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M Mannelli

Publications and source records attributed to M Mannelli.

At least 19 recordsLinked to original sources
PubMed2006

Multi-step approach in a complex case of Cushing's syndrome and medullary thyroid carcinoma.

The diagnosis of Cushing's syndrome (CS) may sometimes be cumbersome. In particular, in ACTH-dependent CS it may be difficult to distinguish between the presence of an ACTH-secreting pituitary adenoma and ectopic ACTH and/or CRH secretion. In such instances, the etiology of CS may remain unknown despite extensive diagnostic workout, and the best therapeutic option for each patient has to be determined. We report here the case of a 54-yr-old man affected by ACTH-dependent CS in association with a left adrenal adenoma and medullary thyroid carcinoma (MTC). He presented with clinical features and laboratory indexes of hypercortisolism associated with elevated levels of calcitonin. Ectopic CS due to MTC was reported previously. In our case hypercortisolism persisted after surgical treatment of MTC. Thorough diagnostic assessment was performed, in order to define the aetiology of CS. He was subjected to basal and dynamic hormonal evaluation, including bilateral inferior petrosal sinus sampling. Extensive imaging evaluation was also performed. Overall, the laboratory data together with the results of radiological procedures suggested that CS might be due to inappropriate CRH secretion. However, the source of CRH secretion in this patient remained unknown. It was then decided to remove the left adenomatous adrenal gland. Cortisol level fell and has remained within the normal range nine months after surgery. This case well depicts the complexity of the diagnostic workout, which is needed sometimes to correctly diagnose and treat CS, and suggests that monolateral adrenalectomy may represent, at least temporarily, a reasonable therapeutic option in occult ACTH-dependent hypercortisolism.

Calcitonin↗
PubMed2006

Unusual association of adrenal pheochromocytoma and para-aortic neurofibroma in pregnancy.

The association of pheochromocytoma (PHEO) and pregnancy is uncommon and life threatening for both the fetus and the mother. Early diagnosis and treatment is essential to decrease maternal and fetal mortality and to differentiate the disease from the more common pre-eclampsia. While medical treatment should be started immediately after diagnosis, the timing of surgical treatment is still debated. We describe the case of a 27-yr-old woman in the 18th week of pregnancy who showed a biochemical pattern typical of PHEO and, by imaging studies, 2 tumors with the same characteristics: the first localized on the right adrenal gland, the second at the right renal hilum. The patient underwent surgery because of suspicion of malignant PHEO with local metastasis, while histology revealed a rare association of a solitary PHEO and para-aortic neurofibroma, both tumors embryologically deriving from a common cell precursor.

Adrenal Gland Neoplasms↗
PubMed2006

Hyponatremia and pituitary adenoma: think twice about the etiopathogenesis.

Pituitary adenomas may be the cause of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), although few cases have so far been reported. We described a case of hypotonic hyponatremia in a 76-yr-old man with a pituitary macroadenoma. He had a recent history of two syncopal attacks which had occurred in the last two months. Baseline assessment demonstrated a sodium serum level of 114 mEq/l. Clinically, the patient appeared euvolemic. Thyroid and adrenal function testing did not show any abnormality. Plasma and urinary osmolality (238 and 186 mOsm/kg, respectively) were in agreement with the diagnosis of SIADH. Accordingly, 3% hypertonic saline solution was started, followed by water intake restriction when natremia reached 126 mEq/l. A computed tomography (CT) scan of the chest revealed the presence of a 2-cm lesion in the azygos-esophageal recess. Because the nature of the lesion appeared uncertain, antibiotic therapy was initiated. After one month, a new CT scan did not show any evidence of the mediastinic mass. Sodium serum level was within the normal range (141 mEq/l) and remained stable thereafter, without fluid restriction. This case very well demonstrates that, in the presence of hyponatremia due to SIADH, more frequently associated co-morbidities (ie mediastinic diseases) have to be searched, even in the presence of a possible, yet rare, cause of this syndrome (ie pituitary adenoma).

Aged↗
PubMed2006

SDH mutations in patients affected by paraganglioma syndromes: a personal experience.

Mutations in genes encoding mitochondrial succinate dehydrogenase (SDH) are frequently involved in the development of neural crest-derived (NCD) tumors, such as pheochromocytomas (PHEOs) or paragangliomas (PGLs). In this study we report the results of sequencing analysis in leukocyte DNA of patients affected by PHEO/PGL who turned out to be SDH mutation carriers. A nonsense germline heterozygous mutation (Q109X) was found in the exon 4 of the SDHD gene in the index cases of six unrelated families affected by PHEO/PGL. Haplotype analysis showed the presence of a founder effect. Affected patients showed high clinical variability, ranging from monolateral to bilateral glomus tumors, variably associated or not with PGLs or PHEOs. A novel missense SDHD variant, T112I, was also found in one of our families. A new missense G106D mutation, involving a highly conserved amino acid, was found in two sisters affected by bilateral glomus tumors. A P81L mutation associated with abdominal and head and neck PGL was detected in three families. A G12S variant of the SDHD gene was found in one patient affected by a PHEO. The finding of this variant in 3 of 100 control subjects suggests that it is a polymorphism and not a mutation. A novel IVS2-1G>T variant was found at intron 2 of SDHD gene in one patient affected by a glomus tumor. All the tumors associated with SDHD mutations were benign. Conversely, the only mutation we found in SDHB gene (IVS3+1G>A) was associated with a malignant PHEO.

Amino Acid Sequence↗
PubMed2005

Unique association of non-functioning pheochromocytoma, ganglioneuroma, adrenal cortical adenoma, hepatic and vertebral hemangiomas in a patient with a new intronic variant in the VHL gene.

We analyzed the clinical, hormonal, immunohistochemical and genetic features in a 69-yr-old Caucasian woman with a very rare "composite and mixed pheochromocytoma". This was characterized by right adrenal pheochromocytoma associated with homolateral ganglioneuroma and controlateral adrenal cortical adenoma. The three tumors, incidentally discovered, proved to be non-functioning (normal secretion of catecholamines and of other neuroendocrine peptides, glucocorticoids, mineralcorticoids and androgens). Accordingly, the patient showed no sign or symptom of endocrine disease. Computed tomography (CT) and magnetic resonance (MR) demonstrated a typical adenomatous lesion on the left adrenal gland with precocious uptake of the radiotracer on radioidine (131I)-norcholesterol adrenal scintigraphy, while the controlateral gland showed hyperdensity on CT, hyperintensity on MR and no uptake at adrenal scintigraphy. In addition, CT and MR revealed a vertebral and two hepatic hemangiomas. The right adrenal gland was surgically removed and, microscopically, pheochromocytoma and ganglioneuroma areas appeared intermixed without a predominant component. The former showed strong immunoreactivity for chromogranin, synaptophysin, vascular endothelial growth factor (VEGF) and CD34, while the latter appeared positive for neuron-specific enolase (NSE) and S-100. Peripheral blood genomic DNA analysis revealed a new intronic variant (5557A > G) in the von Hippel-Lindau gene (VHL) not observed in our control population.

Adrenal Cortex Neoplasms↗
PubMed2005

Phenotype variability of neural crest derived tumours in six Italian families segregating the same founder SDHD mutation Q109X.

BACKGROUND: Mutations in genes coding for the mitochondrial complex II succinate dehydrogenase (SDH) subunits cause familial neural crest derived (NCD) tumours. METHODS: Index cases from six apparently unrelated families affected by NCD tumours were analysed for mutations in the SDHB, SDHC, and SDHD genes. RESULTS: The same nonsense germline heterozygous mutation (Q109X) in exon 4 of the SDHD gene was found in each of the six families. Overall, 43 heterozygotes were identified. These were evaluated for the presence of NCD tumours through radiological examination of the neck, thorax, and abdomen, and measurement of urinary metanephrines and plasma chromogranin A. A novel missense SDHD variant, T112I, which did not segregate with the Q109X mutation and was not associated with phenotypic manifestations, was observed in one of the families. Microsatellite analysis showed a common haplotype in all individuals heterozygous for the Q109X mutation, indicating a founder effect. Overall, 18 heterozygotes were clinically affected by at least one NCD tumour. Every affected patient inherited the germline mutation from the father, confirming SDHD maternal genomic imprinting. Penetrance of the paternally inherited mutation progressively increased from 33% to 83% at 30 and 60 years, respectively. Affected patients showed high clinical variability, ranging from monolateral to bilateral glomus tumours variably associated or not with paragangliomas or phaeochromocytomas. Loss of heterozygosity was observed in tumour cells isolated by laser capture microdissection. CONCLUSIONS: This study shows that a single founder SDHD mutation is present in an area of central Italy and that this mutation is associated with widely variable interfamilial and intrafamilial expressivity.

Adult↗
PubMed2005

Low molecular weight proteomic information distinguishes metastatic from benign pheochromocytoma.

Metastatic lesions occur in up to 36% of patients with pheochromocytoma. Currently there is no way to reliably detect or predict which patients are at risk for metastatic pheochromocytoma. Thus, the discovery of biomarkers that could distinguish patients with benign disease from those with metastatic disease would be of great clinical value. Using surface-enhanced laser desorption ionization protein chips combined with high-resolution mass spectrometry, we tested the hypothesis that pheochromocytoma pathologic states can be reflected as biomarker information within the low molecular weight (LMW) region of the serum proteome. LMW protein profiles were generated from the serum of 67 pheochromocytoma patients from four institutions and analyzed by two different bioinformatics approaches employing pattern recognition algorithms to determine if the LMW component of the circulatory proteome contains potentially useful discriminatory information. Both approaches were able to identify combinations of LMW molecules which could distinguish all metastatic from all benign pheochromocytomas in a separate blinded validation set. In conclusion, for this study set low molecular mass biomarker information correlated with pheochromocytoma pathologic state using blinded validation. If confirmed in larger validation studies, efforts to identify the underlying diagnostic molecules by sequencing would be warranted. In the future, measurement of these biomarkers could be potentially used to improve the ability to identify patients with metastatic disease.

Adolescent↗
PubMed2005

Tomographic evaluation of [131I] 6beta-iodomethyl-norcholesterol standardised uptake trend in clinically silent monolateral and bilateral adrenocortical incidentalomas.

AIM: The aim of this study was three-fold: 1) to quantify [131I]-6beta-iodomethyl-norcholesterol ([131I]-NP-59) adrenal uptake trend in patients with incidentalomas, 2) to identify a specific uptake trend (TREND) capable of characterising pre-clinical Cushing syndrome (PC-CS) patients, 3) to assess the clinical availability of TREND as a prognostic factor of late clinical outcome in a cohort of patients with bilateral adrenal adenomas. METHODS: Fifty-seven consecutive patients were examined using three-head SPECT at 24, 48, 72 hours following intravenous injection of [131I ]-NP-59. On the basis of the absence or presence of hormonal abnormalities, the selected population was classified as GR1 or GR2, respectively. Adrenal glands were classified into 4 groups taking into account both the patient group (GR1, GR2) and the presence (+) or absence (-) of the adenoma (AD) on CT scan. Using ROI technique, adrenal-liver uptake ratio (A/L) was estimated bilaterally at 24, 48 and 72 hours. For each adrenal group, mean [131I]-NP-59 uptake trends were derived. RESULTS: TREND was significantly different between GR1/AD+ and GR2/AD+. Among GR2/AD+ patients, TREND correctly identified PC-CS with a global accuracy of 74%. Two patients with bilateral incidentaloma developed an overt CS. In both patients, TREND correctly identified the hyperfunctioning adrenal, thus permitting an effective sparing adrenalectomy. CONCLUSIONS: TREND seems to be a parameter which closely reflects adrenal physiological behaviour, especially in the case of bilateral adrenal involving. The possibility to quantify even contralateral adrenal uptake as standardised index provides additional useful information about normal adrenal parenchyma and, indirectly, about adenoma functional autonomy.

19-Iodocholesterol↗
PubMed2004

Distinct gene expression profiles in norepinephrine- and epinephrine-producing hereditary and sporadic pheochromocytomas: activation of hypoxia-driven angiogenic pathways in von Hippel-Lindau syndrome.

Pheochromocytomas in von Hippel-Lindau (VHL) syndrome produce exclusively norepinephrine, whereas those in multiple endocrine neoplasia type 2 (MEN 2) produce epinephrine. This study examined the pathways activated in VHL-associated pheochromocytomas by comparing gene expression profiles in VHL and MEN 2 tumors in relationship to profiles in sporadic norepinephrine- and epinephrine-producing tumors. Larger and more distinct differences in gene expression among hereditary than sporadic tumors indicated the importance of the underlying mutation to gene expression profiles. Many of the genes over-expressed in VHL compared with MEN 2 tumors were clearly linked to the hypoxia-driven angiogenic pathways that are activated in VHL-associated tumorigenesis. Such genes included those for the glucose transporter, vascular endothelial growth factor (VEGF), placental growth factor, angiopoietin 2, tie-1, VEGF receptor 2 and its coreceptor, neuropilin-1. Other up-regulated genes, such as connective tissue growth factor, cysteine-rich 61, matrix metalloproteinase 1, vascular endothelial cadherin, tenascin C, stanniocalcin 1, and cyclooxygenases 1 and 2 are known to be involved in VEGF-regulated angiogenesis. Shared differences in expression of subsets of genes in norepinephrine- versus epinephrine-producing hereditary and sporadic pheochromocytomas indicated other differences in gene expression that may underlie the biochemical phenotype. Over-expression of the hypoxia-inducible transcription factor, HIF-2alpha, in norepinephrine-predominant sporadic and VHL tumors compared with epinephrine-producing tumors indicates that expression of this gene depends on the noradrenergic biochemical phenotype. The findings fit with the known expression of HIF-2alpha in norepinephrine-producing cells of the sympathetic nervous system and might explain both the development and noradrenergic biochemical phenotype of pheochromocytomas in VHL syndrome.

Adolescent↗
PubMed2002

Diagnosis and management of pheochromocytoma during pregnancy.

Although the presence of pheochromocytoma in pregnancy is extremely rare, this association deserves much attention as the tumor constitutes a very high risk for both mother and fetus. Any pregnant woman with hypertension, especially if paroxysmal or labile, or with so far unexplained "spells", should induce the clinician to consider the possibility of a pheochromocytoma. Maternal and fetal survival depend a lot on an early diagnosis, a correct medical therapy and a correct timing of delivery and surgery. In this respect, a strict collaboration between obstetricians, endocrinologists, anesthesiologists and surgeons is pivotal.

Adrenal Gland Neoplasms↗
PubMed2001

False serum calcitonin high levels using a non-competitive two-site IRMA.

Dual site antibody-base immunoassays are commonly used in clinical laboratories to quantify the CT serum concentrations as a specific and sensitive marker of medullary thyroid carcinoma (MTC). Heterophile antibodies can interfere with these assays, however, and cause erroneous results. In order to avoid this interference, immobilized and conjugated antibodies from two different animal species or immunoreactive antibody fragments, as well as the addition of non-immune globulins, are generally included among the assay reagents. We describe the case of a 73-year-old man affected by a multinodular goiter, who showed high basal CT plasma levels as measured by a monoclonal antibody based IRMA. The finding of negative results for the presence of MTC at fine needle aspiration (FNA) and the mild increase observed in plasma CT during a pentagastrin (Pg) stimulation test, suggested that the high CT levels might depend on a cross-reaction with heterophilic antibodies. In fact, after the addition of the heterophilic blocking tube (HBT) to each specimen, the CT levels markedly decreased by more than 80% (average decrease+/-SE= 87.6+/-2.668%). Such a decrease strongly suggests that in our case the routinely used F(ab')2 fragments were unable to eliminate all of the interference and that the elevated serum CT levels might have been caused by human heterophilic antibodies. In conclusion, these results indicate a novel cause of CT false positivity, suggesting that high serum CT levels, when combined with a slight increase during Pg stimulation, should be critically interpreted in view of the possible presence of heterophilic antibodies in the specimens.

Aged↗
PubMed2001

Adrenal masses in neoplastic patients: the role of laparoscopic procedure.

BACKGROUND: The incidence of complications resulting from fine-needle biopsy of adrenal masses in patients already treated by radical procedures for primitive neoplasms of the lungs and kidneys substantiates our opinion concerning laparoscopy as both a diagnostic and therapeutic procedure. METHODS: We performed 70 laparoscopic adrenalectomies from April 1995 to December 1999. In five patients, the adrenal mass appeared at follow-up evaluation in patients submitted to surgery for a spinocellular lung cancer. One patient underwent surgery for renal adenocarcinoma. In two patients, the adrenal mass was present already at the time primitive lung tumor was diagnosed, so adrenalectomy was performed at the first lung surgery in one patient and 2 weeks before lung surgery in the other patient. All the patients were placed in a lateral position for a transperitoneal approach. Right adrenal masses were present in seven patients, whereas one patient had an adrenal mass in a left location. RESULTS: No laparotomy was required. The average surgical time was 160 min. (range, 115-120 min). No morbility or mortality occurred, and the average hospital stay was 4 days (range, 3-11 days). All the patients had a complete removal of their masses, which averaged 4.5 cm (range, 2.5-6 cm) in size. Histology confirmed the metastatic origin of the mass in five of seven patients with primary lung cancer, and in one patient with previous kidney cancer. At this writing, three patients were disease free and still alive respectively at 3, 5, and 18 months. Three patients died of brain metastases respectively at 16, 36, and 36 months. An adenoma was proved in the other two cases. CONCLUSIONS: Laparoscopic adrenalectomy allows us to propose a much more aggressive approach to adrenal masses demonstrated at follow-up evaluation or in patients with primary lung or kidney cancer and no masses at other locations. Nevertheless a much larger study is required for definitive conclusions on a survival rate. We believe that a mini-invasive procedure such as laparoscopy may allow us to replace a rational surgical approach with a more certain pathologic diagnosis.

Adenoma↗
PubMed2001

Centrally mediated effects of bromocriptine on cardiac sympathovagal balance.

Bromocriptine, a dopamine agonist, is known to lower cardiovascular mortality in L-dopa-treated patients with Parkinson's disease, probably by reducing the cardiac sympathetic activity. We aimed at unmasking the central effects of bromocriptine on the heart by power spectrum analysis. Ten healthy subjects (aged 31+/-2 years) in supine and sitting positions were evaluated after the administration of bromocriptine (2.5 mg) alone and after pharmacological peripheral D(2)-like blockade by domperidone (20 mg). We calculated (autoregressive method) the following: the low-frequency (LF) component (an index of cardiac sympathetic tone), the high-frequency (HF) component (an index of cardiac vagal tone), and the LF/HF ratio (an index of cardiac sympathovagal balance). With subjects in the supine position, bromocriptine alone induced a significant increase in the LF component and the LF/HF ratio, together with a reduction in norepinephrine plasma levels and blood pressure values. These conflicting effects can be explained as the combined result of direct and indirect (reflex-mediated) actions of bromocriptine in vivo. No changes in cardiac autonomic drive were observed with subjects in the sitting position. After domperidone pretreatment, bromocriptine induced a reduction in the LF component and in the LF/HF ratio. The sitting position caused an increase in heart rate and in the LF/HF ratio. We demonstrated both peripheral and central effects of bromocriptine. In particular, pretreatment with a peripheral antagonist (domperidone) allowed us to unmask the central effect of bromocriptine on cardiac sympathetic drive.

Adult↗
PubMed2001

Variable expression of the transcription factors cAMP response element-binding protein and inducible cAMP early repressor in the normal adrenal cortex and in adrenocortical adenomas and carcinomas.

The molecular mechanisms leading to adrenocortical tumorigenesis have been only partially elucidated so far. Because the pituitary hormone ACTH, via activation of the cAMP pathway, regulates both cell proliferation/differentiation and steroid synthesis in the adrenal cortex, in this study we focused on the cAMP-dependent transcription factors cAMP responsive element modulator (CREM) and cAMP responsive element binding protein (CREB). We studied CREM and CREB expression by RT-PCR in human normal adrenal cortex (n = 3), adrenocortical adenomas (n = 8), and carcinomas (n = 8). We found transcripts corresponding to the isoforms alpha, beta, gamma, and tau2 of the CREM gene in all of the normal adrenal tissues, in the adenomas, and in seven of eight carcinomas. On the other hand, mRNA for the inducible cAMP early repressor isoforms, which derive from an internal promoter of CREM gene, was detected in the normal adrenal and in seven of eight adenomas, but in only three of eight carcinomas. Similarly, CREB transcripts were readily detectable in all normal adrenals and adenomas, whereas they were not found in four of eight adrenal carcinomas. To further characterize the carcinomas, telomerase activity and the expression of the ACTH receptor gene were determined. Telomerase activity in the carcinomas resulted in levels significantly higher than in the adenomas, whereas the levels of ACTH receptor mRNA were lower in the carcinomas. No correlation was found in the carcinomas between the levels of the ACTH receptor transcript and the loss of expression of CREB/inducible cAMP early repressor, suggesting that this alteration is not secondary to an upstream disregulation at the receptor level. In conclusion, our results suggest that an alteration in cAMP signaling may be associated with malignancies of the adrenal cortex.

Adenoma↗
PubMed2001

Guidelines for diagnosis and therapy of MEN type 1 and type 2.

This is a consensus statement from an international group, mostly of clinical endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. MEN1 has no clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical tests yearly and imaging tests less often. Neck surgery includes subtotal or total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton pump inhibitors or somatostatin analogs are the main management for oversecretion of entero-pancreatic hormones, except insulin. The roles for surgery of most entero-pancreatic tumors present several controversies: exclusion of most operations on gastrinomas and indications for surgery on other tumors. Each MEN1 family probably has an inactivating MEN1 germline mutation. Testing for a germline MEN1 mutation gives useful information, but rarely mandates an intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.

Humans↗
PubMed2001

Pheochromocytomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 display distinct biochemical and clinical phenotypes.

This study examined the mechanisms linking different biochemical and clinical phenotypes of pheochromocytoma in multiple endocrine neoplasia type 2 (MEN 2) and von Hippel-Lindau (VHL) syndrome to underlying differences in the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and of phenylethanolamine N-methyltransferase (PNMT), the enzyme that converts norepinephrine to epinephrine. Signs and symptoms of pheochromocytoma, plasma catecholamines and metanephrines, and tumor cell neurochemistry and expression of TH and PNMT were examined in 19 MEN 2 patients and 30 VHL patients with adrenal pheochromocytomas. MEN 2 patients were more symptomatic and had a higher incidence of hypertension (mainly paroxysmal) and higher plasma concentrations of metanephrines, but paradoxically lower total plasma concentrations of catecholamines, than VHL patients. MEN 2 patients all had elevated plasma concentrations of the epinephrine metabolite, metanephrine, whereas VHL patients showed specific increases in the norepinephrine metabolite, normetanephrine. The above differences in clinical presentation were largely explained by lower total tissue contents of catecholamines and expression of TH and negligible stores of epinephrine and expression of PNMT in pheochromocytomas from VHL than from MEN 2 patients. Thus, mutation-dependent differences in the expression of genes controlling catecholamine synthesis represent molecular mechanisms linking the underlying mutation to differences in clinical presentation of pheochromocytoma in patients with MEN 2 and the VHL syndrome.

Adolescent↗
PubMed2001

Cushing's syndrome due to intermittent ectopic ACTH production showing a temporary remission during a pulmonary infection.

OBJECTIVES: In about 15-20% of patients with ACTH-dependent Cushing's syndrome the source of ACTH is outside the pituitary gland. Pulmonary tumours are the most frequent, yet not unique, source of ectopic ACTH. In some instances the localisation of an ACTH-secreting tumour may be problematic. Occult ectopic ACTH secretion indicates the occurrence of ACTH-dependent hypercortisolism with an unknown origin. Another peculiarity of Cushing's syndrome may reside in the episodic cortisol hypersecretion, which can determine a pattern characterised by hypercortisolism together with periods of remission (cyclic Cushing's syndrome). We describe a very challenging case of Cushing's syndrome due to ectopic ACTH hypersecretion, showing virtually all of the most unusual features of the disease. DESIGN: A 55-year-old woman affected by Cushing's syndrome, presenting with biochemical features of ectopic ACTH secretion, has been followed for 7 years. METHODS: Thorough basal and dynamic hormonal assessment through the past 7 years is reported. In addition, the results of extensive imaging studies are presented. RESULTS: The source of ACTH secretion has not been identified so far, and hypercortisolism has been controlled by octreotide treatment. In addition, the patient showed a cyclic pattern of hypercortisolism with a long-term remission period. A unique feature of this case is represented by the fact that we observed a temporary, yet dramatic, short-lasting remission of ACTH and cortisol hypersecretion during a pulmonary infection, which occurred while the patient was hospitalised for a periodic hormonal assessment. CONCLUSIONS: This case well represents the wide spectrum of clinical variability of Cushing's syndrome. Most interestingly, to our knowledge, this is the first report of a case of Cushing's syndrome showing a remission during an acute infection.

Adrenocorticotropic Hormone↗