Pituitary Magnetic Resonance Imaging Scan Research Articles

GH/IGF-1 axis in a large cohort of ß-thalassemia major adult patients: a cross-sectional study

PurposeGH deficit (GHD) could represent an endocrine issue in ß-Thalassemia Major (ßTM) patients. GH/IGF-1 axis has not been extensively explored in ßTM adults, so far. We aim to assess GHD and IGF-1 deficiency prevalence in ßTM adult population, focusing on the relationship with liver disease.MethodsCross-sectional multi-centre study conducted on 81 adult ßTM patients (44 males, mean age 41 ± 8 years) on transfusion and chelation therapy. GHD was investigated by GHRH + arginine test. IGF-1 levels, routine biochemical exams, Fibroscan, Hepatic Magnetic Resonance Imaging (MRI) and pituitary MRI were collected.ResultsEighteen patients were affected by GHD and 63 were not (nGHD) according to GHRH + arginine test, while basal GH levels did not differ. GHD was associated with a higher BMI and a worse lipid profile (p < 0.05). No significant differences were observed regarding liver function between the two groups. Pituitary MRI scan was normal except for one case of empty sella. The 94.4% and 93.6% of GHD and nGHD, respectively, presented lower IGF-1 levels than the reference range, and mean IGF-1 SDS was significantly lower in GHD patients.ConclusionGHD is frequent in adult ßTM patients and is associated with higher BMI and worse lipid profile. nGHD patients present lower IGF-1 levels as well. There was no relationship between IGF-1 levels and liver disease. Further, multicentric studies with larger cohorts and standardized diagnostic protocols are needed.

Visual Vignette

Case presentation: A 23-year-old male presented with a 6-month history of uncontrolled hypertension on 3 agents, with unintentional weight gain. He reported generalized fatigue, lower extremity edema, easy bruising, nocturia, insomnia, and irritability. The patient had no known pertinent personal or family medical history. Physical examination revealed truncal obesity, moon facies, dorsocervical fat pad, and violaceous striae. His laboratory results were as follows: 1-mg overnight dexamethasone suppression test (cortisol, 32.7 μg/dL); 24-hour urine free cortisol (UFC) of 1,643 μg; midnight plasma cortisol of 38.68 μg/dL, late-night salivary cortisol of 1.016 μg/dL (reference, 0.010 to 0.090 μg/dL); adrenocorticotropic hormone (ACTH) of 290 pg/mL (reference, 7.2 to 63.3 pg/mL); hyperglycemia; hypokalemia; and 8-mg dexamethasone suppression test (cortisol, 37.56 μg/dL). Pituitary magnetic resonance imaging scan was normal. A chest computed tomography (CT) scan showed a 3 × 6 cm mass within the left lower lobe, with left hilar lymphadenopathy (Fig. 1). Positron emission tomography (PET) and Octreoscan testing revealed a hypermetabolic left lower lobe mass with concurrent hilar lymphadenopathy and normal physiologic fluorodeoxyglucose activity within the liver (Fig. 2A), with somatostatin receptor avidity (Fig. 2A). Bronchoscopy failed to reveal any intraluminal masses. The patient was referred for resection of the left lower mass by lobectomy and lymph node dissection. The pathology result showed polygonal cells with abundant cytoplasm, round nuclei, and punctate necrosis (Fig. 3). What is the diagnosis?

Pituitary stalk interruption syndrome presenting as short stature: a case report

IntroductionPituitary stalk interruption syndrome is a rare congenital abnormality of the pituitary that is responsible for anterior pituitary deficiency. It is characterized by a classic triad of interrupted pituitary stalk, absent or ectopic posterior pituitary, and anterior pituitary hypoplasia or aplasia. Clinical presentation varies according to age. In adults it presents as short stature and anterior pituitary deficiency. Without early diagnosis and treatment, mortality and morbidity in these patients is high. Early diagnosis and treatment of this rare disease can prevent permanent short statue of the patient. We report the first case of pituitary stalk interruption syndrome from Pakistan.Case presentationA 17-year-old Pakistani young man presented with short stature and underdeveloped secondary sexual characters. His siblings and parents were healthy, with normal height. An examination showed his blood pressure was 90/60mmHg, and his height, weight, and body mass index were 142cm, 34.5kg, and 17.10kg/m2, respectively. He had no hair growth on his face, axilla, or pubis. His testes were between 1 and 2mL in size, with a 4cm-at-stretch micropenis. His lab investigations showed that his thyroid stimulating hormone (TSH) was 8.58uIU/mL (0.4 to 4.2), his free thyroid hormone level FT4 was 0.46ng/dL (0.89 to 1.76), his prolactin was 21.1ng/mL (3.0 to 14.7), and his baseline cortisol was 0.30ug/dL (4.3 to 22.4). His cortisol level after 60 minutes of cosyntropin injection was 3.5ug/dL (4.3 to 22.4), his insulin like growth factor IGF-1 was 31.56ng/mL (247.3 to 481.7), his testosterone level was under 2.5ng/dL (2 to 800), his follicle stimulating hormone FSH was 0.41uIU/mL (0.0 to 10.0), and his leutinizing hormone LH was under 0.1uIU/mL (1.2 to 7.8). His bone age was 10 years according to the Greulich and Pyle method, as shown by X-rays. The results from his pituitary magnetic resonance imaging scan were consistent with pituitary stalk interruption syndrome.ConclusionsWe describe a young man who presented with short stature and was found to have pituitary stalk interruption syndrome. Despite the fact that this is a rare disorder, it should always be kept in the differential diagnosis of a patient presenting with short stature. Patients with this disease have an excellent opportunity to reach normal height if they present before the joining of epiphyses.

The Relationship between Subnormal Peak-Stimulated Growth Hormone Levels and Auxological Characteristics in Obese Children.

Context: The hypothesis that obese children are overdiagnosed with growth hormone deficiency (GHD) has not been adequately investigated in the context of adiposity-related differences in auxology.Aim: To investigate the differences in auxological parameters between short, prepubertal, obese children, and normal-weight peers who underwent growth hormone stimulation testing (GHST).Hypothesis: Over-weight/obese children with GHD [peak growth hormone (GH) < 10 μg/L] will have higher values for growth velocity (GV) standard deviation score (SDS), bone age minus chronological age (BA − CA), and child height SDS minus mid-parental height (MPTH) SDS when compared to normal-weight GHD peers.Subjects and Methods: A retrospective review of anthropometric and provocative GHST data of 67 prepubertal, GH-naïve children of age 10.21 ± 2.56 years (male n = 45, age 10.8 ± 2.60 years; female n = 22, age 8.94 ± 2.10). Inclusion criteria: GHST using arginine and clonidine. Exclusion criteria: hypopituitarism, abnormal pituitary magnetic resonance imaging scan, syndromic obesity, or syndromic short stature. Data were expressed as mean ± SD.Results: The over-weight/obese children with peak GH of <10 μg/L had significantly lower value for natural log (ln) peak GH (1.45 ± 0.09 vs. 1.83 ± 0.35, p = 0.022), but similar values for GV SDS, insulin-like growth factor-I, insulin-like growth factor binding protein-3, bone age, BA − CA, MPTH, and child height SDS minus MPTH SDS compared to normal-weight peers with GHD. After adjusting for covariates, the over-weight/obese children (BMI ≥ 85th percentile) were >7 times more likely than normal-weight subjects (BMI < 85th percentile) to have a peak GH of <10 μg/L, and 23 times more likely to have a peak GH of <7 μg/L (OR = 23.3, p = 0.021). There was a significant inverse relationships between BMI SDS and the ln of peak GH (β = −0.40, r2 = 0.26, p = 0.001), but not for BMI SDS vs. GV SDS, ln peak GH vs. BA, or ln peak GH vs. GV SDS.Conclusion: Subnormal peak GH levels in obese prepubertal children are not associated with unique pre-GHST auxological characteristics.

Gigantism caused by growth hormone secreting pituitary adenoma.

Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.

Pituitary Magnetic Resonance Imaging for Sellar and Parasellar Masses: Ten-Year Experience in 2598 Patients

Sellar and parasellar masses present with overlapping clinical and radiological features ranging from asymptomatic incidental presentations and hormonal effects to compressive local mass effects. Pituitary masses are diagnosed with increased frequency with magnetic resonance imaging (MRI) advancements and availability, but indications and diagnostic outcomes of MRI screening for sellar lesions are not defined. Although pituitary adenomas are the most frequently encountered sellar mass lesions, other etiologies should be considered in the differential diagnosis of a sellar mass. The study was conducted at a tertiary pituitary center. This study was a retrospective review of 2598 subjects undergoing at least one pituitary MRI scan from 1999 to 2009. Prevalence and diagnosis of specific sellar and parasellar masses as screened by pituitary MRI. The most common indications for pituitary imaging, excluding known mass follow-up, were for evaluation of hyperprolactinemia or hypogonadism. A normal pituitary gland was reported in 47% of subjects undergoing pituitary MRI. The most common pituitary adenomas initially identified by MRI included prolactinoma (40%), nonfunctioning adenoma (37%), and GH adenoma (13%). Nonadenomatous sellar masses accounted for 18% of visible lesions, of which the most common were Rathke's cleft cyst (19%), craniopharyngioma (15%), and meningioma (15%). Metastases accounted for 5% of nonpituitary lesions and breast cancer was the most common primary source. Half of all pituitary MRI scans performed in a large patient population yielded no visible lesion. Nonadenomatous pituitary lesions should be considered in the diagnosis of sellar masses observed on MRI, and a high clinical suspicion is required to exclude the presence of a nonfunctioning pituitary adenoma.

Localization of an Adrenocorticotropin-Producing Pheochromocytoma Using 18F-Dihydroxyphenylalanine Positron Emission Tomography

A 67-yr-old man was evaluated for a fulminating ACTHdependent Cushing’s syndrome. The pituitary magnetic resonance imaging scan was normal. Computed tomography revealed a 2-cm left adrenal mass. Somatostatin receptor scintigraphy with In-pentreotide showed no abnormal uptake, but 6-fluoro-[F]L-dihydroxyphenylalanine positron emission tomography showed uptake in the left adrenal mass, highly suggestive of pheochromocytoma (Fig. 1). Plasma-free fractioned metanephrine and urine total fractioned metanephrine (free plus conjugated) were elevated (416.2 ng/liter and 979 g per 24 h, reference values 13.8 – 65.0 and 64.1–301.8). The patient wascured by adrenalectomy (Fig. 2). Histology of the tumor revealed a pheochromocytoma and hyperplasia of the surrounding adrenal cortex. Hydrocortisonesubstitutionwasnecessary for 5 months after surgery; afterward physiological cortisol secretion was restored. Despite extensive evaluation, including computed tomography, magnetic resonance imaging, and somatostatin receptor scintigraphy, in 12–19% of patients with ectopic ACTH

Corticotroph Tumor Progression after Adrenalectomy in Cushing’s Disease: A Reappraisal of Nelson’s Syndrome

Adrenalectomy is a radical treatment for hypercortisolism in Cushing's disease. However, it may lead to Nelson's syndrome, originally defined by the association of a pituitary macroadenoma and high plasma ACTH concentrations, a much feared complication. The objective of the study was to reconsider Nelson's syndrome by investigating corticotroph tumor progression based on pituitary magnetic resonance imaging scan and search for predictive factors. This was a retrospective cohort study. The complete medical records of Cushing's disease patients at Cochin Hospital were studied. Patients included 53 Cushing's disease patients treated by adrenalectomy between 1991 and 2002, without previous pituitary irradiation. Clinical data, pituitary magnetic resonance imaging data, and plasma ACTH concentrations for all patients and pituitary gland pathology data for 25 patients were recorded. Corticotroph tumor progression-free survival was studied by Kaplan-Meier, and the influence of recorded parameters was studied by Cox regression. There was no intervention. Corticotroph tumor progression ultimately occurred in half the patients, generally within 3 yr after adrenalectomy. A shorter duration of Cushing's disease (adjusted hazard ratio: 0.884/yr), and a high plasma ACTH concentration in the year after adrenalectomy [adjusted hazard ratio per 100 pg/ml (22 pmol/liter): 1.069] were predictive of corticotroph tumor progression. In one case, corticotroph tumor progression was complicated by transitory oculomotor nerve palsy. During follow-up, corticotroph tumor progression was associated with the increase of corresponding ACTH concentrations (odds ratio per 100 pg/ml of ACTH variation: 1.055). After adrenalectomy in Cushing's disease, one should no longer wait for the occurrence of Nelson's syndrome: modern imaging allows early detection and management of corticotroph tumor progression.

Sheehan's Syndrome Presenting with Early Postpartum Congestive Heart Failure

We report the case of a young woman with Sheehan's syndrome who presented with ventricular arrhythmia and congestive heart failure. The patient was admitted because of postpartum hemorrhage and hypovolemic shock; a massive blood transfusion was required to restore blood volume. After initial stabilization, the patient developed acute respiratory distress and congestive heart failure accompanied by hemodynamic instability 2 weeks after delivery. Episodes of ventricular tachycardia of the torsade de pointes type and a prolonged QT interval were noted on baseline electrocardiogram. A low cortisol level was found incidentally, which led to the suspicion of hypopituitarism. The diagnosis was later supported by laboratory findings of multiple pituitary hormone deficiencies. After administration of corticosteroids and thyroxine, the patient's clinical condition improved dramatically. A pituitary magnetic resonance imaging scan 32 days after delivery revealed a diminished and flattened pituitary gland with prominent intrasellar cerebrospinal fluid loculation, which was compatible with the clinical diagnosis of empty sella with panhypopituitarism. The syndrome of acute anterior pituitary necrosis secondary to postpartum hemorrhage and shock was first described by Sheehan in 1939. Although the occurrence of Sheehan's syndrome is now rare, it should still be considered in any woman with a history of peripartum hemorrhage who develops manifestations of pituitary hormone deficiency. Appropriate hormone replacement therapy is essential and always results in dramatic clinical improvement.

Octreotide as Primary Therapy for Acromegaly

The effects of octreotide (up to 5 yr) as primary treatment in 26 patients with acromegaly were compared with those in 81 patients with acromegaly who received octreotide as secondary or adjunctive therapy after previous surgery and/or pituitary radiation. These patients were part of a multicenter study that took place between 1989-1995. The study was divided into 3 phases beginning with a 1-month placebo-controlled treatment period followed by a 1-month washout period. In the second phase, patients were randomized to treatment with either 100 or 250 micrograms octreotide, sc, every 8 h for 6 months. Octreotide was then discontinued for 1 month and reinitiated at the lower dose for a total mean treatment duration of 39 months. The dose was titrated by each investigator to improve each patient's individual response, which included improvement in symptoms and signs of acromegaly as well as reduction of GH and insulin-like growth factor I (IGF-I) into the normal range. In the second phase of the study, in which patients were randomized to either 100 or 250 micrograms octreotide, three times daily, mean integrated GH and IGF-I concentrations after 3 and 6 months were equivalent in the primary and secondary treatment groups. During long term open label treatment, mean GH fell from 32.7 +/- 5.2 to 6.0 +/- 1.7 micrograms/L 2 h after octreotide injection in the primary therapy group and remained suppressed for a mean period of 24 months (range, 3-60 months). The mean final daily dose was 777 micrograms. In the patients receiving secondary treatment, mean GH fell from 30.2 +/- 7.6 to 5.6 +/- 1.1 micrograms/L after 3 months and remained suppressed for the remainder of the study (average dose, 635 micrograms daily). Mean IGF-I concentrations fell from 5.2 +/- 0.5 x 10(3) U/L (primary treatment group) and 4.7 +/- 0.4 x 10(3) U/L (secondary treatment group) to a mean of 2.2 +/- 0.3 x 10(3) U/L in both groups after 3 months of open label treatment and remained suppressed. IGF-I was reduced into the normal range during at least half of the study visits in 68% of the primary treatment group and in 62% of the secondary treatment group. Patients whose GH levels fell to at least 2 SD below the baseline mean GH were considered responders. There was no significant difference in the percentage of responders in the primary and secondary treatment groups (70% vs. 61%), nor was there a statistical difference in the mean GH concentrations between the groups. Symptoms of headache, increased perspiration, fatigue, and joint pain were reported at baseline by 46%, 73%, 69%, and 85%, respectively, of patients in the primary therapy group and improved during 3 yr of octreotide treatment in 50-100%. Similarly, these acromegaly-related symptoms were reported by 62%, 58%, 78%, and 60% of patients in the secondary therapy group, and improvement was noted in 62-88%. Pituitary magnetic resonance imaging scans were available in 13 of 26 patients in the primary treatment group before and after 6 months of octreotide treatment. Tumor shrinkage was observed in 6 of 13 patients, with reduction in tumor volume greater than 25% in only 3. Of 6 patients with documented tumor shrinkage, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 5 patients. The degree of tumor shrinkage did not correlate with the percent reduction in IGF-I or GH. In summary, octreotide was equally effective in 26 previously untreated acromegalic patients (primary treatment group) and 81 patients previously treated with either surgery or pituitary radiation (secondary treatment group). These observations call into question the current practice of surgical resection of all newly diagnosed GH-secreting pituitary adenomas regardless of the likelihood of cure. (AB

An audit of the diagnostic usefulness of PRL and TSH responses to domperidone and high resolution magnetic resonance imaging of the pituitary in the evaluation of hyperprolactinaemia.

The usefulness of dynamic tests of PRL release in determining underlying pathology in hyperprolactinaemic patients is not well recognized by endocrinologists, only 15% of whom routinely perform such tests. High resolution pituitary magnetic resonance imaging (MRI) has become more widely available during the past 5 years and is now generally regarded as the pituitary imaging method of choice. Since few prolactinoma patients are now submitted to surgery, it is important to ascertain the usefulness of these techniques in suggesting a pathological diagnosis. A 3 year retrospective audit of the information derived from measurement of PRL and TSH responses to the dopamine antagonist domperidone and from high resolution pituitary MRI in patients being investigated for hyperprolactinemia in regional endocrine unit. Eighty-four patients (10 male, 74 female) whose investigation of hyperprolactinaemia included a domperidone test and high resolution pituitary MRI. Patients who had domperidone tests performed after pituitary surgery or who did not have pituitary MRI were excluded from the analysis. PRL and TSH were measured basally and at 30 and 60 minutes following domperidone (10 mg i.v.) and gadolinium-enhanced pituitary MRI was performed in all patients. 20 patients had a normal PRL response to domperidone (defined as PRL30/PRL0 > 3) and this group included five patients in whom hyperprolactinaemia was not sustained. Pituitary MRI showed evidence of a microadenoma in only two patients, imaging being unequivocally normal in the majority. Sixty-four patients had an abnormal PRL response to domperidone and 18 of these had a macrolesion (nine prolactinomas, nine other tumours). Pituitary MRI was performed in the remaining 46 patients with abnormal PRL response to domperidone and suggested microadenoma in 29 (63%), identified other structural abnormalities in six cases but was entirely normal in 11 cases. Neither the basal PRL level nor the TSH response could refine the diagnosis further because of overlap between the various subgroups. The majority of patients with a normal dynamic response of PRL to domperidone had a normal or near normal pituitary MRI scan. In the two cases where an abnormality was detected it could have been an incidental microadenoma or cyst, thus suggesting that pituitary scanning could normally be omitted in patients whose PRL response to domperidone is normal (24% of our total). The group of patients with an abnormal dynamic response of PRL to domperidone was not generally amenable to further diagnostic refinement by considering the degree of hyperprolactinaemia or the TSH response to domperidone because of overlap of these parameters between the diagnostic subgroups. Therefore any degree of hyperprolactinaemia associated with a blunted PRL response to domperidone warrants pituitary imaging.

Chronic somatostatin analog administration in patients with alpha-subunit-secreting pituitary tumors.

Glycoprotein hormone-producing (GPH) pituitary adenomas represent approximately 25% of all pituitary tumors. Elevated serum levels of intact GPHs or their free alpha- and beta-subunits have been demonstrated in patients with such tumors, and isolated hypersecretion of alpha-subunit has been reported to occur in 7% of patients. Somatostatin has been shown to decrease GPH subunit levels in cultured adenoma cells in vitro, and somatostatin receptors have been identified on the cell membranes of these tumors. We, therefore, investigated the effect of chronic somatostatin analog administration on hormone production and tumor size in six patients with GPH-producing macroadenomas and elevated serum alpha-subunit levels. Patients initially received native somatostatin as an iv 250-micrograms bolus at 0800 h, followed by a constant infusion of 2 mg over 4 h, and serum alpha-subunit concentrations were measured at 30-min intervals after baseline sampling for a total of 9 h. Patients then received a somatostatin analog, octreotide (100 micrograms, twice daily, sc) for 8 weeks. Serum alpha-subunit levels were determined weekly at 30-min intervals before and for 4 h after the 0800 h octreotide dose. Pituitary magnetic resonance imaging scans and visual field testing were assessed before and after the study. During the 4-h somatostatin infusion, four patients had a significant decrease in alpha-subunit levels (P < 0.05). During the 8-week chronic octreotide administration period, two patients had significant decreases in alpha-subunit levels of 34.6% and 26.7% (P = 0.03 and 0.01, respectively). One of these two patients had a small reduction in tumor size. Two patients whose serum alpha-subunit level did not significantly change while receiving octreotide had a reduction in tumor size or definite improvement in visual field abnormalities. Three patients received a maximum octreotide dose of 250 micrograms, three times daily. In one patient, there was a significant decrease in alpha-subunit levels by 45% (P = 0.0001) in association with a marked improvement in visual field abnormalities. In another such patient, continued administration of octreotide to a maximum dose of 250 micrograms, three times daily, was associated with a marked reduction in tumor size. Of the four patients who demonstrated significant decreases in alpha-subunit concentrations during the initial somatostatin infusion, three patients had a significant reduction in alpha-subunit levels while receiving octreotide. One patient who did not have a decrease in alpha-subunit levels during the somatostatin infusion demonstrated a small decrease in tumor size during higher dose octreotide treatment.(ABSTRACT TRUNCATED AT 400 WORDS)