In most developed countries, breast carcinoma is the most common malignancy in women and while thyroid cancer is less common, its incidence is almost three to five times greater in women than in men. Since 1966, studies have demonstrated an association between thyroid and breast cancer and despite these studies, the mechanism/s by which they are related, remains unclear. We present a case of a 56-year-old lady who initially presented in 2014 with a screen detected left breast carcinoma but was subsequently found to have occult metastatic thyroid cancer to the axilla, diagnosed from a sentinel node biopsy from the primary breast procedure. The patient underwent a left mastectomy, left axillary dissection and total thyroidectomy followed by three courses of radioactive iodine ablation. Despite this, her thyroglobulin level continued to increase, which was secondary to a metastatic thyroid cancer parasternal metastasis. Breast and thyroid cancer presents metachronously or synchronously more often than by chance. With improving mortality in primary cancers, such as breast and differentiated thyroid cancer, it is likely that as clinicians, we will continue to encounter this association in practice.
There has been a long-standing observation of an association between breast and thyroid cancer although the exact mechanism of this association remains unclear.
Our patient presented with thyroid cancer with an incidental diagnosis from a sentinel node biopsy during her primary breast operation for breast cancer and was also found to have a parasternal distant bony metastasis.
Thyroid axillary metastases are generally rare.
The interesting nature in which this patient’s metastatic thyroid carcinoma behaved more like a breast carcinoma highlights a correlation between these two cancers.
With improving mortality in these primary cancers, clinicians are likely to encounter this association in clinical practice.
Systemic therapy for metastatic breast and thyroid cancers differ and therefore a clear diagnosis of metastasis is crucial.
Multiple endocrine metastases are a rare but possible complication of lung adenocarcinoma (LAC). Pituitary metastasis is a rare condition with poor clinical expression. Diabetes insipidus (DI) is its most common presenting symptom. Here we report an original case of a pituitary stalk (PS) metastasis from LAC presenting as central DI followed by adrenal insufficiency (AI) from bilateral adrenal metastasis, without known evidence of the primary malignancy. A 45-year-old woman whose first clinical manifestations were polyuria and polydipsia was admitted. She was completely asymptomatic with no cough, no weight loss or anorexia. Chest radiography was normal. Brain MRI showed a thick pituitary stalk (PS). DI was confirmed by water restriction test and treated with vasopressin with great clinical results. Explorations for systemic and infectious disease were negative. Few months later, an acute AI led to discovering bilateral adrenal mass on abdominal CT. A suspicious 2.3 cm apical lung nodule was found later. Histopathological adrenal biopsy revealed an LAC. The patient received systemic chemotherapy with hormonal replacement for endocrinological failures by both vasopressin and hydrocortisone. We present this rare case of metastatic PS thickness arising from LAC associated with bilateral adrenal metastasis. Screening of patients with DI and stalk thickness for lung and breast cancer must be considered. Multiple endocrine failures as a diagnostic motive of LAC is a rare but possible circumstance.
Adrenal metastasis is a common location in lung adenocarcinoma; however, metastatic involvement of the pituitary stalk remains a rare occurrence, especially as a leading presentation to diagnose lung cancer.
The posterior pituitary and the infundibulum are the preferential sites for metastases, as they receive direct arterial blood supply from hypophyseal arteries.
Patients diagnosed with diabetes insipidus due to pituitary stalk thickness should be considered as a metastasis, after exclusion of the classical systemic and infectious diseases.
The diagnosis of an endocrinological metastatic primary lung adenocarcinoma for patients without respiratory symptoms is often delayed due to a lack of correlation between endocrinological symptoms and lung cancer.
The main originality of our case is the concomitant diagnosis of both endocrinological failures, as it was initiated with a diabetes insipidus and followed by an acute adrenal insufficiency.
Papillary thyroid gland carcinoma is the most common type of malignancy of the endocrine system. Metastases to the pituitary gland have been described as a complication of papillary thyroid cancer in few reported cases since 1965. We report the case of a 68-year-old female patient with a well-differentiated form of thyroid gland cancer. Despite it being the most common malignant cancer of the endocrine system, with its papillary form being one of the two most frequently diagnosed thyroid cancers, the case we present is extremely rare. Sudden cardiac arrest during ventricular fibrillation occurred during hospitalization. Autopsy of the patient revealed papillary carcinoma of the thyroid, follicular variant, with metastasis to the sella turcica, and concomitant sarcoidosis of heart, lung, and mediastinal and hilar lymph nodes. Not only does atypical metastasis make our patient’s case most remarkable, but also the postmortem diagnosis of sarcoidosis makes her case particularly unusual.
The goal of presenting this case is to raise awareness of the clinical heterogeneity of papillary cancer and promote early diagnosis of unexpected metastasis and coexisting diseases to improve clinical outcomes.
Clinicians must be skeptical. They should not fall into the trap of diagnostic momentum or accept diagnostic labels at face value. Regardless of the potential mechanisms, clinicians should be aware of the possibility of the coexistence of thyroid cancer and sarcoidosis as a differential diagnosis of lymphadenopathy.
This case highlights the importance of the diagnostic and therapeutic planning process and raises awareness of the fact that one uncommon disease could be masked by another extremely rare disorder.
M L GildCancer Genetics, Kolling Institute of Medical Research, Sydney, New South Wales, Australia Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia Department of Endocrinology and Diabetes, Royal North Shore Hospital, Sydney, New South Wales, Australia
R J Clifton-BlighCancer Genetics, Kolling Institute of Medical Research, Sydney, New South Wales, Australia Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia Department of Endocrinology and Diabetes, Royal North Shore Hospital, Sydney, New South Wales, Australia
B G RobinsonCancer Genetics, Kolling Institute of Medical Research, Sydney, New South Wales, Australia Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia Department of Endocrinology and Diabetes, Royal North Shore Hospital, Sydney, New South Wales, Australia
Struma ovarii is a rare, usually benign ovarian tumour with malignancy occurring in <5% of cases. Metastases, particularly seeding to bone, are extremely rare. Presentation is variable but often features local pain and/or ascites and hyperthyroidism may occur. It is not established how to best treat and follow patients with extensive disease. Case reports of radioiodine (I131) ablative therapy following thyroidectomy have shown reduced recurrence. We describe the case of a 33-year-old woman who presented with bone pain and was diagnosed with skeletal metastases with features of follicular thyroid carcinoma. However, thyroid pathology was benign. She recalled that 5 years prior, an ovarian teratoma was excised, classified at that time as a dermoid cyst. Retrospective review of this pathology confirmed struma ovarii without obvious malignant features. The patient was found to have widespread metastases to bone and viscera and her thyroglobulin was >3000 µg/L following recombinant TSH administration prior to her first dose of I131. At 25 months following radioiodine treatment, she is in remission with an undetectable thyroglobulin and clear I131 surveillance scans. This case demonstrates an unusual presentation of malignant struma ovarii together with challenges of predicting metastatic disease, and demonstrates a successful radioiodine regimen inducing remission.
Malignant transformation of struma ovarii (MSO) is extremely rare and even rarer are metastatic deposits in bone and viscera.
MSO can be difficult to predict by initial ovarian pathology, analogous to the difficulty in some cases of differentiating between follicular thyroid adenoma and carcinoma.
No consensus exists on the management for post operative treatment of MSO; however, in this case, three doses of 6Gbq radioiodine therapy over a short time period eliminated metastases to viscera and bone.
Patients should continue to have TSH suppression for ~5 years.
Monitoring thyroglobulin levels can predict recurrence.
Nivolumab, a monoclonal antibody against programmed cell death-1 receptor, is increasingly used in advanced cancers. While nivolumab use enhances cancer therapy, it is associated with increased immune-related adverse events. We describe an elderly man who presented in ketoacidosis after receiving nivolumab for metastatic renal cell carcinoma. On presentation, he was hyperpneic and laboratory analyses showed hyperglycemia and anion-gapped metabolic acidosis consistent with diabetic ketoacidosis. No other precipitating factors, besides nivolumab, were identified. Pre-nivolumab blood glucose levels were normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. He was diagnosed with insulin-dependent autoimmune diabetes mellitus secondary to nivolumab. Although nivolumab was stopped, he continued to require multiple insulin injection therapy till his last follow-up 7 months after presentation. Clinicians need to be alerted to the development of diabetes mellitus and diabetic ketoacidosis in patients receiving nivolumab.
Diabetic ketoacidosis should be considered in the differential of patients presenting with metabolic acidosis following treatment with antibodies to programmed cell death-1 receptor (anti-PD-1).
Autoimmune islet cell damage is the presumed mechanism for how insulin requiring diabetes mellitus can develop de novo following administration of anti-PD-1.
Because anti-PD-1 works by the activation of T-cells and reduction of ‘self-tolerance’, other autoimmune disorders are likely to be increasingly recognized with increased use of these agents.
Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which acts as immune checkpoint inhibitor against the programmed cell death protein-1, for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as evidenced by venous glucose of 47 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95 and bicarbonate of 6.6 mmol/L. She has had no personal or family history of diabetes mellitus (DM), while random venous glucose, measured 1 week prior to hospitalisation, was 6.1 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12 kIU/L (0–5 kU/L), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab was recommenced without the development of other immune-mediated phenomena until 6 months later, when she developed hypothyroidism with TSH 18 U/L and low free T4. She remains insulin dependent and has required levothyroxine replacement, while she has maintained good radiological and clinical response to immunotherapy. This case is notable for the rapidity of onset and profound nature of DKA at presentation, which occurred two months following commencement of immunotherapy. Despite the association of nivolumab with immune-mediated endocrinopathies, only a very small number of patients developing type 1 DM has been reported to date. Patients should be closely monitored for hyperglycaemia and thyroid dysfunction prior to and periodically during immunotherapy.
Nivolumab can induce fulminant type 1 diabetes, resulting in DKA.
Nivolumab is frequently associated with thyroid dysfunction, mostly hypothyroidism.
Nivolumab-treated patients should be monitored regularly for hyperglycaemia and thyroid dysfunction.
Clinicians should be aware and warn patients of potential signs and symptoms of severe hyperglycaemia.
Constantine StratakisSection on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
Parathyroid carcinoma is an extremely rare endocrine malignancy that accounts for less than 1% of cases of primary hyperparathyroidism. We report a 44-year-old woman who presented with fatigue and diffuse bone pain. Laboratory findings revealed highly elevated serum calcium and parathyroid hormone (PTH) levels and a 4.5 × 3 × 2.5 cm cystic lesion in the lower pole of the right thyroid lobe that was shown histologically to be a parathyroid carcinoma. Ten years later, the patient developed brain and pulmonary metastases and recurrence of PTH-related hypercalcemia. Treatment of hypercalcemia along with localized radiotherapy and various chemotherapy regimens failed to induce a biochemical or radiological response. In conclusion, parathyroid carcinoma is a rare neoplasia that may develop metastases even after prolonged follow-up, for which there is no evidence-based treatment besides surgery. Different chemotherapeutic schemes did not prove to be of any benefit in our case highlighting the need for registering such patients to better understand tumor biology and develop specific treatment.
Metastases can develop many years after parathyroid cancer diagnosis.
Surgery is the only curative treatment for parathyroid carcinoma.
Chemotherapy and radiotherapy prove to be ineffective in parathyroid cancer treatment.
Patient registering is required in order to delineate underlining pathology and offer specific treatment.
Thyroid cancer with cranial metastasis in a pregnant woman is very rare. In the literature, most cases are diagnosed early from neurogenic signs or symptomatic thyroid gland. Pregnancy also contributes to a hesitation toward early surgical and medical treatments. We reported a scalp tumor in a physically healthy 37-year-old pregnant female with a follicular thyroid carcinoma (FTC) with lung, bone and cranial metastasis in initial presentation. Silent neurogenic and physical examinations make an early diagnosis very challenging. Resection of scalp and intracranial tumor, a thyroidectomy, post-operative radioactive iodine therapy and tyrosine kinase inhibitors were employed as treatment. The scalp tumor was confirmed as a metastatic follicular thyroid carcinoma via positive immunoreactivity for thyroglobulin and thyroid transcription factor 1 in tumor cells. Blood examination revealed an elevated thyroglobulin level (>5335 ng/mL). The patient was discharged without any neurological deficit. An asymptomatic scalp tumor in a pregnant woman with a normal thyroid disease history needs differential diagnosis from intracranial origin. Rapid progression and an elevated thyroglobulin level are the indicators that further image study is needed. Aggressive surgical excision of resectable thyroid gland and metastatic tumor are essential for a longer survival rate. There is nothing to indicate that a post-partum operation will worsen prognosis.
Pei-Lung ChenDivision of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan Department of Medical Genetics, National Taiwan University Hospital, Taipei, 100, Taiwan Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, 100, Taiwan Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, 100, Taiwan Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, 100, Taiwan
Tien-Chun ChangDivision of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan Department of Medicine, College of Medicine, National Taiwan University, Taipei, 100, Taiwan
Tien-Shang HuangDivision of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan Department of Medicine, College of Medicine, National Taiwan University, Taipei, 100, Taiwan Department of Social Medicine, College of Medicine, National Taiwan University, Taipei, 100, Taiwan Department of Medicine, Cathay General Hospital, Taipei, 106, Taiwan
Ching-Chung ChangDivision of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan Department of Medicine, College of Medicine, National Taiwan University, Taipei, 100, Taiwan Department of Internal Medicine, China Medical University Hospital, Taichung, 404, Taiwan Department of Internal Medicine, China Medical University, Taichung, 404, Taiwan
We report a case of follicular thyroid carcinoma with concomitant NRAS p.Q61K and GNAS p.R201H mutations, which manifested as a 13.5 cm thyroid mass with lung, humerus and T9 spine metastases, and exhibited good response to radioactive iodine treatment.
GNAS p.R201H somatic mutation is an activating or gain-of-function mutation resulting in constitutively activated Gs-alpha protein and downstream cAMP cascade, independent of TSH signaling, causing autonomously functioning thyroid nodules.
NRAS p.Q61K mutations with GNAS p.R201H mutations are known for a good radioactive iodine treatment response.
Further exploration of the GNAS-activating pathway may provide therapeutic insights into the treatment of metastatic follicular carcinoma.
Parathyroid carcinoma is a rare disease leading to severe hypercalcemia due to hyperparathyroidism. Surgery is the primary treatment option. A more progressive form of the disease is characterized by parathyrotoxicosis, and subsequent hypercalcemia is the most common cause of death. We report a case presenting with severe hypercalcemia due to parathyrotoxicosis from parathyroid carcinoma treated for the first time using the monoclonal antibody denosumab as a rescue therapy and present long-term follow-up data. The 71-year-old patient presented with severe hypercalcemia due to metastatic parathyroid carcinoma. Despite undergoing treatment with bisphosphonates, cinacalcet hydrochloride, and forced diuresis, the patient`s condition deteriorated rapidly due to resistant hypercalcemia. Surgery performed because of spinal metastasis and forced diuresis lowered calcium levels, albeit they remained in the hypercalcemic range and significantly increased when forced diuresis was stopped. Considering a palliative situation to overcome hypercalcemia, we decided to administer denosumab, a monoclonal antibody that binds to the receptor activator of nuclear factor-kappa B ligand. After a single subcutaneous administration of 60 mg denosumab, calcium levels normalized within one day. Subsequent denosumab injections led to permanent control of serum calcium for more than 2 years despite rising parathyroid hormone levels and repeated surgeries. Together with recent cases in the literature supporting our observation, we believe that denosumab is relevant for future trials and represents an effective tool to control hypercalcemia in patients with advanced stages of parathyroid cancer.
Severe hypercalcemia is the most common cause of death in patients with parathyroid carcinoma.
The monoclonal antibody denosumab rapidly lowered severely elevated serum calcium levels due to parathyrotoxicosis.
Denosumab was effective in the long-term treatment of hypercalcemia despite progression of parathyroid carcinoma.