Acromegaly with congenital generalized lipodystrophy – two rare insulin resistance conditions in one patient: a case report

Abstract

Background: Lipodystrophies are a group of diseases which are characterized by abnormal adipose tissue deposition and are frequently associated with metabolic changes. Congenital generalized lipodystrophy is an autosomal recessive syndrome, with a prevalence < 1:10 million. Acromegaly is a rare disease, secondary to the chronic hypersecretion of growth hormone and insulin-like growth factor-1, with characteristic metabolic and somatic effects. "Acromegaloidism" is a term used for patients who manifest clinical features of acromegaly, but do not present a demonstrable hormone growth hypersecretion. The extreme shortage of subcutaneous adipose tissues and muscle hypertrophy confer an acromegaloid-like appearance in these patients. Case presentation: We describe a case of a patient with the rare combination of Berardinelli-Seip congenital lipodystrophy and acromegaly; our patient is a 63-year-old white man, who was referred to an endocrinology consultation for suspected lipodystrophy. He had lipoatrophy of upper and lower limbs, trunk, and buttocks, with muscular prominence, acromegaloid facial appearance, large extremities, and soft tissue tumescence. In addition, he had dyslipidemia and prediabetes. His fat mass ratio (% trunk fat mass/% lower limbs fat mass) was 1.02 by densitometry and he also had hepatomegaly, with mild steatosis (from an abdominal ultrasound), and left ventricular hypertrophy (from an electrocardiogram). His first oral glucose tolerance test had growth hormone nadir of 0.92 ng/mL, and the second test, 10 months afterwards, registered growth hormone nadir of 0.64 ng/mL (growth hormone nadir < 0.3 ng/mL excludes acromegaly). Pituitary magnetic resonance imaging identified an area of hypocaptation of contrast product in relation to a pituitary adenoma and he was subsequently submitted to transsphenoidal surgical resection of the mass. A pathological evaluation showed pituitary adenoma with extensive expression of growth hormone and adrenocorticotropic hormone, as well as a rare expression of follicle-stimulating hormone and prolactin. A genetic study revealed an exon 3/exon 4 deletion of the AGPAT2 gene in homozygosity. Conclusions: Congenital generalized lipodystrophy is a rare disease which occurs with acromegaloid features. As far as we know, we have described the first case of genetic lipodystrophy associated with true acromegaly. Although this is a rare association, the presence of congenital generalized lipodystrophy should not exclude the possibility of simultaneous acromegaly.

Pseudoacromegaly—A challenging entity in the endocrine clinic: A systematic review

“…Lab tests performed to assess the GH/IGF-1 axis, n | 553 every pseudoacromegaly case have a normal GH/IGF-1 axis before assuming a certain condition as the cause of acromegaloid features, 56,57 as acromegaly may coexist with other pseudoacromegaly disorders, as reported in Seip-Berardinelli syndrome, 58 Tatton-Brown-Rahman syndrome, 59 pachydermoperiostosis, 60 and Klinefelter syndrome, 61 or in families with both GH-related pituitary and non-pituitary gigantism. 62 Endocrine specialists are also important to avoid erroneous diagnosis of acromegaly, [17][18][19][20] and prevent inadequate pituitary surgery in pseudoacromegaly cases with pituitary incidentalomas.…”

Hereditary severe insulin resistance syndrome: Pathogenesis, pathophysiology, and clinical management

“…Nevertheless, a differential diagnosis of CGL should be considered in older patients who have a massive loss of subcutaneous fat because CGL has been diagnosed with genetic testing in some older patients. 63 Patients with CGL1 present with generalized loss of subcutaneous fat, muscular hypertrophy, and acromegalic features at birth or early infancy. Subsequently, in early childhood, acanthosis nigricans, hypertriglyceridemia, hirsutism, hepatomegaly with steatosis, micro-albuminemia, myocardial hypertrophy, and insulin resistance appear.…”

“…Pituitary adenoma, umbilical hernia, and polycystic ovarian syndrome have been reported in 20% of the cases. 63 , 64 Most of the patients are diagnosed with type-2 diabetes mellitus in their second decade of life. CGL2 has similar but relatively severe features when compared with CGL1.…”

“…Consequently, patients with mild symptoms are underdiagnosed. 63 , 92 , 93 The immense variability in the clinical presentations of the same form of H-SIRS makes it difficult to be diagnosed in the first clinical encounter. Despite receiving almost the same management, two siblings with the same genetic defect have been reported to show some variations in the clinical course of the syndrome.…”