Glucocorticoid-induced osteoporosis and parathyroid hormone.

Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis. Bisphosphonates are considered the first-line treatment option for the majority of glucocorticoid-treated patients at increased risk of fractures. However, the anti-resorptive mechanism of bisphosphonates does not address the major pathophysiological mechanisms of impaired bone formation during chronic glucocorticoid treatment. PTH, when administered intermittently and at low doses, has effects on bone formation opposite to those of glucocorticoids and therefore is conceptually a more attractive approach. Teriparatide (1-34PTH) has been studied in patients with GIO with effects on bone mineral density and on fracture risk which were shown to be superior to those obtained with alendronate.

Glucocorticoid replacement therapy and vertebral fractures in hypopituitary adult males with GH deficiency.

OBJECTIVE: GH deficiency (GHD) and glucocorticoid excess are associated with increased risk of fragility fractures. We aimed to evaluate whether the prevalence of vertebral fractures may be influenced by glucocorticoid over-replacement in hypopituitary males with GHD. DESIGN: Cross-sectional study. METHODS: Fifty-one adult hypopituitary patients (all males; mean age 55 years, range: 23-81) with severe adult-onset GHD (replaced in 21 patients and untreated in 30 patients) and glucocorticoid deficiency on replacement treatment were studied for vertebral fractures using a radiological and morphometric approach. RESULTS: Vertebral fractures were observed in 31 patients (60.8%) in correlation with untreated GHD, urinary cortisol values, and cortisone doses. Patients were stratified according to treatment of GHD, and current and cumulative cortisone doses. In untreated GHD, vertebral fractures occurred more frequently in patients who had received higher (greater than median) cumulative and current doses of cortisone compared with patients who had received lower (less than median) drug doses (95.2 vs 50.0%, P=0.009 and 90.5 vs 55.6%, P=0.04 respectively). In untreated GHD, fractured patients had significantly higher urinary cortisol values compared with patients without vertebral fractures (84 microg/24 h, range: 24-135 vs 49 microg/24 h, range: 30-96; P=0.04). In treated GHD patients, by contrast, the prevalence of vertebral fractures was not influenced by cumulative and current cortisone doses and urinary cortisol values. CONCLUSIONS: Glucocorticoid over-replacement may increase the prevalence of vertebral fractures in patients with untreated GHD. However, treatment of GHD seems to protect the skeleton from the deleterious effects of glucocorticoid overtreatment in hypopituitary patients.

Pituitary tumours: inflammatory and granulomatous expansive lesions of the pituitary.

Inflammatory and granulomatous diseases of the pituitary are rare causes of sellar masses. Lymphocytic hypophysitis is the most relevant of these disorders, and it is characterised by autoimmune pathogenesis with focal or diffuse inflammatory infiltration and varying degrees of pituitary gland destruction. Endocrine symptoms may include partial or total hypopituitarism, with adrenocorticotropic hormone (ACTH) deficiency being the earliest and most frequent alteration. Pituitary abscess is a rare but potentially life-threatening disease and, in 30-50% of patients, anterior pituitary hormone deficiencies or central diabetes insipidus (DI) at onset may be observed: the earliest manifestation being growth hormone deficiency (GHD), followed by follicle-stimulating hormone (FSH)/luteinising hormone (LH), thyroid-stimulating hormone (TSH) and ACTH deficiencies. Fungal infections of the pituitary are also very rare and include aspergillosis and coccidioidomycosis. Concerning pituitary involvement in systemic diseases, in sarcoidosis endocrine complications are rare, but the hypothalamus and pituitary are the glands most commonly affected. DI is reported in approximately 25-33 % of all neurosarcoidosis cases and is the most frequently observed endocrine disorder. Hyperprolactinaemia and anterior pituitary deficiencies may also occur. Rarely, partial or global anterior pituitary dysfunction may be present also in Wegener's granulomatosis, either at onset or in the course of the disease, resulting in deficiency of one or more of the pituitary axes. Other forms of granulomatous pituitary lesions include idiopathic giant cell granulomatous hypophysitis, Takayasu's disease, Cogan's syndrome and Crohn's disease. The hypotalamic-pituitary system is involved mainly in children with Langerhans' cells histiocytosis who develop DI, which is the most common endocrine manifestation. Anterior pituitary dysfunction is found more rarely and is almost invariably associated with DI. Pituitary involvement may also be observed in another form of systemic hystiocitosis, that is, Erdheim-Chester disease. Tuberculosis is a rare cause of hypophysitis, which may present with features of anterior pituitary dysfunction, such as hypopituitarism with hyperprolactinaemia. In conclusion, in patients with a sellar mass and unusual clinical presentation (DI, neurological symptoms), aggressiveness and onset and in the presence of systemic diseases, inflammatory and granulomatous pituitary lesions should be carefully considered in differential diagnosis.

Prevention and treatment of glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis with fractures occurring in as many as 30-50% of patients receiving chronic glucocorticoid therapy. Calcium and vitamin D are important measures in the primary prevention of GIO. However, vitamin D and calcium alone do not allow to prevent fractures. Estrogens and androgens should be used in patients with documented hypogonadism. Bisphosphonates are the most effective of the various therapies that have been assessed for the management of GIO. These drugs need to be started early in order to correct the increase in bone resorption occurring in the first weeks of glucocorticoid treatment. Anabolic therapeutic strategies are under investigation. Teriparatide seems to be also efficacious for the treatment of patients with GIO.

Biochemical evaluation of patients with active acromegaly and type 2 diabetes mellitus: efficacy and safety of the galanin test.

The oral glucose tolerance test, which is considered the gold standard for the diagnosis of active acromegaly, should not be performed in the presence of basal hyperglycemia. Moreover, false-positive responses may occur in patients with diabetes mellitus. Galanin has previously been demonstrated to induce paradoxical inhibition of growth hormone (GH) secretion in most patients with active acromegaly. In this study, we assessed GH response to galanin infusion in a series of 17 consecutive patients with active acromegaly, 7 of whom had coexistent type 2 diabetes mellitus and 10 were without either diabetes mellitus or impaired tolerance to glucose. 6 acromegalic patients with diabetes mellitus (85.7%) and 7 without diabetes (70.0%) showed a decrease in serum GH values during galanin infusion (chi2 0.9; p = 0.6). The GH nadir occurred at a comparable time in the two groups of acromegalic patients. Moreover, the two groups showed no significant difference (p = 0.45) in DeltaGH during galanin infusion. Galanin infusion did not induce any significant change in plasma glucose levels in both diabetic and non-diabetic patients with acromegaly. The results of our study provide evidence that the galanin test may be of value for the diagnosis of acromegaly in patients with type 2 diabetes mellitus.