Diagnosis and Treatment > Investigation > IGF1
You are looking at 41 - 50 of 70 items
Search for other papers by Cristina Alvarez-Escola in
Google Scholar
PubMed
Search for other papers by Jersy Cardenas-Salas in
Google Scholar
PubMed
Summary
In patients with active acromegaly after pituitary surgery, somatostatin analogues are effective in controlling the disease and can even be curative in some cases. After treatment discontinuation, the likelihood of disease recurrence is high. However, a small subset of patients remains symptom-free after discontinuation, with normalized growth hormone (GH) and insulin-like growth factor (IGF1) levels. The characteristics of patients most likely to achieve sustained remission after treatment discontinuation are not well understood, although limited evidence suggests that sustained remission is more likely in patients with lower GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on an MRI scan and/or in patients who receive long-term treatment. In this report, we describe the case of a 56-year-old female patient treated with lanreotide Autogel for 11 years. Treatment was successfully discontinued, and the patient is currently disease-free on all relevant parameters (clinical, biochemical and tumour status). The successful outcome in this case adds to the small body of literature suggesting that some well-selected patients who receive long-term treatment with somatostatin analogues may achieve sustained remission.
Learning points:
-
The probability of disease recurrence is high after discontinuation of treatment with somatostatin analogues.
-
Current data indicate that remission after treatment discontinuation may be more likely in patients with low GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on MRI, and/or in patients receiving prolonged treatment.
-
This case report suggests that prolonged treatment with somatostatin analogues can be curative in carefully selected patients.
Search for other papers by Nobuhiro Miyamura in
Google Scholar
PubMed
Search for other papers by Shuhei Nishida in
Google Scholar
PubMed
Search for other papers by Mina Itasaka in
Google Scholar
PubMed
Search for other papers by Hirofumi Matsuda in
Google Scholar
PubMed
Search for other papers by Takeshi Ohtou in
Google Scholar
PubMed
Search for other papers by Yasuhiro Yamaguchi in
Google Scholar
PubMed
Search for other papers by Daisuke Inaba in
Google Scholar
PubMed
Search for other papers by Sadahiro Tamiya in
Google Scholar
PubMed
Search for other papers by Tetsuo Nakano in
Google Scholar
PubMed
Summary
Hepatitis C-associated osteosclerosis (HCAO), a very rare disorder in which an extremely rapid bone turnover occurs and results in osteosclerosis, was acknowledged in 1990s as a new clinical entity with the unique bone disorder and definite link to chronic type C hepatitis, although the pathogenesis still remains unknown. Affected patients suffer from excruciating deep bone pains. We report the 19th case of HCAO with diagnosis confirmed by bone biopsy, and treated initially with a bisphosphonate, next with corticosteroids and finally with direct acting antivirals (DAA: sofosbuvir and ribavirin) for HCV infection. Risedronate, 17.5 mg/day for 38 days, did not improve the patient’s symptoms or extremely elevated levels of bone markers, which indicated hyper-bone-formation and coexisting hyper-bone-resorption in the patient. Next, intravenous methylprednisolone pulse therapy followed by high-dose oral administration of prednisolone evidently improved them. DAA therapy initiated after steroid therapy successfully achieved sustained virological response, but no additional therapeutic effect on them was observed. Our results strongly suggested that the underlying immunological alteration is the crucial key to clarify the pathogenesis of HCAO. Bone mineral density of lumbar vertebrae of the patient was increased by 14% in four-month period of observation. Clarification of the mechanisms that develop osteosclerosis in HCAO might lead to a new therapeutic perspective for osteoporosis.
Learning points:
-
HCAO is an extremely rare bone disorder, which occurs exclusively in patients affected with HCV, of which only 18 cases have been reported since 1992 and pathogenesis still remains unclear.
-
Pathophysiology of HCAO is highly accelerated rates of both bone formation and bone resorption, with higher rate of formation than that of resorption, which occur in general skeletal leading to the diffuse osteosclerosis with severe bone pains.
-
Steroid therapy including intravenous pulse administration in our patient evidently ameliorated his bone pains and reduced elevated values of bone markers. This was the first successful treatment for HCAO among cases reported so far and seemed to propose a key to solve the question for its pathogenesis.
-
The speed of increase in the bone mineral content of the patient was very high, suggesting that clarification of the mechanism(s) might lead to the development of a novel therapy for osteoporosis.
Search for other papers by Marlene Tarvainen in
Google Scholar
PubMed
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Search for other papers by Satu Mäkelä in
Google Scholar
PubMed
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Search for other papers by Jukka Mustonen in
Google Scholar
PubMed
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Division of Internal Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
Search for other papers by Pia Jaatinen in
Google Scholar
PubMed
Summary
Puumala hantavirus (PUUV) infection causes nephropathia epidemica (NE), a relatively mild form of haemorrhagic fever with renal syndrome (HFRS). Hypophyseal haemorrhage and hypopituitarism have been described in case reports on patients with acute NE. Chronic hypopituitarism diagnosed months or years after the acute illness has also been reported, without any signs of a haemorrhagic aetiology. The mechanisms leading to the late-onset hormonal defects remain unknown. Here, we present a case of NE-associated autoimmune polyendocrinopathy and hypopituitarism presumably due to autoimmune hypophysitis. Thyroid peroxidase antibody seroconversion occurred between 6 and 12 months, and ovarian as well as glutamate decarboxylase antibodies were found 18 months after acute NE. Brain MRI revealed an atrophic adenohypophysis with a heterogeneous, low signal intensity compatible with a sequela of hypophysitis. The patient developed central (or mixed central and peripheral) hypothyroidism, hypogonadism and diabetes insipidus, all requiring hormonal replacement therapy. This case report suggests that late-onset hormonal defects after PUUV infection may develop by an autoimmune mechanism. This hypothesis needs to be confirmed by prospective studies with sufficient numbers of patients.
Learning points:
-
Pituitary haemorrhage resulting in hypopituitarism has been reported during acute HFRS caused by PUUV and other hantaviruses.
-
Central and peripheral hormone deficiencies developing months or years after HFRS have also been found, with an incidence higher than that in the general population. The pathogenesis of these late-onset hormonal defects remains unknown.
-
This case report suggests that the late-onset hypopituitarism and peripheral endocrine defects after HFRS could evolve via autoimmune mechanisms.
-
The sensitivity of current anti-pituitary antibody (APA) tests is low. A characteristic clinical course, together with typical brain MRI and endocrine findings may be sufficient for a non-invasive diagnosis of autoimmune hypophysitis, despite negative APAs.
Search for other papers by Katia Regina Marchetti in
Google Scholar
PubMed
Search for other papers by Maria Adelaide Albergaria Pereira in
Google Scholar
PubMed
Search for other papers by Arnaldo Lichtenstein in
Google Scholar
PubMed
Search for other papers by Edison Ferreira Paiva in
Google Scholar
PubMed
Summary
Adrenacarcinomas are rare, and hypoglycemic syndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by these tumors have been described infrequently. This study describes the case of a young woman with severe persistent hypoglycemia and a large adrenal tumor and discusses the physiopathological mechanisms involved in hypoglycemia. The case is described as a 21-year-old woman who presented with 8 months of general symptoms and, in the preceding 3 months, with episodes of mental confusion and visual blurring secondary to hypoglycemia. A functional assessment of the adrenal cortex revealed ACTH-independent hypercortisolism and hyperandrogenism. Hypoglycemia, hypoinsulinemia, low C-peptide and no ketones were also detected. An evaluation of the GH–IGF axis revealed GH blockade (0.03; reference: up to 4.4 ng/mL), greatly reduced IGF-I levels (9.0 ng/mL; reference: 180–780 ng/mL), slightly reduced IGF-II levels (197 ng/mL; reference: 267–616 ng/mL) and an elevated IGF-II/IGF-I ratio (21.9; reference: ~3). CT scan revealed a large expansive mass in the right adrenal gland and pulmonary and liver metastases. During hospitalization, the patient experienced frequent difficult-to-control hypoglycemia and hypokalemia episodes. Octreotide was ineffective in controlling hypoglycemia. Due to unresectability, chemotherapy was tried, but after 3 months, the patient’s condition worsened and progressed to death. In conclusion, our patient presented with a functional adrenal cortical carcinoma, with hyperandrogenism associated with hypoinsulinemic hypoglycemia and blockage of the GH–IGF-I axis. Patient’s data suggested a diagnosis of hypoglycemia induced by an IGF-II or a large IGF-II-producing tumor (low levels of GH, greatly decreased IGF-I, slightly decreased IGF-II and an elevated IGF-II/IGF-I ratio).
Learning points:
-
Hypoglycemyndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by adrenal tumors is a rare condition.
-
Hypoinsulinemic hypoglycemia associated with hyperandrogenism and blockage of the GH–IGF-I axis suggests hypoglycemia induced by an IGF-II or a large IGF-II-producing tumor.
-
Hypoglycemia in cases of NICTH should be treated with glucocorticoids, glucagon, somatostatin analogs and hGH.
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
Search for other papers by Emilia Sbardella in
Google Scholar
PubMed
Search for other papers by George Farah in
Google Scholar
PubMed
Search for other papers by Ahmed Fathelrahman in
Google Scholar
PubMed
Search for other papers by Simon Cudlip in
Google Scholar
PubMed
Search for other papers by Olaf Ansorge in
Google Scholar
PubMed
Search for other papers by Niki Karavitaki in
Google Scholar
PubMed
Search for other papers by Ashley B Grossman in
Google Scholar
PubMed
Summary
Pituitary adenomas are a common intracranial neoplasm, usually demonstrating a benign phenotype. They can be classified according to pathological, radiological or clinical behaviour as typical, atypical or carcinomas, invasive or noninvasive, and aggressive or nonaggressive. Prolactinomas account for 40–60% of all pituitary adenomas, with dopamine agonists representing the first-line treatment and surgery/radiotherapy reserved for drug intolerance/resistance or in neuro-ophthalmological emergencies. We present the case of a 62-year-old man with an apparently indolent prolactin-secreting macroadenoma managed with partial resection and initially showing a biochemical response to cabergoline. Five years later, the tumour became resistant to cabergoline, despite a substantial increase in dosage, showing rapid growth and causing worsening of vision. The patient then underwent two further transsphenoidal operations and continued on high-dose cabergoline; despite these interventions, the tumour continued enlarging and prolactin increased to 107 269 U/L. Histology of the third surgical specimen demonstrated features of aggressive behaviour (atypical adenoma with a high cell proliferation index) not present in the tumour removed at the first operation. Subsequently, he was referred for radiotherapy aiming to control tumour growth.
Learning points:
-
The development of secondary resistance to dopamine agonists (DAs) is a serious sign as it may be associated with de-differentiation of the prolactinoma and thus of aggressive or malignant transformation.
-
Significant de-differentiation of the adenoma documented on consecutive histologies suggests a possible transition to malignancy.
-
A combination of histological ‘alarm’ features associated with persistent growth and escape from DAs treatment in recurrent adenomas should alert clinicians and demands close follow-up.
-
A multidisciplinary approach by pathologists, endocrinologists and neurosurgeons is essential.
Search for other papers by Ekaterina Manuylova in
Google Scholar
PubMed
Search for other papers by Laura M Calvi in
Google Scholar
PubMed
Search for other papers by Catherine Hastings in
Google Scholar
PubMed
Search for other papers by G Edward Vates in
Google Scholar
PubMed
Search for other papers by Mahlon D Johnson in
Google Scholar
PubMed
Search for other papers by William T Cave Jr in
Google Scholar
PubMed
Search for other papers by Ismat Shafiq in
Google Scholar
PubMed
Summary
Co-secretion of growth hormone (GH) and prolactin (PRL) from a single pituitary adenoma is common. In fact, up to 25% of patients with acromegaly may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed prolactinoma is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done. Here, we report two cases of well-controlled prolactinoma on dopamine agonists with the development of acromegaly 10–20 years after the initial diagnoses. In both patients, a mixed PRL/GH-cosecreting adenoma was confirmed on the pathology examination after transsphenoidal surgery (TSS). Therefore, periodic routine measurements of IGF-1 should be considered regardless of the duration and biochemical control of prolactinoma.
Learning points:
-
Acromegaly can develop in patients with well-controlled prolactinoma on dopamine agonists.
-
The interval between prolactinoma and acromegaly diagnoses can be several decades.
-
Periodic screening of patients with prolactinoma for growth hormone excess should be considered and can lead to an early diagnosis of acromegaly before the development of complications.
Search for other papers by Chun-Han Lo in
Google Scholar
PubMed
Search for other papers by Ding-Ping Sun in
Google Scholar
PubMed
Summary
Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. Traditionally, inappropriately elevated levels of insulin in the face of hypoglycemia are the key to diagnosis. However, contradictory levels of insulin and C-peptide do not necessarily exclude the diagnosis. A 50-year-old female was brought to our emergency department because of conscious disturbance on the previous night. She had no history of diabetes mellitus, and was not using any medications or alcohol. Laboratory data showed low sugar, a significantly low insulin level, and elevated C-peptide. After admission, she had multiple episodes of spontaneous hypoglycemia after overnight fasts without discomfort. It was considered that a neuroendocrine tumor was the source of her hypoglycemia. CT scan of the abdomen revealed a 1.1cm hypervascular nodule in the pancreatic tail. Elective laparoscopic distal pancreatectomy was incorporated into her treatment course. A 1.2×1.0cm homogenous well-encapsulated tumor was resected. We monitored her glucose levels in the outpatient clinic every month for a period of six months. She did not have another episode of spontaneous hypoglycemia.
Learning points
-
Insulinoma causes endogenous hypoglycemia – it cannot be ruled out in patients presenting with hypoglycemia and low insulin levels; history and imaging studies should be done for further assessment
-
A 24-h fast test has the same clinical significance as that of 72-h fast test
-
C-peptide is a useful biochemical marker in addition to serum insulin, which can be used to diagnose insulinomas
-
CT scan is used to measure the tumor size and localize the tumor. However, definitive diagnosis is only achieved through histopathologic evaluation of diseased tissue
Search for other papers by Ahmed Iqbal in
Google Scholar
PubMed
Search for other papers by Peter Novodvorsky in
Google Scholar
PubMed
Search for other papers by Alexandra Lubina-Solomon in
Google Scholar
PubMed
Search for other papers by Fiona M Kew in
Google Scholar
PubMed
Search for other papers by Jonathan Webster in
Google Scholar
PubMed
Summary
Secondary amenorrhoea and galactorrhoea represent a common endocrine presentation. We report a case of an oestrogen-producing juvenile granulosa cell tumour (JGCT) of the ovary in a 16-year-old post-pubertal woman with hyperprolactinaemia amenorrhoea and galactorrhoea which resolved following surgical resection of the tumour. This patient presented with a 9-month history of secondary amenorrhoea and a 2-month history of galactorrhoea. Elevated serum prolactin at 7081 mIU/l and suppressed gonadotropins (LH <0.1 U/l; FSH <0.1 U/l) were detected. Serum oestradiol was significantly elevated at 7442 pmol/l with undetectable β-human chorionic gonadotropin. MRI showed a bulky pituitary with no visible adenoma. MRI of the abdomen showed a 4.8 cm mass arising from the right ovary with no evidence of metastatic disease. Serum inhibin B was elevated at 2735 ng/l. A right salpingo-oophorectomy was performed, and histology confirmed the diagnosis of a JGCT, stage International Federation of Gynaecology and Obstetrics 1A. Immunohistochemical staining for prolactin was negative. Post-operatively, oestrogen and prolactin levels were normalised, and she subsequently had a successful pregnancy. In summary, we present a case of an oestrogen-secreting JGCT with hyperprolactinaemia manifesting clinically with galactorrhoea and secondary amenorrhoea. We postulate that observed hyperprolactinaemia was caused by oestrogenic stimulation of pituitary lactotroph cells, a biochemical state analogous to pregnancy. To the best of our knowledge, this is the first report of hyperprolactinaemia as a result of excessive oestrogen production in the context of a JGCT.
Learning points
-
Hyperprolactinaemia with bilateral galactorrhoea and secondary amenorrhoea has a wide differential diagnosis and is not always caused by a prolactin secreting pituitary adenoma.
-
Significantly elevated serum oestradiol levels in the range seen in this case, in the absence of pregnancy, are indicative of an oestrogen-secreting tumour.
-
JGCTs are rare hormonally active ovarian neoplasms mostly secreting steroid hormones.
-
Serum inhibin can be used as a granulosa cell-specific tumour marker.
-
JGCTs have an excellent prognosis in the early stages of the disease.
Search for other papers by Taiba Zornitzki in
Google Scholar
PubMed
Sackler School of Medicine, Tel-Aviv University, Tel Aviv, 69978, Israel
Search for other papers by Hadara Rubinfeld in
Google Scholar
PubMed
Search for other papers by Lyudmila Lysyy in
Google Scholar
PubMed
Search for other papers by Tal Schiller in
Google Scholar
PubMed
Search for other papers by Véronique Raverot in
Google Scholar
PubMed
Sackler School of Medicine, Tel-Aviv University, Tel Aviv, 69978, Israel
Search for other papers by Ilan Shimon in
Google Scholar
PubMed
Search for other papers by Hilla Knobler in
Google Scholar
PubMed
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.
Search for other papers by Nicole Maison in
Google Scholar
PubMed
Search for other papers by Esther Korpershoek in
Google Scholar
PubMed
Search for other papers by Graeme Eisenhofer in
Google Scholar
PubMed
Search for other papers by Mercedes Robledo in
Google Scholar
PubMed
Department of Pathology, Reinier de Graaf Hospital, Delft, The Netherlands
Search for other papers by Ronald de Krijger in
Google Scholar
PubMed
Search for other papers by Felix Beuschlein in
Google Scholar
PubMed
Summary
Pheochromocytomas (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors arising from chromaffin cells of the neural crest. Mutations in the RET-proto-oncogene are associated with sporadic pheochromocytoma, familial or sporadic medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia type 2. In the past, only few cases of pigmented PCCs, PGLs, and one case of pigmented MTC have been reported in the literature. Herein, we present the case of a 77-year old woman with a history of Tako-tsubo-cardiomyopathy and laboratory, as well as radiological, high suspicion of pheochromocytoma, who underwent left-sided adrenalectomy. The 3 cm tumor, which was located on the upper pole of the left adrenal, appeared highly pigmented with dark red to black color. Histologic examinations revealed highly pleomorphic cells with bizarre, huge hyperchromatic nuclei, that immunohistochemically were positive for chromogranin A and synaptophysin, focally positive for HMB45 and negative for melan A. These clinical and pathological features led to the diagnosis of the rare variant of a melanotic ‘black’ pheochromocytoma. In our case a somatic RET mutation in exon 16 (RET c.2753T>C, p.Met918Thy) was detected by targeted next generation sequencing. In summary, this case represents a rare variant of catecholamine-producing tumor with distinct histological features. A potential relationship between the phenotype, the cellular origin and the genetic alterations is discussed.
Learning points
-
Pheochromocytoma is a rare neuroendocrine tumor.
-
Pigmentation is seen in several types of tumors arising from the neural crest. The macroscopic black aspect can mislead to the diagnosis of a metastasis deriving from a malignant melanoma.
-
RET mutation are seen in catecholamine and non-catecholamine producing tumors of the same cellular origin.