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Open access

Miriam Hinaa Ahmad and Ismat Shafiq

Summary

We report a case of a 21-year-old African American female with history of pre-diabetes, and a diagnosis of a rare leukemia, blastic-plasmacytoid dendritic neoplasm (BPDCN), who developed diabetic ketoacidosis (DKA) after the third dose of PEG-asparaginase infusion. She was successfully treated with insulin. Asparaginase is a vital part of treatment protocols for acute lymphoblastic leukemia (ALL) in combination with other chemotherapeutic drugs. Asparaginase therapy has been reported to cause hyperglycemia especially when used in conjunction with glucocorticoids for the treatment of ALL in the pediatric population. Multiple mechanisms for hyperglycemia have been hypothesized which include decreased insulin secretion, impaired insulin receptor function and excess glucagon formation. Hyperglycemia is usually self-limiting but can deteriorate to diabetic ketoacidosis. DKA is a rare adverse effect with asparaginase therapy with an incidence rate of about 0.8%.

Learning points:

  • DKA is a rare finding following asparaginase therapy.

  • Hyperglycemia is most commonly seen with asparaginase treatment when used along with glucocorticoid.

  • Frequent blood glucose monitoring and prompt initiation of insulin treatment with hyperglycemia can prevent severe complications.

  • Patients and physician education on this complication can reduce morbidity due to DKA.

Open access

Benedetta Zampetti, Giorgia Simonetti, Roberto Attanasio, Antonio Silvani and Renato Cozzi

Summary

We describe the 20-year course of a 63-year-old male with a macroprolactinoma that acquired resistance to treatment and aggressive behavior after a 4-year successful treatment with cabergoline. He was submitted to multiple surgical resections by a skilled surgeon, fractionated radiotherapy and was eventually treated with temozolomide. After a first 6-month standard cycle, a relapse occurred and he was treated again successfully.

Learning points:

  • Prolactinomas are the most frequent type of pituitary adenoma.

  • They usually have a benign course.

  • In most cases dopamine-agonist drugs, mainly cabergoline, are first-line (and usually only) treatment.

  • Occasionally prolactinomas can have or acquire resistance to treatment and/or aggressive behavior.

  • Temozolomide (TMZ), an oral alkylating drug, can be effective in such aggressive tumors.

  • Multimodal treatment (surgery, radiation, cabergoline and TMZ) is warranted in aggressive pituitary tumors.

  • We describe here successful rechallenge with TMZ after relapse occurring 18 months after a first TMZ cycle.

Open access

Philip D Oddie, Benjamin B Albert, Paul L Hofman, Craig Jefferies, Stephen Laughton and Philippa J Carter

Summary

Adrenocortical carcinoma (ACC) during childhood is a rare malignant tumor that frequently results in glucocorticoid and/or androgen excess. When there are signs of microscopic or macroscopic residual disease, adjuvant therapy is recommended with mitotane, an adrenolytic and cytotoxic drug. In addition to the anticipated side effect of adrenal insufficiency, mitotane is known to cause gynecomastia and hypothyroidism in adults. It has never been reported to cause precocious puberty. A 4-year-old girl presented with a 6-week history of virilization and elevated androgen levels and 1-year advancement in bone age. Imaging revealed a right adrenal mass, which was subsequently surgically excised. Histology revealed ACC with multiple unfavorable features, including high mitotic index, capsular invasion and atypical mitoses. Adjuvant chemotherapy was started with mitotane, cisplatin, etoposide and doxorubicin. She experienced severe gastrointestinal side effects and symptomatic adrenal insufficiency, which occurred despite physiological-dose corticosteroid replacement. She also developed hypothyroidism that responded to treatment with levothyroxine and peripheral precocious puberty (PPP) with progressive breast development and rapidly advancing bone age. Five months after discontinuing mitotane, her adrenal insufficiency persisted and she developed secondary central precocious puberty (CPP). This case demonstrates the diverse endocrine complications associated with mitotane therapy, which contrast with the presentation of ACC itself. It also provides the first evidence that the known estrogenic effect of mitotane can manifest as PPP.

Learning points:

  • Adrenocortical carcinoma is an important differential diagnosis for virilization in young children

  • Mitotane is a chemotherapeutic agent that is used to treat adrenocortical carcinoma and causes adrenal necrosis

  • Mitotane is an endocrine disruptor. In addition to the intended effect of adrenal insufficiency, it can cause hypothyroidism, with gynecomastia also reported in adults.

  • Patients taking mitotane require very high doses of hydrocortisone replacement therapy because mitotane interferes with steroid metabolism. This effect persists after mitotane therapy is completed

  • In our case, mitotane caused peripheral precocious puberty, possibly through its estrogenic effect.

Open access

Senhong Lee, Aparna Morgan, Sonali Shah and Peter R Ebeling

Summary

We report a case of a 67-year-old man with type 2 diabetes presented with diabetic ketoacidosis, two weeks after his first dose of nivolumab therapy for non–small-cell lung carcinoma. He was started on empagliflozin two days prior in the setting of hyperglycaemia after the initiation of nivolumab therapy. Laboratory evaluation revealed an undetectable C-peptide and a positive anti-glutamic acid decarboxylase (GAD) antibody. He was treated with intravenous fluids and insulin infusion and was subsequently transitioned to subcutaneous insulin and discharged home. He subsequently has developed likely autoimmune thyroiditis and autoimmune encephalitis.

Learning points:

  • Glycemic surveillance in patients receiving immune checkpoint inhibitors is recommended.

  • Early glycemic surveillance after commencement of anti-programmed cell death-1 (PD-1) inhibitors may be indicated in selected populations, including patients with underlying type 2 diabetes mellitus and positive anti-glutamic acid decarboxylase (GAD) antibody.

  • Sodium-glucose co transporter-2 (SGLT2) inhibitors should be used with caution in patients on immunotherapy.

Open access

Joseph A Chorny, John J Orrego and José Manuel Cameselle-Teijeiro

Summary

Most medullary thyroid carcinomas (MTCs) are low grade and produce calcitonin. There are some calcitonin-negative MTCs that produce only calcitonin gene-related peptide (CGRP). Rarely, MTCs are negative for calcitonin and CGRP peptides, but contain their corresponding mRNAs. Primary thyroid neuroendocrine neoplasms other than MTCs are extremely rare. We describe a primary high-grade neuroendocrine carcinoma that was negative for CGRP and calcitonin at both the protein and mRNA levels. A 42-year-old woman presented with a rapidly enlarging thyroid mass replacing most of the left lobe and isthmus. A computed tomography-guided core-needle biopsy was performed. The tumor was composed of sheets of small-to-medium sized epithelial cells. The cells were immunoreactive for pancytokeratin, synaptophysin, CD56 and thyroid transcription factor-1, but negative for CK7, CK20, CD45, CD99, ERG, chromogranin A, thyroglobulin, calcitonin, CGRP and carcinoembryonic antigen. The Ki-67 proliferation index was ~90%. In situ hybridization was negative for calcitonin mRNA. The patient was initially diagnosed as having a small cell carcinoma. She was treated with cisplatin and etoposide (VP16), followed by radiation therapy. Given the excellent clinical course, the tumor was reviewed and reclassified as a high-grade neuroendocrine carcinoma (non-small-cell type). Heretofore, only a few other similar high-grade neuroendocrine tumors with negative markers of C-cell derivation have been reported. In our case, the patient is cancer free five years after diagnosis, but in the other cases, the outcome was poor.

Learning points:

  • There are neuroendocrine carcinomas of the thyroid that do not produce calcitonin or calcitonin gene-related peptide.

  • This category of calcitonin-negative neuroendocrine carcinomas is heterogeneous, consisting of low- and high-grade tumors.

  • The high-grade neuroendocrine carcinomas of the thyroid are rare and generally have a poor prognosis. They are divided into small cell and non-small cell or large cell types.

Open access

Carine Ghassan Richa, Khadija Jamal Saad, Georges Habib Halabi, Elie Mekhael Gharios, Fadi Louis Nasr and Marie Tanios Merheb

Summary

The objective of this study is to report three cases of paraneoplastic or ectopic Cushing syndrome, which is a rare phenomenon of the adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome. Three cases are reported in respect of clinical presentation, diagnosis and treatment in addition to relevant literature review. The results showed that ectopic ACTH secretion can be associated with different types of neoplasm most common of which are bronchial carcinoid tumors, which are slow-growing, well-differentiated neoplasms with a favorable prognosis and small-cell lung cancer, which are poorly differentiated tumors with a poor outcome. The latter is present in two out of three cases and in the remaining one, primary tumor could not be localized, representing a small fraction of patients with paraneoplastic Cushing. Diagnosis is established in the setting of high clinical suspicion by documenting an elevated cortisol level, ACTH and doing dexamethasone suppression test. Treatment options include management of the primary tumor by surgery and chemotherapy and treating Cushing syndrome. Prognosis is poor in SCLC. We concluded that in front of a high clinical suspicion, ectopic Cushing syndrome diagnosis should be considered, and identification of the primary tumor is essential.

Learning points:

  • Learning how to suspect ectopic Cushing syndrome and confirm it among all the causes of excess cortisol.

  • Distinguish between occult and severe ectopic Cushing syndrome and etiology.

  • Providing the adequate treatment of the primary tumor as well as for the cortisol excess.

  • Prognosis depends on the differentiation and type of the primary malignancy.

Open access

Nikolaos Asonitis, Eva Kassi, Michalis Kokkinos, Ilias Giovanopoulos, Foteini Petychaki and Helen Gogas

Summary

Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients. It is associated with a poor prognosis, since it reflects an advanced cancer stage. Among all cancer in females, breast cancer is the most common malignancy, and it has the highest prevalence of hypercalcemia. Approximately 70% of patients with breast cancer have bone metastases and 10% of them will have hypercalcemia as a complication at some point in the disease. Herein, we report a 69-year-old female patient with metastatic breast cancer, who developed severe hypercalcemia in the course of her disease and was diagnosed with humoral hypercalcemia of malignancy (HHM). Intense hydration along with corticoisteroids and antiresorptive medication (calcitonin, bisphosphonates and denosumab) were administered to the patient. Despite the above treatment, serum calcium levels remain elevated and calcimimetic cinacalcet was added. Upon discontinuation of cinacalcet, calcium levels were raised and returned back to the normal levels following re-initiation of the calcimimetic. Her calcium level restored to normal, and she was discharged with the following medical treatment: denosumab monthly, and cinacalcet at a titrated dose of 90 mg per day. The patient is followed as an outpatient and 11 months later, her calcium level remained within the normal range.

Learning points:

  • Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients.

  • Breast cancer has the highest prevalence of hypercalcemia.

  • The cornerstone of therapy remains the intense hydration and intravenous bisphosphonates (preferably zoledronic acid).

  • In case of persistent hypercalcemia of malignancy, the administration of calcimimetic cinacalcet could be an additional effective therapeutic option.

Open access

Sulaiman Haji Ali, K Aljenaee, W A Wan Mahmood and M Hatunic

Summary

Hypothyroidism is a recognized side effect of thalidomide drugs. We herein report a case of 83-year-old Irish female with a diagnosis of multiple myeloma and a background history of type 2 diabetes mellitus and hypertension. Our patient received pomalidomide and multiple courses of chemotherapy and achieved very good initial response for her multiple myeloma but subsequently she relapsed. She did not have any past history of thyroid disease or family history of thyroid disorders. Prior to treatment with pomalidomide, her thyroid function test was completely normal. She was commenced on pomalidomide in February 2017. Four weeks post treatment, she presented with worsening fatigue, and as a part of her workup, a thyroid function test was performed. Her free T4 was low at 7.2 pmol/L (reference range: 9.0–20.0) while her TSH was elevated at 44.7 mIU/L (reference range: 0.35–4.94). Pomalidomide treatment was terminated, and she was commenced on thyroid hormonal therapy replacement therapy with thyroxine with good clinical and biochemical response. Practitioners prescribing pomalidomide should be aware of this potential complication and patients who are receiving immunomodulatory drugs like pomalidomide should undergo regular thyroid hormone levels screen.

Learning points:

  • Overt hypothyroidism is a side effect of pomalidomide.

  • Thyroid function test should be included as a screening test with regular review in patients receiving pomalidomide.

  • Unexplained worsening fatigue in patients receiving pomalidomide should raise the possibility of overt hypothyroidism.

Open access

Ana G Ferreira, Tiago N Silva, Henrique V Luiz, Filipa D Campos, Maria C Cordeiro and Jorge R Portugal

Sellar plasmacytomas are rare and the differential diagnosis with non-functioning pituitary adenomas might be difficult because of clinical and radiological resemblance. They usually present with neurological signs and intact anterior pituitary function. Some may already have or eventually progress to multiple myeloma. We describe a case associated with extensive anterior pituitary involvement, which is a rare form of presentation. A 68-year-old man was referred to our Endocrinology outpatient clinic due to gynecomastia, reduced libido and sexual impotence. Physical examination, breast ultrasound and mammography confirmed bilateral gynecomastia. Blood tests revealed slight hyperprolactinemia, low testosterone levels, low cortisol levels and central hypothyroidism. Sellar MRI showed a heterogeneous sellar mass (56 × 60 × 61 mm), initially suspected as an invasive macroadenoma. After correcting the pituitary deficits with hydrocortisone and levothyroxine, the patient underwent transsphenoidal surgery. Histological examination revealed a plasmacytoma and multiple myeloma was ruled out. The patient was unsuccessfully treated with radiation therapy (no tumor shrinkage). Myeloma ultimately developed, with several other similar lesions in different locations. The patient was started on chemotherapy, had a bone marrow transplant and is now stable (progression free) on lenalidomide and dexamethasone. The presenting symptoms and panhypopituitarism persisted, requiring chronic replacement treatment with levothyroxine, hydrocortisone and testosterone.

Learning points:

  • Plasmacytomas, although rare, are a possible type of sellar masses, which have a completely different treatment approach, so it is important to make the correct diagnosis.

  • Usually, they present with neurological signs and symptoms and a well-preserved pituitary function, but our case shows that anterior pituitary function can be severely compromised.

  • Making a more extensive evaluation (clinical and biochemical) might provide some clues to this diagnosis.

Open access

Carlos Tavares Bello, Francisco Sousa Santos, João Sequeira Duarte and Carlos Vasconcelos

Summary

Central diabetes insipidus (DI) is a rare clinical entity characterized by low circulating levels of antidiuretic hormone (ADH) presenting with polyuria and volume depletion. Pituitary surgery is the most common cause of central DI in adults. Pituitary and hypothalamic disease, particularly invasive neoplasms, rarely cause DI, being idiopathic cases responsible for the majority of non-surgical cases. HIV patients, especially those with poor virulogical control, are prone to the development of CNS neoplasms, particularly lymphomas. These neoplasms usually become manifest with mass effects and seizures. Central DI and hypopituitarism are uncommon initial manifestations of primary CNS lymphomas. The authors describe the case of 29-year-old female, HIV-positive patient whose CNS lymphoma presented with DI.

Learning points:

  • Central diabetes insipidus has multiple causes and central nervous system lymphomas are not often considered in the differential diagnosis due to their low prevalence.

  • Accurate biochemical diagnosis should always be followed by etiological investigation.

  • The HIV population is at risk for many neoplasms, especially CNS lymphomas.

  • New-onset polyuria in an HIV-positive patient in the absence of focal neurological signs should raise the suspicion for a central nervous system process of neoplastic nature.

  • This clinical entity usually constitutes a therapeutical challenge, often requiring a multidisciplinary approach for optimal outcome.