Objective Parathyroid Carcinoma is a rare malignant neoplasm, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single centre regarding the management and outcome of patients with parathyroid carcinomas and revise relevant literature. Design Retrospective review of all patients with parathyroid carcinoma evaluated at a tertiary oncologic centre from 1991 until 2021. Results Seventeen patients were identified (10 males), with a mean age at diagnosis of 53 ± 16 years and a median follow‐up of 16.5 years. Most patients presented with hypercalcemia (n = 15), with a mean serum calcium concentration of 13.5 mg/dl (9.6–16.5) and mean PTH of 1173 pg/ml (276–2500). Hyperparathyroidism‐mediated organ damage was observed in most patients (n = 16), with predominant renal (n = 12) and skeletal (n = 9) complications. En bloc surgical resection was performed in nine patients. Three patients underwent adjuvant radiotherapy. Recurrence was observed in 8 cases (47.1%) after a median of 24 months following surgery and no independent predictors of recurrence were identified. The overall survival and disease specific survival at 5‐year was 88% and 94%, respectively. CDC73 mutations were present in 38.5% of analysed patients and one patient was diagnosed with MEN1. Conclusion Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Therefore, preoperatively high index of suspicion is paramount to optimize patient care. This is, to our knowledge, the largest Portuguese cohort published so far.

Pituitary gigantism is extremely rare, resulting from excessive secretion of growth hormone (GH) before fusion of epiphysial growth plates. We report a case of a 13-year-old boy, who presented with increased statural growth and headaches since the age of 10 years. On physical examination, his height was 180.7 cm (+3.3 SD) and Tanner stage V. Investigation revealed increased levels of serum age-adjusted and sex-adjusted insulin-like growth factor 1 (IGF-1) and failure of GH suppression during an oral glucose tolerance test (OGTT). MRI of the sellar region revealed a pituitary macroadenoma. He underwent transsphenoidal surgery and histopathological evaluation revealed mammosomatotropic adenoma. Three months after surgery, IGF-1 normalised, nadir GH during OGTT was less than 1 ng/mL and no residual tumour was found on the MRI. Genetic testing identified a mutation in the AIP gene. This case emphasises the importance of early diagnosis of gigantism, as treatment delay increases long-term morbidity.

Summary Immunotherapy has become an important pillar for the management of advanced cancer. Immune-related adverse events including endocrinopathies have been well described with programmed cell death 1 inhibitors such as pembrolizumab. While thyroid dysfunction is the most common endocrinopathy associated with pembrolizumab, new-onset autoimmune diabetes mellitus (DM) is extremely rare. The authors report a case of pembrolizumab-induced primary hypothyroidism and type 1 diabetes mellitus presenting with diabetic ketoacidosis (DKA). A 59-year-old female patient was treated with pembrolizumab for a stage 4 lung adenocarcinoma. She presented to the emergency department with hyperglycaemia-related signs and symptoms, such as polyuria, polydipsia, weight loss, vomiting, asthenia and dehydration, 3 weeks after her first dose of pembrolizumab. Laboratory evaluation revealed hyperglycaemia, hyperketonaemia and high anion gap metabolic acidaemia consistent with DKA. After prompt and adequate treatment of DKA, she transitioned to s.c. basal-bolus insulin. The diagnose of autoimmune DM was established based on the undetectable C-peptide levels and seropositivity for antiglutamic acid decarboxylase antibodies. Additional hormonal parameters revealed overt hypothyroidism and levothyroxine therapy was initiated. This case highlights the importance of blood glucose and thyroid function monitoring as an integral part of cancer treatment protocols for pembrolizumab and other immune checkpoint inhibitors. Learning points Programmed cell death 1 (PD1) inhibitors such as pembrolizumab can cause endocrine immune-related adverse events (irAE), including thyroid dysfunction and type 1 diabetes mellitus (T1DM). Thyroid dysfunction is the most frequent endocrine irAE secondary to PD1 inhibitors. Autoimmune diabetes and possible resultant diabetic ketoacidosis are rare, but life-threatening adverse events associated with pembrolizumab. Pembrolizumab-induced T1DM often present with relatively low HbAlc levels, reflecting the fulminant onset of β-cell destruction. Patients treated with pembrolizumab and other immune checkpoints inhibitors should be monitored regularly for hyperglycaemia and thyroid dysfunction.

We report a case of a 46-year-old woman who presented with a midline neck mass 2 years after total thyroidectomy for Graves’ disease. Despite levothyroxine treatment withdrawal, she remained biochemically with subclinical hyperthyroidism. Her thyroid stimulating hormone receptor antibodies were consistently elevated. Neck ultrasonography revealed an infrahyoid solid nodule and pertechnetate scintigraphy confirmed an increased uptake at the same level, without any uptake in the thyroid bed. Treatment with methimazole 5 mg/day was initiated with clinical improvement and achievement of euthyroidism. After that, she received 10 mCi of radioactive iodine. Since then, she experienced regression of the neck mass and is doing well on a replacement dose of levothyroxine. Recurrence of Graves’ disease in ectopic thyroid following total thyroidectomy is extremely rare. This diagnose should be considered in patients who underwent total thyroidectomy and remained with thyrotoxicosis despite decreasing the levothyroxine dose.

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