Excessive Growth Hormone Secretion Research Articles

Serum phosphate levels at diagnosis predict long-term risk for hypopituitarism in patients with acromegaly.

Excess growth hormone (GH) secretion in acromegaly has a major impact on mineral balance and serum phosphate levels. However, the clinical utilization of serum phosphate levels as a marker for long-term disease outcomes in acromegaly has not been evaluated. This is a retrospective study of patients with acromegaly who were followed in a tertiary center. Data were retrieved on patient characteristics, endocrine and biochemical evaluation, and tumor parameters. Comparisons were performed by measuring baseline phosphate levels and conductingcorrelation analysis and multivariable logistic regression. Sixty-one patients were followed for 4.5years (range 1-21). Patients with hyperphosphatemia (> 4.5mg/dl) at baseline had larger adenomas (15.0mm [8.0, 47.0] vs. 10.0mm [3.0, 24.0], p = 0.001), a rate chance of invasive adenoma (16 [80.0%] vs. 14 [46.7%], p = 0.02), and lower serum cortisol levels (226.0nmol/l [27.6, 516.0] vs. 294.0nmol/l [32.0, 610.0], p = 0.02). Baseline serum phosphate levels positively correlated with IGF-1 levels (r = 0.43, p = 0.003) and negatively correlated with morning plasma cortisol levels (r = -0.46, p = 0.002). Regarding long-term impact, baseline phosphate levels correlated with the number of pituitary axes involved 6months after diagnosis (r-0.34, p = 0.01). In multivariable analysis, baseline plasma phosphate levels were independently associated with risk for disease progression/recurrence (odds ratio [OR] 9.66, 95% confidence interval [CI] 1.5, 105.9, p = 0.03) and for invasive adenoma (OR 6.21, 95% CI 1.6, 28.7, p = 0.01). Elevated pretreatment serum phosphate levels are associated with a greater risk of disease persistence and recurrence and with altered pituitary function in patients with acromegaly.

Pregnancy and acromegaly: clinical outcomes of retrospectively analysed data from the German acromegaly registry

ContextAcromegaly is a rare disease caused by excessive growth hormone (GH) secretion, mostly induced by pituitary adenomas. The care of pregnant women with acromegaly is challenging, in part due to existing clinical data being limited and not entirely consistent with regard to potential risks for mother and child.ObjectiveTo retrospectively examine data on pregnancy and maternal as well as neonatal outcomes in patients with acromegaly.Design & methodsRetrospective data analysis from 47 pregnancies of 31 women treated in centers of the German Acromegaly Registry.Results87.1% of the studied women underwent transsphenoidal surgery before pregnancy. In 51.1% a combination of dopamine agonists and somatostatin analogs were used before pregnancy. Three women did not receive any therapy for acromegaly. During pregnancy only 6.4% received either somatostatin analogs or dopamine agonists. In total, 70.2% of all documented pregnancies emerged spontaneously. Gestational diabetes was diagnosed in 10.6% and gravid hypertension in 6.4%. Overall, no preterm birth was detected. Indeed, 87% of acromegalic women experienced a delivery without complications.ConclusionPregnancies in women with acromegaly are possible and the course of pregnancy is in general safe for mother and child both with and without specific treatment for acromegaly. The prevalence of concomitant metabolic diseases such as gestational diabetes is comparable to the prevalence in healthy pregnant women. Nevertheless, larger studies with more data in pregnant patients with acromegaly are needed to provide safe and effective care for pregnant women with this condition.

Acromegaly, an Exceptional Cause of High-Grade Heart Blocks

Acromegaly is a rare disorder resulting from the excessive secretion of growth hormone (GH) and causing a specific form of cardiomyopathy. Until now, it has been widely recognized that individuals with acromegaly face an elevated risk of arrhythmias. However, high-grade atrioventricular blocks are a very rare complication of acromegaly. We report the clinical observation of a 75 years old acromegalic male presenting with high-grade atrioventricular block requiring permanent stimulation with a pacemaker.

Basal interaction of the orphan receptor GPR101 with arrestins leads to constitutive internalization

GPR101 is an orphan G protein-coupled receptor that promotes growth hormone secretion in the pituitary. The microduplication of the GPR101 gene has been linked with the X-linked acrogigantism, or X-LAG, syndrome. This disease is characterized by excessive growth hormone secretion and abnormal rapid growth beginning early in life. Mechanistically, GPR101 induces growth hormone secretion through constitutive activation of multiple heterotrimeric G proteins. However, the full scope of GPR101 signaling remains largely elusive. Herein, we investigated the association of GPR101 to multiple transducers and uncovered an important basal interaction with Arrestin 2 (β-arrestin 1) and Arrestin 3 (β-arrestin 2). By using a GPR101 mutant lacking the C-terminus and cell lines with an Arrestin 2/3 null background, we show that the arrestin association leads to constitutive clathrin- and dynamin-mediated GPR101 internalization. To further highlight GPR101 intracellular fate, we assessed the colocalization of GPR101 with Rab protein markers. Internalized GPR101 was mainly colocalized with the early endosome markers, Rab5 and EEA-1, and to a lesser degree with the late endosome marker Rab7. However, GPR101 was not colocalized with the recycling endosome marker Rab11. These findings show that the basal arrestin recruitment by GPR101 C-terminal tail drives the receptor constitutive clathrin-mediated internalization. Intracellularly, GPR101 concentrates in the endosomal compartment and is degraded through the lysosomal pathway. In conclusion, we uncovered a constitutive intracellular trafficking of GPR101 that potentially represents an important layer of regulation of its signaling and function.

FRI356 SIADH In Acromegaly And Cerebrovascular Accident

Abstract Disclosure: S. Siddiqui: None. I.A. Guatemala Funes: None. G. Simranpreet: None. T. Zahedi: None. F. Zhang: None. Introduction: Acromegaly is characterized by excess growth hormone secretion with distinctive features of acral overgrowth, soft tissue swelling, arthralgia, jaw prognostication, hyperglycemia, hyperhidrosis, and frontal bone bossing. Hypotonic hyponatremia may occur in patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypothyroidism, hypocortisolism, polydipsia, medications, heart failure, liver disease, or renal dysfunction. We reported a rare case of a patient with acromegaly treated with octreotide (somatostatin analogue) who was admitted for cerebrovascular accident and developed hyponatremia due to SIADH. Case Report: Patient is an 81 year old female with typical clinical features of acromegaly who presented with expressive aphasia and left sided facial droop. MRI and CT head revealed a 26 x 14 x 29 mm densely calcified/ossified extra-axial mass in the posterior fossa, displacing the brainstem and small vessel ischemia. Patient was treated with monthly intramuscular injection of octreotide for more than 20 years before she was switched to oral octreotide formula two weeks ago. Patient had nausea, vomiting, and altered mental status. Labs showed hyponatremia with serum Na 118 mmol/L, low serum osmolality 247 mOsm/kg, high urine osmolality 437 mOsm/kg, and urine Na 104 mmol/L. Serum Na further dropped to 115 mmol/L after IV normal saline which may be related to the desalination phenomenon of SIADH. Tolvaptan and hypertonic saline were initiated followed by treatment with salt tablets and furosemide. After several days, her serum Na level slowly trending up back to normal 135 mmol/L and patient recovered with no focal neurological deficits. Discussion: Treatment for acromegaly involves multiple approaches, such as somatostatin receptor ligands, GH antagonism, surgery, radiotherapy, and dopamine receptor agonists. Life-treating endocrine disorder may result from pituitary infarction or hemorrhage in patient with acromegaly. Although gastrointestinal sodium loss may precipitate hyponatremia in our patient, her elevated urine sodium and urine osmolality were consistent with SIADH. Clinicians should be cautious of the sudden onset of hyponatremia due to SIADH in acromegaly patients and prompt treatment is warranted. Presentation: Friday, June 16, 2023

Akromegali Hastalarında Hematolojik İndekslerin Değerlendirilmesi

Objective: Acromegaly is a chronic systemic disease characterized by autonomous and excessive secretion of growth hormone (GH). Acromegaly is most commonly caused by ais a somatotroph adenoma of the anterior pituitary. In acromegaly, mortality primarily results from are cerebrovascular, cardiovascular, respiratory diseases and malignancies. Monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), red cell distribution width (RDW), platelet distribution width (PDW) and delta neutrophil index (DNI) are popular inflammatory markers. This study’s purpose was to assess pre/post-treatment levels of NLR, GH, RDW, MLR, PDW and DNI in acromegalic patients and to investigate the impact of acromegaly treatment on these markers. Materials and Methods: Twenty-six patients with acromegaly, treated and followed at our endocrinology outpatient clinic between April 2014 and February 2022 were included in the study. Age, sex, comorbidities, medications, complete blood count, kidney and liver function tests, pathology reports, tumor size, pre/post-treatment levels of IGF-1, GH, DNI, NLR, MLR, RDW and PDW were retrieved from patients’ files and outcomes were evaluated. Results: Among 26 patients included in the study, 12 (46%) were female and 14 (53%) were male. The average age of the patients was 53.73±16.21 years (range, 25-79). There were 11 (42%) patients with type 2 diabetes mellitus and 9 (34%) patients with hypertension. A statistically significant reduction was observed in post-operative GH, IGF-1, NLR, DNI, PDW and RDW values compared to preoperative values (during active disease phase) and at 6 months in patients with postoperative cure, and compared to pretreatment values in patients without postoperative remission who received medical treatment. A reduction was also observed in post-treatment MLR compared to pretreatment ratio but the difference was non-significant. There was no statistically significant correlation between the IGF-1 levels at the time of diagnosis and NLR, RDW, PDW in patients with acromegaly. Conclusion: Studies on the values of circulating inflammatory biomarkers in patients with acromegaly and their relationship to treatment remain unclear. In our study, higher pre-treatment GH, IGF-1, NLR, DNI, PDW, RDW values were found compared to post- treatment. This suggests that having chronically higher than normal values of IGF-1 may also lead to increased inflammatory markers such as NLR and increased atherosclerotic risk. Chronic subclinical inflammation caused by uncontrolled disease might lead to an increase in mortality and morbidity in acromegalic patients. Therefore, early diagnosis and treatment of acromegaly are crucial.

Evaluation of the Medical Treatment of Acromegaly (About 15 Cases)

Acromegaly is a condition caused by an excessive secretion of growth hormone due to a somatotropic pituitary adenoma, leading to an acquired dysmorphic syndrome. The aim of this study is to evaluate the effectiveness and tolerance of medical treatment using Lanreotide LP 120 mg in 15 patients with acromegaly, who were followed up at the endocrinology department of Ibn Sina Hospital in Rabat between 2017 and 2018. The quality of life of the patients after Lanreotide treatment was evaluated using the AcroQol questionnaire. 80% of the patients were found to have acrofacial dysmorphic syndrome, with the diagnosis based on clinical, biological, and radiological data. Magnetic resonance imaging revealed a pituitary macroadenoma in 86.7% of the cases. All patients were treated with medical treatment using Lanreotide LP 120mg. Fourteen patients underwent adenomectomy, with 4 of them receiving GammaKnife radiotherapy. During treatment, complications were observed in 80% of patients, with half of them related to vesicular lithiasis. The AcroQol scores obtained in the study were less satisfactory than expected, indicating a lower quality of life compared to the general population.

Excess Growth Hormone Triggers Inflammation-Associated Arthropathy, Subchondral Bone Loss, and Arthralgia

Growth hormone (GH) is a key mediator of skeletal growth. In humans, excess GH secretion due to pituitary adenoma, seen in patients with acromegaly, results in severe arthropathies. This study investigated the effects of long-term excess GH on the knee joint tissues. One year-old wild-type (WT) and bovine GH (bGH) transgenic mice were used as a model for excess GH. bGH mice showed increased sensitivity to mechanical and thermal stimuli, compared with WT mice. Micro-computed tomography analyses of the distal femur subchondral bone revealed significant reductions in trabecular thickness and significantly reduced bone mineral density of the tibial subchondral bone-plate associated with increased osteoclast activity in both male and female bGH compared with WT mice. bGH mice showed severe loss of matrix from the articular cartilage, osteophytosis, synovitis, and ectopic chondrogenesis. Articular cartilage loss in the bGH mice was associated with elevated markers of inflammation and chondrocyte hypertrophy. Finally, hyperplasia of synovial cells was associated with increased expression of Ki-67 and diminished p53 levels in the synovium of bGH mice. Unlike the low-grade inflammation seen in primary osteoarthritis, arthropathy caused by excess GH affects all joint tissues and triggers severe inflammatory response. Data from this study suggest that treatment of acromegalic arthropathy should involve inhibition of ectopic chondrogenesis and chondrocyte hypertrophy.

Cardiac Findings on Non-Contrast Thoracic Tomography in Patients with Acromegaly

Aim: Acromegaly occurs as a result of excessive and permanent secretion of growth hormone from the pituitary. Mortality is mostly related to cardiovascular system involvement. In our study, we aimed to evaluate the correlation between epicardial fat volume (EFV) and growth hormone level in thorax computed tomography in patients with acromegaly and coronary artery calcification, pulmonary artery diameter, ascending aorta diameter, cardiothoracic ratio (CTO) measurements with the control group patients.
 Method: Our study was retrospective and included 16 patients with acromegaly who were previously diagnosed and treated by the endocrinology clinic and a control group consisting of 32 patients matched for gender and age.In thorax CT, EFV measurement of the patients was performed and main pulmonary artery diameters, ascending aorta diameters, cardio thoracic ratios, presence of coronary artery calcification were evaluated.
 Results: The number of patients with large ascending aorta was higher in patients with acromegaly and it was statistically significant (p=0.041). Although the rate of patients with large main pulmonary artery diameter was higher in patients with acromegaly, no significant difference was found between the groups (p=0.355). There was no significant difference between the groups in terms of increased CTO (p=0.818) and coronary artery calcification (p=0.157).
 Conclusion: In our study, a difference was found between the acromegaly and control group patients only in terms of ascending aorta diameters, but no significant difference was found in terms of other parameters. We think that regular follow-up and treatment of patients is effective in this result. Cardiovascular risks can be reduced in patients with acromegaly with early diagnosis, regular follow-up and treatment.

Frequency of hyperostosis frontalis interna in patients with active acromegaly: is there a possible role of GH excess or hyperprolactinemia in its etiopathogenesis?

Acromegaly is characterized by bone changes due to excessive growth hormone (GH) secretion. Hyperostosis frontalis interna (HFI) is described as an overgrowth in the inner plate of the frontal bone. An increased incidence of HFI has been reported in patients with acromegaly. Since the etiology of HFI is poorly understood, we have analyzed whether there is a relationship between the hormonal and metabolic status of patients with acromegaly (with or without hyperprolactinemia) and the pathogenesis of HFI. Forty-five patients with acromegaly and two control groups consisting of 25 patients with prolactinoma (group 1) and 47 healthy subjects (group 2) were included in this retrospective study. Baseline hormonal data and cranial imaging were obtained from medical records and analyzed. Mean frontal bone thickness was 6.75mm in acromegaly, 4.85mm in group 1, and 5.1mm in group 2 of controls (p < 0.001). The frequency of HFI was higher in acromegalic patients than in the controls (22%, 0%, and 2.2%, respectively). There was no difference between the HFI positive and negative acromegalic patients in basal GH, IGF-1, and PRL levels, IGF-1 index, diagnosis lag time, and insulin resistance. There was no difference between groups regarding parietal and occipital bone thickness. Although the frequency of HFI is 22% in patients with acromegaly, neither excess GH nor hyperprolactinemia plays a role in its etiopathogenesis. Various genetic or epigenetic factors may contribute to its etiology.

Aberrations in carbohydrate metabolism in patients with diagnosed acromegaly - observational study.

Acromegaly is characterized by excessive secretion of growth hormone (GH). The incidence rate of acromegaly is 40 to 70 persons per one million people. Carbohydrate disorders often accompany the above pathology. The aim of this study was to examine the influence of high levels of somatotropin on aberrations in glycaemia in patients with acromegaly, and then a 5-year observation. The study group consisted of 86 patients (48 females and 38 males) with acromegaly diagnosed on the basis of clinical features, elevated insulin-like growth factor 1 (IGF-1) levels, and/or no inhibition of GH ≤ 1 ug/L secretion during 2 hours after an oral glucose load. In the study group type 2 diabetes mellitus (T2DM) was diagnosed in 21 patients (24.4%). There were also 14 cases (16.3%) of the diagnosis of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) combined. The mean age of participants with concomitant T2DM was 52.1 years, while the mean age of those without carbohydrate metabolism disturbances was 46.1 years. During a 5-year observation, we noticed an increase level of glycated haemoglobin (HbA1c) and new cases of pre-diabetes and T2DM. In patients with acromegaly the incidence rate of T2DM is 3-4 times higher than in the rest of the population, and it increases with age, especially after the patient reaches 55 years old.

Cognitive behavioral therapy adapted for patients with acromegaly

In acromegaly, excess secretion of growth hormone and insulin-like growth factor 1 may result in coarse features and enlargement of the extremities. Its negative repercussion on self-esteem can impair quality of life. Ten patients with acromegaly participated in this study. The treatment covered nine weekly group sessions. Unhealthy behaviors, thoughts, and emotions were identified, and healthy behaviors and thoughts were constructed, along with positive reflections on their associated emotions. In Session 7, the “Think healthy and feel the difference” technique was adapted to help patients better deal with their physical appearance and improve their quality of life. Qualitative data was obtained from an analysis of the content of a collaborative exercise developed in Session 7. Factors, especially thoughts, emotions, and advantages and disadvantages associated with both healthy and unhealthy behaviors, were identified. The technique improved quality of life for patients with acromegaly in relation to their acceptance of their physical appearance. UTN U 1111–1220-9846 (September 24th, 2018).

Acromegaly with Predisposition towards Cardiac Failure

Acromegaly is a rare disease caused by excess secretion of growth hormone. Most cases are due to pituitary macro ormicroadenoma. It usually occurs sporadically but some can be familial due to AIP gene mutation1. We report a case of45 year old gentleman with chief complaints of breathlessness since 15 days, increase shoe size, large hands and feet,protruded jaw, which eventually turned out to be acromegaly based on typical clinical appearance, hormonal featureswith chest xray showing features of cardiomegaly. Patient was managed conservatively, and discharged with stablevitals. Prompt and early intervention in such cases can prevent further progression of disease.

Abstract #1183275: Clinical characteristics, treatment and morbidity in Acromegaly. Findings from a medium country

Acromegaly is a rare chronic disease caused by excess secretion of growth hormone (GH), which leads to an increased production of insulin-like growth factor-1 (IGF-1). Due to its low prevalence, data on patient outcome and risk factors are still limited. The aim objective of the present study was to describe the clinical characteristics and morbidity in a cohort of Colombian adults with acromegaly.

Post-surgery Quality of Life in Patients with Acromegaly Using SF36 Quality of Life Questionnaire-prospective Study

Introduction: Acromegaly is chronic progressive disease with multisystem involvement characterised by an excess secretion of growth hormone and increased circulating insulin like growth factor 1 concentration.Aims and Objectives: To assess surgical outcome of acromegaly patients at tertiary care institute using SF 36 quality of life questionnaire. SF-36 scores comprise 3 components: the physical component summary (PCS), the mental component summary (MCS) and role-social component summary (RCS).30 acromegaly patients admitted in Guwahati medical college were enrolled in study and followed up post operatively for surgical remission. All participants completed the SF-36 preoperatively, 1 year and 2 years postoperatively.Material and Method: Out of 30 patients 6 patients had surgical remission post operatively on the basis of postoperative glucose suppressed GH Level done after 12 weeks. Preoperatively subscale scores (physical functioning, role physical, general health) which were below the set standards for the normal population show significant postoperative improvements along with mental health (MH) scores. Similarly, PCS, MCS and RCS scores changed significantly after surgery. We also compared the QOL of 6 patients whose peak GH level was &lt; 0.4 µg/L during postoperative oral glucose tolerance testing with those patients whose nadir GH level was ≥ 0.4 µg/L. There was significant difference between partial and complete remission group in subscale score role physical, social function and mental health. Similarly, PCS and RCS score significantly different in partial and complete remission group than MCS score.Conclusions: QOL is considerably reduced in patients with acromegaly compared to general population which improves significantly after surgical treatment. Patients achieving the new remission criteria had significant improvement in physical and social components than those who did not.

New developments and perspectives in acromegaly

Acromegaly is a rare but severe disorder which is usually due to an excessive secretion of growth hormone (GH) by a pituitary adenoma. Screening mainly relies on the measurement of insulin-like growth factor 1, and confirmatory diagnostics includes a GH suppression test. As delayed diagnosis results in increased morbidity and mortality, we here discuss recently published suggestions regarding the biochemical work-up of suspected cases and the follow-up of co-morbidities. Moreover, new analytical tools (such as automatic identification of typical facial changes using artificial intelligence) are presented, hopefully allowing for an earlier diagnosis in the future. So far, surgery is still regarded as therapy of first choice. In cases without postoperative remission, a new imaging approach (combining sellar magnetic resonance imaging and position emission tomography) may improve the results of repeated surgery. The pharmaceutical arsenal now includes the first orally available somatostatin analogue, and recent data on possible drug combinations and the outcome of radiotherapy are presented. Finally, special attention is paid to older and pregnant patients, as well as certain considerations during the COVID-19 pandemic (where appropriate diagnosis and management of acromegaly is particularly challenging).

Unilateral hydrocephalus from a gangliocytoma-somatotrophinoma: first reported case.

SummaryAlthough pituitary macroadenomas often cause mass effects on surrounding structures, it is extremely rare for pituitary lesions to disturb cerebrospinal fluid circulation. Sellar gangliocytoma-pituitary adenomas (SGPAs) are also extremely rare. Here we report the unique case of a man with the unusual combination of acromegaly from an SGPA, who presented with unilateral hydrocephalus. A 60-year-old man presented with rapid neurological deterioration, bitemporal hemianopia, and acromegalic features. Neuroimaging revealed a large sellar lesion extending superiorly into the left foramen of Monro, causing acute obstructive unilateral hydrocephalus. External ventricular drain placement improved consciousness immediately. Biochemical assessment confirmed acromegaly. Following trans-sphenoidal debulking, histology revealed a mixed gangliocytoma/sparsely-granulated somatotrophinoma. Despite the residual disease, his vision recovered remarkably, low-dose cabergoline controlled residual excess growth hormone (GH) secretion, and the residual tumour has remained extremely stable over 2 years. Hydrocephalus is an extremely rare complication of pituitary lesions, and unilateral hydrocephalus has never been reported previously. GH secretion in SGPAs is more common than for pituitary adenomas in general, raising questions regarding the aetiology and therapeutic approach to this rare combination tumour.Learning pointsPituitary tumours most commonly present with symptoms related to endocrine disturbance or mass effects upon visual pathways (e.g. optic chiasm, nerves in the lateral cavernous sinus). However, extremely rarely, pituitary masses may disrupt cerebrospinal fluid (CSF) circulation resulting in hydrocephalus.Sellar gangliocytomas are very rare tumours and most of them are hybrid tumours with pituitary adenomas (SGPAs).SGPAs are typically indolent and may be functioning or non-functioning tumours.Growth hormone (GH)-producing SGPAs are less likely to respond to somatostatin agonists than classic somatotrophinomas.Primary surgical debulking via a trans-sphenoidal approach was effective in this individual, leading to the restoration of CSF circulation and improvement in visual disturbance, while also negating the need for permanent CSF diversion despite the residual tumour burden.

Diagnosis of a Rare Case of Acromegaly Secondary to Pituitary Macroadenoma Debuting as Sudden DKA

Acromegaly is an uncommon clinical syndrome that results from excessive secretion of growth hormone with an annual incidence of 6 to 8 cases per 1 million of individuals with a mean age of diagnosis between 40-45 years. Pituitary adenomas can be the principal reason for an overgrowth of the anterior pituitary somatotroph cells, and account for approximately one-third of all hormone-secreting pituitary adenomas with a prevalence of about 38-69 cases per 1 million and an incidence of 3-4 cases per 1 million individuals. The onset of acromegaly is insidious, and its progression is usually very slow. At the moment of diagnosis, approximately 75% of patients have presence of macro adenomas, but most cases are diagnosed after several laboratory workups and incidental brain imaging. A characteristic clinical presentation of pituitary adenomas could be secondary to mass effect. Metabolic presentation such as diabetes is one of the most common related conditions preceding the diagnosis of acromegaly. Clinical presentation with abrupt onset of DKA could be a determining factor on disease progression due to higher GH levels correlating with an increased prevalence of insulin resistance. We present a rare case of a 28y/o female G5P3A2 without previous PMHx who presented to ER with abdominal pain, general malaise, slurred speech, headache and gait difficulty of 3 days of evolution. Upon initial evaluation at ER patient was found with hyperglycemia of 317mg/dL, low central bicarbonate, high anion gap and positive serum ketones suggestive of DKA de novo. Based on neurological complaints, head CT performed showed an incidental parasellar/suprasellar/temporal hyperdense mass measuring 2.5cm x 2.6cm with optic chiasm compression features. Upon further specific questioning patient referred amenorrhea for the past 3 years, bitemporal hemianopsia, galactorrhea and marked facial feature changes, frontal bossing, weight gain, and acanthosis nigricans, for the past year. Pituitary adenoma workup revealed low prolactin levels (1.38), markedly increased growth hormone (501) and IGF-1 (893) suggesting diagnosis of acromegaly, most likely secondary to a functioning macroadenoma. Patient initially treated with Cabergoline, uncontrolled diabetes was managed and was referred to Neurosurgery service for further evaluation and tumor removal. Based on current literature, the incidence of acromegaly cases is low, more specifically when presenting with new onset diabetic ketoacidosis, insulin resistance and secondary to functioning macroadenomas. Medical awareness should be promoted to assess for careful consideration of signs and symptoms, workup, management and treatment to assess and minimize further health complications and physical burdens acromegaly and pituitary adenomas could pose for affected individuals.

In Vivo Characterization of Cortical and White Matter Microstructural Pathology in Growth Hormone-Secreting Pituitary Adenoma.

BackgroundThe growth hormone (GH) and insulin-like-growth factor 1 (IGF-1) axis has long been recognized for its critical role in brain growth, development. This study was designed to investigate microstructural pathology in the cortex and white matter in growth hormone-secreting pituitary adenoma, which characterized by excessive secretion of GH and IGF-1.Methods29 patients with growth hormone-secreting pituitary adenoma (acromegaly) and 31 patients with non-functional pituitary adenoma as controls were recruited and assessed using neuropsychological test, surface-based morphometry, T1/T2-weighted myelin-sensitive magnetic resonance imaging, neurite orientation dispersion and density imaging, and diffusion tensor imaging.ResultsCompared to controls, we found 1) acromegaly had significantly increased cortical thickness throughout the bilateral cortex (pFDR < 0.05). 2) T1/T2-weighted ratio in the cortex were decreased in the bilateral occipital cortex and pre/postcentral central gyri but increased in the bilateral fusiform, insular, and superior temporal gyri in acromegaly (pFDR < 0.05). 3) T1/T2-weighted ratio were decreased in most bundles, and only a few areas showed increases in acromegaly (pFDR < 0.05). 4) Neurite density index (NDI) was significantly lower throughout the cortex and bundles in acromegaly (pTFCE < 0.05). 5) lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in extensive bundles in acromegaly (pTFCE < 0.05). 6) microstructural pathology in the cortex and white matter were associated with neuropsychological dysfunction in acromegaly.ConclusionsOur findings suggested that long-term persistent and excess serum GH/IGF-1 levels alter the microstructure in the cortex and white matter in acromegaly, which may be responsible for neuropsychological dysfunction.

Status epilepticus and diabetes ketoacidosis: uncommon clinical presentations of acromegaly.

SummaryAcromegaly is a rare disease caused by hypersecretion of the growth hormone (GH). Most cases are caused by either pituitary microadenoma or macroadenoma. The GH producing tumors present with clinical manifestations of acromegaly due to excessive GH secretion or symptoms resulting from mass effects of the enlarging tumor. The physical changes are usually slow and, therefore, recognition of the disease is delayed. These adenomas are never malignant but can have significant morbidity and mortality. A subgroup of patients with acromegaly present with severe hyperglycemia resulting in diabetic ketoacidosis (DKA) which requires insulin. Rarely are pituitary tumors responsible for generalized convulsions except when they are too large. We hereby present two cases, the first is that of a 26-year-old female who presented with new onset status epilepticus, DKA with a 1-year history of diabetes mellitus (DM). On examination, she had clinical features of acromegaly. The second case is that of a 34-year-old female who presented with new onset status epilepticus, hyperglycemia with a history of recently diagnosed DM, and features of gigantism. In both cases, their diagnosis was confirmed by elevated serum GH and later by elevated insulin-like growth factor type 1 levels, and CT of the head demonstrating large pituitary macroadenoma. The importance of clinical history and examination, as well as investigations is vital in the recognition of acromegaly. The prognosis of acromegalic patients depends on early clinical recognition and tumor size reduction by either medical or surgical therapy.Learning pointsConditions such as status epilepticus and DKA may be clinical presentations in patients presenting with acromegaly.Seizures are rare in people with pituitary adenoma and typically occur when the tumor invades the suprasellar area due to mass effect on the brain.This article shows how best we were able to manage the acromegaly complications in a low resource setting.Hyperprolactinemia in acromegaly may be due to disruption of the normal dopaminergic inhibition of prolactin secretion due to mass effect of the macroadenoma, and around 25% of GH-secreting adenomas co-secrete prolactin.