Pituitary Gigantism - Experience of a Single Center from Western India

Objective: Limited data are available on pituitary gigantism, as it is a rare disorder. This study was carried out to assess the clinical, hormonal, and radiologic profiles and management outcomes of patients with pituitary gigantism.Methods: We conduced a retrospective analysis of 14 patients with pituitary gigantism who presented to a single tertiary care institute from 1990 to 2014.Results: Thirteen patients were male, and 1 was female. The mean age at diagnosis was 21.9 ± 6.1 years, with a mean lag period of 6.5 ± 5.6 years. The mean height SD score at the time of diagnosis was 3.2 ± 0.6. Symptoms of tumor mass effect were the chief presenting complaint in the majority (50%) of patients, while 2 patients were asymptomatic. Six patients had hyperprolactinemia. At presentation, the nadir PGGH (postglucose GH) and insulin-like growth factor (IGF 1)-ULN (× upper limit of normal) were 63.2 ± 94.9 ng/mL and 1.98 ± 0.5, respectively. All (except 1 with mild pituitary hyperplasia) had pituitary macroadenoma. Six patients had invasive pituitary adenoma. Transsphenoidal surgery (TSS) was the primary modality of treatment in 13/14 patients, and it achieved remission in 4/13 (30.76%) patients without recurrence over a median follow-up of 7 years. Post-TSS radiotherapy (RT) achieved remission in 3/5 (60%) patients over a median follow-up of 3.5 years. None of the patients received medical management at any point of time.Conclusion: Gigantism is more common in males, and remission can be achieved in the majority of the patients with the help of multimodality treatment (TSS and RT).Abbreviations: GH = growth hormone GHRH = growth hormone-releasing hormone IGF 1 = insulin-like growth factor 1 MEN 1 = multiple endocrine neoplasia type 1 PGGH = postglucose growth hormone RT = radiotherapy TSS = transsphenoidal surgery     

Morning Serum Cortisol Level After Transsphenoidal Surgery for Pituitary Adenoma Predicts Hypothalamic-Pituitary-Adrenal Function Despite Intraoperative Dexamethasone Use

Objective: Perioperative glucocorticoid (GC) is rarely needed in patients undergoing transsphenoidal surgery (TSS). We instituted a steroid-sparing protocol in the settings of intraoperative dexamethasone use. We evaluated the safety of using a cut off cortisol level of 14 μg/dL on postoperative day (POD)-1 and -6 after dexamethasone use during the surgery. We also analyzed the efficacy of serial morning cortisol levels for weaning GC replacement.Methods: The charts of 48 adult patients who received dexamethasone 4 mg intraoperatively were reviewed. Morning cortisol levels were measured on POD-1. Patients with cortisol ≥14 μg/dL were discharged without CG replacement. Morning cortisol level was checked routinely on POD-6, and GC replacement was initiated when the level was <14 μg/dL. Serial cortisol levels were measured in patients requiring GC after the first postoperative week.Results: Overall, 67% patients had POD-1 cortisol ≥14 μg/dL and did not require GC on discharge. After POD-6, 83% of patients were not on GC replacement. A cosyntropin stimulation testing (CST) was only performed in 3 patients. There were no hospital admissions for adrenal crisis during the postoperative period.Conclusion: A steroid-sparing protocol with POD-1 and -6 morning cortisol levels can be safely and effectively used in the settings of intraoperative dexamethasone administration. It leads to avoidance of GC in more than two-thirds of patients on discharge and more than 80% of patients after the first postoperative week. We found that dynamic adrenal testing could be omitted in the majority of patients by using serial morning cortisol levels to assess the hypothalamic-pituitary-adrenal (HPA) axis.Abbreviations: ACTH = adrenocorticotropic hormone AI = adrenal insufficiency CST = cosyntropin stimulation test ECLIA = electrochemiluminescence immunoassay GC = glucocorticoid HPA = hypothalamic-pituitary-adrenal ITT = insulin tolerance test POD = postoperative day TSS = transsphenoidal surgery     

American Association of Clinical Endocrinologists And American College of Endocrinology Disease State Clinical Review: Postoperative Management Following Pituitary Surgery

Pituitary lesions are common in the general population. Patients can present with a wide range of signs and symptoms that can be related to tumor mass effects or pituitary hormonal alterations. Evaluation involves assessing patients for the extent of tumor burden and pituitary hyper- or hypofunction and includes clinical exams, hormonal testing, and brain imaging. Preoperative diagnosis and treatment planning generally require a multidisciplinary team approach with expertise from endocrinologists, neurosurgeons, neuro-ophthalmologists, and neuroradiologists. This review will outline considerations for the evaluation and management of patients with pituitary masses at each stage in their treatment including the pre-, peri- and postoperative phases.Abbreviations: ADH = antidiuretic hormone CSF = cerebrospinal fluid DDAVP = desmopressin DI = diabetes insipidus GH = growth hormone MRI = magnetic resonance imaging SIADH = syndrome of inappropriate ADH release TSS = transsphenoidal surgery     

Utility of a Glucocorticoid Sparing Strategy in the Management of Patients Following Transsphenoidal Surgery

Objective: Following transsphenoidal surgery (TSS), it is important to assess for and manage adrenal insufficiency (AI). The goal of this study is to assess the efficacy and safety of a glucocorticoid (GC) sparing protocol to limit GC exposure in patients undergoing TSS.Methods: Adult patients undergoing TSS (excluding Cushing disease) with adequate adrenal function prior to surgery underwent TSS without perioperative GC coverage. Following TSS, daily morning fasting serum cortisol levels were tested. GCs were administered at stress doses for serum cortisol <5 mcg/dL, between 5 and 12 mcg/dL in the presence of clinically significant symptoms of AI, or >12 mcg/dL with severe headache, nausea or vomiting, fatigue, anorexia, or hyponatremia. The primary endpoint was the use of GCs in the immediate postoperative period.Results: Of 178 subjects, GCs were administered to 80 (45%) patients for the following indications: 31.3% for serum cortisol <5 mcg/dL; 36.3% for cortisol between 5 and 12 mcg/dL accompanied by symptoms or signs of AI; 8.8% for moderate to severe postoperative hyponatremia; and 7.5% for severe headache, nausea and vomiting, fatigue, or anorexia with cortisol >12 mcg/dL. Logistic regression analysis showed that longer length of hospital stay (odds ratio [OR] 1.22, confidence interval [CI] 1.02–1.45) and the presence of new postoperative anterior pituitary hormone deficiency (OR 3.3, CI 1.26–8.67) were associated with postoperative GC use. By 12 weeks, only 14% of subjects remained on GCs. There were no adverse events related to withholding GCs.Conclusion: Our protocol for managing GC replacement is both safe and effective for limiting GC exposure in patients undergoing TSS.Abbreviations:AI = adrenal insufficiencyCI = confidence intervalFSH = follicle-stimulating hormoneGC = glucocorticoidGH = growth hormoneIGF-1 = insulin-like growth factor-1IV = intravenousLH = luteinizing hormoneLOS = length of hospital stayOR = odds ratioTSS = transsphenoidal surgery     

Pituitary Apoplexy Secondary to Thrombocytopenia Due to Dengue Hemorrhagic Fever: A Case Report and Review of the Literature

Objective:To present a case of pituitary apoplexy secondary to thrombocytopenia associated with dengue hemorrhagic fever (DHF).Methods:In this case study, we review the presentation, evaluation, diagnosis, and management of a case of pituitary apoplexy in the setting of DHF. We also searched the literature for cases of pituitary apoplexy associated with thrombocytopenia and review their clinical presentation, management, and outcome.Results:A 53-year-old man presented with fever, lethargy, and worsening headache. Routine investigations revealed thrombocytopenia secondary to dengue fever. He developed symptoms of a cavernous sinus lesion the next day. Urgent magnetic resonance imaging revealed pituitary apoplexy in a pituitary macroadenoma. A transsphenoidal surgery was done and histology was consistent with apoplexy in a prolactin/follicle-stimulating hormone macroadenoma. Subsequently, the patient developed permanent deficits of anterior pituitary hormones. We review 8 other cases of pituitary apoplexy associated with thrombocyto-penia reported in the literature.Conclusion:Thrombocytopenia due to various causes may be a predisposing factor for pituitary apoplexy in a patient with underlying pituitary disease. In view of the tendency for bleeding associated with thrombocytopenia, the risks of surgical intervention have to be carefully weighed against the potential benefits. Indications for surgery would include progressive alteration of consciousness, visual disturbances, and opthalmoplegia despite conservative management. Patients with underlying pituitary macroadenomas with optic chiasm compression have a worse prognosis, and the chances of recovery, even with early surgery, are limited.     

Clinical Practice Patterns for Postoperative Water Balance After Pituitary Surgery

Objective: Abnormalities of water and sodium balance, including diabetes insipidus and the syndrome of inappropriate antidiuretic hormone (SIADH), are common complications of transsphenoidal surgery. Postoperative practice patterns vary among clinicians, and no consensus guidelines exist to direct their monitoring and management. We aimed to identify and compare practice patterns regarding the evaluation and management to these postoperative complications.Methods: A questionnaire was utilized to capture demographic data and practice habits in the postoperative setting. Respondents were members of the Pituitary Society, an international organization comprised of clinicians and researchers dedicated to the study of pituitary disease.Results: Eighty-six respondents completed at least part of the survey. The geographic distribution of respondents was roughly even between American and non-American practitioners. The majority of respondents practiced at academic institutions (67.4%), worked in multidisciplinary teams (88.4%), and possessed significantly greater than 10 years of clinical experience (71%). Compared to non-American practitioners, American practitioners described a shorter length of stay postoperatively (P<.001) and prescribed more restrictive volume recommendations for postoperative SIADH (P = .0035). Early career clinicians (less than 10 years in practice) checked first postoperative sodium level earlier than later career clinicians (P = .010).Conclusion: Water and sodium dysregulation are common following transsphenoidal surgery, but their management is not well-standardized in clinical practice. We created a questionnaire to define and compare practice patterns. Most respondents practice in academic settings in multidisciplinary teams. The length of clinical experience did not significantly impact practice habits. Practice location influenced length of stay postoperatively and fluid restriction in SIADH.Abbreviations: AVP = arginine vasopressin; DI = diabetes insipidus; LOS = length of stay; SIADH = syndrome of inappropriate antidiuretic hormone     

Endocrine Dysfunction and Follow-Up Outcomes in Patients With Pituitary Abscess

Objective: Endocrine dysfunction caused by pituitary abscess (PA) and its outcomes have not been fully studied. This study aims to investigate endocrine dysfunction and outcomes in patients with PA.Methods: Eight patients (3 males and 5 females) with PA were identified for collecting clinical, hormone, and therapeutic data before and after long-term follow-up lasting 12 to 116 months (median, 25 months) since the first hospitalization, which was regarded as the baseline time. All patients' pituitary and respective target gland functions were evaluated. Six patients had acute onset (less than 1 month), and the other 2 patients had chronic onset (more than 6 months). Five patients underwent surgical therapy, and the other 3 patients underwent conservative therapy. The factors associated with endocrine outcome were analyzed as well.Results: At baseline, the release of 91.7% (22 of 24 total) of pituitary tropic hormones was impaired, but 59.1% (13 of 22) had normalized by the last follow-up. Male gender, acute onset mode, and normal baseline prolactin level seemed to be the factors that favored tropic hormone normalization, whereas surgical operation was not. Two patients received provocative test suggesting decreased reserves of both somatotrophin and prolactin or only somatotrophin. Only 1 patient suffered from permanent diabetes insipidus.Conclusion: The production of almost all pituitary tropic hormones was impaired with PA in the present study, but production of nearly 60% percent of the hormones normalized during follow-up of >1 year. A chronic abscess state may be the most important factor associated with permanent hormone deficiency.Abbreviations: ACTH = adrenocorticotropic hormone GnH = gonadotrophin MRI = magnetic resonance imaging PA = pituitary abscess TSH = thyroid-stimulating hormone     

Incidence of Pituitary Apoplexy and Its Risk Factors in Chinese People: A Database Study of Patients with Pituitary Adenoma

Background

There are few studies of the incidence and clinical characteristics of pituitary apoplexy (PA) in pituitary adenoma patients, and the findings have been inconsistent.

Objective

The aim of the study was to retrospectively assess the incidence, clinical presentation, surgical management and postoperative complications of PA in pituitary adenoma patients.

Methods

A database was specifically designed to collect clinical, therapeutic, prognostic and histological information about pituitary adenoma patients. Using multivariate logistic regression, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to identify associated factors.

Results

A total of 2021 pituitary adenoma patients were recruited. 97 (4.8%) patients had PA. The incidence of PA was 10.11% in patients with pituitary macroadenoma, and 0.36% in patients with microadenoma. Variables for the logistic regression model independently associated with PA were sex (male vs. female, OR = 2.54, 95% CI: 1.59~4.07), tumor type (negative staining vs. positive staining, OR = 2.04, 95% CI: 1.29~3.23), and tumor size (macroadenoma vs. microadenoma, OR = 26.46, 95% CI = 9.66~72.46). Headache, visual deterioration, and vomiting were the most common symptoms in patients with pituitary adenoma. Patients with and without PA had similar frequency of visual deterioration, head trauma, acromegalic appearance, galactorrhoea, cold intolerance and Cushingoid appearance, but headache, vomiting, ptosis, diplopia, fever and blindness were significantly more common in patients with PA. Pearson Chi-Square tests revealed a significant difference in surgical approach between patients with and without PA (95.88% vs. 85.57%, P = 0.01).

Conclusion

Our findings suggest that PA is not a rare event. Male sex, non-functioning tumor, and macroadenoma are associated with an increased risk of PA. Compared with pituitary adenoma patients without PA, patients with PA have more severe symptoms.     

Association of Dengue Hemorrhagic Fever With Multiple Risk Factors for Pituitary Apoplexy

ObjectiveTo describe pituitary apoplexy that developed during the course of dengue hemorrhagic fever.MethodsWe describe the clinical findings, laboratory test results, imaging findings, and clinical course of the study patients.ResultsPatient 1 was a 40-year-old man who developed clinical signs and symptoms of dengue, which was confirmed by serologic testing. He presented with thrombocytopenia and developed severe headache and vomiting. During hospitalization, acromegaly was suspected because of the characteristic disease phenotype. Magnetic resonance imaging confirmed the diagnosis of pituitary apoplexy. Subsequently, the biochemical diagnosis of acromegaly was confirmed, and the patient underwent transsphenoidal surgery. Histopathologic examination showed signs of recent bleeding. Patient 2 was a 38-year-old man with a macroprolactinoma, who had been treated with cabergoline for 10 weeks and had shown improvement on laboratory testing and imaging. The patient then presented with clinical symptoms of dengue (confirmed serologically) and thrombocytopenia. He developed bilateral hemianopsia, and magnetic resonance imaging showed enlargement of the pituitary adenoma with signs of intratumoral bleeding. The patient underwent transsphenoidal surgery, and histopathologic examination documented a pituitary adenoma diffusely infiltrated by blood cells.ConclusionsWe describe dengue as a probable novel condition for pituitary apoplexy because it may be associated with multiple risk factors for pituitary infarction or bleeding. Physicians should suspect pituitary apoplexy in patients with dengue hemorrhagic fever who develop a rapid onset of severe headache and vision defects, even in those without known pituitary adenomas. (Endocr Pract. 2012;18:e97-e101)     

Gonadotropin-Releasing Hormone Agonist-Induced Pituitary Apoplexy in Treatment of Prostate Cancer: Case Report and Review of Literature

ObjectiveTo describe a case and review the literature on the rare complication of pituitary apoplexy after administration of a gonadotropin-releasing hormone agonist (GnRHa) for treatment of patients with prostate cancer.MethodsWe present a detailed case report of a patient with immediate signs of pituitary apoplexy after receiving a GnRHa and review the 6 previously reported cases in the literature.ResultsA 60-year-old man presented to a local hospital with severe headache, nausea, vomiting, and diplopia. Prostate cancer had recently been diagnosed, and he had received his first dose of a GnRHa 4 hours before this presentation. On physical examination, he was confused and had ptosis of the left eye. A head computed tomographic scan without contrast enhancement showed soft tissue filling the sella, without intracranial hemorrhage or mass effect. He was discharged with the diagnosis of viral meningitis. Three weeks later, he presented again with severe headache and diplopia. He had confusion, lethargy, disorientation, a blood pressure of 88/64 mm Hg, and left cranial nerve III, IV, and VI paralysis. Magnetic resonance imaging of the brain revealed an enhancing pituitary mass with hemorrhage extending to the optic chiasm, consistent with pituitary apoplexy. Laboratory results were consistent with panhypopituitarism. Surgical excision revealed a necrotic pituitary macroadenoma with hemorrhage. Tumor immunohistochemical staining was positive only for luteinizing hormone.ConclusionWe describe a rare adverse effect of GnRHa therapy, which unmasked a gonadotropin-secreting pituitary macroadenoma. This case adds to the 6 previously reported cases of GnRHa administration inducing pituitary apoplexy in men with prostate cancer. (Endocr Pract. 2007;13:642-646)     

Unexpected Clinical Course During Treatment of a TSH-Secreting Pituitary Adenoma

ObjectiveTo report the rare occurrence of a patient with thyrotropinoma that transitioned into a secretory thyro-somatotroph adenoma during medical treatment with somatostatin analogue.MethodsWe report the case of a patient with a thyrotroph pituitary adenoma who developed de novo evidence of growth hormone cosecretion following one year of successful medical treatment.ResultsA 78-year-old woman was diagnosed with a thyroid stimulating hormone (TSH) secreting pituitary macroadenoma (TSHoma) based on classical clinical and biochemical features. There was no clinical or biochemical evidence of growth hormone (GH) cosecretion. She declined surgical resection and was treated with primary medical therapy, octreotide long acting repeatable (LAR), to which she had an antitumor and antisecretory response; however, following 12 months of successful medical treatment she developed de novo hypersecretion of growth hormone despite involution of the tumor mass. TSH-secreting pituitary adenomas may rarely become plurihormonal during apparently successful medical treatment. This may represent an unusual form of secondary resistance to somatostatin analogue or the rarer phenomenon of tumor transformation into a secretory thyro-somatotroph adenoma.ConclusionThe unexpected clinical course of this case highlights the need for careful long-term surveillance in patients with TSH secreting pituitary adenomas. (Endocr. Pract. 2013;19:e88-e91)     

Pituitary Apoplexy in Nonfunctioning Pituitary Macroadenomas: A Case-Control Study

ObjectivePituitary apoplexy (PA) is an endocrinologie emergency characterized by headache, visual abnormalities, and hemodynamic instability in the context of hemorragic infarction of a pituitary adenoma. Our goal was to estimate the incidence, precipitating factors, clinical characteristics, and outcome of PA in a cohort of patients with nonfunctioning pituitary macroadenomas (NFPMAs).MethodsA retrospective, case-control study of 46 patients with PA and 47 controls matched for age, gender, and tumor invasiveness. Clinical, hormonal, and tumoral charactersitics, as well as the presence of potential precipitating factors and long-term outcome were evaluated using both bivariate and multivariate analysis.ResultsThe prevalence of PA was 8%. Cases and controls were similar in regards to the prevalence of diabetes, hypertension, use of antiplatelet agents, and the presence of headaches and visual field defects. Oculomotor paralysis was present in 18% of cases and in none of the controls (P = .001). Prior use of dopamine agonists was significantly more frequent among cases than in controls on both bivariate and multivariate analysis. Pituitary hormone deficiencies were more common among cases than in controls on bivariate but not on multivariate analysis. Early and late surgical treatment was carried out in 11 and 25 patients, respectively; 11 patients were managed conservatively. Visual and endocrine outcomes were similar among the 3 groups.ConclusionPA represents a life-threatening medical emergency. Prior use of dopamine agonists and the presence of oculomotor abnormalities clearly distinguished patients with NFPMA who developed PA from those who did not. (Endocr Pract 2014;20:1274-1280)     

Random Postoperative Day-3 Cortisol Concentration as a Predictor of Hypothalamic-Pituitary-Adrenal Axis Integrity after Transsphenoidal Surgery

ObjectiveTo determine whether a random postoperative day-3 cortisol value of 10 μg/dL or greater is predictive of adrenal sufficiency 3 to 10 weeks after transsphenoidal surgery (TSS) and during long-term clinical follow-up.MethodsWe retrospectively reviewed the case records of patients who underwent TSS at our institution between 1991 and 2008. Inclusion criteria were as follows: random cortisol measured on the morning of postoperative day 3, adrenal dynamic testing performed 3 to 10 weeks after TSS, and clinical assessment of the hypothalamicpituitary-adrenal (HPA) axis at least 6 months after TSS.ResultsA total of 466 patients underwent TSS at our institution during the study period. Eighty-three patients met study inclusion criteria. Sensitivity of a random postoperative day-3 serum cortisol value of 10 μg/dL or greater for the prediction of adrenal sufficiency at a median follow-up of 42 days was 64.81% (95% confidence interval, 50.6%-77.32%), with an odds ratio of 3.1 (95% confidence interval, 1.08-8.58). Specificity was 62.1% (95% confidence interval, 42.3%-79.3%). At a median follow-up of 500 days, only 2 patients with a postoperative day-3 cortisol value of 10 μg/dL or greater required hydrocortisone replacement, both of whom had multiple anterior pituitary hormone deficiencies and evidence of pituitary dysfunction during the perioperative period.ConclusionsIn the appropriate clinical context, a postoperative day-3 cortisol value of 10 μg/dL or greater accurately predicts the integrity of the HPA axis. The final decision regarding corticosteroid replacement should be personalized, considering the postoperative day-3 cortisol level, the clinical context in which the measurement was obtained, and any evidence of concomitant pituitary dysfunction in the perioperative period. (Endocr Pract. 2011;17:717-726)     

The Role of Temozolomide in the Treatment of a Patient With a Pure Silent Pituitary Somatotroph Carcinoma

ObjectiveTo describe a case of a pure silent somatotroph pituitary carcinoma.MethodsWe describe a 54-year-old female with a clinically nonfunctioning pituitary macroadenoma diagnosed 15 years earlier.ResultsThe patient underwent transsphenoidal surgery and no visible tumor remnant was observed for 6 years. A magnetic resonance imaging (MRI) detected the recurrence of a 1.2 × 1.5 cm macroadenoma. The patient was submitted to conventional radiotherapy (4500 cGy), and the tumor volume remained stable for 7 years. Then, an MRI revealed a slight increase in tumor size, and 2 years later, a subsequent MRI detected a very large, invasive pituitary mass. The patient was resubmitted to transsphenoidal surgery, and the histopathological examination showed diffuse positivity for growth hormone (GH). The nadir GH level during an oral glucose tolerance test was 0.06 ng/mL, and the pre- and postoperative insulin like growth factor type I (IGF-I) levels were within the normal range. Abdominal, chest, brain, and spine MRI showed multiple small and hypervascular liver and bone lesions suggestive of metastases. Liver biopsy confirmed metastasis of GH-producing pituitary carcinoma. The patient has been treated with temozolomide and zoledronic acid for 7 months and with octreotide long-acting release (LAR) for 4 months. The primary tumor and metastases are stable.ConclusionDespite being an extremely rare event, pituitary carcinoma may develop several years after the successful treatment of even a silent GH-producing pituitary adenoma, which suggests that close long-term follow-up is necessary. (Endocr. Pract. 2013;19:e145-e149)     

High-Precision Conformal Fractionated Radiotherapy Is Effective In Achieving Remission In Patients With Acromegaly After Failed Transsphenoidal Surgery

Objective: Variable efficacy of pituitary radiotherapy in acromegaly is reported. Here we sought to assess the efficacy of high-precision conformal fractionated radiotherapy (CRT) in patients with acromegaly after failed TSS.Methods: A retrospective analysis was conducted a in tertiary care referral center between 1999 to 2013 on 36 acromegaly patients (M: 16, F: 20; median age: 36.0 years) with macroadenoma and mean growth hormone (GH) and insulin-like growth factor-1 (IGF1) upper limits of normal (ULN) of 15.9 ± 14.3 ng/mL and 1.74 ± 0.43, respectively. The cohort was divided into 2 groups: 30 patients (M: 13, F: 17) who were medical treatment naïve, and 6 patients (M: 3, F: 3) who received medical treatment after CRT.Results: Normalization of GH (fasting GH <1 ng/mL), normalization of IGF1 (ULN <1), and remission (normalization of GH and IGF1) were achieved in 20 (55%), 23 (63%) and 20 (55%) patients, respectively. The mean time required to achieve remission was 63 ± 33.4 months. Follow-up duration was the only predictor of achieving remission. GH level declined exponentially by 65% and 89% at 2 and 5 years, respectively. New onset hypopituitarism was noted in 33% of patients. Tumor control was achieved in 100% of patients. In groups 1 and 2, 18 (60%) and 2 (33.3%) achieved remission post-CRT, and the mean times required to achieve remission were 58.6 ± 30.7 months and 102 ± 42.4 months, respectively.Conclusion: High-precision CRT is an effective modality to achieve remission in patients with acromegaly after failed TSS.Abbreviations:CRT = conformal fractionated radiotherapyCT = computed tomographyCTV = clinical target volumeDA = dopamine agonistsGH = growth hormoneGTV = gross tumor volumeIGF1 = insulin-like growth factor 1MRI = magnetic resonance imagingRT = radiotherapyPTV = planning target volumeSA = somatostatin analogueSRS = stereotactic radiosurgeryTSS = transsphenoidal surgeryULN = multiple of upper limit of normalWHO = World Health Organization     

Pituitary Stalk Thickening in a Large Cohort: Toward More Accurate Predictors of Pituitary Dysfunction and Etiology

Objective: To summarize the characteristics of patients with pituitary stalk thickening, analyze the association between pituitary stalk width and hypopituitarism, and develop a diagnostic model to differentiate neoplastic and inflammatory origins.Methods: A total of 325 patients with pituitary stalk thickening in a tertiary teaching hospital between January 2012 and February 2018 were enrolled. Basic characteristics and hormonal status were evaluated. Indicators to predict etiology in patients with histologic diagnoses were analyzed.Results: Of the 325 patients, 62.5% were female. Deficiency in gonadotropin was most common, followed by corticotropin, growth hormone, and thyrotropin. The increase in pituitary stalk width was associated with a risk of central diabetes insipidus (odds ratio &lsqb;OR], 3.57; P<.001) and with a combination of central diabetes insipidus and anterior pituitary deficiency (OR, 2.28; P = .029). The cut-off pituitary stalk width of 4.75 mm had a sensitivity of 69.2% and a specificity of 71.4% for the presence of central diabetes insipidus together with anterior pituitary deficiency. Six indicators (central diabetes insipidus, pattern of pituitary stalk thickening, pituitary stalk width, neutrophilic granulocyte percentage, serum sodium level, and gender) were used to develop a model having an accuracy of 95.7% to differentiate neoplastic from inflammatory causes.Conclusion: Pituitary stalk width could indicate the presence of anterior pituitary dysfunction, especially in central diabetes insipidus patients. With the use of a diagnostic model, the neoplastic and inflammatory causes of pituitary stalk thickening could be preliminarily differentiated.Abbreviations: APD = anterior pituitary dysfunction; AUC = area under the curve; CDI = central diabetes insipidus; GH = growth hormone; MRI = magnetic resonance imaging; OR = odd ratio; PHBS = posterior hypophyseal bright spots; PST = pituitary stalk thickening; PSW = pituitary stalk width     

Remission of Acromegaly After Pituitary Apoplexy: Case Report and Review of Literature

ObjectiveTo identify and present cases of acromegaly in which pituitary apoplexy resulted in remission of acromegaly, with normalization of insulinlike growth factor-I and growth hormone levels.MethodsWe present a case history of a personal patient and review the related literature in PubMed and Ovid MEDLINE.ResultsA 34-year-old man with classic acromegaly had spontaneous pituitary apoplexy, resulting in remission of his acromegaly and diabetes. Moreover, we identified 21 other similar cases in the literature and analyze the clinical presentations, possible apoplexy triggers, and hormonal sequelae. All these patients were “cured” of acromegaly, and 68% of them experienced other pituitary hormone insufficiencies after pituitary apoplexy, including 2 cases of panhypopituitarism.ConclusionPituitary apoplexy can result in remission of acromegaly and in partial or complete anterior or posterior (or both) pituitary insufficiency. Thus, after suspected or confirmed pituitary apoplexy, pituitary hormone secretion must be reevaluated. This assessment may result in initiation of appropriate substitution therapy, a change in management of growth hormone overproduction, or both interventions. (Endocr Pract. 2009;15:725-731)     

Pituitary Imaging By Mri and its Correlation with Biochemical Parameters in the Evaluation of Men with Hypogonadotropic Hypogonadism

Objective: A significant ambiguity still remains about which patient deserves a magnetic resonance imaging (MRI) scan of the pituitary during evaluation of hypogonadotropic hypogonadism (HH) in men.Methods: Retrospective case series of 175 men with HH referred over 6 years.Results: A total of 49.7% of men had total testosterone (TT) levels lower than the Endocrine Society threshold of 5.2 nmol/L. One-hundred forty-two patients (81.2%) had normal appearance of pituitary MRI, whereas others had different spectrum of abnormalities (empty sella &lsqb;n = 16], macroadenoma &lsqb;n = 8], microadenoma &lsqb;n = 8], and pituitary cyst &lsqb;n = 1]). In men with TT in the lowest quartile, MRI pituitary findings were not significantly different from men in the remaining quartiles (P = .50). Patients with raised prolactin had higher number of abnormal MRI findings (38.9% vs. 13.7%; P = .0014) and adenomatous lesions (macro and micro) (27.8% vs. 4.3%; P = .01) in comparison to men with normal prolactin. The prolactin levels (median &lsqb;interquartile range]) were highest in men with macroadenomas in both groups (9,950 &lsqb;915]; P = .007 and 300 &lsqb;68.0] mU/L; P = .02, respectively), with concomitant lower levels of other pituitary hormones. Multivariate logistic regression showed an association of abnormal pituitary MRI with insulin-like growth factor 1 (IGF-1) standard deviation score (SDS) (odds ratio &lsqb;OR], 1.78 &lsqb;95% confidence interval (CI), 1.15 to 2.77]; P = .009) and prolactin (OR, 1.00 &lsqb;95% CI, 1.00 to 1.03]; P = .01).Conclusion: MRI of the pituitary is not warranted in all patients with HH, as the yield of identifiable abnormalities is quite low. Anatomic lesions are likely to be present only when low levels of TT (<5.2 nmol/L) are found concomitantly with high levels of prolactin and/or low IGF-1 SDS.Abbreviations: CI = confidence interval; FT4 = free thyroxine; GH = growth hormone; HH = hypogonadotropic hypogonadism; IGF-1 = insulin-like growth factor; LH = luteinizing hormone; MRI = magnetic resonance imaging; OR = odds ratio; SDS = standard deviation score; TSH = thyroid-stimulating hormone; TT = total testosterone     

Venus by Botticelli and Her Pituitary Adenoma

Objective: Simonetta Vespucci, considered the most beautiful woman of the Renaissance, is the inspiration and face of one of the most famous paintings of all times, “The Birth of Venus,” by Botticelli. She died in 1476 at the age of 23 years. We postulate she suffered from a pituitary-secreting tumor progressing to pituitary apoplexy. The goals of this study were 3-fold: (i) verify that the subject depicted by Botticelli in different paintings represents the same woman; (ii) identify the facial traits affected by the progression of a growth hormone– and prolactin-secreting tumor; and (iii) confirm that the observed changes of the face traits observed in the portraits of Simonetta Vespucci are compatible with the facial traits changes identified earlier.Methods: Comparison among face traits was based on the analysis of the face regions measured by means of fiducial points and their distances, and after pose compensation based on three-dimensional head modelling.Results: In favor of the hypothesis that Simonetta suffered from a pituitary growth hormone– and prolactin-secreting tumor stands changes of her lineaments, a feature which becomes evident over the years and particularly manifest in the Allegorical Lady, where galactorrhea is depicted.Conclusion: We conclude that sufficient evidence is presented to suggest that Simonetta Vespucci, the Venus depicted by Botticelli, suffered from pituitary adenoma secreting prolactin and growth hormon with parasellar expansion. The current interpretation of the Venus strabism should be revisited according to this finding.Abbreviation: GH = growth hormone     

Limitations of Current Approaches For The Treatment of Acromegaly

Objective: Acromegaly is a rare disease characterized by hypersecretion of growth hormone (GH), typically from a benign pituitary somatotroph adenoma, that leads to subsequent hypersecretion of insulin-like growth factor 1 (IGF-1). Patients with acromegaly have an increased risk of mortality and progressive worsening of comorbidities. Surgery, medical therapy, and radiotherapy are currently available treatment approaches for patients with acromegaly, with overall therapeutic goals of lowering GH levels and achieving normal IGF-1 levels, reducing tumor size, improving comorbidities, and minimizing mortality risk. Although surgery can lead to biochemical remission in some patients with acromegaly, many patients will continue to have uncontrolled disease and require additional treatment.Methods: We reviewed recently published reports and present a summary of the safety and efficacy of current treatment modalities for patients with acromegaly.Results: A substantial proportion of patients who receive medical therapy or radiotherapy will have persistently elevated GH and/or IGF-1. Because of the serious health consequences of continued elevation of GH and IGF-1, there is a need to improve therapeutic approaches to optimize biochemical control, particularly in high-need patient populations for whom current treatment options provide limited benefit.Conclusion: This review discusses current treatment options for patients with acromegaly, limitations associated with each treatment approach, and areas within the current treatment algorithm, as well as patient populations for which improved therapeutic options are needed. Novel agents in development were also highlighted, which have the potential to improve management of patients with uncontrolled or persistent acromegaly.Abbreviations:AACE = American Association of Clinical EndocrinologistsAE = adverse eventATG = AutogelCFRT = conventional fractionated radiotherapyDA = dopamine agonistENDO = Endocrine SocietyGH = growth hormoneGHRA = growth hormone receptor antagonistIGF-1 = insulin-like growth factor 1LAR = long-acting releaseLFT = liver function testSC = subcutaneousSRS = stereotactic radiosurgerySSA = somatostatin analoguesst = somatostatin receptorsst₂ = somatostatin receptor subtype 2sst₅ = somatostatin receptor subtype 5TSS = transsphenoidal surgery