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Query: UMLS:C0011854 (type 1 diabetes)
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GH hypersecretory states include organic and functional causes. Among functional GH hypersecretory states, enhanced somatotroph secretion physiologically occurs at birth associated with reduced IGF-I levels reflecting the still immature sensitivity of liver to circulating GH levels; this may also occur in women exposed to oral extrogens. Pathophysiological conditions of GH hypersecretion are generally associated with congenital or acquired/functional conditions of peripheral GH insensitivity. Genetic alterations of the GH receptor lead to the so called Laron's syndrome. On the other hand, a relevant number of clinical conditions (malnutrition, malabsorption, anorexia nervosa, liver cirrhosis, renal failure, Type 1 diabetes mellitus) are associated with acquired GH insensitivity and a more or less pronounced GH hypersecretion. Both organic and acquired conditions of GH insensitivity show low IGF-I synthesis and release and therefore lack the negative IGF-I feedback action on somatotroph function. GH hypersecretion may be associated with renal failure; however, in this case, the alteration in the metabolic clearance rate of GH would also have a role; moreover, IGF-I levels are generally normal in this condition. Hyperthyroidism is another condition connoted by elevated GH levels that reflects a true GH hypersecretory state and is, in fact, associated with high-normal IGF-I levels; this peculiar condition is likely to be reflecting the stimulatory effect of thyroid hormones on both GH and IGF-I secretion and is promptly reversed by treatment-induced euthyroidism. Apart from these "functional" hypersecretory state, the classic organic GH hypersecretory state is represented by acromegaly or giantism. In these conditions GH hypersecretion is generally sustained by a pituitary adenoma hypersecreting GH alone or together with another pituitary hormone, mostly PRL; less frequently GH hypersecretion may be due to ectopic GHRH hypersection. Exaggerated GH secretion elicits exaggerated IGF-I synthesis and secretion that is, in turn, responsible for the large majority of endocrine signs and symptoms. In the appropriate clinical context of acromegalic features, evidence of concomitant marked GH and IGF-I hypersecretion at baseline demonstrates active acromegaly or giantism and indicates the need for magnetic resonance imaging in order to verify the presence of a pituitary tumor. However, as random measurement of basal GH levels is not reliable for definite diagnosis of acromegaly, it is considered mandatory to rely on the lack of GH suppression below 1 microg/l during oral glucose tolerance test (OGTT) coupled with elevated IGF-I levels. The same criteria are assumed, at present, to define true cure of the disease after (or under) treatment. There is consensus about the assumption that concomitant normalization or persistent abnormality of both OGTT-induced GH nadir and IGF-I levels define a successfully or a poorly controlled disease status, respectively. On the other hand, acromegalic patients with GH nadir above 1 microg/l or IGF-I levels persistently elevated are inadequately controlled and their disease should not be considered inactive. It has been clearly demonstrated that an extended exposure to GH and IGF-I excess level, even if slight, has a very harmful effect on patients; therefore early diagnosis of acromegaly and appropriate definition of its cure are of fundamental extreme in order to plan a prompt and appropriate therapeutic intervention(s) guaranteed also by the continuous improvement in the therapeutic tools available to treat this systemic disease.
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PMID:Hormonal diagnosis of GH hypersecretory states. 1549 57

The spectrum of adipose tissue diseases ranges from obesity to lipodystrophy, and is accompanied by insulin resistance syndrome, which promotes the occurrence of type 2 diabetes, dyslipidemia and cardiovascular complications. Lipodystrophy refers to a group of rare diseases characterized by the generalized or partial absence of adipose tissue, and occurs with or without hypertrophy of adipose tissue in other sites. They are classified as being familial or acquired, and generalized or partial. The genetically determined partial forms usually occur as Dunnigan syndrome, which is a type of laminopathy that can also manifest as muscle, cardiac, neuropathic or progeroid involvement. Gene mutations encoding for PPAR-gamma, Akt2, CIDEC, perilipin and the ZMPSTE 24 enzyme are much more rare. The genetically determined generalized forms are also very rare and are linked to mutations of seipin AGPAT2, FBN1, which is accompanied by Marfan syndrome, or of BANF1, which is characterized by a progeroid syndrome without insulin resistance and with early bone complications. Glycosylation disorders are sometimes involved. Some genetically determined forms have recently been found to be due to autoinflammatory syndromes linked to a proteasome anomaly (PSMB8). They result in a lipodystrophy syndrome that occurs secondarily with fever, dermatosis and panniculitis. Then there are forms that are considered to be acquired. They may be iatrogenic (protease inhibitors in HIV patients, glucocorticosteroids, insulin, graft-versus-host disease, etc.), related to an immune system disease (sequelae of dermatopolymyositis, autoimmune polyendocrine syndromes, particularly associated with type 1 diabetes, Barraquer-Simons and Lawrence syndromes), which are promoted by anomalies of the complement system. Finally, lipomatosis is currently classified as a painful form (adiposis dolorosa or Dercum's disease) or benign symmetric multiple form, also known as Launois-Bensaude syndrome or Madelung's disease, which are sometimes related to mitochondrial DNA mutations, but are usually promoted by alcohol. In addition to the medical management of metabolic syndrome and the sometimes surgical treatment of lipodystrophy, recombinant leptin provides hope for genetically determined lipodystrophy syndromes, whereas modifications in antiretroviral treatment and tesamorelin, a GHRH analog, is effective in the metabolic syndrome of HIV patients. Other therapeutic options will undoubtedly be developed, dependent on pathophysiological advances, which today tend to classify genetically determined lipodystrophy as being related to laminopathy or to lipid droplet disorders.
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PMID:How to diagnose a lipodystrophy syndrome. 2274 2


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