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Said Darawshi Department of Endocrinology, Rambam Health Care Campus, Haifa, Israel
The Faculty of Medicine, Technion, Haifa, Israel

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Mahmoud Darawshi Clalit Health Services, Northern District – Arrabah, Israel

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Deeb Daoud Naccache Department of Endocrinology, Rambam Health Care Campus, Haifa, Israel
The Faculty of Medicine, Technion, Haifa, Israel

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Severe hypocalcaemia in breast cancer with bone metastasis is a rare finding usually associated with an advanced stage of the disease. We report a case of a 45-year-old woman with a history of local ductal carcinoma in situ (DCIS) of the breast, who presented with muscle tremors and general weakness. Hypocalcaemia was evident, with a positive Chvostek sign and a serum calcium level of 5.9 mg/dL (1.47 mmol/L), phosphorus 5.9 mg/dL (normal range: 2.3–4.7 mg/dL) with normal levels of albumin, magnesium and parathyroid hormone. High oral doses of alpha calcitriol and calcium with i.v. infusion of high calcium doses were instituted, altogether sufficient to maintain only mild hypocalcaemia. A whole-body CT revealed bone lesions along the axial skeleton. A biopsy from a bone lesion revealed a metastasis of breast carcinoma. With this pathological finding, leuprolide (GNRH analogue) and chlorambucil (alkylating agent) were initiated, followed by prompt tapering of infused calcium down to full discontinuation. Serum calcium was kept stable close to the low normal range by high doses of oral alpha calcitriol and calcium. This course raises suspicion that breast metastases to the skeleton caused tumour-induced hypocalcaemia by a unique mechanism. We assume that hypocalcaemia in this case was promoted by a combination of hypoparathyroidism and bone metastasis.

Learning points

  • Severe hypocalcaemia can a presenting symptom for breast cancer relapse.

Open access
Deeb Daoud Naccache Institute of Endocrinology and the Centre for Excellence in Diabetes and Obesity, Rambam Health Care campus, Haifa, Israel

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Summary

Ten years after the successful withdrawal from heroin abuse, a person with diabetes suffered intractable pain and severe muscular emaciation consistent with the syndrome of diabetic neuropathic cachexia. Anti-neuropathic medications failed neither to alleviate suffering and reverse weight loss, nor to stop muscular emaciation. Vigilant evaluation for weight loss aetiologies revealed no responsible aetiology. Prescribing medical cannabis became mandatory, with the intention to alleviate neuropathic pain, regain muscular mass and strengthen legs, enable standing upright and walking normally. Medical cannabis for pain-relief, and the orexigenic properties of tetrahydrocannabinol (THC) ingredient successfully achieved these goals.

Learning points:

  • Medical cannabis can serve to promptly alleviate severe diabetic neuropathic pain.

  • Past history of heroin abuse was not an absolute contraindication to medical cannabis use.

  • Medical cannabis increased appetite and reversed muscular emaciation.

  • Medical cannabis decreased chronic pain and hence, its catabolic consequences.

Open access
Viviana Ostrovsky Diabetes, Endocrinology and Metabolic Disease Institute, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Rehovot, Israel

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Barak Bar-Zakai Surgery A Department, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Rehovot, Israel

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Rafael Miller Surgery A Department, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Rehovot, Israel

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Tal Schiller Diabetes, Endocrinology and Metabolic Disease Institute, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Rehovot, Israel

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Alena Kirzhner Diabetes, Endocrinology and Metabolic Disease Institute, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Rehovot, Israel

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Hilla Knobler Diabetes, Endocrinology and Metabolic Disease Institute, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Rehovot, Israel

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Taiba Zornitzki Diabetes, Endocrinology and Metabolic Disease Institute, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Rehovot, Israel

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Summary

Well-differentiated thyroid cancer (WDTC), including papillary, follicular, and Hurthle-cell types, is characterized by a slow course and usually remain localized to the thyroid. However, a minority of these cases develop distant metastases with the most common sites being lungs, bones, and lymph nodes. Liver metastases of WDTC are rare and are usually found along with other distant metastases sites and in a multiple or diffuse pattern of spread. The recognition of distant metastasis in WDTC has a significant impact on the treatment and prognosis. However, because of their low incidence and awareness, distant metastases are often diagnosed late. Herein, we describe a case of a 71 years old woman who during routine surveillance of a follicular variant of papillary thyroid cancer (FV-PTC), 5 years after being treated for her primary thyroid tumor, was found to have a single liver metastasis and underwent liver segmental resection. This case highlights the importance of maintaining vigilant surveillance of patients with WDTC, and illustrates the possibility of unique metastasis at unexpected sites. Further studies are needed to understand the organ tropism of some WDTC leading to distant metastases development and to better prediction of an aggressive course.

Learning points:

  • WDTC patients with distant metastases have a poor prognosis with a 10-year survival of about 50%. The most common sites of distant metastases are lung, bone and lymph nodes.

  • Liver metastases are rare in WDTC, are usually multiple or diffuse and are found along with other distant metastases sites.

  • Single liver metastasis of WDTC is an unexpected pattern of spread, and very few cases are reported in the literature.

  • Rare sites of distant metastases in WDTC can manifest many years after the primary tumor, stressing the importance of maintaining vigilant surveillance.

  • More studies are needed to predict which WDTC tumors may develop a more aggressive course, allowing clinicians to individualize patient management.

Open access
Zaina Adnan Endocrinology and Metabolism Department, Zvulon Medical Center, Clalit Medical Health Care Services, Haifa, Israel

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David Nikomarov Orthopedic Surgery Department, Nuclear Medicine Department, Rambam Health Care Campus, Haifa, Israel

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Michal Weiler-Sagie Michal Weiler-Sagie, Nuclear Medicine Department, Rambam Health Care Campus, Haifa, Israel

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Noga Roguin Maor Clalit Medical Health Care and the Clinical Research Unit, Haifa and Western Galilee, Haifa, Israel

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Summary

Phosphaturic mesenchymal tumor (PMT) represents a rare cause of osteomalacia. The clinical signs and symptoms are vague and these lead to diagnosis delay. In the presence of hypophosphatemia and relatively high urine phosphate excretion, this entity should be taken into consideration in the deferential diagnosis of osteomalacia. In the present article, we report 81-year-old man presented to our clinic for evaluation due to osteopenia. His laboratory results disclosed hypophosphatemia, relatively increased urine phosphate excretion and increased level of intact fibroblast growth factor 23 (FGF23). A 68Gallium DOTATATE PET/CT revealed pathological uptake in the upper aspect of the left shoulder adjacent to the coracoid process. For suspected PMT a wide resection of the tumor was performed and pathological findings were consistent for PMT. Laboratory tests were normalized postoperatively. Reviewing the literature, we had identified 33 reported cases of PMTs among elderly patients age ≥70 years. Unlike previously reported data, where tumors predominantly localized in the lower extremities and pelvis, our search disclosed a high rate of tumor localization (10 cases – 33.3%) in the head with equal number of tumors (14 cases – 42.4%) localized in the head and upper extremity as well as in pelvis and lower extremity. The present case describes unique tumor localization in an elderly patient and our literature search demonstrated for the first time a high rate of tumor localization in the head among this group of patients.

Learning points:

  • PMTs represent a rare entity that should be considered in the differential diagnosis of elderly patients presented with persistent hypophosphatemia.

  • Unlike previously reported data, head and neck tumor localization is frequent among elderly patients.

  • 68Gallium-conjugated somatostatin peptide analogs, such as 68Ga-DOTATATE PET/CT demonstrated the greatest sensitivity and specificity for tumor localization in patients with phosphaturic mesenchymal tumors (PMTs).

  • Wide tumor resection using intraoperative ultrasound is of major importance in order to ensure long-term cure.

Open access
Ilan Rahmani Tzvi-Ran Department of Internal Medicine F, Soroka University Medical Center, Beer Sheva, Israel

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Judith Olchowski Department of Internal Medicine F, Soroka University Medical Center, Beer Sheva, Israel

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Merav Fraenkel Department of Internal Medicine F, Soroka University Medical Center, Beer Sheva, Israel

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Asher Bashiri Department of Internal Medicine F, Soroka University Medical Center, Beer Sheva, Israel

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Leonid Barski Department of Internal Medicine F, Soroka University Medical Center, Beer Sheva, Israel

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Summary

A previously healthy 24-year-old female underwent an emergent caesarean section without a major bleeding described. During the first post-operative days (POD) she complained of fatigue, headache and a failure to lactate with no specific and conclusive findings on head CT. On the following days, fever rose with a suspicion of an obstetric surgery-related infection, again with no evidence to support the diagnosis. On POD5 a new-onset hyponatremia was documented. The urine analysis suggested SIADH, and following a treatment failure, further investigation was performed and demonstrated both central hypothyroidism and adrenal insufficiency. The patient was immediately treated with hydrocortisone followed by levothyroxine with a rapid resolution of symptoms and hyponatremia. Further laboratory investigation demonstrated anterior hypopituitarism. The main differential diagnosis was Sheehan’s syndrome vs lymphocytic hypophysitis. Brain MRI was performed as soon as it was available and findings consistent with Sheehan’s syndrome confirmed the diagnosis. Lifelong hormonal replacement therapy was initiated. Further complaints on polyuria and polydipsia have led to a water deprivation testing and the diagnosis of partial central insipidus and appropriate treatment with DDAVP.

Learning points:

  • Sheehan’s syndrome can occur, though rarely, without an obvious major post-partum hemorrhage.

  • The syndrome may resemble lymphocytic hypophysitis clinically and imaging studies may be crucial in order to differentiate both conditions.

  • Hypopituitarism presentation may be variable and depends on the specific hormone deficit.

  • Euvolemic hyponatremia workup must include thyroid function test and 08:00 AM cortisol levels.

Open access
Hashem Bseiso Department of Medicine, Neuroendocrine Tumor Unit, Endocrinology & Metabolism Service

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Naama Lev-Cohain Department of Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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David J Gross Department of Medicine, Neuroendocrine Tumor Unit, Endocrinology & Metabolism Service

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Simona Grozinsky-Glasberg Department of Medicine, Neuroendocrine Tumor Unit, Endocrinology & Metabolism Service

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Summary

A 55-year-old woman diagnosed with sporadic MTC underwent total thyroidectomy 20 years ago. After the first surgery, elevated calcitonin levels in parallel with local disease persistence were noted and therefore she underwent repeated neck dissections. During follow-up, multiple foci of metastatic disease were noted in the neck and mediastinal lymph nodes, lungs and bones; however, the disease had an indolent course for a number of years, in parallel with a calcitonin doubling time of more than two years and without significant symptoms. During a routine follow-up visit 2 years ago, findings suggestive of Cushing’s syndrome were observed on physical examination. The biochemical evaluation demonstrated markedly elevated serum calcitonin level, in parallel with lack of cortisol suppression after an overnight 1 mg dexamethasone suppression test, lack of cortisol and ACTH suppression after high-dose IV dexamethasone 8 mg, elevated plasma ACTH up to 79 pg/mL (normal <46 pg/mL) and elevated 24-h urinary free cortisol up to 501 µg/24 h (normal 9–90 µg/24 h). After a negative pituitary MRI, she underwent IPSS, which was compatible with EAS. Whole-body CT demonstrated progressive disease at most of the tumor sites. Treatment with vandetanib at a dosage of 200 mg/day was commenced. The patient showed a significant, rapid and consistent clinical improvement already after two months of treatment, in parallel with biochemical improvement, whereas a decrease in tumor size was demonstrated on follow-up CT.

Learning points:

  • Ectopic Cushing’s syndrome due to ectopic ACTH secretion (EAS) by MTC is an uncommon and a poor prognostic event, being associated with significant morbidity and mortality.

  • We demonstrate that vandetanib is effective in controlling the signs and symptoms related to the EAS in patients with advanced progressive MTC.

  • We demonstrate that vandetanib is effective in decreasing tumor size and in inducing tumor control.

Open access
Taiba Zornitzki Endocrinology, Diabetes and Metabolic Unit, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Bilu 176100, Rehovot, Israel

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Hadara Rubinfeld Institute of Endocrinology and Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, 49100, Israel
Sackler School of Medicine, Tel-Aviv University, Tel Aviv, 69978, Israel

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Lyudmila Lysyy Endocrinology, Diabetes and Metabolic Unit, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Bilu 176100, Rehovot, Israel

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Tal Schiller Endocrinology, Diabetes and Metabolic Unit, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Bilu 176100, Rehovot, Israel

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Véronique Raverot Laboratoire d'Hormonologie – CBPE, Hospices Civils de Lyon, 59 bd Pinel69677, Bron Cedex, France

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Ilan Shimon Institute of Endocrinology and Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, 49100, Israel
Sackler School of Medicine, Tel-Aviv University, Tel Aviv, 69978, Israel

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Hilla Knobler Endocrinology, Diabetes and Metabolic Unit, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Bilu 176100, Rehovot, Israel

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Summary

Acromegaly due to ectopic GHRH secretion from a neuroendocrine tumor (NET) is rare and comprises <1% of all acromegaly cases. Herein we present a 57-year-old woman with clinical and biochemical features of acromegaly and a 6 cm pancreatic NET (pNET), secreting GHRH and calcitonin. Following surgical resection of the pancreatic tumor, IGF1, GH and calcitonin normalized, and the clinical features of acromegaly improved. In vitro studies confirmed that the tumor secreted large amounts of both GHRH and calcitonin, and incubation of pNET culture-derived conditioned media stimulated GH release from a cultured human pituitary adenoma. This is a unique case of pNET secreting both GHRH and calcitonin. The ability of the pNET-derived medium to stimulate in vitro GH release from a human pituitary-cell culture, combined with the clinical and hormonal remission following tumor resection, confirmed the ectopic source of acromegaly in this patient.

Learning points

  • Signs, symptoms and initial work-up of acromegaly due to ectopic GHRH secretion are similar to pituitary-dependent acromegaly. However, if no identifiable pituitary lesion is found, somatostatin receptor scan and further imaging (CT, MRI) should be performed.

  • Detection of GHRH in the blood and in the tumor-derived medium supports the diagnosis of ectopic GHRH secretion.

  • Functional bioactivity of pNET-secreted GHRH can be proved in vitro by releasing GH from human pituitary cells.

Open access
Avital Nahmias Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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Simona Grozinsky-Glasberg Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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Asher Salmon Department of Oncology, Hadassah-Hebrew University Medical Center, Kiryat Hadassah, Jerusalem, POB 12000, 91120, Israel

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David J Gross Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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Summary

Approximately 35% of the pancreatic neuroendocrine tumors (pNETs) are functional, the most common of which is an insulinoma. Rarely can initially nonfunctioning tumor undergo biological transformation to a hormone-secreting tumor with subsequent changes in the clinical picture. We present here three unique patients with long-standing pNETs who developed life-threatening hyperinsulinemic hypoglycemia along with tumor progression. In two of the patients, everolimus (Afinitor) was administered in an attempt to control both tumor growth and hypoglycemia. In two cases everolimus therapy resulted in the abolishment of hypoglycemia and induced significant tumor regression; however these beneficial responses were transient. These cases highlight the exceptional ability of pNETs to change biological behavior in parallel with disease progression. Our experience concurs with recently published studies demonstrating the utility of everolimus for the control of both hypoglycemia and tumor progression.

Learning points

  • Nonfunctional pNET can gain new features such as insulin secretion with related morbidity.

  • Gain of function in a previously nonfunctional pNET signifies tumor progression and is usually associated with poor prognosis.

  • Everolimus proved to be a viable treatment for hypoglycemia in insulinoma patients and was also proven highly effective in the patients presented here.

  • As disease progresses, the effect of everolimus on hypoglycemia wanes. We report for the first time the development of hypoglycemia during everolimus treatment.

Open access
Mahmud Abo Salook Endocrine Institute

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Carlos Benbassat Endocrine Institute
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

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Yulia Strenov Pathology Laboratory, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel

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Amit Tirosh Endocrine Institute
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

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Summary

A 55-year-old male, with a positive medical history for hypothyroidism, treated with stable doses for years was admitted with subacute thyroiditis and a feeling of pain and pressure in the neck. Laboratory tests showed decrease in TSH levels, elevated erythrocyte sedimentation rate, and very high antithyroid antibodies. Owing to enlarging goiter and exacerbation in the patient's complaints, he was operated with excision of a fibrotic and enlarged thyroid lobe. Elevated IgG4 plasma levels and high IgG4/IgG plasma cell ratio on immunohistochemistry led to the diagnosis of IgG4-mediated thyroiditis. We concluded that IgG4-thyroiditis and IgG4-related disease should be considered in all patients with an aggressive form of Hashimoto's thyroiditis.

Learning points

  • IgG4-related disease is a systemic disease that includes several syndromes; IgG4-related thyroiditis is one among them.

  • IgG4-thyroiditis should be considered in all patients with an aggressive form of Hashimoto's thyroiditis.

  • Patients with suspected IgG4-thyroiditis should have blood tested for IgG4/IgG ratio and appropriate immunohistochemical staining if possible.

Open access