Non-functioning Pituitary Microadenoma Research Articles

Resistance to thyroid hormone and nonfunctioning pituitary microadenoma in a 13-year-old boy with THRB mutation.

Resistance to thyroid hormone (RTH) is a rare syndrome characterized by elevated serum free iodothyronines levels and non-suppressed thyroid stimulating hormones (TSH). The most common cause of RTH is heterozygous pathogenic mutations in thyroid hormone receptor β gene (THRB). Because of the similarities in biochemical profiles, differential diagnosis between RTHβ and TSH-secreting pituitary adenoma (TSHoma) is important, and accurate RTHβ diagnosis is essential to prevent inappropriate treatment. A 13-year-old boy was referred to our hospital for a microadenoma and uncontrolled hyperthyroidism despite use of methimazole for more than one year. He suffered from thyrotoxic clinical features and elevated serum T3 and fT4, and normal ranges for TSH and other pituitary hormones were noted. TSH receptor antibody was undetectable, and pituitary MRI revealed a 3mm-sized microadenoma. A TRH stimulation test showed normal TSH response, and the TSH-α-subunit level was not elevated, which is consistent with RTH. The patient was diagnosed with RTHβ and coexistent non-functioning pituitary microadenoma based on identification of a heterozygous mutation, c.1021C>G (p.Leu341Val), in THRB. Methimazole treatment was stopped, and a β-adrenergic blocking agent was started, subsequently thyrotoxic symptoms were relieved. Currently, only one pediatric case diagnosed with RTH and TSHoma has been reported so far, and this case is the first to report a pediatric case of coexistence of RTH and non-functioning pituitary microadenoma. Also, this case shows that inappropriate secretion of thyroid hormones requires careful clinical diagnosis to avoid unnecessary and potentially harmful management.

P-14 A case of Paget's disease of bone presenting at early stages of life

Abstract Paget's disease of bone is the metabolic bone disease that affects 2-4% of individuals over age 55 in European nations. The disease may be asymptomatic and can be detected incidentally through x-rays or biochemical tests conducted for another condition. It can also manifest as bone pain, deformity, fracture, Here, we present a case of Paget's bone disease that manifested at a young age. A 47-year-old female was referred to an endocrinology outpatient clinic due to a nonfunctional pituitary gland microadenoma. She has had constant pain in the right thigh region for the past two years, and no fractures have ever been reported. During the physical examination, the patient's right femur was sensitive to palpation. The results of the standard laboratory test were as follows: Creatinine: 0.61 mg/dl (0-1.2 mg/dl), Albumin: 50 g/L (35-52 g/L), Calcium: 9.8 mg/dl (8.8-10.6 mg/dl), Phosphorus: 4.2 mg/dl (2.6-4.5 mg/dl), PTH (Parathyroid Hormone): 33 ng/L (15-65 ng/L), Alkaline Phosphatase: 524 U/L (33-98 U/L) and 25-OH vitamin D is 43.7 mcg/L. A bone scintigraphy was performed due to the patient's elevated alkaline phosphatase levels and bone pain. The scintigraphy revealed elevated osteoblastic activity in a sclerotic lesion expanding the right femoral cortex, and the results were reported in accordance with Paget's disease. A biopsy of the right femur lesion was performed due to the patient's young age and to rule out other diagnosis such as osteosarcoma or bone metastases. The pathology results revealed thickened and distinct cement lines along with calcified bone fragments, consistent with Paget's disease. The patient was administered 5 mg of IV zoledronic acid, and the alkaline phosphatase level was determined to be 123 U/L (Reference Range: 33-98) at the one-month control following treatment. Paget's disease can be diagnosed in young people. Therefore, it is important to take into account even a slight increase in ALP levels that is linked to early radiological abnormalities.

FRI555 A Misdiagnosis Of TSH-secreting Adenoma With Thyrotoxicosis In A Patient With Graves’ Disease

Abstract Disclosure: J. Huynh: None. A. Makawi: None. G. Elshimy: None. Introduction: Modern healthcare relies on laboratory and imaging results for accurate diagnosis and medical decision-making. However, the collection and distillation of laboratory results is a multi-step process with the potential for error at each stage. This may result in diagnostic errors. A review of salient cases is one avenue to improving awareness of the risk for failure in the laboratory assessment process. We present one such case of a patient initially referred to neurosurgery for management of a thyroid stimulating hormone (TSH) secreting microadenoma, which is a rare disease and accounts for less than 1% of all pituitary adenomas, with incongruent laboratory presentation including elevation in TSH and free T4. Endocrinology consultation prompted further investigations which led to the diagnosis of Graves’ disease with a concomitant nonfunctional pituitary microadenoma. Case Presentation: This is a case of a 61-year-old white male who presented with 30-lb weight loss, insomnia, palpitations, and diaphoresis. Initial thyroid stimulating hormone (TSH) from outside facility was > 90 mcIU/mL with elevated free T4 of 23.4 pg/mL. MRI of the brain shows a 3x3 mm pituitary microadenoma raising concern for an atypical case of TSH-secreting adenoma. The patient referred to Neurosurgery for evaluation by primary care. Endocrinology was consulted for evaluation prior to any surgical intervention. A large goiter was noted on exam. Clinical presentation was highly concern for Graves’ disease. Repeated labs included undetectable TSH with FT4 of 4.4 pg/mL and free T3 12.9 pg/ml. TPO-ab was elevated at 17.1 IU/mL. TSIg index was low. Ultrasound of the thyroid gland revealed a normal thyroid without nodules. He was diagnosed with Graves’ disease and was initiated on methimazole and propranolol with symptomatic improvement. His pituitary panels continued to show suppressed TSH pre and post treatment with no other significant pituitary abnormalities hence the diagnosis of a concomitant nonfunctional pituitary microadenoma was made. Discussion: Ultimately, the initial TSH-secreting microadenoma has deemed a misdiagnosis and he was subsequently treated appropriately for Graves’ disease with normalization of thyroid functions. Standard of care for any laboratory abnormalities is to assess for reproducibility of the result. In our patient, subsequent in-house and outside assays were unable to demonstrate elevation of both TSH and FT4. Instead, the patient had suppressed TSH with elevated FT4, without evidence of nodules consistent with Graves’ disease. Treatment of Graves’ disease differs greatly from the treatment of TSH-secreting pituitary adenoma, which includes surgical resection, radiotherapy, and/or, a somatostatin analog based on the clinical picture. Correct diagnosis prevented our patients from unnecessary surgical complications and lifelong morbidity. Presentation: Friday, June 16, 2023

Rare association of Kallman Morsier syndrome with a non-functioning pituitary microadenoma

Kallmann's syndrome (KS) is a form of hypogonadotropic hypogonadism associated with a defect in the sense of smell, due to abnormal migration of gonadotropin-releasing hormone-producing neurons. We report the case of a patient aged 16 years and 6 months who presented a micropenis with poor development of secondary sexual characteristics and anosmia. Plasma levels of luteinizing hormone, follicle stimulating hormone and testosterone were very low, while chromosomal analysis showed a 46XY karyotype. Hypothalamic-pituitary MRI showed bilateral agenesis of the olfactory bulbs associated with a 4 mm pituitary microadenoma. The patient was put on hormone replacement therapy with a good response.

A Complete Form of Pachydermoperiostosis Accompanied by a Pituitary Microadenoma

Pachydermoperiostosis is a rare genetic disease that is associated with HPGD (15-hydroxyprostaglandin dehydrogenase) and SLCO2A1 (solute carrier organic anion transporter family member 2A1) gene mutations. It is characterized by three major phenotypes, namely, pachydermia, periostosis, and digital clubbing. Clinically, misdiagnoses such as acromegaly and thyroid acropachy are commonly confused with pachydermoperiostosis. Integral medical history, physical examination, endocrinological tests, and multiple disciplinary cooperation are extremely significant in the accurate diagnosis of pachydermoperiostosis. The co-existence of pachydermoperiostosis and pituitary adenoma is rarely recorded and discussed. In this case, we present a young male patient with a complete form of pachydermoperiostosis and a nonfunctional pituitary microadenoma, which has rarely been reported.

Non-functioning pituitary microadenoma in children and adolescents: Is follow-up with diagnostic imaging necessary?

PurposeNo consensus exists regarding follow-up recommendations for suspected pituitary microadenoma in children. To address this knowledge gap, we investigated the growth potential of pituitary solid and cystic lesions <10 mm in children and evaluated the accuracy of magnetic resonance imaging (MRI) measurements.MethodsThe children included were <18 years at first pituitary MRI and radiologically diagnosed with a non-functioning microadenoma or cyst <10 mm. Lesion size at first and latest MRI as well as all individual MRI examinations were re-evaluated.ResultsIn total, 74 children, median age 12 years (range 3–17), had a non-functioning microadenoma, probable microadenoma, or cyst. Of these, 55 underwent repeated MRI (median 3, range 2–7) with a median follow-up of 37 months (range 4–189). None of the pituitary lesions without hormonal disturbances increased significantly during follow-up. Two radiologists agreed that no lesion could be identified in 38/269 (14%) MRI examinations, and in 51/231 (22%) they disagreed about lesion location. In 34/460 (7%) MRI measurements size differed >2 mm, which had been considered significant progression.ConclusionNon-functioning pituitary microadenoma in children has small size variations, often below the spatial resolution of the scanners. We suggest lesions <4 mm only for clinical follow-up, lesions 4–6 mm for MRI after 2 years and ≥7 mm MRI after 1 and 3 years, with clinical follow-up in between. If no progression, further MRI should only be performed after new clinical symptoms or hormonal disturbances.

Case report: Kallmann syndrome associated with a non-functional pituitary microadenoma

Case report: Kallmann syndrome associated with a non-functional pituitary microadenoma

Pseudoacromegaly Associated with Non-Functioning Pituitary Adenoma.

Acromegaly is characterized by excess skin and soft tissue growth due to increased growth hormone (GH) levels. Patients with similar physical findings but without somatotroph axis abnormalities are considered to have pseudoacromegaly. The list of pseudoacromegaly differential diagnoses is long. It may be caused by several congenital and acquired conditions and diagnosis can be challenging due to its rarity and occasional overlapping of some of these conditions. The presence of a pituitary tumour in such cases may lead to a misdiagnosis of acromegaly, and thus, biochemical evaluation is key. Here, we present a case of pseudoacromegaly with an acromegaloid phenotype, normal IGF levels, a supressed GH response to an oral glucose tolerance test, moderate insulin resistance and non-functioning pituitary microadenoma.LEARNING POINTSThere are several conditions that present with clinical aspects of acromegaly or gigantism but without growth hormone (GH) excess. Such cases are described as “pseudoacromegaly” or “acromegaloidism”.In cases of excessive soft tissue growth with normal GH levels, other growth promotors (for example, thyroid hormone, sex hormones, insulin and others) should be taken into consideration.Biochemical confirmation of GH excess in patients presenting with clinical features of acromegaly and pituitary adenoma should always be considered to avoid unnecessary surgeries.

Pituitary Microadenoma Presenting with Panhypopituitarism and Hyponatremia: A Case Report

The prevalence of pituitary adenomas is rising as more are incidentally reported on Magnetic Resonance Imaging (MRI) and Computerized Tomography (CT) imaging studies. While most exist without causing clinical symptoms or laboratory abnormalities, a non-functional sellar mass can initially present with panhypopituitarism. We present a case of pituitary microadenoma that presented with severe hyponatremia and panhypopituitarism. This patient had a non-functional pituitary microadenoma and was hospitalized many times for hyponatremia before finally being diagnosed with panhypopituitarism.

Paediatric and young adult manifestations and outcomes of multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia 1 (MEN 1) is an autosomal dominant disease presenting as hyperplasia and neoplasia of parathyroid, pituitary and enteropancreatic tissues. Over 90% of gene carriers develop phenotypic disease by age 30years, potentially with onset of asymptomatic disease during childhood and adolescence. To describe the paediatric and young adult manifestations of MEN 1. Descriptive retrospective study of 180 patients with a common MEN1 genotype. The paediatric and young adult (age <22years) manifestations were determined using hospital records and disease surveillance data. Primary hyperparathyroidism (PHPT) was identified in 42 patients (mean age 17.2±3.3years). Parathyroidectomy was performed in 16 (38.1%; mean age 17.8±3.2). Four patients experienced recurrent PHPT (25%), and six (37.5%) developed permanent hypoparathyroidism. Pituitary disease was identified in 13 patients. Prolactinoma was found in nine patients (mean age 16.6±2.6years) of whom four (44.4%) had macroprolactinoma. Two patients required surgical intervention; dopamine agonists showed efficacy in six patients. Two patients with Cushing's disease were successfully treated surgically. Three patients with nonfunctioning pituitary microadenoma managed conservatively. Pancreatic neuroendocrine neoplasms (pNENs) were diagnosed in 12 patients (mean age 17.0±2.6years): three patients with insulinoma successfully resected (two resected and one exhibiting perineural invasion) and nine patients with nonfunctioning adenomas (NFAs). Pituitary adenomas, PHPT and pNENs are encountered in the paediatric and young adult MEN 1 population. Successful outcomes are typically achieved using standard medical and surgical paradigms; however, parathyroidectomy was associated with a substantial complication rate.

Clinical Course of Nonfunctional Pituitary Microadenoma in Children: A Single-Center Experience.

Pituitary lesions consistent with microadenomas are increasingly discovered by MRI. Sparse data are available on the long-term clinical and imaging course of such lesions in children. The aim of this study was to define the clinical and imaging course of pituitary lesions representing or possibly representing nonfunctioning microadenomas in children to guide clinical management. Retrospective observational study. The clinical data warehouse at a tertiary care academic children's hospital was queried with the terms "pituitary" AND "microadenoma" and "pituitary" AND "incidentaloma." The electronic health records of the identified subjects were reviewed to extract data on the clinical and imaging course. A total of 78 children had nonfunctioning pituitary lesions incidentally discovered during clinical care, of which 44 (56%) were reported as presumed or possible microadenomas. In the children with microadenoma (median age 15 years, interquartile range 2), a majority (70%) underwent imaging for nonendocrine symptoms, the most common being headache (n = 16, 36%). No significant increase in the size of the microadenoma or cysts or worsening of pituitary function was seen over the average clinical follow-up of 4.5 ± 2.6 years. Four cases of drug-induced hyperprolactinemia resolved with discontinuation of the offending medication. Asymptomatic pituitary lesions representing cysts, microadenomas, or possible microadenomas follow a benign course in children. In the absence of new endocrine or visual symptoms, repeat MRI may not be needed, and if performed, should be done in no less than a year. When possible, it is prudent to discontinue hyperprolactinemia-inducing medications before imaging.

Anterior pituitary insufficiency in clinically non-functioning pituitary microadenoma

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

MON-321 Metastatic Melanoma with Unknown Primary Site in a Patient with Multiple Endocrine Neoplasia Type 1

Background: MEN1 is a rare hereditary tumor syndrome caused by germline inactivating mutations of the tumor suppressor gene MEN1 and is characterized by a predisposition to endocrine tumors primarily of parathyroid, enteropancreatic, and anterior pituitary origin, as well as nonendocrine neoplasms. Cutaneous manifestations mainly include lipomas, angiofibromas, and collagenomas. Melanoma has been observed in MEN1 with 9 cases described in the literature, including 2 cases with unknown primary site (Nord et al. 2000; Baldauf et al. 2009; Brown et al. 2015). Clinical Case: A 45 year old man with MEN1 syndrome manifesting as primary hyperparathyroidism, metastatic pancreatic neuroendocrine tumor (NET), Zollinger-Ellison syndrome, nonfunctional pituitary microadenoma, anterior mediastinal mass and skin angiofibromas presented with a left neck mass that developed over 1 year. CT neck confirmed a 2.2 cm left lateral neck level V mass. Further evaluation revealed stable NET disease with the exception of an enlarging 1.3 cm anterior mediastinal nodule. 18F-FDG PET/CT demonstrated more activity in the left neck mass and mediastinal mass than 68Ga-DOTATATE PET/CT. Biopsy of the left neck mass revealed a high grade malignant neoplasm with epithelioid features and markedly elevated MIB1. Tumor cells were positive for CD56, SOX-10 and S-100 protein, but negative for CD20, CD3, CD5, chromogranin, synaptophysin, AE1/AE3, CAM5.2, C-Kit and p53. Molecular analysis showed pathogenic variants in BRAF, TERT, PIK3C, and RB1, a likely pathogenic variant in FBXW7, and a variant of uncertain significance in PMS2. Given these histologic and molecular findings, the diagnosis of metastatic melanoma was favored. Ophthalmological evaluation, skin examination and biopsy of suspicious cutaneous lesions did not reveal the primary site of melanoma. PCR did not reveal MEN1 loss of heterozygosity (LOH) of the neck mass, though there was insufficient material to evaluate for large MEN1 deletions. Conclusion: Of the 9 cases of melanoma previously reported in MEN1, only 1 was evaluated for MEN1 LOH, which was not demonstrated. MEN1 LOH has been described in sporadic melanoma and in vitro and in vivo studies in mice suggest a role for MEN1 as a tumor suppressor gene in melanoma (Gao et al. 2011, Fang et al. 2013). Whether melanoma in MEN1 is related to the germline MEN1 mutation or is sporadic is still unclear. Evaluation of melanomas for MEN1 LOH initially with targeted sequencing of the germline mutation followed by LOH for markers in and near the MEN1 gene at 11q13, may help further elucidate the role of MEN1 in melanoma.

SAT-310 18F-FDOPA PET/CT Accurately Identifies Pheochromocytoma in 70-Year-Old Male with MEN1

18F-FDOPA PET/CT accurately identifies pheochromocytoma in 70-year-old male with MEN1 Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited disorder that causes tumors most often in the parathyroid, pancreas, and pituitary. Pheochromocytoma in MEN1 is extremely rare (< 2% of cases). Identifying tumor functionality by imaging is challenging given the multiplicity of tumors in MEN1. Case Report: We are reporting a case of a 75-year old male first diagnosed at age 60 with MEN1. Sequencing of MEN1 revealed the pathogenic variant c.249_252delGTCT causing a frameshift mutation. At the time of diagnosis, he was found to have mild hyperparathyroidism status post 2-gland resection, non-functional pituitary microadenoma and bilateral adrenal masses (2.6 cm left; 2.4 cm right). The patient was normotensive and asymptomatic, with elevated plasma normetanephrine 114 pg/mL (upper limit of normal 112) and metanephrine 148 pg/mL (upper limit of normal 61). The remainder of his biochemical workup at that time was normal. The patient remained normotensive and asymptomatic, and routine yearly CT evaluation demonstrated growth of the left adrenal mass to 3.9 cm (9 Hounsfield unit (HU) pre-contrast, and post-contrast HU of 15), and right adrenal mass to 2.6 cm. Follow-up biochemical evaluation revealed an adrenergic biochemical phenotype with elevated plasma metanephrine 432 (12-61 pg/ml) and normetanephrine 291 (18-112 pg/ml) levels, with normal norepinephrine 198 (84-794 pg/ml), dopamine <25 (0-25 pg/ml) but elevated epinephrine 126 (0-57 pg/ml) levels. FDG-PET/CT demonstrated bilateral adrenal uptake (6.36 SUV on the left, and 4.38 SUV on the right) and I-123-MIBG scintigraphy demonstrated abnormal uptake of tracer corresponding to both adrenal masses. However, 18F-FDOPA PET/CT demonstrated a centrally photopenic left adrenal mass (28.7 SUV) and physiologic 18F-FDOPA PET uptake on the right adrenal mass. 68Ga-DOTATATE was not available at the time. The patient underwent an uneventful left adrenalectomy for pheochromocytoma in June 2016 and has had normalization of his previously elevated biochemical results. Loss of heterozygosity at 11q13 was analyzed and determined to be positive. Conclusion: Pheochromocytoma in MEN1 is extremely rare. Despite a lack of symptoms, enlarging adrenal nodules should be screened for pheochromocytoma. Particularly in the setting of elevated plasma metanephrines and undetermined adrenal masses by anatomic imaging, FDG-PET/CT and/or I-123-MIBG, 18F-FDOPA PET/CT may be beneficial.

A case of Kallmann syndrome associated with a non-functional pituitary microadenoma.

SummaryKallmann syndrome (KS) is a form of hypogonadotropic hypogonadism in combination with a defect in sense of smell, due to abnormal migration of gonadotropin-releasing hormone-producing neurons. We report a case of a 17-year-old Tunisian male who presented with eunuchoid body proportions, absence of facial, axillary and pubic hair, micropenis and surgically corrected cryptorchidism. Associated findings included anosmia. Karyotype was 46XY and hormonal measurement hypogonadotropic hypogonadism. MRI of the brain showed bilateral agenesis of the olfactory bulbs and 3.5 mm pituitary microadenoma. Hormonal assays showed no evidence of pituitary hypersecretion.Learning points:The main clinical characteristics of KS include hypogonadotropic hypogonadism and anosmia or hyposmia.MRI, as a non-irradiating technique, should be the first radiological step for investigating the pituitary gland as well as abnormalities of the ethmoid, olfactory bulbs and tracts in KS.KS may include anterior pituitary hypoplasia or an empty sella syndrome. The originality of our case is that a microadenoma also may be encountered in KS. Hormonal assessment indicated the microadenoma was non-functioning. This emphasizes the importance of visualizing the pituitary region in KS patients to assess for hypoplastic pituitary malformations or adenomas.

Stature-weight growth delays: Clinical and etiological aspects.

Background:Stature–weight growth delay (SWGD) is a frequent motivation of consultation. It could be a consequence of a known chronic affection, congenital or acquired affection. The purpose of this study is to describe epidemiological, clinical, paraclinical, and etiological aspects of SWGD.Patients and Methods:This retrospective study included 103 patients presenting a growth delay with an average age of 14.44 years and ranging between 5 and 21 years. Male predominance was noticed in 68.93% of cases. Patients showed a stature lower to −2 standard deviation (SD) for corresponding age compared to Sempe and Pedron reference. Patients were hospitalized in Endocrinology and Metabolic Diseases Department of the University Hospital of Fez, Fez, Morocco.Results:Patient's history included a perinatal suffering in 6.7% of cases, a chronic pathology follow-up in 17.6% of cases, and psychomotor development disorder in 10.6% of cases. The average weight was −2.37 SD with extremes varying from −4 to −0.5 SD. The stature values varied between −4.5 and −2 SD for the given age, with an average of −3.12 SD. A severe stature delay (< −3 SD) was recorded in 39.6% of cases and the targeted average size was −2.44 SD with extremes varying from −4 to −1.5 SD. Growth delay etiologies were dominated by a deficit in growth hormones (GHs) in 60% of cases.Discussion and Conclusion:Dynamic tests objectified a total deficit and partial deficits in GH in 41.7 and 30% of patients, respectively. The hypothalamo–pituitary magnetic resonance imaging was pathological in 23.3% of patients and showed a syndrome of interruption of pituitary stem in seven patients, pituitary hail gland in three patients, a craniopharyngioma in two patients, prolactin microadenoma in one patient, and nonfunctional pituitary microadenoma in one patient. GH treatment was established in 16 children that were presenting a deficit in GH, and two girls presenting Turner syndrome, whereas etiological treatment was suggested in all remaining cases.

Perception of health and cognitive dysfunction in acromegaly patients

As therapeutic options improve for pituitary adenomas, we like to think we are capable of ‘curing’ patients with these diseases. However, in parallel to the availability of instruments to evaluate the patient’s subjective perception of outcome of the disease, evidence is accumulating on residual morbidity despite endocrine control of hormonal dysfunction. Over the last few years, cognitive dysfunction has been identified as one of the most common co-morbidities of pituitary tumours. Why this occurs is still unclear and could be related to neurovascular decline, ageing, suffering a chronic disease, apart from hormone imbalance, either chronic hormone excess or deficiency (mainly GH or cortisol). Evaluation of cognitive dysfunction in acromegaly has revealed contradictory findings. While Tiemensma et al. [1] reported normal cognitive function in patients with long-term cured acromegaly, several other studies showed deficits in attention, executive functions and memory [2– 4]. In their paper, Yedinak and Fleseriu [5] show cognitive dysfunction in 10 patients with active acromegaly, 17 with controlled acromegaly (defined as normal IGF-I and GH after an oral glucose tolerance test of \1 ng/mL) and 14 non-functioning pituitary microadenoma (NFPA), which were prospectively enrolled over a 3 year period in a tertiary referral centre in the US. They evaluated selfperception of cognitive deficits and quality of life/health by selecting and modifying relevant questions of questionnaires, originally designed for other diseases. Certain questions (16 of the original 37) from the Functional Assessment of Cancer Therapy Cognitive Scale (FACTCog) were selected, which reflected subsets of cognition, like ability to learn, concentration and distractibility, mental agility, memory and recall and verbal recall. Additionally, patients were asked to rate on a 1–5 scale how their health compared today with their desired health and to 12 months before. These questions are focused on patient perception, not objective cognitive measures, and this self-perception of cognitive function is influenced by the patient’s goals, expectations, standards, concerns, personality, as well as life events. For example, increased psychopathology (mainly anxiety and depression), maladaptive personality traits or less effective coping strategies, all previously described in patients with controlled acromegaly, may determine how these questions are answered [1, 6, 7]. The main findings of Yedinak and Fleseriu were that prevalence of cognitive dysfunction, in parallel to severity score for each of the 5 subsets of questions, was higher in NFPA (69 %) than in both groups of acromegalic patients, with no difference in prevalence between the latter (54 % in controlled vs. 57 % in active acromegaly). When the five specific cognitive areas were analysed, significant differences were observed for each subset; NFPA expressed greater cognitive dysfunction for mental agility, memory/ recall and verbal recall, but for ability to learn and concentration/distractibility, the group with active acromegaly expressed more problems and more severe dysfunction. This result is in line with previous studies that have reported attention and memory problems, and attenuation of electrophysiological brain activity in naive acromegaly I. Crespo S. M. Webb Endocrinology/Medicine Departments, Hospital Sant Pau, Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII, IIB-Sant Pau, Pare Claret 167, 08025 Barcelona, Spain

A case of ACTH-independent macronodular adrenal hyperplasia associated with multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant neoplasia syndrome characterized by the occurrence of tumors in the parathyroid glands, pancreas, and anterior pituitary. Approximately 30-40% of MEN1 patients also have adrenal lesions, such as hyperplasia, benign adenoma, and adrenocortical carcinoma. Most of the cases are hormonally silent. We describe the case of a 60-year-old man with bilateral macronodular adrenal lesions, in addition to parathyroid tumors, multiple insulinomas, and non-functioning pituitary microadenoma. Endocrinological tests revealed subclinical hypercortisolism; midnight cortisol level rose slightly (8.0 µg/dL), although basal plasma ACTH and cortisol levels were within the normal range (19.5 pg/mL and 12.0 µg/dL, respectively). One and 8 mg dexamethasone suppression tests showed cortisol levels of 2.3 and 9.8 µg/dL, respectively. (131)I-adosterol scintigraphy under dexamethasone suppression revealed bilateral adrenal uptake with right-sided predominance. The histological features of the removed right adrenal gland were consistent with ACTH-independent macronodular adrenal hyperplasia (AIMAH): immunoreactivity of 17α-hydroxylase was predominantly observed in the small compact cells, while that of 3β-hydroxysteroid dehydrogenase was exclusively expressed in the large clear cells. The glucose-dependent insulinotropic polypeptide (GIP) receptor was expressed at high levels in compact cells, suggesting that GIP is responsible for the development of AIMAH. Unilateral small adrenal lesions were detected in the patient's 2 children, who also presented with MEN1 symptoms. Genetic abnormalities in the MEN1, p27, and p18 genes were not found, however, the present case may provide a clue to the understanding of the etiology of MEN1 and AIMAH.

Asymptomatic Children with Multiple Endocrine Neoplasia Type 1 Mutations May Harbor Nonfunctioning Pancreatic Neuroendocrine Tumors

Multiple endocrine neoplasia type 1 (MEN1) is characterized by the occurrence of parathyroid, pituitary, and pancreatic tumors. MEN1, an autosomal dominant disorder, has a high degree of penetrance, such that more than 95% of patients develop clinical manifestations by the fifth decade, although this is lower at approximately 50% by age 20 yr. However, the lower penetrance in the younger group, which is based on detecting hormone-secreting tumors, may be an underestimate because patients may have nonfunctioning tumors and be asymptomatic. The aim of the study was to evaluate the occurrence of nonfunctioning pancreatic neuroendocrine tumors in asymptomatic children with MEN1. Twelve asymptomatic Northern European children, aged 6 to 16 yr, who were known to have MEN1 mutations were studied. Two asymptomatic children, who were aged 12 and 14 yr, had normal plasma fasting gastrointestinal hormones and were found to have nonfunctioning pancreatic neuroendocrine tumors that were more than 2 cm in size. Surgery and immunostaining revealed that the tumors did not have significant expression of gastrointestinal hormones but did contain chromogranin A and synaptophysin, features consistent with those of nonfunctioning pancreatic neuroendocrine tumors. The tumors had a loss of menin expression. The 14 yr old also had primary hyperparathyroidism and a microprolactinoma, and the 12 yr old had a nonfunctioning pituitary microadenoma. Three other children had primary hyperparathyroidism and a microprolactinoma. Nonfunctioning pancreatic neuroendocrine tumors may occur in asymptomatic children with MEN1 mutations, and screening for such enteropancreatic tumors in MEN1 children should be considered earlier than the age of 20 yr, as is currently recommended by the international guidelines.