Growth hormone deficiency treatment

Individuals surviving cancer and brain tumors may experience growth hormone deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence 1).

Perturbations in pituitary function continue to occur during the first year after TBI and SAH, but only a few patients need replacement therapy.

In patients with Growth Hormone Deficiency (GHD), low doses of recombinant human Growth Hormone (rhGH) have a similar or better long-term clinical effect than higher doses. Pharmacogenetic studies suggest that Growth Hormone receptor (GHR) polymorphism influences only some metabolic parameters. Nonetheless there is no clear scientific evidence proving the effects of lower rhGH dose regimens on metabolic parameters. The aim of a prospective study was to evaluate the effects of GHR polymorphism in adult GHD patients treated with low rhGH dose during short (6 and 12 months) and long-term (5 years) follow-up.

Sixty-nine GHD adult patients were studied, before and during treatment with rhGH, using a standardized low-dose protocol calculated on the basis of body weight (0.01-0.03 mg/kg/week) and monitored by IGF-I plasma assay, anthropometric and metabolic parameters. The GHR genotype (flfl, fld3, or d3d3) was determined from peripheral blood.

d3-GHR carriers showed a more effective short and long-term response to low rhGH dose in LDL reduction, body composition and blood pressure (homozygous patients only); d3-GHR homozygosity is related to a significant IGF-I increase during short-term follow-up. Regression analysis demonstrated that rhGH dose, age at diagnosis and GHR genotype are the major determinants of IGF-I increase at 6 and 12 months of replacement therapy.

the d3d3-GHR genotype may influence some metabolic effects during short and long-term follow-up of low rhGH dose and could be an independent determinant of the increase of IGF- I during short-term follow-up 2).

Dwarfism occurs when an individual person or animal is short in stature resulting from a medical condition caused by abnormal (slow or delayed) growth. In humans, dwarfism is sometimes defined as an adult height of less than 4 feet 10 inches (58 in; 147 cm).

Dwarfism can be caused by about 200 distinct medical conditions, such that the symptoms and characteristics of individuals with dwarfism vary greatly. Disproportionate dwarfism is characterized by one or more body parts being relatively large or small in comparison to those of an average-sized adult, with growth variations in specific areas being apparent. In cases of proportionate dwarfism, the body appears normally proportioned, but is unusually small.

The inherent anatomical abnormalities of the spine present in achondroplastic dwarfism predispose these patients to an increased incidence of spinal deformity as well as neurogenic claudication and potential radicular symptoms. The risks associated with prolonged general anesthesia and intolerance of significant blood loss in these patients makes them ideal candidates for minimally invasive spinal surgery.

Majewski osteodysplastic primordial dwarfism Type II (MOPD II) is a rare genetic disorder. Features of it include extremely small stature, severe microcephaly, and normal or near-normal intelligence. Previous studies have found that more than 50% of patients with MOPD II have intracranial vascular anomalies, but few successful surgical revascularization or aneurysm-clipping cases have been reported because of the diminutive arteries and narrow surgical corridors in these patients. Here, the authors report on a large series of patients with MOPD II who underwent surgery for an intracranial vascular anomaly.

In conjunction with an approved prospective registry of patients with MOPD II, a prospectively collected institutional surgical database of children with MOPD II and intracranial vascular anomalies who underwent surgery was analyzed retrospectively to establish long-term outcomes. RESULTS Ten patients with MOPD II underwent surgery between 2005 and 2012; 5 patients had moyamoya disease (MMD), 2 had intracranial aneurysms, and 3 had both MMD and aneurysms. Patients presented with transient ischemic attack (TIA) (n = 2), ischemic stroke (n = 2), intraparenchymal hemorrhage from MMD (n = 1), and aneurysmal subarachnoid hemorrhage (n = 1), and 4 were diagnosed on screening. The mean age of the 8 patients with MMD, all of whom underwent extracranial-intracranial revascularization (14 indirect, 1 direct) was 9 years (range 1-17 years). The mean age of the 5 patients with aneurysms was 15.5 years (range 9-18 years). Two patients experienced postoperative complications (1 transient weakness after clipping, 1 femoral thrombosis that required surgical repair). During a mean follow-up of 5.9 years (range 3-10 years), 3 patients died (1 of subarachnoid hemorrhage, 1 of myocardial infarct, and 1 of respiratory failure), and 1 patient had continued TIAs. All of the surviving patients recovered to their neurological baseline.

Patients with MMD presented at a younger age than those in whom aneurysms were more prevalent. Microneurosurgery with either intracranial bypass or aneurysm clipping is extremely challenging but feasible at expert centers in patients with MOPD II, and good long-term outcomes are possible 3).

Boguszewski MCS, Cardoso-Demartini AA, Boguszewski CL, Chemaitilly W, Higham CE, Johannsson G, Yuen KCJ. Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors-a review of research and clinical practice. Pituitary. 2021 Jul 25. doi: 10.1007/s11102-021-01173-0. Epub ahead of print. PMID: 34304361.
Bianchi A, Giampietro A, Tartaglione L, Chiloiro S, Gentilella R, Bima C, Anile C, Olivi A, Pontecorvi A, De Marinis L. Short and long-term responsiveness to low dose GH in adult Growth Hormone Deficiency (GHD): role of GH receptor (GHR) polymorphism. J Neuroendocrinol. 2019 Feb 3:e12692. doi: 10.1111/jne.12692. [Epub ahead of print] PubMed PMID: 30712287.
Teo M, Johnson JN, Bell-Stephens TE, Marks MP, Do HM, Dodd RL, Bober MB, Steinberg GK. Surgical outcomes of Majewski osteodysplastic primordial dwarfism Type II with intracranial vascular anomalies. J Neurosurg Pediatr. 2016 Dec;25(6):717-723. PubMed PMID: 27611897.
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