mm hypoechoic area. Abdominal MRI showed a 27 mm mass in the head of the pancreas and a 6 mm lesion in the tail. Lanreotide-Autogel 120 mg/month reduced GHRH by 45% and IGF-1 by 20%. Following pancreaticoduodenectomy, four NETs were identified with positive GHRH and calcitonin staining and Ki-67 index of 2% in the largest lesion. The pancreas tail lesion was not removed. Post-operatively, GHRH and calcitonin levels were undetectable, IGF-1 levels normalised and GH suppressed normally on glucose challenge. Post-operative fasting glucose and HbA1c levels have remained normal at the last check-up. While adolescent-onset cases of GHRH-secreting pNETs have been described, to the best of our knowledge, this is the first reported case of ectopic GHRH in a paediatric setting leading to gigantism in a patient with MEN1. Our case highlights the importance of distinguishing between pituitary and ectopic causes of gigantism, especially in the setting of MEN1, where paediatric somatotroph adenomas causing gigantism are extremely rare. Learning points It is important to diagnose gigantism and its underlying cause (pituitary vs ectopic) early in order to prevent further growth and avoid unnecessary pituitary surgery. The most common primary tumour sites in ectopic acromegaly include the lung (53%) and the pancreas (34%) (1): 76% of patients with a pNET secreting GHRH showed a MEN1 mutation (1). Plasma GHRH testing is readily available in international laboratories and can be a useful diagnostic tool in distinguishing between pituitary acromegaly mediated by GH and ectopic acromegaly mediated by GHRH. Positive GHRH immunostaining in the NET tissue confirms the diagnosis. Distinguishing between pituitary (somatotroph) hyperplasia secondary to ectopic GHRH and pituitary adenoma is difficult and requires specialist neuroradiology input and consideration, especially in the MEN1 setting. It is important to note that the vast majority of GHRH-secreting tumours (lung, pancreas, phaeochromocytoma) are expected to be visible on cross-sectional imaging (median diameter 55 mm) (1). Therefore, we suggest that a chest X-ray and an abdominal ultrasound checking the adrenal glands and the pancreas should be included in the routine work-up of newly diagnosed acromegaly patients.

A Case Report of Calcium-Sensing Receptor Gene Variant and Primary Hyperparathyroidism

Introduction: Primary hyperparathyroidism (PHPT) is an endocrinopathy that results from excessive production of parathyroid hormone from one or more overactive parathyroid gland(s). An estimated 90% of PHPT cases are sporadic, and 10% are inherited, comprising familial hyperparathyroidism (FHP). In FHP syndromes, variable clinical features are partly attributed to genetic heterogeneity. While there is not a consensus whether Familial hypocalciuric hypercalcemia (FHH) is a distinct entity or a form of FHP, accurate diagnosis is critical in guiding proper decision-making. The utility of genetic testing is multi-fold: help inform most likely diagnosis, guide prognosis and management, and inform familial recurrence risk. We report a patient with early-onset hypercalcemia, post subtotal parathyroidectomy, notable family history, with a likely pathogenic variant in the calcium-sensing receptor gene, CASR. Case Presentation: A 42 yo, female with history of nephrolithiasis and hypercalcemia diagnosed in her 20’s with PHPT was referred to our endocrinology clinic. Preoperative work up showed calcium of 11.1mg/dL, albumin 4.2g/dL, PTH of 177pg/mL, creatinine 0.92mg/dL. Sestamibi showed persistent activity in the mid to inferior aspect of right thyroid lobe suspicious for parathyroid adenoma. She underwent 3 gland parathyroidectomy and pathology showed mildly hypercellular parathyroid in left superior & right superior gland, normocellular left inferior gland. PTH levels normalized post-surgery. PTH levels normalized post surgery. Genetic evaluation was done, given her early-onset hypercalcemia, multi-gland involvement, and notable family history (maternal grandfather with parathyroidectomy for hypercalcemia and mother reportedly undergoing a hyperparathyroidism workup). Invitae hyperparathyroidism genetic panel revealed a likely pathogenic variant in CASR (c.659G>A; p.R220Q). Discussion: To date, our case with PHPT is the second report of the likely pathogenic variant CASR (c.659G>A; p.R220Q), which affects a conserved extracellular domain residue, thought to be important in sensing extracellular calcium. This variant has been previously reported in another family with FHH with 5 affected relatives. The reported 29-year old proband also had recurrent pancreatitis, which resolved with subtotal parathyroidectomy, but remained hypercalcemic. Despite the marked phenotypic heterogeneity in our patient and the case with FHH in terms of clinical presentation and response to treatment with surgery; both shared a history of hyperparathyroidism and a family history of hypercalcemia, suggesting contributions from the same CASR gene variant. With limited existing data about the variable expressivity of variants in genes implicated in the pathogenesis of both FHH and FHP; our case adds value to the existing evidence that supports its possible genetic contribution to PHPT