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.

Ectopic Intact PTH Secretion Causing Humoral Hypercalcemia of Malignancy

Background: Tumor-generated ectopic intact PTH is difficult to diagnose and should be suspected in patients with apparent primary hyperparathyroidism but with normal parathyroid glands. Clinical Case: A 72-year-old man presented with symptoms of hypercalcemia including generalized weakness, polyuria, and polydipsia. Initial labs were consistent with primary hyperparathyroidism: calcium 12.1 mg/dL (n 8.6–10.3 mg/dL, albumin-corrected 12.5 mg/dL), intact PTH (iPTH) 115.6 pg/mL (n 10–65 pg/mL), low normal 25-OH vitamin D (25 ng/mL, n 25–100 ng/mL), and relatively high normal 1,25 dihydroxyvitamin D (52 pg/mL, n 18–78 pg/mL). 24-hour urine calcium was 381 mg/day (n 100–300 mg/day) and PTHrP was 1.6 pmol/L (n <4.2 pmol/L). Neck ultrasound demonstrated a 0.5 x 1 cm hypoechoic mass near right thyroid inferior pole, though sestamibi SPECT/CT scan did not reveal scintographic evidence of a parathyroid adenoma. He underwent subtotal parathyroidectomy with largest excised gland weighing 0.262 grams. The left inferior parathyroid gland appeared normal intraoperatively, thus was clipped and left in place. PTH decreased from 194 pg/mL to 98 pg/mL postoperatively. Pathological examination revealed three normocellular parathyroid glands with enlargement of only the right superior gland. Venous sampling of the parathyroid vasculature failed to identify the source of autonomous iPTH post operatively. Due to refractory hypercalcemia, cinacalcet was initiated. However, hypercalcemia as high as 12.6 mg/dl and hyperparathyroidism to 672 pg/mL persisted despite dose escalation. He eventually received pamidronate with subsequent transition to denosumab due to declining renal function. A 68Ga DOTATATE scan was performed to locate occult ectopic parathyroid, which reported multiple foci of presumed somatostatin receptor expression involving the liver and intra-abdominal lymph nodes without significant uptake in the neck concerning for metastatic disease. Liver lesion biopsy was consistent with pancreato-biliary adenocarcinoma. Surprisingly, the biopsy was negative for iPTH and neuroendocrine tumor markers on staining/immunohistochemistry. Given his poor prognosis and multiple comorbidities, the patient opted not to pursue any further workup or therapy for his malignancy. Conclusion: Occult malignancy should be suspected for a patient with persistent hyperparathyroidism after parathyroidectomy. Treatment of the malignancy may lead to an improvement in hypercalcemia and iPTH levels. Employment of iPTH mRNA testing or intra-abdominal venous sampling to prove ectopic iPTH secretion would be ideal, as iPTH staining could be falsely negative. Further testing was not completed as the patient declined further evaluation.