Clinical Overview > Hormone > PTH

You are looking at 31 - 40 of 50 items

Nikolaos Asonitis National and Kapodistrian University of Athens, First Department of Internal Medicine, Laikon Hospital, School of Medicine, Athens, Greece
Msc Metabolic Bone Diseases, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece

Search for other papers by Nikolaos Asonitis in
Google Scholar
PubMed
Close
,
Eva Kassi National and Kapodistrian University of Athens, First Department of Internal Medicine, Laikon Hospital, School of Medicine, Athens, Greece
Msc Metabolic Bone Diseases, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece

Search for other papers by Eva Kassi in
Google Scholar
PubMed
Close
,
Michalis Kokkinos National and Kapodistrian University of Athens, First Department of Internal Medicine, Laikon Hospital, School of Medicine, Athens, Greece

Search for other papers by Michalis Kokkinos in
Google Scholar
PubMed
Close
,
Ilias Giovanopoulos National and Kapodistrian University of Athens, First Department of Internal Medicine, Laikon Hospital, School of Medicine, Athens, Greece

Search for other papers by Ilias Giovanopoulos in
Google Scholar
PubMed
Close
,
Foteini Petychaki National and Kapodistrian University of Athens, First Department of Internal Medicine, Laikon Hospital, School of Medicine, Athens, Greece

Search for other papers by Foteini Petychaki in
Google Scholar
PubMed
Close
, and
Helen Gogas National and Kapodistrian University of Athens, First Department of Internal Medicine, Laikon Hospital, School of Medicine, Athens, Greece

Search for other papers by Helen Gogas in
Google Scholar
PubMed
Close

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
Elda Kara Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

Search for other papers by Elda Kara in
Google Scholar
PubMed
Close
,
Elisa Della Valle Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

Search for other papers by Elisa Della Valle in
Google Scholar
PubMed
Close
,
Sara De Vincentis Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

Search for other papers by Sara De Vincentis in
Google Scholar
PubMed
Close
,
Vincenzo Rochira Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Unit of Endocrinology, Department of Internal Medicine, Endocrinology, Metabolism, and Geriatrics, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy

Search for other papers by Vincenzo Rochira in
Google Scholar
PubMed
Close
, and
Bruno Madeo Unit of Endocrinology, Department of Internal Medicine, Endocrinology, Metabolism, and Geriatrics, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy

Search for other papers by Bruno Madeo in
Google Scholar
PubMed
Close

Summary

Spontaneous or fine-needle aspiration (FNAB)-induced remission of primary hyperparathyroidism (PHPT) may occur, especially for cystic lesions. However, the disease generally relapses over a short time period. We present a case of PHPT due to an enlarged hyperfunctioning parathyroid that underwent long-term (almost 9 years) clinical and ultrasonographic remission after the disappearance of the lesion following ultrasound (US)-assisted FNAB. A 67-year-old woman with PHPT underwent biochemical and US examinations that confirmed the diagnosis and showed a lesion suggestive for parathyroid adenoma or hyperplasia. US-FNAB of the lesion confirmed its parathyroid nature by means of elevated levels of parathyroid hormone within the needle washing fluid. At the second visit, the patient referred slight neck swelling that resolved spontaneously in the days after the US-FNAB. At subsequent follow-up, the enlarged parathyroid was not found; it was visible neither with US nor with magnetic resonance imaging. Biochemical remission persists after 9 years. This is the first reported case of cure of PHPT after US-FNAB performed on a hyperfunctioning parathyroid resulting in its complete disappearance over a period of 9 years of negative biochemical and ultrasonographic follow-up.

Learning points:

  • Spontaneous or fine-needle aspiration-induced remission of primary hyperparathyroidism can occur.

  • Both circumstances may present disease relapse over a variable time period, but definite remission is also possible even though long-term periodic follow-up should be performed.

  • Parathyroid damage should be ruled out in case of neck symptomatology after parathyroid fine-needle aspiration or spontaneous symptomatology in patients with history of primary hyperparathyroidism.

Open access
Kingsley Okolie National Health Co-op, Australian Capital Territory (ACT), Canberra, Australia

Search for other papers by Kingsley Okolie in
Google Scholar
PubMed
Close
,
Sumathy Perampalam Department of Endocrinology, Canberra Hospital, Canberra, ACT, Australia
Australian National University Medical School, Canberra, ACT, Australia

Search for other papers by Sumathy Perampalam in
Google Scholar
PubMed
Close
,
Anthony Barker Forensic Mental Health, Justice Health and Alcohol and Drug Services, Canberra, ACT, Australia

Search for other papers by Anthony Barker in
Google Scholar
PubMed
Close
, and
Christopher J Nolan Department of Endocrinology, Canberra Hospital, Canberra, ACT, Australia
Australian National University Medical School, Canberra, ACT, Australia

Search for other papers by Christopher J Nolan in
Google Scholar
PubMed
Close

Klinefelter syndrome (KS) is a chromosomal disorder affecting males, with the typical karyotype of 47,XXY due to a supernumerary X chromosome, which causes progressive testicular failure resulting in androgen deficiency and infertility. Despite it being the most common sex chromosomal disorder, its diagnosis is easily missed. In addition to its classical clinical features of tall stature, gynaecomastia, small testes, and symptoms and signs of hypogonadism including infertility, KS is also often associated with neurocognitive, behavioural and psychiatric disorders.

We present a 44-year-old man with KS who, despite having erectile dysfunction, paradoxically had increased libido. He used sildenafil to overcome his erectile dysfunction. Hypersexuality was manifested by very frequent masturbation, multiple sexual partners most of whom were casual, and a sexual offence conviction at the age of 17 years.

Discussion focuses on the frequent failure of clinicians to diagnose KS, the neurocognitive, behavioural and psychiatric aspects of KS, this unusual presentation of hypersexuality in a man with KS, and the challenges of medical management of hypogonadism in a man with a history of a sexual offence.

Learning points:

  • Klinefelter syndrome (KS) is common in men (about 1 in 600 males), but the diagnosis is very often missed.

  • In addition to classic features of hypogonadism, patients with KS can often have associated neurocognitive, behavioural and/or psychiatric disorders.

  • More awareness of the association between KS and difficulties related to verbal skills in boys could improve rates of early diagnosis and prevent longer-term psychosocial disability.

  • Hypersexuality in the context of hypogonadism raises the possibility of sex steroid independent mechanistic pathways for libido.

  • Testosterone replacement therapy in KS with hypersexuality should be undertaken with caution using a multidisciplinary team approach.

Open access
Maryam Heidarpour Isfahan University of Medical Sciences Isfahan Endocrine and Metabolism Research Center Ringgold Standard Institution, Isfahan, Iran

Search for other papers by Maryam Heidarpour in
Google Scholar
PubMed
Close
,
Mehdi Karami Isfahan University of Medical Sciences Isfahan Endocrine and Metabolism Research Center Ringgold Standard Institution, Isfahan, Iran

Search for other papers by Mehdi Karami in
Google Scholar
PubMed
Close
,
Pegah Hedayat Isfahan University of Medical Sciences Isfahan Endocrine and Metabolism Research Center Ringgold Standard Institution, Isfahan, Iran

Search for other papers by Pegah Hedayat in
Google Scholar
PubMed
Close
, and
Ashraf Aminorroaya Isfahan University of Medical Sciences Isfahan Endocrine and Metabolism Research Center Ringgold Standard Institution, Isfahan, Iran

Search for other papers by Ashraf Aminorroaya in
Google Scholar
PubMed
Close

Summary

Primary hyperparathyroidism revealed by thoracic spine brown tumor and peptic ulcer bleeding is rare. We presented a case of 33-year-old male patient who was admitted with paraplegia. Thoracic spine magnetic resonance imaging (MRI) showed extradural lesion at T4 level. He underwent surgical decompression in T4. According to histopathologic finding and elevated serum parathormone (PTH) and hypercalcemia (total serum calcium 12.1 mg/dL), the diagnosis of brown tumor was down. Ultrasonography of his neck showed a well-defined lesion of 26 × 14 × 6 mm. The day after surgery, he experienced 2 episodes of melena. Bedside upper gastrointestinal endoscopy showed gastric peptic ulcer with visible vessel. Treatment with intragastric local instillation of epinephrine and argon plasma coagulation was done to stop bleeding. After stabilization of the patient, parathyroidectomy was performed. Histologic study showed the parathyroid adenoma without any manifestation of malignancy. At discharge, serum calcium was normal (8.6 mg/dL). On 40th day of discharge, standing and walking status was normal.

Learning points:

  • Thoracic spine involvement is a very rare presentation of primary hyperparathyroidism.

  • The issue of whether primary hyperparathyroidism increases the risk of peptic ulcer disease remains controversial. However, gastrointestinal involvement has been reported in association with classic severe primary hyperparathyroidism.

  • The treatment of brown tumor varies from case to case.

Open access
Marta Araujo Castro Endocrinology and Nutrition Department, Hospital Puerta de Hierro, Majadahonda, Madrid, Spain

Search for other papers by Marta Araujo Castro in
Google Scholar
PubMed
Close
,
Ainhoa Abad López Endocrinology and Nutrition Department, Hospital Puerta de Hierro, Majadahonda, Madrid, Spain

Search for other papers by Ainhoa Abad López in
Google Scholar
PubMed
Close
,
Luz Martín Fragueiro Pathological Anatomy Department, Hospital Puerta de Hierro, Majadahonda, Madrid, Spain

Search for other papers by Luz Martín Fragueiro in
Google Scholar
PubMed
Close
, and
Nuria Palacios García Endocrinology and Nutrition Department, Hospital Puerta de Hierro, Majadahonda, Madrid, Spain

Search for other papers by Nuria Palacios García in
Google Scholar
PubMed
Close

Summary

The 85% of cases of primary hyperparathyroidism (PHPT) are due to parathyroid adenomas (PA) and less than 1% to parathyroid carcinomas (PC). The PA usually measure <2 cm, weigh <1 g and generate a mild PHPT, whereas the PC usually exceeds these dimensions and are associated with a severe PHPT. However, giant PA (GPA), which is defined as those larger than 3 g, has been documented. Those may be associated with very high levels of PTH and calcium. In these cases, their differentiation before and after surgery with PC is very difficult. We present a case of severe PHPT associated with a large parathyroid lesion, and we discuss the differential aspects between the GPA and PC.

Learning points:

  • In parathyroid lesions larger than 2 cm, the differential diagnosis between GPA and PC should be considered.

  • Pre and postsurgical differentiation between GPA and PC is difficult; however, there are clinical, analytical and radiographic characteristics that may be useful.

  • The depth/width ratio larger or smaller than 1 seems to be the most discriminatory ultrasound parameter for the differential diagnosis.

  • Loss of staining for parafibromin has a specificity of 99% for the diagnosis of PC.

  • The simultaneous presence of several histological characteristics, according to the classification of Schantz and Castleman, is frequent in PC and rare in GPA.

Open access
Shinsuke Uraki The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Search for other papers by Shinsuke Uraki in
Google Scholar
PubMed
Close
,
Hiroyuki Ariyasu The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Search for other papers by Hiroyuki Ariyasu in
Google Scholar
PubMed
Close
,
Asako Doi The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Search for other papers by Asako Doi in
Google Scholar
PubMed
Close
,
Hiroto Furuta The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Search for other papers by Hiroto Furuta in
Google Scholar
PubMed
Close
,
Masahiro Nishi The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Search for other papers by Masahiro Nishi in
Google Scholar
PubMed
Close
,
Takeshi Usui Department of Medical Genetics, Shizuoka General Hospital, Shizuoka City, Japan

Search for other papers by Takeshi Usui in
Google Scholar
PubMed
Close
,
Hiroki Yamaue The 2nd Department of Surgery, Wakayama Medical University, Wakayama, Japan

Search for other papers by Hiroki Yamaue in
Google Scholar
PubMed
Close
, and
Takashi Akamizu The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Search for other papers by Takashi Akamizu in
Google Scholar
PubMed
Close

Summary

A 54-year-old man had gastrinoma, parathyroid hyperplasia and pituitary tumor. His family history indicated that he might have multiple endocrine neoplasia type 1 (MEN1). MEN1 gene analysis revealed a heterozygous germline mutation (Gly156Arg). Therefore, we diagnosed him with MEN1. Endocrinological tests revealed that his serum prolactin (PRL) and plasma adrenocorticotropic hormone (ACTH) levels were elevated to 1699 ng/mL and 125 pg/mL respectively. Immunohistochemical analysis of the resected pancreatic tumors revealed that the tumors did not express ACTH. Overnight 0.5 and 8 mg dexamethasone suppression tests indicated that his pituitary tumor was a PRL-ACTH-producing plurihormonal tumor. Before transsphenoidal surgery, cabergoline was initiated. Despite no decrease in the volume of the pituitary tumor, PRL and ACTH levels decreased to 37.8 ng/mL and 57.6 pg/mL respectively. Owing to the emergence of metastatic gastrinoma in the liver, octreotide was initiated. After that, PRL and ACTH levels further decreased to 5.1 ng/mL and 19.7 pg/mL respectively. He died from liver dysfunction, and an autopsy of the pituitary tumor was performed. In the autopsy study, histopathological and immunohistochemical (IHC) analysis showed that the tumor was single adenoma and the cells were positive for ACTH, growth hormone (GH), luteinizing hormone (LH) and PRL. RT-PCR analysis showed that the tumor expressed mRNA encoding all anterior pituitary hormones, pituitary transcription factor excluding estrogen receptor (ER) β, somatostatin receptor (SSTR) 2, SSTR5 and dopamine receptor D (D2R). PRL-ACTH-producing tumor is a very rare type of pituitary tumor, and treatment with cabergoline and octreotide may be useful for controlling hormone levels secreted from a plurihormonal pituitary adenoma, as seen in this case of MEN1.

Learning points:

  • Although plurihormonal pituitary adenomas were reported to be more frequent in patients with MEN1 than in those without, the combination of PRL and ACTH is rare.

  • RT-PCR analysis showed that the pituitary tumor expressed various pituitary transcription factors and IHC analysis revealed that the tumor was positive for PRL, ACTH, GH and LH.

  • Generally, the effectiveness of dopamine agonist and somatostatin analog in corticotroph adenomas is low; however, if the plurihormonal pituitary adenoma producing ACTH expresses SSTR2, SSTR5 and D2R, medical therapy for the pituitary adenoma may be effective.

Open access
Rowena Speak Departments of Oncology and Metabolism, University of Sheffield

Search for other papers by Rowena Speak in
Google Scholar
PubMed
Close
,
Jackie Cook Department of Genetics, Sheffield Children’s Hospital, Sheffield, UK

Search for other papers by Jackie Cook in
Google Scholar
PubMed
Close
,
Barney Harrison Endocrine Surgery, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

Search for other papers by Barney Harrison in
Google Scholar
PubMed
Close
, and
John Newell-Price Departments of Oncology and Metabolism, University of Sheffield
Endocrinology

Search for other papers by John Newell-Price in
Google Scholar
PubMed
Close

Mutations of the rearranged during transfection (RET) proto-oncogene, located on chromosome 10q11.2, cause multiple endocrine neoplasia type 2A (MEN2A). Patients with mutations at the codon 609 usually exhibit a high penetrance of medullary thyroid cancer (MTC), but a sufficiently low penetrance of phaeochromocytoma that screening for this latter complication has been called to question. Patients with other RET mutations are at higher risk of younger age onset phaeochromocytoma if they also possess other RET polymorphisms (L769L, S836S, G691S and S904S), but there are no similar data for patients with 609 mutations. We investigated the unusual phenotypic presentation in a family with MEN2A due to a C609Y mutation in RET. Sanger sequencing of the entire RET-coding region and exon–intron boundaries was performed. Five family members were C609Y mutation positive: 3/5 initially presented with phaeochromocytoma, but only 1/5 had MTC. The index case aged 73 years had no evidence of MTC, but presented with phaeochromocytoma. Family members also possessed the G691S and S904S RET polymorphisms. We illustrate a high penetrance of phaeochromocytoma and low penetrance of MTC in patients with a RET C609Y mutation and polymorphisms G691S and S904S. These data highlight the need for life-long screening for the complications of MEN2A in these patients and support the role for the screening of RET polymorphisms for the purposes of risk stratification.

Learning points:

  • C609Y RET mutations may be associated with a life-long risk of phaeochromocytoma indicating the importance of life-long screening for this condition in patients with MEN2A.

  • C609Y RET mutations may be associated with a lower risk of MTC than often quoted, questioning the need for early prophylactic thyroid surgery discussion at the age of 5 years.

  • There may be a role for the routine screening of RET polymorphisms, and this is greatly facilitated by the increasing ease of access to next-generation sequencing.

Open access
Anna Casteràs Department of Endocrinology

Search for other papers by Anna Casteràs in
Google Scholar
PubMed
Close
,
Lídia Darder Department of Maxilofacial Surgery

Search for other papers by Lídia Darder in
Google Scholar
PubMed
Close
,
Carles Zafon Department of Endocrinology

Search for other papers by Carles Zafon in
Google Scholar
PubMed
Close
,
Juan Antonio Hueto Department of Maxilofacial Surgery

Search for other papers by Juan Antonio Hueto in
Google Scholar
PubMed
Close
,
Margarita Alberola Department of Endocrine Surgery, University Hospital Vall d’Hebron, Barcelona, Spain

Search for other papers by Margarita Alberola in
Google Scholar
PubMed
Close
,
Enric Caubet Department of Pathology

Search for other papers by Enric Caubet in
Google Scholar
PubMed
Close
, and
Jordi Mesa Department of Endocrinology

Search for other papers by Jordi Mesa in
Google Scholar
PubMed
Close

Summary

Skeletal manifestations of primary hyperparathyroidism (pHPT) include brown tumors (BT), which are osteoclastic focal lesions often localized in the jaws. Brown tumors are a rare manifestation of pHTP in Europe and USA; however, they are frequent in developing countries, probably related to vitamin D deficiency and longer duration and severity of disease. In the majority of cases, the removal of the parathyroid adenoma is enough for the bone to remineralize, but other cases require surgery. Hyperparathyroidism in MEN1 develops early, and is multiglandular and the timing of surgery remains questionable. To our knowledge, there are no reports of BT in MEN 1 patients. We present a 29-year-old woman with MEN 1 who developed a brown tumor of the jaw 24 months after getting pregnant, while breastfeeding. Serum corrected calcium remained under 2.7 during gestation, and at that point reached a maximum of 2.82 mmol/L. Concomitant PTH was 196 pg/mL, vitamin D 13.7 ng/mL and alkaline phosphatase 150 IU/L. Bone mineral density showed osteopenia on spine and femoral neck (both T-scores = −1.6). Total parathyroidectomy was performed within two weeks, with a failed glandular graft autotransplantation, leading to permanent hypoparathyroidism. Two months after removal of parathyroid glands, the jaw tumor did not shrink; thus, finally it was successfully excised. We hypothesize that higher vitamin D and mineral requirements during maternity may have triggered an accelerated bone resorption followed by appearance of the jaw BT. We suggest to treat pHPT before planning a pregnancy in MEN1 women or otherwise supplement with vitamin D, although this approach may precipitate severe hypercalcemia.

Learning points:

  • Brown tumors of the jaw can develop in MEN 1 patients with primary hyperparathyroidism at a young age (less than 30 years).

  • Pregnancy and lactation might trigger brown tumors by increasing mineral and vitamin D requirements.

  • Early parathyroidectomy is advisable in MEN 1 patients with primary hyperparathyroidism, at least before planning a pregnancy.

  • Standard bone mineral density does not correlate with the risk of appearance of a brown tumor.

  • Removal of parathyroid glands does not always lead to the shrinkage of the brown tumor, and surgical excision may be necessary.

Open access
Jerena Manoharan Department of Visceral Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse35043, Marburg, Germany

Search for other papers by Jerena Manoharan in
Google Scholar
PubMed
Close
,
Caroline L Lopez Department of Visceral Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse35043, Marburg, Germany

Search for other papers by Caroline L Lopez in
Google Scholar
PubMed
Close
,
Karl Hackmann Faculty of Medicine Carl Gustav Carus, Institute for Clinical Genetics, TU Dresden, Fetscherstrasse 7401307, Dresden, Germany
German Cancer Consortium (DKTK), Dresden, Germany, German Cancer Research Center (DKFZ), Heidelberg, Germany, National Center for Tumor Diseases (NCT), Dresden, Germany

Search for other papers by Karl Hackmann in
Google Scholar
PubMed
Close
,
Max B Albers Department of Visceral Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse35043, Marburg, Germany

Search for other papers by Max B Albers in
Google Scholar
PubMed
Close
,
Anika Pehl Department of Pathology, Philipps University Marburg, Baldingerstrasse35043, Marburg, Germany

Search for other papers by Anika Pehl in
Google Scholar
PubMed
Close
,
Peter H Kann Division of Endocrinology and Diabetology, Department of Gastroenterology and Endocrinology, Philipps University Marburg, Baldingerstrasse35043, Marburg, Germany

Search for other papers by Peter H Kann in
Google Scholar
PubMed
Close
,
Emily P Slater Department of Visceral Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse35043, Marburg, Germany

Search for other papers by Emily P Slater in
Google Scholar
PubMed
Close
,
Evelin Schröck Faculty of Medicine Carl Gustav Carus, Institute for Clinical Genetics, TU Dresden, Fetscherstrasse 7401307, Dresden, Germany
German Cancer Consortium (DKTK), Dresden, Germany, German Cancer Research Center (DKFZ), Heidelberg, Germany, National Center for Tumor Diseases (NCT), Dresden, Germany

Search for other papers by Evelin Schröck in
Google Scholar
PubMed
Close
, and
Detlef K Bartsch Department of Visceral Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse35043, Marburg, Germany

Search for other papers by Detlef K Bartsch in
Google Scholar
PubMed
Close

Summary

We report about a young female who developed an unusual and an aggressive phenotype of the MEN1 syndrome characterized by the development of a pHPT, malignant non-functioning pancreatic and duodenal neuroendocrine neoplasias, a pituitary adenoma, a non-functioning adrenal adenoma and also a malignant jejunal NET at the age of 37 years. Initial Sanger sequencing could not detect a germline mutation of the MEN1 gene, but next generation sequencing and MPLA revealed a deletion of the MEN1 gene ranging between 7.6 and 25.9 kb. Small intestine neuroendocrine neoplasias (SI-NENs) are currently not considered to be a part of the phenotype of the MEN1-syndrome. In our patient the SI-NENs were detected during follow-up imaging on Ga68-Dotatoc PET/CT and could be completely resected. Although SI-NENs are extremely rare, these tumors should also be considered in MEN1 patients. Whether an aggressive phenotype or the occurrence of SI-NENs in MEN1 are more likely associated with large deletions of the gene warrants further investigation.

Learning points

  • Our patient presents an extraordinary course of disease.

  • Although SI-NENs are extremely rare, these tumors should also be considered in MEN1 patients, besides the typical MEN1 associated tumors.

  • This case reports indicate that in some cases conventional mutation analysis of MEN1 patients should be supplemented by the search for larger gene deletions with modern techniques, if no germline mutation could be identified by Sanger sequencing.

Open access
Reiner Jumpertz von Schwartzenberg Department of Endocrinology and Metabolic Diseases, Charité – Universitätsmedizin, Charitéplatz 1, Berlin, 10117, Germany

Search for other papers by Reiner Jumpertz von Schwartzenberg in
Google Scholar
PubMed
Close
,
Ulf Elbelt Department of Endocrinology and Metabolic Diseases, Charité – Universitätsmedizin, Charitéplatz 1, Berlin, 10117, Germany

Search for other papers by Ulf Elbelt in
Google Scholar
PubMed
Close
,
Manfred Ventz Department of Endocrinology and Metabolic Diseases, Charité – Universitätsmedizin, Charitéplatz 1, Berlin, 10117, Germany

Search for other papers by Manfred Ventz in
Google Scholar
PubMed
Close
,
Knut Mai Department of Endocrinology and Metabolic Diseases, Charité – Universitätsmedizin, Charitéplatz 1, Berlin, 10117, Germany

Search for other papers by Knut Mai in
Google Scholar
PubMed
Close
,
Tina Kienitz Department of Endocrinology and Metabolic Diseases, Charité – Universitätsmedizin, Charitéplatz 1, Berlin, 10117, Germany

Search for other papers by Tina Kienitz in
Google Scholar
PubMed
Close
,
Lukas Maurer Department of Endocrinology and Metabolic Diseases, Charité – Universitätsmedizin, Charitéplatz 1, Berlin, 10117, Germany

Search for other papers by Lukas Maurer in
Google Scholar
PubMed
Close
,
Thomas Rose Division of Rheumatology and Clinical Immunology, Medical Department, Charité – Universitätsmedizin, Charitéplatz 1, Berlin, 10117, Germany

Search for other papers by Thomas Rose in
Google Scholar
PubMed
Close
,
Jens C Rückert Department of General Visceral Vascular and Thoracic Surgery, Charité – Universitätsmedizin, Charitéplatz 1, Berlin, 10117, Germany

Search for other papers by Jens C Rückert in
Google Scholar
PubMed
Close
,
Christian J Strasburger Department of Endocrinology and Metabolic Diseases, Charité – Universitätsmedizin, Charitéplatz 1, Berlin, 10117, Germany

Search for other papers by Christian J Strasburger in
Google Scholar
PubMed
Close
, and
Joachim Spranger Department of Endocrinology and Metabolic Diseases, Charité – Universitätsmedizin, Charitéplatz 1, Berlin, 10117, Germany

Search for other papers by Joachim Spranger in
Google Scholar
PubMed
Close

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.

Learning points

  • 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.

Open access