Acromegaly in a family without a mutation in the menin gene

Abstract

Familial pituitary tumors are rare. Only 45 cases in 20 families with acromegaly have been reported. A third of the cases (30%) is related to multiple endocrine neoplasia type 1 (MEN 1). We report two cases of acromegaly in one family with pituitary macroadenomas. A 46-year-old woman with elevated serum growth hormone (GH) and insulin-like growth factor (IGF-1) and a failure to supress GH in the glucose tolerance test underwent transsphenoidal surgery 4 years ago. Three years later her 24-year-old son also presented with typical signs of acromegaly. A pituitary macroadenoma was identified by MRT and he also underwent transsphenoidal surgery. There were no symptoms of McCune-Albright syndrome or other forms of endocrine hyperfunction in the two patients. In an attempt to identify the molecular etiology of the tumours DNA was extracted from paraffin fixed tissue from both patients. Exon 7 to 13 of the Gsp-protein and exons 1 to 10 of the menin gene were amplified by PCR. Although Gsp mutations have been identified in 40% of somatotroph tumors, direct sequencing of the PCR products showed no mutations in exons 7 to 13 of Gs alpha. Moreover no mutations were found in exons 1 to 10 of the menin gene. Therefore, molecular causes other than Gsp or menin gene mutations have to be considered as the molecular etiology of acromegaly in this family.

Where is the culprit? A case of acromegaly that defied the management algorithm

“…MEN-1, also an autosomal-dominant syndrome, consists of hyperplastic or adenomatous parathyroid glands, endocrine pancreas and anterior pituitary 4. Isolated familial acromegaly or gigantism not associated with MEN has rarely been reported 5 6. Low prevalence germline mutations of the aryl hydrocarbon receptor-interacting protein (AIP, located on 11 q 13.3) gene were reported as predisposing to a subset of patients with familial acromegaly and gigantism;7 15% of families with isolated familial acromegaly exhibit AIP mutations, and tumours are encountered earlier in subjects harbouring a mutation 8 9.…”

Herbal therapy: A review of emerging pharmacological tools in the management of diabetes mellitus in Africa

“…[ 8 9 10 11 12 13 ] Another approach which has been tried is the prevention of autoimmune attack using immunosuppressive compounds. [ 14 15 16 17 18 ] Transplantation of either the pancreas or preparations of islet tissues has also been tried. [ 17 18 ] Regardless of the efficiency of the above-mentioned methods used in the management of the disease, they have several drawbacks.…”

“…In general, it is preferable to start a specific immuno-modulatory treatment while substantial β-cells mass remains; that's during the prediabetic phase. [ 14 42 ] The vitamin B-complex nicotinamide is currently undergoing a multicentre trial in Europe. Nicotinamide is thought to protect against damage acting as an antioxidant and thus inhibits the deleterious effects of free radicals.…”