Gigantism: microsurgical treatment by transsphenoidal approach and prognostic factors.

PURPOSE: We present the results of transsphenoidal microsurgical treatment in 14 patients with gigantism. The influence on the prognosis of factors such as the tumor size and preoperative levels of GH and IGF-1 is also quantified. MATERIALS AND METHODS: The patients, operated between 1982 and 2004, were reviewed retrospectively in June 2022. All patients had complete endocrinological studies in the preoperative period and a postoperative control between 6 days and 3 weeks. Follow-up has been supported with annual check-ups between 3 and 31 years. We have compared the preoperative levels of GH and IGF-1 of these patients with the levels of a series of acromegalic patients operated on in the same Center. RESULTS: In this series there were 4 women and 10 men. The age ranged between 14 and 21 years. In 6 patients, postoperative hormone levels achieved the disease control criteria (42.8%). The CT/MRI studies revealed the existence of invasive tumors in 10 of the patients (71.4%). Postoperative CT/MRI showed no tumor tissue in 3 patients but in 7 patients there were tumor remains. The remaining 4 patients had abnormal images although not considered as tumor. A statistical comparison of preoperative serum GH and IGF-1 levels in patients with gigantism and patients with acromegaly showed a significant elevation in the former. CONCLUSION: Pituitary adenomas that cause gigantism are generally large and invasive, which makes them difficult to cure. High preoperative levels of GH and IGF-1 are also factors that decrease remission.

Macrodystrophia Lipomatosa of Thoracic Spine Causing Progressive Neurodeficit: A Case Report and Review of Literature.

CASE: We report the first case of a 21-year-old male patient with macrodystrophia lipomatosa (MDL), with local gigantism involving the thoracic spine and progressively worsening neurodeficit. Imaging studies revealed fatty infiltration and hypertrophied intercostal nerves, dextroscoliosis, osseous hypertrophy between C4 and T2, and severe canal stenosis at the T4 to T5 level secondary to lamino-facetal hypertrophy. He underwent debulking of the lesion and posterior instrumented decompression in a staged manner. His neurodeficit improved postoperatively and was ambulant without support at the end of the 2-year follow-up. CONCLUSION: Surgery in patients with MDL is technically challenging and fraught with complications such as neurological deficit and significant blood loss.

Surgical trauma induces overgrowth in lower limb gigantism: regulation with use of rapamycin is promising.

We describe an unclassified overgrowth syndrome characterised by unregulated growth of dermal fibroblasts in the lower limbs of a 35-year-old woman. A PIK3CA gene mutation resulted in lower limb gigantism. Below the waist, she weighed 117 kg with each leg measuring over 100 cm in circumference. Her total adiposity was 50% accounted for by her legs mainly. Liposuction and surgical debulking were performed to reduce the size of the limbs but had exacerbated the overgrowth in her lower limbs. Systemic sepsis from an infected foot ulcer necessitated treatment by an above-knee amputation. Postoperatively, the stump increased in size by 19 kg. A trial of rapamycin to reverse the growth of the stump has shown promise. We discuss the clinical and genetic features of this previously unclassified disorder and the orthopaedic considerations involved.

What treatment for a child with tall stature?

Tall stature is statistically defined as a height standard deviation score (SDS) above 2 for a given age, sex and population group. The most common cause of tall stature is constitutional (often familial) tall stature. However, underlying endocrine or genetic disorders must be considered as some of them may require specific treatment or management. In constitutional tall stature, healthy children are referred to discuss treatment aiming at reducing adult height. The indications of treatment are rare and usually discussed in girls with extremely tall stature (height SDS>4, corresponding to 185cm in girls). The treatment options for tall children are limited and concerns have been raised about their long-term safety. Indeed, recent studies have suggested that high-dose estrogens in adolescent girls may be associated with an increased risk of infertility, as well as increased risk of cancer. Surgical epiphysiodesis has also been reported to reduce adult height but this invasive procedure in healthy children can be questionable and further data on its safety profile are required.

Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.

X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome.

Retalho tenar adipofascial reverso para cobertura do nervo mediano hipertrofiado em macrodactilia / The reverse adipofascial thenar flap for coverage of the hypertrophied median nerve in macrodactyly

A macrodactilia é uma anomalia congênita infrequente, caracterizada pelo crescimento desproporcional dos tecidos ósseo, gorduroso, nervoso, vascular e dérmico nos dedos das mãos ou dos pés. Existem muitas teorias sobre a sua etiopatogenia, sendo a mais aceita a hiperestimulação por fatores de crescimento enviados através dos nervos. Foram descritos alguns casos associados com a síndrome do túnel do carpo. Apresenta-se um caso clínico de síndrome do túnel do carpo por hipertrofia do nervo mediano, evidenciando um aumento de conteúdo dentro do retináculo flexor, o qual foi tratado cirurgicamente com sucesso pela realização de uma retinaculotomia do ligamento anular do carpo junto a um retalho de transposição tenar adipofascial reverso da região tenariana hipertrofiada visando à cobertura do nervo mediano na região do punho.

Macrodactyly is a rare congenital anomaly characterized by the disproportionate growth of bone, fat, nervous, vascular, and dermal tissue in the digits . There are many different theories about its etiopathogenesis, the most accepted being a hyperstimulation by growth factors conducted through nerves. A few cases have been described in conjunction with carpal tunnel syndrome. Here, a clinical case of carpal tunnel syndrome due to hypertrophy of the median nerve is presented, showing an increase of content within the flexor retinaculum. Successful surgical treatment was accomplished by conducting a retinaculotomy of the anterior annular ligament along with a reverse transposition adipofascial flap of the hypertrophied thenar region for coverage of the median nerve at the wrist.

Síndrome de Proteus: relato de casos / Proteus Syndrome: case reports

INTRODUÇÃO: A síndrome de Proteus é uma doença complexa e rara, classificada nos grupo das hamartoses. Foi primeiramente descrita em dois pacientes, em 1979, por Cohen e Hayden. Existe dificuldade no diagnóstico, sendo comum a confusão com síndromes de Klippel-Trenaunay-Weber, neurofibromatose ou Stuge-Weber. Apresentamos dois casos tratados no Serviço de Cirurgia Plástica e Reparadora da Universidade Federal do Paraná. MÉTODO: Paciente masculino (caso 1), que chegou ao serviço aos 6 anos de idade, tendo como principais apresentações lipomatoses e assimetrias. A segunda paciente (caso 2) deu entrada no serviço com 20 anos de idade e diagnóstico de síndrome de Klippel-Trenaunay-Weber, que posteriormente mostrou se tratar de síndrome de Proteus. CONCLUSÃO: A hipótese etiológica mais aceita para a doença é genética. Acredita-se que exista mosaicismo somático e que a doença seja letal no estado não mosaico. Morte prematura é bastante frequente. Entretanto, a sequela mais comum é a ocorrência de tumores incomuns. O cuidado dos pacientes portadores da síndrome é um desafio devido às suas consequências médicas e psicossociais.

INTRODUCTION: Proteus syndrome is a complex and rare disorder classified as a hamartomatous disease. It was first described in two patients in 1979, by Cohen and Hayden. Proteus syndrome is difficult to diagnose, and is often confused with Klippel-Trenaunay-Weber syndrome, neurofibromatosis, or Sturge-Weber syndrome. In this study we describe two patients who were treated at the Plastic and Reconstructive Surgery Service of the Federal University of Paraná. METHOD: A 6-year-old male patient (case 1) presented to the Service with lipomatosis and asymmetry, as the primary findings. A 20-year-old (case 2) was admitted to the Service with a diagnosis of Klippel-Trenaunay-Weber syndrome, which later was shown to be Proteus syndrome. CONCLUSION: The etiological hypothesis that is most accepted for this disease is genetic. It is believed that somatic mosaicism may occur during pathogenesis, which can be lethal in the mosaic state. Premature death is common. However, the most common sequelae are the occurrence of unusual tumors. The care of patients with this syndrome is a challenge due to medical and psychosocial consequences.

Imaging features of macrodystrophia lipomatosa: an unusual cause of a brawny arm.

Macrodystrophia lipomatosa (MDL), a rare non-hereditary congenital disorder of localised gigantism, is characterised by progressive proliferation of all mesenchymal elements, with a disproportionate increase in fibroadipose tissue. We report a case of a 19-year-old man who presented with a history of painless enlargement of the left upper limb since childhood, which was gradually increasing in size and predominantly involving the radial aspect of the upper limb with relative sparing of the ulnar aspect. The patient was imaged with X-ray and MRI. Imaging and clinical features were classical of MDL. The patient underwent stage 1 reduction plasty of the left forearm; preoperative and histopathological findings confirmed the preoperative diagnosis.

Gigantism treated by pure endoscopic endonasal approach in a case of McCune-Albright syndrome with sphenoid fibrous dysplasia: a case report.

McCune-Albright syndrome (MAS) is an uncommon polyostotic manifestation of fibrous dysplasia in association with at least one endocrinopathy that is mostly associated with precocious puberty and hyperpigmented skin macules named café-au-lait spots. We present an atypical manifestation of McCune-Albright syndrome in a 19-year-old man with the uncommon association of polyostotic fibrous dysplasia and gigantism in the absence of café-au-lait spots and precocious puberty. He presented with a height increase to 202 cm in the previous 3 years, which had become more progressive in the few months prior. Physical examination revealed only a mild facial asymmetry; however, a computed tomography (CT) scan discovered vast areas of voluminous bones with ground-glass density and thickening involving the craniofacial bones and skull base. Magnetic resonance imaging (MRI) found a right stalk shift of the pituitary with a 20 mm pituitary adenoma. We describe the diagnostic and endoscopic endonasal transsphenoidal approach for excision of the tumor.

Anesthesia in a 12 year old boy with somatic overgrowth secondary to pericentric inversion of chromosome 12.

The management of a splenectomy in a boy with an unusual form of somatic overgrowth is presented. Except for a moderately difficult airway, no unusual reactions to anesthesia and surgery were encountered. Possible anesthetic implications of different somatic overgrowth syndromes in children are presented.

Macrodystrophia lipomatosa.

OBJECTIVE: We present a series of six cases of macrodystrophia lipomatosa (MDL) and their outcome after debulking surgery. MATERIAL AND METHODS: The study was conducted from 2002 to 2005; the cases are selected from outpatients department of postgraduate institute of medical education and research. The patients were in the age group of 2-5 years of age with the complaints of progressive increase in size of the toe, difficulty in walking and recurrent injury to the foot. RESULTS: There were no complication in three (50%) cases but two cases (33%) had skin blackening along the suture margins, One case (16%) was under corrected. And none of the cases had recurrence. CONCLUSION: Simple debulking surgery is sufficient for MDL.

Hereditary pituitary hyperplasia with infantile gigantism.

CONTEXT: We report hereditary pituitary hyperplasia. OBJECTIVE: The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. DESIGN: The study is a retrospective analysis of three cases from one family. SETTING: The study was conducted at the National Institutes of Health, a tertiary referral center. PATIENTS: A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. INTERVENTIONS: The condition was treated by total hypophysectomy. MAIN OUTCOME MEASURE(S): We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. RESULTS: All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. CONCLUSIONS: This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.

On the shoulders of giants: Harvey Cushing's experience with acromegaly and gigantism at the Johns Hopkins Hospital, 1896-1912.

A review of Dr. Cushing's surgical cases at Johns Hopkins Hospital revealed new information about his early operative experience with acromegaly. Although in 1912 Cushing published selective case studies regarding this work, a review of all his operations for acromegaly during his early years has never been reported. We uncovered 37 patients who Cushing treated with surgical intervention directed at the pituitary gland. Of these, nine patients who presented with symptoms of acromegaly, and one with symptoms of gigantism were selected for further review. Two patients underwent transfrontal 'omega incision' approaches, and the remaining eight underwent transsphenoidal approaches. Of the 10 patients, 6 were male. The mean age was 38.0 years. The mean hospital stay was 39.4 days. There was one inpatient death during primary interventions (10%) and three patients were deceased at the time of last follow-up (33%). The mean time to death, calculated from the date of the primary surgical intervention, and including inpatient and outpatient deaths, was 11.3 months. The mean time to last follow-up, calculated from the day of discharge, was 59.3 months. At the time of last follow-up, two patients reported resolution of headache; four patients reported continued visual deficits, and two patients reported ongoing changes in mental status. This review analyzes the outcomes for 10 patients who underwent surgical intervention for acromegaly or gigantism, and offers an explanation for Cushing's transition from the transfrontal "omega incision" to the transsphenoidal approach while practicing at the Johns Hopkins Hospital.

Dorsal resection of a thoracic hemivertebra in a 4-year-old boy with endochondral gigantism. A case report.

The authors present what appears to be the first case of congenital kyphosis due to a T12 hemivertebra in a four-year-old boy with endochondral gigantism syndrome of unknown origin. Because of his overgrowth, the patient had severe medical and orthopaedic problems and was almost immobile. Prior to surgery, he experienced a rapidly progressive thoracolumbar kyphosis to 600 (T10-L2). MRI of the brain and spine showed critical protraction of the spinal cord and myelopathy from compression at T12. Single-stage posterior resection of the hemivertebra with spinal shortening and dorsal transpedicular instrumentation of T10-L2 was performed. Although the bone tissue was cartilaginous and dysplastic, 420 (30%) correction was achieved along with decompression of the spinal canal. The patient experienced no neurological impairment post-operatively. At follow-up examination 1.5 year after surgery, the patient's movement disorder had improved markedly and he was able to stand and walk. This very rare case demonstrates that single-stage posterior hemivertebra resection and transpedicular instrumentation for correction of congenital kyphosis can be a safe and effective procedure even in a very challenging case.

Síndrome de Sotos y escoliosis: tratamiento quirúrgico y seguimiento a los 10 años / Sotos syndrome and scoliosis: surgical treatment: a 10-year follow-up

Introducción: El síndrome de Sotos es causado por una deleción genética de transmisión autosómica dominante. La hipotonía, la hiperlaxitud y el gigantismo cerebral son características de este síndrome. Materiales y métodos: Fueron evaluados retrospectivamente 42 pacientes con diagnóstico de síndrome de Sotos tratados en el Hospital Garrahan en el período comprendido entre 1988 y marzo de 2009. Se revisaron las historias clínicas y los estudios por imágenes. Resultados: Ocho pacientes (19 por ciento) presentaron escoliosis y 7 de ellos requirieron cirugía (87 por ciento). El promedio de seguimiento fue de 9,5 años (rango 3 a 18 años). La edad promedio en la primera consulta fue de 5,2 años (rango 1,2 a 11,2). El valor angular medio en la primera consulta fue de 34,3º (rango 20º a 42º). La media de edad en el momento de la cirugía fue de l 1,2 años (rango 3 a 18,10). Los procedimientos quirúrgicos realizados fueron artrodesis posterior instrumentada sola o combinada con artrodesis anterior, artrodesis anterior instru

Síndrome de Sotos y escoliosis: tratamiento quirúrgico y seguimiento a los 10 años / Sotos syndrome and scoliosis: surgical treatment: a 10-year follow-up

Introducción: El síndrome de Sotos es causado por una deleción genética de transmisión autosómica dominante. La hipotonía, la hiperlaxitud y el gigantismo cerebral son características de este síndrome. Materiales y métodos: Fueron evaluados retrospectivamente 42 pacientes con diagnóstico de síndrome de Sotos tratados en el Hospital Garrahan en el período comprendido entre 1988 y marzo de 2009. Se revisaron las historias clínicas y los estudios por imágenes. Resultados: Ocho pacientes (19 por ciento) presentaron escoliosis y 7 de ellos requirieron cirugía (87 por ciento). El promedio de seguimiento fue de 9,5 años (rango 3 a 18 años). La edad promedio en la primera consulta fue de 5,2 años (rango 1,2 a 11,2). El valor angular medio en la primera consulta fue de 34,3° (rango 20° a 42°). La media de edad en el momento de la cirugía fue de l 1,2 años (rango 3 a 18,10). Los procedimientos quirúrgicos realizados fueron artrodesis posterior instrumentada sola o combinada con artrodesis anterior, artrodesis anterior instrumentada y, en un paciente actualmente, distracción sucesiva. El VAM preoperatorio fue de 72,3° (rango 46° a 130°) y el VAM posoperatorio, de 45,5° (rango 6° a 90°). Hubo 3 complicaciones inmediatas (derrame pleural en 2 casos y 1 sepsis con óbito) y 2 tardías (cifosis supraartrodesis y salida de los ganchos proximales). Conclusiones: La incidencia de escoliosis en los pacientes con síndrome de Sotos es alta en comparación con la registrada en la población general. Es importante realizar el seguimiento de los pacientes durante su crecimiento para efectuar el diagnóstico temprano. En el momento de la instrumentación se deben considerar la laxitud y la hipotonía, y evitar las fusiones cortas.

Macrodystrophia lipomatosa: macrodactyly related to affected nerves, and a review of the literature.

Macrodystrophia lipomatosa (ML) is a rare disease causing congenital local gigantism of part of an extremity mostly through proliferation of fibro-adipose tissue. This study is one of few that specifically describe 8 ML patients with histological confirmation of the diagnosis combined with the 79 histologically confirmed cases already described in the literature. The goals of this study are to describe this malformation by using only histologically confirmed cases, to offer some insight on current opinions on ML by reviewing the histologically confirmed cases described in the literature, and to make the postulation of autonomic nerve dysfunction as the aetiology of ML more plausible.

Management of type 2 diabetes mellitus associated with pituitary gigantism.

Pituitary gigantism, a condition of endogenous growth hormone (GH) hypersecretion prior to epiphyseal closure, is a rare condition. In the adult condition of GH excess, acromegaly, the occurrence of type 2 diabetes mellitus (T2DM) and diabetic ketoacidosis (DKA) have been reported, with resolution following normalization of GH levels. We report the case of a 16-year-old male with pituitary gigantism due to a large invasive suprasellar adenoma who presented with T2DM and DKA. Despite surgical de-bulking, radiotherapy and medical treatment with cabergoline and pegvisomant, GH and insulin-like growth factor-I (IGF-I) levels remained elevated. However, the T2DM and recurrent DKA were successfully managed with metformin and low-dose glargine insulin, respectively. We review the pathophysiology of T2DM and DKA in growth hormone excess and available treatment options.