Pegvisomant and current approaches to the medical treatment of acromegaly (literature review and case report)

This review provides the main results of clinical trials and the literature on the experience of using pegvisomant, the first drug from the class of growth hormone receptor antagonists. The mechanism of action of the drug, its effectiveness with respect to disease control and its effect on complications, information on adverse events, and brief information on the experience of use during pregnancy are discussed in detail. In conclusion, a clinical observation of successful use of pegvisomant in resistant to standart treatment acromegaly is given. A discussion of the available literature data, the results of clinical studies and practical experience allows us to conclude that the drug is highly effective in terms of achieving biochemical remission of acromegaly, and also has a number of additional valuable properties: it is capable of improvement of patients’ glucose metabolism and quality of life and has a minimal amount of adverse events. Pegvisomant is currently registered in the Russian Federation only for use in monotherapy; the possibility of combination therapy with somatostatin analogues will additionally allow to reliably control the growth of the pituitary adenoma and significantly cut treatment costs by reducing the dose of pegvisomant. These features of the drug make it very relevant when discussing issues related to drug therapy of acromegaly, and suggest a good prospect for use in clinical practice

Federal clinical guidelines on diagnosis and treatment of diabetes insipidus in adults

We do not recommend population screening for diabetes insipidus (DI) (B3). We recommend to perform diagnostic testing for central diabetes insipidus (CDI) in patients who underwent neurosurgery, after skull and brain trauma, subarchnoid hemorrhage (B3). We recommend excluding thirst impairment during all stages of diagnostic assessment (С3). We recommend excluding DI in cases of persistent hypotonic polyuria: excretion of more than 3 L. or more than 40 mL/kg of urine daily; urine osmolality less than 300 mOsm/kg or urinary specific gravity less than 1004 g/L in all urine samples or during Zimnitsky test (В3). After hypotonic polyuria is confirmed, we recommend excluding of the main causes of nephrogenic diabetes insipidus (NDI) (B3). We recommend simultaneous measurement of urine osmolality and blood osmolality/sodium level in order to confirm DI. Blood hyperosmolality (more than 300 mOsm/kg) and/or hypernatremia with low urine osmolality (less than 300 mOsm/kg) confirms DI (B2). If testing does not reveal these findings, we recommend performing a fluid deprivation test to exclude primary polydipsia (PP) (B2). Desmopressin test is recommended to distinguish CDI and NDI (B2). In cases of CDI we recommend to perform head MRI with contrast (B3). In cases of NDI we recommend assessing renal structure and function and possible electrolyte disturbances (C3). In cases of PP we recommend to refer a patient to psychiatrist (B3). We recommend treating CDI with synthetic vasopressin analogue – desmopressin (B1). We recommend an individual approach in choosing desmopressin dosage form (B2). As the initial dose is difficult to predict when starting desmopressin treatment, we recommend titrating the dosage using two approaches: “the average dose” and “as required” (C4). We recommend educating the patients to ensure knowledge of the features of various desmopressin dosage forms (C4). To decrease the risk of water intoxication, we recommend educating the patients to the water intake regimen adherence (С4). When CDI is accompanied by thirst impairment, we recommend titrating the dose in a clinical setting, with assessment of blood sodium, bodyweight and/or urine volume (C4)